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This week, the Maier's get together to discuss: bathroom reno, back to work, work/life balance, Schwann's, Conservative family, crossing the border, golf, SOW, Airhouse, and Spring playlist. Reach Us: @kmaemaier @chrismaierbc @hwywhoney hwywhoney@gmail.com
Matador (Afsnit 03) (1978) Kronologisk gennemgang af serien. www.janoghenrik.dk/ www.henrikogjan.dk/ Skiftedag. 1930 - Ikke alle klarer sig så godt som Mads Andersen-Skjern (Jørgen Buckhøj). Det gælder for eksempel indehaveren af Damernes Magasin, Albert Arnesen (Preben Mahrt), der bliver nødt til at invitere sin førstemand, Hr. Schwann, (Arthur Jensen), som netop har fået en mindre arv, ind som kompagnon, for at afværge en truende fallit. Arnold (Esper Hagen) bliver udlært og tager arbejde ovre hos Mads. 30'erne er netop startet - en tid med turbulens, ikke mindst på det politiske område. Dønningerne kommer til Korsbæk, hvor der agiteres højrøstet - både på den konservative og den socialistiske front. Mads gifter sig med Ingeborg (Ghita Nørby) og adopterer hendes datter Ellen (Helle Nielsen). Tekst fra Danskefilm.dk
A North Dakota couple, fans of the podcast, share some great stories from small town shenanigans in ND. The Schwann truck man creeps into a teepee and a Moose chases a kid down the dirt roads of Montana.
Today we're talking Schwann's dairy, Amazon Fresh, the rebirth of Hot & Now and beef jerky business cards?As always, find us here:https://www.speakpipe.com/InTheWeedsWithBenRandallhttps://www.facebook.com/groups/774902433251568https://www.instagram.com/chefbenrandall/ https://podcasts.apple.com/us/podcast/in-the-weeds-with-ben-randall/id869521547intheweedswbr.comhttps://www.redbubble.com/people/enzwell/shopintheweedswbr@gmail.com
Wisconsin's cattle industry's getting ready for some changes in animal identification standards. Since 2013, breeding cattle over the age of 18 months, dairy cattle, and any cattle used for shows, etc. needed to have an official ID to move between states. This spring, USDA amended that rule so that the IDs have to be both visually AND electronically readable. Stephanie Hoff finds out how it'll impact farmers with Tressa Lacy, president of the Wisconsin Cattlemen's Association.Yellow trucks rolling in the driveway usually meant a treat for kids in rural Wisconsin. Now it's going away. Schwann's, now known as Yelloh, is ceasing operations by the end of November.Weather is really helping the state's farmers keep rolling in the harvest, but breakdowns can stop them in their tracks. Getting big farm equipment fixed these days isn't easy. Ben Jarboe talks to Danielle Waterworth, North America VP of Dealer and Customer Support for Case IH and New Holland. She says they're turning to technology to help speed assistance. Consumers may not realize that the prices we share on the radio don't correlate to organic producers. Shawna Nelson, executive vice president of membership with Organic Valley, says organic milk pricing stands on its own. Bryce Wyndecker, broker analyst with EverAg, joins Pam Jahnke to discuss the recent collapse in the barrel cheese price. He also recaps recent milk production figures.See omnystudio.com/listener for privacy information.
Critical minerals are a key part of Saskatchewan's energy and resources plan. Last week, the province announced new incentives to grow Saskatchewan's mining sector further. Pam Schwann, president of the Saskatchewan Mining Association (SMA) joins Evan to discuss critical minerals in the province.
By special request - more info from the book The Invisible Rainbow by Arthur Firstenberg on the importance of the myelin sheath in transmission of energy throughout the body - and what can go wrong with Electromagnetic pollution.00:00 Intro to the book02:00 The importance of electrical energy in healing damaged tissue - porphyrins as transmitters of energy within cells - haemoglobin in red blood cells05:16 Electrical polarity of the brain can be reversed to cause anaesthesia, pain reduction and healing08:00 Porphyrins are energy transmitters in the mitochondria (as cytochrome c in the electron transport chain) but also those in the myelin sheath complexed with zinc, (chlorophyll uses magnesium, haem uses Iron). 11:00 With a porphyrin manufacture problem excess precursors builds up in tissue along with excess zinc causing hyper excitability of the neurons - predisposes to electro-sensitivity and chronic fatigue syndrome?13:06 Robert Becker's investigation in bioelectric healing in bone and nerves - electro-chemical transmission allows much of our activity16:25 'Currents of injury' - point to another information system that allows regeneration and healing18:17 Myelin sheaths/Schwann/glial cells are intimately involved in signal transmission and energy production in the brain and nervous system19:45 Electro-chemical sensitivity may interact with high zinc in brain and nerves, and other parts of body. EDTA (a chelators) complexes Zn and will take it out the body and can reverse cognitive decline22:00 90% of oxygen consumption occurs in brain from glial cells - myelin may be the major energy powerhouse completely independent of mitochondria24:02 Excess zinc is everywhere in the environment, car tyres a major factor along with denture cream, water supply, etc. 25:40 Are highly sensitive people (HSP's) the canaries in the coalmine with problems in the porphyrin pathways? What can we do to protect ourselves particularly during sleep and add highly coloured foods into our diet.*Watch another video**THE INVISIBLE RAINBOW PART 1 https://youtu.be/CYZFxL57paMTHE INVISIBLE RAINBOW PART 2 https://youtu.be/VgWSzIPBgHAHEAL YOUR SPIRIT TO HEAL CFS/ME https://youtu.be/hXGaOjrV6PAWHATS THE MATTER WITH MEDICINE - IAIN MCGILCHRIST https://youtu.be/CdE1QphYKoUHOW TO HEAL BIRTH TRAUMA WITH EMDR https://youtu.be/JmtarRiGsgYEMOTIONAL RESILIENCE https://youtu.be/E5TYi9dEBEUWHY ANXIETY IS NOT A MIND ISSUE https://youtu.be/Ty-J2pu37tAHOW CHILDHOOD EMOTIONS STILL AFFECT YOU: https://youtu.be/8LzR8yhR8u8 *If you're suffering from Chronic pain, fatigue or anxiety, I CAN HELP*CONTACT ME: https://www.alchemytherapies.co.uk/Alchemy Therapies & Emotional MasterclassOTHER USEFUL RESOURCESGroup Healing Program: http://myemotionalaudit.comAuthor/Book site: https//patriciaworby.comPodcast: https://www.alchemytherapies.co.uk/po...121 and group therapy and training for stress related conditions like anxiety, fatigue and pain: https://alchemytherapies.co.ukSee in particular: Thrive! - an introductory mindbody connection program and The Emotional Audit for more intensive training.COMING SOON:Intensive Training Program: https://emotionalmasterclass.com
Ein British Airways Airbus A320 am Flughafen Heathrow entging knapp einem großen Schaden, als eine mobile Treppe während der heißesten Tag des Jahres in Flammen aufging. Das Flugzeug war gerade aus Athen angekommen und wurde für den nächsten Flug vorbereitet, als das Feuer ausbrach. Glücklicherweise konnten die Reinigungskräfte das Flugzeug schnell verlassen und die Tür schließen, bevor die Flammen das Flugzeug erreichten. Die Feuerwehr konnte das Feuer schnell löschen, aber das Flugzeug wurde aus dem Betrieb genommen, um es zu überprüfen. Es gab keine Passagiere an Bord und keine Verletzten.#BritishAirways #A320 #Feuer #Heathrow #Flugzeug #Notfall #Sicherheit #Luftfahrt #NachrichtenFragen des Tages: Ist die Strafe von 12 Jahren gerecht? Wie findet ihr den "weissen Schwan" Boeing 787 von Austrian Airlines?00:00 Willkommen zu Frequent Traveller TV02:24 Boeing übernimmt bald Spirit Aerosystems05:14 Airbus muss Jahresziel reduzieren07:20 Geiselnehmer vom Hamburger Flughafen muss 12 Jahre in den Knast09:540 Austrian Airlines Boeing 787 “weisser Schwann” wird erst im Winter neu lackiert13:02 British Airways A320 entkommt Feuerschaden15:30 Skytrax 202419:32 World of Hyatt Promotion 1.000 Punkte und doppelte Statusnächte in FloridaFragen des TagesTake-OFF 25.06.2024 – Folge 144-2024 Kanalmitglied werden und exklusive Vorteile erhalten:https://www.youtube.com/channel/UCQyWcZxP3MpuQ54foJ_IsgQ/joinHier geht es zu eurem kostenlosen Consulting Link - https://FTCircle.as.me/Damit Du von unserem Wissen profitieren kannst, kannst du ein mindestens 60 minütiges und vor allem auf dich zugeschnittenes Punkte, Meilen, Status Coaching buchen. Nach dem Call bekommst du ein Jahr Zugang zu dieser Gruppe und zahlst so nur 10 Euro pro Monat und kannst sofort profitieren. Hier ist nun der Link zu deinem neuen Punkte, Meilen und Status Deals.MY SOCIALSWhatsApp - https://wa.me/message/54V7X7VO3WOVF1FACEBOOK | Lars F Corsten - https://www.facebook.com/LFCorsten/FACEBOOK | FQT.TV - https://www.facebook.com/FQTTVFACEBOOK | FTCircle - https://www.facebook.com/FTCircleTWITTER | Lars F Corsten - https://twitter.com/LFCorstenINSTAGRAM | Lars F Corsten - https://www.instagram.com/lfcorsten/LINKEDIN - https://www.linkedin.com/in/lfcorsten/Clubhouse - @LFCorsten
It's Saskatchewan Mining Week and this year's theme is critical careers for Saskatchewan's critical minerals. This week marks an opportunity to continue raising public awareness of the importance of the mining industry in the province and its benefits. Pam Schwann, president of the Saskatchewan Mining Association (SMA), and Guy Hiltz from the SMA's emergency response mine rescue competition committee join Evan.
This week on The Less Stressed Life Podcast, I am joined by the lovely August Brice of TechWellness. In this episode, August tells us how EMF (electromagnetic fields) affects our health and wellness. We talk about the research August has done and how to get the most bang for your buck when it comes to EMF protection devices. Get 15% OFF Digital Detox Collection with Code LESSSTRESSEDKEY TAKEAWAYS:My journey with the SomavedicWhat EMF Protection works - Chips & ShieldsHow to hardwire your internetNational Toxicology Study The findings of his research were most recently edified in 2018 by our government's own National Toxicology Program where links were found to cellphone radiation: Increased incidences of glioma, a rare, aggressive and highly malignant brain cancerIncreased incidence of schwannoma (a rare tumor of the nerve sheath) of the heartIncreases of these cancers were found in both sexes of rats, but reached statistical significance only in malesIncreased incidences of rare, proliferative changes in glial cells of the brain and in Schwann cells in the hears of bot sexes of rats while not a single unexposed control animal developed these precancerous changes.DNA damage was induced with both modulations of radiofrequency radiation (RFR) in both rats and mice (in the frontal lobe plus other tissues).ABOUT GUEST:August's passion is finding solutions for mindful living in our digital world. Her online platform, TechWellness.com is the only comprehensive online source that addresses all the challenges of our modern digital world - from EMF Radiation and effects of blue light, to Cyber security and mental wellbeing with tech. On top of her on-going research, August has built an Advisory Team consisting of world-renown experts in each area, who consult with Tech Wellness and review all major content on the site. All solutions are purchased and tested, never supplied by or sponsored by manufacturers to avoid any influence.WHERE TO FIND:Website: https://techwellness.com/ Instagram: https://www.instagram.com/techwellness/***WORK WITH CHRISTA***: https://www.christabiegler.com/fssWHERE TO FIND CHRISTA:Website: https://www.christabiegler.com/Instagram: @anti.inflammatory.nutritionistPodcast Instagram: @lessstressedlifeYouTube: https://www.youtube.com/@lessstressedlifeLeave a review, submit a questions for the podcast or take one of my quizzes here: https://www.christabiegler.com/linksEPISODE SPONSOR:A special thanks to Jigsaw Health for sponsoring this episode. Get a discount on any of their products! Use the code lessstressed10
Raghu Ramesh and John Svaren discuss their paper, “JUN Regulation of Injury-Induced Enhancers in Schwann Cells,” published in Vol. 42, Issue 34 of JNeurosci, with Megan Sansevere from SfN's Journals' staff. Find the rest of the Spotlight collection here. With special guests: Raghu Ramesh and John Svaren Hosted by: Megan Sansevere On Neuro Current, we delve into the stories and conversations surrounding research published in the journals of the Society for Neuroscience. Through its publications, JNeurosci, eNeuro, and the History of Neuroscience in Autobiography, SfN promotes discussion, debate, and reflection on the nature of scientific discovery, to advance the understanding of the brain and the nervous system. Find out more about SfN and connect with us on Twitter, Instagram, and LinkedIn.
Vorlesungen zur Linguistik und Sprachgeschichte des Deutschen
„Ein Verb, das ist so, wie wenn man im dunklen Raum das Licht anknipst. Mit einem Schlag ist die Szene da.“ Hans Jürgen Heringer. 1984. Neues von der Verbalszene. In: Gerhard Stickel (Hg.). Pragmatik in der Grammatik. Düsseldorf: Schwann. 34-64, 49. Damit ist an und für sich und prinzipiell alles zur Idee der Valenzgrammatik gesagt -- aber wie bestimmt man die Valenz eines Verbs? Ich stelle verschiedene Möglichkeiten und digitale Ressourcen im Kontext der Beispielanalyse des Satzes "Versehentlich schickt sie den Brief an Storch.", der es in sich hat, vor. Die Vorlesung "Basiswissen Sprachwissenschaft" ist konzipiert als Überblicksvorlesung über die zentralen Sprachwissens- und Kommunikationsmodelle, die in der modernen Linguistik unser Bild von Sprachwissen und Kommunikation maßgeblich prägen. Präsentation (*.pdf): Alexander Lasch. 2023. Basiswissen Sprachwissenschaft. Zenodo. DOI: https://doi.org/10.5281/zenodo.8388691. Videoaufzeichnungen: https://youtube.com/@AlexanderLasch. Informationen & Material zu allen Vorlesungen: https://kurzelinks.de/fl7f. Intro: "Reflections" von Scott Holmes (CC BY via FMA). #Linguistik #OER #Sprache
In this episode of the Titans of Foodservice podcast, host Nick Portillo speaks with Scott Tomes, CRO of Bongards Creameries. Scott shares his remarkable journey in the food service industry, starting as a division manager at Schwann's. Today, he is a trailblazer in the industry, leading Bongard's to new heights of success. Scott discusses the challenges he faced, the strategies he implemented, and the valuable lessons he learned along the way. He also talks about the value of perseverance, leadership, and building strong relationships in the food service industry.Quotes“In today's competitive environment, you have to compete. But what is going to set you apart? That service level. The attention to detail. It's that relationship.” -Scott Tomes [09:22]“I don't want to put myself on a pedestal, but I tell my kids if you can pick up the phone, talk to someone as a human being and a person, you're going to already outflank 75% of your competition. I really believe that.” -Scott Tomes [29:02]TIMESTAMPS03:26 Scott's journey and role as a strike force division manager13:19 Varied sales training programs in food companies15:19 Lack of young talent in the food industry22:17 Techniques for hiring brokers and finding manufacturers28:04 Advice for aspiring chief revenue officers: Never stop learning34:11 COVID's impact on the food service industry38:41 Encouraging respect and open-mindedness in the industryRESOURCESPortillo SalesCONTACT Nick: nick.portillo@portillosales.comScott: https://www.linkedin.com/in/scotttomes/
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.25.550402v1?rss=1 Authors: Lowenstein, E. D., Misios, A., Buchert, S., Ruffault, P.-L. Abstract: The vagal ganglia, comprised of the superior (jugular) and inferior (nodose) ganglia of the vagus nerve, receive somatosensory information from the head and neck, or viscerosensory information from the inner organs, respectively. Developmentally, the cranial neural crest gives rise to all vagal glial cells and to neurons of the jugular ganglia, while the epibranchial placode gives rise to neurons of the nodose ganglia. Crest-derived nodose glial progenitors can additionally generate autonomic neurons in the peripheral nervous system, but how these progenitors generate neurons is unknown. Here, we found that some Sox10+ neural crest-derived cells in, and surrounding, the nodose ganglion transiently expressed Phox2b, a master regulator of autonomic nervous system development, during early embryonic life. Our genetic lineage tracing analysis revealed that despite their common developmental origin and extreme spatial proximity a substantial proportion of glial cells in the nodose, but not in the neighboring jugular ganglia, have a history of Phox2b expression. Lastly, we used single cell RNA-sequencing (scRNA-seq) to demonstrate that these progenitors give rise to all major glial subtypes in the nodose ganglia, including Schwann cells, satellite glia and glial precursors, and mapped their spatial distribution by in situ hybridization. Our work demonstrates that these crest-derived nodose glial progenitors transiently express Phox2b, give rise to the entire complement of nodose glial cells and display a transcriptional program that may underlie their bipotent nature. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Uma rede de controle e integração de processos fisiológicos. Separe meia horinha do seu dia e descubra, com a Mila Massuda, o que é e como atua o nosso sistema nervoso. Apresentação: Mila Massuda (@milamassuda) Roteiro: Mila Massuda (@milamassuda) e Emilio Garcia (@emilioblablalogia) Edição: @Matheus_Herédia (@mewmediaLAB) Produção: Prof. Vítor Soares (@profvitorsoares) e BláBláLogia (@blablalogia) REFERÊNCIAS: JUNQUEIRA, Luiz C.; CARNEIRO, José. Histologia básica. 13ª edição. Rio de Janeiro - RJ: Guanabara Koogan, 2017. KIM, Jong Kuk; LEE, Hye Jeong; PARK, Hwan Tae. Two faces of Schwann cell dedifferentiation in peripheral neurodegenerative diseases: pro-demyelinating and axon-preservative functions. Neural regeneration research, v. 9, n. 22, p. 1952, 2014. LORACH, Henri et al. Walking naturally after spinal cord injury using a brain–spine interface. Nature, p. 1-8, 2023. XING, Liujing et al. Wnt/β-catenin signaling regulates ependymal cell development and adult homeostasis. Proceedings of the National Academy of Sciences, v. 115, n. 26, p. E5954-E5962, 2018.
Olaparib + Abiraterone is FDA approved for mutated-BRCA prostate cancers. Olaparib has a bit of convoluted story to unpack in this patient population. Have we finally found a way to minimize the peripheral neuropathy from paclitaxel.....with cilostazol? PROpel: https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200043 Cilostazol RCT: https://doi.org/10.1002/phar.2830 Cilostazol effect on Schwann cells: https://doi.org/10.1016/j.neuropharm.2021.108514
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.05.535701v1?rss=1 Authors: Nikolaev, Y. A., Ziolkowski, L. H., Pang, S., Li, W.-P., Feketa, V. V., Xu, C. S., Gracheva, E. O., Bagriantsev, S. N. Abstract: Mechanosensory corpuscles detect transient touch and vibratory signals in the skin of vertebrates, enabling navigation, foraging, and precise manipulation of objects1. The corpuscle core comprises a terminal neurite of a mechanoreceptor afferent, the only known touch-sensing element within corpuscles, surrounded by terminal Schwann cells called lamellar cells (LCs)2-4. However, the precise corpuscular ultrastructure, and the role of LCs in touch detection are unknown. Here we used enhanced focused ion beam scanning electron microscopy and electron tomography to reveal the three-dimensional architecture of avian Meissner (Grandry) corpuscle5. We show that corpuscles contain a stack of LCs innervated by two afferents, which form large-area contacts with LCs. LCs form tether-like connections with the afferent membrane and contain dense core vesicles which release their content onto the afferent. Furthermore, by performing simultaneous electrophysiological recordings from both cell types, we show that mechanosensitive LCs use calcium influx to trigger action potential firing in the afferent and thus serve as physiological touch sensors in the skin. Our findings suggest a bi-cellular mechanism of touch detection, which comprises the afferent and LCs, likely enables corpuscles to encode the nuances of tactile stimuli. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.02.535224v1?rss=1 Authors: Prior, R., Silva, A., Vangansewinkel, T., Idkowiak, J., Kumar Tharkeshwar, A., Hellings, T. P., Michailidou, I., Vreijling, J., Loos, M., Koopmans, B., Vlek, N., Straat, N., Agaser, C., Kuipers, T., Michiels, C., Rossaert, E., Verschoren, S., Vermeire, W., de Laat, V., Dehairs, J., Eggermont, K., van den Biggelaar, D., Bademosi, A. T., Meunier, F. A., vandeVen, M., Van Damme, P., Mei, H., Swinnen, J. V., Lambrichts, I., Baas, F., Fluiter, K., Wolfs, E., Van Den Bosch, L. Abstract: Duplication of PMP22 causes Charcot-Marie-Tooth disease type 1A (CMT1A) and is known to disrupt the lipid metabolism in myelinating Schwann cells by unknown mechanisms. By using two CMT1A mouse models overexpressing human PMP22, we discovered that PMP22 dose-dependently downregulates genes that are involved in lipid and cholesterol metabolism. Lipidomic analysis on CMT1A mouse sciatic nerves confirmed lipid metabolic abnormalities primarily associated with cholesterol and sphingolipids. We observed similar lipidomic profiles and downregulation of genes associated with lipid metabolism in human CMT1A patient induced pluripotent stem cell-derived Schwann cell precursors (iPSC-SCPs). We confirmed these findings by demonstrating altered lipid raft dynamics and plasma membrane fluidity in CMT1A iPSC-SCPs. Additionally, we identified impaired cholesterol incorporation in the plasma membrane due to altered lipid storage homeostasis in CMT1A iPSC-SCPs, which could be modulated by changing the lipid composition of the cell culture medium. These findings suggest that PMP22 plays a role in regulating the lipid composition of the plasma membrane and lipid storage homeostasis. Targeting lipid metabolism may hold promise as a potential treatment for CMT1A patients. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.18.533291v1?rss=1 Authors: Ptak, C. P., Peterson, T. A., Hopkins, J. B., Ahern, C. A., Shy, M. E., Piper, R. C. Abstract: Mutations in Myelin Protein Zero (MPZ) account for 5% of Charcot-Marie-Tooth cases and can cause demyelinating or axonal phenotypes, reflecting the diverse roles of MPZ in Schwann cells. MPZ holds the apposing membranes of the myelin sheath together, with the adhesion role fulfilled by the extracellular Immunoglobulin-like domain (IgMPZ), which can oligomerize. Current knowledge for how the IgMPZ might form oligomeric assemblies involving 3 weakly-interacting interfaces has been extrapolated from a protein crystal structure in which individual rat IgMPZ subunits are packed together under artificial conditions. These interfaces include one that organizes the IgMPZ into tetramers, a 'dimer' interface that could link tetramers together, and a third hydrophobic interface that could mediate binding to lipid bilayers or the same hydrophobic surface on another IgMPZ domain. There are at present no data confirming whether the proposed IgMPZ interfaces actually mediate oligomerization in solution, whether they are required for the adhesion activity of MPZ, whether they are important for myelination, or whether their loss results in disease. We performed NMR and SAXS analysis of wild-type IgMPZ as well as mutant forms with amino-acid substitutions designed to interrupt its presumptive oligomerization interfaces. Here, we confirm the interface that mediates IgMPZ tetramerization, but find that dimerization is mediated by a distinct interface that has yet to be identified. We next correlated CMT phenotypes to subregions within IgMPZ tetramers. Axonal late-onset disease phenotypes (CMT2I/J) map to surface residues of IgMPZ proximal to the transmembrane domain. Early-onset demyelinating disease phenotypes (CMT1B/Dejerine-Sottas syndrome) map to two groups: one is described by variants that disrupt the stability of the Ig-fold itself and are largely located within the core of the Ig domain; whereas another describes a surface on the distal outer surface of IgMPZ tetramers. Computational docking studies predict that this latter disease-relevant subregion may mediate dimerization of IgMPZ tetramers. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.18.533004v1?rss=1 Authors: Raut, N. G., Maile, L. A., Oswalt, L. M., Mitxelena, I., Adlakha, A., Sprague, K. L., Rupert, A. R., Bokros, L., Hofmann, M. C., Patritti-Cram, J., Rizvi, T. A., Queme, L. F., Choi, K., Ratner, N., Jankowski, M. P. Abstract: Pain of unknown etiology is frequent in individuals with the tumor predisposition syndrome Neurofibromatosis 1 (NF1), even when tumors are absent. Schwann cells (SC) were recently shown to play roles in nociceptive processing, and we find that chemogenetic activation of SCs is sufficient to induce afferent and behavioral mechanical hypersensitivity in mice. In mouse models, animals show afferent and behavioral hypersensitivity when SC, but not neurons, lack Nf1. Importantly, hypersensitivity corresponds with SC-specific upregulation of mRNA encoding glial cell line derived neurotrophic factor (GDNF), independent of the presence of tumors. Neuropathic pain-like behaviors in the NF1 mice were inhibited by either chemogenetic silencing of SC calcium or by systemic delivery of GDNF targeting antibodies. Together, these findings suggest that Nf1 loss in SCs causes mechanical pain by influencing adjacent neurons and, data may identify cell-specific treatment strategies to ameliorate pain in individuals with NF1. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.17.533188v1?rss=1 Authors: Handler, A., Zhang, Q., Pang, S., Nguyen, T. M., Iskols, M., Nolan-Tamariz, M., Cattel, S., Plumb, R., Sanchez, B., Ashjian, K., Shotland, A., Brown, B., Kabeer, M., Turecek, J., Rankin, G., Xiang, W., Pavarino, E. C., Africawala, N., Santiago, C., Lee, W.-C. A., Xu, C. S., Ginty, D. D. Abstract: Specialized mechanosensory end organs within mammalian skin -- hair follicle-associated lanceolate complexes, Meissner corpuscles, and Pacinian corpuscles -- enable our perception of light, dynamic touch. In each of these end organs, fast-conducting mechanically sensitive neurons, called A{beta} low-threshold mechanoreceptors (A{beta} LTMRs), associate with resident glial cells, known as terminal Schwann cells (TSCs) or lamellar cells, to form complex axon ending structures. Lanceolate-forming and corpuscle-innervating A{beta} LTMRs share a low threshold for mechanical activation, a rapidly adapting (RA) response to force indentation, and high sensitivity to dynamic stimuli. How mechanical stimuli lead to activation of the requisite mechanotransduction channel Piezo2 and A{beta} RA-LTMR excitation across the morphologically dissimilar mechanosensory end organ structures is not understood. Here, we report the precise subcellular distribution of Piezo2 and high-resolution, isotropic 3D reconstructions of all three end organs formed by A{beta} RA-LTMRs determined by large volume enhanced Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) imaging. We found that within each end organ, Piezo2 is enriched along the sensory axon membrane and is minimally or not expressed in TSCs and lamellar cells. We also observed a large number of small cytoplasmic protrusions enriched along the A{beta} RA-LTMR axon terminals associated with hair follicles, Meissner corpuscles, and Pacinian corpuscles. These axon protrusions reside within close proximity to axonal Piezo2, occasionally contain the channel, and often form adherens junctions with nearby non-neuronal cells. Our findings support a unified model for A{beta} RA-LTMR activation in which axon protrusions anchor A{beta} RA-LTMR axon terminals to specialized end organ cells, enabling mechanical stimuli to stretch the axon in hundreds to thousands of sites across an individual end organ and leading to activation of proximal Piezo2 channels and excitation of the neuron. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
A new research paper was published on the cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 5, entitled, “AAV1.NT-3 gene therapy prevents age-related sarcopenia.” Sarcopenia is progressive loss of muscle mass and strength occurring during normal aging with significant consequences on the quality of life for elderly. Neurotrophin 3 (NT-3) is an important autocrine factor supporting Schwann cell survival and differentiation and stimulating axon regeneration and myelination. NT-3 is involved in the maintenance of neuromuscular junction (NMJ) integrity, restoration of impaired radial growth of muscle fibers through activation of the Akt/mTOR pathway. In this new study, researchers Burcak Ozes, Lingying Tong, Morgan Myers, Kyle Moss, Alicia Ridgley, and Zarife Sahenk from Nationwide Children's Hospital and The Ohio State University used a triple muscle-specific creatine kinase (tMCK) promoter to restrict NT-3 expression to the skeletal muscle and self-complimentary adeno-associated virus serotype 1 (scAAV1) as vector to assess the therapeutic efficacy of AAV1.NT-3 in wild type-aged C57BL/6J mice, a model for natural aging and sarcopenia. “Quantitative histopathologic parameters served to address age-related changes in muscle, peripheral nerve and NMJ.” The treatment efficacy was assessed at 6 months post-injection using run to exhaustion and rotarod tests, in vivo muscle contractility assay, and histopathological studies of the peripheral nervous system, including NMJ connectivity and muscle. AAV1.NT-3 gene therapy in WT-aged C57BL/6 mice resulted in functional and in vivo muscle physiology improvements, supported by quantitative histology from muscle, peripheral nerves and NMJ. Hindlimb and forelimb muscles in the untreated cohort showed the presence of a muscle- and sex-dependent remodeling and fiber size decrease with aging, which was normalized toward values obtained from 10 months old WT mice with treatment. The molecular studies assessing the NT-3 effect on the oxidative state of distal hindlimb muscles, accompanied by western blot analyses for mTORC1 activation were in accordance with the histological findings. “When considering the burden of sarcopenia on the lifestyle of elderly, and on the healthcare system, we believe this preclinical study is providing strong support for AAV.NT-3 gene therapy in the successful management of sarcopenia, as a serious and plausible option in the future.” DOI: https://doi.org/10.18632/aging.204577 Corresponding Author: Zarife Sahenk - zarife.sahenk@nationwidechildrens.org Keywords: sarcopenia, gene therapy, aging, NT-3, muscle remodeling Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204577 About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.01.530693v1?rss=1 Authors: Shi, Y., Sun, S., Li, J., Wang, S., Yu, Y., Guo, K., Yang, J., Han, L., Wei, W., Qiu, J. Abstract: Introduction: Understanding the cellular composition and trajectory of human tooth development is valuable for dentistry and stem cell engineering research. Previous single-cell studies have focused on mature human tooth and developing mice tooth, but cell landscape on human embryonic dental development is still lacking. Objective: We aimed to construct the spatiotemporal cell atlas of aborted fetus tooth germ. Methods: We collected tooth germ tissues from aborted fetus (17-24 week) for single cell RNA sequence and spatial transcriptome. Subsequent clustering, spatial projection, pseudotime, gene regulation network, pathway enrichment and signaling network analysis were applied to reveal the cellular composition as well as its biological significance. Results: We classified all cells into seven subclusters of epithelium, seven clusters of mesenchyme and other cell types like Schwann cell precursor and pericyte. For epithelium, the matrix cell-striatum intermedium branch and the ameloblast branch diverged from a same set of KRT15+-HOPX+-ALCAM+ epithelial stem cell lineage, but the spatial distribution of two branches were not clearly distinct. This trajectory received spatially adjacent regulation signals from mesenchyme and pericyte, including JAG1 and APP. The differentiation of pulp cell and pre-odontoblast showed four waves of temporally distinct gene expression, which involved regulation networks of LHX9, DLX5 and SP7 and were regulated by upstream ligands like BMP family. Conclusion: We provided a reference landscape for the research on human early tooth development, covering different spatial structures and developmental periods. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Jason read an article by Tom Silverstein in the Milwaukee Journal Sentinel, and he thought "Spoon" and Tausch were on the same page about something Brian Gutekunst said in Indianapolis. Wilde & Tausch Trivia, including reminiscing on yesterday's tough performance. And Homer joins for his weekly appearance one day after Marquette clinched its first Big East regular season championship ever...and he claims he's not talking about Aaron Rodgers until there's actual news?
