Long projection on a neuron that conducts signals away
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18 episodes with axons
2 episodes with axons
2 episodes with axons
2 episodes with axons
2 episodes with axons
2 episodes with axons
2 episodes with axons
In this episode, Justin and Matt speak with Andrew Culp. Andrew Culp (MA 2009, Ph.D. 2013) is a Professor of Media History and Theory and Program Director of the MA Aesthetics and Politics program (starting Spring 2023) in the School of Critical Studies and in the MA Aesthetics and Politics Program, California Institute of the Arts (CalArts). In his first book, Dark Deleuze (University of Minnesota Press, 2016), he proposes a revolutionary new image of Gilles Deleuze's thought suited to our 24/7 always-on media environment, and it has been translated into eight languages. With his second book, A Guerrilla Guide to Refusal (University of Minnesota Press, 2022), he arms the reader with critical theory as part of a journey through anarchist infowar, queer outlaws, and Black insurgency. He is currently working on two projects: a new structuralist theory of the state's arkhḗ, and a critical history of cybernetics from those subverting it from its inside. Culp's writing on these and other topics has appeared in Flügschriften, Radical Philosophy, symplokē, parallax, angelaki, Deleuziana, The Alienocene, and Boundary 2 online. As part of The Destructionist International, he also makes films and other media. His most recent is the experimental documentary Machines in Flames (2022), which explores the legacy of techno-sabotage. Andrew Culp: http://www.andrewculp.org/ Link to PDF of Guerilla Guide to Refusal: https://drive.google.com/file/d/1ml50d6vO80Ev2bF03yZGkP1RjNPGhpo1/view?usp=drive_link Destructionist International: https://destructionist.international/ warmachinepodcast.com Music for this episode: Exhausted Divinity, Niky Nine https://lazerdiscs.bandcamp.com/track/exhausted-divinity-2 Primitivo, Axons https://onsetaudio.bandcamp.com/track/primitivo Bone Orchard, Void Stasis https://cryochamber.bandcamp.com/track/bone-orchard
In this episode, Clayton Crockett joins Matt and Justin to discuss Catherine Malabou's recent book, "Stop Thief! Anarchism and Philosophy". Clayton Crockett is a Professor in the Department of Philosophy and Religion and the Director of the interdisciplinary Religious Studies program at University of Central Arkansas. He regularly teaches courses on Exploring Religion; Philosophy of Religion; Religion, Science and Technology; and Religion and Psychology. He has authored or edited a number of books, including Religion, Politics and the Earth; The Future of Continental Philosophy of Religion, Derrida After the End of Writing, and Energy and Change: A New Materialist Cosmo-theology. He is a member of a national organization that promotes religious literacy, the Westar Institute, and their “Seminar on God and the Human Future.” He is also a Distinguished Research Fellow for the Global Centre for Advanced Studies, an online graduate school (www.gcas.ie). Finally, he is a co-editor of an academic book series called “Insurrections: Critical Studies in Religion, Politics, and Culture” for Columbia University Press. Get the book: https://www.amazon.com/Stop-Thief-Philosophy-Catherine-Malabou/dp/1509555234/ref=sr_1_1?crid=2MQOAK76CXRV8&dib=eyJ2IjoiMSJ9.Y-B1tad_2xDcPgoLNWGrC_wQRtwCQ80-bc5wMe9LnPk.ykUS4H8Lmhiv7i7PKAj4PTgAm1RGGIDioDxJEfpBJNQ&dib_tag=se&keywords=stop+thief+malabou&qid=1719253683&sprefix=stop+thief+malabou%2Caps%2C97&sr=8-1 Music for this episode: Primitivo, Axons
Charles Skaggs & Jesse Jackson discuss "Quantum of Axos", the third audio drama from Big Finish Productions' Doctor Who: Tenth Doctor Classic Companions set from 2022, featuring David Tennant as the Tenth Doctor, Sophie Aldred as Dorothy "Ace" McShane, John Leeson as K9 Mark IV, and the return of the Axons! Find us here:X/Twitter: @NextStopWho @CharlesSkaggs @JesseJacksonDFW Instagram: @nextstopeverywherepodcast Facebook: Facebook.com/Nextstopeverywherepodcast Email: NextStopWho@gmail.com Listen and subscribe to us in Apple Podcasts and leave us a review!
"The Claws of Axos" Production GGG March 13 - April 3, 1971 An alien race offers a cure all for humanity, but it comes at a terrible price. Podcaster John S. Drew and writer/editor Jim Beard join forces once again to become the masters of time and space as they watch and review every single episode of the Classic Doctor Who series. In this episode, they discuss freak weather conditions, Bill Filer - Man of Action, and the Doctor's selfishness. Please make sure you are subscribed to our podcast via any of the major popular podcasting apps. You can write and comment or ask questions of us via email at thedoctorsbeardpodcast@gmail.com or by joining our Facebook community. Join our Patreon community where your sponsorship earns you early access to new episodes as well as exclusive content. Click on the link here to take you to the Patreon page.
It's not often that you get to chat with a neuroscientist. Still less often to chat with a neuroscientist that is also a doctor. Still less often to chat with a neuroscientist that is a doctor and also autistic. And less often still to chat with a neuroscientist who is also a doctor and also autistic and also a horseman. Finally, it's about a chance in a million, maybe more, to chat with a neuroscientist that is a doctor, is autistic, is a horseman and who is also a renowned horse trainer and published author on horse training and behaviour. Dr Stephen Peters is that man. His book, Evidence Based Horsemanship, is rapidly becoming something of a bible among those who would understand how their horse's brain and their human brain could best come together in working harmony. Of course, for those of us in the Equine Assisted World, whether we are practitioners, clients, or simply curious onlookers – or whether we are the horses upon whom the entire process depends – knowledge of the brain is key. If we are dealing with a physical issue, we first have to reach the person's brain before we can start that therapizing stuff. If we are working with neuro cognitive conditions, a basic working knowledge of the neuroscience of learning and cognition would seem essential – yet very few programs outside of Horse Boy Method offer this. If you are training and maintaining the therapy horse, understanding your own brain as well as, to some extent, that of your four-legged colleague would also seem to be an advantage. One day, the therapeutic approaches will hopefully begin to put neuroscience front and centre of their professional trainings. Axons, dendrites, myelination, BDNF and other neurotrophins, cerebral spinal fluid, the amygdala, cortisol, oxytocin and serotonin, the dance between the re frontal cortex and the rough emotional seas of the limbic system: it's a lot to navigate. So sit back, grab a pen, paper and beverage, and let Dr Stephen initiate you into the mysteries of that organ you work with every day; the noggin. Links and books mentioned:Evidence base horsemanship Martin Black and Dr. Steve Peters Courses with Dr. Steven Peters & Sarah Schlote course https://equuscience.com/Contact Dr. StephenHorsebrainscience.info Find our other shows and programs:https://rupertisaacson.com
