Podcasts about downregulation

Watch on Youtube!

Tanner Tattered joins Dave Crosland & Scott McNally TIME STAMPS BELOW Chapters: 00:00:00 - Teaser 00:00:15 - Intro and Sponsors and welcome Tanner ! 00:04:12 - Dispelling Myths about Young People's Views on Bodybuilding 00:08:02 - The Reality of Turning Pro 00:12:13 - Answering the Same Questions Over and Over Again 00:15:45 - Making an Informed Decision about Steroids 00:19:54 - The Reality of TRT and its Impact on Fertility and Mental Health 00:27:41 - Negative Experience with Deca 00:32:00 - The Impact of Different Steroid Dosages 00:36:14 - The Down Regulation of Dopamine and Its Impact on Joyfulness 00:40:14 - Injectable Pre-Workout Experience 00:44:33 - Injectable Oral Steroids 00:48:36 - Oral Testosterone and Lymphatic System 00:52:49 - The Suppressive Factor of SARMs 00:56:54 - Enforcement and Legal Issues in Research Chemical Industry 01:03:30 - The Use of Anabolics to help with "Baby face" 01:13:37 - Aging effects of testosterone therapy 01:17:21 - Balancing Recklessness and Advice 01:19:20 - Semaglutide and hair loss? 01:24:30 - Equipoise & Kidney function 01:29:02 - Taking Control of Your Destiny 01:32:57 - Conclusion and Thank You ✅ Amino Asylum code THINK for 20% off research chems, peptides, l-carnitine and more https://aminoasylum.shop/ref/122/

Watch Here : https://www.youtube.com/watch?v=qlBj9GlnhlY Website: https://vigoroussteve.com/ Consultations: https://vigoroussteve.com/consultations/ eBooks: https://vigoroussteve.com/shop/ YouTube Channel: http://www.youtube.com/user/VigorousSteve/ Workout Clips Channel: https://www.youtube.com/channel/UCWi2zZJwmQ6Mqg92FW2JbiA Instagram: https://instagram.com/vigoroussteve/ TikTok: https://www.tiktok.com/@vigoroussteve Reddit: https://www.reddit.com/r/VigorousSteve/ PodBean: https://vigoroussteve.podbean.com/ Spotify: https://open.spotify.com/show/2wR0XWY00qLq9K7tlvJ000 Patreon: https://www.patreon.com/vigoroussteve

Just like putting a fitness program together to train the body to be healthy, fit, flexible, and strong; we can do the same for your brain. Sustainable high performance requires an inside out approach and there are critical inflection points in our lives where it is vital to 'do an inside job.' Are you armed with the skills to do this?Listen to a live recording of Andrew presenting his Inside Job presentation to ACTA, where he leverages neuroscience (scientific study of the nervous system and brain) performance psychology and 20 years experience coaching some of the world's leading athletes, CEOs, and entrepreneurs.   Performance psychology shows training the mind is like learning a new skill, like playing the guitar or ice skating. And we need to keep practising (reps and sets) and have the right coaching and support until we become competent and gain mastery.Learn to be calm under pressure through front-loading cognitive skills, so they can then be drawn upon when needed most. In this episode Andrew explores:3:40 His backstory and why he needs to tap into mental skills on a daily basis.6:25 The challenges facing leaders, listening to your body's warning signs and getting excited (or not) about living to 100 years old.11:40 Critical inflection points in your life where you need to do and Inside Job and the biological and sociological defaults we all have to navigate.17:35 How to do an IOS upgrade on your mind, the 12 Essential Mental Skills and why stoicism is such an important part of storytelling.22:05 How to deal with the 70,000 thoughts you have reach day, the Reticular Activating System and Andrew's first real heart break.29:00 Self-awareness, Tim Tszyu's dedication to training his body and brain, the importance of storytelling.35:20 Being calm is trainable, getting the right balance between stress and recovery right, and the physiology of stress.38:10 A day in the life of an athlete vs a a day in the life of a corporate worker, micro recovery breaks, and the inverted U hypothesis.42:00 Andrew and Angela Poon's experience participating in the Royal Australian Navy's Helicopter Underwater Escape Training (HUET), the 3x3x3 Down Regulation method and how to Up Regulate (add energy when you need it).52:30 How Commonwealth Bank CEO Matt Comyn trains mental skills, awareness around how you show up as a leader and being aware of energy levels for you and your team energy (social contagion theory) 58:15 Q&A session led by Chris Mclachlan from CBA Use Code "PIPODCAST10" to get 10% off your Lumo Coffee order:https://lumocoffee.com/Learn more about Andrew and Performance Intelligence: www.andrewmay.com Find out more about Andrew's Keynotes : https://www.andrewmay.com/keynotes/Follow Andrew May: https://www.instagram.com/andrewmay/If you enjoy the podcast, we would really appreciate you leaving a short review on Apple Podcasts, Spotify or Google Play. It takes less than 60 seconds and really helps us build our audience and continue to provide high quality guests.

Watch Here : https://www.youtube.com/watch?v=CoIQP3O75sA Website: https://vigoroussteve.com/ Consultations: https://vigoroussteve.com/consultations/ eBooks: https://vigoroussteve.com/shop/ YouTube Channel: http://www.youtube.com/user/VigorousSteve/ Workout Clips Channel: https://www.youtube.com/channel/UCWi2zZJwmQ6Mqg92FW2JbiA Instagram: https://instagram.com/vigoroussteve/ TikTok: https://www.tiktok.com/@vigoroussteve Reddit: https://www.reddit.com/r/VigorousSteve/ PodBean: https://vigoroussteve.podbean.com/ Spotify: https://open.spotify.com/show/2wR0XWY00qLq9K7tlvJ000 Patreon: https://www.patreon.com/vigoroussteve

NOA|AON, also known as Pavel Stuchlik. Pavel is an ex-professional cyclist, an expert in self-realization technique and application, an internationally conscious DJ/producer, serial impact entrepreneur and investor, certified Ambassador of Peace, and Wim Hof Instructor.As the founder of NOA|AON, Pavel's mission is to bring people back to their center and connect them with others through the power of movement and harmony. The name NOA represents movement, while AON stands for 'all or none.' The #noamovement is all about embracing our differences and working together to create a better world.With his diverse background and unique set of skills, Pavel is a true visionary and leader in the wellness and entrepreneurial space. He is passionate about helping others achieve their full potential and live their best lives.Join us as we dive deeper into Pavel's journey, his insights on self-realization and conscious entrepreneurship, and how NOA|AON is making a positive impact in the world. SHOWNOTES:

In this compelling episode of "Taco Bout Fertility Tuesday," join Dr. Mark Amols as we 'Dial Down' into one of the most crucial yet often overlooked aspects of IVF – Down-Regulation. Ever wondered what really goes on behind the scenes of your IVF journey? This episode shines a light on the significance of down-regulation, explaining how this vital step can make or break the success of your fertility treatment.Dr. Amols expertly demystifies the science behind down-regulation, exploring why it's not just a procedural step, but a cornerstone in preparing your body for IVF. We delve into the hows and whys, the impact on egg quality, and the overall importance of this phase in synchronizing your cycle for optimal outcomes.Packed with insightful anecdotes, expert knowledge, and a touch of humor, "Dialing Down on IVF" promises to not only educate but also engage. Whether you're in the midst of your fertility journey, considering IVF, or simply curious about reproductive medicine, this episode is an essential listen. Tune in and discover the intricate dance of hormones and healthcare that defines down-regulation, and why understanding it can be a game-changer for anyone embarking on IVF.

Is your relationship with pain keeping you from feeling relief? Vinny Crispino, founder of Pain Academy, joins the show and shares valuable insights derived from his transformative journey from overcoming a grueling back injury along with battling addiction during recovery and how it led him on the path to helping people get out of chronic pain. Vinny also sheds light on the critical aspect of changing one's relationship with pain to facilitate quicker healing. The discussion extends to injury-proofing the body for running, with insights into optimal fueling for performance and recovery. The episode wraps with a deep dive into the methods that have proven effective in helping thousands liberate themselves from chronic pain through the innovative approach of Pain Academy. Key Points: Going from an All-American swimmer to pursuing a career as a pro-Surfer Suffering a fractured T12 vertebrae and multiple herniations in his back while surfing Dealing with addiction to narcotics while recovering from the injury What to do when you hit rock bottom Maxing out credit cards to fund his recovery and still not seeing results Going back to school to learn how to heal his injuries Divine intervention led him to the person who would heal him How downregulation of the nervous system expedites the healing process Biggest mistake that people in corrective exercise make How to communicate better with your central nervous system for incredible results Changing your relationship with pain can help you heal quicker Learning to injury-proof his body after getting into running How to fuel for performance and recovery in running Overcoming mental, physical, and emotional hurdles to finish a 50-mile race How Pain Academy was born and their methods that have helped thousands of people get out of pain Vinny's definition of Pure Ambition Check out Pain Academy: Website Instagram TikTok YouTube Connect with me: Join my FREE community: Upspace App Instagram: @dominicfusco TikTok: @dom_fusco YouTube: Dominic Fusco LinkedIn: Dominic Fusco Want to help the show grow? Sweet! Here's what you can do: Share this episode with someone who would find value in it. Leave a 5-star rating and review on the podcast app and let me know your honest opinion! Share this episode on your IG story and tag me @dominicfusco SPONSORS Get 20% off the best products on the market to look, feel, and perform your best in all areas of life with Organifi: www.organifishop.com/discount/DOM Elevate your hydration and hit your protein goals with no sugar and nothing artificial and get 20% off with code DFUSCO20 at https://pwrlift.com/discount/DFUSCO20 Improve your metabolic health, get into flow state, and start living better with and get 30% off Ketone-IQ with code “FUSCO” at https://hvmn.com/FUSCO

Andrew and Dr Tom have been working together for 19 years under 5 different business iterations, with a mutual interest and desire to bridge the gap between the science of human performance and the reality of the human experience.They have discovered a fine dance between pushing the body's physical and psychological resources to bend and not break, to stretch and not snap.The 5 factors to become Burnout Proof include Down Regulation, Physiological Capacity, Personal Productivity, Social Connectedness and Purpose Alignment,  You can download the Burnout Proof whitepaper by visiting andrewmay.com/burnoutproof Find out more about Andrew's Keynotes : https://www.andrewmay.com/keynotes/Follow Andrew May: https://www.instagram.com/andrewmay/Follow StriveStronger: https://www.instagram.com/strive.stronger/If you enjoy the podcast, we would really appreciate you leaving a short review on Apple Podcasts, Spotify or Google Play. It takes less than 60 seconds and really helps us build our audience and continue to provide high quality guests.

If you're like me and have survived trauma, first Id like to say IM PROUD OF YOU! Keep Healing. Here are some techniques I find helpful! Try them!!! --- Send in a voice message: https://podcasters.spotify.com/pod/show/tearsandflowers/message

Grandpa Bill welcomes back for his second appearance today, Simon Luthi joins me as we overview his Lucia N°03 Meditation Lamp for BH Sales Kennel Kelp Holistic Healing Hour with Simon Lüthi What is the Lucia N°03 Meditation Lamp? The Lucia N°03 is a neurostimulator that uses flickering light to guide users into a hypnagogic trance, offering a path to deep meditation without the need for drugs or years of training. How it Works: Light Enters the Body: Wide-spectrum flickering light enters through closed eyes, stimulating the pineal gland and thalamus. System Activation: Light triggers brainwave patterns associated with deep meditation, leading to relaxation and altered states of consciousness. Immersion in Meditation: Users experience vibrant visual phenomena, including colors, shapes, and journeys. What to Expect: Unique Journeys: Each session is unique, with personal visions, memories, and insights emerging. Downregulation and Exploration: Experience deep relaxation, clarity, and creativity. Visionary Exploration: Access hypnagogic states for profound healing, lucid dreaming, and creative inspiration. Pricing: Demo (15 minutes) - FREE Short Journey (30 minutes) - $ Extended Session (45 minutes) - $ Advanced Session (60 minutes) - $ 10-pack (shareable) - $ (Every 7th journey free with punch card) Warnings: Not recommended for individuals with epilepsy. Additional Information: Developed by clinical psychologists and a neurologist. Medical-grade engineering and small-batch assembly. Website: www.healthee.world Probing Questions for Simon Lüthi: How does the Lucia N°03 differ from traditional meditation techniques? What are the potential benefits of using the Lucia N°03? What are some common experiences people have with the Lucia N°03? How can the Lucia N°03 be used for personal growth and development? #LuciaLight #Meditation #Hypnagogia #Wellness #Healing #LightTherapy Unlocking Your Inner Potential with the Lucia N°03 Meditation Lamp Exploring Hypnagogia: A Journey Beyond Consciousness with the Lucia N°03 Meditation Made Easy: Introducing the Lucia N°03 Simon's expertise in Applied Neuro-Cellular Therapy and his other websites. Consider showcasing visuals of the Lucia N°03 and the visual experiences it can evoke. Encouraging listeners to contact Simon directly for more information or to book a session. There is nothing like a dream to create the future.”VICTOR HUGO INTERACT WITH OUR DAILY SHOW POLLS WE APPRECIATE YOUR INPUT LEAVE A VOICEMAIL MESSAGE AT THE BH SALES KENNEL KELP HOLISTIC HEALING HOUR --- Send in a voice message: https://podcasters.spotify.com/pod/show/bhsales/message

In this episode of HSS Presents, Dr. Matthew Conti, a foot and ankle surgeon at HSS, talks about Autonomic downregulation with Steve Forti, HSS's Chief Wellness and Resiliency Officer. Join them as they discuss stress management tools such as sleep hygiene, breathwork, postural realignment, and more.

Andrew and Dr Tom have been working together for 19 years under 5 different business iterations, with a mutual interest and desire to bridge the gap between the science of human performance and the reality of the human experience.They have discovered a fine dance between pushing the body's physical and psychological resources to bend and not break, to stretch and not snap.The 5 factors to become Burnout Proof include Down Regulation, Physiological Capacity, Personal Productivity, Social Connectedness and Purpose Alignment, In this episode Andrew and Dr Tom discuss:4:00 The definition of burnout and the human energy crisis9:30 Burnout statistics and the difference between the younger and older generations14:00 Is lack of recovery and respite causing burnout? And the client that had to leave his career19:30 The importance of heart rate, organisational burnout and the 5 factors to make you Burnout Proof23:15 The 1st factor – Down Regulating38:55 The 2nd factor – Physiological Capacity47:15 Kids drinking Prime and the effects of caffeine53:50 The 3rd factor  - Personal Productivity1:04:50 The 4th factor - Social Connectedness1:18:00 The 5th factor - Purpose Alignment1:32:30 Angela Poon and Shannon Frost's reflections You can download the Burnout Proof whitepaper by visiting andrewmay.com/burnoutproof Find out more about Andrew's Keynotes : https://www.andrewmay.com/keynotes/Follow Andrew May: https://www.instagram.com/andrewmay/Follow StriveStronger: https://www.instagram.com/strive.stronger/If you enjoy the podcast, we would really appreciate you leaving a short review on Apple Podcasts, Spotify or Google Play. It takes less than 60 seconds and really helps us build our audience and continue to provide high quality guests.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.24.550266v1?rss=1 Authors: Ramirez-Franco, J., Debreux, K., Sangiardi, M., Belghazi, M., Kim, Y., Lee, S.-H., Leveque, C., Seagar, M., El Far, O. Abstract: The Kv1 members (KCNA, Shaker) of the voltage-gated potassium channels are implicated in determining key functional neuronal properties from spike generation at axonal initial segments to the control of synaptic strength at nerve terminals. In animal models of LGI1-dependent autosomal dominant lateral temporal lobe epilepsy (ADTLE), Kv1 channels are downregulated, suggesting their crucial involvement in epileptogenesis. The molecular basis of Kv1 channel-downregulation in LGI1 knock-out mice has not been elucidated and how the absence of this extracellular protein induces an important modification in the expression of Kv1 remains unknown. In this study we analyse by immunofluorescence the detailed modifications in neuronal Kv1.1 and Kv1.2 distribution throughout the hippocampal formation of LGI1 knock-out mice. We show that Kv1 downregulation is not restricted to the axonal compartment, but also takes place in the somatodendritic region and is accompanied by a drastic decrease in Kv2 expression levels. Moreover, we find that the downregulation of these Kv channels is associated with an important increase in bursting patterns. Finally, mass spectrometry uncovered key important modifications in the Kv1 interactome that highlight the epileptogenic implication of Kv1 downregulation in LGI1 knock-out animals. 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/2023.07.26.550695v1?rss=1 Authors: Hood, E. M., Lipinski, R. A. J., Lipinski, D. M. Abstract: PURPOSE ARPE19 cells are a commonly used cell culture model for the study of retinal pigment epithelial cell biology and pathologies. However, numerous studies have demonstrated that ARPE19 undergo morphologic, transcriptomic and genomic alterations over time and with increasing passage number. Herein, we explore the mechanisms underlying increased resistance to the delivery of exogenous genetic material via transfection in ARPE19 cells using mass spectrometry. METHODS ARPE19 cells (N=5 wells/reagent) were seeded in 6-well plates at passages 24 through 30. At 70% confluency an mCherry reporter construct was delivered via transfection using Lipofectamine 3000, Lipofectamine LTX, Lipofectamine Stem, or PEI (polyethylenimine) reagents. After 72 hours, transfection efficiency was quantified by fluorescence microscopy and flow cytometry. Mass spectrometry and immunofluorescence of ARPE19 cells were performed at passages 24 and 30 to evaluate altered protein synthesis and localization between passage numbers. RESULTS ARPE19 transfection showed a maximum transfection efficiency of 32.4% at P26 using Lipofectamine 3000 reagent. All lipofectamine based reagents demonstrated statistically significant decreases in transfection efficiency between passages 24 and 30. Mass spectrometry analysis revealed 18 differentially expressed proteins, including down-regulation of clathrin light chain B (CLTB) and legumain (LGMN) that was confirmed via immunofluorescence imaging, which indicated altered intracellular localization. CONCLUSIONS ARPE19 cells demonstrate passage number dependent changes in lipofectamine-based transfection efficiency. Mass spectrometry and immunofluorescence indicates the observed decrease in transfection efficiency involves the dysregulation of endocytosis and intracellular endolysosomal trafficking at later passages. 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/2023.07.24.550336v1?rss=1 Authors: Kumar, R., Tatiya, P., Dey, D., Ratra, Y., Mian, S. Y., Chaudhary, S., Suhag, K., Basak, S., Banerjee, M. Abstract: Downregulation of the host cell pro-apoptotic pathways confers a selective advantage to viral pathogens, and many viruses interfere with such regulatory mechanisms in order to enhance their propagation in infected cells. The Scribble cell polarity complex, which is composed of multiple adapter proteins including human Scribble, Dlg and MAGI, controls a variety of host cell functionalities including apoptosis, morphology, polarity, signaling and migration. In the recent years, components from several viral pathogens, including oncogenic viruses, have been found to associate with and modulate the activities of this complex, particularly that of the pro-apoptotic protein Scribble. Here, we establish a critical role for the downregulation of Scribble expression for the potentiation of Chikungunya Virus (CHIKV) infection. CHIKV is a well-known mosquito-borne alphavirus, which has caused outbreaks in more than 100 countries and constitutes a global health hazard. While the majority of the CHIKV proteome is well characterized, the role of a small structural protein 6K, and its transframe variant, TF, which is generated from the 6K sequence by ribosomal slippage and frameshifting, is not established as yet. We show that TF triggers the punctation, ubiquitination and degradation of Scribble during CHIKV infection, and that the downregulation of Scribble during CHIKV infection. We show that the association of TF with the PDZ domains of Scribble is mediated through a PDZ-domain binding motif at the C-terminus of TF. Thus, our work establishes a role for the downregulation of Scribble in alphavirus infections for the first time, while allocating a novel role in host modulation to the mysterious 6K/TF component of alphaviruses. 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/2023.06.30.547296v1?rss=1 Authors: Lee, H., Kang, H., Moon, C., Youn, B. Abstract: Cranial irradiation is used for prophylactic brain radiotherapy as well as treatment of primary brain tumors. Despite its high efficiency, it often induces unexpected side effects, including cognitive dysfunction. Herein, we observed that mice exposed to cranial irradiation exhibited cognitive dysfunction, including altered spontaneous behavior, decreased spatial memory, and reduced novel object recognition. Analysis of actin cytoskeleton revealed that ionizing radiation (IR) disrupted the filamentous/globular actin (F/G-actin) ratio and downregulated the actin turnover signaling pathway p21-activated kinase 3 (PAK3)-LIM kinase 1 (LIMK1)-cofilin. Furthermore, we found that IR could upregulate microRNA-206-3p (miR-206-3p) targeting PAK3. As the inhibition of miR-206-3p through antagonist (antagomiR), IR-induced disruption of PAK3 signaling is restored. In addition, intranasal administration of antagomiR-206-3p recovered IR-induced cognitive impairment in mice. Our results suggest that cranial irradiation-induced cognitive impairment could be ameliorated by regulating PAK3 through antagomiR-206-3p, thereby affording a promising strategy for protecting cognitive function during cranial irradiation, and promoting quality of life in patients with radiation therapy. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