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.27.530298v1?rss=1 Authors: Grove, M., Kim, H., Pang, S., Amaya, J. P., Hu, G., Zhou, J., Lemay, M., Son, Y.-J. Abstract: The hippo pathway transcriptional effectors, YAP/TAZ, are crucial for Schwann cells (SCs) to myelinate axons but the mechanisms are poorly defined. Although TEAD1 has been implicated as a partner transcription factor, how it supports the transcriptional regulation of myelination and which aspects of the process it affects are unknown. Here, using conditional and inducible knockout mice, we report that TEAD1 is essential for SCs to develop, grow, and regenerate myelin sheaths. TEAD1/2/3/4 are present in SCs, but YAP/TAZ strongly favors TEAD1. It promotes myelination by positively and negatively regulating SC proliferation, enabling Krox20/Egr2 to upregulate myelin proteins, and upregulating the cholesterol biosynthetic enzymes FDPS and IDI1. We also show stage-dependent redundancy of TEAD1 and that non-myelinating SCs have a unique requirement for TEAD1 to enwrap nociceptive axons in Remak bundles. Our findings establish TEAD1 as a crucial partner of YAP/TAZ in developmental myelination and functional nerve regeneration and as a novel transcription factor regulating Remak bundle integrity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.24.525436v1?rss=1 Authors: Vasilijic, S., Atai, N., Hyakusoku, H., Worthington, S., Ren, Y., Sagers, J. E., Sahin, M. I., Fujita, T., Landegger, L. D., Lewis, R., Welling, B. D., Stankovic, K. M. Abstract: Vestibular schwannoma (VS) is intracranial tumor arising from neoplastic Schwann cells, causing hearing loss in about 95% of patients. The traditional belief that hearing deficit is caused by physical expansion of the VS, compressing the auditory nerve, does not explain the common clinical finding that patients with small tumors can have profound hearing loss, suggesting that tumor-secreted factors could influence hearing ability in VS patients. Here, we conducted profiling of patients plasma for 67 immune-related factors on a large cohort of VS patients (N greater than 120) and identified candidate biomarkers associated with tumor growth (IL-16 and S100B) and hearing (MDC). We identified the 7-biomarker panel composed of MCP-3, BLC, S100B, FGF-2, MMP-14, eotaxin, and TWEAK that showed outstanding discriminatory ability for VS. These findings revealed possible therapeutic targets for VS-induced hearing loss and provided a unique diagnostic tool that may predict hearing change and tumor growth in VS patients and may help inform the ideal timing of tumor resection to preserve hearing. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.05.522786v1?rss=1 Authors: Walker, L. J., Guevara, C., Kawakami, K., Granato, M. Abstract: A critical step for functional recovery from peripheral nerve injury is for regenerating axons to connect with their pre-injury targets. Reestablishing pre-injury target specificity is particularly challenging for limb-innervating axons as they encounter a plexus, a network where peripheral nerves converge, axons from different nerves intermingle, and then re-sort into target-specific bundles. Here, we examine this process at a plexus located at the base of the zebrafish pectoral fin, equivalent to tetrapod forelimbs. Using live cell imaging and sparse axon labeling, we find that regenerating motor axons from three nerves coalesce into the plexus. There, they intermingle and sort into distinct branches, and then navigate to their original muscle domains with high fidelity that restores functionality. We demonstrate that this regeneration process includes selective retraction of mistargeted axons, suggesting active correction mechanisms. Moreover, we find that Schwann cells are enriched and associate with axons at the plexus, and that Schwann cell ablation during regeneration causes profound axonal mistargeting. Our data provide the first real time account of regenerating vertebrate motor axons navigating a nerve plexus and reveal a previously unappreciated role for Schwann cells to promote axon sorting at a plexus during regeneration. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.14.520389v1?rss=1 Authors: Catasus, N., Torres-Martin, M., Negro, A., Kuebler, B., Rosas, I., Casals, G., Mazuelas, H., Roca-Ribas, F., Amilibia, E., Aran, B., Veiga, A., Raya, A., Gel Moreno, B., Blanco, I., Serra, E., Carrio, M., CASTELLANOS, E. Abstract: Background: The appearance of bilateral vestibular schwannomas (VS) is one of the most characteristic features of NF2-related schwannomatosis (NF2-related SWN), an autosomal dominant syndrome that predisposes to the development of tumours of the nervous system. VS are caused by the bi-allelic inactivation of the NF2 gene in a cell of the Schwann cell lineage. Our current understanding of VS initiation and progression as well as the development of new effective therapies is hampered by the absence of human non-perishable cell-based models. Principal Findings: We generated and characterized induced pluripotent stem cell (iPSC) lines with single or bi-allelic inactivation of NF2 by combining the direct reprogramming of VS cells with the use of CRISPR/Cas9 editing. Despite the difficulty of maintaining merlin-deficient iPSCs, we were able to differentiate them into neural crest (NC) cells. At this stage, these cells showed spontaneous expression of the SC marker S100B and the impossibility of generating Schwann cells in 2D cultures. Nevertheless, by applying a 3D Schwann cell differentiation protocol, we successfully generated NF2(+/-) and NF2(-/-) spheroids homogeneously expressing classical markers of the NC-SC axis. Conclusions: Our results show a critical function of NF2 for both reprograming and maintaining a stable pluripotent state. In addition, merlin-deficient cultures also denoted an altered differentiation capacity of merlin-deficient cells towards the NC-SC axis, in the in vitro conditions used. Finally, the generated NF2(+/-) and NF2(-/-) spheroids show potential as a genuine in vitro model of NF2-related tumours. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.12.517822v1?rss=1 Authors: Carnicer-Lombarte, A., Barone, D. G., Fawcett, J., Franze, K. Abstract: Spinal cord injuries have devastating consequences for humans, as mammalian neurons of the central nervous system (CNS) cannot regenerate. In the peripheral nervous system (PNS), however, neurons may regenerate to restore lost function following injury. While mammalian CNS tissue softens after injury, how PNS tissue mechanics changes in response to mechanical trauma is currently poorly understood. Here we characterised mechanical rat nerve tissue properties before and after in vivo crush and transection injuries using atomic force microscopy-based indentation measurements. Unlike CNS tissue, PNS tissue significantly stiffened after both types of tissue damage, likely mainly due to an increase in collagen I levels. Schwann cells, which crucially support PNS regeneration, became more motile and proliferative on stiffer substrates in vitro, suggesting that changes in tissue stiffness may play a key role in facilitating or impeding nervous system regeneration. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.08.519209v1?rss=1 Authors: Fazal, S. V., Mutschler, C., Chen, C., Turmaine, M., Chen, C.-Y., Hsueh, Y.-P., Loreto, A., Casillas-Bajo, A., Cabedo, H., Franklin, R. J., Barker, R. A., Monk, K., Steventon, B., Coleman, M., Gomez-Sanchez, J. A., Arthur-Farraj, P. Abstract: SARM1 is a central regulator of programmed axon death and is required to initiate axon self-destruction after traumatic and toxic insults to the nervous system. Abnormal activation of this axon degeneration pathway is increasingly recognized as a contributor to human neurological disease and SARM1 knockdown or inhibition has become an attractive therapeutic strategy to preserve axon loss in a variety of disorders of the peripheral and central nervous system. Despite this, it remains unknown whether Sarm1/SARM1 is present in myelinating glia and whether it plays a role in myelination in the PNS or CNS. It is important to answer these questions to understand whether future therapies inhibiting SARM1 function may have unintended deleterious impacts on myelination. Here we show that Sarm1 mRNA is present in oligodendrocytes in zebrafish but only detectable at low levels in Schwann cells in both zebrafish and mice. We find SARM1 protein is readily detectable in murine oligodendrocytes in vitro and in vivo and activation of endogenous SARM1 in oligodendrocytes induces cell death. In contrast, SARM1 protein is not detectable in Schwann cells and satellite glia in the adult murine nervous system. Cultured Schwann cells contain negligible functional SARM1 and are insensitive to specific SARM1 activators. Using zebrafish and mouse Sarm1 mutants, we show that SARM1 is not required for initiation of myelination nor myelin sheath maintenance by oligodendrocytes and Schwann cells. Thus, strategies to inhibit SARM1 function in the nervous system to treat neurological disease are unlikely to perturb myelination in humans. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.07.519441v1?rss=1 Authors: Fuentes-Flores, A., Geronimo-Olvera, C., Necunir-Ibarra, D. S., Patel, S. K., Bons, J., Wright, M. C., Geschwind, D., Höke, A., Gomez-Sanchez, J. A., Schilling, B., Campisi, J., Court, F. A. Abstract: After peripheral nerve injuries, successful axonal growth and functional recovery requires the reprogramming of Schwann cells into a reparative phenotype, a process dependent on the activation of the transcription factor c-Jun. Nevertheless, axonal regeneration is greatly impaired in aged organisms or after chronic denervation leading to important clinical problems. This regenerative failure has been associated to a diminished c-Jun expression by Schwann cells, but whether the inability of these cells to maintain a repair state is associated to the transition into a phenotype inhibitory for axonal growth, has not been evaluated so far. We find that repair Schwann cells transitions into a senescent phenotype, characterized by diminished c-Jun expression and secretion of factor inhibitory for axonal regeneration in both aging and chronic denervation. In both conditions, elimination of senescent Schwann cells by systemic senolytic drug treatment or genetic targeting improves nerve regeneration and functional recovery in aging and chronic denervation, associated with an upregulation of c-Jun expression and a decrease in nerve inflammation. This work provides the first characterization of senescent Schwann cells and their impact over axonal regeneration in aging and chronic denervation, opening new avenues for enhancing regeneration, and functional recovery after peripheral nerve injuries. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
My guest today is a true savage, and the definition of a renaissance man. Not only does Tommy Schwann run the regional division of Cardinal Financial, but he owns and manages 30 rental properties, he owns a ticket broker busines, he invests in a sports medicine company, and he's been involved in countless other businesses over the years. This is one of the most riveting episodes we've had, so you don't wanna miss it. --- Send in a voice message: https://anchor.fm/charles-weinraub/message
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.31.514415v1?rss=1 Authors: Kantarci, H., Elvira, P. D., Thottumkara, A. P., Iyer, M., Donovan, L. J., Ambiel, N., OConnell, E. M., Granados, A., Zeng, H., Saw, N. L., Lutz, A. B., Sloan, S. A., Gray, E. E., Tran, K. V., Vichare, A., Yeh, A. K., Munch, A. E., Huber, M., Agrawal, A., Morri, M., Shamloo, M., Tawfik, V. L., Du Bois, J., Zuchero, J. B. Abstract: Excitability, the ability to fire action potentials, is a signature feature of neurons. How neurons become excitable during development, and whether excitability is an intrinsic property of neurons or requires signaling from glial cells, remain unclear. Here we demonstrate that Schwann cells, the most abundant glia in the peripheral nervous system, promote somatosensory neuron excitability during development. We find that Schwann cells secrete prostaglandin E2, which is necessary and sufficient to induce somatosensory neurons to express normal levels of voltage-gated sodium channels and fire action potential trains. Inactivating this signaling pathway specifically in Schwann cells selectively impairs nociceptor and proprioceptor somatosensory neuron subtypes, leading to corresponding sensory defects in thermoception, inflammatory pain, and proprioception. Our studies thus reveal a cell non-autonomous mechanism by which glia regulate neuronal excitability to enable the development of normal sensory functions. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.28.514178v1?rss=1 Authors: Jiravejchakul, N., Abe, G. L., Loza, M., Park, S., Matangkasombut, P., Sasaki, J.-I., Imazato, S., Diez, D., Standley, D. M. Abstract: In-depth knowledge of the cellular and molecular composition of dental pulp (DP) and the crosstalk between DP cells that drive tissue homeostasis or regeneration are not well understood. To address these questions, we performed data analysis of publicly available single-cell transcriptomes of DP. This analysis revealed that DP resident fibroblasts have a unique gene expression profile when compared with fibroblasts from 5 other reference tissues: blood, bone marrow, adipose tissue, lung, and skin. Genes coded for heparin-binding growth-factors, pleiotrophin (PTN) and midkine (MDK), possessed the highest differential expression levels in DP fibroblasts. In addition, we identified extensive crosstalk between DP fibroblasts and several other DP cells, including Schwann cells, MSCs and odontoblasts. These findings suggest that fibroblast-derived growth factors regulate DP niches, and thus have a potential role as dental therapeutic targets. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
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Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.25.509350v1?rss=1 Authors: Daboussi, L., Costaguta, G., Gullo, M., Pessino, V., O'Leary, B., Lettieri, K., Driscoll, S., Pfaff, S. L. Abstract: Schwann cells respond to acute axon damage by transiently transdifferentiating into specialized repair cells that restore sensorimotor function. However, the molecular systems controlling repair cell formation and function are not well defined and consequently it is unclear whether this form of cellular plasticity has a role in peripheral neuropathies. Here we identify Mitf as a transcriptional sensor of axon damage under the control of Nrg-ErbB-PI3K-PI5K-mTorc2 signaling. Mitf regulates a core transcriptional program for generating functional repair Schwann cells following injury and during peripheral neuropathies caused by CMT4J and CMT4D. In the absence of Mitf, core genes for epithelial-to-mesenchymal transition, metabolism and dedifferentiation are misexpressed and nerve repair is disrupted. Taken together, our findings demonstrate that Schwann cells monitor axonal health using a phosphoinositide signaling system that controls Mitf, which is critical for activating cellular plasticity and counteracting neural disease. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.08.25.505298v1?rss=1 Authors: Willows, J. W., Gunsch, G., Paradi, E., Blaszkiewicz, M., Tonniges, J. R., Pino, M. F., Smith, S. R., Sparks, L. M., Townsend, K. L. Abstract: Peripheral neuropathy is a pathophysiological state of nerve degeneration and loss of tissue innervation. The most prominent cause of small fiber neuropathy is diabetes which can be demyelinating in nature, but this has not yet been explored in adipose tissue. Both demyelinating neuropathies and axonopathies implicate Schwann cells (SCs), the peripheral glial required for nerve myelination and regeneration after injury. Here, we perform a comprehensive assessment of SCs and myelination patterns of subcutaneous white adipose tissue (scWAT) nerves, including changes that occur with obesity and other imbalanced energy states in mice and humans. We found that mouse scWAT is densely innervated by both myelinated and unmyelinated sensory and sympathetic nerves. Accordingly, scWAT is home to both myelinating and non-myelinating SCs; the greater proportion of which are myelinating. Furthermore, SCs were found closely associated with synaptic vesicle-containing nerve terminals in scWAT. Obese BTBR ob/ob mice exhibit diabetic peripheral neuropathy in scWAT, and display concordant demyelination specific to small fibers, which was also associated with a decrease in the pan-SC marker Sox10 and compensatory increase in Krox20 gene expression. Together this suggests that adipose SCs may be involved in regulating the plasticity or the neuropathy of adipose tissue nerves. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer
A new research paper was published in Oncotarget on July 19, 2022, entitled, “CUDC907, a dual phosphoinositide-3 kinase/histone deacetylase inhibitor, promotes apoptosis of NF2 Schwannoma cells.” Neurofibromatosis Type 2 (NF2) is a rare tumor disorder caused by pathogenic variants of the merlin tumor suppressor encoded by NF2. Patients develop vestibular schwannomas (VS), peripheral schwannomas, meningiomas, and ependymomas. There are no approved drug therapies for NF2. Previous work identified phosphoinositide-3 kinase (PI3K) as a druggable target. Researchers Julianne Huegel, Christine T. Dinh, Maria Martinelli, Olena Bracho, Rosa Rosario, Haley Hardin, Michael Estivill, Anthony Griswold, Sakir Gultekin, Xue-Zhong Liu, and Cristina Fernandez-Valle, from the University of Central Florida and the University of Miami Miller School of Medicine, conducted an unbiased chemical compound screen of the Library of Pharmacologically Active Compounds (LOPAC) as a pilot high-throughput screen to identify NF2 schwannoma targets for inhibition. “Here we screened PI3K pathway inhibitors for efficacy in reducing viability of human schwannoma cells.” The lead compound, CUDC907, a dual histone deacetylase (HDAC)/PI3K inhibitor, was further evaluated for its effects on isolated and nerve-grafted schwannoma model cells, and primary VS cells. CUDC907 (3 nM IG50) reduced human merlin deficient Schwann cell (MD-SC) viability and was 5–100 fold selective for MD over WT-SCs. CUDC907 (10 nM) promoted cell cycle arrest and caspase-3/7 activation within 24 hours in human MD-SCs. Western blots confirmed a dose-dependent increase in acetylated lysine and decreases in pAKT and YAP. In a 14-day treatment regimen, CUDC907 decreased tumor growth rate by 44%, modulated phospho-target levels, and decreased YAP levels. In five primary VS, CUDC907 decreased viability, induced caspase-3/7 cleavage, and reduced YAP levels. Its efficacy correlated with basal phospho-HDAC2 levels. CUDC907 has cytotoxic activity in NF2 schwannoma models and primary VS cells and is a candidate for clinical trials. “In summary, we demonstrated that CUDC907 reduced the activity of three major signaling pathways in NF2 schwannomas (HDAC, PI3K, and YAP) and consistently reduced viability and induced apoptosis in several schwannoma cell models and in all five genetically unique primary VS studied. These consistent results offer the possibility that CUDC907 will promote schwannoma regression in patients with diverse NF2 mutations and support clinical evaluation of CUDC907 for NF2-associated schwannomas and potentially other cancers driven by NF2 pathogenic variants [45]. Current use of this drug in clinical trials for other indications reveals clinical interest in multi-modal drugs over monotherapies.” DOI: https://doi.org/10.18632/oncotarget.28254 Correspondence to: Cristina Fernandez-Valle – Email: cfv@ucf.edu Keywords: fimepinostat, Schwann cell, vestibular schwanomma, merlin, nerve allograft About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.
In this episode of the Lexman Artificial Podcast, we discuss the consistory, Schwann cells, asyndetons, and heterostyly. Simon Sinek, founder and CEO of The4Hs, joins us to discuss how these simple structures protect our cells and how they can be improved to better serve the organism.
(09-15-2017) - Ralph Holguin joined Randy from his garage in Long Beach, Ca. and talked about cars he grew up in, his fascination with classic Schwann "Sting Ray" bikes like the "Apple Crate" and his classic builds and TV shows....and the unusual name his family gave one of his parents' cars.
Intro: Boz's brain hurts, Ozark, the ordinariness of crime, drug running in Tijuana, Molly, Jerry Harris and Season 2 of Cheer, unpleasant surprisesLet Me Run This By You: I didn't do anything wrong.Interview: We talk to Carolyn Hoerdemann about Steppenwolf's From The Page to The Stage, John C. Reilly, tenacity, hyper-empaths, Oscar Wilde's fairy tales, Tarrell Alvin McCraney, feminist theatre, Pump Boys and Dinettes, Faith Wilding, Rob Chambers' Bagdad Cafe, Ominous Clam, Zak Orth, Good Person of Szechwan, European Repertory's production of Agamemnon, Danny Mastrogiorgio, Michael Moore's Roger & Me, Chicago Shakespeare Theater, the anti-memoir memoir, and Ann Dowd.FULL TRANSCRIPT (unedited):1 (8s):And Jen Bosworth from me this and I'm Gina Polizzi. We went to theater school together. We survived it, but we didn't quite understand it. 20 years later, we're digging deep talking to our guests about their experiences and trying to make sense of it all. We survived theater school and you will too. Are we famous yet? I have a place to go to do with, it's not my one bedroom with my dog and my husband, but it's still a lot of work, like an and so, and then on top of that, I mean, I just feel like literally, you know what, I texted you yesterday and you said you knew the feeling like my brain is hurting me, but not in a bad way.1 (50s):I don't have a headache. Like I don't, I just was, you know, telling our couple surface, like, I feel like I can literally hear my brain turning and growing and groaning and like working. I've never had that feeling before in my life, which is weird. But like that, that feeling of, oh, I'm doing or knowing that what it was, what it was like, I'm doing a lot of work, you know, like my brain is doing so ridiculous, but that's how I feel, but it's all like, it, it doesn't feel, you know, what it is. I'm used to doing a lot of physical work.1 (1m 32s):Like I'm used to my body doing a lot of work. Like whether it's, you know, like the jobs I've had, like even the jobs that I, when I was a therapist account, you know, a counselor at social services, like I spent a lot of my time, like moving cases of diet Coke and cause we were in like a halfway house. So like I did a lot of manual labor and lot and case management and case management management is a lot of manual labor, like taking clients to appointments. And like, so when using my brain now in this different way, like literally I wished I would have been a camera on me when I was redoing my resume and cover letter specifically for the ad industry, because it is like making something out of nothing and also using words to like basically, you know, trick people, not trick people, but you know, get them to think what you want them to think.1 (2m 27s):And you think, oh, well she's, you know, television writing. The thing about that is like, you can make up anything like television writing really. You can really say, and then pigs flew out of his asshole and then people are like, oh, that's a weird show. But when you're trying to sell yourself to a particular industry with a particular set of skills, trying to make your skills meld into the skills they want, I was like, I couldn't see. After a while I was like, I don't even know what this, like using words like in this space, you leave space is a big word now.2 (2m 59s):So Metta that you are selling yourself to an advertising1 (3m 8s):Up girl.2 (3m 10s):So the PR how I understand it is there is somebody affiliated with this that is an advocate of yours, a champion of yours. And she wants, she wants you in that industry.1 (3m 23s):Okay. Yes, you are understanding. And there's like multiple things here. So she's, she's a screenwriter that I met and she continued on with the master's program. But her big job is her. Her day job is she's like a creative director at an ad agency in the, in the copy department. Right? So she's a big wig and she edits, she's like, she's the big editor there right at this. And I guess they hop around from agency to agency. Look, I don't know how it works, but so she started this new job and she's like, I want you to come work in the copyright. She also gets a very large bonus for every person that comes on that she refers, which I good look, do what you need to do.1 (4m 6s):But I think it's like five grand per person that she brings. I that's what I'm led to believe from the website. So anyway, there's like a, and so she literally Gina. So I sent her my updated resume and cover letter letter looked great. And then she applied me for 30 jobs. So then I have two.2 (4m 27s):Wow.1 (4m 29s):So which sounds great, which is awesome. Copywriting, all different kinds of copywriting. But for each of those jobs, I have to fill out demographic form. So last night I literally was up after myself tapes one self-tape last night clicking. I am not a veteran. Yes, I am Latina. No, I'm not disabled2 (4m 53s):Online. I was going to say, why don't they have one form, but it's1 (4m 58s):Yeah. It's a different job number. Right? So like every time, oh my God. So then, and sign, you have to sign every, so I literally was like, by the time I went to that, my brain, I was like, what? I'm not a veteran. I'm not a veteran like that. I was like mumbling to myself. And so, so, but I have to say like, you know, it's a good skill to build for. Like, I think that thing about, we only use 5% of our brain. They they've like debunked that right. They've said like that. You can't, but I'm telling you my brain, just like the Grinch's heart grew three sizes that day. My brain is like literally growing three side.1 (5m 41s):I don't know if it's three sizes, but it's, I can feel my, my, my like pathways changing in terms of the skills that I'm using. So that's great. You know,2 (5m 51s):I don't know. I mean, it can't be bad. Nothing. The good news is all of this work you're doing can't lead to anything bad to something. Yeah. Not illegal, You know, honestly, it's really saying something. I finally started watching Ozark. Oh God. And I, what strikes me about it is like, oh, this is not, it's not that this could happen to anybody, but you just think about like how ordinary crime really can be, you know, and how criminals aren't all in a layer or living in a way it's just, it's just moms and dads and, and people who need it, who need money in and who needs to run around and get it right quick.2 (6m 40s):Yeah. And I don't know, I will, I'm only one, not even the full first season in, so there may be a lot of stuff that I don't know, but like, it seems to me that this Jason Bateman guy was just a regular guy who got kind of wrapped up in this criminal enterprise1 (6m 58s):Didn't happen. You, I can see like most of my clients that I saw like were knowingly doing, you know, they were like, oh, I'm going to be a drug dealer and a gang member now. And no, but there were occasionally people that got involved in like scams, you know, financial fraud that you could see how it would start off and, and, and case in point miles. And I have a friend, an older guy, friend, we won't name because this is so illegal was like, Hey, what are you guys doing over Christmas break? And we're like, we're going, doing whatever. And he's like, Hey, do you want to, I shit, you not do you, if you'd let me know if you want to make some money, driving a camper from here to Tijuana.1 (7m 41s):And I, why like, what are you talking about? He's like, yeah, we'll give you like each $5,000 of it. And I said, well, what do you mean? Why do you need the, the, the, the camper and Tijuana? And he was like, oh, there's drugs in it. There's marijuana. And I was like, no. And miles was like, absolutely not. I'm like, have you met miles? Are you boy?2 (8m 3s):Oh, not, not marijuana, I guess,1 (8m 5s):Because it's marijuana. I don't, I don't2 (8m 7s):Think it's legal. Why do they have to do1 (8m 9s):That? I don't know. I think it was like a mass quantity or something like that. I don't know. Like, you're not allowed to like traffic, like large amounts of marijuana from different countries to over the border. Like, but so, especially in Mexico, like what? So I don't know. And we were like, Myles was like, absolutely not. I mean, miles is a lawyer. Like, what are you talking about?2 (8m 34s):Well, it's funny how just one casual aside a reference can really change your whole perspective on somebody you've known for a long time. Like I thought I've been in that situation before, you know, you think, you know, somebody and then they just casually say like, well, you know, we're swingers or1 (8m 55s):The other, the other, the other day I was meeting with somebody. Totally. And this actually didn't make me think less of him, but it was just like, he's like a totally looks like a total straight laced guy. If you're going to look at him, you know, white dude, thirties, balding, whatever. And he's like, yeah, I met him like the first time I, he was talking and he was like, oh yeah, the first time we met, we did Molly. And I was like, wait, what? At first I thought, Tina that's crystal meth. And I thought, but that wasn't, that it's Molly is whatever, HBM,2 (9m 25s):Whatever,1 (9m 26s):MTMA Molly. And I, like, I was so weird and we're like old people, what is happening? It's sitting in a cafe and you're talking about Molly. I don't know. I just it's, it totally rocked my world, which is, I think why I like to write too is because I do like to write those things in where you're like, wait, what? You know? Like, like,2 (9m 53s):Yeah, I have to say just, just the thought of learning, something like that, about somebody that I know is scary to me. And it, it just made me remember that I, after you mentioned season two of cheer, I started watching it. And I forgotten about the whole thing about that guy, Jerry Harris. And it was so heartbreaking to me when that happened. Not that it's worse or better if the person is well-known, it's just, you know, he, he seemed like a person who has such a hard life and it seemed like he was finally getting some, you know, something that he really deserved.2 (10m 38s):And then, and of course, I understand that when I hurt that hurt people, hurt people. And that he was probably doing this because this has been done to him. I don't know, man, I don't, these are surprises. I don't care for, I wanted it to stand for the rug and like for these kids to go on and being abused, that's not it at all. It's just, it's so disheartening. Well, it's really1 (11m 5s):It's. So there is, so yeah, it goes beyond grief. It's like goes beyond disappointment. It's like grief. And it's also, I think for me anyway, and I don't know about for you recreates the feeling of which is what I felt all the time with my parents, which is, oh, I know these people. I can trust these people. Oh God, I'm not safe around these2 (11m 30s):People. Okay. Thank you. That's exactly what it is.1 (11m 33s):I have that experience in Los Angeles, 40 times a day. Right. We're like, I want to like someone and then they'll say some fucking shit. And you're like, okay, well this is, you're a psychopath. Okay. Right. Like I'm talking to this. There's like, I meet them all the time at co-working because you know, co-working attracts like everybody, you just have to have money to have an office here. It's not like they, you know, vet people and some I'll be having a conversation with someone who seems relatively normal. And then they'll be like, oh yeah. You know, I was like, I really admire this Japanese porn star that like really knew what she wanted in life.1 (12m 13s):And it's not that there's anything wrong with being a Japanese porn star. It's that this guy like casually dropping, you know, and then talking about the kind of porn she does in a coworking setting. I I'm like, dude, I gotta go. I gotta make a fucking resume over here. Like I don't need to, but it's it's that in with him. It's just, I was just more like, oh, you're that you're going to bring this up to a stranger. Then I'm getting better about like, what's safe and not safe. But I do think that when you invest in something like Jerry or the cheer or a parent, and then they fucking do some shit, you're like, oh great. I'm not safe with you. That's,2 (12m 50s):It's what it is. It makes the feeling of own. And then, because I tend towards misanthropy, I'm like, okay, nobody's say if you can't trust anybody, everybody's out to get you, which is not true either. But it becomes, that is my defensive posture that I immediately tack back to, you know, I could go away thinking like, oh, there's goodness in the world. And some people and humans are inherently good. And then boom, something happens and I fail. And instead of, and I don't do the opposite when somebody does something good. I don't say yes, it's P you know what I mean? I don't, I don't have the same positive connotation that when somebody does something bad, it makes me say everybody's terrible.1 (13m 34s):It's really interesting because I'm having the experience of having to, what is it? So having to have a little more caution with people, I tend to really, really, really love everybody at first. Like really like I'm like, that person is awesome, but then they start talking crazy shit. And in the past I would have dismissed it and been like, no, I'm just sensitive. Right. Or I'm just so I'm trying now to be like, no, I wasn't there. When I was in therapy yesterday, I was like, no, no. Like in that moment I felt like this is not good for me.1 (14m 16s):And if I am not going to stand up for myself and take care of myself, nobody else is. So I have to mix a little more of the caution in with my, what can be Pollyanna kind of stuff. I have to be mindful of what my instincts are telling me about somebody, because I then will end up, you know, talking about very explicit Japanese porn techniques for half an hour and then walk away feeling violated and fucked up.2 (14m 49s):Yeah, yeah, yeah. Yeah. You know, I knew this. I ha I know somebody who's exceedingly reserved. She doesn't, I like her I'm we're friends, but she doesn't tell you anything about herself. Like, or it takes a long time. And it's just this little snip, like, as an example, I don't know how old she is. And I bring up my age all the time and I, and I think she's younger than I am, but somebody recently said, oh, actually I don't think she's. I think she's more like your age, but that's, but she's never chimed in whenever I've said anything about how old I am.2 (15m 31s):She, she, she won't tell she's, she's a mystery. And on the one hand, I think, oh, she's just, she's just protecting herself for the reason that you just said. I mean, you know, she, she knows me kind of, but it's not like she really, really knows me. Some people really wait until some people don't just give out their confidence to anybody for some people you really, and I, you know, I guess like good for her. Maybe that's the way to go. I don't know. I, I tend to be more like you, not that I love everybody, but that I assume, I assume everybody has good intentions.2 (16m 13s):And, and then it's very surprising and sad and shocking to me when they don't like the thing that happened to me last week, this fricking guy, I was at the, I was picking my son up from tennis and where I've been, where I've been. Yes. And the place has bad vibes. I, I w I don't like the place. The parking is annoying, but yeah, the parking is annoying anyway. So you're, you're not supposed to wait by the curb. The parents aren't supposed to wait by the curb and align for their kids to come out, but everybody does. Right. It's just how it goes. Cause there's nowhere to go. Right. And it's, and it's been really icy here. So even sometimes I will park whatever, but this time I'm thinking, well, it's really icy.2 (16m 57s):And I just don't want him to, it's not lit up really in the parking lot. I just don't want him to fall. So I'm waiting in line and the guy in the car behind me hunks, and I, I assume he's not honking at me. Why would he behind me? Me? I'm just, my car is just sitting there honks again. Hong's a third time. And I put my arm out, like, go, go around. I just thought maybe he didn't think he could go around me. I still honking. So I just kind of opened the door a little bit. I look behind me and I'm like, what's the deal? And he's just yelling something. So I think, okay, whatever, I'll just loop around, pull over, go through the parking lot, turn to come back. And the guy I had the right of way.2 (17m 39s):And he just zoomed in, in front of me made so that I had to slam on the same guy. So I had to slam on my brakes, but then he gets out of the car and walks up, walks over to me. Of course, I lock my doors and he's like just screaming obscenities at me. Now later on, I had the thought this of course had nothing to do with me. Of course, this is how, you know, I didn't do anything wrong. This is about a person who really wanted to kick the dog. And he found that he found somebody to, to do that with absolutely. But I tend to go through my life in kind of this bubble of like, everybody's got everybody's well-intended and maybe even he was well-intended it just, it just didn't come across in the, in this experience.2 (18m 30s):And1 (18m 32s):Did he walk away?2 (18m 34s):I said, get the fuck away from me. Get the fuck away from me. By the way, my dog was in the back of my dog, who barks at literally every leaf like Wallace.1 (18m 54s):What kind of wing man are you? You fucker anyway. Okay. Yeah. I mean, I think those experiences are very particularly about driving and cars and obviously there's a whole road rage. Like there's literally a television show about road rage, right? Like the truth really? Oh my God. Yeah. It's a horrible it's so triggering. Don't watch it, but okay. I mean, yeah, it's ridiculous. But that being said it's very, to me, what happens to me in that situation? I'm sorry, that happened to you is yeah. Like what you mentioned on social media, which is feeling completely powerless and like, it's scary.1 (19m 38s):It's out of control. It's traumatizing. It's I, it's not good. It's not good. And it is also to me that what the feeling is being ambushed, right? Like you're being ambushed by, by a fucking crazy ass and you didn't do anything wrong. See, the thing is, I get into this thing of like, I didn't do anything wrong. And again, if I can get to the core of it, which is as a kid, I literally didn't do anything wrong. And all this shit rained down upon me, this trauma and this and this in this bullying and this whatever. And it triggers that in me. Like, wait a minute.1 (20m 19s):I, all I'm trying to do is do good, protect my son, pick up my thing, do this merge into the fucking freeway. It doesn't matter. And then I get like, this is not fair. Like I get really hurt is what it is. I get hurt. I'm shocked and hurt. And then the person, there is no, there is no resolution, right? Like the guy doesn't then call you later and say, I'm so sorry I acted a Dick. Or you can't even call the police and be like, this guy acted like a Dick. We're like, they're like, well, did he threaten you? No. Did he? Then they're like, fuck yourself.2 (21m 5s):Right. To say that it's, it