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.14.548969v1?rss=1 Authors: Jacak, W. A., Jacak, J. Abstract: Ion plasmon-polariton model of stimulus in myelinated axons and in C fibers of pain sensation is developed. This solves a long standing problem in neuroscience of by 2 - 3 orders of magnitude discrepancy between the observed fast speed of the saltatory conduction in myelinated axons or in C fibers with the upper limit of diffusive ion current velocity in these axons. The latter, described in the framework of so-called cable model, is too low in axons because of poor conductivity of neuron inner cytosol. The compliance with observations has been achieved upon plasmonic model of ionic local oscillations synchronized in periodically corrugated axons and propagating with high speed in the form of wave-type plasmon-polariton without any net diffusion current, thus not limited by resistivity. The new model of stimulus in myelinated axons reveals the different controlling role of myelin than previously thought from cable model. The control mechanism in non-myelinated C fibers is also proposed in agreement with observations. Recognition of plasmon model of neural signaling may be important for identifying a new targets for the future treatment at demyelination diseases and for fighting pain. 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/2023.07.03.547522v1?rss=1 Authors: Bryson, M., Kloefkorn, H., Idlett-Ali, S., Garraway, S. M., Hochman, S., Martin, K. Abstract: Spinal cord injury (SCI) leads to hyperexcitability and dysfunction in spinal sensory processing. As hyperexcitable circuits can become epileptiform we explored whether such activity emerges in a thoracic SCI contusion model of neuropathic pain. Recordings from spinal sensory axons in multiple below-lesion segmental dorsal roots (DRs) demonstrated that SCI facilitated the emergence of spontaneous ectopic burst spiking in afferent axons, which synchronized across multiple adjacent DRs. Burst frequency correlated with behavioral mechanosensitivity. The same bursting events were recruited by afferent stimulation, and timing interactions with ongoing spontaneous bursts revealed that recruitment was limited by a prolonged post-burst refractory period. Ectopic bursting in afferent axons was driven by GABAA receptor activation, presumably via conversion of subthreshold GABAergic interneuronal presynaptic axoaxonic inhibitory actions to suprathreshold spiking. Collectively, the emergence of stereotyped bursting circuitry with hypersynchrony, sensory input activation, post-burst refractory period, and reorganization of connectivity represent defining features of epileptiform network. Indeed, these same features were reproduced in naive animals with the convulsant 4-aminopyridine (4-AP). We conclude that SCI promotes the emergence of epileptiform activity in spinal sensory networks that promote profound corruption of sensory signaling. This includes sensory circuit hypoexcitability during the refractory period and ectopic hyperexcitability during bursting via spiking in afferent axons that propagate bidirectionally via reentrant central and peripheral projections. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Welcome to this week's episode of the Multiple Sclerosis Weekly Update, where we cover the most recent and impactful news related to MS. This week, we delve into a groundbreaking study that reveals a genetic variant influencing the severity and progression of MS in certain patients. We also unpack a legal dispute between Biogen and Novartis over the biosimilar of Tysabri and explore what this means for branded biologic-drug makers. Additionally, we discuss the surprising impact of myelin on axons in MS, compare the efficacy of rituximab and ocrelizumab, and reflect on Christina Applegate's journey with MS. Stay tuned for these stories and more in this week's episode.Here are the like to the articles: https://www.healthline.com/health-news/ms-symptoms-progress-more-quickly-in-certain-people-researchers-think-they-know-whyhttps://news.bloomberglaw.com/health-law-and-business/details-emerge-in-biogens-failure-to-block-biosimliar-tysabrihttps://www.news-medical.net/news/20230630/Myelin-can-be-harmful-to-axons-in-multiple-sclerosis.aspxhttps://www.physiciansweekly.com/comparing-the-efficacy-of-rituximab-and-ocrelizumab-for-relapsing-remitting-multiple-sclerosis/https://www.sportskeeda.com/health-and-fitness/news-david-faustino-speaks-christina-applegate-s-struggle-multiple-sclerosis-diagnosisThe Just MS (Multiple Sclerosis) Show, w host Justin Loizos, is a podcast that connects, educates and tries to uplift others living with multiple sclerosis. It provides real-life stories, interviews, and information about DMTs (disease modification therapies) and updates on research developments.www.justmultiplesclerosis.com
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.03.539245v1?rss=1 Authors: Pani, A. M., Favichia, M., Goldstein, B. Abstract: Wnt signaling performs critical functions in development, homeostasis, and disease states. Wnt ligands are secreted signaling proteins that often move between cells to activate signaling across a range of distances and concentrations. In different animals and developmental contexts, Wnts utilize distinct mechanisms for intercellular transport including diffusion, cytonemes and exosomes [1]. Mechanisms for intercellular Wnt dispersal remain controversial in part due to technical challenges with visualizing endogenous Wnt proteins in vivo, which has limited our understanding of Wnt transport dynamics. As a result, the cell-biological bases for long-range Wnt dispersal remain unknown in most instances, and the extent to which differences in Wnt transport mechanisms vary by cell type, organism, and/or ligand remain uncertain. To investigate processes underlying long-range Wnt transport in vivo, we utilized C. elegans as an experimentally tractable model where it is possible to tag endogenous Wnts with fluorescent proteins without disrupting signaling [2]. Live imaging of two endogenously tagged Wnt homologs revealed a novel mode for long-distance Wnt movement in axon-like structures that may complement Wnt gradients generated by diffusion and highlighted cell type-specific Wnt transport processes in vivo. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.26.538466v1?rss=1 Authors: Siddiq, M. M., Toro, C. A., Johnson, N. P., Hansen, J., Xiong, Y., Mellado, W., Tolentino, R. E., Johnson, K., Jayaraman, G., Suhail, Z., Harlow, L., Beaumont, K. G., Sebra, R. G., Willis, D. E., Cardozo, C. P., Iyengar, R. Abstract: Introduction- Neurons transport mRNA and translational machinery to axons for local translation. After spinal cord injury (SCI), de novo translation is assumed to enable neurorepair. Knowledge of the identity of axonal mRNAs that participate in neurorepair after SCI is limited. We sought to identify and understand how axonal RNAs play a role in axonal regeneration. Methods- We obtained preparations enriched in axonal mRNAs from control and SCI rats by digesting spinal cord tissue with cold-active protease (CAP). The digested samples were then centrifuged to obtain a supernatant that were then sequenced. We used bioinformatics analyses to identify DEGS and map them to various biological processes. We validated the DEGs by RT-qPCR and RNA-scope. Results- The supernatant fraction was highly enriched for axonal mRNA. Using Gene Ontology, the second most significant pathway for all differentially expressed genes (DEGs) was axonogenesis. Among the DEGs was Rims2, which is predominately a circular RNA (circRNA) in the CNS. We show that Rims2 RNA within spinal cord axons is circular. We found an additional 200 putative circRNAs in the axonal-enriched fraction. Knockdown in primary rat cortical neurons of the RNA editing enzyme ADAR1, which inhibits formation of circRNAs, significantly increased axonal outgrowth. Focusing on Rims2 we used Circular RNA Interactome to predict that several of the miRNAs that bind to circRims2 also bind to the 3 prime UTR of GAP-43, PTEN or CREB1, all known regulators of axonal outgrowth. Axonally-translated GAP-43 supports axonal elongation and we detect GAP-43 mRNA in the rat axons by RNAscope. Discussion- By using our method for enrichment of axonal RNA, we detect SCI induced DEGs, including circRNA such as Rims2. Ablation of ADAR1, the enzyme that regulates circRNA formation, promotes axonal outgrowth of cortical neurons. We developed a pathway model using Circular RNA Interactome that indicates that Rims2 through miRNAs can regulate the axonal translation GAP-43 a known regulator of axonal regeneration indicating that axonal mRNA contribute to regeneration. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.19.533385v1?rss=1 Authors: Janusonis, S., Haiman, J. H., Metzler, R., Vojta, T. Abstract: The self-organization of the brain matrix of serotonergic axons (fibers) remains an unsolved problem in neuroscience. The regional densities of this matrix have major implications for neuroplasticity, tissue regeneration, and the understanding of mental disorders, but the trajectories of single fibers are strongly stochastic and require novel conceptual and analytical approaches. In a major extension to our previous studies, we used a supercomputing simulation to model 1000 serotonergic fibers as paths of superdiffusive fractional Brownian motion (FBM), a continuous-time stochastic process. The fibers produced long walks in a complex, three-dimensional shape based on the mouse brain and reflected at the outer (pial) and inner (ventricular) boundaries. The resultant regional densities were compared to the actual fiber densities in the corresponding neuroanatomically-defined regions. The relative densities showed strong qualitative similarities in the forebrain and midbrain, demonstrating the predictive potential of stochastic modeling in this system. The current simulation does not respect tissue heterogeneities, but can be further improved with novel models of multifractional FBM. The study demonstrates that serotonergic fiber densities can be strongly influenced by the geometry of the brain, with implications for brain development, plasticity, and evolution. 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/2023.02.28.530461v1?rss=1 Authors: Radivojevic, M., Rostedt Punga, A. Abstract: Mammalian axons are specialized for transmitting action potentials to targets within the central and peripheral nervous system. A growing body of evidence suggests that, besides signal conduction, axons play essential roles in neural information processing, and their malfunctions are common hallmarks of neurodegenerative diseases. The technologies available to study axonal function and structure integrally limit the comprehension of axon neurobiology. High-density microelectrode arrays (HD-MEAs) allow for accessing axonal action potentials at high spatiotemporal resolution, but provide no insights on axonal morphology. Here we demonstrate a method for electrical visualization of axonal morphologies based on extracellular action potentials recorded from cortical and motor neurons using HD-MEAs. The method enabled us to reconstruct up to 5-centimeter-long axonal arbors and directly monitor axonal conduction across thousands of recording sites. We reconstructed 1.86 meters of cortical and spinal axons in total and found specific features in their structure and function. 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/2022.12.26.521945v1?rss=1 Authors: Zang, Y., Marder, E., Marom, S. Abstract: The Na+ channels that are important for action potentials show rapid inactivation, a state in which they do not conduct, although the membrane potential remains depolarized1,2. Rapid inactivation is a determinant of millisecond scale phenomena, such as spike shape and refractory period. Na+ channels also inactivate orders of magnitude more slowly, and therefore have impacts on excitability over much longer time scales than those of a single spike or a single inter-spike interval3-9. Here, we focus on the contribution of slow inactivation to the resilience of axonal excitability10,11 when ion channels are unevenly distributed across the axonal membrane. We study models in which the voltage-gated Na+ and K+ channels are unevenly distributed along axons with different variances, capturing the heterogeneity that biological axons display12. In the absence of slow inactivation many conductance distributions result in spontaneous tonic activity. Faithful axonal propagation is achieved with the introduction of Na+ channel slow inactivation. This normalization effect depends on relations between the kinetics of slow inactivation and the firing frequency. Consequently, neurons with characteristically different firing frequencies will need to implement different sets of channel properties to achieve resilience. The results of this study demonstrate the importance of the intrinsic biophysical properties of ion channels in normalizing axonal function. 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/2022.11.29.518323v1?rss=1 Authors: Nilssen, E. S., Jacobsen, B., Doan, T. P., Girao, P. J. B., Witter, M. P. Abstract: Functionally distinct information encoded by the two main divisions of the entorhinal cortex (EC), the lateral EC (LEC) and the medial EC (MEC), is thought to be first integrated at the level of the hippocampus. Here we examine a circuit connecting MEC to LEC that supports functional interplay at the level of the two entorhinal domains. Using a combination of anatomical, in vitro electrophysiological and behavioral experiments in the mouse, we report that axons from MEC somatostatin-expressing GABAergic neurons densely distribute in layer I of LEC, where they drive strong and near selective inhibition of principal neurons in layer IIa. This inhibitory pathway is accompanied by MEC glutamatergic axons that innervate multiple layers of LEC and preferentially synapse onto principal neurons in layers IIb and III. Our findings indicate that excitatory and inhibitory projections from MEC may separately regulate the activity of different populations of hippocampal-projecting principal neurons in LEC. 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/2022.11.23.517748v1?rss=1 Authors: Newman, B. T., Patrie, J. T., Druzgal, T. J. Abstract: Puberty is a key event in adolescent development that involves significant, hormone-driven changes to many aspects of physiology including the brain. Understanding how the brain responds during this time period is important for evaluating neuronal developments that affect mental health throughout adolescence and the adult lifespan. This study examines diffusion MRI scans from the cross-sectional ABCD Study baseline cohort, a large multi-site study containing thousands of participants, to describe the relationship between pubertal development and brain microstructure. Using advanced, 3-tissue constrained spherical deconvolution methods, this study is able to describe multiple tissue compartments beyond only white matter (WM) axonal qualities. After controlling for age, sex, brain volume, subject handedness, scanning site, and sibling relationships, we observe a positive relationship between an isotropic, intracellular diffusion signal fraction and pubertal development across a majority of regions of interest (ROIs) in the WM skeleton. We also observe regional effects from an intracellular anisotropic signal fraction compartment and extracellular isotropic free water-like compartment in several ROIs. This work suggests that changes during pubertal development elicit a complex response from brain tissue that cannot be completely described by traditional methods focusing only on WM axonal properties. This work brings in vivo human neuroimaging studies more into line with work performed on animal models, which describe an interaction between increased myelination, neurogenesis, angiogenesis, and glial cell proliferation in response to pubertal hormones. 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/2022.11.01.513927v1?rss=1 Authors: Neel, D. V., Basu, H., Gunner, G., Bergstresser, M. D., Giadone, R. M., Chung, H., Miao, R., Chou, V., Brody, E. M., Jiang, X., Lee, E. B., Marques, C., Held, A., Wainger, B., Lagier-Tourenne, C., Zhang, Y.