DrBeen#28 Spike Proteins Disrupt Nitric Oxide Ep 28: Spike Proteins Disrupt Nitric Oxide Let's review how the spike protein alone can cause dysregulation of the ACE2 bearning cells. One important mechanism is the reduction in the expression of the endothelial nitric oxide synthase (eNOS) enzyme. Let's review. DrBeen: Medical Education Onlinehttps://www.drbeen.com/ FLCCC | Front Line COVID-19 Critical Care Alliancehttps://covid19criticalcare.com/ URL list from Sunday, Oct. 9 2022 SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2 | Circulation Researchhttps://www.ahajournals.org/doi/10.1161/CIRCRESAHA.121.318902 Mitochondrial Dynamics in SARS-COV2 Spike Protein Treated Human Microglia: Implications for Neuro-COVID - PMChttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487226/ Endothelial NOS - Wikipediahttps://en.wikipedia.org/wiki/Endothelial_NOS The novel coronavirus' spike protein plays additional key role in illness - Salk Institute for Biological Studieshttps://www.salk.edu/news-release/the-novel-coronavirus-spike-protein-plays-additional-key-role-in-illness/ ACE/ACE2 balance might be instrumental to explain the certain comorbidities leading to severe COVID-19 cases - PMChttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856554/ The spike protein of SARS-CoV-2 induces endothelial inflammation through integrin α5β1 and NF-κB signaling - PMChttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820157/ Oxidative stress-induced endothelial dysfunction and decreased vascular nitric oxide in COVID-19 patients - eBioMedicinehttps://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(22)00077-9/fulltext l-Arginine and COVID-19: An Update - PMChttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619186/ l-Arginine supplementation enhances eNOS expression in experimental model of hypercholesterolemic rabbits aorta - PubMedhttps://pubmed.ncbi.nlm.nih.gov/19168337/ Implications of SARS-Cov-2 infection on eNOS and iNOS activity: Consequences for the respiratory and vascular systems - ScienceDirecthttps://www.sciencedirect.com/science/article/pii/S1089860321000380 Induction of citrulline-nitric oxide (NO) cycle enzymes and NO production in immunostimulated rat RPE-J cells - PubMedhttps://pubmed.ncbi.nlm.nih.gov/12589771/ Disclaimer:This video is not intended to provide assessment, diagnosis, treatment, or medical advice; it also does not constitute provision of healthcare services. The content provided in this video is for informational and educational purposes only. Please consult with a physician or healthcare professional regarding any medical or mental health related diagnosis or treatment. No information in this video should ever be considered as a substitute for advice from a healthcare professional.

DrBeen#29 How Spike Protein Causes Pathologies in Our Tissues and Vessels Ep 29: Spikopathy - How Spike Protein Causes Pathologies in Our Tissues and Vessels In this discussion we will go over the important pathologic mechanisms behind the diseases caused by the spike protein. DrBeen: Medical Education Onlinehttps://www.drbeen.com/ FLCCC | Front Line COVID-19 Critical Care Alliancehttps://covid19criticalcare.com/ URL list from Friday, Oct. 21 2022 Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies | Acta Pharmacologica Sinicahttps://www.nature.com/articles/s41401-022-00998-0 Frontiers | SARS-CoV-2 Spike Protein Induces Degradation of Junctional Proteins That Maintain Endothelial Barrier Integrityhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.687783/full SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2 | Circulation Researchhttps://www.ahajournals.org/doi/10.1161/CIRCRESAHA.121.318902 Mitochondrial Dynamics in SARS-COV2 Spike Protein Treated Human Microglia: Implications for Neuro-COVID - PMChttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487226/ The spike protein of SARS-CoV-2 induces endothelial inflammation through integrin α5β1 and NF-κB signaling - PMChttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820157/ IJMS | Free Full-Text | New Therapeutic Implications of Endothelial Nitric Oxide Synthase (eNOS) Function/Dysfunction in Cardiovascular Disease | HTMLhttps://www.mdpi.com/1422-0067/20/1/187/htm Molecular mimicry and autoimmunity - PubMedhttps://pubmed.ncbi.nlm.nih.gov/30509385/ Endothelial NOS - Wikipediahttps://en.wikipedia.org/wiki/Endothelial_NOS ACE/ACE2 balance might be instrumental to explain the certain comorbidities leading to severe COVID-19 cases - PMChttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856554/ Oxidative stress-induced endothelial dysfunction and decreased vascular nitric oxide in COVID-19 patients - eBioMedicinehttps://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(22)00077-9/fulltext l-Arginine and COVID-19: An Update - PMChttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619186/ l-Arginine supplementation enhances eNOS expression in experimental model of hypercholesterolemic rabbits aorta - PubMedhttps://pubmed.ncbi.nlm.nih.gov/19168337/ Implications of SARS-Cov-2 infection on eNOS and iNOS activity: Consequences for the respiratory and vascular systems - ScienceDirecthttps://www.sciencedirect.com/science/article/pii/S1089860321000380 Induction of citrulline-nitric oxide (NO) cycle enzymes and NO production in immunostimulated rat RPE-J cells - PubMedhttps://pubmed.ncbi.nlm.nih.gov/12589771/ Oct 21, 2022 at 4:58 PMOxidative Stress, Nitric Oxide Synthase, and Superoxide Dismutasehttps://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.107.103226 Oct 21, 2022 at 5:09 PMCritical Role of the Nitric Oxide/Reactive Oxygen Species Balance in Endothelial Progenitor Dysfunctionhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135185/ Disclaimer:This video is not intended to provide assessment, diagnosis, treatment, or medical advice; it also does not constitute provision of healthcare services. The content provided in this video is for informational and educational purposes only. Please consult with a physician or healthcare professional regarding any medical or mental health related diagnosis or treatment. No information in this video should ever be considered as a substitute for advice from a healthcare professional. covid 19dr beenflcccspike proteinspikopathy

We live in a world that heavily bought into Piere de Coubertin's Olympic motto 'Citius, Alltius, Fortius' (Faster, Higher, Stronger) over 130 years ago. The challenge with this motto however is it never addressed core human physiological and psychological needs to periodically reduce intensity and recharge.Join Angela Poon as she turns the tables and interviews Andrew about the vital importance of strategic down regulation. As the founder of digital wellbeing consultancy StriveStronger.com and juggling a keynote speaking, podcast and mental skills coaching business, plus being a father of four, Andrew understands how essential it is to stay composed and be present in all parts of his life.Drawing from expertise in human biology, physiology, psychology and 25 years experience working with elite athletes and executives, Andrew takes us on a journey into the overlooked realm of strategic recovery for the body and brain. In this episode, Angela Poon (StriveStronger Operations Director) and Andrew discuss:4:15 The definition of down regulation and why it can feel so hard to do 11:20 Hyper-connectivity and operating rhythm of farmers as a lesson in sustainability14:30 How infants learn to down regulate, and how you can expand energy capacity 18:45 What happens physically and psychologically when you are always ON26:00 Difference types of brainwaves and how they impact performance33:00 Teaching down regulation to children in school28:45 How Andrew down regulates and stays energised during a crazy week44:00 Andrew's disdain for 'hacks'44:30 'Hurry Up & Relax' -  30 sec examples of the 3x3x3 Down Regulation format to shift state 53:40 'Performance Moment Reset' - 3 min recharge examples to get ready for key moments1:00:00 'The Double Dip' - 30 min examples that down regulate the body and brain1:10:00 Angela and The Wizard's reflections on this interview with Andrew Watch the Performance Intelligence Podcast on Youtube: https://rb.gy/vqaof Find out more about Andrew's Keynotes : https://www.andrewmay.com/keynotes/Follow Andrew May: https://www.instagram.com/andrewmay/Follow StriveStronger: https://www.instagram.com/strive.stronger/If you enjoy the podcast, we would really appreciate you leaving a short review on Apple Podcasts, Spotify or Google Play. It takes less than 60 seconds and really helps us build our audience and continue to provide high quality guests.

A new research paper was published in Oncotarget's Volume 14 on March 24, 2023, entitled, “Downregulation of angulin-1/LSR induces malignancy via upregulation of EGF-dependent claudin-2 and TGF-β-dependent cell metabolism in human lung adenocarcinoma A549 cells.” Abnormal expression of bicellular tight junction claudins, including claudin-2 are observed during carcinogenesis in human lung adenocarcinoma. However, little is known about the role of tricellular tight junction molecule angulin-1/lipolysis-stimulated lipoprotein receptor (LSR). In the present study, researchers Wataru Arai, Takumi Konno, Takayuki Kohno, Yuki Kodera, Mitsuhiro Tsujiwaki, Yuma Shindo, Hirofumi Chiba, Masahiro Miyajima, Yuji Sakuma, Atsushi Watanabe, and Takashi Kojima from Sapporo Medical University School of Medicine examined expression of claudin-2 in the lung adenocarcinoma tissues and found it was higher than in normal lung tissues, while angulin-1/LSR was poorly or faintly expressed. “We investigated how loss of angulin-1/LSR affects the malignancy of lung adenocarcinoma cell line A549 and normal human lung epithelial (HLE) cells.” The researchers found that the EGF receptor tyrosine kinase inhibitor AG1478 prevented the increase of claudin-2 expression induced by EGF in A549 cells. Knockdown of LSR induced expression of claudin-2 at the protein and mRNA levels and AG1478 prevented the upregulation of claudin-2 in A549 cells. Knockdown of LSR induced cell proliferation, cell migration and cell metabolism in A549 cells. Knockdown of claudin-2 inhibited the cell proliferation but did not affect the cell migration or cell metabolism of A549 cells. The TGF-β type I receptor inhibitor EW-7197 prevented the decrease of LSR and claudin-2 induced by TGF-β1 in A549 cells and 2D culture of normal HLE cells. EW-7197 prevented the increase of cell migration and cell metabolism induced by TGF-β1 in A549 cells. EW-7197 prevented the increase of epithelial permeability of FITC-4kD dextran induced by TGF-β1 in 2.5D culture of normal HLE cells. In conclusion, downregulation of angulin-1/LSR induces malignancy via EGF-dependent claudin-2 and TGF-β-dependent cell metabolism in human lung adenocarcinoma. “In conclusion, AG1478 and EW-7197 demonstrated potent in vitro anti-lung adenocarcinoma therapeutic activities via LSR/CLDN-2 and the cell metabolism. The use of both AG1478 and EW-7197 may provide a clinical therapeutic approach for lung adenocarcinoma caused by loss of angulin-1/LSR.” Full research paper: DOI: https://doi.org/10.18632/oncotarget.27728 Correspondence to: Takashi Kojima - ktakashi@sapmed.ac.jp Keywords: angulin-1/LSR, claudin-2, cell metabolism, malignancy, lung adenocarcinoma About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.01.530630v1?rss=1 Authors: Libe-Philippot, B., Iwata, R., Recupero, A. J., Wierda, K., Ditkowska, M., Gaspariunaite, V., Vermaercke, B., Peze-Heidsieck, E., Remans, D., Charrier, C., Polleux, F., Vanderhaeghen, P. Abstract: Human-specific (HS) genes are potential drivers of brain evolution, but their impact on human neuron development and disease remains unclear. Here we studied HS genes SRGAP2B/C in human cortical projection neurons (CPNs) in vivo, using xenotransplantation in the mouse cortex. Downregulation of SRGAP2B/C in human CPNs greatly accelerated synaptic development, indicating their requirement for human-specific synaptic neoteny. SRGAP2B/C acted by downregulating their ancestral paralog SRGAP2A, thereby upregulating postsynaptic levels of SYNGAP1, a major intellectual deficiency/autism spectrum disorder (ID/ASD) gene. Combinatorial genetic invalidation revealed that the tempo of synaptogenesis is set by a balance between SRGAP2A and SYNGAP1, which in human CPNs is tipped towards neoteny by SRGAP2B/C. Our results demonstrate that HS genes can modify the phenotypic expression of ID/ASD mutations through regulation of synaptic neoteny. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Huberman Lab Podcast Notes Key Takeaways Even if you don't have a specific goal (e.g., marathon, competition), having a training plan is always more effective than not having a plan – you'll achieve more results in the same amount of time (or less)Work within the constraints of the non-negotiables in your life (e.g., family, work, time, etc.) Imagine everything in your life falls into one of four buckets: business, relationships, fitness, or recovery – distribute 10 total points across the four areas and spend some time critically analyzing whether you are allocating energy in the right places and set goals accordinglyBefore you even worry about exercise selection: think about where you want to go, how you're going to get there, and restrictions based on the reality of life, lastly select exercises and balance across the weekExercise choice: select patterns you can execute, balance muscle patterns and movement joints, specifically target goal muscles or movements, and consider progression strategyIdentify high and low friction training days: bookend the day you can anticipate having your best/most flexible/highest energy day and worst/most exhausting/shortest on time day and plan accordingly Choose harder workouts on lighter days and easier workouts when you know you'll be tired and/or short on timeApproaching progressive overload: increase load or intensity for 6 weeks then take a de-load week– this should leave you progressing well, without burnout, and avoiding injuryChaos management: outline what you want to do then take a day to think about it and make sure you have addressed areas of potential failure or reflection – set yourself up for successIf you find yourself wanting to change your workout too frequently, stop and reassess where you are – are you getting lazy? Are you tired today? – listen to your body and stay within the plan or it'll be difficult to progressively overload if you train on the fly regularly If there are too many days you want to go harder, make sure it's for the right reasons (i.e., not just vanity) and it's not impacting recoveryIf you want to have fun working out with someone to bond, have a rule not to change your program more than 3 daysRead the full notes @ podcastnotes.orgIn episode 4 of a 6-part series, Andy Galpin, PhD, explains how to design an effective training program for fitness, health and longevity through a 10-step approach. He covers goal setting, exercise selection, balancing, recovery periods and real-world challenges. He provides a year-long training example that considers sleep, sunlight and social connection. The program is modifiable for personal fitness goals and experience. For the full show notes, visit hubermanlab.com. Thank you to our sponsors AG1 (Athletic Greens): https://athleticgreens.com/huberman Eight Sleep: https://eightsleep.com/huberman InsideTracker: https://www.insidetracker.com/huberman Supplements from Momentous https://www.livemomentous.com/huberman Timestamps (00:00:00) Optimal Fitness Programming (00:07:19) Sponsors: Momentous, Eight Sleep (00:09:53) #1: Plan Fitness Goals, S.M.A.R.T. Goals (00:19:52) Intermediate Goals, Dopamine, Identify Your “Defender”, Goal Timing (00:26:25) Multiple Goals, Synergistic Goals, Interference Effects (00:36:13) AG1 (Athletic Greens) (00:37:060 Physical Goal “Bins”, Specificity  (00:48:02) Tool: #2: Identify Your “Defender”, Quadrant System, “Drop Everything and…” (01:04:330 InsideTracker (01:05:35) #3: Goal Timeframe & Life Events; #4: Weekly Training Frequency (01:10:33) #5: Exercise Selection, Progression  (01:18:200 #6: Exercise Order, Identify Friction (01:29:20) Exercise Timing & Sleep, Down Regulation, Caffeine (01:36:24) #7: Intensity, #8: Volume, Progressive Overload, “Deloading” (01:43:59) #9: Rest Intervals, #10: “Chaos Management” (01:49:06) Fitness, Health & Longevity Goals, Proprioception & Non-Structured Exercise (01:53:41) Tool: Year-Long Program Example for Overall Fitness (02:07:58) Tool: Overall Fitness Template by Quarter, Matching Goals & Seasons (02:25:49) Training & Life Challenges: Sleep, Illness  (02:32:10) Tool: Program Flexibility, 3-Day Weekly Training Program (02:37:12) Physical Activity vs. Exercise (02:40:12) Tool:4-Day Weekly Training Program, Muscular Endurance (02:51:15) Tool: 5/6-Day Weekly Training Program, Recovery (02:54:06) Program Modification, Balancing Joy (03:04:47) Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Neural Network Newsletter Title Card Photo Credit: Mike Blabac Disclaimer