is linked to, you know, growing up in a dysfunctional family. I'm for myself, looking a little bit more deeply into that. And because I, and I'm not saying this is the case for you, but for me, I think that I have said that I think that I have convinced myself that I'm never doing anything wrong, you know? And, and not just say that I was doing something necessarily wrong in the situation with the sky, although actually, you know, if I could have crafted it better, I would have paid attention to the flag from really from the first time they honk, which is like, there's something wrong with this person.2 (21m 51s):Do you know what I mean? Like, and yes,1 (21m 55s):Like get away, let me remove2 (21m 57s):My instinct. My instinct is to want to fight back. In fact, I remember this time that the some concert or something like that with Aaron, it was early in our relationship. So I was in my early twenties and this guy kept whatever. He kept stepping too close to me something. And I, I pushed him and pushed him. He, and of course, what did he do? He looked at Aaron like, are you gonna like, don't do that to me. I don't want to, you know, and it's, but it's not fair. He's encroaching on my space. He's like fair. Who, who told you the thing that we're going to be fair? Like it's, you know, so I guess that's the thing is I sometimes go out in the world thinking like, I'm an, a student and therefore, you know, nothing.2 (22m 42s):I don't, I shouldn't be getting any demerits. And if I get into merit, it's not my fault. I do that a lot.1 (22m 50s):I have the same thing. Yeah. I mean, I, I do it where it's like, I, yeah, I have my version of that is like, I'm a nice person. Like I do good. I'm nice. How dare you do bad or do wrong or treat me bad. Yeah. I mean, he it's, all this stuff is so layered. And2 (23m 10s):As far back, like it takes a lot. Yeah. Yeah. It's so far back. If it took this many years for us to form this way, imagine how long it's going to take us to On the podcast we are talking to Carolyn. Carolyn has a BFA from a theater school and imitate from the school of the art Institute of3 (23m 45s):Chicago. Carolyn is a performer and a professor and a lovely and pathic, amazing human. So please enjoy our conversation with Carolyn Bournemouth.4 (24m 8s):We're not here to talk about cancer. I've got no theaters because the Rick Murphy shirt Murphy's now this is actually made by Kevin Foster, who was my, that student. But I guess so I directed a workshop that he was in. He's a wonderful man. He ended up moving to Alaska, teaching people how to climb ice mountains. And now has a wife and a baby and never left Alaska. So we had that weird connection. Cause I lived in Alaska for the summer in between my first and second year of school, which I guess is it's like another theater school story in a way. I forgot about that one.2 (24m 47s):We're here. So Carolyn Hornimann, congratulations. You survived theater school. Yes you do.4 (24m 56s):You survived it. I know. That's why I bought this very expensive mix. So I would get lots of voiceover work that I never get.2 (25m 2s):Hey, maybe this is going to be your open Amy4 (25m 4s):Visit shit. This is it. This is my ticket. This is my ticket. I love podcasts.2 (25m 10s):So you survived as a student and you teach4 (25m 13s):DePaul. I teach there. I mainly teach the non-majors, which I love, but I have directed a couple of a workshop, intro type things. But many years ago, I keep putting in proposals. They don't ask me to do again, supposedly next year, maybe I will be, which would be awesome because I have this idea to do a version of Bernhardt Hamlet with all genders and just like totally gender fluid. So2 (25m 42s):You have to submit a proposal4 (25m 44s):For a show. That's a whole nother story. I'm probably another podcast, but I have submitted proposals. But oddly enough, a couple of times I did direct. I was just asked to, and that, I guess we're going backwards to go forwards. Are we always bad and make it go forward? Right. Which is that amazing? I think it's David Ball. The book that they made us read called backwards and forwards. Do you guys think I read In HDL, you had to read this book called backwards and forwards. Anyway, I used it in my master's thesis too. Cause it's brilliant. But anyway, backwards and forwards, I was in graduate school.4 (26m 24s):Rick Murphy was like kind of very interested in what I was doing. I was doing work on performing new feminisms and he was like, what the fuck is that? What's going on at the white cards? You can curse. Oh, no podcast. And, and that's a whole nother story because actually Rick Murphy was not my teacher. I had David AVD, Collie, and I went into to Rick Murphy's office. Like I guess it was probably my senior year to ask him advice about wanting to go to London, to study his full cereals. Right. As if I hadn't already been studying for serious. Right. Cause I wanted to go to Europe and be a fancy pants, real actor. And he was like, why are you going to do that? Why don't you just stay here and find a company that does European work.4 (27m 7s):So then I was in the European repertory company for 12 years. Oh,1 (27m 10s):Oh, that's a, that's a nice long run. Is that, is that company still around?4 (27m 14s):No, that's another story.1 (27m 16s):You have so many stories4 (27m 18s):We need to have, like, I have too many stories, too many stories. I don't even1 (27m 21s):Know where to start. Well, here's where I'll start. Did you just let's get the facts? So you went to BFA at the theater school, but you got to be MFA somewhere.4 (27m 32s):Oddly enough. No, I got, what is an M a E a masters of art and art education from the art Institute of Chicago, which is funny. Cause the Goodman started at the art Institute. So I guess I'm like super Chicago already.1 (27m 45s):You did that. Okay. I wanted to get the facts down. That is why. So then I would like to start when you were a child, were you always this awesome where you just like, fuck it. I'm going to4 (27m 59s):Just be crunchy. I have cool glasses, like YouTube,1 (28m 2s):There's serial killer glasses that we have just FYI.4 (28m 7s):I am from a small town down south. And I guess in a way I knew somehow that I wanted to be an actor from like watching old Betty Davis movies with my mom,1 (28m 17s):Her like Betty Davis.4 (28m 20s):And then I, my dad died when I was a sophomore in high school unexpectedly. And I was with my English teacher who taught us Shakespeare. He was fabulous. Mr. Beaver, very eccentric man who was probably gay and was not able to be out in our little small town. And Mr. Beaver took us to another small farm town school bus to all in, to see the show that was coming in from Chicago. And it was from the page to the stage Shakespeare by step and1 (28m 55s):Walk, a little company called4 (28m 59s):John C. Riley was one of the two count of two actors. There was a man and a woman. I wish I knew who she was. I went on deep dive search last night to find out and I can't find it anywhere on the internet. Was that my computer making a noise? Oh,1 (29m 15s):I didn't hear, I didn't hear it either. So something, well, here's the thing I'm sort of in touch with John C. Riley for various weird reasons. So I might ask him,4 (29m 27s):Please ask him, oh, he's the only one that will know. It's not anywhere on the internet. And I don't talk to him, although he's very close with Rick Murphy, oddly enough. They're like buds. But so, so anyway, we're in this, you know, school editorial, I'm watching this Shakespeare show with Jonsi rally and this woman that was also amazing. I hate that. I only know the guy, right. But they had a trunk and they would pull out costumes and props from the trunk. And they went through several scenes of Shakespeare. It was, you know, like devised, wonderful, amazing theater traveling the country, like the old frickin work progress association do used to do with the federal theater, which we should still have. Thank you very much.4 (30m 7s):And I, you know, had the PR I remember holding the program to like, with like, who are these people? What did they do? Where did they go to school? Oh, theater school, DePaul university. That's one question. Okay. How old were you? Like 15 amazing. Maybe 16. Cause I looked and it said it was 86. My dad died in 85. I was 15. I was 16. So I then also had, I was the president of the thespians of Lincoln community high school in Lincoln, Illinois. And I had, we, one of the things that we got was I forgot what it was. Oh, I wish I remembered it was a fabulous name. Like it wasn't forensics theater or something.4 (30m 49s):The, the title of the magazine you would get, it was like a high school theater magazine. And you got a free subscription of that for a year. Cause you, you know, you were the president of the Philippines and it also of course had a wonderful little spread about the theater school. So then I decided it was either going to be NYU theater school. My mom wanted me to go to ISU and kept saying, John Malcovich went there. John Malcovich went there because that was only 45 minutes away from me. So she really wanted me to go there, you know, cause my dad had just fucking died and she and I had moved from the country into the town and she wanted me to stay close, but she wasn't going to say that. But I know that now that that's what she wanted. Plus it was a lot cheaper and also Webster, which is in St. Louis. I think so somehow I got into, I think ISU in Webster, but I don't remember auditioning.4 (31m 33s):I think I just like had to write an essay and say I wanted to go Tish. I didn't even, I don't think pursue it because I couldn't afford to go to New York to audition. I only auditioned at the theater school. I addition to in my junior year I got in and my junior year, I knew where I was going for my senior year of high school. That's awesome. My brother drove me there and his, he had this old convertible. I remember driving down lake shore drive with my brother. It's my brother who now has cancer. And he took me to this audition. I don't know where he went or what he did with his big, long, old, like 67 do you know, muscle car that he had. But I went in and I did the audition and I did the voice and I did the weird movement and I did my two monologues and I don't remember exactly who was there.4 (32m 16s):I think it was maybe Phyllis Gemma stuff. Maybe it was his Carol Delk person who was a movement teacher who then I never really had. But anyway, yeah, I got, I got in, I remember getting the letter. I remember standing on my stairs in my house in Lincoln, Illinois, because then, you know, you've got to actually better in the mail. There's no emails or anything. And I was standing on the stairs is my, mom's stood at the foot of the stairs and opening it and being like, and then she's like, well, you know, we'll figure it out2 (32m 47s):Time out for one second. Do you think that kids think about us opening letters? The way that we think about people opening scrolls1 (32m 55s):Or telegrams? Yeah.4 (32m 59s):I have to explain to my students with snail mail is because at the end of every quarter I send everyone a little card, just a little thank you card. I've been doing it for like 15, 16 years now. So I can't stop now that I started this tradition and I'll ask them for their snail mail and they'll be like, what's that? And then I'll have to explain to them what it is and then they'll give it to me and they'll leave off like there's zip code or the town on her. I'm like, no, you have to put everything.1 (33m 19s):So there is a, I met someone at my coworking space who is like, I think 25 and they didn't know to put stamps on letters. So he just4 (33m 34s):Imagined that he1 (33m 34s):Was going to the post box and I said, oh, you're going to the postbox. I said, oh, you forgot your stamp. He goes, what? I was like, oh my God. Anyway.2 (33m 46s):And also I have to backtrack about one of the things that John C. Reilly thing was that a DePaul production or Novus Devin4 (33m 54s):Oh seven2 (33m 55s):Will forever. Right? Okay.4 (33m 57s):It must've been one of his first jobs out of school cause it was 1986. And I was also looking because there was this amazing picture of him from Gardenia, I think in the brochure. So then not only are in the magazine that I had, I don't think I ever got a brochure in the mail. It was this magazine. I'm going to find out the name of it. Cause it was just a cool little magazine that the theater kids, theater nerd, Scott, and we, and I got it for free when I was the president of, at that speeds. And so there was this wonderful picture that was some of the, you know, lovely glorious lady like grabbing, holding onto his leg or something was very dramatic. And this story goes further because then I'm at the theater school is my freshman year and there was the God squad party.4 (34m 39s):Nobody's really talked about the gods squad a little2 (34m 41s):Bit.4 (34m 43s):So the God squad party, I don't remember who my God parent was. I don't even, I must not been very good cause I have no idea who it was, but I was at this party and John C. Riley was there.2 (34m 56s):You must've been levitating.4 (34m 59s):And Don Elko was there. There was teachers therapy for smoking and drinking with the teachers. I was like, mind blonde, what's going on? And I said, I want it to John C. Riley in the kitchen, leaning up against the kitchen sink with like a beer or something. And I was like, excuse me. I need to tell you it's still on me about why I'm here. You know? Like I got tell him2 (35m 22s):That he's4 (35m 23s):A nice guy. Remember what he said? I don't remember anything. I was just like, that's1 (35m 27s):So good that,4 (35m 29s):And this is before yeah, it was famous. Right. And he might not have even ended up being famous. This is like, I thought he was that famous from skiing. That fricking page, the stage new person traveling around tiny little rural towns of Illinois.1 (35m 45s):That's amazing.4 (35m 47s):So I would love to know what he thinks of that, that show. If he has memories of doing it, who the other,1 (35m 53s):This podcast. I mean like you'll listen, you'll listen to, if you listen to some of the podcasts, you'll hear my John C. Riley story. It's pretty, it's pretty funny.4 (36m 1s):Oh, you have one too. Okay. I've been, I went this way. I have bags. I went down deep dive last night.2 (36m 9s):I love that. A lot of people do that. A lot of people when they find the podcast go and listen to a bunch of. So what was the experience like for you? You were walking down memory lane. What was it making you feel?4 (36m 21s):Ooh, I don't know. Now it's making me want to cry. It was, you know, I was 17 and I started there. I had no idea what I'd got myself into and a lot of it, you know, really broke my heart, but I also think it may, you know, like everyone else has said it made me who I am, made me kind of a tough skinned bad-ass, but I'm also a hyper empath and have trauma. And so now I have to deal with, you know, all of that in my old age. But I did have experiences there in classes with certain teachers, with certain instructors, certain directors, I lived with five girls in a two bedroom apartment on the corner of Sheffield and Belden.4 (37m 13s):We were all poor. Nobody could afford anything else I could barely afford to go to showcase. It was only in New York that year was when they went back and forth between New York and LA I guess, or I don't think we'd even started doing LA. It was the only New York and yeah, I don't know. I mean the whole casting pool process, the whole cutting process. I mean, obviously it didn't get cut, but that was, you know, traumatic. I've heard other people talk about how they didn't really think about it or this and that. Like Eric Slater was like, I don't really think about it. And I was like, I have to say,2 (37m 45s):I hope that isn't over the wrong way. A lot of men didn't really4 (37m 47s):Think about it. I was going to say, it goes a little bit ago and I know him, I'm friends with him and sat there for a little bit of privilege there.2 (37m 55s):Just like, it's just, it's like how a fish doesn't know it's in water. Like you just don't know.1 (38m 1s):Yeah. I mean, they just are doing their set dance. Right. And everyone's dancing around them, but we sort of had to do our own thing. What do you think the tears are about? Like when you, when is it just raw motion or is there like tears for young, a young version of you? Or like it's just a lot.4 (38m 22s):I'm a very teary person. I think. I don't know exactly what it is. I'm in therapy. It's I know. I just,1 (38m 29s):I am the same way. Like I,4 (38m 32s):I get, I get overwhelmed. I get really moved just by kind of yeah. And that sort of strange and weird that I'm still there in some weird way. Like I'm an adjunct, I teach the non-majors, but I'm there. And I went back actually, Rick Murphy directed a show that I adapted for the children's theater called the selfish giant and other wild tales. W I L D E all the Oscar Wilde's fairytales and Alvin McCraney was in it. First of all, Oscar Wilde wrote, wrote, he wrote fairytales and I had actually adapted another book that somebody else ended up having the rights to.4 (39m 13s):And so Rick was like, well, you know, I know you really wanted to do that one, but if you find something else, I'll still direct it. And so I was like, okay, let's do this. And so I adapted us, grows fairytales. Awesome. For me to read, love, to read that I can find it somewhere. Might actually be a hard copy of it and I'd have to like scale or something. I don't know where it is. That was like 2002. I think there's also pictures of that. I also found which I didn't know the production history of the theater school online. You get the pictures for almost everything and they're almost all taken by John Bridges, right. Bridges, which is amazing. Cause these, I don't know why I only have these two printed out of the old whore and the sister-in-law from the good person of such one, which actually is like a happy, sad, weird story because I auditioned to be course and I was called back for it and I really wanted it.4 (40m 8s):And it was that awful time where they would post on our side of the theater school, glass doors that casting it like midnight. So we would come there while we waited and we went to the door and not only did I not get it, but one of my friends got it, of course. Cause how were, how was it not going to be your friend gets it? And, and then I see old whore and sister-in-law, and I just, I had heels on and I took them off and I started running and I like cut my feet up, running in the street crying and like old 18 years old. And your sister-in-law told her, well, that's another thing, you know, because of my voice and my larger frame, I've always been cast older.4 (40m 53s):Even in high school. I have a very traumatic story actually being in high school. And my father dying when we were doing cheaper by the dozen, which if you know the story, the dad leaves at the end and doesn't come back cause he dies and we're doing this play. And it was must have been like the end of the rehearsals right before we opened. And my director who was one of the English teachers at my high school, I remember being on the phone with her because I remember exactly where I was standing in my house. And instead of being like really sympathetic about my dad dying, she was talking about how I was the younger of three of the sisters and the girl that got the older sister, which is the part I wanted, who was the daughter of another English teacher who was always getting all the parts I wanted.4 (41m 34s):She didn't have as big of breasts. And my English teacher was like, maybe we can, you know, tape you down. And I thought, why didn't you just cast me as the older sister plus I was wearing this like beautiful, old, like 40 suit. That was my mom's was vintage suit that I loved. So it was kind of tight and probably did really show my frame. I was 15 and my dad had just died. This woman's telling me to tape my breasts down.2 (42m 7s):So yeah,4 (42m 7s):I always, I always got cast older and I can see what2 (42m 10s):He went down the road of wanting to do feminist theater. I mean, it sounds like from an early age, you were, you were made aware of double standards and beauty standards and all that kind of stuff.4 (42m 21s):1994, I think it was, I had graduated. I was auditioning. And it was when you had to look in like this paper for the auditions and there was like a line you called, oh God, I wish I could remember it. It was, you had to call this line and stay on hold forever and listen to all the audition notices. And there was an audition for pump boys and dynamics, which I was excited about. Cause I'd seen it when I was younger with my mom and I thought, oh, that's fun. And it literally said the men will be paid. And I got a fucking article in the Chicago Tribune about that.2 (42m 55s):You did. Oh, tell us about it. You just wrote about,4 (42m 60s):You know, they they're, they're like backpedaling about, it was like, well it's because the musicians they're going to get paid and the musicians are mad at first of all, now I'm thinking back like, why did the musicians have to be men? And you literally still wrote, the men will be paid. He didn't write, the musicians will be pay. So yeah. I don't know how I did it now. Now it's all kind of a blur. I just started calling places and I got a reporter from the Tribune to like talk to me and do a whole article about it.2 (43m 25s):Oh. So you're really tenacious. That's what I'm getting. I'm getting that. You get something, whether it's a goal or you're trying to write an injustice and you attach yourself to it,4 (43m 36s):Right. I'm an Aquarius moon. I know this. Isn't an astrology podcast, but I've looked at your side. I've learned in the last couple of years, I'm Scorpio, sun cancer, rising, thus the tears and then Aquarius moon, thus the righteous justice for all.2 (43m 52s):I love that. I love that you4 (43m 54s):Did tons of work after school ended up doing tons of work like in, in schools, after-school programs, writing and drama programs and things like that, which ended up taking me to go back to graduate school and get the Mae and education. But then that was like a lot of solo performance work I did too, with this woman, faith wilding, who was like, look her up. She likes started women house it, I think Cal arts and like the seventies, she has this famous piece where she rocks in a rocking chair and says, I'll, I'll wait until I'm old enough. I'll wait till I fall in the I'll wait until I'm married. I'll wait. You know, just incredible woman who taught this class called new feminisms. She taught one called body skin sensation.4 (44m 37s):I mean just, and so I was doing all this incredible work again, looking at myself and being a woman and being an actor and what the trauma that I'd been through. And then my thesis was doing a performance experiment with a bunch of young women from all over Chicago, like high school age women talking about their mothers and feminism and teaching them about feminism and1 (45m 1s):Well what, okay, so, so a question for you, first of all, I tidbit I have to share that we ha we spoke with, I think it was Joel Butler who was a stage manager and said that they would come out and walk to tease us. When we were waiting for the list to come home, they would pretend that they had news and go like the people who weren't involved. Anyway, I just have to say the whole thing was a setup. Like the whole thing was a fucking setup. So all it was like the hunger games and it was also that in itself was a play like a theatrical experience of man.4 (45m 41s):I don't really know how they do it now. It's all online.1 (45m 44s):It's all online. Yeah. They sent you an email with your casting, but I'm just saying like, when I look back, my little corner of the world was walk, walk, walk, look at the list. Feel like shit, walk, walk, walk. But there was a whole play happening around us of everyone knew what the fuck was going on. And it was part of the thing to have this sort of, yeah, it was, it was a production, it was a fucking production, a tragedy for most of us. Right? Like, and anyway, it just was interesting to hear the perspective, like everyone knew what was going on and everyone played a part is what I'm saying is what I get from the theater school. Like it was all back in the day. Anyway, it was all part of a thing.1 (46m 24s):And like, you get the idea2 (46m 26s):We're working through for some of the faculty who, you know, themselves couldn't realize their professional dreams. And you know,4 (46m 35s):That makes me so sad. I hope that it's really not1 (46m 40s):Okay. I mean, like it's not okay, but it's like, they, we, a lot of times we talk on this podcast, right. About the psychology of never fixing what you needed to fix in the first place inside of yourself gets fucking played out all over everywhere.4 (46m 54s):We are living in a new time of awakening and people being able to talk about their trauma. That was not that time. And that was also the time, like I said, where the teachers were coming to parties with us and drinking and somebody else was mentioned, somebody else was mentioning, you know, relationships between faculty and students. I only knew a couple of those instances, but yeah, the fact that they happen at all and yeah, yeah. I've found that like in my own teaching, like even, even in the last couple of years and I've been doing it for a long time, I just I've become so much more transparent. Like I talk about my own mental health issues or what's going on with me or I, I check in and check out with them every day. And it's like, what's something beautiful you saw today.4 (47m 35s):What, what are you going to do good for yourself when you leave this zoom glass, whatever, you know, like, so I think that as a culture we're evolving as facilitators instructors teachers, but yeah, we were there at a really hard, whoa time. I, for sure. I mean, you were there pretty shortly after that, but also I had some amazing experiences. I loved Betsy Hamilton. I loved John Jenkins. Jim. I still laugh. I actually had for two years cause Adam second year and fourth year, which nobody did because he randomly taught second year acting one year for some reason. And everybody had him for fourth year for what that was called, like ensemble or exit or whatever the hell it was called.4 (48m 19s):So I had him second and fourth year. He actually told me at one point, heard him out, what you're doing, why are you an actor? You should be a singer. And so then I sang in the, oh no, it was after I sang in this, it was Rob chambers thesis show Baghdad cafe. And I sang backstage live for just a couple parts of the show. Just Rob asked me to do this. I don't even remember how that all came about. And, and you know, Jim being the jazz and music aficionado called me to his office and was like, what are you doing? You should be a singer. Shouldn't be the act. But was that ever a, a w dream of yours to be a singer? I was in rock band called dominance clam I did say I did sing a lot that there was a summer.4 (49m 7s):I wasn't even 21. So I would go, I've sang it like the Metro and I wasn't really supposed to be in there and, and Zach wards and Steve Sal and all these people from my class came to see me. And yeah, I wanted to do that and I would audition for musicals and stuff after I graduated, but just like Marriott Lincoln Shire and all those like fancy places would never hire me. And I would always end up in shows where I sent, but they weren't musicals, you know? And I also think I have a little bit of trauma around singing. I started singing in my church after my dad died. I was the song leader in Catholic church. Believe it or not. And I would go out the night before and be like smoking and drinking with my friends and then sitting on the alter with like the breeze and like, like Christ, what the hell are we doing?4 (49m 55s):I would say at funerals, I sang at my mom's second wedding. I sang at my brother's wedding, my sister's wedding, my other brothers. But yeah, I say I sang a lot. I haven't really been singing recently cause I, I usually end up crying when I sing. I had a very traumatic audition, 2008. I think it was where I cried when I was singing the song. And the song was about the girl's dad a little bit on the high note and it cracked and the casting director will remain nameless called my agent and told them that they thought I had mental problems and needed help. Okay. Again, this is something that would never happen today.4 (50m 37s):Right. But it wasn't that long ago, 2008, she also said that I was dressed in appropriately. I wore a forties style suit and a pillbox hat, because that was the period of the show. How is that inappropriate? That's someone who's. And why you calling my agent how intrusive to call my agent and tell them that you think I'm. And then the funny thing about it was I had just gone through a huge breakup and had moved and gotten a new job and all this other stuff was going on, but that had nothing to do with it. And that's nobody's business and I was moved by the song. And don't you want somebody, that's just somebody who, who is scared of their own emotions, like, correct. That's all that is. Yeah. So anyway, I digressed cause that's like post theater, school drama,2 (51m 20s):But I've had auditioning. Okay. So you arrived at the theater school at a tender young age. You4 (51m 28s):17. I was 17 because I have a November birthday, 17.2 (51m 32s):And you did your whole BFA there. Tell us about some of your show experiences.4 (51m 41s):Well, the one that I was going to talk about was the good person of such one. Cause oddly enough, it's the only one that I have printed pictures of. And I don't even remember when or how I acquired them. I think I got them from John Bridges cause he took all these pictures and that one of me is the sister-in-law. I don't know that that one was like a production photo. I think that was him coming up. And he saw me in this moment and like had to get this shot. So not only was I not cast as Shantay, which I want it to be now I'm the, the sister-in-law on the old whore. So I'm like, I'm going to kill this. I had 16 lines between the two characters, my old whore. If you look at that picture, I have a blonde wig. I didn't wear a bra. I have a tube, top, a pleather red skirt. I had these hoes that had a dragon up the side.4 (52m 22s):So it looked like I had a dragon tattoo on my leg and high, high red pumps that I think were mine actually from when I was in a beauty contest in high school anyway, and I got these earrings, oh my God. I think I found those earrings too. They were Chinese lanterns like that opened up, but they were earrings and they were huge. And I smoked a cigar. Oh. And I, I don't know if you remember this or if they did this when you were there, but after shows closed, mainly the main stage shows they had like this post mortem, postpartum, whatever you call it in the lobby and everybody and they would critique. I probably blacked that right out while you sat there and just took it.4 (53m 7s):And, but I don't know if it was during that or like after that, I would just be like walking in the halls and all these teachers, some that I had and some that I hadn't yet even had made a point of coming to tell me how excellent I wasn't that. Sure. And it was not false. It was not put on. But I mean, come on. Those people did not give compliments unless they really felt1 (53m 29s):Whatever. Yeah, yeah,4 (53m 30s):No. And I was like, yeah, cause I freaking killed it. Cause I took it so seriously. I was like, I'm going to make these roles so deep and so real. And if you, if you look on the production photos, they have this screen and, and, and, and people would make shadow play on the screen at the beginning of the show to show like the street life of the pool or the Sichuan and stuff. And I got to ride a bike and I rode a bike across and you see the shadow of the girl on the bike and I'm like, I still look at that. And I'm like that.1 (53m 57s):So do you think that's, I love hearing that. That's a great story for me to hear. For some reason, it just really warm, but warms my heart, but also talks about Gina's calling you on being tenacious. But do you think that that sort of set a tone for, cause what I'm getting from you is that like you're simultaneously a, bad-ass a bit of an outsider never given your chance. Never really given the chance to maybe in terms of outside casting, do what you could really do. So then you take what you get and then you fucking kill it. Does that ring a bell4 (54m 37s):Kind of? I think so. And I think I've always been that way really. And that also being in that show, Joe sloth directed, it was Bertolt Brecht. And really got me thinking about political theater and theater for social movement and theater for change. And I really believe when I graduated and I started doing work at the European repertory company, I believed that doing theater could change the world. You don't think that anymore change sometimes, you know, it beats you down pretty hard when you, when you work and work and work and work and you have to have three other jobs. Cause you're in a theater company that doesn't pay you any money.4 (55m 17s):And I, I still like the best work of my life was at that place. I was client of Nestor and Agamemnon for three years. I mean, I, Y you know, yeah, the best work of my life, but was it going to say that there's a different, and I think it's good. There's a different culture, a different mindset. Now students now would never graduate and say, yes, I'm going to be in a school or I'm going to be in a theater company for 12 years that never pays me and I'm going to have three or four jobs. And it was nice to kind of almost like a martyr, poor theater, Jersey, Petoskey board theater mindset of like, I'm an artist. Well, of course I'm, I'm struggling and I'm poor and I'm, you know, but I'm for the oppressed. And so I must experience that.4 (55m 59s):I don't, I dunno, like it just, I wonder how much I manifested that, right. Because I, I would have auditions for TV and film stuff that I would get close to and just not get, or it took me. I was, I think, 30 when I finally gotten a show at the Goodman or no, wait, I was 30 when I got at apt in Wisconsin. I think I was even older when I got in the show at the Goodman. But anyway, yeah. You know, eventually I have done shows larger theaters, but I still will say, I mean, people that saw the stuff I did at the European rep and I was like 24, 25, but I played clouded minister and it was Steven Berkoff's choir master. So it was like the most rockstar frickin, you know, I made my own costume.4 (56m 41s):It was, it was all like fishnet. And I just like punched my hands through fish nets to make sleeves and high heels and crazy Kabuki makeup. And I stood at the top of this ladder Agamemnon. And I came out at the end with like Hershey's syrup on my hands after I'd feel them. And I was like, I mean, if you saw that as hit, you were blown away, this was three years while we did it, like in a regular run. And then it was so popular. It was so popular that we did it on Friday, Saturday nights, like late night. And then we were doing, cause we want it to be a real repertory. So at the time we were doing Agamemnon Electra, uncle Vanya, and this show called all of them are just, yes.4 (57m 32s):And we would also change this. You remind me, okay, this is what I think Steven Davis was talking about when he said he was in four shows at the same time he, he was in, he was in all those shows and yeah. So, oh my God,2 (57m 51s):That's super intense4 (57m 53s):Looking at my notes2 (57m 54s):That like, though, while you're looking at your notes, I mean, was that draining, not just the number of shows you did4 (58m 4s):The physical training. Well, also I was, yeah, I was like a waitress during the day. I mean, I had a job I had to live and I was a waitress where I could only work lunches because all the shows were at nights. So lunches weren't as busy. And if it was really slow at lunch, I mean, so I would find myself every day while I was working calculating in my head, how many tables I had to have, how many tips I had to get just to make enough for that week to pay the rent, you know? And at the time I was living with two British guys, actually, they're the ones that brought me into the European rep, my friend, Charlie, Charlie Sherman, who is a actor and director in and out of Chicago for years. I met him when I was 18.4 (58m 44s):And I worked at cafe Roma, which was down the street from the school. That was my job. Cause I also worked when I was in school. And so when other people were like, we're going to the dead show. You want to come? I was like, you get, not only do I not have money for that, but I got to work all weekend. Right. So anyway, he, he knew that I wanted to do the play Caligula and he called me up one day and he's like, oh my God, this company is already doing it. Maybe you should audition. And this was right when I got out of school. So I auditioned and I got in the chorus and like the first week, the girl that was supposed to place, Zonea had gotten a movie and left and they were like, okay, now you're the lead. And I was like, okay. And that, and that was the company that I ended up being with for 12 years.4 (59m 27s):But it was exhausting as it was. I know we did. We were also all like drinking and smoking and going to the bar every night after the show is2 (59m 35s):You is a powerful force. I was just thinking the other day, remember when you used to wake up in the morning and no matter what had happened to you the night before, and you're like, okay, well, but anyway, it's time to do it today. I haven't had that feeling in years. I haven't had that. Like I can even when some we've once a day, I'm super excited about, I don't ha I don't wake up with this body, like readiness that I remember feeling in my twenties and thirties. Okay. So look at your notes. What are you, what are some of, some of the points that you wanted to get to?1 (1h 0m 7s):So if a showcase question, I have a showcase. Cause I'm obsessed. Since I live in Los Angeles, now I'm obsessed.4 (1h 0m 12s):Oh my God, are you guys going to try to avoid? No, no, no, no, no,1 (1h 0m 15s):No, no, no. I'm obsessed with the idea of the showcase because I made such an ass out of myself at my showcase that I, we went to LA, but I know you were in New York, but what was that? I'm obsessed with the showcase experience because I think it is really one interesting, but two where DePaul lacked in so many ways to getting people to the showcase and then after the showcase.4 (1h 0m 42s):Okay, great. This was before stars and all that. So nobody was collecting money for us. You just had to, you either had the money or you didn't. And so I was able to get enough money to buy a plane ticket, but then I wasn't going to have anywhere to stay. So my friend, Sarah Wilkinson, who was also at the school, but a couple of years behind me, her boyfriend, Daniel master Giorgio, who's also been in a lot of TV shows and on, on, you know, Lincoln stage and public theater, like this dude that went to Juilliard, actually I stayed in his dorm at Juilliard on the floor cause I didn't have money to stay anywhere. And I also could only stay for like a couple of days where like other people were like staying the rest of the week or going out and partying.4 (1h 1m 23s):And I remember having like just enough money to do one of the things