-J., Petrucelli, L., Young-Pearse, T., Chen-Plotkin, A., Rubin, L. L., Lieberman, J., Chiu, I. Abstract: Mitochondrial dysfunction and axon loss are hallmarks of neurologic diseases. Gasdermin (GSDM) proteins are executioner pore-forming molecules that mediate cell death, yet their roles in the central nervous system (CNS) are not well understood. Here, we find that one GSDM family member, GSDME is expressed by both mouse and human neurons. GSDME plays a role in mitochondrial damage and axon loss. Mitochondrial neurotoxins induced caspase-dependent GSDME cleavage and rapid localization to mitochondria in axons, where GSDME promoted mitochondrial depolarization, trafficking defects, and neurite retraction. The frontotemporal dementia (FTD)/amyotrophic lateral sclerosis (ALS)-associated proteins TDP-43 and PR-50 induced GSDME-mediated damage to mitochondria and neurite loss. GSDME deficiency prolonged survival, ameliorated motor dysfunction, and rescued motor neuron loss in the SOD1G93A mouse model of ALS. GSDME knockdown also protected against neurite loss in ALS patient iPSC-derived motor neurons. Thus, we identify GSDME as an executioner of neuronal mitochondrial dysfunction that contributes to neurodegeneration. 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/2022.09.28.509944v1?rss=1 Authors: Kim, H., Skuba, A., Xia, J., Han, S. B., Zhai, J., Yoo, R., Hu, H., Kang, S. H., Son, Y.-J. Abstract: Adult mammalian spinal cord stops re-entering sensory axons, resulting in incurable sensory loss after dorsal root injury. Challenging the prevailing view, we previously showed that axons rapidly stop by forming synaptic, not dystrophic endings, and that myelin inhibitors and CSPGs are not the primary mechanism arresting axons. Here, we report that in adult mice dystrophic endings are formed by occasional axons embedded in fibrous collagens, exclusively at the CNS:PNS boundary where oligodendrocyte precursor cells (OPCs, or NG2 glia) are sparse. Most axons stop beyond the boundary in extensive contacts with OPC processes. Live imaging, immuno-EM and OPC-DRG co-culture show that axonal synapses form on OPCs. Genetic OPC ablation, although incomplete, enables many axons to continue regenerating deep into the spinal cord. These data, together with earlier findings, conclusively demonstrate that axons stop largely because OPCs stimulate presynaptic differentiation. We identify OPCs as a major regenerative barrier at the CNS:PNS border. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.18.508427v1?rss=1 Authors: Gianatti, M., Garvert, A. C., Vervaeke, K. Abstract: Neuronal signals encoding the animal's position, originally discovered in the hippocampus, widely modulate neocortical processing. While it is assumed that these signals depend on hippocampal output, their origin has not been investigated directly. Here, we asked which brain region sends position information to the retrosplenial cortex (RSC), a key circuit for navigation and memory. Using two-photon axonal imaging in head-fixed mice performing a spatial task, we performed a comprehensive functional characterization of long-range inputs to agranular RSC. Surprisingly, most long-range pathways convey position information, but with key differences. We found that axons from the secondary motor cortex transmit the most position information. By contrast, axons from the posterior parietal- anterior cingulate- and orbitofrontal cortex and thalamus convey substantially less position information. Axons from the primary- and secondary visual cortex make a negligible contribution. These data show that RSC is a node in a widely distributed ensemble of networks that share position information in a projection-specific manner. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.15.508178v1?rss=1 Authors: Mitchell, M., Cook, L. F., Shiers, S., Tavares-Ferreira, D., Akopian, A. N., Dussor, G., Price, T. J. Abstract: Fragile X Mental Retardation Protein (FMRP) regulates activity-dependent RNA localization and local translation to modulate synaptic plasticity throughout the CNS. Mutations in the FMR1 gene that hinder or ablate FMRP function cause Fragile X Syndrome (FXS), a disorder associated with sensory processing dysfunction. FXS pre-mutations are associated with increased FMRP expression and neurological impairments including sex dimorphic presentations of chronic pain. In mice, FMRP ablation causes dysregulated DRG neuron excitability and synaptic vesicle exocytosis, spinal circuit activity, and decreased translation-dependent nociceptive sensitization. Activity-dependent, local translation is a key mechanism for enhancing primary nociceptor excitability which promotes pain in animals and humans. These works indicate that FMRP likely regulates nociception and pain at the level of the primary nociceptor or spinal cord. Therefore, we sought to better understand FMRP expression in the human dorsal root ganglion (DRG) and spinal cord using immunostaining in organ donor tissues. We find that FMRP is highly expressed in DRG and spinal neuron subsets with substantia gelatinosa exhibiting the most abundant immunoreactivity in spinal synaptic fields. Here, it is expressed in nociceptor axons. FMRP puncta colocalized with Nav1.7 and TRPV1 receptor signals suggesting a pool of axoplasmic FMRP localizes to plasma membrane-associated loci in these branches. Interestingly, FMRP puncta exhibited notable colocalization with calcitonin gene-related peptide (CGRP) immunoreactivity selectively in female spinal cord. Our results support a regulatory role for FMRP in human nociceptor axons of the dorsal horn and implicate it in the sex dimorphic actions of CGRP signaling in nociceptive sensitization and chronic pain. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.02.506344v1?rss=1 Authors: Hu, H., Hostetler, R. E., Agmon, A. Abstract: Oscillations of extracellular voltage, reflecting synchronous rhythmic activity in large populations of neurons, are a ubiquitous feature in the mammalian brain and are thought to subserve critical, if not fully understood cognitive functions. Oscillations at different frequency bands are hallmarks of specific brain or behavioral states. At the higher end of the scale, ultrafast (400-600 Hz) oscillations in the somatosensory cortex, in response to peripheral stimulation, were observed in human and a handful of animal studies; however, their synaptic basis and functional significance remain largely unexplored. Here we report that brief optogenetic activation of thalamocortical axons ex-vivo elicited precisely reproducible, ~410 Hz local field potential wavelets ("ripplets") in middle layers of mouse somatosensory (barrel) cortex. Fast-spiking (FS) inhibitory interneurons were exquisitely synchronized with each other and fired spike bursts in anti-phase with ripplets, while excitatory neurons fired only 1-2 spikes per stimulus. Both subtypes received shared excitatory inputs at ripplet frequency, and bursts in layer 5 FS cells required intact connection with layer 4, suggesting that layer 4 excitatory cells were driving FS bursts in both layers. Ripplets may be a ubiquitous cortical response to exceptionally salient sensory stimuli, and could provide increased bandwidth for encoding and transmitting sensory information. Lastly, optogenetically-induced ripplets are a uniquely accessible model system for studying synaptic mechanisms of fast and ultrafast oscillations. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer
Jon Pertwee plays the Third Doctor along with Jo Grant and UNIT as they go up against the Axons. And of course the Master is along for the ride. We talk about this 1971 story and determine if it is any good. Thanks for listening - Notes Music by PJM25595/Dalekium https://soundcloud.com/pjm25595 Podcast - https://soundcloud.com/user-432517125 Facebook - https://www.facebook.com/GallifreyanGazette
Charles Skaggs & Jesse Jackson discuss "The Claws of Axos", the third serial from Doctor Who Season 8 in 1971, featuring Jon Pertwee as the Third Doctor, Katy Manning as Jo Grant, Nicholas Courtney as the Brigadier, and Roger Delgado as the First Master! Find us here:Twitter: @NextStopWho, @CharlesSkaggs, @JesseJacksonDFW Instagram: @nextstopeverywherepodcast Facebook: Facebook.com/Nextstopeverywherepodcast Email: NextStopWho@gmail.com Listen and subscribe to us in Apple Podcasts and leave us a review!