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.17.528950v1?rss=1 Authors: Gayen, N., Mitra, S., Roy, S., Mandal, A. K. Abstract: The stability and activity of CRAF kinase are stringently regulated by heat shock protein 90 (Hsp90). Hsp90-mediated client folding and maturation is governed by its co-chaperones, but their functionality in chaperoning CRAF/Raf1 kinase to accomplish signaling under physiological conditions remains poorly understood. Here, we show that Hsp70/Hsp90 organizing protein (HOP) associates with CRAF kinase for maintaining its kinase activity and facilitates the activation of the MAPK pathway. Such activation is mediated by TPR2A-2B-DP2 domain of HOP and requires efficient binding to Hsp90. Being a recruiter of Hsp90, Cdc37 is unable to supplement the function of HOP/Sti1. Downregulation of HOP/Sti1 in yeast and in vitro cell culture significantly reduces the CRAF signaling. Our data suggest that Hsp90 is recruited to CRAF in two steps, separately initiated by co-chaperones HOP and Cdc37 respectively during CRAF folding/maturation, and again upon CRAF activation mediated by HOP during MAPK signaling. Therefore, HOP is a regulator of CRAF kinase during activation of MAPK pathway and serves as a sensor of growth signaling beyond its client folding and maturation function. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In this episode, Betina and Nic recap their time at Super Bowl LVII, partying post-game and training while traveling with a child. They share their nighttime routines and activities that help to optimize sleep, like sleep tracking, avoiding late-night meals and blue light blocking. The duo discusses their down regulation practices and touches on marijuana and journaling.  They close by talking about alcohol's effect on sleep, the importance of mouth tape and nose breathing, and the mindfulness practice that completes their routine.  Have questions for Betina & Nic? Email the show at contact@beyondtheroutinepodcast.com for a chance to have your question answered on a future episode.  Follow us on Instagram: @beyondtheroutinepodcastVisit us beyondtheroutinepodcast.com Products & Books mentioned. We do use affiliate codes when possible. The Oxygen Advantage: Simple, Scientifically Proven Breathing Techniques to Help You Become Healthier, Slimmer, Faster, and FitterOura Ring Sleep Strip Mouth Tape Disclaimer: This podcast represents the opinions of Beyond the Routine hosts Betina and Nic Shimonek and their guests. Views and opinions expressed in the podcast are their own and should not be taken as medical advice. The podcast content is for informational purposes only. Please consult your healthcare professional for any medical questions. 

In episode 4 of a 6-part series, Andy Galpin, PhD, explains how to design an effective training program for fitness, health and longevity through a 10-step approach. He covers goal setting, exercise selection, balancing, recovery periods and real-world challenges. He provides a year-long training example that considers sleep, sunlight and social connection. The program is modifiable for personal fitness goals and experience. For the full show notes, visit hubermanlab.com. Thank you to our sponsors AG1 (Athletic Greens): https://athleticgreens.com/huberman Eight Sleep: https://eightsleep.com/huberman InsideTracker: https://www.insidetracker.com/huberman Supplements from Momentous https://www.livemomentous.com/huberman Timestamps (00:00:00) Optimal Fitness Programming (00:07:19) Sponsors: Momentous, Eight Sleep (00:09:53) #1: Plan Fitness Goals, S.M.A.R.T. Goals (00:19:52) Intermediate Goals, Dopamine, Identify Your “Defender”, Goal Timing (00:26:25) Multiple Goals, Synergistic Goals, Interference Effects (00:36:13) AG1 (Athletic Greens) (00:37:060 Physical Goal “Bins”, Specificity  (00:48:02) Tool: #2: Identify Your “Defender”, Quadrant System, “Drop Everything and…” (01:04:330 InsideTracker (01:05:35) #3: Goal Timeframe & Life Events; #4: Weekly Training Frequency (01:10:33) #5: Exercise Selection, Progression  (01:18:200 #6: Exercise Order, Identify Friction (01:29:20) Exercise Timing & Sleep, Down Regulation, Caffeine (01:36:24) #7: Intensity, #8: Volume, Progressive Overload, “Deloading” (01:43:59) #9: Rest Intervals, #10: “Chaos Management” (01:49:06) Fitness, Health & Longevity Goals, Proprioception & Non-Structured Exercise (01:53:41) Tool: Year-Long Program Example for Overall Fitness (02:07:58) Tool: Overall Fitness Template by Quarter, Matching Goals & Seasons (02:25:49) Training & Life Challenges: Sleep, Illness  (02:32:10) Tool: Program Flexibility, 3-Day Weekly Training Program (02:37:12) Physical Activity vs. Exercise (02:40:12) Tool:4-Day Weekly Training Program, Muscular Endurance (02:51:15) Tool: 5/6-Day Weekly Training Program, Recovery (02:54:06) Program Modification, Balancing Joy (03:04:47) Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Neural Network Newsletter Title Card Photo Credit: Mike Blabac Disclaimer

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.30.526170v1?rss=1 Authors: Mauri, S., Bernardo, G., Martinez, A., Favaro, M., Trevisan, M., Cobraiville, G., Fillet, M., Caicci, F., Whitworth, A. J., Ziviani, E. Abstract: Stress-induced mitophagy, a tightly regulated process that targets dysfunctional mitochondria for autophagy-dependent degradation, mainly relays on two proteins, PINK1 and Parkin, which genes are mutated in some forms of familiar Parkinson Disease (PD). Upon mitochondrial damage, the protein kinase PINK1 accumulates on the organelle surface where it controls the recruitment of the E3-ubiquitin ligase Parkin. On mitochondria, Parkin ubiquitinates a subset of mitochondrial resident proteins located on the outer mitochondrial membrane, leading to the recruitment of downstream cytosolic autophagic adaptors, and subsequent autophagosome formation. Importantly, PINK1/Parkin-independent mitophagy pathways also exist that can be counteracted by specific deubiquitinating enzymes (DUBs). Downregulation of these specific DUBs can presumably enhances basal mitophagy, and be beneficial in models in which accumulation of defective mitochondria is implicated. Among these DUBs, USP8 is an interesting target because of its role in the endosomal pathway and autophagy, and its beneficial effects, when inhibited, in models of neurodegeneration. Based on this, we evaluated autophagy and mitophagy levels when USP8 activity is altered. We used genetic approaches in D. melanogaster to measure autophagy and mitophagy in vivo, and complementary in vitro approaches to investigate the molecular pathway that regulates mitophagy via USP8. We found an inverse correlation between basal mitophagy and USP8 levels, in that inhibition of USP8 correlates with increased Parkin-independent mitophagy. These re-sults suggest the existence of a yet uncharacterized mitophagic pathway that is inhibited by USP8. 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/2023.01.09.523359v1?rss=1 Authors: Inoue, D., Narita, T., Ishikawa, K., Maeno, K., Motoyama, A., Ono, T., Aoki, H., Shibata, T. Abstract: Background: Intensive studies have revealed pleiotropic melanocytic factors for age spot formation. In particular, dysfunctional keratinocyte differentiation is thought to be an upstream cause of age spot formation. Although keratinocyte differentiation is mediated by a cell-cell contact factor, E-cadherin, its involvement in age spots remains unknown. To find the origin of age spots and an integrated solution, we focused on E-cadherin. Methods: Immunofluorescent staining with cutaneous tissues and cultured cells was performed. Keratinocytes treated with siRNAs were cocultured with melanocytes. With the supernatants of the keratinocyte culture, secretion factors were identified using proteomic analysis. For the activity of melanogenesis and the ingredient screening, a quantitative PCR was performed. For the behavioral analysis of melanocytes, time-lapse imaging of melanocytes was done by confocal laser scanning microscopy. Results: In age spots, E-cadherin expression in the epidermis was downregulated, suggesting that E-cadherin is implicated in age spot formation. E-cadherin knockdown (E-cad-KD) keratinocytes not only promoted the secretion of melanocytic/inflammatory factors, but also increased melanogenesis by upregulating the expression of melanogenesis factors. Furthermore, live imaging showed E-cadherin downregulation detained melanocyte dynamics and accelerated melanin-uptake. Finally, we identified Rosa multiflora fruit extract as a solution for upregulating E-cadherin in keratinocytes. Conclusion: Our findings showed that E-cadherin downregulation triggers various downstream melanocytic processes such as secretion of melanocytic factors and melanogenesis. Additionally, we showed that Rosa multiflora fruit extract upregulates E-cadherin expression in keratinocytes. 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/2022.12.14.520496v1?rss=1 Authors: Balivada, S., Tapia, G. P., Pawar, H. N., Khan, A. M., Kenney, M. J. Abstract: The rostral ventrolateral medulla (RVLM), a part of the medullary reticular formation, plays a major role in several physiological responses, including cardiovascular and sympathetic nervous system functions. Although aging causes disturbances in the responses of these physiological systems, RVLM involvement in these age-related changes is not clear. Previous work using high-throughput gene expression analysis of the RVLM in aged animals suggested that chemical neurotransmission-related genes might be downregulated with advancing age. Since RVLM function involves a balance of signals from inhibitory and excitatory inputs, which is largely mediated by gamma-aminobutyric acid (GABA) and excitatory amino acid (EAA) neurotransmission, we hypothesized that aging is associated with altered excitatory and/or inhibitory neurotransmission-related gene expression in the RVLM. To test this hypothesis, we micropunched an RVLM-containing area from young (3-5 months), middle-aged (12-14 months), and aged (22-26 months) Fischer 344 male rats. RNA purified from these micropunches was analyzed using GABA and Glutamate RT2 Profiler PCR arrays (n= 8-10). Each profiler array has primers for 84 GABA and glutamate neurotransmission related genes. In addition, the expression of selected genes was validated at the RNA level using TaqMan(R) based- qPCR and at the protein level using western blotting. All the genes that displayed significant differential expression (1.5-fold, p less than .05, FDR less than .05) were identified to be downregulated in the RVLM of aged and middle-aged rats compared to young rats. This downregulation did not appear to be a result of RVLM tissue sampling differences among the age groups, since a separate validation of our sampling method, which involved careful mapping of micropunched regions to a standardized brain atlas, revealed no spatial differences in sampled sites among age groups. Among the downregulated genes, the percentage of glutamate neurotransmission-related genes was higher than GABA neurotransmission-related genes. The Solute carrier family 1 member 6 (Slc1a6) gene showed the highest fold downregulation at the RNA level in the RVLM of aged compared to young rats, and its protein product, Excitatory amino acid transporter 4 (EAAT4), showed a downregulatory trend in the RVLM of aged and middle-aged rats. These results suggest that molecular constituents of both GABA and glutamate neurotransmission might be altered in the RVLM of aged and middle-aged rats, and the changes in glutamate neurotransmission might be more prominent. Investigating age-associated anatomical and functional changes in RVLM GABA and glutamate neurotransmission might provide a foundation for understanding the effects of aging on physiological function. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

A new research paper was published in Oncotarget's Volume 13 on November 2, 2022, entitled, “MK256 is a novel CDK8 inhibitor with potent antitumor activity in AML through downregulation of the STAT pathway.” Acute myeloid leukemia (AML) is the most lethal form of AML due to disease relapse. Cyclin dependent kinase 8 (CDK8) is a serine/threonine kinase that belongs to the family of Cyclin-dependent kinases and is an emerging target for the treatment of AML. MK256, a potent, selective, and orally available CDK8 inhibitor was developed to target AML. In this new study, researchers Jen-Chieh Lee, Shu Liu, Yucheng Wang, You Liang, and David M. Jablons from the University of California San Francisco and Touro University sought to examine the anticancer effect of MK256 on AML. “In CD34+/CD38- leukemia stem cells, we found that MK256 induced differentiation and maturation.” Treatment of MK256 inhibited proliferation of AML cell lines. Further studies of the inhibitory effect suggested that MK256 not only downregulated phosphorylated STAT1(S727) and STAT5(S726), but also lowered mRNA expressions of MCL-1 and CCL2 in AML cell lines. Efficacy of MK256 was shown in MOLM-14 xenograft models, and the inhibitory effect on phosphorylated STAT1(S727) and STAT5(S726) with treatment of MK256 was observed in vivo. Pharmacologic dynamics study of MK256 in MOLM-14 xenograft models showed dose-dependent inhibition of the STAT pathway. Both in vitro and in vivo studies suggested that MK256 could effectively downregulate the STAT pathway. In vitro ADME, pharmacological kinetics, and toxicity of MK256 were profiled to evaluate the drug properties of MK256. “Our results show that MK256 is a novel CDK8 inhibitor with a desirable efficacy and safety profile and has great potential to be a promising drug candidate for AML through regulating the STAT pathway.” DOI: https://doi.org/10.18632/oncotarget.28305 Correspondence to: Jen-Chieh Lee -jenchieh.lee@ucsf.edu, Shu Liu - shu.liu@ucsf.edu Keywords: AML, CDK8, kinase inhibitor, STAT pathway, xenograft Video: https://www.youtube.com/watch?v=8bRgqTg9-c8 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