people were doing, which was go to a jazz club with Frick and Jim Osstell Hoff, which I did. And that was really cool. The other part of that, that was kind of messed up was in the, in the, you know, audition class that Jane alderman, God rest her soul. And I love her dearly and became closer to her. I probably more after school than during school, but in our audition class where you brought, you know, monologues, I had brought this monologue and then she loved it and wanted me to do it and was just like, that's the, when you're doing. And then I had this total panic about it and was like, I don't think this is right. I don't think this shows me in a good light.4 (1h 2m 3s):I'm going to pick something else. And I don't remember what my other second or third choice was. I did, I did have something else. And I remember calling her on the phone. I don't know if I called her office or at home. And again, before cell phones. So I remember the little window I was sitting in my apartment on the corner of Sheffield and Belden on our little phone, talking to Jane alderman, all nervous. Cause I was going to tell her I'm not doing that when it's not right for me. And she still talked me into it and I did this monologue from Roger and me, the film. Did you see it?2 (1h 2m 34s):The Michael Moore movie4 (1h 2m 36s):About the Michael Moore movie, Roger,2 (1h 2m 40s):The documentary about the auto industry. I mean, yeah.4 (1h 2m 44s):Yes. And it was the poor woman, poor white woman who sold rabbits. Pets are mate. Right? Pets are me. Got it.2 (1h 2m 55s):That's what I did. Wait a minute though. I have a feeling.4 (1h 2m 60s):So I actually became, I probably did, but I actually came from where they had tried to, to suppress and to change and to mold me into anything. But this hit girl from Southern Illinois. And then I did that. Right. And that's what I, I wore my boots. I wear my cowboy boots. I think I had my friend's jacket on my long hair. And I came out and I was like pets for me. Oh my God, mortified, mortified. And I only got, I got like a couple of calls, like one was from like a soap opera. And then another one, I don't remember. That was another weird thing. Like the same thing with the casting call we waited in, I was in somebody else's hotel room.4 (1h 3m 42s):Cause remember I didn't have a hotel. I was staying on the other side of town and the dorm room of somebody who went to Julliard. And so we're in somebody's hotel room waiting for Jim Mostel Hoff. And whoever else was with us to come in with like this list, it was literal. It was like my notes here. There was just like tiny pieces of paper with like telling us who got what calls. Some people were like, got nothing, got 10 that too, about whatever. Yeah. And, and mine were not meetings. Mine were just like, these people want you to call them or send your resume. I was like, they already got my resume. Everybody got what, what? So, you know, like I wanted to move to New York. I wanted to be a New York fancy actor, you know? So that was like really devastating too.4 (1h 4m 23s):But then I was like, well, if I don't get that, I'm going to be an amazing Chicago theater actor. And I'm going to show everybody that Chicago theater is actually better anyway.2 (1h 4m 31s):Yeah. I don't to remember VAs if I've told this on the podcast before, but remember how I did that thing or if I didn't get any meetings. And so then I snuck into administrative office at DePaul after showcase and I found a list of all of our names and everybody had gotten, everybody had agencies or agents names written next to theirs, but not everybody was told that. Yeah. Yeah. So,4 (1h 5m 5s):Oh, podcasts, then couldn't see my face gaping. Now what, what did you do? Did you tell, did you, what?2 (1h 5m 12s):I swallowed it and carried it around resentfully for the next 20 years. Yes ma'am I did my God. And you know, who knows? Maybe there was an important reason for that. Maybe it was, these are shady characters. I don't know what it would have been, but I, I know that I would have4 (1h 5m 36s):That you didn't feel. Yeah. I feel so bad for you that you didn't feel like you could, you know, go further, ask more. I don't know. Probably2 (1h 5m 44s):Carolyn it probably didn't occur to me. I'm sure it did. I'm sure. The way I thought about it was, well, this has happened now. It is over, this is the thing that it is forever such. I just, I would have never thought that way. I would have never thought to advocate for myself. I mean, I fought to find out,4 (1h 6m 4s):Snuck in there. You thought, well, enough of yourself to sneak in there,2 (1h 6m 9s):You know, whatever. That's that's for me to figure out because I, I, I that's what, but that's what I did with it. I, I took it. I took a carried it around like a shame instead of, oh, by the way, I didn't mean to blow anybody up. I just needed to say like, what's the deal? Like what happened happened, right. Yeah.1 (1h 6m 29s):I feel like it's interesting. It is. It is. It is just really, now that we have this podcast, we spend a lot of our time being like, well, yeah, what's the deal. Why did that happen? And, and what,4 (1h 6m 41s):I wonder what John Bridges or somebody like that would say about that.2 (1h 6m 46s):I I'm sure. John Bridges, who is a theater school loyalist to the end when say that, that I, that I misunderstood. He tells them he doesn't tell the truth. I'm saying, listen. And, and by that I've said a thousand times we understand that we couldn't possibly know all of the factors that went into any decisions like casting and stuff like that. And that there are certain things that happened. That felt terrible. That were for my own good, you know, but Yeah, because getting back to that whole thing about casting, I mean, I'm sure that the guiding principle in their minds was, this is what it's like, you know, you want to move to New York.2 (1h 7m 33s):I mean, Don, we had another person on here who told us living in New York. You, you you'd have to go wait in line in the morning at a theater so that you could get your audition later. And if you wanted to have, it had to be a lunchtime thing, so you could leave work. And those sl
And then there were 4! 4 teams remain after the NFL weekend and 4 Hosts break it down as Chris Little, aka “Miner 49er” joins the Boys. Justin takes us down memory lane of the Schwann's food delivery truck, and Dylan pays homage to HOF Coach Sean Peyton retiring. --- Send in a voice message: https://anchor.fm/robert-brandt5/message
Synopsis On today's date in 1910, Gustav Mahler conducted the New York Philharmonic in a concert billed as “the first of a series arranged in chronological sequence, comprising the most famous composers from the period of Bach to the present day.” Mahler's program included works of Handel, Rameau, Gretry and Haydn, and opened with his own arrangement of music from Bach's Orchestral Suites. Now, Bach's music had been appearing on Philharmonic programs for decades, but some were shocked to see how Mahler presented it. Rather than standing in front of the orchestra with his baton, Mahler led the orchestra seated at the keyboard of a “Bach-Klavier” (a Steinway piano whose action had been tinkered with to make it sound more like a harpsichord). THAT bit of “historically informed performance” was something brand new back then. In a letter to a friend back in Europe, Mahler wrote: “I had great fun recently with a Bach concert, for which I worked out the basso continuo conducting and improvising quite in the style of the old masters … This produced a number of surprises for me – and also for the audience. It was as though a floodlight had been turned on to this long-buried literature.” Music Played in Today's Program J.S. Bach (arr. Gustav Mahler) — Orchestral Suite (Berlin Radio Symphony; Peter Schwarz, cond.) Schwann 11637
Bruce Carter joins TWiN to discuss the peripheral nervous system: the development of nerves that convey sensory information like touch from the tips of your toes to the brain, and Schwann cells, which are necessary for ensuring that those sensory signals are sustained as they travel long distances to the brain. Hosts: Vincent Racaniello, Timothy Cheung, and Vivianne Morrison Guest: Bruce Carter Subscribe (free): iTunes, Google Podcasts, RSS, email Become a patron of TWiN! Links for this episode Control of neuron survival by p75 (J Neurosci) Sympathetic nervous system (Nat Rev Neurosci) Charcot-Marie-Tooth and PMP22 protein (J Biol Chem) Satellite glial cells (Nat Rev Neurosci) Timestamps by Jolene. Thanks! Music is by Ronald Jenkees Send your neuroscience questions and comments to twin@microbe.tv
Optimal Health Strategist Gunther Mueller has developed what he calls the 'Magnetic Mind Method." This means he helps people tap into our subconscious to create and manifest the life we've always wanted.=============================================Ari Gronich0:14Welcome back to another episode of creating a new tomorrow. I am your host Ari Gronich today with me is Gunther Mueller. And Gunther is a certified magnetic mind coach now, you know, I'm gonna let him explain that but 30 years of successfully being an entrepreneur, optimal health strategist, you have, you know, you have three kids alongside all the work that you've done, but you've actually taken and builds a business in three years to $20 million in the anti-aging, I believe, field, founded another company, you've bought and sold several companies. So today, we're going to talk a lot about not just the health and wellness, not just the mindset, but also kind of the deep and down and dirty parts of business a little bit. And I'm going to kind of take you on a journey today audience that hopefully will lead you into a place where you could go, Oh, yeah, I got this. And I can move ahead tomorrow, creating my new tomorrow, today. So anyway, Gunther, tell us a little bit about yourself.Gunther Mueller1:24Hey, Ari, thank you so much for having me on, create a new tomorrow. It's amazing to be here because the title of your show is completely in alignment with the information I'm passionate about sharing today. And hopefully the audience gets a lot out of this today. So a little bit about me and I grew up middle class in New York City, bolted out of there in 1984 to go skiing in Colorado and go to school out there because scheme was my thing and need to go ski the bigger mountains but you know, did the thing that you were supposed to do get good grades, go to college, you know, do that whole rigamarole thing. And then I became a professional ski bum for four years after college. So I lived in Vail, lived in a steamboat for a while and commercial fish in Alaska, worked on the Valdez oil spill. If anybody remembers what that was, I was in Prince William Sound for about 60 days, moving people around and equipment and things like that. And then I started my sales career basically in the 90s, selling meat and seafood door to door because I had experience in the seafood industry. You know, I knew what good stuff was. I built about 3000 customers in the Colorado mountainous region. This is the days before Sam's Club and before you know, Costco and all that.Ari Gronich2:41So I just want to say this. So when I was 17 and a half 18. And I'm just finishing up school, high school and rural Oregon. Right? Yeah, I was selling meat and seafood door to door in Oregon on the back of a truck with a freezer on the back of a truck just like a regular big old freezer, laying in the bed of a truck. And so. Gunther Mueller3:14Hey I did it for 10 years. And I loved it because I got to wear shorts and a golf shirt every day. And I had great customers all over the place and loved it. And then I turned it into an online company in 1998 and then sold that company to one of my suppliers. And then I got into the restaurant business for 14 years. I had about four restaurants that I managed and so food was kinda in my blood food distribution. I work for a we'll start up coffee roaster and then I created America's freshest coffee for the Schwann food company for a while. I went to go to the corporate gig as a regional vice president for them managed a million square mile territory did really well. But the corporate world was not of my liking or choosing. So I you know, get this entrepreneurial blood in my in my veins. And I think I got that from my mom, she know how to sell. She's a travel agent for 50 years, and just knew how to get people to go great places, right. And so then after that I've been in the solar industry did really well used to sell $4 million a month worth of solar panels. And then from solar. I got into the medical industry, which I've been in for over 10 years now. And that's where I created that company and about three years doing about 20 million a year and it was really changing the paradigm of medicine with your average ob-gyn and family practice doctor to optimize hormones and optimize nutrition instead of being so pharmaceutically based. I mean it was really a quantum shift in medicine for a lot of people I was really specialized in something called pellet therapy, which was getting hormones actually inserted into the body and it's you know, it's everywhere now, but when I did it 10 years ago, nobody knew what a pellet was. It was, so I was kind of one of the spear hitters of that therapy in the United States.Ari Gronich5:06Very cool. So nowadays, you know, you're not doing that exactly. You're, you're doing this thing called the magnetic mind. Right, coach. Now, I want to get into this a little bit. So how did you get started working with mind? How did mindset play a role in your sales? So I'm kind of doing a multi question here. So how did mindset play a role in your sales? How did you get into mindset? I know for a friend of mine, oh, he was with Xerox for a while, and they had Zig Ziglar, and all these sales training. So just kind of that background. And then what made that turn into what you're doing now? And how do you see this as kind of that next evolution? Gunther Mueller5:54Yeah, great question Ari, I love answering it. So what happened was in those days of selling meat and seafood, like I was always a true seeker, even from being a little kid, you know, I used to go walk by a church and think, oh, God lives there. You know what I mean? And but how does that all work out? What's the reality of the universe? Basically, I want to know how things work, right? And nobody really was able to answer it for me. And so in my days of selling meat and seafood door to door, my vehicle was my university, I listened to not the radio or pop music or anything, I listened to the greats like Zig Ziglar. You know, one of my favorite quotes from Zig Ziglar is you can have anything in life if you help enough other people get what they want. You know, and he was a great guy. And, you know, the Brian Tracy's of the world, the Tony Robbins of the world. Look, I what I'm here to share today, I did not create, right, I stand on the shoulders of giants, okay, who have investigated every aspect of personal development, human consciousness, you know, the whole quantum physical research over the last 40 years, there's so much science behind understanding the power that we have in our mind. But it all started with reading, thinking Grow Rich, it was one of the first books and it's the quintessential text, you know, in, let's call it getting what you want in life, or, you know, creating a new tomorrow, like, how do you do it, you know, you're living your life, and you want something different, you want something better. And we're gonna talk about that a little bit later. But you want something different, you want something better, there's a difference between the two ideas on so I started doing that one book after another one cassette tape after another really dating myself there, right? cassette tapes was the thing. And then the DVDs, and I used to drive 100, 200 miles a day. So all that education, all that content, all of that listening to a different way to think about things. And that kind of got embedded in my cellular structure from all those years of doing that. And today, I think the magnetic mind method is really a revolution in the personal development space. Because I'm at the place today to tell everyone that look, you're not broken. There's nothing for you to fix. And a lot of the history of the personal development movement has always been going back, to fix yourself to do something to get something right, something's broken inside of your personality, or something's broken in your being, and you have to fix it first in order to get what you want. I'm here today to tell everyone that we look we need to back out of the problem-solving reality and move into the creator stance. And the creator stances that power position. It's like, we need to remember who we truly are that we are connected to an infinite field of possibilities. And when we become consciously creative, we can create whatever situation reality manifest anything that we want. And this is backed up by science.Ari Gronich8:54So I'm gonna ask you, I'm gonna, I'm gonna go back a step. I'm gonna ask you a question you may not have heard before. So I started doing asked when I was eight, life spring, landmark forum, I mean, Cyworld, MIT. I've done so many of these self-improvement movement, workshops and programs and weekends and events and things. What I watch, what I observe, is about 90 so odd percent of the people go there are motivated for about two weeks to a month, and then it dies down. 5% start following the practices that they hear and maybe last a year or two or three until some trauma, gets them out of it. And then there's about 4%, right, that really buy in and get the information and then about 1% or so. This is being this is just my statistics and my, my, what I've watched that actually like live, the information that they've been taught. So here's my question to you. You have done all of these things. And you've taken it. And you've actually become I don't know which percentage but one of the 10, let's say, part of that 10% of the people, right? What makes you have that ability versus say, somebody else? What do you think is the difference between what you were able to do with the information and technology and experiences that you received? That you think the 90% of people who don't ever shift haven't gotten? What do you think that break is that delineation?Gunther Mueller10:55The break is truly listening to your own voice inside your head, okay, because especially today in the era of social media, we are so enamored or concerned with what other people think. I mean, it's getting to the point of ridiculousness, where our self-esteem if we don't look out for it is really coming from what other people do, do they like us, do they share us, do they do this kind of thing, right? And so back that when you asked me that question, the first thing that pops up in my mind is, I have had the ability to listen to my own voice. Now, I'm not saying that everything that I've done has been successful. Look, the path to success is laced with failure. And it's in failure, that you learn the most important lessons, if you had nothing but success in life, you would not be very seasoned, you would not be very skilled, you would not be very proficient in anything. It's through failure, it's through challenge. And this is really the human experience. A lot of people will say, look, I'd like to have a life with just no problems. I'm telling you, you'd be bored out of your mind, if you had no problems, okay? If there were no challenges, no problems, nothing to deal with in life, you would be bored out of your skull. That's just not why we're here as human beings, we're going to have this human experience. Now the beautiful place to be is to be consciously creative to kind of be an observer of what's going on, you know, an airplane at 30. 40,000 feet can see the landscape, right. And when you have that observer mentality, but this takes some practice, this takes some training, right? They don't teach it in school, they don't teach it in college, most of your parents don't teach it to their kids. Unless you become a hungry seeker to a degree and find this out for yourself and your percentages, I agree with so many people get information, they get knowledge. But look, the power is in the knowledge applied. You can go course after course, book after book, seminar, after seminar, do all these retreats, do all kinds of thing, like you said, you feel good for about a month. And then you just forget because you have not applied. And so then the second piece, listening to your own inner voice, because look, you know what if your desires are, let's call it God's plan for your life. What if those desires, What if those things that voice that's trying to speak to you is the directional signal in your life, and you keep ignoring it, you don't listen to it, you never take any time, you've got noise blaring at you all the time, and you never listen to the little voice that's inside and then trusted enough to follow it and not worry so much about what others may think of you. Correct? That's one of the key points right there.Ari Gronich13:51I'm pondering that because there's definitely a level of truth to I think that people go home after getting motivated. And then, you know, somebody says, Well, that wasn't probably what you know, like, or that's not going to work or that's not you know, that you get excited about what you're doing. So I can understand that. I think it goes a little deeper into the depths of the psyche, though. So that concept that you've stated of worrying about what other people think of you, right? goes deeper. So let's drop down into a deeper level of that.Gunther Mueller14:33Love it. So to go deeper is that we all have some self-sabotaging identities that we have acquired through this, let's call it the life stream of this life. And it really is impactful from like zero to seven years old, you know, the data and the science tells us that that's when we just really have an open mind. And we are trying to figure out how it is here. We're trying to figure out You know how to get love. We're trying to figure out how to get nourishment. We're trying to figure out how to get a safe place to sleep. We're trying to figure out how to get what we want, when we're in that stage of development. And so we make certain decisions about life about how it is here. That's all it is. It's just we're trying to figure out what's it like here? And how do I survive. And so if you have abuse, or if you have trauma, or you have some episodes in your life that are unpleasing, the human reality is that we avoid pain. And we move to pleasure. But we avoid pain, a hell of a lot more than we move to pleasure. So what the reality is, is mediocrity becomes okay. Because it's not painful, right? It's just tight, I'm not in excruciating pain. I'm not in a, you know, ecstasy or pleasure. So I am okay with mediocrity. And the part of our mind, we have the conscious mind, the subconscious mind, and what I'm going to introduce to you is the superconscious mind, and there's different names for that, but we like to call it the superconscious. In the subconscious programming, we have put things in there to prevent pain or to keep us safe. And the job of the egoic mind that conscious mind is to maintain the status quo. The conscious mind does not like change, because it knows how to navigate what is successfully. Right. And so some of the sabotaging identities that we pick up through a lifetime of experience, is things like I'm not good enough. I'm not worthy. I'm not capable, meaning I don't know enough, I'm not. This is an example of someone that never gets out of school. And they continually go for the next degree and the next degree in the next degree, right? I'm not, I'm just not capable of any one more thing. And then I'll be okay. I'm insignificant, I'm small, I'm not big enough, right, I'm insignificant, I'm not perfect. Many of us have this perfectionist stream in our mind can't do that, till I perfect this, this has to be just absolutely perfect before I get what I want. And then another big one is I don't belong; this is what we just talked about is this belonging. And it's okay to belong, it's okay to have a great tribe and a cool group of people, but you still have to be you. And so in light of the probably the top six self-sabotaging identities, and everybody has one or two of them, or all six of them in different degrees that we've incorporated into our subconscious program. And I want, I want you to be thinking about the subconscious like Windows 10 on your computer, okay, when you turn on your computer, Windows 10, boots up, the thing just runs, you don't know how it's running, you don't know the code, you don't know anything like every once in a while an update gets sent to Windows NT update, and you restart. And now the program is different than it was before. So we have to do the same thing to our subconscious program, because it's running completely unconsciously. And we put things in there to keep us safe. So when we when I say we need to step out of the problem solving reality, and take the creator stance, most of the audience is saying probably what does he mean by that? Right? What do you mean by a creative stance? Let me give you four examples of what I'm going to call true choices. And…Ari Gronich18:16First let's go through what problem solving is. Right? And then we'll go into that because we've gone through an automatic response system, which is your conscience, right.Gunther Mueller18:31So problem solving is what we've always been trained to do. We want what we want. So how do we get what we want? So the problem is to figure out a way to get what we want, and we do it consciously.Ari Gronich18:45So you're saying that the problem is wanting something that we don't have?Gunther Mueller18:51Yeah, but that's not the problem. Your desire, your desire is totally fine. You can desire and want whatever you want. That's not the wrong part. The part is that we've been trained to figure out in our conscious mind, how to solve the problem of not having it. Right. One having it is not the problem. It's the way we go about getting it anything comes the problem. So to think about goal setting, right? We've been taught to set SMART goals, and you got to have a date on it. You got to be clear about what you want. And then there's 5, 6, 10 steps or whatever to get what you want. And those things have to happen by a certain date. So when you do a SMART goal, you have in your own conscious mind figured out how it needs to happen. You have allowed no space for the field of infinite possibilities to provide the solution to you in some let's call it magical way. Okay, so you've spent your conscious energy your mind solving the problem. Let's take the idea of abundance, financial abundance. Right. Let's create a new tomorrow. And my two choices, I want to have the experience of having more than enough. I just want this experience of financial abundance and abundance in all aspects of my life. That's my true choice. I just always want to be in the experience of having more than enough. Well, how do I do that? Being in the entrepreneurial world, I deal with a lot of entrepreneurs that have decided or chosen that they need a big successful business in order to have that. And I always have to put the brakes on a little bit and say, Look, the business may not be the true choice. What your true choice is, is you want to have the experience of abundance. Having a successful business made give you the experience of massive struggle, okay, if you don't start a business, having the end in mind, you will get to a completed business that potentially you might hate it, you might not want, it may dominate your life. I mean, how many business owners are there where the business owns them? They don't own the business. Right? So be careful what you ask for Be careful what you wish for. Because if you do it in that problem-solving thing, you're looking at it from a field of limited possibilities. And when I say step out of the problem-solving thing, it's focusing on what you want, not on how it's going to show up, not on how it's going to manifest not on the how to how truly is up to the infinite field and the superconscious. Because look, abundance could happen by finding $100 million in a suitcase on the street. You could find it floating in the ocean, you want. And when we talk about infinite possibilities, I mean, infinite possibilities, whatever your imagination could imagine, and how abundance could show up for you. It's possible. But our conscious mind rationally goes in and say, Well, if you have these sabotaging identities, they're well, I'm not worthy of that that's never gonna happen to me, or I'm not good enough. That can never happen to me or I don't have enough knowledge. I don't have this. I'm insignificant, too small. I would never find that suitcase. Like, I'm just not lucky. You know what I mean? Like I do, I've walked right by the suitcase, and I'd miss it. And I would never find it right. So the programming and the tape that's running in that subconscious mind really rules the day. And so did I answer your question about what I mean by problem solving?Ari Gronich22:30Yes. And I just want to kind of get into what I heard was Basic Law of Attraction, right? So going to the experience that you want to experience, you know, whether it's visioning and feeling all the feelings of the perfect day or all, you know, those kinds of things. So that's cool. Because obviously, I want to experience the abundance of life fully, never needing or wanting anything, just everything is available at all times. Right. Now, the key thing that I believe was missing from the law of attraction was the step of action. Now, within what you just said, the confines of what you said is, we're not doing the SMART goal where we're creating the necessary actions from a problem solving point of view, we're going into the infinite. How does one get to the action side from that place?Gunther Mueller23:31So that's the fifth step in the five-step magnetic mind method. So it's the last thing we do? And we asked the question, okay, what is the next obvious action? And that you're right, that's where the secret, you know, great shows and opening the mind to a lot of possibilities and the power of the mind. And why I always like to say is the law of attraction, the secret is trying to solve the problem from the conscious mind. So this is where affirmation is. And I'm not saying they're wrong. And I'm not saying they don't work. They just take time. And they take that discipline, as you said in the beginning, right? People feel great for a month and they do it, and then it Peters off. Why is that? Because they don't see instantaneous results. Which is another concept I just want to throw in here as a seasoning real quick is the idea of as soon as possible. You see when you use a SMART goal, and you put a date on it, and the date goes by and it didn't happen. What most people do. Give up, or quit. Oh, well, didn't happen. I guess goal setting must not be for me. Goal setting doesn't work for me. Right? I tried, it doesn't work. So take any of the great personalities that we look to an Elan musk or you know, Prince or Madonna or you know, any of these celebrity type people that we look at. You think they have ever had to pick themselves up and try again, and try again, and keep going. Keep going for what they loved. Kept going like you look at Richard Branson, right? Just the other day he got into space. I mean, how long is that dream been manifesting, for him, of putting together all the engineers and you know, the concept laced with failure. And he's does other things and he's failed just as much as he succeeded in his life, maybe even failed a little bit more than he's succeeded, right. Way more. And he is not a perfect personality, right? If you got to know any of these people, they are not perfect beings in every aspect of their life, there is not, but they went after what they love to do, they went after that desire and focused on nothing else, you know, taken Oprah Winfrey or something like that, you know, built her media empire, she focused on what she loved, and she had perfect human, the perfect individual of No. And that's where this whole idea of perfection and all that comes in these things, we just have to let go. Right. That you have to let these things go. And there's a process to doing that. But when we try to solve the problem from the conscious mind, we're bumping into that subconscious programming. And what I'm going to share with you is how we go from the superconscious side, we just send an update to the subconscious, we do that with something called recode. Where we go in, we send an update, and we don't need to know what the problem was, we don't need to know what created the problem. We don't need to know if it was mommy or daddy or a teacher or some other situation going on. Right?Ari Gronich26:27So this sounds very different than, say, a bug fix for a software update, where when you go through the update, now all of a sudden, all the programs start acting wonky, you know, and then you get the blue screen of death. So we don't want to have the blue screen of death with our with our upgrades, right? We want to have the bugs, you know, eliminated. So how do we do the difference between those two, right? How do we get the upgrade to be smooth?Gunther Mueller26:59We do that because you're super conscious self, this highest version of yourself that is connected to the field, the infinite field and a great book to read on the field as Lynne McTaggart book just called the field. So much research has been done. We as human individuations are all part of this field, whether you're conscious of it or not. Okay, you're connected. And we are all connected. And if you look into the science, you look at all the experiments that have happened, we've proven this the field exists. So we're just going to take that as a given for the moment. If you don't believe me, you don't trust me, do your own research, dig in, right? got the field. And so we're connected into the field. So when you go to the superconscious level superconscious already knows what's happened in the past superconscious already knows all the connections knows all the dynamics. And when we do read code, we're basically asking for what we want. We say superconscious do you see the desire? Do you see the true choice? Do you see these two choices of experiencing infinite abundance? And when you connect into the field superconscious will respond usually in Yes, no answers. That's why you always ask questions in the yes and no type field, right? And, yeah, I see it. And then we go through a process of creating a structural tension, where the tension because the mind likes to resolve tension. And it likes to do it in a way that it's the path of least resistance. And so resistance is really the thing that keeps us from having what we want. And it is the identity structure that is congruent with the current reality. So Principle number one really is we have to take responsibility for the way it is now. And that's probably a big stepping stone that many people may have to get over. And that you I want to say this, you know, I say I'm gonna teach you how to become superconscious The truth is you already are. And you've already created everything that you're experiencing right now. So you are already a superconscious great, and now you just created some stuff that you might not like.Ari Gronich29:06I want to go back a little bit so you had said something regarding I just had it in my head a second ago. It was I love that I can edit these videos. It's so nice. Alright, keep going and I'll get back to it.Gunther Mueller29:32So we were on this track. Now I lost the track while we were talking aboutAri Gronich29:38Superconscious. Talking about superconscious going from above. Oh, I know what it was. So resistance. So I have a little bit different take on the resistance. Sustained resistance is what stops you. spurts of resistance are what drive you forward. And I'll tell you what I mean by that is the resistance in a lobster shell is what makes them want to go get another show. Right? It's that uncomfortable place that launches them into that next place. And so that's where I just want to, I want to delineate, at least for me, if thing is sustained resistance, if you let the resistance go, if you never change the shell, and you just keep building the resistance, yes, that is going to stop change. For me, the resistance is the signal that says change is needed now. And let's do that.Gunther Mueller30:32So I would equate that piece that you're saying that that is the true choice. That is the desire when you get to that place. And you've been, let's say, living this Groundhog Day reality, because there's only three places we can be, we can be stuck. We can be what we call oscillating, oscillating feels like three steps forward, two steps back one step forward, one step back, right, we're oscillating all we can be in a flow state flows, where we turn thoughts into things, and anybody that's done any high level athletics or anything like that are seeing the interviews with top athletes, they get into the zone. And they can make that three-point shot because they've done it a million times before and they're just in that zone, it just Swish, right? That's the zone feeling. And we can do that in our lives where we just turn thoughts desires into things. And I want to touch on this real quick. Well, how does that happen? As manifestation happened? The idea is, is that you're actually collapsing a part of the field into the present moment experience. So of the field of infinite possibilities, we're focusing on one possibility, with consistency. And the field actually collapses into the present moment. This is manifestation, this is how it happens. And it's photons is the smallest particles in the quantum physical reality. And the experiments that have proven This is that the particles don't even exist until the scientist intends to observe them. Meaning that the particle shows up for the experiment, when the observer intends to measure it, accelerate it, do whatever they're going to do with it to test it out. That's when the particle actually shows up. So the same thing happens in our manifestation. And when we have a true choice, we have a true desire. And we're focusing on that not trying to solve the problem, but we're focused on what we want. And we recode the resistance out of the way from the superconscious level, that true choice shows up as soon as possible. I'm not saying it's going to show up tomorrow.Ari Gronich32:40Got it. So that's where the as soon as possible comes in from the SMART goals. So we've kind of wrapped around. So let's get into that that as well. When we say something like, as soon as possible, kind of like one of the things that I say is how can it get any better than this? It's an open-ended question, right? That has no specifics to it, that allows the conscious mind to solve its own problem. Right. So here's the here's the question to you is, isn't that problem solving? Or is that something else? Gunther Mueller33:18Well, I was just going to stop and say it's not the conscious mind doing the problem solving when we're doing what we're doing is we're just asking superconscious to recognize the resistance, it's back to the resistant your piece of resistance, I would equate to being the true choice and the desire, that sustained resistance is the sabotaging