Invading the Earth used to be so simple: Either land or crash your spaceship in Britain, wait for the local Time Lord to show up, then coerce them into helping you by threatening the people they care about. But it gets a little complicated when two Time Lords show up, which was oddly the norm back in the UNIT days, what with the Master constantly trying to both one-up the Doctor and do some invading/conquering/destroying of his own. It's enough to confuse even the most determined alien menace, but you're probably particularly vulnerable if you're a gestalt entity with a penchant for psychological attacks that resemble a bad acid trip. We're looking at you, Axons. The Claws of Axos might be deeply embedded in the Earth's crust, but we get the feeling its heart just isn't in this. Special guest Nathan Bottomley (@nathanbottomley) from Flight Through Entirety podcast and creator of therandomiser.net joins! Please leave a review on Apple Podcasts! Follow us on: TikTok! @pulltoopen Instagram: @pulltoopen63 Twitter: @pulltoopen63 Story Essentials Season 8, Serial 3 Story number: 56, per the The Pull To Open Codex Production Code: GGG Writers: Bob Baker and Dave Martin Producer: Barry Letts Aired 13 March – 3 April 1971 Pull To Open: The Claws of Axos Season 3 Episode 19
Well, this has been a busy week. Google has obviously drawn the most attention. At a bumper Google I/O event the search giant not only showed off Android 13 and its new Wear OS, but also (deep breath) the Pixel 6a, Pixel Watch, Pixel Buds Pro, Pixel 7 and 7 Pro, and an entirely new Pixel tablet. Only hours early Sony held its own livestream, revealing the new Xperia 1 IV flagship and more affordable Xperia 10 IV - though there's no sign of the expected compact Xperia 5 IV. But with a familiar design and only minor spec tweaks, are these destined to be yet more Sony also-rans? Finally, ZTE also unveiled its new flagship line-up, the Axon 40 series. As expected this includes the company's third-gen under-display selfie camera - but what else do the Axons have to offer? This podcast is produced by Foundry. Watch on YouTube: https://www.youtube.com/playlist?list=PLCrL1ZLeIgENlS1nEZzSiueFAiV1Cujvx Facebook: https://www.facebook.com/techadvisorhq Twitter: https://twitter.com/TechAdvisorHQ Instagram: https://www.instagram.com/techadvisorhq Read more: https://www.techadvisor.com
Ready for a jangly dream pop album about the ballsy bedsheet escape of two prisoners from Chicago's Metropolitan Correctional Center 10 years ago? That's the concept behind the new Axons release, “I Object to Everything” (out on 4/8). Adele of Axons joins me tonight to talk about the criminal justice system, the story that inspired the album and prison life. See Axons at the Hideout on 4/7/22!
This week, Features co-director Jessi D speaks with Adele Nicholas of Axons about their most recent release, I Object to Everything. They discuss her career within Axons and the bands current three-piece format, her day job as a civil rights attorney, and her inspiration from and deep research into a prison breakout - I Object to Everything is a concept album inspired by the true and almost mythological story of Kenneth Conley and Joseph "Jose" Banks, two inmates who escaped from the Metropolitan Correctional Center in downtown Chicago in 2012. "There were certain parts of this story that just were so emotionally compelling that I just knew they had a song in them." - Adele Nicholas Axons will be hosting a release show at the Hideout on Thursday, April 7, 2022. Produced by Jessi D. Photo credit: Jazmyne Fountain
Our first dip into the Third Doctor's era sees Jim and Martin discussing The Claws of Axos.
Alzheimer's Disease is the 6th leading cause of death in Wisconsin. One in six people over the age of 65 are affected with the disease. The good news is the monumental ongoing effort to identify, track, treat and prevent the disease. Perpetual Notion Machine host Patrick Sajbel welcomes back Dr. Nathaniel Chin, assistant professor in […] The post Alzheimer's: A Fresh Look and New Resources appeared first on WORT 89.9 FM.
Rusty is coming back to Doctor Who. No, not that one. It's Russell T Davies, back to regenerate the greatest show on TV with his old production team. It remains to be seen whether he can recapture the magic, but the BBC must be desperate. Gaming PCs are incredibly rare, and they're likely to get even rarer. This means people will pay a massive premium, and that entry level parts don't really exist anymore. This makes us sad. Everyone should have the opportunity to build a PC and learn about electronics. Maybe in the post apocalyptic future there will be enough supply to meet demand. An Aussie team has created a significantly cheaper and easier to make solar panel that outperforms traditional panels. The sunniest place on Earth could really use some of those. They still need to scale up, but it's great to see Aussie scientists making huge strides. Doctor Who: A New Hope? - https://twitter.com/bbcdoctorwho/status/1441405833997217798 Affordable PCs are now a pipe dream- https://www.pcgamer.com/rip-cheap-graphics-cards/Tech Start Up makes new Solar Cell- https://www.abc.net.au/news/2021-09-21/australian-start-up-creates-world-s-most-efficient-solar-cell/100476152Other topics discussedBBC - 5 things the Doctor does in any worrying situation | @Doctor Who - BBC- https://www.youtube.com/watch?v=l0ED6CGmjm4Russell T Davies (a Welsh screenwriter and television producer whose works include Queer as Folk, The Second Coming, Casanova, the 2005 revival of the BBC One science fiction franchise Doctor Who, Cucumber, Years and Years and It's a Sin.)- https://en.wikipedia.org/wiki/Russell_T_DaviesTorchwood (a British science fiction television programme created by Russell T Davies. A spin-off of the 2005 revival of Doctor Who, it aired from 2006 to 2011.)- https://en.wikipedia.org/wiki/TorchwoodBad Wolf (production company) (a British television production company founded by Julie Gardner and Jane Tranter in 2015, with its headquarters in Cardiff, Wales.)- https://en.wikipedia.org/wiki/Bad_Wolf_(production_company)Olly Alexander set to be new Doctor Who as first gay actor to play Time Lord- https://www.thesun.co.uk/tv/15405348/olly-alexander-doctor-who-actor-gay/Ruth Clayton (a human identity assumed by the Fugitive Doctor, who hid on Earth using a Chameleon Arch.)- https://tardis.fandom.com/wiki/Ruth_ClaytonJo Martin (Jo Martin played Ruth Clayton/Fugitive Doctor in the Doctor Who television stories Fugitive of the Judoon and The Timeless Children, alongside Jodie Whittaker's Thirteenth Doctor. She was the first non-white actor to be cast in the role of the Doctor in the DWU.)- https://tardis.fandom.com/wiki/Jo_MartinDoctor Who: actor Christopher Eccleston reveals he has anorexia- https://www.bbc.co.uk/newsround/49719101Christopher Eccleston is the Doctor!- https://www.bigfinish.com/news/v/christopher-eccleston-is-the-doctorMurray Gold (an English composer for stage, film, and television and a dramatist for both theatre and radio. He is best known as the musical director and composer of the music for Doctor Who from 2005, until he stepped down in 2018 after the tenth series aired in 2017. He has been nominated for five BAFTAs.)