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.04.515212v1?rss=1 Authors: Panessa, G. M., Pires, M. R., Pires, R. R., Jekabson, R., Tsuchida, E. T., de Souza-Pinto, N. C., da Cunha, F. M., Cussiol, J. R. R. Abstract: Inositol is a six-carbon sugar that functions as a precursor for signaling molecules such as phosphoinositides and inositol polyphosphates, which are involved in the regulation of important biological processes such as energy metabolism, environmental stress response, phosphate signaling, among others. Given its role in a myriad of signaling pathways, regulation of inositol synthesis is essential for cellular homeostasis. In budding yeast, transcription of genes involved in inositol metabolism is regulated by the transcriptional repressor Opi1, which repress transcription of genes containing cis-acting inositol-sensitive upstream activation sequences (UASINO). Upon genotoxic stress, cells activate the DNA Damage Response (DDR) to coordinate DNA repair and cell cycle progression. It has been proposed that inositol containing molecules might act as modulators of the DDR, but evidences are still scarce. Herein, we report that opi1 cells fail to downregulate the inositol phosphate pathway leading to sensitivity to genotoxins and replication defects. Moreover, cells lacking Opi1 show decreased gamma-H2A levels which might indicate that Opi1 contributes to the activation of the DDR kinases Mec1/Tel1 (ATR/ATM in mammals). Importantly, we show that deletion of the inositol pyrophosphate kinase Kcs1 (IP6K1/2/3 in mammals), which leads to inhibition of inositol pyrophosphate synthesis, rescues the MMS sensitivity and replication defects of opi1 cells. Further, overexpression of Kcs1 recapitulates the MMS sensitivity of cells lacking Opi1. Therefore, we propose that cells must downregulate inositol pyrophosphate synthesis during replication stress in order to trigger an effective DNA Damage Response. 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/2022.11.03.515033v1?rss=1 Authors: Krumbein, M., Oberman, F., Cinnamon, Y., Golomb, M., May, D., Vainer, G., Belzer, V., Meir, K., Fridman, I., Haybaeck, J., Poelzl, G., Kehat, I., Beeri, R., Kessler, S., Yisraeli, J. K. Abstract: The IGF2BP family of RNA binding proteins consists of three paralogs that regulate intracellular RNA localization, RNA stability, and translational control. Although IGF2BP1 and 3 are oncofetal proteins, IGF2BP2 expression is maintained in many tissues, including the heart, into adulthood. Previous studies indicated that IGF2BP2 is upregulated in cardiomyocytes during cardiac stress and remodelling and returns to normal levels in recovering hearts. These results suggested that IGF2BP2 might play an adaptive role during cardiac stress and recovery. Using a conditional, inducible transgenic mouse line, we found that enhanced expression of the IGF2BP2 transgene in newborn or adult hearts leads to dilated cardiomyopathy (DCM), with remodelling, fibrosis, and death within 3-4 weeks. Downregulation of the transgene after 2 weeks, however, rescues these mice, with complete recovery by 12 weeks. Proteomic analysis identified a downregulation of sarcomeric and mitochondrial proteins in hearts overexpressing IGF2BP2, and electron microscopy revealed fragmented mitochondria and elongated, thinner sarcomeres. Consistent with these results, IGF2BP2 is upregulated in patients with DCM or after myocardial infarction. These results show that cardiac stress upregulates IGF2BP2, leading to remodelling and compensation of the heart. Prolonged expression, however, leads to heart failure and death, making it an attractive target for therapeutic intervention. 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/2022.11.04.515188v1?rss=1 Authors: Bidaud-Meynard, A., Nicolle, O., Bourdais, A., Duclos, M., Saleh, J., Ruemmele, F., Farin, H. F., Delacour, D., Moshous, D., Michaux, G. Abstract: Intestinal microvillus atrophy is a major cause of enteropathies such as idiopathic or congenital diarrhea that are often associated with severe morbidity. It can be caused by genetic disorders, inflammatory diseases, toxins or pathogens. In particular, Microvillus inclusion disease (MVID) is characterized by a chronic intractable diarrhea and a severe microvillus atrophy. It is triggered by mutations in MYO5B, STX3, MUNC18.2 or UNC45A which alter epithelial polarity by affecting apical trafficking in intestinal epithelial cells. Furthermore, we recently established that the depletion of the V0 sector of the V-ATPase complex induces an MVID-like phenotype in C. elegans. In this study we investigated the function of the V0-ATPase complex in mouse intestinal organoids. We found that its depletion also triggers a very severe microvillus atrophy in this model. Furthermore, we established that the polarity of intestinal cells is affected in a patient carrying mutations in TCIRG1 which encodes a V0-ATPase subunit. However, V0-ATPase depletion does not recapitulate other MVID-specific phenotypes such as subapical vesicle accumulation and Rab11+ endosomes mislocalization. Finally, we found that the apical localization of the V0-ATPase is disrupted in MVID patients. Altogether these results suggest a role for the V0-ATPase in microvillus atrophy which might be independent from apical trafficking. 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 as "Aging (Albany NY)" by Medline/PubMed and "Aging-US" by Web of Science) Volume 14, Issue 20, entitled, “Downregulation of senescence-associated secretory phenotype by knockdown of secreted frizzled-related protein 4 contributes to the prevention of skin aging.” There is growing evidence that the appearance and texture of the skin that is altered during the aging process are considerably enhanced by the accumulation of senescent dermal fibroblasts. These senescent cells magnify aging via an inflammatory, histolytic, and senescence-associated secretory phenotype (SASP). Secreted frizzled-related protein 4 (SFRP4) was previously determined to be expressed in dermal fibroblasts of aging skin, and its increased expression has been shown to promote cellular senescence. However, its role in the SASP remains unknown. In this new study, researchers Kento Takaya, Toru Asou and Kazuo Kishi from Keio University School of Medicine's Department of Plastic and Reconstructive Surgery investigated the classical model of skin fibroblasts based on Hayflick's mitotic limit, the observation of SFRP4 expression in replicating senescent cells, and the effect of regulating this on the suppression of SASP and aging skin. “These results may contribute to the development of new therapies to ameliorate skin aging.” The researchers found that SFRP4 was significantly expressed in p16ink4a-positive human skin fibroblasts and that treatment with recombinant SFRP4 promoted SASP and senescence, whereas siRNA knockdown of SFRP4 suppressed SASP. They also found that knockdown of SFRP4 in mouse skin ameliorates age-related reduction of subcutaneous adipose tissue, panniculus carnosus muscle layer, and thinning and dispersion of collagen fibers. These findings suggest a potential candidate for the development of new skin rejuvenation therapies that suppress SASP. “This study shows that SFRP4, which is specifically expressed in aged p16ink4a-positive skin fibroblasts, contributes to SASP, and that treatment with SFRP4 causes worsening of this phenotype. To the best of our knowledge, the present study is the first to report that the suppression of SFRP4 expression in vivo ameliorates skin aging-related phenotypes, that is, adipose tissue atrophy and collagen fiber thinning, via SASP suppression.” DOI: https://doi.org/10.18632/aging.204273 Corresponding Author: Kento Takaya - Email: kento-takaya312@keio.jp Keywords: skin, fibroblast, SASP, SFRP4 Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204273 About Aging-US: Launched in 2009, Aging (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 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 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/agingus​ LinkedIn – https://www.linkedin.com/company/aging/ Reddit – https://www.reddit.com/user/AgingUS Pinterest – https://www.pinterest.com/AgingUS/ For media inquiries, please contact media@impactjournals.com. Aging (Aging-US) Journal Office 6666 E. Quaker Str., Suite 1B Orchard Park, NY 14127 Phone: 1-800-922-0957, option 1

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.04.506474v1?rss=1 Authors: Chen, F., Chen, Y., Ke, Q., Wang, Y., Chen, X., Peng, X., Cai, Y., Li, S., Sun, Y., Ji, Y., Jiang, Y., Wu, W., Wang, Y., Cui, L. Abstract: The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); host cell entry by this virus relies on the interaction between the receptor-binding domain (RBD) of its spike glycoprotein and the angiotensin-converting enzyme 2 (ACE2) receptor on cell membranes. In addition to serving as a receptor for SARS-CoV-2, ACE2 was originally discovered as a protective factor in the renin-angiotensin system (RAS) that catalyses the degradation of angiotensin II (Ang II) to Ang 1-7, which is involved in multiple organ pathology. Recent genetic and clinical studies reported that ApoE4 expression is associated with increased susceptibility to SARS-CoV-2 infection and the development of severe COVID-19, but the underlying mechanism is currently unclear. In the present study, by using immunofluorescence staining, molecular dynamics simulations, proximity ligation assay (PLA) and coimmunoprecipitation (Co-IP) combined with a biolayer interferometry (BLI) assay, we found that ApoE interacts with both the spike protein and ACE2 but does not show obvious isoform-dependent binding effects. These data suggest that ApoE4 increases SARS-CoV-2 infectivity in a manner that may not depend on differential interactions with the spike protein or ACE2. Importantly, further immunoblotting and immunofluorescence staining results showed that ApoE4 significantly downregulates ACE2 protein expression in vitro and in vivo and subsequently decreases the conversion of Ang II to Ang 1-7, which could worsen tissue lesions; these findings provide a possible explain by which ApoE4 exacerbates COVID-19 disease. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Episode 19: How Spike Protein Damages Mitochondria Spike protein. It is something we have heard a lot about over the past couple of years in relation to COVID-19. But how does the spike protein actually cause cell damage? In this study, researchers provide unique insight into the mechanism of damage and the evidence of damage in brain microglial cells using a Raman microspectrometer. Let's review. DrBeen: Medical Education Online https://www.drbeen.com/ FLCCC | Front Line COVID-19 Critical Care Alliance https://covid19criticalcare.com/ URL list from Thursday, Jul. 28 2022 Mitochondrial Dysfunction: A Prelude to Neuropathogenesis of SARS-CoV-2 - PMC https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8790819/#ref9 Mitochondrial Dynamics in SARS-COV2 Spike Protein Treated Human Microglia: Implications for Neuro-COVID - PMC https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487226/ SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2 | Circulation Research https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.121.318902 SARS-CoV-2 membrane protein causes the mitochondrial apoptosis and pulmonary edema via targeting BOK | Cell Death & Differentiation https://www.nature.com/articles/s41418-022-00928-x SARS-CoV-2 membrane protein causes the mitochondrial apoptosis and pulmonary edema via targeting BOK https://www.nature.com/articles/s41418-022-00928-x.pdf Raman Microspectrometer | Raman Spectra | Supplier https://www.microspectra.com/support/learn/raman-microspectrometer#:~:text=The%20Raman%20microspectrometer%20allows%20the,from%20the%20microscopic%20sampling%20area. Disclaimer: This video is not intended to provide assessment, diagnosis, treatment, or medical advice; it also does not constitute provision of healthcare services. The content provided in this video is for informational and educational purposes only. Please consult with a physician or healthcare professional regarding any medical or mental health related diagnosis or treatment. No information in this video should ever be considered as a substitute for advice from a healthcare professional.

In today's episode I amplify the importance of engaging with our higher activation states in the body in order to allow the body to remember its self regulating capacity that is often fragmented during traumatic experience. Although down regulating the nervous can be incredibly helpful in moment of intense stress, when chronically used, it may mean we are working against the physiology of what the traumatized state is communicating.  I discuss the importance of taking the time and space to get to the root of the nervous system high activation state so we aren't always reliant on parasympathetic strategies to get through our day. Enjoy the show! Be sure to rate, review, and share the show with those who you feel like would enjoy the show! Thanks for listening! To join my free community, head to https://dr-danielle-mcginnis.mn.co/share/ To follow me on social media, head to @drdaniellemcginnis To find my website, head to www.drdaniellemcginnis.com

Listen to a blog summary of a trending research paper selected as the cover for Volume 14, Issue 7 of Aging (Aging-US), entitled, "Downregulation of IGFBP5 contributes to replicative senescence via ERK2 activation in mouse embryonic fibroblasts." ___________________________________ In 1961, Leonard Hayflick and Paul Moorhead proposed a theory later named the Hayflick Limit. They discovered that a normal human cell can divide between 50 and 70 times before it can no longer proliferate and eventually dies. Researchers have since continued to explore this phenomenon and, today, this aging process is known as cellular (replicative) senescence. “There are currently several experimental models of cellular senescence. Hayflick and Moorhead observed that primary human fibroblasts in culture exhibit a limited proliferative capacity [6]. This growth arrest during passages is called replicative senescence.” This permanent cessation of the cell cycle is universally found in biology due to known and unknown causes, including the shortening of telomeres. While telomere shortening plays an important role, it is not the only event responsible for inducing cellular senescence. Thus, researchers have spent decades under the microscope experimenting with cellular models of replicative senescence. In a new study released on April 4, 2022, researchers from Sapporo Medical University in Sapporo, Japan, investigated mechanisms of replicative senescence in vitro. Their research paper was published on the cover of Aging (Aging-US) Volume 14, Issue 7, and entitled, “Downregulation of IGFBP5 contributes to replicative senescence via ERK2 activation in mouse embryonic fibroblasts.” Full blog - https://aging-us.org/2022/04/trending-with-impact-underlying-mechanisms-of-replicative-senescence/ DOI - https://doi.org/10.18632/aging.203999 Corresponding author - Atsushi Kuno - kuno@sapmed.ac.jp Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.20399 Keywords - aging, IGFBP5, replicative senescence, mouse embryonic fibroblasts, ERK2, ERK1 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 http://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/agingus​ LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Aging-US is published by Impact Journals, LLC: http://www.ImpactJournals.com​​ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay.Marking the beginnings of today's episode, narrating the glory and essence of a LIBRARY, I will be talking about the Regulation of receptors. I will thoroughly explain the terms up regulation and down regulation of receptors. I will also talk about connected terms like supersensitivity and desensitisation of receptors. Mechanism. consequences and examples of all these phenomena will be detailed. Hope you all find this episode of great importance and value.... For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!!You can access various links viahttps://linktr.ee/ispharmacologydifficult

Debunk health - It is a journey not destination Redefine health as consistency and lifestyle Do these things consistently and intently  80/20 - Be ON it for 80% of the time, OFF for 20% (1 day a week you can indulge in the "bad" stuff, but get right back on it the next day) Whole 30 - whole foods, "healthier" choices of food https://whole30.com/whole30-program-rules/ Walking at least 10,000 steps a day Quality sleep - build a routine to make yourself sleepy i.e. no liquids or food 2 hours before bed, read, drink tea, etc Downregulation - meditation, Disney December, light show, listening to music, walking, praying etc.

With Jen Esquer, DPT, you'll learn how to use breathwork to control your autonomic nervous system, how to manipulate your diaphragm to turn on downregulation, and how your vision affects your nervous system.✶ ◢ To get more information, head to my blog at VibrantBlueOils.com, get a copy of my book, Essential Oils to Boost The Brain & Heal The Body, or email me at info@VibrantBlueOils.com. Better yet, get snag your FREE Parasympathetic Toolkit - exclusive to podcast listeners. Click the link or send me an email to activate the most important nerve in your body. ☄ ☄ ✪ JEN ESQUER, DPT - www.docjenfit.com ❂ JODI - Facebook: Vibrant Blue Oils Discussion Group | Instagram: @VibrantBlueOils | Youtube: Vibrant Blue Oils

Es geht weiter mit meinem ICSI Tagebuch - ich starte in meine zweite ICSI Behandlung. Diesmal geht es mit der Downregulation mit dem Synarela Nasenspray los - denn ich werde im langen Protokoll mit einem GnRH Agonisten stimuliert. Ich erkläre euch auch kurz, was es mit dem Flare Up zu tun hat und verrate euch in meinem Kinderwunsch Tagebuch auch, ob ich mit Nebenwirkungen zu kämpfen hatte während der Downregulation. Außerdem verrate ich euch, was es mit meiner Nominierung zu Miss Germany 2022 auf sich hat! Für mich kann die Meldung super überraschend und ich freue mich unglaublich, unter den TOP160 für Miss Germany 2022 sein zu dürfen! Mehr zu meiner Mission bei Miss Germany findet ihr auch in meiner offiziellen Vorstellung als TOP160 Kandidatin: https://www.instagram.com/p/CRT-UyHB3Ur/ ----

Site your sources! Well we have done it. We show how spike proteins affect the VACCINATED and UNVACCINATED. There are risks involved for everyone these days and we're here to show you what's currently happening and discuss the repercussions of our actions. In true Resurrecting Our Freedom fashion there's no sugar coating on our reality and we're all called to stand for our beliefs in this wonderful country we call home. God Bless America! Share this with all those you care for and as many strangers as you can. We attached links to all the information used in this podcast for you to do your due diligence and educate yourself and your families. We love you all! Thanks for all the support you have given us!Documents, Research Papers and Articles used in this PodcastPfizer's Protocol Document:http://82.221.129.208/pfizervax.pdfAmerica's Frontline Doctors Brief for Citizens, Policymakers and Physicians:“IDENTIFYING POST-VACCINATION COMPLICATIONS & THEIR CAUSES: AN ANALYSIS OF COVID-19 PATIENT DATA”https://americasfrontlinedoctors.org/action_alerts/identifying-post-vaccination-complications-their-causes-an-analysis-of-covid-19-patient-data/Research Article “ Microbiology and Infectious Diseases”:https://scivisionpub.com/pdfs/covid19-rna-based-vaccines-and-the-risk-of-prion-disease-1503.pdfPfizer Confirms COVID-Vaccinated People Can ‘Shed' Spike Proteins And Harm The Unvaccinated:https://christiansfortruth.com/confirmed-covid-vaccinated-people-can-shed-spike-proteins-and-harm-the-unvaccinated/UK Report Predicts Up To 70% Of People Who Die In ‘Third Wave' Of Pandemic Will Have Received Two Doses Of COVID Vaccine:https://christiansfortruth.com/uk-report-predicts-up-to-70-of-people-who-received-two-covid-vaccine-doses-will-die-or-be-hospitalized-in-third-wave-of-pandemic/SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2:https://www.biorxiv.org/content/biorxiv/early/2020/12/04/2020.12.04.409144.full.pdf

This episode is also available as a blog post: http://biopatrika.com/2021/05/21/interview-stress-induced-nuclear-condensation-mediates-transcriptional-downregulation-and-cell-survival-upon-heat-shock/

 In this 79th in a series of live discussions with Bret Weinstein and Heather Heying (both PhDs in Biology), we discuss the state of the world through an evolutionary In this 79th in a series of live discussions with Bret Weinstein and Heather Heying (both PhDs in Biology), we discuss the state of the world through an evolutionary lens. In this episode, we again discuss the research showing that SARS-CoV2’s spike protein is sufficient on its own to cause disease. The authors believe that this is good news with regard to the vaccines currently in circulation; they may be right. We discuss the paper, the authors’ clarification. Then: lab leak  hypothesis  continues to gain ground. And: Portland erupts in more violence. The Evergreen State College cannot manage to hire a new president—what are they doing wrong, and what does it suggest about the future of higher ed? Finally, robins and crows face-off. Our book, A Hunter-Gatherer’s Guide to the 21st Century, is now available for pre-sale at amazon. Publication date: 9-14-21: https://www.amazon.com/dp/0593086880/...​ DarkHorse merchandise now available at: store.darkhorsepodcast.org Find more from us on Bret’s website (https://bretweinstein.net​) or Heather’s website (http://heatherheying.com​). Become a member of the DarkHorse LiveStreams, and get access to an additional Q&A livestream every month. Join at Heather's Patreon. Like this content? Subscribe to the channel, like this video, follow us on twitter (@BretWeinstein, @HeatherEHeying), and consider helping us out by contributing to either of our Patreons or Bret’s Paypal. Looking for clips from #DarkHorseLivestreams​? Here are some, updated frequently: @DarkHorse Podcast Clips Theme Music: Thank you to Martin Molin of Wintergatan for providing us the rights to use their excellent music. Q&A Link: https://youtu.be/MwcW6TB327w Mentioned in this episode: Lei et al 2021. SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2. Circulation Research 128(9): 1323–1326. https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.121.318902 Salk Institute news release, modified since May 1: https://www.salk.edu/news-release/the-novel-coronavirus-spike-protein-plays-additional-key-role-in-illness/ Blog post on Science Translational Medicine by Derek Lowe on Spike Protein Behavior: https://blogs.sciencemag.org/pipeline/archives/2021/05/04/spike-protein-behavior Video interview with Uri Manor, one of the authors on the Lei et al 2021 paper: https://www.youtube.com/watch?v=Uydsf51Lzv8 Wade, Support the show (https://www.patreon.com/bretweinstein)