identity. Okay, that's what creates the oscillating. And it just feels like you know, many times I've had what I wanted, I've been there. It's like, when I've created companies, I get there to the end, I have it life's good. Got the cash flow, get everything. There's still something missing. I wasn't really clear enough about what I want here. So my self-sabotaging reality was I could create anything I could build stuff. My thing was, I wasn't good enough to keep it. Yeah, I was great. I was creator, I could do this. I could build anything. But then when it was completely built and humming and running, you got taken away from me, or something happened and it cratered. But that's the underlying identity. Because the identity has to be congruent with the reality. If your identity never changes from like, I'm not good enough to I am good enough. I am capable, I am worthy. If that never changes, you can create a bunch of things and they won't sustain this happens in relationships. This happens, you know, in intimate love relationships, like you get there. It's the best thing in the world and the whole thing, just craters and goes away and you got to start over. What is that? Right That's what we're talking about here. So that resistance is in the center. unconscious program, it is a self-sabotaging identity. And so we can create it through affirmation and conscious work and all that. But it takes a long time to do that. And it takes diligent effort on our part to do it consistently. And so why I think the magAri Gronich35:18We're a fast food nation. So you know, that's been, you know, when I look at cognitive behavioral therapy, and the old paradigm of trauma work, I look at this long process, lifelong process of question and discovery, as to why your mind feels a certain way about a certain thing. I mean, I was seven when I was sent to my first psychologist, right. And I look at that as such a primitive way of doing therapy. Whereas, like, back in the, in the day, you know, tribal societies used plant medicines, and used tribal and cultural togetherness, deal with people's stuff. So let's accelerate what you're talking about. So we're going to accelerate from this old paradigm of subconscious moving things. So we're going to go to the superconscious and accelerate things. What does that look like?Gunther Mueller36:25Yeah, so I'm going to share that. But I don't want to say like everything that's been is not bad. Okay. We do the best we know how to do with what we know. And seven-year-old ongoing see the psychotherapist and he says the best that maybe your parents or whoever you had to do at the time, those were the tools, right? So think of everything is huge evolution that's happening. And this is awakening to the place that we're at today. And today, we have something called the magnetic mind method where, you know, what if it could be easy, what if it doesn't take 10 years of psychotherapy to figure out why I am the way that I am, and why I can't have what I want, or I get what I want, and it gets taken away. So when we go to superconscious, superconscious already knows. And we don't need to spend all that time digging in and asking the questions and figuring out where the connections were and where the misalignments were in Well, you know, I thought something but it wasn't really true. And I had, I gotta straighten all this out. superconscious can straighten that out in a blink, just because it already knows and you don't have we don't have to tell it any of the details, all we have to do is focus on what we want. And it's really the experience of what we want. So you mentioned earlier about, you know, getting into the emotions, getting into the emotion of the end result is step three, and the five step method because, you know, Einstein said, Look, there's only two things in the universe, there's information and there's energy, the information is the desire, the what, what do I want, okay. And the energy is the emotion. And it's like a holographic movie that when those two things come together, it's actually how a hologram is created. Okay, the energy and the information come together and shoot the manifests a hologram. So think of your life as like a holographic movie, where you are manifesting, you are, things are showing up in real time. And think of yourself for a second, as you're the director, you're the producer, you're the screenwriter, you've handed everybody their parts, and everything is happening, not to you, but for you to have the experience that's congruent with your identity. So you get treated by the characters, you know, as Shakespeare said, you know, all the world's a stage, and we're just actors on it, right? But you're the main guy, even in a movie, imagine walking into the screen and you becoming the main character. And when you look at some movies or series or something like that, some characters get written out a script. Right, they die off something terrible happens, they no longer exist. And the whole dynamic of the movie changes Think of your life in that way. The people that are there the circumstances, the conditions, the what is now is just what is. And when we focus on something else. And is the key point here also, we can focus on the problem, we can focus on how to fix the problem, and try to create, invent or figure out how to solve the problem. But what we focus on grows. So the more we focus on the actual problem, the bigger the problem sometimes gets. That's where we have to back out of that go into the creator stance and focus on what we would love focus on what we would just purely want. And that's how you know you have a true choice. If I asked you why do you want what you want? And you give me an answer and it sounds like a stepping stone on to something else. As a coach, I'm going to tell you that's not really the true choice because you're choosing something to get something else we have to get to the final end result. So I want to share just four creative stances with you real quick, to give you the perspective, a good creator stance is something like I choose to live my true nature and purpose. I just choose it. I choose to live my true nature and purpose because I'm going to tell you the only power that we really have in life is the power of choice. Think about it from the moment you wake up in the morning, what time do I get up? What are we going to wear, when we're going to go, we're going to drive, I'm going to take a bus, you know, when am I going to take lunch, it's a series of choices. And every choice has a result, or call it a consequence, right? So I choose to live my true nature and purpose. Another one is I choose to be the predominant creative force in my life.Gunther Mueller0:00I choose to live the life that I love. And this comes in alignment with your actions, right? The person that is living a life that they love, or this imaginative person that you see right now living a life that they love and the desire with that emotion of the end result, you're seeing the life that you love. What would you be doing right now, that's in alignment with that true choice. The action has to become an alignment, the identity needs to shift, but the actions have to be in alignment with their true choice. In other words, I choose to be healthy and vital. You know, the health issues we have going on in this country in the world and all that, you know, when your body is not working, and supporting you in the life that you love, it's a problem, you don't get to do the things that you love to do, because your body's not cooperating. So having a true choice, and I choose to be healthy and vital. And so let's just take a serious condition right now, if you're dealing with cancer of some level, the two choice is not to be cancer. The true choice is to be healthy and vital to have the experience. It's not the problem solving of how do I beat cancer? What therapy Do I need to beat cancer and all that the mindset shift needs to be creative and say, I choose infinite health and vitality? And what would it feel like to be infinitely healthy and vital. And you get into that stance? Because I'm going to tell you that everything that's ever been created, has been created twice, once in the mind. And once in a three-dimensional physical experience.Ari Gronich1:31Yeah, you know, it's funny, because I watched a lot of Jim Rohn stuff. And one of the things that Jim Rohn says is, is you wouldn't build a hotel until it was done. Right. You wouldn't build the thing until you had the blueprints until it was done. In your mind. If you just started to build something, you had brick, and you didn't know what you were building, people would ask you, you know, what are you building? I don't know, I'm just putting bricks together and they'd send you away. You know, he's like we are human beings are the one species that can program in and pre plan and choose what they're going to create. And…Gunther Mueller2:19sees are on instinct right. They're instinctual beings. Right? We have this creativeness. And if you ever read scripture in the beginning, I mean, it starts out right in the beginning says we were created in the image of the Creator. And so if we were in the image of the Creator, what are we? We are creative?Ari Gronich2:40I mean, if you're religious and believe that that is the line, absolutely. If you're not religious, and you don't believe that that's the line in a book, that means anything, it's still we create our kids, right? We create our imagination; I tell people on this show a lot. Like, we made this shit up. This is all a figment of our imagination. All of it, every single thing that we see here, taste do, everything is a figment of our imagination.Gunther Mueller3:17And the science backs that up. Our thoughts are perceptions and illusory, they're illusion, our emotions are illusion, they're not real. Okay, we make you sad. It's a simply we make this shit up, we create the reality we experience. And that's why you already are a superconscious creator. And all we have to do is what are you focused on? Are you focused on solving the problem to get what you want? Or do you really take back your power as a creator and choose to be the predominant creative force in my life? Ari Gronich3:56So we're gonna go back to your sales background a little bit, okay? Is what you just said? Ring a picture in my head of a billboard with a sign that says buy something to do something to get somewhere, right? So people are watching social media, advertising, how do they even know what is their true choice? How would they how would you even at this level, in this day and age, right, the bombardment of information and problems and stuff, right? How does somebody get to what that true choice is and while avoiding the noise of the sales of that advertisingGunther Mueller4:52Great question, because that is step one. In the five step magnetic mines. How do you choose a true choice? How do you actually get to it? And a true choice. The simple answer is if I asked you like, give me something you would just love. Give me something you would just really want. What's something?Ari Gronich5:09I'll just go to the, you know, question that life spring always or landmark always asked is chocolate or vanilla? Okay, for ice cream, like, what do you choose, chocolate or vanilla. Gunther Mueller5:21Choice of chocolate or vanilla or the choice of chocolate? Doesn't really doesn't matter. One day, I'll choose chocolate one day, I'll choose vanilla, because I like variety. Right? Okay, so that but that choice doesn't have any consequences. Right? So let's say let's say somebody chooses, let's take it in business, right? Um, you know, be like, Ari if you're coaching them are those on the show today, I got to start this business because I'm sick and tired of my nine to five job and I'm tired of my boss, I want to work for myself, you know, and they've seen the glitz on social media of people who've made it big, and they're driving lambos and stuff like that, you know, and you're just like, I want that, I want that. But the only way I'm going to get that I'm not going to get that at my job doing what I'm doing right now. Because my boss is cheap, and he's never gonna pay me more. I'm not getting paid what I want, what I'm worth, you hear the story that goes on mouth is a story, right? And so they would come to a coach like myself or like you, right? And we'd be like, well, I'm gonna do this, I need help doing this. And I'm gonna ask the question, Well, why do you want that? And if the answer is not just because I want it, it's not a true choice. If the answer becomes I want it, because when I have it, then I can be this or I can get that or it can become something else. Or it gets me to another place, then that thing that you just told me you wanted is not the true choice. It's just a stepping stone on to what you really want. So a true choice gets answered with I want it just because I would love to experience that. I want it just because I want it my being my desire, I just want that. I don't care what anybody else thinks. I don't get anybody else's input, whether it's a good choice, bad doesn't matter. I want it because I want to experience it experience is a very important thing. Because it's maybe not be a thing. It may not be something, it may be just an experience, like infinite abundance, or, you know, optimal vital health. Right?Ari Gronich7:30So true choice. I still, and I just want you to go deeper, I guess into it. I still see. Let's say I want joy, I want infinite joy. I want to experience joy at will. Gunther MuellerWhy do you want that? Why do you want to experience joy? On an infinite level? Ari GronichRight? That's what I'm saying is like, if somebody's saying that there's, at least in my case, it would be cuz I don't, but it would be. I haven't experienced enough joy in my life. So I want to experience at will the experience of joy. I love watching joy when I watch American Idol and I see somebody win. And they're just like, sheer joy. I want that. Right? It never, it never seems like a true choice. Because there's always is an outside perspective or an outside. If it's something I have not experienced, right, then it's outside of me. It's something I've been told would be good, right?Gunther Mueller8:35Your key right there, it's something I've been told would be good. And I should go do that. I should want that. That would be good for me. Someone else said. And then somebody else says that somebody else says somebody else says because all these somebody else's said it, it must be true. And it's not. So that's why coming into two choices and exercise that I do. It's called seven levels deep. And so you say the first thing that you really want, whatever it is, and I'm gonna ask you. So when you get that, what does that give you? Well, what do you get when you get that? What does that do for you? You say? Well, when I get that, I'm going to get this and it goes down to the next level. Okay, so when you get that, what does that do for you? But what do you get when you get that? Well, when I have that, then it's going to give me this. Okay, take that down. You have to third level now, right? You do that for seven levels deep. I want this because it gets me that then well, why do you want this? Well, because when I have this I can have that. And when I have this then I can have that and he push it down about seven levels and when you get down to the very bottom, and a lot of times you need a coach to do this because people will immediately say I don't know. And a coach will be like you do know you are connected to your infinite field that infinite consciousness. You do know, there's an aspect there's a resistance of you that doesn't want to recognize that, you know, because there may be a latent fear there, there may be something there that's blocking that, that real connection. And so it's a great exercise to go seven levels deep and Okay, so I say I want this thing, what do I want that? Okay, when I get that was like, What do I want that and you take it all the way down, that's how you get what I really want, is the experience of freedom. And no one ever getting to tell me what the hell to do. That's what I really want. Freedom, like for me is one of the operative words that have pushed me through life is the word freedom. And I was when I was in Alaska, I was working on a boat called the Born Free. no coincidence. Okay, the Born Free. And that's I identified with that name right away, like I am born free. It's not a I choose to statement like I knew it my consciousness that I am born free, free to choose what I want, when I want, who I want to do it with how much of it I want to do, it's me. And some people will flip that around while you just being selfish. No, it's in that same vein, that I can help whoever I want, I can provide for whoever I want, I can do all things with that type of freedom. And so when you look at the human desires of what it is we truly want, and you do a seven levels, deep exercise like that, I can tell you're going to get to the nitty gritty of what it is you really want. And that leads me to the two most important questions in life, which is Who are you? Who is it that you say you are? How do you operate? you operate with honesty, integrity, you know, things like that, like how do you I want to give you all the words, but how do you describe who is it that you say you are Who are you? And most of us have not spent any time contemplating that question, Who am I really Who am I? And then the second question is, what do I want, based on who I am what do I want. And all the social media, all the noise, all the influence from parent's school programming, peer pressure, whatever you want to call it, all that noise needs to cease for a moment, or lots of moments. So that you can actually get into your own being and understand what it is you truly would choose just because you would love it. See, we've never been given the opportunity in our programming really, to choose from a place of love. We choose from a place of elimination, sometimes, well, I got three crappy choices. Okay, so get rid of that one, get rid of that, I guess I choose that we choose by default, because we don't see any other choices, I don't have any. So I got to do that. And we choose by consensus. Before I make a decision, let me check with everybody and make sure everybody's gonna be on board with my decision. That's not a true choice. Where the fear is, if I choose something, my friends don't agree with me, I'm gonna lose my friends. That's fear. Right? So be conscious, observe how you choose what you choose. And that's a practice also, that's something that we just have to become conscious of? And what is our motivation? What are we really? Why do we want what we want? Is it to impress others? Is it to be liked? is it to have this feeling of belonging? is it to have this feeling of significance or being capable or admired, or to be beautiful or to be whatever, right? Whatever that desire is, it's a process of becoming conscious now, we don't have to go back and unravel everything because we are not broken. What is, is, and this is another key point I want to share the future will not be better. Many of us to say my life will be better when, my life will be better when this happens, or that happens when I get this, then I'll be able to do that. And everything is contingent on the future showing up. That's not how you create because the future is not going to be better because you are still going to be you in the future. Okay, what's it's just going to be different. And if we can just hold that thought for a second, the future is not going to be better. It's just going to be a different experience. And what I'm experiencing right now is just what is it's not bad. It's not horrible, because we just naturally our conscious mind like to throw labels on stuff. This suck. That's bad. That's wrong da da da.., right? And I want this because it's gonna be better. It's not going to be better. It's just going to be different experience than what is now If we can hold that for a second, we can achieve a level of contentment in the present moment, we can just be okay with what is. And we can just observe the current reality. And what is right now as just that is just what is and I choose something different. The feel the feel the difference of that it's not a half two, it's not anything like that it's I want, I just, I'm okay with where I am right now. It's just what it is. I created it all anyway. And I'm just choosing a different experience.Ari Gronich15:37Right. So that kind of ties into the Create a new tomorrow, you know, ideal is, as we started off with at the beginning of this is how to create a new tomorrow today. How do we? How do we get out of our own way? How do we, you know, stop the madness, you and I started before we hit record, we started talking about kind of what's going on in the world. I mean, the president of Haiti was assassinated, we've got the Cuba stuff going on, we got all of this madness around us. And the way that I always see have seen it is when the madness is happening around me, the only way for me to be the eye is for me to go inside. And outwardly focus from within my energy so that I'm pushing at the hurricane, so to speak versus and I'm in the eye instead of being in in the storm. But and obviously that works. Sometimes it doesn't work others, that's just the visual that I have. But we were talking about this, like, how does somebody get out of this place of madness that they're in? Whether it's web site, I don't care if the political or religious or scientific spectrum or cultural spectrum? It's everywhere right now. It's like, it's like a furnace has been lit. And and it's building pressure, right? I think something like we're in a pressure cooker. Yeah, let's talk about how do we let the steam out of the pressure cooker a little bit and then pop the top. So we're not in it? And do that in a safe way. But, you know, like, how do we get to that place from where we're at? Because what you're talking about feels very idealistic. I want to take it out of the idealism and into realism into how can somebody how can we do this? Now? How can we be in this?Gunther Mueller17:45So the idea, let's take the analogy of the pressure cooker. What if you do not have to reduce the pressure? But what if you can exist within the pressure and not be affected by the pressure?Ari Gronich18:04I guess that that's how I feel within like that I have a hurricane. Right?Gunther Mueller18:10It's a great visual, it is a great visual because there is infinite calm in the eye of the hurricane. To the left, there's chaos to the right, there's chaos, stuff blowing up, getting knocked down over here, stuff blowing up and knocked out over there. But in the middle, no wind, no storm in the eye could even be sunny in the middle of the hurricane. You know, it's like this whole Sun comes through and beautiful day. But the Hurricanes moving right. So the idealism, it only seems ideal, because it's a new concept. And just as asked was a new concept, you know, 30 years ago, that kind of thing, right? And rebirthing, we talked about that offline to so many techniques and things like that, to what to help us feel better. That's really what the human experience is, we want to just feel better. We want, we want what we want, which is to sum it up, less pain, more satisfaction, we want less pain and more satisfaction, you can throw the words meaning fulfillment in there. And what we talked about offline briefly was this pressure cooker feeling is like I described as people I think are getting to the point globally. Now. You mentioned all the places where there's unrest and problems going on. They are tired. They've had enough of not having enough. And I've always thought this look when you have nothing to lose. You have nothing to lose. And so you're going for it all because the current situation is not worth maintaining anymore. There's nothing in it anymore. It's painful, is gotten to the point where the pain of that existence. It is time to do something about it. But again, if you look at the world, they're solving it from the problem-solving real reality, we need to overthrow the dictator, we need to get a new government, we need to be left or right, we need to do this we the problem solving is there. So to answer your question that you asked me earlier a little bit, I wanted to inject the idea of we need to be it in order to see it. And the personal development movement have had has had that switched around a little bit, that as we start seeing results, we can be more that of that thing, right? I get when I have a billion dollars, I can be generous, right? So I need to create all this stuff. I gotta be a billionaire. And then I'll be able to, you know, be generous, like, if you're not generous now, in the current situation, you will not be generous. how many billionaires Do you know, I don't know that many of them. But I've heard of, and I read their stories, right? They're in fear of losing what it is they have. They don't have the bliss and the peacefulness and the calm in their life, and the experience that most of us really want or the freedom, okay, and we think that Oh, being that person like, the responsibility that comes with that position, the number of people that are trying to take your stuff, when you're in that position, the attacks that are coming at you, we think, oh, because, you know, we're in our secure Oh, it'd be so much better to be that guy. I'm here to tell you, not really not unless you structure it properly with the end in mind. Now, there are some people that have that, let's say kind of wealth, and I talk about wealth, not because it's the most important thing, because it's on a lot of people's minds. It's easy to measure, right? And when you look at the world, that seems to be what the irritation is, is not having enough. Ari Gronich21:53Let's say, you know, we go to the statistic 1.87, I believe trillion dollars into the like, top 10, 20 people in the world, their wealth over the course of COVID. Right. Whereas we spent, I think it's around 3 trillion. So I'm just going to correlate it right. So I correlate it, like the government spent 3 trillion of taxpayers money, 2 trillion of that approximately went into 20 people's hands. Right. So there's a correlation between wanting, I guess, fairness or equanimity and these kinds of things within the situation that that we aren't seeing, right. So if we're not seeing the fairness and equanimity that pain level goes up, as you were saying, and then the pressure cooker arises. But I don't think that people correlate the two things like they don't say, two, or 3 trillion came out of people's hands and into 20 people's hands, like out of a few 100 million into 20 people's hands. They don't say that they don't, they just say during this period of time, these top 20 people, their wealth skyrocketed, and these people their wealth went, right. So if we don't get the correlation, how do we get to the end, I'm going to use the word solution but as a problem solving, but how do we get to that place where equanimity fairness, those things, where as they're not guaranteed in life, are at least structured more appropriately or so that people can have the sense that when they do something like this magnetic mind, you know, and they're doing these five steps that they actually think that that true choice can happen?Gunther Mueller24:03Yeah, so anything high Einstein said this to write anything that you can imagine, you can create, anything that's ever been created started in the imagination first, but you have to think of your life in little bubbles, you are in this little bubble right here. Okay. And that's just you, your desires, your true choices, the experience that you want in the current reality, and you want this experience just because you'd love it, just because you want it just because that's the experience you want to have. It does not mean that the entire world has to change for you to have this experience in your life. And let's just stick with the wealth or abundance type thing. In order for you to have the experience of abundance. It doesn't mean you have to be one of the 20 people. Ari, I want to use an example of breathing The last time you thought about how much air was available to you today to breathe.Ari Gronich25:06I'm a weird one, I think about it because I think about cleanliness and the air. But you know. Gunther MuellerThat's different from quantity, right? Ari GronichThat is different. quality versus quantity. Yeah, that's different.Gunther Mueller25:17But our experience as human beings is that we've always had pretty much unless you're drowning, or you're locked in a sealed box or something like that we've had an infinite air supply, we can breathe as much as we want as fast as we want. We've never really thought about, you know, is there going to be enough air today for me to survive? Know the so even in the current reality in the current moment, if you focus on just breathing, you can have the experience of abundance. That's what abundance feels like having more than enough. And so let's say in our lives, if we want to create that experience of abundance, if you have $10, left over from your budget, at the end of the month, you have more than you needed, you just have $5 left over at the end of the month. That is an experience of abundance, it may not match your desire. But this is what creates the contentment in the moment just for a time since you can plant your feet. And you can be it now. Okay, you can be it now you can experience abundance of what it feels like to be abundant in your little bubble. All right now around this bubble, is your family, friends and influence your little tribe is around there. And these are the ones that could be speaking, some sort of negativity into your thing, right, but you're in this bubble, you have a true choice, you have a desire, you have the thing that you would just love to experience for no other reason than the fact that you want it, you love it. And this field here is either going to you're going to influence this field or this field is going to influence you. And the more you secure yourself in your own being listening to your own voice, your own desires, and you focusing on that which you want, and not trying to solve for world peace or trying solve all the ills and all the problems in the world. It's the analogy of the airplane, right, you have to put your oxygen mask on first, before you can help anyone else. So getting in to the conscious creator stance, and choosing that which you want, creates this little bubble. And you can experience that which you choose to experience in this little bubble and it does work. Okay, the magnetic mind method has even restored eyesight, we're not promising that but we had a blind person go through a series of recodes and restored the eyesight because the identity shifted from a person that did not see to a person that now sees, we've had people get out of wheelchairs, because the identity has shifted, again, extreme examples of what is not promising that everybody, but when the identity shifts, the current reality changes. And that reality includes the bubble of your family may not like how your family and friends treat you or done it enough. But that can change too. When this changes, then this changes when this bigger bubble then changes, then the outer bubble changes and the more people that are taking this responsibility for themselves and manifesting their own true choice experience. And imagine if more and more and more people did this on a regular basis. And I regular by i mean you know, once or twice a day is getting into that field and being clear about what you want. Because you have to send that vibration into the field superconscious needs to know that you're serious about what you want. It can't just
Samantha is an international award-winning underwater photographer whose work concentrates on ecologically unique areas of the ocean. She is a Mission Blue Alliance Partner. With thousands of dives from the tropics to under the ice and to 100m, she is also an accomplished diver. Welcome to Dive In The Podcast, your favorite podcast about all types of diving, SCUBA, Tec, Freediving, and more, we cover it all. Every week on Monday we post new episodes filled with diving news, interesting dive topics, ocean advocacy, and much more. Join Justin, Nic, April, and Amit the hosts of Dive In: The Podcast. Guest: Samantha Schwann www.samanthaschwann.com Instagram @samanthaschwann Episode Links: News: Blue whale remains found at N.S. beach will be studied — giant eyeball included News: Results – AIDA Individual Depth Freediving World Championship 2021 – Limassol, Cyprus Support this Podcast on Patreon Episode Sponsor: TorpedoRays.com Find Us At- www.DiveInPod.com Contact and Subscription Links - https://linktr.ee/diveinthepodcast Find us on Social Media- This Podcast @DiveInPod April Weickert @aprilweickert Justin Miller @idiveok Nicolas Winkler @nicolaswinklerphotography NicolasWinkler.com Torpedo Rays @torpedorays Seafoxes @seafoxes_ Halifax Freediving Club @halifaxfreedivingclub Music Credits: RetroFuture Dirty Kevin MacLeod Link: incompetech.filmmusic.io/song/4278-retrofuture-dirty Upbeat Forever by Kevin MacLeod Link: incompetech.filmmusic.io/song/5011-upbeat-forever RetroFuture Clean by Kevin MacLeod Link: incompetech.filmmusic.io/song/4277-retrofuture-clean Life of Riley by Kevin MacLeod Link: incompetech.filmmusic.io/song/3976-life-of-riley License: creativecommons.org/licenses/by/4.0/
In this week's episode of the Spine & Nerve podcast Drs. Nicolas Karvelas and Brian Joves discuss a clinical case regarding a patient with Persistent Spinal Pain Syndrome (PSPS). To review, PSPS is not a single diagnosis, but rather an encompassing term that includes persistent painful disease with spinal origin. This disease can be linked to the predisposition of the human spine to develop painful pathology over time. The distribution of the symptoms in PSPS can be axial and/or radicular, and although commonly involves the lumbosacral spine, the cervical, and thoracic spine can also be the site of pathology. Importantly, spinal surgery may or may not have occurred, and may or may not be the primary contributor. Listen as the doctors talk through this clinical scenario of a gentleman in his 50s with PSPS and discuss treatment options including neuromodulation, specifically in this case Differential Target Multiplexed spinal cord stimulation (DTM SCS). DTM SCS targets not only neurons, but also glial cells (all forms of SCS most likely impact glial cells to some degree, however DTM SCS specifically works to optimize the neuromodulation of glial cells). Glial cells include oligodendrocytes, microglia, and astrocytes in the central nervous system; as well as Schwann cells and satellite glial cells in the periphery. All of these cells play critical roles in essential functions which include, but are not limited to regulation of fluid and ion homeostasis, protection of neurons, and creation and maintenance of blood-brain barrier. When glial cells are pathologically, chronically, and abnormally activated they play a critical role in the development and maintenance of chronic pain disease processes. In the setting of abnormal glial cell activity, the most common clinical manifestations for patients include pain sensitivity, fatigue, cognitive disruption, sleep disorders, and mood disorders. For a deeper dive specifically into glial cells, please see our prior conversation (https://anchor.fm/spine/episodes/Glial-cells--glial-cells--glial-cells----The-pain-cascade--modulation--and-chronic-pain-e5fb38) including a discussion with Dr. Ricardo Vallejo (https://anchor.fm/spine/episodes/More-glial-cells---Dr--Ricardo-Vallejo--science-that-matters--and-thinking-beyond-the-neuron-eb4m4i). And please listen to the conversation with Dr. Michael Fishman for a deeper dive on this study (https://anchor.fm/spine/episodes/Profound-Data-with-Dr--Michael-Fishman-elmp3f). This podcast is for information and educational purposes only, it is not meant to be medical or career advice. If anything discussed may pertain to you, please seek council with your healthcare provider. The views expressed are those of the individuals expressing them, the may not represent the views of Spine & Nerve. References: 1. Fishman M, Cordner H, Justiz R, Provenzano D, Merrell C, Shah B, Naranjo J, Kim P, Calodney A, Carlson J, Bundschu R, Sanapati M, Mangal V, Vallejo R. Twelve-Month results from multicenter, open-label, randomized controlled clinical trial comparing differential target multiplexed spinal cord stimulation and traditional spinal cord stimulation in subjects with chronic intractable back pain and leg pain. Pain Pract. 2021 Aug 7. 2. Vallejo R, Kelley CA, Gupta A, Smith WJ, Vallejo A, Cedeño DL. Modulation of neuroglial interactions using differential target multiplexed spinal cord stimulation in an animal model of neuropathic pain. Mol Pain. 2020 Jan-Dec;16:1744806920918057. doi: 10.1177/1744806920918057. PMID: 32290778; PMCID: PMC7160773.
The Internet is a Literal WebCongratulations to friend of the show, Ian Leslie, and to Industry West for ranking on 2PM's DNVB list and for Adobe Experience Maker Awards. Phillip and Brian talk about the Adobe Experience Maker Awards, the rankings, and ask the question of how some brands are ranked so highly. Millennials didn't invent meal prep delivery. Schwann foods, and catalog delivery — even the milkman — are all examples of modern reimagining of pre-existing retail models.In eCom news, Shopify continues to eat the world, bringing in another investment of Stripe, and launching payments buttons across Google Shopping and Facebook — without the need to be operating a Shopify store. The BNPL ecosystem has stratified into much clearer offerings, as Phillip lays out the roadmap for Afterpay, Affirm, and Klarna.“The world is reopening… New York City no longer has any covid restrictions. San Francisco opened up officially yesterday; the biggest cities are coming out of covid and physical retail is back. I feel like Afterpay is the big winner here in the latter half of the year, if I had to bet the way that people would be using this like everyone, every channel has to deal with the fact that physical retail is coming back.” - Phillip“The internet is held together by spider webs.” - BrianMost people's first ecommerce purchase was probably a digital property. Paula's Choice is the original direct to consumer brand, and predates what we know as the modern web. Launched in 1995 it was one of the first beauty brands online, and predated Google by 3 years. The first-ever secure online purchase was a copy of “Ten Summoner's Tales”, a solo album by Sting. Associated Links:Insiders #088: Paula's Choice: On Blind Spots and Phase CancellationIndustry West2PM DTC Power ListAdobe Experience Maker AwardsSubscribe to our weekly newsletter: futurecommerce.fm/subscribe Check out our latest research piece, Service is the New StorefrontHave any questions or comments about the show? Let us know on Futurecommerce.fm, or reach out to us on Twitter, Facebook, Instagram, or LinkedIn. We love hearing from our listeners!
ExZac, Matisse and late arrival John Ward head to Speak Studios to shoot the shit about cancel culture, psychedelics, and that one time the exorcist turned out to be the Schwanns guy.
ExZac, Matisse and late arrival John Ward head to Speak Studios to shoot the shit about cancel culture, psychedelics, and that one time the exorcist turned out to be the Schwanns guy.