- https://en.wikipedia.org/wiki/Murray_GoldDaleks and Cybermen- https://www.youtube.com/watch?v=UCsXO7r6-z4Bob Baker (scriptwriter) (a British television and film writer. Baker and Martin devised for Doctor Who the robotic dog K-9 (created for The Invisible Enemy), the renegade Time Lord Omega (created for The Three Doctors, Doctor Who's 10th anniversary story) and the Axons. K-9 was originally intended to appear in one story only, but the BBC decided to make it a recurring character. )- https://en.wikipedia.org/wiki/Bob_Baker_(scriptwriter)Elisabeth Sladen (an English actress. She became best known as Sarah Jane Smith in the British television series Doctor Who, appearing as a regular cast member from 1973 to 1976, alongside both Jon Pertwee and Tom Baker, and reprising the role many times in subsequent decades, both on Doctor Who and its spin-offs, K-9 and Company (1981) and The Sarah Jane Adventures (2007–2011).)- https://en.wikipedia.org/wiki/Elisabeth_SladenSarah Jane Smith (a fictional character played by Elisabeth Sladen in the long-running BBC Television science fiction series Doctor Who and two of its spin-offs.)- https://en.wikipedia.org/wiki/Sarah_Jane_SmithThe Sarah Jane Adventures (In addition to Sladen, the first series of the programme stars Yasmin Paige as Maria Jackson, Sarah Jane's 13-year-old neighbour in Ealing, west London, and Tommy Knight as a boy named Luke, who is adopted by Sarah Jane at the conclusion of the introductory story.)- https://en.wikipedia.org/wiki/The_Sarah_Jane_Adventures#Cast_and_crewSadie Miller (an English actress and author. She is known for her portrayal of Natalie Redfern in the Sarah Jane Smith audio drama series by Big Finish, her novel, Moon Blink, from Candy Jar Books's series, Lethbridge-Stewart, as well as her association with the science fiction series, Doctor Who. She is the daughter of actors Brian Miller and Elisabeth Sladen.)- https://en.wikipedia.org/wiki/Sadie_MillerSean Pertwee (the son of Jon Pertwee, who played the Third Doctor. He briefly appeared as himself in the 50th anniversary story The Five(ish) Doctors Reboot.)- https://tardis.fandom.com/wiki/Sean_PertweeJon Pertwee (played the Third Doctor from 1970 to 1974, beginning from Spearhead from Space to Planet of the Spiders.)- https://tardis.fandom.com/wiki/Jon_PertweeGotham (TV series) (an American crime drama television series developed by Bruno Heller, produced by Warner Bros. Television and based on characters published by DC Comics and appearing in the Batman franchise, primarily those of James Gordon and Bruce Wayne.)- https://en.wikipedia.org/wiki/Gotham_(TV_series)Showrunner Russell T. Davies wants a Doctor Who Cinematic Universe- https://winteriscoming.net/2021/01/25/doctor-who-cinematic-universe-russell-t-davies/The Day of the Doctor (a special episode of the British science fiction television programme Doctor Who, marking the programme's 50th anniversary.)- https://en.wikipedia.org/wiki/The_Day_of_the_DoctorJourney's End (TV story) (Journey's End was the thirteenth and final episode of series 4 of Doctor Who. It was the final regular appearance of all the Tenth Doctor's companions, though they would all appear in cameos in The End of Time (barring Catherine Tate and Bernard Cribbins who prominently feature) to commemorate David Tennant's final story.)- https://tardis.fandom.com/wiki/Journey%27s_End_(TV_story)Torchwood: Miracle Day (the fourth series of the British science fiction television programme Torchwood, a spin-off from the long-running show Doctor Who.)- https://en.wikipedia.org/wiki/Torchwood:_Miracle_DayDay One (Torchwood) (the second episode of the first series of the British science fiction television series Torchwood. The episode centres on Gwen Cooper (Eve Myles) working her first case with the alien hunters Torchwood in Cardiff, when she lets loose a purple alien gas that survives on the energy of orgasms. Over the course of the episode, the team hunt for Carys before the gas kills her.)- https://en.wikipedia.org/wiki/Day_One_(Torchwood)Everything Changes (Torchwood) (the first episode of the British science fiction television programme Torchwood, which was first broadcast on 22 October 2006. The story is told from the perspective of Gwen Cooper (Eve Myles), who comes across the Torchwood team through her job as a police officer with the South Wales Police, who are investigating a series of strange deaths in Cardiff.)- https://en.wikipedia.org/wiki/Everything_Changes_(Torchwood)Resurrection gauntlet (The resurrection gauntlet — also known as the resurrection glove or just the glove, and, jokingly, the risen mitten — was a metal gauntlet that had the ability to revive the dead for a limited time, though with unfortunate and usually deadly consequences.)- https://tardis.fandom.com/wiki/Resurrection_gauntletTorchwood: Children of Earth (Children of Earth is the banner title of the third series of the British television science fiction programme Torchwood, which broadcast for five episodes on BBC One from 6 to 10 July 2009.)- https://en.wikipedia.org/wiki/Torchwood:_Children_of_EarthRyzen (a brand of x86-64 microprocessors designed and marketed by Advanced Micro Devices (AMD) for desktop, mobile, server, and embedded platforms based on the Zen microarchitecture. It consists of central processing units (CPUs) marketed for mainstream, enthusiast, server, and workstation segments and accelerated processing units (APUs) marketed for mainstream and entry-level segments and embedded systems applications.)- https://en.wikipedia.org/wiki/RyzenWhy is there a chip shortage?- https://www.bbc.com/news/business-58230388Nvidia sold $155 million in crypto mining chips last quarter, but PC gaming remains its biggest market- https://www.cnbc.com/2021/05/26/nvidia-pc-gaming-still-more-important-than-crypto-for-revenue.htmlThe Life of a Miner - Crypto Mining Farm at Apartment | August 2021 Update- https://www.youtube.com/watch?v=VB7NV7SR3bAChubbyemu - A Bitcoin Miner Heatstroked In His Sleep. This Is What Happened To His Organs.- https://www.youtube.com/watch?v=fr8bp8a2QS4PCPartPicker - Asus Radeon RX 580 8 GB DUAL Video Card- https://au.pcpartpicker.com/product/jkFXsY/asus-radeon-rx-580-8gb-dual-video-card-dual-rx580-o8g?history_days=730China's top regulators ban crypto trading and mining, sending bitcoin, rivals tumbling- https://www.abc.net.au/news/2021-09-25/chinas-top-regulators-ban-crypto-trading-/100491122Chrome OS (a Gentoo Linux-based operating system designed by Google. It is derived from the free software Chromium OS and uses the Google Chrome web browser as its principal user interface. Unlike Chromium OS, Chrome OS is proprietary software.)- https://en.wikipedia.org/wiki/Chrome_OSSolarCity (a publicly traded company headquartered in Fremont, California that sold and installed solar energy generation systems as well as other related products and services to residential, commercial and industrial customers.)- https://en.wikipedia.org/wiki/SolarCityElon Musk's Battery Farm Has Been a Total Triumph. Here Comes the Sequel.- https://www.popularmechanics.com/science/green-tech/a34598095/elon-musk-battery-farm-sequel-australia-tesla-powerpack/Hornsdale Power Reserve (a 150MW/194MWh grid-connected energy storage system owned by Neoen co-located with the Hornsdale Wind Farm in the Mid North region of South Australia, also owned by Neoen. During 2017 Tesla, Inc. won the contract and built the Hornsdale Power Reserve, for a capital cost of A$90 million, leading to the colloquial Tesla big battery name.)- https://en.wikipedia.org/wiki/Hornsdale_Power_ReserveHornsdale Power Reserve (Elon Musk placed a wager that the battery would be completed within "100 days from contract signature", otherwise the battery would be free. Tesla had already begun construction, and some units were already operational by 29 September 2017, the time the grid contract was signed. The battery construction was completed and testing began on 25 November 2017. It was connected to the grid on 1 December 2017. The 63 days between grid contract and completion easily beat Musk's wager of "100 days from contract signature", which started when a grid connection agreement was signed with ElectraNet on 29 September 2017, 203 days after Musk's offer on 10 March (in Australia).