In this 78th in a series of live discussions with Bret Weinstein and Heather Heying (both PhDs in Biology), we discuss the state of the world through an evolutionary lens. Our book, A Hunter-Gatherer’s Guide to the 21st Century, is now available for pre-sale at amazon. Publication date: 9-14-21: https://www.amazon.com/dp/0593086880/...​ DarkHorse merchandise now available at: store.darkhorsepodcast.org Find more from us on Bret’s website (https://bretweinstein.net​) or Heather’s website (http://heatherheying.com​). Become a member of the DarkHorse LiveStreams, and get access to an additional Q&A livestream every month. Join at Heather's Patreon. Like this content? Subscribe to the channel, like this video, follow us on twitter (@BretWeinstein, @HeatherEHeying), and consider helping us out by contributing to either of our Patreons or Bret’s Paypal. Looking for clips from #DarkHorseLivestreams​? Here are some, updated frequently: @DarkHorse Podcast Clips Theme Music: Thank you to Martin Molin of Wintergatan for providing us the rights to use their excellent music. Q&A Link: https://youtu.be/dF12Kvfl0Uo Mentioned in this episode: Joe Rogan’s original clip, with commentary by CNN: https://www.cnn.com/2021/04/29/media/joe-rogan-clarifies-vaccine-comments/index.html Fauci responds to Joe, April 28, 2021: https://www.youtube.com/watch?v=2QVPjioDvEc Joe Rogan clarifies his vaccine comments, April 29, 2021: https://www.youtube.com/watch?v=PloZ-GB9tzA Washington Post joins the fray, piles on with “experts,” April 29, 2021:https://www.washingtonpost.com/technology/2021/04/28/joe-rogan-podcast-vaccine-coronavirus/ CDC chart on risk for COVID-19 cases, hospitalizations and deaths by age cohort: https://www.cdc.gov/coronavirus/2019-ncov/covid-data/investigations-discovery/hospitalization-death-by-age.html Risk estimator from The Economist, March 11, 2021:https://www.economist.com/graphic-detail/covid-pandemic-mortality-risk-estimator “The novel Coronavirus’ spike protein plays additional key role in illness” from the Salk Institute, April 30, 2021: https://www.salk.edu/news-release/the-novel-coronavirus-spike-protein-plays-additional-key-role-in-illness/ Original research: Lei et al 2021. SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2. Circulation Research 128:1323–1326. https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.121.318902 The Washington Post is concerned about ivermectin, April 8, 2021: https://www.washingtonposSupport the show (https://www.patreon.com/bretweinstein)

Gary takes on the real issues that the mainstream media is afraid to tackle. Tune in to find out the latest about health news, healing, politics, and the economy.  Gut microbiome implicated in healthy aging and longevity Data from over 9,000 people reveal a distinct gut microbiome signature that is associated with healthy aging and survival in the latest decades of life Institute for Systems Biology (Seattle), February 18, 2021 The gut microbiome is an integral component of the body, but its importance in the human aging process is unclear. ISB researchers and their collaborators have identified distinct signatures in the gut microbiome that are associated with either healthy or unhealthy aging trajectories, which in turn predict survival in a population of older individuals. The work is set to be published in the journal Nature Metabolism. The research team analyzed gut microbiome, phenotypic and clinical data from over 9,000 people - between the ages of 18 and 101 years old - across three independent cohorts. The team focused, in particular, on longitudinal data from a cohort of over 900 community-dwelling older individuals (78-98 years old), allowing them to track health and survival outcomes.  The data showed that gut microbiomes became increasingly unique (i.e. increasingly divergent from others) as individuals aged, starting in mid-to-late adulthood, which corresponded with a steady decline in the abundance of core bacterial genera (e.g. Bacteroides) that tend to be shared across humans. Strikingly, while microbiomes became increasingly unique to each individual in healthy aging, the metabolic functions the microbiomes were carrying out shared common traits. This gut uniqueness signature was highly correlated with several microbially-derived metabolites in blood plasma, including one - tryptophan-derived indole - that has previously been shown to extend lifespan in mice. Blood levels of another metabolite - phenylacetylglutamine - showed the strongest association with uniqueness, and prior work has shown that this metabolite is indeed highly elevated in the blood of centenarians. "This uniqueness signature can predict patient survival in the latest decades of life," said ISB Research Scientist Dr. Tomasz Wilmanski, who led the study. Healthy individuals around 80 years of age showed continued microbial drift toward a unique compositional state, but this drift was absent in less healthy individuals.  "Interestingly, this uniqueness pattern appears to start in mid-life - 40-50 years old - and is associated with a clear blood metabolomic signature, suggesting that these microbiome changes may not simply be diagnostic of healthy aging, but that they may also contribute directly to health as we age," Wilmanski said. For example, indoles are known to reduce inflammation in the gut, and chronic inflammation is thought to be a major driver in the progression of aging-related morbidities. "Prior results in microbiome-aging research appear inconsistent, with some reports showing a decline in core gut genera in centenarian populations, while others show relative stability of the microbiome up until the onset of aging-related declines in health," said microbiome specialist Dr. Sean Gibbons, co-corresponding author of the paper. "Our work, which is the first to incorporate a detailed analysis of health and survival, may resolve these inconsistencies. Specifically, we show two distinct aging trajectories: 1) a decline in core microbes and an accompanying rise in uniqueness in healthier individuals, consistent with prior results in community-dwelling centenarians, and 2) the maintenance of core microbes in less healthy individuals." This analysis highlights the fact that the adult gut microbiome continues to develop with advanced age in healthy individuals, but not in unhealthy ones, and that microbiome compositions associated with health in early-to-mid adulthood may not be compatible with health in late adulthood. "This is exciting work that we think will have major clinical implications for monitoring and modifying gut microbiome health throughout a person's life," said ISB Professor Dr. Nathan Price, co-corresponding author of the paper.      Rosmarinic acid suppresses cognitive decline in Alzheimer disease mouse model University of Tokyo (Japan), February 15, 2021   According to news originating from the University of Tokyo , research stated, “Rosmarinic acid (RA), a polyphenol found in Lamiaceae herbs, is a candidate of preventive ingredients against Alzheimer’s disease (AD) as it potently suppresses the aggregation of amyloid b (Ab); however, the effect of RA on tau phosphorylation and cognitive dysfunction remains unclear.” Financial supporters for this research include Japan Society for the Promotion of Science; Japan Agency for Medical Research and Development; Cross-Ministerial Strategic Innovation Promotion Program. The news editors obtained a quote from the research from University of Tokyo: “The present study revealed that RA intake inhibited the pathological hallmarks of AD, including Ab and phosphorylated tau accumulation, and improved cognitive function in the 3 x Tg-AD mouse model. Additionally, RA intake suppressed hippocampal inflammation and led to the downregulation of the JNK signaling pathway that induces tau phosphorylation. Feeding with RA exerted an anti-inflammatory effect not only in the central nervous system but also in the periphery.” According to the news editors, the research concluded: “Downregulation of the JNK signaling pathway in hippocampus may be a potential mechanism underlying the inhibition of progression of pathology and cognitive deficit by RA feeding.”       Excess fatty tissue accumulated in the neck increases the chances of suffering heart problems, according to a new study University of Granada (Spain), February 15, 2021 Researchers from the University of Granada warn that an accumulation of fatty tissue in the neck (both the double chin and the deeper deposits, located between muscles and around the cervical vertebrae) is a predictor of central and overall adiposity, cardiometabolic risk, and a pro-inflammatory profile in sedentary young adults. Traditionally, the accumulation of visceral adipose tissue has been considered one of the factors most strongly related to cardiometabolic risk and chronic (low-grade) inflammation in humans. However, this well-established association has led researchers to neglect, to some degree, the study of other fatty deposits and their clinical/biological relevance. "Curiously, several studies have demonstrated that the accumulation of fat in the neck (both superficial deposits such as the double chin or jowls and the deeper deposits, located between the muscles and around the cervical vertebrae) increases in direct proportion to the weight or adiposity of the individual and that it follows specific accumulation patterns, according to gender," explains María José Arias Téllez, a researcher at the UGR and one of the main authors of this work.  In fact, a greater accumulation of fat in certain neck tissue compartments, particularly the deeper ones, is linked to a greater likelihood of cardiometabolic risk. Arias Téllez says, "However, the evidence accumulated to date has been based on experiments performed on patients with benign/malignant tumors or other chronic conditions, and it remains to be seen whether it can be generalized to relatively healthy adults." The study carried out at the UGR is part of the ACTIBATE project (Activating Brown Adipose Tissue through Exercise—seeprofith.ugr.es/actibate). The research was led by Jonatan Ruiz Ruiz and its results have been published in the International Journal of Obesity. The study shows that the accumulation of fat in the neck—measured with computed tomography scanning—as well as its distribution in different compartments, is associated with greater overall and central adiposity, greater cardiometabolic risk, and a greater inflammatory status among healthy young adults, regardless of the amount of total and visceral fat. In addition, among the most relevant findings, the researchers observed that this accumulation of fat in the neck was as powerful a factor (in terms of direction and magnitude) as the accumulation of visceral fat in the prediction of cardiometabolic risk and inflammatory status, especially in men. "Therefore, these results underline the need for further research in this new direction, to better understand the effect of fat accumulation in the upper part of the trunk (including the neck) and its clinical repercussions, especially in cardiometabolic riskand inflammation," explains Francisco Miguel Acosta Manzano, one of the main authors of the research. "We still have much work to do. We need to investigate the adipose tissue of the neck in greater depth, to understand its pathogenic role in obesity and associated comorbidities, as well as its biological importance. Furthermore, we only have scant knowledge about the morphological or molecular characteristics of the adipocytes in these deposits, and here basic studies are required. As we increase our knowledge of this deposit, we can also determine whether specific interventions (for example, physical exercise and/or restricted calorie intake) could help reduce the accumulation of fat in the neck (as well as total fat) and implement them clinically," explain Arias Téllez and Francisco Miguel Acosta Manzano, both Ph.D.s students on the Biomedicine program of the UGR's International School for Postgraduate Studies    Effects of saffron extract supplementation on mood, well-being and response to a psychosocial stressor in healthy adults Northumbria University (UK), February 16, 2021 According to news reporting originating from Newcastle upon Tyne, United Kingdom, research stated, “Anxiety, stress, and low mood are closely related and may contribute to depressive symptoms. Among non-pharmacological solutions to improve subclinical mood symptoms and resilience to stress, natural products such as saffron-identified as promising following preliminary beneficial effects in major depressive disorder-represent a relevant strategy.” Our news reporters obtained a quote from the research from Northumbria University: “This study aimed to assess the efficacy of 8 weeks’ supplementation with 30 mg standardized saffron extract on emotional well-being in healthy adults with subclinical feelings of low mood and anxiety and/or stress and evaluate the acute effect of saffron in response to a lab-based psychosocial stressor. The study adopted a double-blind, randomized, parallel groups design in which 56 healthy male and female individuals (18-54 years) received either a saffron extract or a placebo for 8 weeks. Chronic effects of saffron on subjective anxiety, stress, and depressive feelings were assessed using a questionnaire battery [including Profile of Mood State-2, (POMS)] and acute effects in response to a lab-based psychosocial stressor were measured through psychological and physiological parameters. Urinary crocetin levels were quantified. Participants who received the saffron extract reported reduced depression scores and improved social relationships at the end of the study. Urinary crocetin levels increased significantly with saffron supplementation and were correlated with change in depression scores. The typical stress-induced decrease in heart rate variability (HRV) during exposure to the stressor was attenuated following acute saffron intake.” According to the news editors, the research concluded: “Saffron extract appears to improve subclinical depressive symptoms in healthy individuals and may contribute to increased resilience against the development of stress-related psychiatric disorders. Clinical trials number: NCT03639831.”     The science of siestas: New research reveals the genetic basis for daytime napping Massachusetts General Hospital and University of Murcia (Spain), February 13, 2021   How often a person takes daytime naps, if at all, is partly regulated by their genes, according to new research led by investigators at Massachusetts General Hospital (MGH) and published in Nature Communications. In this study, the largest of its kind ever conducted, the MGH team collaborated with colleagues at the University of Murcia in Spain and several other institutions to identify dozens of gene regions that govern the tendency to take naps during the day. They also uncovered preliminary evidence linking napping habits to cardiometabolic health Napping is somewhat controversial,” says Hassan Saeed Dashti, Ph.D., RD, of the MGH Center for Genomic Medicine, co-lead author of the report with Iyas Daghlas, a medical student at Harvard Medical School (HMS). Dashti notes that some countries where daytime naps have long been part of the culture (such as Spain) now discourage the habit. Meanwhile, some companies in the United States now promote napping as a way to boost productivity. “It was important to try to disentangle the biological pathways that contribute to why we nap,” says Dashti.    Previously, co-senior author Richa Saxena, Ph.D., principal investigator at the Saxena Lab at MGH, and her colleagues used massive databases of genetic and lifestyle information to study other aspects of sleep. Notably, the team has identified genes associated with sleep duration, insomnia, and the tendency to be an early riser or “night owl.” To gain a better understanding of the genetics of napping, Saxena’s team and co-senior author Marta Garaulet, Ph.D., of the Department of Physiology at the University of Murcia, performed a genome-wide association study (GWAS), which involves rapid scanning of complete sets of DNA, or genomes, of a large number of people. The goal of a GWAS is to identify genetic variations that are associated with a specific disease or, in this case, habit.   For this study, the MGH researchers and their colleagues used data from the UK Biobank, which includes genetic information from 452,633 people. All participants were asked whether they nap during the day “never/rarely,” “sometimes” or “usually.” The GWAS identified 123 regions in the human genome that are associated with daytime napping. A subset of participants wore activity monitors called accelerometers, which provide data about daytime sedentary behavior, which can be an indicator of napping. This objective data indicated that the self-reports about napping were accurate. “That gave an extra layer of confidence that what we found is real and not an artifact,” says Dashti.   Several other features of the study bolster its results. For example, the researchers independently replicated their findings in an analysis of the genomes of 541,333 people collected by 23andMe, the consumer genetic-testing company. Also, a significant number of the genes near or at regions identified by the GWAS are already known to play a role in sleep. One example is KSR2, a gene that the MGH team and collaborators had previously found plays a role in sleep regulation.   Digging deeper into the data, the team identified at least three potential mechanisms that promote napping: Sleep propensity: Some people need more shut-eye than others. Disrupted sleep: A daytime nap can help make up for poor quality slumber the night before. Early morning awakening: People who rise early may “catch up” on sleep with a nap.   “This tells us that daytime napping is biologically driven and not just an environmental or behavioral choice,” says Dashti. Some of these subtypes were linked to cardiometabolic health concerns, such as large waist circumference and elevated blood pressure, though more research on those associations is needed. “Future work may help to develop personalized recommendations for siesta,” says Garaulet.  Furthermore, several gene variants linked to napping were already associated with signaling by a neuropeptide called orexin, which plays a role in wakefulness. “This pathway is known to be involved in rare sleep disorders like narcolepsy, but our findings show that smaller perturbations in the pathway can explain why some people nap more than others,” says Daghlas.   One or more soda a day could decrease chances of getting pregnant Boston University School of Public Health,  February 13, 2021 The amount of added sugar in the American diet has increased dramatically over the last 50 years. Much of that increase comes from higher intake of sugar-sweetened beverages, which constitute approximately one-third of the total added sugar consumption in the American diet. While consumption of these beverages has been linked to weight gain, type 2diabetes, early menstruation, and poor semen quality, few studies have directly investigated the relationship between sugary drinks and fertility. Now, a new study led by Boston University School of Public Health (BUSPH) researchers has found that the intake of one or more sugar-sweetened beverages per day—by either partner—is associated with a decreased chance of getting pregnant. The study was published in Epidemiology. "We found positive associations between intake of sugar-sweetened beverages and lower fertility, which were consistent after controlling for many other factors, including obesity, caffeine intake, alcohol, smoking, and overall diet quality," says lead author Elizabeth Hatch, professor of epidemiology. "Couples planning a pregnancy might consider limiting their consumption of these beverages, especially because they are also related to other adverse health effects." About 15 percent of couples in North America experience infertility. Identifying modifiable risk factors for infertility, including diet, could help couples conceive more quickly and reduce the psychological stress and financial hardship related to fertility treatments, which are associated with more than $5 billion in annual US healthcare costs. Through the Pregnancy Study Online (PRESTO), an ongoing web-based prospective cohort study of North American couples, the researchers surveyed 3,828 women aged 21 to 45 living in the United States or Canada and 1,045 of their male partners. Participants completed a comprehensive baseline survey on medical history, lifestyle factors, and diet, including their intake of sugar-sweetened beverages. Female participants then completed a follow-up questionnaire every two months for up to 12 months or until pregnancy occurred. Both female and male intake of sugar-sweetened beverages was associated with 20 percent reduced fecundability, the average monthly probability of conception. Females who consumed at least one soda per day had 25 percent lower fecundability; male consumption was associated with 33 percent lower fecundability. Intake of energy drinks was related to even larger reductions in fertility, although the results were based on small numbers of consumers. Little association was found between intake of fruit juices or diet sodas and fertility. "Given the high levels of sugar-sweetened beverages consumed by reproductive-aged couples in North America, these findings could have important public healthimplications," the authors concluded.