We are joined by Mr Tom Quick for our first ever video podcast on everything orthopaedic surgeons need to know about nerve injuries.You can listen to the audio here as usual, but you can see the video plus a little extra on our YouTube channel here!We have had some teething issues trying out this new video format and so you may hear an occasional glitch in the audio. Apologies if so, this has been fully rectified going forwards and we will fully return to the rich, golden tones you are so accustomed to. Even more reason to check out this first video!Tom is a consultant orthopaedic surgeon working at the renowned Peripheral Nerve Injury Unit at the Royal National Orthopaedic Hospital and an ABC Fellow 2020/22. He also holds honorary consultant appointments at Great Ormond Street Hospital and the Evelina's Children Hospital. In addition, he is an Honorary Associate Professor at University College London.In this fun and fascinating conversation, we discuss:functions of nerves and the classifications of nerve injuriesneurapraxia vs neuropraxia (and how to really annoy a PNI surgeon)what actually happens when a nerve is injureda practical guide for the assessment of nerve injuriesclinical examination and how to do itspecial tests- Nerve Conduction Studies & EMG finally made simple!what to do if you find a nerve intra-operatively that looks damaged or cutthe Brachial Plexus and why injuries here are so significantsome common everyday clinical scenarios with nerve injuries and what to dothe key facts about nerve transfers vs tendon transfersneuropathic pain and how to deal with itTom's passion for open water swimming and the health benefits of sub-zero temperatures...beekeeping and the health benefits of honeyYou'll have a newfound respect for Schwann cells before the end too!Please subscribe to the show on your podcast player and leave us a rating and a review (with actual words)!You can also find us on YouTube, LinkedIn, Twitter, Facebook, Instagram and at www.orthohub.xyzTwitter:@orthohubxyz@kashakhtar@petebates
Justin Allen is an author, musician, and father from Michigan. He recently published his novel "Vera" on Amazon last year. Justin is a really creative personality and considers himself pretty lucky to be able to chase his dreams. He is currently working on several other new works as well. Topics of discussion:Vera, available exclusively on Amazon. Hunting coyotes in MichiganThe Schwann's manAnd several other random topics. Thanks for Listening!Hit Subscribe if you like the show.YouTube FeedVisit the website: notreallythatfamous.comCheck out the merch shop!Facebook/Instagram @notreallythatfamousYou can find Justin on Facebook.
In dieser Folge erfährst du, 1) was dein Nervensystem so kann... 2) wie es unterteilt wird und 3) wie das Neuron aufgebaut ist. Es ist ein "sanfter" Einstieg in das Thema Neurobiologie :-) Fachbegriffe in dieser Folge: peripheres..., zentrales..., autonomes (vegetatives)..., somatisches Nervensystem, efferent, afferent, Effektor, sensorisch, motorisch, Parasymathikus ("Rest & Digest") Sympathikus ("Fight or Flight"), Adrenalin, innervieren, Soma, Perikaryon, Axon, Axonhügel, Schwann'sche Zelle, Ranvier'scher Schnürring, Synapse, Endknöpfchen, synaptischer Spalt, Erregungsleitung, Gliazellen, Oligodendrozyten... Viel Spaß beim Lernen - schau gerne auch unterstützend in das Skript oder schreib deine Fragen an biologopodcast@googlemail.com
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.23.352872v1?rss=1 Authors: Kalinski, A. L., Yoon, C., Huffman, L. D., Duncker, P. C., Kohen, R., Passino, R., Hafner, H., Johnson, C., Kawaguchi, R., Carbajal, K. S., Jara, J. S., Hollis, E., Segal, B., Giger, R. J. Abstract: Sciatic nerve crush injury triggers sterile inflammation within the distal nerve and axotomized dorsal root ganglia (DRGs). Granulocytes and pro-inflammatory Ly6C high monocytes infiltrate the nerve first, and rapidly give way to Ly6C negative inflammation-resolving macrophages. In axotomized DRGs, few hematogenous leukocytes are detected and resident macrophages acquire a ramified morphology. Single-cell RNA-sequencing of injured sciatic nerve identifies five macrophage subpopulations, repair Schwann cells, and mesenchymal precursor cells. Macrophages at the nerve crush site are molecularly distinct from macrophages associated with Wallerian degeneration. In the injured nerve, macrophages "eat" apoptotic leukocytes, a process called efferocytosis, and thereby promote an anti-inflammatory milieu. Myeloid cells in the injured nerve, but not axotomized DRGs, strongly express receptors for the cytokine GM-CSF. In GM-CSF deficient (Csf2-/-) mice, inflammation resolution is delayed and conditioning-lesion induced regeneration of DRG neuron central axons is abolished. Thus, carefully orchestrated inflammation resolution in the nerve is required for conditioning-lesion induced neurorepair. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.20.348011v1?rss=1 Authors: Henzi, A., Aguzzi, A. Abstract: The cellular prion protein (PrP) is essential to the long-term maintenance of myelin sheaths in peripheral nerves. PrP activates the adhesion G-protein coupled receptor Adgrg6 on Schwann cells and initiates a pro-myelination cascade of molecular signals. Because Adgrg6 is crucial for peripheral myelin development and regeneration after nerve injury, we investigated the role of PrP in peripheral nerve repair. We performed experimental sciatic nerve crush injuries in co-isogenic wild-type and PrP-deficient mice, and examined peripheral nerve repair processes. Generation of repair Schwann cells, macrophage recruitment and remyelination were similar in PrP-deficient and wild-type mice. We conclude that PrP is dispensable for sciatic nerve regeneration after crush injury. Adgrg6 may sustain its function in peripheral nerve repair independently of its activation by PrP. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.06.327957v1?rss=1 Authors: Wagstaff, L. J., Gomez-Sanchez, J. A., Fazal, S. V., Otto, G., Kilpatrick, A. M., Michael, K., Wong, L. Y. N., Ma, K. H., Turmaine, M., Svaren, J., Gordon, T., Arthur-Farraj, P., Velasco-Aviles, S., Cabedo, H., Benito, C., Mirsky, R., Jessen, K. R. Abstract: After nerve injury, myelin and Remak Schwann cells reprogram to repair cells specialized for regeneration. Normally providing strong regenerative support, these cells fail in aging animals, and during chronic denervation that results from slow axon growth. This impairs axonal regeneration and causes significant clinical problems. In mice, we find that repair cells express reduced c-Jun protein as regenerative support provided by these cells declines during aging and chronic denervation. In both cases, genetically restoring Schwann cell c-Jun levels restores regeneration to control levels. We identify potential gene candidates mediating this effect and implicate Shh in the control of Schwann cell c-Jun levels. This establishes that a common mechanism, reduced c-Jun in Schwann cells, regulates success and failure of nerve repair both during aging and chronic denervation. This provides a molecular framework for addressing important clinical problems, suggesting molecular pathways that can be targeted to promote repair in the PNS. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.04.324335v1?rss=1 Authors: Budak, M., Grosh, K., Corfas, G., Zochowski, M., Booth, V. Abstract: Hidden hearing loss (HHL) is an auditory neuropathy characterized by normal hearing thresholds but reduced amplitude of the sound-evoked auditory nerve compound action potential (CAP). It has been proposed that in humans HHL leads to speech discrimination and intelligibility deficits, particularly in noisy environments. Animal models originally indicated that HHL can be caused by moderate noise exposures or aging, and that loss of inner hair cell (IHC) synapses could be its cause. A recent study provided evidence that transient loss of cochlear Schwann cells also causes permanent auditory deficits in mice which have characteristics of HHL. Histological analysis of the cochlea after auditory nerve remyelination showed a permanent disruption of the myelination patterns at the heminode of type I spiral ganglion neuron (SGN) peripheral terminals, suggesting that this defect could be contributing to HHL. To shed light on the mechanisms of different HHL scenarios and to test their impact on type I SGN activity, we constructed a reduced biophysical model for a population of SGN peripheral axons. We found that the amplitudes of simulated sound-evoked SGN CAPs are lower and have greater latencies when the heminodes are disorganized, i.e. they are placed at different distances from the hair cell rather than at the same distance as seen in the normal cochlea. Thus, our model confirms that disruption of the position of the heminode causes desynchronization of SGN spikes leading to a loss of temporal resolution and reduction of the sound-evoked SGN CAP. We also simulated synaptopathy by removing high threshold IHC-SGN synapses and found that the amplitude of simulated sound-evoked SGN CAPs decreases while latencies remain unchanged, corresponding to what has been observed in noise exposed animals. This model can be used to further study the effects of synaptopathy or demyelination on auditory function. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.09.288100v1?rss=1 Authors: Siddiqui, A. M., Islam, R., Cuellar, C. A., Silvernail, J. L., Knudsen, B., Curley, D. E., Strickland, T., Manske, E., T Suwan, P., Latypov, T., Akhmetov, N., Zhang, S., Summer, P., Nesbitt, J. J., Chen, B. K., Grahn, P. J., Madigan, N. N., Yaszemski, M. J., Windebank, A., Lavrov, I. Abstract: We report the effect of newly regenerated neural fibers via bioengineered scaffold on reorganization of spinal circuitry and restoration of motor functions with electrical epidural stimulation (EES) after spinal transection (ST). Restoration across multiple modalities was evaluated for 7 weeks after ST with implanted scaffold seeded with Schwann cells, producing neurotrophic factors and with rapamycin microspheres. Gradual improvement in EES-facilitated stepping was observed in animals with scaffolds, although, no significant difference in stepping ability was found between groups without EES. Similar number of regenerated axons through the scaffolds was found in rats with and without EES-enabled training. Re-transection through the scaffold at week 6, reduced EES-enabled motor function, remaining higher compared to rats without scaffolds. The combination of scaffolds and EES-enabled training demonstrated synaptic changes below the injury. These findings indicate that sub-functional connectivity with regenerated across injury fibers can reorganize of sub-lesional circuitry, facilitating motor functions recovery with EES. Copy rights belong to original authors. Visit the link for more info
He says he is a passionate entrepreneur and mindset junkie from Canada who married young and had kids and went through the typical struggles of a young family and aspiring entrepreneur including bankruptcies. Through all of the challenges he went through, mindset became front and center for him. He discovered this when selling door to door food sales for Schwann’s. His manager at the time gave him a copy of Think and Grow Rich which sent him down the path of discovering how to master his own mind. He calls this a “gateway” to the world of mindset and personal development. Expanding your perception of your worth is critical to growth and mindset. Our lizard brain doesn’t under good vs bad, it only knows if you are alive or dead. John Asarraf Book The Answer Change of routine triggers fear in the unconscious mind which is way more powerful than the conscious mind. It becomes important to change the habit patterns. This requires a great deal of hard work to break the pattern. Awareness of the want to change and paying attention to what you say and do in order to make different choices in the moment to install new neuron firing in the brain. “I can’t afford that” is a common thing people looking to gain abundance use and this sends a signal to the subconscious you are where you are and not going to get more money. A technique he uses is to cay “CANCEL CANCEL, How can I afford that”. This is powerful. When you set an intention, do not worry about the how. Focus on what you can do differently. I am statements are not the most effective because they are lying to yourself and your subconscious won’t respond. Say instead, “I am not where I want to be but am getting better every day.” He talked about how he and his came into their relationship with beliefs they developed over their lives. Trevor Moawad Why do you want to make a change is an important question to ask yourself. And, how will it feel when you have achieved that? That feeling is what is important. The mind needs to be aligned to a positive emotion in order for a change to happen. Tony is not a fan of news programs. He recommends turning off the news and be more selective about what you take in information wise. Change the channel on your thoughts much like you change the channel on tv. Though Tony does say do not go to bed with the TV on. This Too Shall Pass is a mantra Tony encourages everyone to use often. http://thatmotivationalguy.com/podcast/ Https://www.johnracine.com Https://www.instagram.com/johnracinejr
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.01.180919v1?rss=1 Authors: Schwaller, F., Begay, V., Garcia, G., Taberner, F., Moshourab, R., McDonald, B., Docter, T., Kuehnemund, J., Ojeda-Alonso, J., Paricio-Montesinos, R., Lechner, S. G., Poulet, J. F., Millan, J., Lewin, G. R. Abstract: Fingertip mechanoreceptors comprise sensory neuron endings together with specialized skin cells that form the end-organ. Exquisitely sensitive vibration-sensing neurons are associated with Meissner's corpuscles and Pacinian corpuscles. Such end-organ structures have been recognized for more than 160 years, but their exact functions have remained a matter of speculation. Here we examined the role of USH2A in touch sensation in humans and mice. The USH2A gene encodes a transmembrane protein with a very large extracellular domain. Pathogenic USH2A mutations cause Usher syndrome associated with hearing loss and visual impairment2. We show that patients with biallelic pathogenic USH2A mutations also have profound impairments in vibrotactile touch perception. Similarly, mice lacking the USH2A protein showed severe deficits in a forepaw vibrotactile discrimination task. Forepaw rapidly-adapting mechanoreceptors (RAMs) recorded from Ush2a-/- mice innervating Meissner's corpuscles showed profound reductions in their vibration sensitivity. However, the USH2A protein was not expressed in sensory neurons, but was found in specialized terminal Schwann cells in Meissner's corpuscles. Loss of this large extracellular tether-like protein in corpuscular end-organs innervated by RAMs was sufficient to reduce the vibration sensitivity of mechanoreceptors. Thus, USH2A expressed in corpuscular end-organs associated with vibration sensing is required to properly perceive vibration. We propose that cells within the corpuscle present a tether-like protein that may link to mechanosensitive channels in sensory endings to facilitate small amplitude vibration detection essential for the perception of fine textured surfaces. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.05.136226v1?rss=1 Authors: Martineau, E., Arbour, D., Vallee, J., Robitaille, R. Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motoneurons in a motor-unit (MU) dependent manner. Glial dysfunction contributes to numerous aspects of the disease. At the neuromuscular junction (NMJ), early alterations in perisynaptic Schwann cell (PSC), glial cells at this synapse, may impact their ability to regulate NMJ stability and repair. Indeed, muscarinic receptors (mAChR) regulate the repair phenotype of PSCs and are overactivated at disease-resistant NMJs (Soleus muscle) in SOD1G37R mice. However, it remains unknown whether this is the case at disease-vulnerable NMJs and whether it translates into an impairment of PSC-dependent repair mechanisms. We used Soleus and Sternomastoid muscles from SOD1G37R mice and performed Ca2+-imaging to monitor PSC activity and used immunohistochemistry to analyze their repair and phagocytic properties. We show that PSC mAChR-dependent activity was transiently increased at disease-vulnerable NMJs (Sternomastoid muscle). Furthermore, PSCs from both muscles extended disorganized processes from denervated NMJs and failed to initiate or guide nerve terminal sprouts at disease-vulnerable NMJs, a phenomenon essential for compensatory reinnervation. This was accompanied by a failure of numerous PSCs to upregulate Galectin-3 (MAC-2), a marker of glial axonal debris phagocytosis, upon NMJ denervation in SOD1 mice. Finally, differences in these PSC-dependent NMJ repair mechanisms were MU-type dependent, thus reflecting MU vulnerability in ALS. Together, these results reveal that neuron-glia communication is ubiquitously altered at the NMJ in ALS. This appears to prevent PSCs from adopting a repair phenotype, resulting in a maladapted response to denervation at the NMJ in ALS. Copy rights belong to original authors. Visit the link for more info
Te Whatarangi Dixon is a man with much "Mana' (The Maori word that means to have great authority, presence to command respect). Despite his relative youth at age just 30 he has twice already stared his own mortality in the face. He was the victim of Guellain Barre Syndrome or GBS for short. Guillain-Barre ) syndrome is a rare disorder in which your body's immune system attacks your nerves. Weakness and tingling in your extremities are usually the first symptoms. These sensations can quickly spread, eventually paralysing your whole body. In its most severe form Guillain-Barre syndrome is a medical emergency and in this case is what severe and meant Te Whatarangi was months in hospital. The exact cause of Guillain-Barre syndrome is unknown. But two-thirds of patients report symptoms of an infection in the six weeks preceding. These include respiratory or a gastrointestinal infection or Zika virus. Te Whatarangi lost all control over his body and literally watched his body fail and start to die while his brain remained fully conscious. The fear, the uncertainty, not knowing if he would live or die or if he lived if he would ever have any quality of life again or be trapped in a body that no longer worked sent Te Whatarangi through a long night of the soul. But he eventually emerged. Stronger, more resilient, more empathetic and more driven that ever before. This is a comeback story of survival and of love. The importance of family and how they helped him through. Te Whatarangi is now a qualified neuro-physio and knows exactly what his patients and clients are going through. He knows the battles they face and he guides them back on the path to their goals. Heartwarming and raw this interview will inspire you and make you grateful for the blessings you have. Te Whatarangi's greeting to you all in Maori Ko Putauaki te māunga Ko Rangitaiki te awa Ko Mataatua te waka Ko Ngāti Awa tōku iwi Ko Te Pahipoto tōku hapū Ko Wayne Haeata tōku matua Ko Kay Mereana tōku whaea Ko Blair Te Whatarangi Dixon ahau I have come from very humble beginnings. I am a product of my whānau (family) and I would not be the man I am today without them supporting me every step of the way. Everything that I am and everything that I strive to be is a reflection of not only myself but my whānau. I represent them and I hope to make them just as proud as I am of them. I was diagnosed with Guillain-Barre Syndrome (GBS) in 2014 and again in 2019 where only 1 in 100'000 people are diagnosed globally with a 1% chance of contracting it twice. Always an optimist and through my journey of self-discovery having faced the possibility of my own mortality, I am now proud to call myself a Neurophysiotherapist. My journey has been challenging yet unique and I wish to share my story with the world in the hope others feel inspired and to allow their light to shine. We would like to thank our sponsors for this show: For more information on Lisa Tamati's programs, books and documentaries please visit www.lisatamati.com For Lisa's online run training coaching go to https://www.lisatamati.com/page/runni... Join hundreds of athletes from all over the world and all levels smashing their running goals while staying healthy in mind and body. Lisa's Epigenetics Testing Program https://www.lisatamati.com/page/epigenetics/ measurement and lifestyle stress data, that can all be captured from the comfort of your own home For Lisa's Mental Toughness online course visit: https://www.lisatamati.com/page/mindsetu-mindset-university/ Lisa's third book has just been released. It's titled "Relentless - How A Mother And Daughter Defied The Odds" Visit: https://relentlessbook.lisatamati.com/ for more Information ABOUT THE BOOK: When extreme endurance athlete, Lisa Tamati, was confronted with the hardest challenge of her life, she fought with everything she had. Her beloved mother, Isobel, had suffered a huge aneurysm and stroke and was left with massive brain damage; she was like a baby in a woman's body. The prognosis was dire. There was very little hope that she would ever have any quality of life again. But Lisa is a fighter and stubborn. She absolutely refused to accept the words of the medical fraternity and instead decided that she was going to get her mother back or die trying. This book tells of the horrors, despair, hope, love, and incredible experiences and insights of that journey. It shares the difficulties of going against a medical system that has major problems and limitations. Amongst the darkest times were moments of great laughter and joy. Relentless will not only take the reader on a journey from despair to hope and joy, but it also provides information on the treatments used, expert advice and key principles to overcoming obstacles and winning in all of life's challenges. It will inspire and guide anyone who wants to achieve their goals in life, overcome massive obstacles or limiting beliefs. It's for those who are facing terrible odds, for those who can't see light at the end of the tunnel. It's about courage, self-belief, and mental toughness. And it's also about vulnerability... it's real, raw, and genuine. This is not just a story about the love and dedication between a mother and a daughter. It is about beating the odds, never giving up hope, doing whatever it takes, and what it means to go 'all in'. Isobel's miraculous recovery is a true tale of what can be accomplished when love is the motivating factor and when being relentless is the only option. Here's What NY Times Best Selling author and Nobel Prize Winner Author says of The Book: "There is nothing more powerful than overcoming physical illness when doctors don't have answers and the odds are stacked against you. This is a fiercely inspiring journey of a mother and daughter that never give up. It's a powerful example for all of us." —Dr. Bill Andrews, Nobel Prize Winner, author of Curing Aging and Telomere Lengthening. "A hero is someone that refuses to let anything stand in her way, and Lisa Tamati is such an individual. Faced with the insurmountable challenge of bringing her ailing mother back to health, Lisa harnessed a deeper strength to overcome impossible odds. Her story is gritty, genuine and raw, but ultimately uplifting and endearing. If you want to harness the power of hope and conviction to overcome the obstacles in your life, Lisa's inspiring story will show you the path." —Dean Karnazes, New York Times best selling author and Extreme Endurance Athlete. Transcript of the Podcast: Speaker 1: (00:01) Welcome to pushing the limits, the show that helps you reach your full potential with your host, Lisa Tamati, brought to you by Lisatamati.com Speaker 2: (00:13) You're listening to pushing the limits with Lisa Tamati. Today I have a guest to Te Whatarangi Dixon from Rotorua who is an amazing young man. He's a neurophysio something I'm very interested in. But he is also a victim of the Guellain Barre Syndrome. Very hard to say. We'll call it GBS. Now this is a syndrome that's a rare disorder in which the body's immune system, attacks your nerves, weakness and tingling in the extremities are usually the first sort of symptoms and the spread right throughout his body and it can be fatal. And he was certainly in deep die trouble for many weeks in the hospital and he shares his story today and his comeback journey. It's a really interesting, I'm very interested in people who have overcome the odds in comeback. Journeys for obvious reasons. And I think this journey just really that fax has been on is incredible and why he's tackled it in the way he's coped with it. Speaker 2: (01:09) He was then gone on because of this to become a neurophysio. So he's used what was a terrible thing in his life to do something good. So it was a real honor to have him on the show. I just want to remind you before we go over and talk to te there, my book is now available on audio. It's available on ebook, on Amazon on my website every which way you can get it now. Relentless. It's also in the bookshops. I had the greatest pleasure the other day when I walked finally into a shop and there was my book. So that was a pretty exciting moment. After seven weeks on lockdown, it's finally out there. So if you're interested in getting that, the book is called relentless and you can grab it on my book, my website at lisatamati.com Right now over the to the show with Te Whatarangi Dixon. Speaker 1: (01:54) Them. Speaker 3: (01:57) Well, hi everyone. Welcome back to the sharp pushing the limits. It's fantastic to have you back again. I am sitting with Te Whatarangi Dixon all the way over in the Rotorua. How are you doing mate? Good, thank you. Good. Thank you. Super excited to have you on the show. It's really cool. We've connected through your father in law who is a lovely man, Steven who I spoke for. He is a great man. He is a lovely man. And he just said, you've got to talk to my son in law. He's so interesting and I thought, yes, he is very interesting and I want him on my show. So today I was going to hear a little bit about Whatarangi and we're going to call them facts from here on. And and now Whatarangi is a equally a neurophysio. You're just just qualifying right now, sort of in the midst of finishing things up and getting him into a new career and job. Speaker 3: (02:49) But the reason, one of the reasons I want, I want to talk to you about that, but I also want to talk to you about you've got an inspiring comeback story. Can you tell us a little bit about GBS we, we you've had GBS twice and we're trying to pronounce it before Guellain Barre Syndrome, something like that. So yeah, it's a very big word. So we'll call it GBS and can you explain what that is and your, your journey with us a little bit and a little bit who you are for status. Speaker 4: (03:22) Yep. Okay. So my story basically starts from a little town called tickle. So that's where I'm actually from and my family is, and I grew up pretty much in the Bay. TNT. I think probably people will always think that my story is interesting is because Guellain Barre Syndrome or GBS as we call it is as 100, a hundred thousand people, I think contracted, well that's the neurological condition. And then basically a textual, your peripheral nervous system. So it's quite similar. That's how I kind of describe it to people. I'm totally on the stand that getting into the technical kind of tends of things is similar to that. You miss you miss the textural central nervous system either and GBS a textual peripheral nervous system. Wow. Cause people get what that is so they can proceed. It's kind of similar but there are differences. Speaker 4: (04:20) So I had a strength called ampersand, which is what's a text basically or your motor neurons. Annual sensory neurons. You can have different trends with the tech, just primarily your motor neurons or your sensory or I think he got five different Sharon's, I'm not, can't remember specifically about each one, but yeah, those two. Yeah. I had em send, so I took an attack my motor neurons in my, in my sensory neurons. But the potential for it to recover as higher because you have a special cell called Schwann cells in your peripheral nervous system and they can regenerate over time. So that's why if you have, if I wouldn't wish it upon anybody, but basically if you had GBS your what your and you and you were able to stop it from progressing, quite possibly, even people have, it can't be fatal. Speaker 4: (05:11) But if you at the interventions from the hospital placed on you I think within three to four weeks until you sat on told JPA starts to kind of overtake your body, you'll be lucky to recovering this quite high but post four weeks and you haven't had an intervention with they call it immunoglobulin therapy or plasma faceless where they basically take our, your white blood cells and replace it with others. Wow. so basically you'll be your pasta, your, your ability to recover. That's a lot higher with your peripheral nervous system because your central nervous system are made out of oligodendrocytes and that's what they make up are once they damage, they don't rip you. Wow. So if you about a motorway system, once you've got an issue major, such a major highway, so one roads basically destroyed, it'll never be recovered. Speaker 4: (06:05) You'll be able to actually try and tap into other areas and go off road and then come back on, wow, I want to kind of destroy their part of the road and we'll never recover. Whereas Guellain Barren Syndrom, once that Schwann cell is basically damaged, if they're forced to before the damage, its ability to, to re regenerate as higher Scwh is in. This isn't the bird Swan. Swan. So S C W H. Okay. So that's a german. SCWH. Okay. So how does it manifest itself in your body? So you've got the, luckily not the central nervous system one, but more of the peripheral. How did that sort of manifest and what were the symptoms? Okay, so for me in 2014 mindset of half the thing is they don't actually fully understand why it HIPAA or like what actually causes causes a bacteria virus. Speaker 4: (07:09) We don't yet, but they understand what happens to once it starts. What's a, what's a begins to happen. So for me how they described the words, I, I basically called a guarantee Stein bug basically a month before GBS kind of started to could have been related. I go to my body, yes. So what they, what they perceive as what happens, it's an auto immune disease. So I had discussion or anti Stein nonfiction and I recovered from that. But however, what happened is you obviously when you get sick, you build up your immune cell or your immune system starts to kick in and you build get your killer T cells and then eventually you'll have resistant T-cells to action to buy down the killer T cells. Cause they've already destroyed the bug. Yep. What's happened is in my immune system, my resistant T cells to to actually hinder and stop the killer T cells from producing and actually start to generate around the body, they don't actually start to kick in. Speaker 4: (08:12) So your immune system had all these killer T cells floating around. And then I think obviously then I just got another random cold bug about a month later. And because you had these killer cells, so floating around in my body, I'm talking kind of later and I used to help you find fully understand it's important. Yeah. And so basically what's happened is my immune cell, my immune system has decided to, they've got this new bug, these qualities are the floating around. I have no idea what to do with this new bug and all of a sudden have started to just manipulate itself and then attach in a tech my, my peripheral nervous system. So phone cells instead of that classic auto immune shoot all the goodies and the baddies at the same time. Yeah. So it spawns my, my immune system starts to attack my own body. Speaker 4: (09:03) Yep. Essentially. Yeah. And so you don't, you don't know whether it's coming from there you know, that that gastrointestinal thing or not, but quite likely that that's caused that caused this reaction in the body. Obviously when you, when you're sick, obviously you get increased inflammation, which means that increases your immune system. And so it just, just helps you like a, like a, like as if you're standing in front of her train. And so basically how mine started was I just started getting pins and needles and my peripheral, like basically in my hands and my feet. Yeah. And it slowly kind of, I started basically just getting pins and needles and it started gradually kind of coming out of my arm of my legs. And then I started losing sets on my sensory kind of went, went away first. So SABIC losing sensation. Speaker 4: (09:54) And then basically as it came up through my, through my feet and into my ankles, we have a thing called proprioception. And they basically tell us it helps you understand its joints on the stand we are in relation to space. And that's that it's to dissipate and actually kind of disappear for me. So I started losing balance. It wasn't anything wrong with my brain, it's just that I couldn't get the right signals from my feet and from the white bearings, my weight bearing joints to my brain to understand and tell my body where I was. I had that with mum, but from a brain injury. Yeah. And so she didn't know who she was away. She stopped the way the world started. Special awareness because it's very hard to explain. Yeah. So this all just started happening. I don't know why, what's happening? Speaker 4: (10:43) You just kind of just randomly came on. So I started losing sensation and eventually started losing weakness in my hands. My jaw. I just knew something was wrong. I went to the doctors. The first time when I started getting pins and needles actually seeping into a physio, like some form of nerve issue of my lower back or, or something. Cause at the time I had, I had an injury, I'm a little bit. Yep. So say me, the basically nothing happened. A week later it started getting worse. Went back to my GP. He doesn't know, he didn't know what was happening. Obviously we could have the GP and had, you know, had I had signs of symptoms, they kind of live on possibly being meningitis as well. Yeah. He's sent me into, he see me in hospital, showed away basically after their next visit. Speaker 4: (11:31) So this was two weeks after that sort of started happening. A huge and obviously because he sent me diagnosed me possibly with a hypothesis of possible, possibly meningitis. I was treated for meningitis when I got there. By winter it wasn't, it wasn't I went and had my spinal taps. Yeah, spinal tap generally for meningitis in GBS cause they do present quite similar if they, if they think so. They're trying to cross the cross all the T's. We then, and then as they actually, when I went into hospital, I started getting huge migraines. I was getting migraines and I was skinning photophobia. So I've kind of actually optimized the life would just penetrate and just give me huge headaches. So I, when I was presenting what's, you know, and that's even another sign of possibly being in Jarvis and migraines. I, however, I didn't have a rash. That was, I need public one real, something they usually would get from in a data cell. We then had my spinal tap done, went for a CT scan. And then I was isolated basically because if I'm in a ditis spread it out at this point they still didn't know what I actually had. They were just going on. You know, the signs and symptoms on me, possibly heavy meningitis skins fascination and hits the spinal tap, then CT scan. Speaker 3: (12:55) Yep. Carry on. Mum's bringing in the middle of the webcast. She always does. Everybody who listens to the podcast knows this is a key ring from Mark to carry on mate. Speaker 4: (13:08) Yeah. And then and then I'll, then they for a week nothing basically improved. So all the all the drugs that they go to me throughout the time to help me try and beat meningitis were working. I was getting worse and I started losing what I'd done in relevance to that. I was actually getting really weak, but I couldn't actually convey that to them because I started getting, you know, I started losing my, my, I couldn't breathe and I started, I get to be on a ventilation also just so much pain. So I started getting hyper sensitivity. So basically cold felt like hot hot, felt like cold, a polo felt like a waste of time. I felt like I was driving into into the beat. So when I was just lying on the bed, I felt like I was getting pulled down by gravity. So [inaudible] rotation or anything kind of going out of whack, you everything just becomes imbalanced and it might, your brain can not understand or what, and it's trying to rebalance itself. And in that process that's kind of having, it's actually being detrimental to your, to your ability to kind of actually understanding the world just cause everything. Like basically if you'll need to bombard your nurse to actually understand, you know touch smells like every foot of sensation that you can basically think of. Speaker 3: (14:27) We had for granted so much and we know that this is, yeah, something's touching my right hand or I'm feeling my left hand or, Speaker 4: (14:35) And then basically third weekend I had an MRI and then the neurologist was actually away at the time. So the neurologist said that was actually from the house and told him the hospital for us. He was a white, you ever sees on a, on a spent sabbatical at another hospital. And so the neurologist from Palm smelt was coming up two or three times a week. Yep. So he came up and he basically once they won't say best, so he thought busters, a meningitis B bike. And I started and I had an Ida, my sister in law, she found a possible link to being something more neurological because I had this window of opportunity. We actually felt, you know, everything kind of normal, a little bit full for a time. And I asked Glen to kind of do some, do some assistance on me, who's my sister in law. Speaker 4: (15:25) She's now registered, now open a hospital. Wow. and she just chose a fifth year medical student at the time and she just done some systems on me and she felt my reflex is going through. I couldn't, my sensation was, was basically gone and she just went straight to straight to my consultant. My consultant got the neurologist to come in and they're all just basically look there, make straight away any new show way that ITVS basically Australian. I went straight into HDU. I was throwing spirometry, so I actually checked around my lung capacity was gone of the migraines. They organized for me to go for an MRI just to see what type of thing my