Wenn es zu viel Hormon war Bei Hormonmangel braucht es Hormone, um den Mangel auszugleichen. Einfache Geschichte. Um ein Minus auszugleichen, muss mal was drauf geben. Was aber, wenn es zu viel "drauf geben" war? Ist das dann ein Problem oder macht das nix? Eine der größten Fragen im Hormoncoaching ist die Frage, nach der Hormondosierung beziehungsweise, wie frau "von der hohen Hormondosierung wieder runterkommen" kann. Zu viel Hormon ist auch nicht gut Ist eigentlich eh klar, oder? Auch das stört das feine hormonelle Gleichgewicht. Und wird schneller als gedacht zum Problem. Nur zeigt sich das Problem wieder mit den gleichen Beschwerden, wie bisher (kleiner Hint - Das hat mit der Downregulation zu tun). Wer jetzt sofort "cold turkey", also in den kalten Entzug geht, tut dem Körper keinen Gefallen. Abruptes Absetzen von Hormoncremes und Co. ist keine Lösung. Wie du von deiner hohen Hormondosierung runterkommen kannst Lass es langsam angehen und unterstütze deinen Stoffwechsel bestmöglich. Welche Phytotherapeutika, Nährstoffe und vieles mehr du einsetzen solltest, um die Auscheidung der überschüssigen Hormone zu unterstützen, erzähle ich dir in der heutigen Podcastfolge. Hör unbedingt rein, wenn deine Hormonprobleme trotz Hormoncreme NICHT besser werden. Es lohnt sich, versprochen! "Nimm deine Gesundheit wieder selbst in die Hand!" Herzlichst deine Alex ______________________________________________ Hier sind Links, um raus aus dem Hormonchaos zu kommen: Webseite: www.alexbroll.com Kostenlose Hormonsprechstunde: www.alexbroll.com/sprechstunde Youtube: https://bit.ly/2hzB6dl Instagram: https://bit.ly/3ajVaHG

This past November I experienced a seminar focused on Breath and exposure. I knew at this time just a little bit about the benefits of breath and cold exposure, but I was intrigued to learn more as I desire to always further my knowledge on ways to optimism my health and overall wellbeing. I knew many of the benefits already, but I wanted to take it up a notch and learn how to properly do a cold plunge bath. So I dived right in by taking a seminar based in Venice Beach, Ca instructed by Kimmy Moss. In this 3 hours seminar I learned so much, that now I have more tools added to my belt of ways to optimism and master my body and mind. Today you will learn just that. We all breathe, although we learn today how to maximize and utilize our breath as an advantage in life and any stressful situation. Learn the benefits of cold and hot exposure and why it is such an essential tool to master your body and mind.  Meet my guest Kimmy Moss. Kimmy, currently coaches Breath & Exposure at DEUCE Gym in Venice, CA. She is one of less than 10 XPT Level 3 coaches in the world, trained by Power Speed Endurance Art of Breath, Patrick McKeown of The Oxygen Advantage, and mentored by Laird Hamilton & Gabby Reece, & founders of XPT. Committed to a lifetime of better understanding human perception, Kimmy is passionate about teaching others how breath work can help them live happier, healthier, more peaceful lives.   We Talk About: How to get a proper breath and actually breathe correctly Why we should we breathe through our nose Why we should develop a carbon dioxide tolerance Upregulation and Downregulation with your breath How your breath can give you energy Benefits of cold exposure and hot exposure How to use both as a tool to optimism your life Mental fortitude How anyone can do cold exposure and where to begin For full show notes and episode resources head to https://ericalippy.com/kimmy-moss/ Are you a Los Angeles local? Take the Breath + Exposure Seminar in Venice, CA. with Kimmy Moss https://breathandexposure.com/ Not local, but want to learn more about mastering your breath (discount code below) Everyday breathing course 25% off using my code: HAPPY2021 (available till 1/31) Find our guest at: https://breathandexposure.com/ http://www.deucegym.com/community/author/kimmymoss/ facebook/kimmy.moss @kimmy.moss Please don't forget to subscribe and leave a review! PASSION LOVE PURSUIT INSTAGRAM: https://www.instagram.com/passionlovepursuit/ PASSION LOVE PURSUIT FACEBOOK: https://www.facebook.com/passionlovepursuit/ PASSION LOVE PURSUIT PODCASTS: https://ericalippy.com/the-podcast/    

This first episode of the Plant Medicine Podcast in 2021 features a conversation with Dr. Reid Robison, discussing the potentials of using psychedelics to treat eating disorders. Dr. Robison is a board-certified psychiatrist and the chief medical officer at Novamind. He is also the co-founder of Cedar Psychiatry, founder of the Polizzi Free Clinic, and adjunct faculty at the University of Utah. Dr. Robison serves as the medical director of Center for Change—a top eating disorder treatment center—and he is currently the coordinating investigator for the upcoming MAPS study looking at the potential for MDMA-assisted psychotherapy as a treatment for eating disorders. In this conversation, Dr. Robison dissects the intricacies of various eating disorders and shares his experience using ketamine-assisted psychotherapy. At Center for Change, Dr. Robison conducted an IRB-approved study looking at the use of ketamine as a potential treatment for eating disorders. In the study, participants were regularly administered ketamine in a small group setting with therapeutic and integration work happening between sessions. Dr. Robison shares some anecdotal reports as well as the objective data from the study, both of which show promising results. In particular, Dr. Robison notes how ketamine can promote a sense of embodiment for individuals struggling with eating disorders, helping them return to a more intuitive connection with food and eating.  Additionally, Dr. Robison discusses topics such as neuroplasticity and the default mode network as potential key factors explaining why this type of treatment could be effective. Since compounds such as ketamine can promote neuroplasticity and downregulate the default mode network, this gives the therapist a window to do particularly effective work with the patient, as they are in a more malleable state and less burdened by routines and habitual thought patterns. Dr. Robison closes with a discussion of the upcoming MAPS study which will look at the possible efficacy of MDMA-assisted psychotherapy for anorexia and binge eating disorders.  In this episode: Dr. Robison's study of ketamine-assisted psychotherapy for eating disorders The therapeutic modalities Dr. Robison's team uses alongside ketamine for addressing eating disorders Psycholytic vs transformative applications of ketamine in psychotherapy The co-occurrence of eating disorders and conditions such as depression, anxiety, and PTSD Details of the upcoming MAPS study on MDMA-assisted psychotherapy for anorexia and binge eating disorder. Quotes: "If you look at eating disorders, they're pretty underfunded and there are no FDA approved medicine treatment options for anorexia, for example." [3:25] "Ketamine and other psychedelic medicines are therapy aids, therapy boosters, accelerators, or catalysts to the therapeutic process." [10:42] "But I do believe that there are lasting benefits, especially when you pair it with the psychotherapy—when you have this window of opportunity of neuroplasticity to do some deeper work." [21:07] "Healing can be disruptive sometimes and you do feel worse before you feel better in some cases." [25:23] "Downregulation of the default mode is such a powerful and welcome break from the day-to-day patterns in these conditions." [37:43] Links: Novamind Cedar Psychiatry Center for Change Upcoming MAPS study on MDMA-Assisted Psychotherapy for Eating Disorders Psychedelic Medicine Association Porangui  

Hello everyone and welcome to the WPB Health Consulting Podcast where we bring clarity to coaching. IF you are a first time or former guest we welcome you. We want to bridge the gap between research, anecdote, and practical application. So please check out our page @wpbconsulting on Instagram and Facebook to learn more about our guests and our coaching services. On today’s podcast, we have a bodybuilding coach and craftsman, Mr. Paul Serafini (IG @paulie_rocket) . Paul Serafini has built his coaching practice around his foundation in the academic setting. He has had multiple successes’ with competitors in the NPC and IFBB divisions. Paul's approach to coaching is rooted in the application of his academic and practical coaching expertise to enhance the experience and potential of his clients as they move toward their strength and physique goals. Paul has a Master’s Degree in Applied Exercise and Health Science and is a successful researcher with several published peer-reviewed studies (18). Today, we will be discussing nutrition, training, and the anabolic discussion of anabolic agents on bodybuilding prep and performance. All content found on the WPB Health Consulting LLC pages, including text, images, audio, or other formats were created for informational purposes only. The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health providers with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this site. If you think you may have a medical emergency, call your doctor, go to the emergency department, or call 911 immediately. WPB Health Consulting LLC does not recommend or endorse any specific tests, physicians, products, procedures, opinions, or other information that may be mentioned on WPB Health Consulting LLC pages. Reliance on any information provided by WPB Health Consulting LLC employees, contracted writers or medical professionals presenting content for publication to WPB Health Consulting LLC is solely at your own risk. The site may contain health- or medical-related materials or discussions regarding anabolic agents. If you find these materials offensive, you may not want to use our Site. The Site and its Content are provided on an "as is" basis. Links to educational content not created by WPB Health Consulting LLC are taken at your own risk. WPB Health Consulting LLC is not responsible for the claims of external websites and education companies. WPB Health Consulting Topics Discussed in order: Paul's Passion and How He Got Started with Coaching Discussing Up and Down-Regulation in Performance Assessing Feeback: Using performance as a measure to ensure short and long-term progress Lab Work and Reference Ranges The Individualized Approach to Contest Prep Discussing the effects of prep on mood, cognition, and mindset. What the hell is up with SARM's? Short and Long-Term Training Progress Sarcoplasmic Hypertrophy and Research Research: Haun, C. T., Vann, C. G., Osburn, S. C., Mumford, P. W., Roberson, P. A., Romero, M. A., ... & Moon, J. R. (2019). Muscle fiber hypertrophy in response to 6 weeks of high-volume resistance training in trained young men is largely attributed to sarcoplasmic hypertrophy. PLoS One, 14(6), e0215267.

This is a follow up episode to the show titled 'Controlling Blood Sugar - Diet.'     Instead of focusing on my personal experience, we cover the science of how berberine is supposed to help with blood sugar levels.     Clarifications:   I state that a possible benefit of berberine is to inhibit (stop) gluconeogenesis.      I believe I interpreted the literature wrong. It used the term inhibit, but in this case inhibit means to hinder.      So by downregulating (which I also got the definition wrong) gluconeogenic enzymes, gluconeogenesis is reduced.     Downregulation in this context is to diminish the stimulus response of the enzymes on the liver.      Questions/Comments:   Head over to howardsblend.com, and click Contact Us, or   email howard@howardsblend.com   You can also find me on social media...   Instagram @howardsblend   LinkedIn Howard Blend   If you enjoy and find value in this show's content, please leave a review on Apple Podcasts, leave a 5 star rating on Apple Podcasts, and subscribe on Apple Podcasts.   If Apple Podcasts is not your preferred platform, then you can listen to this show on howardsblend.com(recent episode), Google Play, Spotify, and Stitcher.   T-shirts with the Howard's Blend logo are now available on howardsblend.com as well.  If you need a new t-shirt and want to support the show, then head on over to the site to check it out.   Resources:     https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839379/     https://www.healthline.com/human-body-maps/hypothalamus#anatomy-and-function     https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855276/     https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855276/     https://www.sciencedirect.com/science/article/pii/S1388198118303354#:~:text=ATGL%20mRNA%20expression%20is%20positively,tissues%20upon%20fasting%20%5B30%5D.     https://examine.com/supplements/berberine/research/#pharmacology_absorption     https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/atp-binding-cassette-transporter     https://pubmed.ncbi.nlm.nih.gov/12489979/     https://examine.com/supplements/berberine/research/#safety-and-toxicology_general  

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.09.243477v1?rss=1 Authors: Deng, J., Song, L., Yang, Z., Zheng, S., Du, Z., Luo, L., Liu, J., Jin, X., Yang, J. Abstract: Neonatal lipopolysaccharide (LPS) exposure can lead to depressive-like behaviors in mice through inducing pro-inflammatory cytokines including interferon(IFN)-{gamma}. ATP8A2 is a phospholipid transporter located on the cell membrane. Studies have shown that the decrease in ATP8A2 expression in the prefrontal cortex (PFC) is associated with depressive behavior. Moreover, it has been reported that IFN-{gamma} could reduce ATP8A2 expression in non-neuronal cells. These findings prompted us to hypothesize that neonatal LPS exposure might induce ATP8A2 down-regulation in PFC in mice by increasing the IFN-{gamma} level. Mice pups consisting approximately evenly of both sexes were intraperitoneally injected with 3 doses of LPS (50 g/kg body weight for each dose) on postnatal day (PND5), PND7 and PND9. Here, we first found that PFC ATP8A2 expression decreased significantly and transiently till ten days after neonatal LPS exposure with the lowest level at two days after it. Moreover, a negative correlation of PFC ATP8A2 expression was found with the PFC level of IFN-{gamma}, rather than the other LPS-induced pro-inflammatory cytokines. Using anti-IFN-{gamma} neutralizing mAb, IFN-{gamma} was identified as the key mediator of LPS-induced ATP8A2 down-regulation in PFC in mice. Besides, neutralizing IFN-{gamma} partially but significantly rescued the depressive-like behaviors in adulthood induced by neonatal LPS exposure. In sum, the present study showed that neonatal LPS exposure induced ATP8A2 down-regulation in PFC and depressive-like behaviors in mice through increasing the IFN-{gamma} level. Copy rights belong to original authors. Visit the link for more info

Alexander Technique Teacher Imogen Ragone in Conversation with Trauma Awareness Activist Shay Seaborne. Imogen and Shay talk about how the neuroscience of stress and trauma connects with Alexander Technique practices and skills. Imogen talks with Shay about what she has learned from neuroscience about the neurobiology of stress and trauma. In particular they discuss three important concepts that support recovery and healing – Down-Regulation, Titration and Co-Regulation – and the ways Alexander Technique and BodyIntelligence have helped her implement these three important coping strategies. This podcast was originally broadcast as a live video on Facebook at Facebook.com/CalmConfidentControl Imogen’s website: ImogenRagone.com Imogen’s Facebook group, the BodyIntelligence Community: Facebook.com/groups/bodyintelligencecommunity Shay’s website and blog: ShaySeaborne.com More general information about the Alexander Technique: AlexanderTechnique.com You can learn how to support this and other Alexander Technique websites at AlexanderTechnique.com/support

Hello fellow birth workers! Today's episode is a little different. Here's some background before I explain. Life has been a lot, for all of us. Personally, I'm quite sensitive to being overwhelmed and overstimulated. I've cut way back on my own podcast consumption and really being very mindful of what I read, watch and listen too. This mindfulness as helped support my mental and emotional health over the last few months. I've had to reassess how I serve in my business with all these transitions. Being in a house and isolated from my community has been rough, and so I'm having to make adjustments. One of those adjustments is putting the Thriving Birth Worker Podcast on hiatus. I always want my work to be an authentic reflection of who I am, and right now, I'm not able to put more noise out into this noisy world authentically....

Hello fellow birth workers! Today's episode is a little different. Here's some background before I explain. Life has been a lot, for all of us. Personally, I'm quite sensitive to being overwhelmed and overstimulated. I've cut way back on my own podcast consumption and really being very mindful of what I read, watch and listen too.  This mindfulness as helped support my mental and emotional health over the last few months.  I've had to reassess how I serve in my business with all these transitions. Being in a house and isolated from my community has been rough, and so I'm having to make adjustments. One of those adjustments is putting the Thriving Birth Worker Podcast on hiatus. I always want my work to be an authentic reflection of who I am, and right now, I'm not able to put more noise out into this noisy world authentically....

Talking about breathing seems counter intuitive, but the reality of it is, there is probably so many of us out there that breath incorrectly. With proper breathing strategies we can improve our fitness, strength and performance and through breathwork we can improve the other end of the spectrum of recovery and speeding up the injury healing process.

The goal of The Win Your Life Podcast is to illuminate the intersection between prevention and performance. The fitness industry is focused on performance and not always concerned with prevention. On the other hand, our health care system is focused, by necessity, on combatting the overwhelming amount of disease, illness and injury in our society. At the intersection of prevention and performance, there is a group of coaches, medical professionals, business leaders, athletes, and thought leaders that are working to help you Win Your Life. In this series, we are addressing the idea of 'Universal Prescriptions', the notion that there is a best way for us all to exercise, eat, sleep, breath and live.  In this episode, Catalyst Athletics Athlete & TPHMN Performance Coach Caitlin Schad tells her story of making the Catalyst Team and tells us how her breathing and meditation practice has helped her in her sport. Caitlin explains why her approach to training, breathwork and meditation is not a one-size-fits all approach and how this has influenced her coaching.  Caitlin Podcast Shownotes    (1:44) Plainview, MN  (https://plainviewmn.com/) (2:23) Kinesiology Bachelor of Science at University of Minnesota (https://www.cehd.umn.edu/kin/) (3:00) Tucker Center on Girls & Women in Sport (https://www.cehd.umn.edu/tuckercenter/) (4:30) The sport of weightlifting  (https://www.olympic.org/weightlifting) (4:55) Link to U25 Nationals Footage, Caitlin is in the 76kg category (https://www.teamusa.org/usa-weightlifting/live/blue-platform) (5:51) Catalyst Athletics  (https://www.catalystathletics.com/) (9:38) Olympic Weightlifting by Greg Everett (https://www.amazon.com/Olympic-Weightlifting-Complete-Athletes-Coaches/dp/0990798542) (11:20) Bulgarian Method in Olympic Weightlifting  (https://startingstrength.com/article/the_bulgarian_method_of_training_olympic_weightlifters) (16:23) training camp with greg & pyros dimas (https://www.instagram.com/p/B69Um_6l2Tn/) (16:42) Power vs Aerobic responder considerations  (https://blog.dnafit.com/training-to-your-genes-power-vs-endurance) (21:04) Overhead range of motion (https://www.ptonthenet.com/articles/olympic-weightlifting-part-2a-flexibility-and-movement-requirements-1634) and strength considerations (https://exrx.net/Testing/WeightLifting/StrengthStandards) for weightlifting  (22:27) PTSMN (https://ptsmnhealth.org/) working overhead  (25:43) Recovery Methods: Napping (https://www.mayoclinic.org/healthy-lifestyle/adult-health/in-depth/napping/art-20048319) , Contrast Method (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633882/) (Heat and Ice, Shower), Downregulation (https://www.merriam-webster.com/medical/downregulation)   (26:38) Breathwork & Meditation for Training and State Optimization  (https://powerspeedendurance.com/artofbreath/) (28:21) Wim Hof (https://www.wimhofmethod.com/) , Shift State (https://shiftstate.io/) (31:08) Link to Caitlin hitting a big clean (https://www.instagram.com/p/CAWL8Q1Fvkw/) (31:32) Buffalo link on Max’s linkedin (https://www.linkedin.com/posts/max-lipset-7935726a_fearlessleader-confidence-strength-activity-6662436110926516224-Joip) (34:25) Parasympathetic vs Sympathetic State  (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1959222/) (34:30) Brian Mackenzie Art of Breath  (https://www.youtube.com/watch?v=HglseeK-nLU) (34:55) Nasal Breathing and Parasympathetic State  (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681046/) (35:12) Mouthbreathing and Sympathetic State (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070065/) , Tunnel Vision & Sympathetic State (https://www.ncbi.nlm.nih.gov/books/NBK539845/) (36:30) Superventilation & Wim Hof  (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605164/) (38:28) ‘The mind is the king of the senses, the breath is the king of the mind.’ B.K.S. Iyengar (https://www.amazon.com/Light-Yoga-Bible-Modern/dp/0805210318) (40:45) Why Zebras Don’t Get Ulcers, PS vs S tone (https://www.amazon.com/Why-Zebras-Dont-Ulcers-Third/dp/0805073698) (41:59) Superventiliation vs Hyperventilation (https://www.youtube.com/watch?v=tybOi4hjZFQ) (44:43) diaphragmatic breathing  (https://my.clevelandclinic.org/health/articles/9445-diaphragmatic-breathing) (45:00) the benefits of nasal breathing (https://www.washingtonpost.com/lifestyle/wellness/when-it-comes-to-breathing-during-exercise-youre-probably-doing-it-wrong/2019/01/23/b4d3c338-1e59-11e9-8b59-0a28f2191131_story.html) , intro to nasal breathing (https://vimeo.com/397981709)   (45:08) Dr. Andrew Weil (https://www.drweil.com/) , 4-7-8 Breathing Technique  (https://www.youtube.com/watch?v=yHsE4z1gba0) (47:20) Meditation Practice (https://www.nytimes.com/guides/well/how-to-meditate) : Headspace (https://www.headspace.com/?utm_source=google&utm_medium=cpc&utm_campaign=1919439341&utm_content=68065219102&utm_term=409649586657&headspace&gclid=Cj0KCQjwzZj2BRDVARIsABs3l9LBVeVvMb1-xmgnaPZxMmtZFzUHsCDDYSontpCkCa8psUYfZvveu3YaAotpEALw_wcB) (49:50) Waking Up App by Sam Harris (https://wakingup.com/)   (52:42) The observer of your thoughts  (https://medium.com/personal-growth/you-are-the-observer-realize-the-power-you-have-within-759dceceaefe) (56:42) @therealcaitshady (https://www.instagram.com/therealcaitschady/?hl=en) , @thepowerhousemn (https://www.instagram.com/thepowerhousemn/?hl=en) (57:03) wu-tang forever (https://open.spotify.com/album/4r3TaXjF2b1qwCpxjIpW43) (58:00) 4thworld (https://www.instagram.com/4theworld/?hl=en) , lastnamelipset,  (https://www.instagram.com/lastnamelipset/)

Now accepting new clients into my private practice Why your digestive issues might be kicking up right now Pain flares & fear How to groom your relaxation response (and why you must) Practices for downregulating the nervous system during high stress times Why extra nervous system support can help Resources mentioned in this show: Work with Erin: https://www.erinholthealth.com/membership A la carte tests & services: https://www.erinholthealth.com/tests-and-consults Eat to Achieve: https://www.erinholthealth.com/eat-to-achieve Erin on Insta: https://instagram.com/erinholthealth Robert VDH Breath work: @askrobertvdh Erin Telford Breathwork: https://erintelford.com/resources Cheri Keirstead EFT: https://cherikeirstead.com/ DNRS: Retrainingthebrain.com Coyote River Hemp Co. Goodandcompany.com Free shipping ALL orders FREE local door delivery within 20 mile radius from Portsmouth - includes CBD, hemp products and beverages Use code FUNK10 to save 10% off any order You can also call or text your order: 603-285-1245 Houston Enzymes 20% discount* Coupon Code: houston20 Apply at checkout at www.houstonenzymes.com OR call to order at 866-757-8627 *not to be combined with any other discounts Good for your first order One use per household. Expires May 31, 2020

Paying tribute to my interview the other day. Our topic today is all about Upregulation and Downregulation. What does it mean and why is it important? This is different than where we get our energy from. Tune in and learn about the difference between introversion/extroversion and this energy regulation.

Professor Serhan expands on the application of SPMs inside the inflammation-resolution cycle and outside this cycle, highlighting alternative mechanisms, the wide scope of SPM therapy and exciting new treatment considerations currently within the field of lipid research. Prof Serhan background on moving into studying lipid mediators. (1:30) Aspirin triggers biosynthesis of lipid mediators. (4:57) Old to new: Review of inflammation and stimulating resolution processes. (6:55) Resolvins reduce neutrophilic infiltration and inducing “self-limitation”. (11:14) Plasticity of macrophage poles – key function of SPMs. (13:48) Healthy human breast milk contains SPMs. (19:45) Structures, receptors and functional location of Resolvins. (20:44) Downregulation of biosynthetic enzymes and using SPMs. (25:00) Aged mice with enhanced inflammatory response and diminished resolution response. (29:00) SPMs in obesity models. (31:00) Role of SPMs in additional chronic inflammatory conditions. (40:05) SPM killing and clearance of infections without immune suppression. (44:34) SPMs, macrophage types and tumor reduction. (46:45) Topical SPM application in animal models. (49:51) Future publication on periodontal disease. (52:53)

Professor Serhan expands on the application of SPMs inside the inflammation-resolution cycle and outside this cycle, highlighting alternative mechanisms, the wide scope of SPM therapy and exciting new treatment considerations currently within the field of lipid research. Prof Serhan background on moving into studying lipid mediators. (1:30) Aspirin triggers biosynthesis of lipid mediators. (4:57) Old to new: Review of inflammation and stimulating resolution processes. (6:55) Resolvins reduce neutrophilic infiltration and inducing “self-limitation”. (11:14) Plasticity of macrophage poles – key function of SPMs. (13:48) Healthy human breast milk contains SPMs. (19:45) Structures, receptors and functional location of Resolvins. (20:44) Downregulation of biosynthetic enzymes and using SPMs. (25:00) Aged mice with enhanced inflammatory response and diminished resolution response. (29:00) SPMs in obesity models. (31:00) Role of SPMs in additional chronic inflammatory conditions. (40:05) SPM killing and clearance of infections without immune suppression. (44:34) SPMs, macrophage types and tumor reduction. (46:45) Topical SPM application in animal models. (49:51) Future publication on periodontal disease. (52:53)

Ein Bote im Blut Deine Hormone sind Botenstoffe. Das heißt sie transportieren eine Botschaft zu einer Zelle. Die Botschaft ist also von Zelle zu Zelle unterschiedlich, so dass eine Zelle im Darm eine andere Botschaft erhält, als eine Muskelzelle. Das Hormon ist wirkungslos ohne Rezeptor Solange das Hormon im Blut unterwegs ist, ist es wirkungslos. Meist wird es sogar von einem Transporter (einem Protein) von einem zum anderen Ort transportiert. Solange das Hormon an diesen Transporter gebunden ist, ist es wirkungslos. Das Schlüssel-Schloss-Prinzip Gelangt das Hormon, zum Beispiel das Estradiol, ein Östrogen-Hormon in die Zelle, ist es immer noch inaktiv. Erst wenn das Hormon an einen Rezeptor auf dem Zellkern bindet, wird es aktiv. Das Hormon wirkt also wie der Schlüssel in einem Schloss, der die geschlossene Tür öffnet und aktiviert mit der Bindung an den Rezeptor die Botschaft des Hormons. Ein Zuviel an Hormon reguliert die Freisetzung Der Körper kann sich, in der Regel, wunderbar selbst regulieren. Das heißt, hat ein Hormon eine Maximalmenge erreicht, ist das die Botschaft an das Gehirn die Freisetzung weiterer Hormone zu unterbrechen. So kann eine Überproduktion verhindert werden und ein Gleichgewicht wird erreicht. Der Zellkern weiß genau, was er gerade braucht Auch der Zellkern weiß sie zu helfen. Durch eine vergrößerte Bereitstellung von Rezeptoren kann der Zellkern die Aktivität der Hormone erhöhen. Das nennt man dan Up-Regulation. Durch eine Down-Regulation kann der Zellkern sich vor einer Überaktivität schützen. In der aktuelle Podcastfolge erläutere ich die die genaue Wirkungsweise deiner Hormone und erkläre dir, warum eine sanfte und geringe Dosierung von bioidentischen Hormonen so wichtig ist.

Fitzie is a truck driver and delivery guy in Local 25. He teaches yoga to calm up and coaches mobility to improve everyday life. Check him out on Instagram @fitzie_says_hi

Joey chats with John Marsh a man who's deeply passionate about helping humans optimise their life through meditation and mindfulness. He's an interesting feller, having been an Aerospace Engineer, Strength Coach, and Gym Owner. We discuss down-regulation, central nervous system, breathing and meditation. A very worthwhile listen for those who feel like they might benefit from a little more exercise of the mind The post JBcast #22: Getting Better Results In The Gym Through Down-Regulation appeared first on Jungle Brothers Strength and Movement.

Joey chats with John Marsh a man who's deeply passionate about helping humans optimise their life through meditation and mindfulness. He's an interesting feller, having been an Aerospace Engineer, Strength Coach, and Gym Owner. We discuss down-regulation, central nervous system, breathing and meditation. A very worthwhile listen for those who feel like they might benefit from a little more exercise of the mind The post JBcast #22: Getting Better Results In The Gym Through Down-Regulation appeared first on Jungle Brothers Strength and Movement.

Laurel is a yoga teacher and teacher trainer in New York City. She is an outside the box thinker, innovative movement practitioner, and skilled educator. Find out more about Laurel at laurelbeversdorf.com

This week Joe interviews world-renowned human performance specialist - Brian MacKenzie. Brian has studied performance and movement since 2001 with altitude, hypoxia, breathing mechanics & methods, along with heat and cold exposure. While listening to this week's podcast, you will hear Brian discuss the following topics: What it takes to complete a 100-mile run; The unique way in which Brian utilizes the "Training Mask"; The importance of nasal breathing; The affect that mouth-breathing has on your immune system; Step-by-step instruction through one of Brian's favorite breathing protocols...and much, Much MORE!  For Show Notes & Timestamps go to www.IndustrialStrengthShow.com

This week Joe interviews world-renowned human performance specialist - Brian MacKenzie. Brian has studied performance and movement since 2001 with altitude, hypoxia, breathing mechanics & methods, along with heat and cold exposure. While listening to this week's podcast, you will hear Brian discuss the following topics: What it takes to complete a 100-mile run; The unique way in which Brian utilizes the "Training Mask"; The importance of nasal breathing; The affect that mouth-breathing has on your immune system; Step-by-step instruction through one of Brian's favorite breathing protocols...and much, Much MORE!  For Show Notes & Timestamps go to www.IndustrialStrengthShow.com

Episode 01: Dr. Jacob Wilson & Rudy Mawer discuss the following points: - Mistakes when dieting - Why and how to periodize your diet - Metabolic adaptations to dieting & Adaptive Thermogenisis - Common errors with one day Refeeds / cheats - How to reduce metabolic down regulation from dieting. More info on the FB page: /themuscleprof /RMcoach

Aspergillus fumigatus is a major opportunistic, filamentous fungal pathogen causing invasive aspergillosis (IA), a fatal systemic infection in immunocompromised patients with significant mortality rate. The fungal cell is protected by a rigid but highly dynamic cellular structure, the cell wall that forms the first level of defence against environmental stress. The cell wall being an essential and unique structure of the fungus has always been an ideal drug target. The major antifungal drugs used currently either target the fungal cell membrane or cell wall. However, due to the poor efficacy of current antifungal therapy, the CWI (cell wall integrity) pathway has emerged as the focus of research in recent years to discover potential molecular drug targets for designing antifungal therapy with novel mode of action. This signaling cascade is dedicated to monitoring and maintaining functional integrity of the cell wall, remodelling its structure in response to cell surface stress. This MAPK (mitogen activated protein kinase) cascade is highly coordinated to transduce the stress signals to the nucleus and consequently trigger necessary gene expression to counteract the stress. In this study, we explored the pivotal role of guanine nucleotide exchange factor (GEF), Rom2 in cell wall stress response and antifungal drug susceptibility. The findings of this work reveal that the Rom2 GEF is essential for viability of the pathogen. Additionally, characterization of a conditional rom2 mutant functionally links it to the previously identified CWI sensors, namely, Wsc1, Wsc3 and MidA in A. fumigatus. The conditional mutant shows severe growth defects under repressive conditions such as hyper-susceptibility to heat, Calcofluor white and Congo red, similar to the ∆midA mutant. Additionally, similar to the ∆wsc1, the rom2 mutant cultured under repressive conditions is increasingly susceptible to the actively used antifungal and inhibitor of cell wall β-1,3-glucan synthesis, echinocandin such as caspofungin. Furthermore, the Rom2 shows a sub-cellular localization similar to the Rho1 GTPase to hyphal tips and also physically interacts with the GTPase. Thus, these relevant findings establish the integral role of Rom2 as an intermediate relay molecule acting between the cell surface sensors and Rho1 GTPase as well as the downstream MAPK module. This study also reports a novel mechanism imparting echinocandin tolerance to the pathogen. This work explores two possibilities that may explain the fungistatic nature of echinocandins against Aspergillus: one either owing to incomplete inhibiton of β-1,3-glucan synthesis or that the cell wall β-1,3-glucan is not essential for A. fumigatus viability. In order to evaluate the role of the β-1,3-glucan synthase subunit, Fks1 in viability, growth and antifungal response of the mold, a conditional fks1 mutant was generated. Downregulation of fks1 expression results in characteristic growth behaviour which phenocopies the effect of wild type treated with echinocandins. The mutant cultured under repressive growth conditions also displays significant decrease in cell surface β-1,3-glucan and enhanced galactomannan shedding, marked with a compensatory increase in chitin content. Importantly, the growth of the conditional fks1 mutant is not completely abolished in presence of echinocandin and an fks1 deletion mutant is surprisingly viable. These results strongly reflect that β-1,3-glucan is not essential in A. fumigatus, and thereby justifies the limited activity of β-1,3-glucan synthesis inhibitor echinocandin on the mold. The novel findings of the work also suggest that presence of septa is an essential means of survival for A. fumigatus upon echinocandin treatment. Compounds inhibiting septum formation exhibit significant synergism with the echinocandin caspofungin. Thus, the present study identifies and proposes that septum inhibition is a promising strategy for enhancing echinocandin fungicidal potency and improving existing antifungal therapy.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to exert an unexpected pro-survival, pro-proliferative and pro-invasive effect on a subset of human cancer cell lines. Recent clinical studies report that increased expression of endogenous TRAIL is associated with decreased disease-specific survival in renal cell carcinoma and cholangiocarcinoma which are resistant to TRAIL induced apoptosis. The present work investigated the role of endogenous TRAIL as an intrinsic growth factor in apoptosis-resistant human cancer cells. Several cell lines derived from solid human tumors were studied, among them the neuroblastoma cell line KELLY, a cancer cell line resistant to TRAIL-induced apoptosis. First, to investigate whether TRAIL-knockdown could inhibit cell growth, the use of small interfering RNAs (siRNA) for endogenous TRAIL was established and a successful knockdown was verified on both mRNA and protein level. Second, the functional impact of the knockdown of endogenous TRAIL was investigated by measuring cell growth and cell death after transfection: Interestingly, the human neuroblastoma cell line KELLY unexpectedly showed markedly reduced cell growth upon knockdown of endogenous TRAIL. Furthermore, knockdown of TRAIL induced cell death in KELLY cells, which was dependent on caspase-signaling and rescued by the addition of soluble TRAIL. Thus, endogenous TRAIL functions as an intrinsic survival and growth factor in the neuroblastoma cell line KELLY. The present work provided first evidence that the expression of endogenous TRAIL can be specifically downregulated through siRNA knockdown to inhibit survival and growth of cancer cells in-vitro, which are resistant to TRAIL induced apoptosis. The present data strongly supports the potential of endogenous TRAIL to function as a novel therapeutic target in cancer therapy. In the light of the emerging clinical use of siRNAs for cancer therapy, targeting TRAIL by RNA interference may provide a valuable treatment approach for patients with cancers resistant to TRAIL induced apoptosis and high expression levels of endogenous TRAIL.

Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that plays a key role in the pathogenesis of osteoarthritis (OA). Growth factors (GFs) capable of antagonizing the catabolic actions of cytokines may have therapeutic potential in the treatment of OA. Herein, we investigated the potential synergistic effects of insulin-like growth factor (IGF-1) and platelet-derived growth factor (PDGF-bb) on different mechanisms participating in IL-1β-induced activation of nuclear transcription factor-κB (NF-κB) and apoptosis in chondrocytes. Primary chondrocytes were treated with IL-1β to induce dedifferentiation and co-treated with either IGF-1 or/and PDGF-bb and evaluated by immunoblotting and electron microscopy. Pretreatment of chondrocytes with IGF-1 or/and PDGF-bb suppressed IL-1β-induced NF-κB activation via inhibition of IκB-α kinase. Inhibition of IκB-α kinase by GFs led to the suppression of IκB-α phosphorylation and degradation, p65 nuclear translocation and NF-κB-regulated gene products involved in inflammation and cartilage degradation (COX-2, MMPs) and apoptosis (caspase-3). GFs or BMS-345541 (specific inhibitor of the IKK) reversed the IL-1β-induced down-regulation of collagen type II, cartilage specific proteoglycans, β1-integrin, Shc, activated MAPKinase, Sox-9 and up-regulation of active caspase-3. Furthermore, the inhibitory effects of IGF-1 or/and PDGF-bb on IL-1β-induced NF-κB activation were sensitive to inhibitors of Src (PP1), PI-3K (wortmannin) and Akt (SH-5), suggesting that the pathway consisting of non-receptor tyrosine kinase (Src), phosphatidylinositol 3-kinase and protein kinase B must be involved in IL-1β signaling. The results presented suggest that IGF-1 and PDGF-bb are potent inhibitors of IL-1β-mediated activation of NF-κB and apoptosis in chondrocytes, may be mediated in part through suppression of Src/PI-3K/AKT pathway, which may contribute to their anti-inflammatory effects.

Background: Nelfinavir is an HIV protease inhibitor that has been used for a long period of time to treat HIVinfected individuals. It has recently emerged that nelfinavir could represent a prospective new anti-cancer drug, prompting us to test the effect of nelfinavir on leukemia cells. Methods: By combining in vitro and ex vivo studies, the effect of nelfinavir on leukemia cells and non-malignant, bone marrow-derived tissue cells was analyzed. Results: At a concentration of 9 mu g/ml, nelfinavir induced death of 90% of HL60, IM9, and Jurkat cells. At the same concentration and treatment conditions, less than 10% of aspirated human bone marrow cells showed nelfinavir-induced cell damage. Nelfinavir-induced death of leukemia cells was accompanied by activation of caspases 3, 7, and 8. Despite caspase activation, the upregulation of the anti-apoptotic bcl-2 family member protein mcl-1 that resulted from nelfinavir treatment stabilized the mitochondrial membrane potential, resulting in primarily mitochondria-independent cell death. Pharmacological downregulation of mcl-1 expression by treatment with sorafenib (2 mu g/ml) significantly enhanced nelfinavir-induced apoptosis even at lower nelfinavir concentrations (5 mu g/ml), but did not have additional detrimental effects on non-malignant bone marrow cells. Conclusions: The ability of nelfinavir to induce apoptosis in leukemia cells as a single agent in a mitochondria-independent manner might suggest it could be used as a second or third line of treatment for leukemia patients for whom standard mitochondria-directed treatment strategies have failed. Combination treatment with nelfinavir and sorafenib might further enhance the efficacy of nelfinavir even on chemo-resistant leukemia cells.

Mon, 15 Jun 2009 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/10672/ https://edoc.ub.uni-muenchen.de/10672/1/Sonuc_Niluefer.pdf Sonuc, Niluefer

Introduction Severe tissue trauma results in a general inflammatory immune response (SIRS) representing an overall inflammatory reaction of the immune system. However, there is little known about the functional alterations of monocytes in the early posttraumatic phase, characterized by the battle of the individual with the initial trauma. Methods Thirteen patients with severe multiple injury; injury severity score (ISS) >16 points (17 to 57) were included. The cytokine synthesis profiles of monocytes were characterized on admission, and followed up 6, 12, 24, 48, and 72 hours after severe multiple injury using flow cytometry. Whole blood was challenged with lipopolysaccharide (LPS) and subsequently analyzed for intracellular monocyte-related TNF-alpha, IL-1 beta, IL-6, and IL-8. The degree of organ dysfunction was assessed using the multiple organ dysfunction syndrome (MODS)-score of Marshall on admission, 24 hours and 72 hours after injury. Results Our data clearly show that the capacity of circulating monocytes to produce these mediators de novo was significantly diminished very early reaching a nadir 24 hours after severe injury followed by a rapid and nearly complete recovery another 48 hours later compared with admission and controls, respectively. In contrast to the initial injury severity, there was a significant correlation detectable between the clinical signs of multiple organ dysfunction and the ex vivo cytokine response. Conclusions As our data derived from very narrow intervals of measurements, they might contribute to a more detailed understanding of the early immune alterations recognized after severe trauma. It can be concluded that indeed as previously postulated an immediate hyperactivation of circulating monocytes is rapidly followed by a substantial paralysis of cell function. Moreover, our findings clearly demonstrate that the restricted capacity of monocytes to produce proinflammatory cytokines after severe injury is not only an in vitro phenomenon but also undistinguishable associated with the onset of organ dysfunction in the clinical scenario.

Adenosin-Rezeptoren (AdoR) zeigen als Komponenten des Adenosin-Signalweges komplexe Interaktionen untereinander, sowie mit weiteren Komponenten, wie der Ecto-5´-Nukleotidase (CD73) und der Adenosin-Desaminase (ADA). Diese Rezeptoren sind zudem mit den verschiedensten Signaltransduktionswegen verschaltet. Innerhalb dieser Arbeit sollten mögliche Mechanismen gemeinsamer potentieller Regulationen dieser Komponenten anhand von eukaryontischen Modellsystemen, wie auch anhand einer klinischen Studie zur chronisch lymphatischen Leukämie (CLL) untersucht werden. Für die Untersuchung transkriptioneller Regulationen wurde eine semiquantitative RT-PCR mit Hilfe eines heterologen Standards für alle 4 AdoR-Subtypen (A1, A2a, A2b, A3) etabliert. Die Spezifität dieser Systeme konnte mittels Restriktionsverdaus sowie Untersuchung von Transfektanten in AdoR-freien Zelllinien („Chinese Hamster ovary“ CHO) nachgewiesen werden. Densitometrische Auswertung der Amplifikate ermöglichte eine gute Quantifizierung der untersuchten mRNS-Niveaus, die noch Unterschiede in den subtypspezifischen cDNS-Niveaus von weniger als 40% deutlich auflöste. Für Untersuchungen in eukaryontischen Modellsystemen wurden C-terminale EGFPFusionskonstrukte aller 4 AdoR in pEGFP-N1 (Clontech) etabliert und in CHO- bzw. HeLa-Zelllinien transfiziert. Erfolgreicher Nachweis der Etablierung der Konstrukte erfolgte über Sequenzierung der neusynthetisierten Adaptersequenzen und über spezifische Restriktionsverdaus. Desweiteren konnte über die membranorientierte Fluoreszenzverteilung der Fusionskonstrukte in den Transfektanten auf eine erfolgreiche posttranslationale Prozessierung und Transport des Konstruktes in die Zellmembran zurückgeschlossen werden. RT-PCR-Analyse von RNS-Präparationen dieser Transfektanten zeigte eine erfolgreiche Transkription der Konstrukte. Innerhalb der HeLa-Zelllinie konnten alle 4 Subtypen erfolgreich exprimiert werden, wobei jedoch inhibitorische AdoR (A1AdoR; A3AdoR) leichter zu transfizieren waren als die excitatorischen A2aAdoR/A2bAdoR-Konstrukte. Letztere Transfektanten zeigten deutlich höhere Tendenzen zum Absterben, was mit einem erhöhtem cAMPNiveau dieser Zellen zusammenhängen könnte. Physiologische Aktivität des A3AdoR-Konstruktes konnte durch Verminderung der Teilungsrate der Transfektante beobachtet werden. Innerhalb der einzelnen Transfektanten konnten keine großen Änderungen der mRNS-Niveaus des entsprechenden transfizierten Subtypen festgestellt werden, was mit einer „Downregulation“ des nativen Subtypes erklärbar sein könnte. Jedoch zeigten sich zum Teil deutliche Niveau-Änderungen in den jeweils anderen Subtypen der Transfektante, was auf eine Interaktion der AdoR-Subtypen auf der Transkriptionsebene hindeutet. Verschiedene Wechselbeziehungen könnten mit - zum Teil von physiologischen Interaktionen her- bekannten Beziehungen der AdoR in verschiedenen Zelltypen in Zusammenhang gebracht werden. Induktion der Transfektanten mit AdoR-Agonisten, wie 5`-N-Ethyl-Carboxamido- Adenosin (NECA) oder (R)-N6-(1-Methyl-2-phenylethyl)-Adenosin (R-PIA) ergab einen Anstieg aller AdoR-cDNS-Niveaus im Falle der Aktivierung der Adenylylcyclase (A2a/A2bAdoR), bzw. eine Abnahme bei deren Inhibierung (A1/A3AdoR), die auch zum Teil subtypabhängige Modulationen und deutliche Abweichungen zur Kontrolllinie (EGFP-HeLa) zeigte. Behandlung der Zellen mit Alkohol als apoptosisstimulierendes Signal führte zu einer starken Erhöhung aller Subtyp-Niveaus, wobei besonders die A2aAdoR- und die A3AdoR-Transfektante die größten apoptotischen Tendenzen und auch die größten Modulationen der Subtyp-Niveaus zeigten. Transfektion der Konstrukte in die CHO-Zelllinie ergab gut exprimierende Klone der A1AdoR- und A3AdoR-Transfektante, die über membranorientierte Fluoreszenz des EGFP-Anhanges, wie auch über Nachweis der mRNS nachgewiesen werden konnten. Im Falle der excitatorischen AdoR erhielt man nur schwach exprimierende Klone der A2aAdoR-Transfektante, die deutliche Tendenzen zum Absterben zeigte. Wiederum fand man bei der A3AdoR-Transfektante einen erheblich verlangsamten Zellzyklus, was auf einer zellzyklusmodulierenden Wirkung des A3AdoR in verschiedenen Zelltypen beruht und somit auf eine erfolgreiche Signalfortleitung in der Transfektante hindeutet. Induktion der A1AdoR-Transfektante führte zu einer zeitabhängigen Konzentrierung und Internalisierung der Fluoreszenz, was auf eine intakte Regulation und Desensibilisierung dieses Subtypes innerhalb dieses Klones hindeutet. Die B-lymphoblastoide Zelllinie Raji wurde als Modellsystem für AdoR-Signalwege innerhalb des lymphatischen Systems untersucht. Eine starke Präsenz des A2aAdoR konnte mittels RT-PCR nachgewiesen werden, dessen Stimulation mit dem AdoR-Agonisten NECA wiederum zu einem Anstieg der mRNS-Niveaus aller AdoR-Subtypen führte. Behandlung mit Alkohol führte zu einem größeren Anteil an absterbenden Zellen sowie zu einem leichten Anstieg aller AdoR-Subtypen und deutet wiederum auf eine Beteiligung der AdoR an apoptotischen Antworten hin. Inwiefern substratmodulierende Komponenten des AdoR-Signalweges, insbesondere CD73 und ADA, in Regulationsmechanismen dieses Weges integriert sind, wurde in einem induzierbaren B-lymphoblastoiden Modellsystem, der 493-6-Zelllinie untersucht. Hierbei wurden durch induzierbare transkriptionelle Aktivierung zweier Mitogene, c-myc und EBNA2, vier unterschiedliche proliferative Zustände erzeugt und die Auswirkungen auf die Komponenten des Ado-Signalweges untersucht. Northern Blot-Analyse der 4 Zustände zeigten eine Zunahme der CD73- und A2aAdoR-mRNS-Niveaus mit sukzessiver Abschaltung der Mitogene, wobei EBNA2- Abschaltung den deutlichsten Effekt zeigte. ADA-mRNS-Niveaus zeigten meistens eine leichte Abnahme mit Abschaltung der Mitogene, was aber nicht eindeutig bestätigt werden konnte. Untersuchung der Zustände mit semiquantitativer RT-PCR ergaben eine Präsenz aller AdoR mit einer starken Überrepräsentierung des A2aAdoR. Wiederum konnte mit sukzessiver Abschaltung der Mitogene ein deutlicher Anstieg des A2aAdoR beobachtet werden, der wiederum deutlicher bei Abschaltung von EBNA2 ausfiel. Andere AdoR-Subtypen zeigten jedoch so gut wie keine Respons. Abschaltung der Mitogene führte sowohl bei EBNA2, wie auch bei cmyc nach ca. 3 bis 6 Stunden zu einem deutlichen Anstieg der A2aAdoR-Niveaus, sowie generell zu einer Abnahme des ADA-Niveaus im Falle der c-myc-Abschaltung. NECA-abhängige Erhöhung des cAMP-Niveaus korrelierte mit den A2aAdoRNiveaus der entsprechenden Proben. Ebenso konnte in diesem Labor eine Erhöhung der CD73-Aktivität mit Abschaltung der Mitogene nachgewiesen werden. Diese Ergebnisse deuten auf eine Rolle des A2aAdoR bei der Bereitstellung mitogener Signale und einer damit verbundenen Gewährleistung des Überlebens dieser Zelllinie bei inaktivierten Mitogenen, sowie auf modulatorische Interaktionen zwischen der CD73 und A2aAdoR hin. Modulierte CD73-Aktivitäten und Beteiligung der AdoR an apoptotischen Vorgängen in der chronisch lymphatischen Leukämie sind bereits länger bekannt. Innerhalb einer klinischen Studie zur CLL wurden 48 Patienten und 10 Kontrollpersonen auf Modulationen der AdoR-, sowie c-myc- als auch ADA-Niveaus, untersucht und auf eine klinische Relevanz hin überprüft. Im Bezug auf den Mittelwert der Kontrollgruppe konnten oft Modulationen der mRNSNiveaus der untersuchten Komponenten innerhalb der Patientengruppe gefunden werden. Korrelationsanalyse der Patientendaten ergab verschiedene Zusammenhänge der AdoR, wie auch der c-myc und der ADA untereinander, die zum Teil gegenläufig zu denen in der Kontrollgruppe waren. A2aAdoR-Niveaus korrelierten negativ mit der Leukozytenanzahl, einem Marker der CLL. Es konnte auch ein deutlicher Zusammenhang zwischen der CD73-Aktivität und der Leukozytenanzahl in diesem Labor gezeigt werden. Ebenso fand man einen starken Zusammenhang zwischen den c-myc- und ADANiveaus, sowie zwischen der ADA bzw. c-myc und diversen AdoR-Subtypen. Diverse, aus physiologischen Zusammenhängen bekannte Korrelationen fand man auch in der CLL wieder, was auf eine geregelte Modulation der AdoR-Niveaus in der CLL hindeutet, wobei jedoch keine Zusammenhänge mit den prognostischen Stadien nach Binet gefunden werden konnten. Ein aktive Modulation des A2aAdoR bei der Expansion der malignen B-Lymphozyten konnte anhand der Ergebnisse von 4 Folgeuntersuchungen vermutet werden. Wiederholung der Untersuchung nach 6 Monaten bis zu 1,5 Jahren zeigte eine deutliche negative Korrelation der Leukozytenzahl mit dem A2aAdoR-Niveau.

Mono-Mac-6 cells, but not U937 cells, can be Induced to rapidly express tumor necrosis factor (TNF) mRNA and protein when triggered with Ilpopolysaccharlde (LPS) at 1 pg/mI. Preincubatlon of the cells for 3 d with low amounts of LPS (10 ng/mI) results In nearly complete suppression of TNF secretion. This downreguiatlon appears to occur at the pretranslational level since specIfIc mRNA is virtually undetectable under these conditions. By contrast, the same prelncubatlon with 10 ng/mI LPS results in enhanced phagocytosls (28.6-67.2% for Staphylococcus aureus), demonstrating that not all monocyte functions are suppressed. While these results show that only stringent exclusion of LPS from culture media allows for Induction of TNF In the Mono-Mac-6 cell line, the pronounced effect of LPS preincubatlon may also provide a suitable model with which to study the mechanisms of LPS-lnduced desensitizatIon.

The density and affinity of beta-2-adrenoceptors on mononuclear cells from peripheral blood were studied in fifteen patients with cirrhosis of different severity and in thirteen controls. There was no significant difference between cirrhotic patients and controls in density or affinity of beta-2 binding sites. Within the cirrhotic group, however, the number of binding sites per cell was significantly lower in patients with severe ascites than in patients with mild to moderate or no ascites. This down-regulation of beta-adrenoceptors could influence the haemodynamic response to beta-blockers.