body information was. And all of my, you know, all of my CRP scans, we were just through the roof. White blood cell counts were through the roof. So they knew that your, your menu system, but they couldn't, they didn't know what was happening on it. And obviously people, it's so rare you know, you, you come across that every, I don't know, once or twice in your lifetime. Speaker 4: (16:33) Okay. So now you're, you're in the, the finally worked out does it, is this thing. Yep. What sort of a battle did you have on your hands then? I was in the battle. Basically, they're trying to save my life. Wow. Yeah. Yeah. So my, my, basically my, my lungs started to shut down. I immediately went down to about 50% capacity. As soon as I went into HDU I was intubated with mechanical ventilation to the full Monte, so conscious, so my brain's still, they're not just getting migraines. Stuff's like, it's still kind of occupational life. Nothing's happening mentally. It's all just the, my physical body shutting down. I can't move. I started all like, basically I lost all control of my bowels and whatnot as well. So there was things we didn't see wise. It was just, it just, everything went away. Speaker 4: (17:29) So like a massive brain damage. Yeah, something's happened to the brain, but it's just a little bit, it's just my, my peripheral nervous system is shutting down. So I was 23. Wow. I was 20. It started 2014 and yeah, so that, that all happened aren't you baited? And they basically, they started me on what they call immunoglobulin therapy, which is basically other people's antibodies. So, and that's about $1,500 a bottle. And I had about, I don't know, I think it was a call center of over five days, three bottles a day. Sorry, I'm trying to overpower it with, with normal white blood cells. Yeah. So basically trying to combat my immune system so they're pumping and you know what white blood cells from other, basically it's basically a blood transfusion into my body to basically, it can't stop DBS, it can only spoke. Speaker 4: (18:41) So the progress of it. So like I said before, you know, these, they're four week kind of if their month window that month window to try and stop it to get possibly from being a fatal condition. So I was in the third week, halfway through the three weeks, so they just water them. And you know, I already got to the stage where basically I was a vegetable and basically I was just trying to save my life. So I was intubated, heading immunoglobulin, stuck to a wall hours days. And I was in the hospital for about three months in ICU for about a month and a half. And then I went up to just the general ward. So it was amazing. So once they open up here, but it's just a waiting game, you can't really, you can't do much, they can do something else. Speaker 4: (19:30) You can do. You just watch you just hoping that, you know, me being a young kind of 24 year old at the time, it was going to kind of, that was going to be in a box, which to me, thankfully it was. It was. Yeah. And that's very grateful. Someone under the age of basically 50, 40, 50 to get genius. Wow. cause you, have, you got, you know, I, I love diving into the body. Do you think you have a predisposition to immune and overreactive immune system? Have you even thought about functional genomics and doing some testing along that lines to see? Well, you know, I've always thought that I'd always thought about looking at basically my DNA cause but you know, when I look at my, look at my look at my family, but I look at my family history, I've got none of that in my family. No kind of history of a neurological emission. We've got you know, quite a, the only thing we probably have in my family is the Alzheimer's cancer in our family. We don't have you know, you know, really what do you call it? Systemic kind of conditions, you know, mommy and my family have died of heart attacks. I think one. Yeah. [inaudible] Speaker 3: (20:50) We've got type two diabetes, but that's not genetic. That's just, you know, your modifiable risk factors that you can change. Well there is genetic fathers did it as well. Yeah. But it would be interesting. I mean I'm just fascinated by functional genomics and looking at understanding of why your immune system would kick into overdrive and actually cause an S is this likely to happen again? Not GBS. Well, we'll get to that in a minute, but you know, for other immune responses now here on land. Yeah, I'll definitely be interested in looking at research that we can. When I'm working with the DNA company and I've had dr mincer on the say they've just opened their labs up again and it'll be a few months before I'm qualified. But I can definitely connect you this if you want to have a look at that just to, I mean it's, I think it's something that everybody should do once in their life anyway. Speaker 3: (21:49) Yeah, it's fantastic, Dan. The stain, it can definitely help you plan and prepare for your future. Not stupidly, but just preparation was, you know, you'll tell him to stay on what's happened. Like what could possibly happen for you and what, you know, change it while you can change in regards to modifying your lifestyle to be able to enjoy, enjoy your, you know, your quality of life to the full extent. And even like things like, and this is getting a bit off topic, but you know what medications you might interact with in a, in a bad way or you know what your detox pathways are like. So do you need to be super vigilant when it comes to outside toxins, that type of thing or your hormone pathways or everything like that is involved at, so it's pretty, pretty, pretty good information to have. It's like, I reckon it should be like passport. Speaker 3: (22:43) So you have it, you know, and then you take the interventions to stop problems. But back, back to give a story. So you, you, you're fighting for your life now in your, you've, you've gotten through that really bad, horrific stage. How were you mentally coping with us as a 23 year old when you started to come back to life, if you like what you've been through, this traumatic, horrific experience. Have you dealt with that? You know, I've probably, I'm a very optimistic person, just like as a put my personality. I have a very optimistic look and I'm just in life in general. It was really tough. So at the challenge me a lot I wish I knew my wife, that's, it would've been easier, definitely been easier. You know, just being, you're being 23 and I'm very much a mum mama's boy. Yeah, absolutely. Nothing wrong with that. And my mum at the time Speaker 4: (23:47) You know, after raising my brother, my sister and I her entire life as a single mother. Wow. yeah, it's off to half. Yeah. I have a lot of, a lot of things in life. She was in Spain, so she decided, you know, how all of us, we're all growing up, we're living our lives. We started our new careers and, you know, looking, you know, what's going on in our own adult lives. If you took this opportunity, you know, to actually just enjoy this and go off on another Valium sabbatical for six, seven months over in Spain, lift my lift, my stepdad, he just say, I'm going to Spain. I'm going to go off and have all that. And she was basically two months in over there, and then they'll say, great. Trip as well. You know, I tried to, we rang basically nearly ever tried to ring every night through Oh, he used to be called Viber, you know, the original kind of. Yep. I guess. And you know, I basically said to every single time, as hard as it was to me, just to say on the phone was, you know, I said, I kept on saying to mum, don't come back. I'm going to beat this. And I'm not gonna pray, I'm not going to buy as much as I probably cried a lot of the time thinking that I was going to die. Speaker 4: (25:17) Yeah. To face your own mortality though, I mean ridiculously young age you know, like how do you see that now? What's your relationship with it now? I mean it's a pretty hard thing to buddy. Others that's I think I look at it more is I don't ever look at it as a, it's a fear concept. I probably look at it as a, as an opportunity to kind of, like I said, like before we even started a podcast, that's just an opportunity to actually still learn. Even though, even though I was going through this, I was like knocking it, if I get through this, what am I going to learn from this? So that's how I actually probably got me through. A lot of it was, you know, I'm not going to let this beat me, so what can I do with my life if I, you know, not if I was going to, it's like I was spicy. Speaker 4: (26:06) I was trying to tell myself that I wasn't going to, but you know, facing, facing that possible. Yeah, it was either I have my down moments. You know, you sometimes you're probably just thinking about wanting just to give up because it was just so that was quite hard and you know, seeing my family and my family and my family just probably, which has definitely been, you know, my Maori being from a Maori family, my and my mum overseas, I'd always had someone next to me. So yeah, my aunties, my uncles, my brothers, my sisters, my Dad, they all kind of took their time out of their days to kind of one at a time, go on a roster and just be there 24, seven basically, isn't it? It's so important to have that support. Yeah. And you know, like I'm a big, I'm a very holistic kind of person. Then before MALDI back home we have a thing called all, you know, like mother that can be, and so basically in anything, so a person, an object or you know, any inanimate kind of thing. But by them being there, they actually predicting them announcing me, if that makes sense. Absolutely makes sense. You know, if I didn't have them, I don't know if I'd even be here. Being beside your loved ones and having walking with them and their dark times is just so, so, so crucial. Like very family orientated person. So yeah. Speaker 4: (27:36) And you got a good one. I didn't have them beside me. I don't think I definitely would not have probably made it on my own. Because they were actually my thyroid, my motivation to actually fight and fight cause you need to fight, you need to fight when you're in deep, deep trouble and to find that fight when you're in pain and in, in terror and fear and all the rest of it. And the reason probably why I say I would show my wife at the time was because she's actually given me that strength and power to actually on the same or separate afflictions. Yes. I never actually fully understood it and she comprehended it. So I was obviously me being a 20 young, 23, all these just think of the physical aspects of life. And I never really considered, you know, how impactful the mental side of things, the emotional side of things and the spiritual side of things. Speaker 4: (28:25) But it's actually, she really helped me also is actually trying to understand who I am, what my identity is. Wow. I shocked. Cause if I had that back then as well, you know, I definitely would. Mmm. Fully understand and actually I would have been a hell of a lot better position to actually get full without ever even thinking or considering those kinds of things I would consider and think about them, but I wouldn't have, I wouldn't, you know, consume me. Yup. Yup. If they make sense. So I'm a big believer in if you have a strong, I didn't say even cultural identity, if you understand who you are, yeah. It gets you through. So, and that's, you know, being honest to yourself, being yeah, even on the others. And just taking them one step at a time, you know, it's not going to, you need to fully appreciate it. Speaker 4: (29:17) I understand that sometimes you do need that time to just kind of look at yourself and understand who you are. Cause if we don't, then you struggle. So this has brought you wisdom beyond your years really, isn't it? Yeah. So, okay, so, so you, you were in the rehab now for over a year trying to come from this thing and what was that better like? Like was it like coming back from a stroke or a brain injury? Was it like that now? Yeah, so basically it was really weird. So for me, I actually quite enjoyed it, but obviously obviously food through. I, I enjoyed the rehab, but the time that I was in the hospital, that was the tough part. So yeah, it wasn't until I probably got past it every elevation there point where I knew I wasn't going to buy. Yeah. Basically once they, once their fear of my own mortality here to pass, I was, you know, basically they basically told me, I was like, I've been in it and now all I have to do is put the work in. Yep. So be able to give myself from where I am right now, being dependent and now becoming, you know, my independent self again. Wow. I'm still alive so I'm stoked. Speaker 4: (30:39) I'm going to fight like crazy to get better. So I'd never looked at it as being, you know, I never looked at myself as being disabled ever. Maybe sometimes I maybe shouldn't because I know I probably pushed a lot of stress and, and you know I'm on my family when I was going through it there first time cause I, you know, obviously I think we forgot to mention them. I got this last year as well. Yeah, yeah, yeah. This is what we've got to get to yet. So, yeah. So that, you know, I wish I probably was able to be honest. If I say, you know, on, on basically my family going through a lifetime because I know how stressful it was for them to kind of see me in that position and all they wanted to do was just help me and all in all I would do was just kind of internalize it and just keep it to myself and say, no, I almost went homeless and do it myself. Speaker 4: (31:36) Right. But, you know, that was a very selfish thing. Like when I look back on it, it's a very selfish approach that I had on it, even though I know they called me it. But that's because I was only ever thinking about the physical side of things still because you were young and I was young and you know, for me, being a 23 year old, you know, the physical side of life, very, very important. And being a man, you know, you messed the and he gets challenged and it was very, very hard to kind of get through that without ever feeling like I was burdening my family. So, you know, and that way when I look at it now, I, that was the wrong approach. But yeah, so basically once I got past, they pointed at this past the point that I wasn't going to be, that wasn't going to die. I was in hospital until basically I was my, I wasn't head. I took out the mechanical ventilation and I started doing some form of physiotherapy in the hospital and then they had organized me to go to a festival or a Ferguson. I know I Speaker 3: (32:40) Tried to get mum in there, couldn't get her and sorry. Speaker 4: (32:43) I got, I don't know where I got my funding from yeah since I was three months in hospital. And my rehab basically consisted of a lot of it was orientated around my goals and what I wanted to reach back to. However, when I read what I really enjoyed about lower foods, and it's basically like a campus that's a rehabilitation campus and it's for people that are under the age of 60. So it's not a, it's not a retirement village. It's actually for people that are, wants a big goal, be there long term. They had some of them who have long term conditions and took some of them terminal to a certain extent, but they're all there for the purpose of what's in there. Try and get better. Speaker 3: (33:29) Love that. I love that. Yeah. I did try to get my mum in there. She was too old to get there and we couldn't get funding and so on. But it did feel like a place where you were going to actually do something because I must say you're a neurophysio now, so we'll get to that shortly. But I must say the physio care that we had in the hospital was nothing short of atrocious. Yeah. I could have done it in my sleep. I think they went, they'd eat the lunch. That's pretty harsh. But that's, that's how I felt. Speaker 4: (34:02) And it's, it's really hard when I think about that because they are quite restricted in a lot of what they can provide. You know, me being like going through placements in one note as well in the hospitals, they all want to change how they approach things on the hospitals. That's why they're trying to implement, you know, code rehabilitation, gems and whatnot there as well to get more involved. But at the same time it's really tough because systems at the system is built around, you know, you've got so many patients that you have to see on a ward and you've got what, 10, 2030, 30 minutes at the met with them. Speaker 3: (34:41) I must say I must, I must re repair what I just said. The ones that were came round to us on the ward during the acute phase were lovely. Awesome. Yeah. When we were later put into the rehab with mum I fought to get her back into the system to get, you know, cause they said at the beginning she's never going to do anything again. We're not going to bother basically. And I fought and after a year I got her back in for two times a week and there was atrocious. And I felt like a box ticking exercise. The ones on the ward were different. They were very passionate and really, really wanting to help. So in, and this is no indictment on any one person or thing, but there was a systemic problem and there is a systemic problem with the way that the, the things are run at least an hour, the, our hospital and the way that you are judged, I remember and don't want to take her out for the interview, but six weeks she had as a block of two times a week. Speaker 3: (35:43) And honestly what she would do in that six weeks I would have done in a day with her. The tests that they tried to put her through, she was intimidated. She felt like a school girl, so she was not interacting with them. Because they were very judging her all the time, whether she should continue in the program. And at the very end of the program, they had a big panel where they all came in to decide your fate, whether you'd be considered to continue in the program. And they, they talked to me not to hear who's sitting next to them and says she's below the level of the worst dementia patient we've ever seen. You know, she's never going to do anything and this is a waste of time. And I turned to my mom and I said, well how does that make you feel mum? Speaker 3: (36:28) And she said, you know, well I was feeling quite empowered until I came in here. Now I feel totally, you know, down before. And they just looked at me and then jaws drop cause I had never heard her speak because they had never spoken to her as a intelligent person. So she had responded because she was intimidated by that medical setting and I knew that she was a nurse. I knew she had a, you know, stuff going on and she was intelligent and she was coming back. I believed in her and I just said to them, you can stick your program up there somewhere. I'm going to bring my mum back. And I did. From that point on I was like, right there is no help. I will go and do this all myself. And that's, you know, that's, that's just that particular bunch of people in one particular place. And that's not an indictment on them all. But that was, that was quite sad. And then I had a wonderful neurophysio. So let's get onto your neurophysio cause you've gone down this path now after going through this. Was that the reason that you went and studied neurophysiology? Speaker 4: (37:35) Yeah, definitely swung my Martha sessions that go that way. Yeah. I wasn't actually through PSI. I had an amazing neurophysio and when I went, when I was at Laura, focus on the reason why I decided to go down this path though you know, it was just, she just knew how to push me in the right ways and I wanted to do that for other people. And even when I was at Laura Ferguson, I met so many amazing people that had never asked the, you know, to have a stroke, to have no image, to have Huntington's disease, to have pockets. And so, you know, they never, never, they never asked for that. And just to be able to have it's just you know, the, the, the thing I think about the most is people, there's dependent, you know, if you're, if you lose your independence, I feel that's the huge, like the biggest thing as a human, you don't read it like it, it's that old cliche of, you know, you don't know what you have until it's gone. Speaker 4: (38:36) And so basically it's a pout. Somebody that does the pendant become independent again. That's the most rewarding thing that I can even think of from from, from absolutely. When I, when people ask me why I wanted to become a pussy, I say there's three things. So one of those I knew I always wanted to help people work from a health perspective. And originally I actually wanted to become a doctor and do medicine. So they laid onto their leads onto my second reason. That was the reason why I toasted the physio and it's purely because I probably had hit the, you know, Gordon, she was amazing. I'm going to start her name out there because she is amazing. They she made me understand that being a physiotherapist you just were able to have. And there's just this natural and therapeutic relationship that you just can't have as a doctor is, you know, as a relationship proficient. Speaker 4: (39:34) Yeah. Your ability to be able to have those real deep connection with, with your patients was like, there was, that's the reason why I really got back to where I am today because of that. So, yeah. Yeah, yeah. I'm a very people person. So having that intense of kind of relationship with each other collectively, you know, having that shared goal of kind of getting to that, to that same, to that shared place where they want to, that they want to achieve. As you know, second to none. It's a bond for life really, isn't it? I can see how much you love and respect what she did for you and how much it means. And this is why it's on me to becoming a physiotherapist rather than a doctor. The complete opposite of like, I had a neurophysio too who came to our house afterwards and he was wonderful. Speaker 4: (40:31) He gave me the belief that we could do this. He gave me the basic tools so that I could work every day with here cause I couldn't afford obviously everything. But he gave me the information that I could then put that into practice on a day by day by day basis. It's really common sense. It's just being able to apply it in the right way and try to break movements down. Now how do you teach someone to, I specifically look at it in three ways, you know, narrow cause as I think of it as he got function, strategy and impairment, that's basically, that's, that's my, that's like my go to for anything basically. So you know what you wanna achieve as function, you have strategies to achieve that function and then by you have an impairment which affects the strategy to be able to perform the function. Speaker 4: (41:18) Yes. Yep. So obviously the goal is function by why you have to do a specifically time work on the impairment and then effectively your strategies should try and improve and then you start, that's how you progress to the next kind of thing. And then, then what happens is you'll be able to perform their function again. It's like a soap tech. I'm like, I'm trying to simplify it, but that's how I try and approach things. Yeah, no, that makes absolute sense to me. Yeah. That's like free three steps and there's a variety of ways of how you can integrate your treatment methods. So there's a variety of treatment methods that you can use, but that's the ultimate call it, that's the, that's the basis of it that I run by. Wow, I'm going to bring them up to see you one day, what's the next thing I can do with it? Speaker 4: (42:06) So they basically, when I funded, when I recovered, I decided to become a therapist. So I enrolled into A A T and started in 2016. Obviously because I got a dog, cause 2015 had already started because I had a bit of paper and I just kinda wanted to give them my stuff that either actual year where I just worked and just got back on it to actually get back to normality. And then I decide to go on on the intake in 2016. And AAT is now I'm gonna fly should be an, it should be an advertisement for them or something. Yeah. Yeah. They're amazing. So I love that. I love being a part of that. They invest like the way our lectures were, they all came from a clinical experience. They weren't, they were heavily based on the theory. Speaker 4: (43:02) So, you know, they, they basically, they, they pushed down a farts to be able to have a clinical reasoning. And maybe I want to think on a fetus practitioners as clinicians, I want us to be clinicians. They want, they don't want us to be bookworms and lab and just writing, research things out all the time. Cause at the end of the day, you know, our, we're providing a service and we want it to be based around real good quality service. Not just, you know, anyone go on Google and find out and do this, you know, you know, I can do that. We want it to be able to, so they've really and forced their kind of encourage and encourage that type of learning. So it was very practical. And I'm a very practical kind of person. And it's really weird, you know, obviously when I was going through my rehab with his 2014 and they're learning and become in basically going through my physiotherapy degree, I look back on when I was through my rehab and I could see all the little tricks that you said. They will create these signs and your physio you create like the games and really it's actually, it's an objective measure for being. So I didn't really realize that it was actually like a, she's, she's testing me but I didn't know that. Wow. We've got them on or big take tests in all photos just to help me with like picking up things and putting them in. But secretly she had been timing me. Speaker 4: (44:37) She had made it basically. She made a lot of things cause I'm very sport all of my sports. So she made a lot of things in the games like paying the, we you know, you just, you can be as creative as you like as a neurophysio just to get that function back. Yeah. and you know, you learn, you learn basically all the main three, which is cardio, musculoskeletal and neuro. You always remember the principles of all three. Highly effective when you come out of uni, you kind of the side, we really want to kind of stop that all like basically to down and down. And so I obviously obviously matches. Obviously neuro, I do have a miscarriage. I do like that as well. And most people do do musculoskeletal. That's like your normal, full possessive, your body. Everybody knows about. Speaker 4: (45:28) But yeah, my interest is always possibly always going to be neurons just purely from an empathetic point of view. Having that rewarding feeling of being able to help someone get from a to B and just being a part of their journey with them. Yeah. They've ever wanted to be a credited with any of the, you know, them getting there. It's because it's all in. It's just being able to share their journey with them. But it's amazing to be able to, to provide that framework for people to, to learn from and to grow from. And so I just wanna like wrap up in a few minutes, but I want you, you got this again. Yes. You went through this whole thing again in January this year. Speaker 4: (46:12) August last August, 2019 so I was the special 1% of the entire world to get GPS twice. Wow. That's insane. It's super, super unlucky. But this time I have my wife, yes. Father-In-Law. I can never be grateful and thankful enough for them because this time, at least they, we knew what we were dealing with and we see Australia and stuff. It was just a lot and was still very tough and I still kind of, you know, internalized a lot of things. And you know, that, that same thing that the last time when I kind of found my cell phone with regards to my, you know, challenging my masculinity and keeping things internalized, trying to get through myself instead of feeling like I'm burdening everyone else with what's going on with me. But you know, Claire and Steven definitely helped me get through that. And I should apologize to my wife because I know it's probably very, very, very tough on it. Anyone you love and when you're going through hard times, you're always going to have moments where you didn't do what you wanted to do. When you look back afterwards. I mean, I've had times like with where I've been, like Speaker 3: (47:30) Afterwards gone, shit that wasn't good behavior, you know, on my behalf and, or you think, you know, but you're just in a desperate state of exhaustion and fatigue and the grind of it all and you did things that you're not surprised of. Now, you know, in my case where you think, you know, we have yelled at her for something or you know, just gotten frustrated and gone, Oh for goodness sake, you know, and then you're like, that's Speaker 4: (48:03) Time is as much as I was plus time round. It was amazing. Effectively Steven was my head of Gordon the farm. That's, you know, we went, we went to the polls basically three times a week and we went into the hospital twice a week. And he was the one basically taking me through all of my exerciser and whatnot and you know, clearly had to obviously go to work every day. But at the end of the day, she's like my biggest inspiration, the person that I aspire to be like, cause she knows who she is. She sounds awesome. Gotta meet. He's he always makes me want to be a better person or just a better man. Yeah. She, she sees me like she, she can, she sees through me if they make sense, she feeds me. She knows me better than I did myself. Yeah, Speaker 3: (48:52) You can be, you can be real with her too. You, you are who you are and she loves you for all the, all the good, the bad and the ugly. And isn't that what it's a wonderful thing. Yeah. Speaker 4: (49:05) Well the whole my kids look, I mean to me I couldn't make it bad side loss basically up to my elbows, into my knees as time. So I still had function and my, you know, basically my, it wasn't as bad, but it was still GBS even still take like six to seven months before I can actually, he's coming out the other end of this couldn't have been on myself. Yeah. Speaker 3: (49:31) Right. We're gonna wrap up now. What's the message? You know, there's a couple of good messages that have come out of today saying like, as a, as a young Mari, you know, men, you've faced us with amazing strengths and the wisdom that you are beyond your years. I mean, what are you now, 29, 2030 29 30 turning 30 wisdom beyond your years because of what you've been through and that is going to help so many people and your career and what you, what you do. And I'm very excited as it is. I know Steven is to see where you go in life because you know the power and the money that you already have now because of what you've experienced and your openness and your thing. I just think it's fantastic. And you're going to really be empowering lots of other people going through and this is probably, you know, your life's call and you know, is to help people and to do this and to share your story. You know, I think it's important. So this is hopefully the first time you were sharing it and won't be the last, I guess Speaker 4: (50:37) My take home is search after everything that I've been through with everything and all the people that I met. And then I have my wife and Steve and everyone inclusive my family. I think the biggest thing for me will be I think I'll probably look at it at this time of the kind of leader that I want to be like. So it's really, as I said before, it's being able to understand and having their perception of others, you know, never worrying, never caring about the perception of myself. You'll never, if you, if you can understand the perception of others you want to have, you always have an empathetic point of view on my fear. You'll be able to actually stand on the feet, stand in their shoes, sorry. And then understand, tied on the stand, what they're going through and instead of a sympathetic point in life, because at a point when you can become too sympathetic in not feeling sorry for them and then that's not going to help them at all. Empathetic, sympathetic. So that's the kind of leader that I want to be like. And that's what I want to, Speaker 3: (51:41) You're well on your way to doing that and you have a lot of money. You can see it. It just comes out through the screen. So thank you very much for sharing so openly and honestly today, your journey because it is empowering to other people who are going through difficult times. And this is, you know, part of the job of the show is to educate people around, you know, health and fitness and the latest science and the latest stuff. But also to make us understand like we're all human and we all have these feelings and we can get through tough times strategies and tools to do that. And you obviously found a few along the way. So I wish you well and you know, I'm excited to see where you go mate. And any last words, any last words before? Speaker 4: (52:29) Speaker 3: (52:35) Love it. Thanks. Thanks. Bye. Speaker 1: (52:37) That's it this week for pushing the limits. Be sure to write, review and share with your friends and head over and visit Lisa and her team lisatamati.com.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.23.049056v1?rss=1 Authors: DECK, M., Van Hameren, G., Campbell, G., Bernard-Marissal, N., Devaux, J., Berthelot, J., Lattard, A., Medard, J.-J., Gautier, B., Quintana, P., Chao De La Barca, J. M., Reynier, P., Lenaers, G., Chrast, R., Tricaud, N. Abstract: Whether glial cells use a particular metabolism to support axonal metabolism and function remains controversial. We show here that the deletion of PKM2, an enzyme essential for the Warburg effect, in mature myelinating Schwann cells (mSC) of mice leads to a deficit of lactate in these cells and in peripheral nerves, and to motor defects despite no alteration of the myelin sheath. When electrically stimulated, peripheral nerve axons of mutant mice failed to maintain lactate homeostasis, resulting in an impaired production of mitochondrial ATP. Action potential propagation was not changed but axonal mitochondria transport was altered, muscle axon terminals retracted and motor neurons showed cellular stress. Further reducing lactate availability through dichloroacetate treatment definitely aggravated axonal malfunction in mutant mice. Thus, cancer-like Warburg effect is essential in mSC for the long term maintenance of peripheral nerve axons physiology and function. Copy rights belong to original authors. Visit the link for more info
This episode is beefy. It has A LOT of corrections/clarifications from Episodes 2, 3, and 4. Don’t worry, Ruka and Libby eventually get around to discussing gray vs. white matter. Learn about the little sweaters knit by your Grandma Glia. Key Words axon hillock, axon terminal, axon, dendrite, glia, gray matter, initial segment, neuron, oligodendrocytes, Schwann cells, soma, ultracrepidarian, white matter Old West Word of the Day Exfluncticate Connect with us! FB @HeadshakeShow T @HeadshakeShow ‘Sta @HeadshakeNinja Site headshake.show OR headshake.ninja Reference Textbook: Vander’s Human Physiology, 13th Edition Music Bushwick Tarantella by Kevin MacLeod is licensed under a Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) Source: http://incompetech.com/music/royalty-free/index.html?isrc=USUAN1300002 Artist: http://incompetech.com/ Modified from original with volume fading and cuts Disclaimer This podcast is for entertainment and education only. Neither of the hosts is a medical doctor, and nothing they say is medical advice. Please consult with your physician before making decisions about your health.
Clint Howard delivers ice cream and one liners as a murderous Schwann's delivery guy. Is he the Pied Piper or just every other ice cream man? With top cops, Jan Michael Vincent and Lee Majors II on his case, how can he possibly get caught? While we're not entirely sure what this movie is, we can tell you one thing - it's a lot of fun. It doesn't rise to the so bad it's good level that Troll 2 does, but that's likely to Clint Howard being too talented - but it definitely falls into that same category and tone. The two would make a great double feature. When the push-pops hit the fan about 2/3 of the way through - hold on to your seats. Some of the weirdest gore scenes ever captured are here in this film. I won't reveal any highlights but expect lots of wildness with severed heads. Jan Michael Vincent - wow. He's clearly drunk throughout the whole movie. Scenes cut just as he's about to deliver his lines as all I can guess is that he's about to barf instead. His big scene is a juxtaposition between him shambling through an insane asylum vs his partner, Lee Majors II, doing "action" in the same scenario. It's one of the greatest scenes in bad movies on how awful it is. Imagine Hobbs and Shaw but The Rock is drunk and Jason Statham is trying to show up his dad. It's wonderful. Ice Cream Man is an absolutely great time, belongs in any bad horror movie discussion and is a much watch from all three of us. Do it.
Las Neuronas son la Unidad estructural y funcional de nuestro sistema nervioso. Posee tres partes: El Soma o pericarion o cuerpo celular es la parte principal de las neuronas, Su función es que los impulsos nervioso se trasladen con mayor velocidad. Las partes de las Neuronas son El soma, Las dendritas, Axon, otras partes de las neuronas son Nódulos de Ranvier, Celulas de Schwann, Vains de Mielina
Raphael and Schwann talk about all post-UFC Sao Paulo developments and discuss other news from the week. --- Support this podcast: https://anchor.fm/mmaratings/support
Raphael and Schwann talk about all post-UFC 244 news, look forward to UFC Moscow, and recap some of the news from the week. --- Support this podcast: https://anchor.fm/mmaratings/support
Will and Mango dig into all the biggest bicycle questions: From how bikes seriously altered the dating scene, to how blind people ride bikes through traffic, to the ingenious way Kermit pedaled his Schwann in the Muppets Movie. Grab a helmet and join us! Learn more about your ad-choices at https://news.iheart.com/podcast-advertisers
Raphael and Schwann talk about all the big news heading into UFC 244 and more. --- Support this podcast: https://anchor.fm/mmaratings/support
Raphael and Schwann talk about all the big news, including Nate Diaz's statement, Jorge Masvidal's response, UFC 244, and more. --- Support this podcast: https://anchor.fm/mmaratings/support
Raphael and Schwann talk about Israel Adesanya's rise to champion, the weight issues surrounding Michelle Waterson vs. Joanna Jedrzejczyk, the UFC and China, and much more. --- Support this podcast: https://anchor.fm/mmaratings/support
This episode features Catie’s interview with Wendy who studies the cellular and molecular responses to peripheral nerve injury, focusing on Schwann cells.
Hey guys, welcome to part two of Library magic.Eric and I are celebrating one year of upside, and as he mentioned last week in part one, we were particularly struck by Monique Villa's comment in our fifth Coffee Chat:“It's sort of like novelists, whenever you read a book, you're getting the benefit of someone's life's work that they've put into book form. And I really think of founders that way. Anytime I meet a founder, I'm absorbing something that they've been working on for years or sometimes decades -- sometimes longer than I've been alive -- and I just love diving into something and learning about a new industry. And learning about a new way that this industry is being looked at by people who have been, frankly, often times confined by the traditional industry and, and see this opportunity of what the world could become.”We've spoken to over 100 founders in this past year, and published more than 40 of those conversations as episodes here on upside. That's over 100 “founder novels” in our library.But these aren't your typical books. We're not interested in collecting an incremental set of Harry Potter books, and more interested in collecting the rare books that are difficult to find or discarded based on their cover.We're looking for what the book world calls, “first editions.”First editions are prized because they are as close as a reader can get to the source. They are the way the book first appeared to readers, with the original cover art, and sometimes even the original typos.One of my virtual mentors, Seth Godin, also talked about the value of books in his interview on the Tim Ferriss Show:“A book is a screaming bargain. You pay $15-20, and you have something that might change your life; you have something that reminds you 20 years later, sitting on the shelf, where you were when you read it.”I'd say the same is true of running a podcast for a year. It's an order of magnitude more expensive and a whole lot more work, but you build a library that no one else has. You have control over your library.And our library is eclectic. Over the past year, we've spoken with founders in more than 30 cities, including founders outside of the United States.We've spoken with bootstrapped founders and we've spoken to venture investors.We've spoken with community builders and we've spoken with community members.We've spoken to immigrants, and we've spoken to former academics.Our conversations have ranged from virtual reality athletic training to enterprise blockchain to children's toys.We've augmented our learning with the perspectives of guests that are users of a product or investors in a particular market.And while reading the books of others, we were writing our own.Our story is one of exploring the fringes. We're just as interested in learning about defense drones as we are in material science and Quantum Dots.We look through an investors' lens through most of our interviews, but we're just as interested in exploring the fringes of the financing options that are available to bootstrappers and indie hackers like TinySeed and Earnest Capital.For a long time, the founders we speak with were considered on the fringes of investable geography. Investors weren't all that interested in traveling to Tulsa, Oklahoma, or Lincoln, Nebraska.But these locations aren't by chance…Preteckt, a commercial vehicle prognostics company and SOMAVAC, an out-patient medical device, found a home in Memphis, Tennessee, where accelerators brought them to the doorstep of their ideal clients.Freshfry, a technology that purifies cooking oil, calls Louisville home, where they can sit within the franchising capital of the world.Frank Jackman of Local Crate setup shop in Minneapolis, where he both learned from Schwann's and build his geographical advantage through local depots for food delivery....and they aren't the disadvantage they were assumed to be.Corbett Morgan of LOOP Returns is building a reverse-logistics infrastructure to let ecommerce companies all over the country compete with Amazon.ShearShare is located outside of Dallas where they have access to the largest percentage of licensed cosmetologists, while employing a remote team of engineers.The same is true of Vlipsy, a consumer app in Ohio that promises its engineers a better life through remote work.It turns out, it's not so crazy to start a financial data platform in Florida, or a travel and swim apparel company in St. Louis. The advantages of areas inside the coasts aren't just cost-savings, but instead include things like proximity to customers, supply chain and logistic advantages, and access to Fortune 500 companies who Summer Crenshaw told us would take her call when you're in their backyard, “because they are nice, and they want to help.”And you don't have to get giant checks to start -- sometimes, like in the case with Nick Potts, living in a trailer in your parents' backyard can afford the runway to get your first contract with a national pharmacy chain.These founders are scrappy. That may be teaching themselves to code in the case of Seth Miller of Rapchat, or that may be finding non-dilutive funding through grants and pitch competitions like Tony Bova of Mobius.Of course, it's not all sunshine and rainbows, and sure, some founders are located by happenstance. There are still strides to be made in terms of investor education in local ecosystems and convincing investors to invest in other ecosystems. Just about every ecosystem we speak with could use more density and diversity in terms of talent, capital, and support.Our episode with Stephanie Manning was my first exposure to the idea of a “platform” team within Venture Capital. I think “platform” as a concept will mature first within ecosystems, and then across ecosystems.Because none of the founders we've spoken to bought into the narrative that you must be in Silicon Valley to start a company. None of the community builders either. They're finding a way and writing their own narrative.And with this podcast, we just so happen to be the beneficiaries of those narratives.Now, as Eric would tell you, I don't read a lot of paper books. When you're a founder, you don't have time to learn for learning's sake. Instead of picking up a book “just in case” you need that knowledge later, you're more often forced to learn things “just in time” for you to use them. And for the last several years, I've found myself in this camp.And it's for this reason that I often find myself opting to learn directly from the “books” of others. When a problem comes up, I find someone I know has already faced or solved that problem, and I look first for their insight.I gravitate to audiobooks and recorded conversations, just like we have here on the podcast. Looking forward, we will continue to collect new and interesting stories here on our show. We're always looking for those first editions.Thanks to our earliest guests for jumping under the microscope with nothing but an idea. Thanks to Matt Pasternack and Pat Gibson for helping us create the look and sound of the show without a moment's hesitation.Thank you to Andy Curran and Alex Wittenberg for recording our first interviews which were so bad that they'll never see the light of day.Thanks to Taft for making their first podcast sponsorship with us.Thanks to Nathan for making Eric and I sound much smarter in post-production than we ever do in actual production.And thanks to you for listening to our show and supporting us. We're always grateful to hear from you, and look forward to sharing more with you over the next trip around the sun. I assure you, we'll keep exploring those fringes.Follow upside on Twitter: https://twitter.com/upsidefm
INTRODUCCIÓN A LAS CÉLULAS La célula es la unidad estructural y funcional de los seres vivos. Los organismos formados por una sola célula se denominan unicelulares. TIPOS DE CÉLULAS 2- Tipos de células Según su estructura las células se pueden dividir en dos grandes grupos: - Células procariontes: Las células procariotas no contienen núcleo que proteja al material genético. Los organismos procariotas son las bacterias y las algas, todo pertenece al Reino Mónera - Células eucariontes: Tiene el material genético protegido por una membrana formando el núcleo. En donde se encuentra el material genético ( ADN) IMPORTANCIA DE LAS CÉLULAS NERVIOSAS Las células nerviosas forman el tejido nervioso, son las células encargadas de transmitir la información a lo largo del cuerpo humano, a través de todo el sistema nervioso. son un tipo de células del sistema nervioso cuya principal característica es la excitabilidad de su membrana plasmática; están especializadas en la recepción de estímulos y conducción del impulso nervioso (en forma de potencial de acción) entre ellas o con otros tipos celulares ESTRUCTURA Y FUNCIÓN DE LAS CÉLULAS NERVIOSAS Se componen de tres partes: las dendritas, situadas en torno al citoplasma; el cuerpo celular o soma, y el axón. El axón tiene una doble misión: por una parte, une a las neuronas entre sí (proceso denominado sinapsis) y, por otra, al reunirse con cientos o miles de otros axones, da origen a los nervios que conectan al sistema nervioso con el resto del cuerpo. El sistema nervioso se compone de una unidad primordial llamada neurona, un tipo de célula altamente especializada cuya principal característica es su incapacidad para reproducirse. Esto significa que el ser humano nace con una cantidad determinada de neuronas, las que, si bien no pueden duplicarse, han demostrado ser unidades muy plásticas y capaces de generar reacciones en situaciones bastante desfavorables. Las neuronas miden menos de 0.1 milímetro; no obstante, como en el sistema nervioso periférico cada fibra nerviosa en toda su longitud es una prolongación de una sola célula nerviosa, ellas pueden llegar a medir más de un metro. Las neuronas poseen una estructura llamada vaina de mielina, formada por células de apoyo -células de Schwann- ubicadas en el axón. Contiene una sustancia blanca y grasa que ayuda a aislar y proteger a los axones y que aumenta la transmisión de los impulsos nerviosos. El sistema nervioso posee otro tipo de células nerviosas de apoyo, llamadas células gliales, que desempeñan funciones como el mantenimiento del ambiente neuronal, eliminando el exceso de neurotransmisores; la destrucción de microorganismos; el aislamiento de los axones neuronales, y la circulación del líquido cefalorraquídeo que recubre los principales órganos de este sistema.
Chris, Anne, and Carter discuss Walmart’s latest innovation, the Sezzle of payment innovation, IKEA, Schwann’s, and why weed is an experience. For the full transcript of this podcast: https://omnitalk.blog/wp-content/uploads/2020/03/wT41oP_1583182720.txt
In this episode co-hosts Kristina Stykos and Emily Howe discuss an imagined mothball invasion, an unidentified object, acting stupid as a life strategy, one generation of snobbery, shopping with donkeys, being jealous of your dead friend’s friends, a nuanced look at the cliché coop shopper, a much needed update on man buns, how to make cheap, healthy meals, always bumping into the same person, the stress of bagging herbs, an Italian Thanksgiving, advantages to living in obscurity, renegade lettuce, car wash for cows, treasure found in the storage hamper, cling plastic for the studio window, proving your mettle on the Appalachian Gap, making bad weather videos, the joys of sliding backwards on ice, dangerous sledding, laughing at the wrong time, the educational benefits of small mishaps, acting like an adult before you are one, faith as pragmatism, the collision of cultures at Dan & Whit’s, prohibitive pricing from the local woolen industry, a horrifying new development at Schwann’s, imagining a world of frozen food without refrigeration, what happened to the paddle boat, mixing up and conflating fables, being alone yet productive on holidays, Murphy’s Law as it relates to cats, formidable rabbits, gossip as a non-malicious outlet, managing recurring waves of self doubt, the value of success, embracing your creative landscape, practicing the art of perseverance, different functions and levels of art, how a debacle can help you get ahead, dialing back your volunteerism - and so much more! Featuring music from Vermont musicians & friends: Patrick Ross & Aaron Johnson [Flintlock]; Pete Sutherland [Hard Hearted Hills]; Steve Mayone [It’s Beautiful]. Subscribe to our podcast on iTunes, Apple Podcasts or Youtube, or tune in Fridays at 11 am to hear this show live on WFVR-FM South Royalton, Vermont 96.5 FM, streaming online and rebroadcast at Royalton Community Radio and visit our website at www.11thHourRadio.com. Made possible in part by generous support from station sponsors Howvale Farm, The Tunbridge Grease Collective, Rivendell Restoration and the Mountain Folk Concert Series. For more information: 11th Hour Radio Official Website 11th Hour Radio on Facebook Kristina on Facebook Emily on Facebook Kristina's Website
Esta nueva aventura del Brujo ha sido posible gracias a: Antonio Rama como Narrador y Almizclete Este servidor como Geralt, Schwann, los Gnomos del banco y secundarios diversos Sergio DiMaggio como Jaskier Adán Mariscal como Dainty Biverbeldt Ana Oli como Vespula JOS como Vimme Vivaldi Fernando Jaro como Chappelle Y Enrique Ambel como El Posadero. Como podéis ver nuestro equipo ha crecido, comentad que os parecen las nuevas incorporaciones. Lamentablemente esta semana no habrá bonus veraniego del miercoles porque me voy de viaje... pero no os preocupeis, la semana que viene seréis resarcidos... Os recuerdo que tenéis a vuestra disposición nuestra pagina de Facebook, a traves de las cuales podréis hablar con nosostros, comentad vuestras opiniones y participar en el desarrollo del podcats. Nos despedimos hasta la semana que viene con mas Relatos Salvajes...
Esta nueva aventura del Brujo ha sido posible gracias a: Antonio Rama como Narrador y Almizclete Este servidor como Geralt, Schwann, los Gnomos del banco y secundarios diversos Sergio DiMaggio como Jaskier Adán Mariscal como Dainty Biverbeldt Ana Oli como Vespula JOS como Vimme Vivaldi Fernando Jaro como Chappelle Y Enrique Ambel como El Posadero. Como podéis ver nuestro equipo ha crecido, comentad que os parecen las nuevas incorporaciones. Lamentablemente esta semana no habrá bonus veraniego del miercoles porque me voy de viaje... pero no os preocupeis, la semana que viene seréis resarcidos... Os recuerdo que tenéis a vuestra disposición nuestra pagina de Facebook, a traves de las cuales podréis hablar con nosostros, comentad vuestras opiniones y participar en el desarrollo del podcats. Nos despedimos hasta la semana que viene con mas Relatos Salvajes...
In this episode co-hosts Kristina Stykos and Emily Howe discuss guys, predawn lawn mowing, “ghetto paddock”, the impact of poorly thought-out signs, a mistaken dead horse, changes at Uncle Welch’s, the many defects of miniature equines, coveting Mert Vesper’s collie, a lingering Lassie fascination, a brief analysis of Little Timmy’s problems, preventing cat throw-up with butter, Emily’s ongoing disdain for people who watch smarty pants artsy films, wanting to have another child, crawling to the bottom, some thoughts on the name Debby, an imagined scenario in which a rotund train conductor makes unwanted contact with Kristina, pre-guest housework inertia, the questionable technology of sponge mops, confusion about myriad cleaning apparatus, guilt associated with destroying spider webs, issues with the word “gubernatorial”, forgetting your shoes, the biggest problem in the whole world, sub-categories of gossip, the best use of confidantes, keeping your finger on the pulse, naturally distressed jeans, an update on the local Schwann’s truck, strange spicy sausage balls, the power of early morning sunlight on the grass, emotional connections to childhood, the fifth dimension, convincing yourself to relax, the story of song order, the joys of depressing music, planning for more drumming to uplift the spirit, the ways and means of making our show - and so much more! Featuring music from Vermont musicians & friends: The Stephen Wentworth Band [Bootleg Whiskey]; Neal Massa [Cute]; Linda Warnaar [Daya]. Subscribe to our podcast on iTunes, Apple Podcasts or Youtube, or tune in Fridays at 11 am to hear this show live on WFVR-FM South Royalton, Vermont 96.5 FM, streaming online and rebroadcast at Royalton Community Radio and visit our website at www.11thHourRadio.com. Made possible in part by generous support from station sponsors Howvale Farm, The Tunbridge Grease Collective, Rivendell Restoration and the Mountain Folk Concert Series. For more information: 11th Hour Radio Official Website 11th Hour Radio on Facebook Kristina on Facebook Emily on Facebook Kristina's Website
Kate and Matthew talk about the history of the Miami Project to Cure Paralysis, the Schwann Cell human clinical trial and the upcoming Working 2 Walk Symposium in Miami.
Brace yourself, the F bombs are about to fly! After drooling over Schwann's desserts, the girls get surprisingly passionate about bullet journals & elaborate gender reveals. We learn how music festivals bring out Erin's introvert, and Kaedi celebrates her basic-ness by loving the Royal wedding and hair feathers. --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app Support this podcast: https://anchor.fm/relevant/support
Monica and Mike positive spin frozen food! They also discuss favorite buttons, quartists, the Schwann’s man, and ...
Full text - http://bit.ly/2hR9kW0 Oncotarget | Interview with Dr. Hirbe from the Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA talking about their featured cover paper in Oncotarget Volume 7 Issue 7 “Spatially- and temporally-controlled postnatal p53 knockdown cooperates with embryonic Schwann cell precursor Nf1 gene loss to promote malignant peripheral nerve sheath tumor formation” Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N www.Oncotarget.com
The fellas debate UPS vs. Schwann's, Uncles vs. Dads, and Read (Candle) vs. Read (Reece) Receipts.
We’re now at the most important moment of the book, and the section that could be claimed to have secured the reputation of ‘The Riddle of the Sands’ as one of the greatest British adventure novels of all time. It’s the row to the island of Memmert in a thick fog on October 22: a fantastic feat of navigation and physical strength by our two heroes, Carruthers and Davies. But can it actually be done? And what of the dinner afterwards at the Dollmans on the Schwannallee in Norderney? This podcast covers amazing feats of dinghy rowing, bird wardens, the holiday exploits of Chancellor von Bülow, and German (and Norwegian) dinner parties. First up, we explain again why you should be supporting our efforts to create a brand new Handbook Edition of our favourite book, all yours for just £25 with Field Audiobook and an online adventure thrown in for free. Full details at https://unbound.co.uk/books/riddle-of-the-sands. (01:44) Tim notCarruthers consults the maps, the text and Yahoo Answers, then does the maths (in a very rough way) and concludes that the row to Memmert is probably a very tall tale indeed(05:30). He goes on to discuss real-life ocean rowers Harbo and Samuelsen (13:20), and the larger-than-life John Fairfax (15:33). Lloyd NotDavies evaluates our chances of making it to Memmert at all on a real adventure next year (20:20), and talks about the only people to have lived on the islands in the last 100 years - a strange family of bird wardens and rabbit hunters. (21:07) We then go in search of the Schwannallee and find only the Bülowallee (27:18). Much talk about Schwann the physicist, and Bülow the Chancellor, with speculation about Norderney as a place for ‘all-male gatherings’(30:58). We sit down to dinner and consider what kind of meal would be had in 1898 (36:07), rediscovering ‘Babette’s Feast’ along the way (37:28), and enjoying Germany’s funniest ever TV comedy sketch to boot. (40:24) Club Business. Inspired by talk of foghorns in a previous podcast, John tells us about ‘The Hornster’ (45:10); Gordon wants to know more about McMullen’s ‘Down Channel’, so we oblige (45:58); EC Childers tells us more about Erskine’s personal library of sailing books (48:17); Emma on Facebook calls out Victoria BC for poor sewage management (49:23); Ian on Twitter points us back towards Latakia, the possible source of our pipe tobacco (51:09); instructions on how to pack a pipe come from Sergeant Matron of the Kervaig Pipe Club (52:04). MUSIC CREDITS Great Open Sea by the Wellington Sea Shanty Society: http://freemusicarchive.org/music/Wellington_Sea_Shanty_Society/none_given_1098/12_-_Wellington_Sea_Shanty_Society_-_Great_Open_Sea The Ballad of Harbo and Samuelsen by Jerry Bryant: https://youtu.be/-rdqQxlx9hI Dinner For One: https://youtu.be/b1v4BYV-YvA The Hornster: https://youtu.be/_9nonCqesLI
The Minimalist Shoe Index, Pincer toe nails, toe problems, anteromeniscofemoral impingement syndrome and much more on today's show ! Other Gait Guys stuffB. iTunes link:https://itunes.apple.com/us/podcast/the-gait-guys-podcast/id559864138C. Gait Guys online /download store (National Shoe Fit Certification & more !) http://store.payloadz.com/results/results.aspx?m=80204D. other web based Gait Guys lectures:Monthly lectures at : www.onlinece.com type in Dr. Waerlop or Dr. Allen, ”Biomechanics”-Our Book: Pedographs and Gait Analysis and Clinical Case StudiesElectronic copies available here:-Amazon/Kindle:http://www.amazon.com/Pedographs-Gait-Analysis-Clinical-Studies-ebook/dp/B00AC18M3E-Barnes and Noble / Nook Reader:http://www.barnesandnoble.com/w/pedographs-and-gait-analysis-ivo-waerlop-and-shawn-allen/1112754833?ean=9781466953895https://itunes.apple.com/us/book/pedographs-and-gait-analysis/id554516085?mt=11-Hardcopy available from our publisher:http://bookstore.trafford.com/Products/SKU-000155825/Pedographs-and-Gait-Analysis.aspxShow notes:1. New Cameras In Japan Can Detect Drunks At Train Stationshttp://www.popsci.com/cameras-japan-detect-drunks-train-stations2. It takes a lot of nerve: Scientists make cells to aid peripheral nerve repairhttp://www.medicalnewstoday.com/releases/297854.php-Scientists at the University of Newcastle, UK, have used a combination of small molecules to turn cells isolated from human skin into Schwann cells 3. The Minimalist Shoe Definition studyhttp://www.jfootankleres.com/content/8/1/42A consensus definition and rating scale for minimalist shoesJean-Francois Esculier123, Blaise Dubois13, Clermont E. Dionne14, Jean Leblond2 andJean-Sébastien Roy12* http://www.jfootankleres.com/content/8/1/42modified Delphi study, 42 experts from 11 countrieshttp://www.jfootankleres.com/content/supplementary/s13047-015-0094-5-s1.pdf-ResultsThe following definition of minimalist shoes was agreed upon by 95 % of participants: "Footwear providing minimal interference with the natural movement of the foot due to its high flexibility, low heel to toe drop, weight and stack height, and the absence of motion control and stability devices". Characteristics to be included in MI were weight, flexibility, heel to toe drop, stack height and motion control/stability devices, each subscale carrying equal weighing (20 %) on final score. 4. CASE:Ivo: broken toe, prioprioceptionthis: http://www.ncbi.nlm.nih.gov/pubmed/2245598 and this http://www.ncbi.nlm.nih.gov/pubmed/199552895. CASE: anterior meniscofemoral impingment syndromehttp://tmblr.co/ZrRYjx1d8503Whttp://thegaitguys.tumblr.com/post/17713779565/anterior-knee-pain-in-a-young-marathon-hopeful6. Pincer Toe nails: http://thegaitguys.tumblr.com/post/127638788139/pincher-nails-who-knew-note-there-are-two--
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 18/19
Neuregulin-1 (NRG1) type III is a growth factor on the surface of neurons in the peripheral nervous system (PNS). It is required for initial myelination of nerves by Schwann cells after birth and for remyelination after injury. Neuregulin-1 type III is activated by cleavage (shedding) in its extracellular juxtamembrane region generating a membrane-bound N-terminal fragment (NTF) that contains a bioactive epidermal growth factor (EGF)-like domain. This domain signals to neighboring Schwann cells in a contact-dependent manner prompting the cells to initiate myelination. The β-site APP cleaving enzyme 1 (BACE1) was identified as the enzyme that cleaves NRG1 type III and promotes myelination. Consequently, loss of BACE1 cleavage results in dramatically reduced myelin sheaths around nerves in the PNS of BACE1 knockout mice. Besides its role in myelination, BACE1, better known as β-secretase, is also involved in the generation of the neurotoxic amyloid β-peptide (Aβ) which is the main component of amyloid plaques in the brain of patients suffering from Alzheimer’s disease (AD). The Aβ peptide is derived through sequential cleavage of the amyloid precursor protein APP, first by BACE1 in the extracellular domain and subsequently by the γ-secretase in the transmembrane domain (TMD). Inhibition of BACE1 and γ-secretase is therefore considered a promising therapeutic strategy for AD. However, this approach harbors the risk of mechanism-based side effects due to impaired processing of substrates beside APP such as NRG1 type III which is not only a substrate for BACE1 but like APP is also cleaved in its TMD by the γ-secretase. Adding another layer of complexity, ADAM10 and ADAM17, the so-called α-secretases of AD, also cleave NRG1 type III. In the first part of this study, the proteolytic processing of NRG1 type III in its ectodomain was investigated in detail. The precise juxtamembrane shedding sites of BACE1, ADAM10 and ADAM17 were determined by mass spectrometry and two novel cleavage sites of BACE1 and ADAM17 N-terminal of the EGF-like domain were discovered. Cleavage at these novel sites by ADAM17 and BACE1 results in the secretion of the EGF-like domain from NRG1 type III as α-sEGF and β-sEGF, respectively. Using novel monoclonal antibodies generated against the identified cleavage sites the processing of NRG1 type III could also be confirmed in primary neurons. The soluble EGF-like domains were found to be functionally active and induced signaling pathways required for myelination in cultured Schwann cells. Furthermore, β-sEGF rescued the myelination deficit in the PNS of a zebrafish model lacking BACE1, thereby demonstrating its activity in vivo. Using cell culture and the zebrafish model the effects of BACE1- and ADAM17-mediated shedding on the activity of the soluble EGF-like domains were carefully dissected. In contrast to published evidence, however, both the BACE1- as well as the ADAM17-shed sEGF were found to be equally active and to promote myelination in vivo. Together this suggests that NRG1 type III dependent myelination is not only controlled by membrane-retained NRG1 type III but also in a contact-independent manner via proteolytic liberation of the EGF-like domain. The second part of this study investigates the processing of the C-terminal fragment (CTF) which remains after shedding of NRG1 type III. Intramembranous cleavage of the CTF by the γ-secretase was previously shown to release the NRG1 intracellular domain, which acts as transcriptional regulator of proteins involved in neuronal maturation and brain plasticity. Interestingly, a mutation within the TMD of NRG1 type III is associated with an increased risk of schizophrenia linking γ-secretase processing of NRG1 type III to this neurological disorder. Using a novel antibody against the N-terminus of the NRG1 CTF it was possible to detect a NRG1 β-peptide that is secreted during γ-secretase cleavage and could potentially serve as marker for this processing. Moreover, by means of mass spectrometry, the precise cleavage sites within the TMD of NRG1 could be identified. Strikingly, the ɛ-like cleavage site was found to be located exactly at the position of the schizophrenia-associated mutation providing a possible mechanism for the reported interference of this mutation with γ-secretase cleavage. The evidence presented unambiguously establishes NRG1 type III as a γ-secretase substrate and provides a basis for further investigation of the mechanisms which link its processing to the development of schizophrenia. In summary and with regard to BACE1 and γ-secretase being prime targets for a potential AD therapy, the results of this work call for further careful investigation of the consequences of altered NRG1 type III signaling due to chronic treatment with inhibitors.
Listen to Professor Rick Dobrowsky discussing his recent ASN NEURO paper on how Hsp70 induction is sufficient to prevent NRG1 (neuregulin-1 type 1)-induced demyelination by enhancing the proteasomal degradation of c-Jun
Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 01/07
Summary Microsurgical reconstruction of cavernosal nerves within silicone tubes seeded with Schwann cells in rats. Resection of the cavernosal nerves is often necessary during radical prostatectomy and causes erectile dysfunction. Autologous nerve transplantats seemed to be the treatment of choice in the past. Further detailed knowledge of the regeneration of peripheral nerves and the importance of Schwann cells provides new investigation in this topic over the last few years. Using rats as a model, we wanted to show that silicone tubes seeded with Schwann cells provide a better environment for regeneration of peripheral nerves. Resection of 0.5 cm of the cavernosal nerve was performed on both sides of Fischer 344 rats. One group received a bilateral nerve-grafting of the genitofemoral nerve, another group had implantation of empty silicone tubes and the other group had implantations of silicone tubes seeded with autologous Schwann cells. The positive control group under went a sham operation with laparotomy only. A group with resection of the cavernosal nerves on both sides served as negative control. 3 months post operation, erectile function and pressure changes in the corporal bodies are evaluated by electrostimulation of the regenerated nerves. Comparison of empty tubes, nerve grafts and those filled with homologous Schwann cells show a higher rate of erections and increased intracavernosal pressure elevation of the Schwann cell group. 3 months after the implantation of tubes with Schwann cells, erections rise up 91%. By interposition of empty silicone tubes the erection rate is only 50% and nerve grafting results in an erection rate of 30%. Histological examination reveals a more organized and thicker nerve by using silicone tubes seeded with Schwann cells.
The structure of the rat ciliary neurotrophic factor (CNTF) gene and the regulation of CNTF mRNA levels in cultured glial cells were investigated. The rat mRNA is encoded by a simple two-exon transcription unit. Sequence analysis of the region upstream of the transcription start-site did not reveal a typical TATA-box consensus sequence. Low levels of CNTF mRNA were detected in cultured Schwann cells, and CNTF mRNA was not increased by a variety of treatments. Three-week-old astrocyte-enriched cell cultures from new-born rat brain contained easily detectable CNTF mRNA. In astrocyte-enriched cultures, upregulation of CNTF mRNA levels was observed after treatment with IFN-. CNTF mRNA levels were down-regulated in these cells by treatments that elevate intracellular cyclic AMP and by members of the fibroblast growth factor (FGF) family. The implications of these results for potential in vivo functions of CNTF are discussed
The phenotype of a fully differentiated, mature Schwann cell is appar-ently largely determined by Schwann cell-axon interactions. In vitro, elevation of intra-cellular cAMP levels in Schwann cells induces a phenotype which resembles that of a mature, i.e., axon-related, Schwann cell. Therefore, an important role for cAMP as a second messenger of axon-Schwann cell interactions in vivo is assumed. However, the effects of cAMP on Schwann cells are not restricted to induction of features of a mature phenotype. For example, elevation of intracellular cAMP levels results of also in a markedly increased synthesis of nerve growth factor (NGF) mRNA, which is barely detectable in intact sciatic nerves of adult animals. Furthermore, since cAMP induces myelin gene expression in cultured Schwann cells, additional regulatory mechanisms have to be postulated for the induction and maintenance of a mature non-myelinating Schwann cell phenotype. Here we show that a soluble protein growth factor can partially induce a non-myelinating mature Schwann cell phenotype in vitro. Treatment with transforming growth factor 1 (TGF-1) results in a marked and rapid downregulation of the low affinty NGF receptor (NGFR) on cultured Schwann cells without induction of PO gene expression. In contrast, in agreement with previous studies, an increase in PO mRNA levels and a reduction in NGFR mRNA after cAMP elevation is much slower when compared with the effect of TGF-1, suggesting the involvement of different intracellular mechanisms. Consistent with this hypothesis, we did not observe an induction of mRNA coding for TGR- isoforms after cAMP elevation in cultured Schwann cells which constitutively synthesize TGF-1 mRNA
We isolated two cDNAs that encode isoforms of agrin, the basal lamina protein that mediates the motor neuron-induced aggregation of acetylcholine receptors on muscle fibers at the neuromuscular junction. Both proteins are the result of alternative splicing of the product of the agrin gene, but, unlike agrin, they are inactive in standard acetylcholine receptor aggregation assays. They lack one (agrin-related protein 1) or two (agrin-related protein 2) regions in agrin that are required for its activity. Expression studies provide evidence that both proteins are present in the nervous system and muscle and that, in muscle, myofibers and Schwann cells synthesize the agrin-related proteins while the axon terminals of motor neurons are the sole source of agrin.
Potassium uptake, possibly together with chloride, is one of the presumed functions of Schwann cells in the peripheral nervous system. However, the presence of chloride channels has not been demonstrated in adult Schwann cells. We present here a new method which allows single channel recordings to be made from Schwann cells in situ without enzymatic treatment. Isolated rat spinal roots were split mechanically into several bundles. Within about 30 min after this procedure small belb-like vesicles (20-30 m in diameter) with a clean surface appeared at the edges of the fibre bundles. Immunofluorescence microscopy with a surface marker for Schwann cell membranes (monoclonal antibody O4) revealed that the vesicles originate from Schwann cells. In standard patch clamp recordings with symmetrical bath and pipette solutions (excised inside-out configuration) an anion channel with the following characteristics was mainly observed: (1) single channel slope conductance of 337 ± 5 pS in 125 mM KCl and 209 ± 6 pS in 125 mM K+ methylsulphate; (2) ion permeability ratio: PCl/PK/Pgluconate = 1/0.12/0.06; (3) linear current-voltage relationship (range ± 60 mV) and (4) voltage- and time-dependent inactivation (the channel was most active at potentials ± 20mV). Pharmacologically, the channel was completely blocked with zinc (1 mM) and barium (10 mM). A similar anion channel, showing characteristics 1 - (4), has been described in cultured Schwann cells of newborn rats (Gray et al., 1984). We now demonstrate that this channel is also present in adult Schwann cells in situ.
The reeent explosive interest in eell adhesion molecules (CAMs) is a direet eonsequence of the fundamental roles they are thought to play during early embryogenesis and tissue formation [1,2]. The most weIl known of them, studied independently under the names of N-CAM [3] (neural-CAM), 02 protein [4] and BSP-2 [5], has been shown to consist in brain of a family of three glyeoproteins of Mr 180000, 140000 and 120000 [6,7] which are implicated in neurone-neurone adhesion by a homophilie binding meehanism [8,9]. While N-CAM was originally considered to be limited to neurones in adult tissues, ultrastruetural immunoeytochemical studies have sinee provided unequivocal evidenee that glial cells, both astrocytes [6,10] and Schwann cells [11], also express N-CAM (see also [12,13]). Apart from a very limited expression by skeletal muscle at the neuromuscular junetion [14], its expression in the adult Correspondence address: O.K. Langley, Unite 44 de I'INSERM, and Centre de Neurochirnie du CNRS, 5 rue Blaise Pascal, 67084 Strasbourg Cedex, France has been largely though not exclusively considered to be limited to nervous tissues. N-CAM has been found in eertain eells outside the nervous system (e.g. chromaffin eells in the adrenal medulla [11]) but such eells are derived from the neural crest. Here we extend our previous observations on endocrine eells in the adrenal gland and investigate the possible expression of N-CAM by other endoerine eells whieh have a non-neural origin. The present results indieate a mueh wider distribution of N-CAM in adult tissues than has previously been supposed. N-CAM is shown by immunoeytoehemistry to be expressed by several endoerine eells of non-neural origin. Immunoehemieal data eonfirm the presenee of N-CAM determinants typical of brain in endoerine eells although the relative proportions differ markedly. In addition, in two of the tissues examined a lower molecular mass NCAM positive polypeptide was also detected.