- https://en.wikipedia.org/wiki/Hornsdale_Power_Reserve#ConstructionNorwich Games Festival - Ashens - Gallery of Shame - 1 June 2019- https://www.youtube.com/watch?v=wFF9O73iwkoS.S. Antarctica (a battleship owned by the penguins of Antarctica.)- https://simpsonswiki.com/wiki/S.S._AntarcticaSS Penguin (a New Zealand inter-island ferry steamer that sank off Cape Terawhiti after striking a rock near the entrance to Wellington Harbour in poor weather on 12 February 1909.)- https://en.wikipedia.org/wiki/SS_PenguinElden Ring (an upcoming action role-playing game developed by FromSoftware and published by Bandai Namco Entertainment. The game is a collaborative effort between game director Hidetaka Miyazaki and fantasy novelist George R. R. Martin.)- https://en.wikipedia.org/wiki/Elden_RingBandai Namco Selects “My Dark Souls Story” Contest Winners- https://www.gameinformer.com/b/news/archive/2016/03/11/bandai-namco-selects-my-dark-souls-story-contest-winners.aspxNerdy, Inc. - My Dark Souls Story: Biography of the Chosen Undead - The Dark Souls Story- https://www.youtube.com/watch?v=mbiLl-m0Ry4NASA's Mars Rover Curiosity Had Planetary Protection Slip-Up- https://www.space.com/13783-nasa-msl-curiosity-mars-rover-planetary-protection.htmlAmazon Women in the Mood (the first episode in season three of Futurama.)- https://en.wikipedia.org/wiki/Amazon_Women_in_the_MoodApocalypse Now (a 1979 American epic psychological war film directed and produced by Francis Ford Coppola. It stars Marlon Brando, Robert Duvall, Martin Sheen, Frederic Forrest, Albert Hall, Sam Bottoms, Laurence Fishburne, Harrison Ford, and Dennis Hopper.)- https://en.wikipedia.org/wiki/Apocalypse_NowCast Party: A Dungeons & Dragons Podcast (TNC podcast)- https://www.patreon.com/CastPartyShout Outs 20th September 2021 – Mick McGinty, Legendary Video Game Artist, passes away - https://www.nintendolife.com/news/2021/09/legendary_street_fighter_ii_artist_mick_mcginty_has_passed_away Mick McGinty, an artist that produced cover art for video games like Street Fighter II and Streets of Rage 2, has died. While many gamers might not know McGinty by name, those that grew up in the '90s will immediately recognize his art. The artist contributed some of the most iconic images in all of gaming, telling stories that immediately captivated players. McGinty was an immensely talented artist, as is evidenced by the impressive collection of work on his personal site, but for gamers of the '90s, his output will be almost synonymous with video game covers. He is perhaps most famous with Nintendo fans for creating the western cover artwork for the SNES version of Street Fighter II. While many people took issue with the 'westernisation' of the artwork at the time, it was very common practice for companies like Nintendo to commission entirely new artwork which was better suited to a particular region. McGinty's cover – which features Chun-Li fighting Blanka over the prone body of Ryu – has gone down as one of the most recognisable video game covers of all time. McGinty's association with Street Fighter would continue with Street Fighter II: Champion Edition on the Mega Drive / Genesis, Street Fighter II Turbo on the SNES and Super Street Fighter II.21st September 2021 – Endangered South African penguins killed by swarm of bees near Cape Town - https://www.bbc.com/news/world-africa-58622482Sixty-three endangered African penguins have been killed by a swarm of bees in a rare occurrence near Cape Town, bird conservationists in South Africa say. The protected birds, from a colony in Simonstown, were found on the shore with multiple bee-stings. They had no other physical injuries. National parks officials told the BBC this was the first known attack at the world-famous Boulders Beach, which attracts up to 60,000 visitors a year. "Usually the penguins and bees co-exist," said Dr Alison Kock, a marine biologist with South Africa's national parks agency (SANParks). "The bees don't sting unless provoked - we are working on the assumption that a nest or hive in the area was disturbed and caused a mass of bees to flee the nest, swarm and became aggressive," she added. "Unfortunately the bees encountered a group of penguins on their flight path." Post-mortems found that the birds had been stung around the eyes and on their flippers. That is because "those are the parts that are not covered by feathers," Dr Katta Ludynia, from the Southern African Foundation for the Conservation of Coastal Birds (Sanccob), told the BBC. Penguins have pink sweat glands around their eyes and "that area is particularly thin - similar to human fingers," explained Shanet Rutgers, senior penguin keeper at Cape Town's Two Oceans Aquarium. One of the penguins had been stung 27 times. African penguins are distinctive for their small size, and live on the coast and islands of South Africa and Namibia - though some have been spotted as far north as Gabon.Their populations are rapidly declining, the International Union for Conservation of Nature says. The national body said in a statement on Sunday that it was still conducting toxicity and disease checks on the birds, and would continue to monitor the situation.22nd September 2021 – 10th Anniversary of Dark Souls - https://www.glitched.online/landmark-rpg-dark-souls-celebrates-its-10th-anniversary-today/ Ten years ago to the day, Japanese video game developer From Software released the critically acclaimed dark fantasy action RPG, Dark Souls, which would go on to change the gaming landscape forever. Refining the formula already established in Demon's Souls while introducing a bevy of new mechanics that have been adopted and replicated by other titles, Dark Souls would spearhead an entirely new sub-genre of gaming. Today, Dark Souls officially celebrates its 10th anniversary. Dark Souls‘ history is relatively straightforward in comparison to many other success stories in gaming. From Software first dabbled in the dark fantasy setting with Demon's Souls, showcasing their ability to tell epic but narratively mysterious tales featuring fantastical beasts, ambiguous NPCs and deceptively challenging gameplay. The last part has remained the foundation of all From Software games since, increasing their difficulty in newer titles like Bloodborne and Sekiro while still retaining their creative power for captivating and immersive stories, worlds and characters. Dark Souls was well-received by fans, often cited as their favourite game of all time. It's success went on to spawn two sequels, Dark Souls II and Dark Souls III; two creative spiritual successors in Bloodborne and the upcoming Elden Ring; and a Tenchu-styled action title Sekiro: Shadows Die Twice that heavily borrowed elements from From Software's trademark style. Demon's Souls may have been the first, but it was really Dark Souls that put the Japanese studio on the map, leaving behind a legacy that has been the source of inspiration for a number of games like the Nioh series, The Surge, Lords of the Fallen, Mortal Shell, and numerous others. Dark Souls is not only remembered for its staple difficulty, but inspired world design, creative boss encounters, a plot that simply begged to be dissected and explored further, and a blueprint for a new style of game that bounced off the success of this defining RPG.24th September 2021 – 20th anniversary of Ico - https://www.nme.com/en_au/features/gaming-features/ico-minimalist-masterclass-in-cinematic-and-emotional-storytelling-3051674 Released between those two films in 2001 and 2002, Ico (pronounced ‘ee-ko' – but don't worry if you get it wrong, I did so too for a very long time) is a single-player action-adventure game developed by Sony's Japan Studio. This game kicked off the career of Fumito Ueda. It was the first in a series of games that featured similar themes, including beloved titles like Shadow of the Colossus and The Last Guardian. Ico is special in the way it handles abandonment and isolation. Devoid almost entirely of all dialogue, Ico essentially works like a silent film. There's a clear sense of loneliness that's present throughout the entire game. But there's also a feeling of hope. Ico's soundtrack is almost suffocating at times, though it also presents a number of beautiful pieces. “Heal,” for example, is one of the best save themes in any game. Ico's soundtrack is almost suffocating at times, though it also presents a number of beautiful pieces. “Heal,” for example, is one of the best save themes in any game. One of the game's fans is also Hidetaka Miyazaki of FROM Software. Miyazaki, the creator of Demon's Souls, and in turn the Souls series, is one of the biggest game industry figures of the last decade. Much in the way the game would inspire Straley and Druckmann, Miyazaki cites Ico as a game that showed him the different possibilities that video games as a medium had to offer.Remembrances21st September 1954 – Mikimoto Kōkichi - https://en.wikipedia.org/wiki/Mikimoto_K%C5%8DkichiA Japanese entrepreneur who is credited with creating the first cultured pearl and subsequently starting the cultured pearl industry with the establishment of his luxury pearl company Mikimoto. He was inducted into the house of peers by imperial decree and posthumously awarded the Grand Cordon of the Order of the Sacred Treasure. On April 18, 1985, the Japan Patent Office selected him as one of Ten Japanese Great Inventors. The company was ranked as one of the world's most luxurious brands by Women's Wear Daily Magazine and Mikimoto was considered one of the best Japanese financial leaders of the 20th century by Nihon Keizai Shimbun. He is also known as the founder of Mikimoto Pharmaceuticals, a company specialising in beauty products containing pearl calcium. Mikimoto Pearl Island is named after him. In addition, the "Phoenix Mikimoto Crown" used by Miss Universe winners as well as the pageant crown used by Miss International is credited to his patented work. Mikimoto began his search of an alternative method to produce pearls as the chairman of the Shima Marine Products Improvement Association. At this point the demand for pearls had severely outweighed the supply, prompting the consideration of an effort to protect the oysters. In 1888, Mikimoto obtained a loan to start his first pearl oyster farm at the Shinmei inlet on Ago Bay in Mie prefecture with his wife and partner Ume. On 11 July 1893, after many failures and near bankruptcy, he was able to create the hemispherical cultured pearls. The pearls were made by seeding the oyster with a small amount of mother of pearl. In 1927, Mikimoto met with inventor, Thomas Edison, who was in awe of Mikimoto's cultured pearls as it was "supposed to be biologically impossible". He died at the age of 96 in Japan.Famous Birthdays21st September 1902 – Allen Lane - https://en.wikipedia.org/wiki/Allen_LaneA British publisher who together with his brothers Richard and John Lane founded Penguin Books in 1935, bringing high-quality paperback fiction and non-fiction to the mass market. In 1967 he started a hardback imprint under his own name, Allen Lane. He rose quickly at Bodley Head, becoming managing editor in 1925 following the death of his uncle. After conflict with the board of directors who were wary at first—for fear of being prosecuted—of publishing James Joyce's controversial book Ulysses, Lane, together with his brothers Richard and John, founded Penguin Books in 1935 as part of the Bodley Head. Penguin Books became a separate company the following year. The legend goes that on a train journey back from visiting Agatha Christie in 1934, Lane found himself on an Exeter station platform with nothing available worth reading. He conceived of paperback editions of literature of proven quality which would be cheap enough to be sold from a vending machine; the first was set up outside Henderson's in Charing Cross Road and dubbed the "Penguincubator". Lane was also well aware of the Hamburg publisher Albatross Books and adopted many of its innovations. Most booksellers and authors were against the idea of paperbacks. They believed that paperbacks would result in individuals spending less money on books. Lane was a person that was very stubborn when it came to his company. He operated mainly on intuition and imagination. "He thrived in an atmosphere of crisis and came most fully alive under the challenge of great dilemmas." He was a creative genius that once he had an idea he would not stop until it came to fruition. Once he decided on creating paperbacks he set about in deciding what the books should look like and finding a name. He had decided that the books would be reprints so he also needed to approach other publishers to see if they and their authors would be willing to sublease the rights of the books. He was quoted as saying, "I have never been able to understand why cheap books should not also be well designed, for good design is no more expensive than bad." He was born in Bristol.Events of Interest21th September 2003 – The Galileo spacecraft is terminated by sending it into Jupiter's atmosphere. - https://en.wikipedia.org/wiki/Galileo_project#End_of_mission_and_deorbit When the exploration of Mars was being considered in the early 1960s, Carl Sagan and Sidney Coleman produced a paper concerning contamination of the red planet. In order that scientists could determine whether or not native life forms existed before the planet became contaminated by micro-organisms from Earth, they proposed that space missions should aim at a 99.9 percent chance that contamination should not occur. This figure was adopted by the Committee on Space Research (COSPAR) of the International Council of Scientific Unions in 1964, and was subsequently applied to all planetary probes. The danger was highlighted in 1969 when the Apollo 12 astronauts returned components of the Surveyor 3 spacecraft that had landed on the Moon three years before, and it was found that microbes were still viable even after three years in that harsh climate. An alternative was the Prime Directive, a philosophy of non-interference with alien life forms enunciated by the original Star Trek television series that prioritized the interests of the life forms over those of scientists. Given the (admittedly slim) prospect of life on Europa, scientists Richard Greenberg and Randall Tufts proposed that a new standard be set of no greater chance of contamination that that which might occur naturally by meteorites. Galileo had not been sterilized prior to launch and could have carried bacteria from Earth. Therefore, a plan was formulated to send the probe directly into Jupiter, in an intentional crash to eliminate the possibility of an impact with Jupiter's moons, particularly Europa, and prevent a forward contamination. On April 14, 2003, Galileo reached its greatest orbital distance from Jupiter for the entire mission since orbital insertion, 26 million km (16 million mi), before plunging back towards the gas giant for its final impact. At the completion of J35, its final orbit around the Jovian system, Galileo impacted Jupiter in darkness just south of the equator on September 21, 2003, at 18:57 UTC. Its impact speed was approximately 48.26 km/s (29.99 mi/s).21st September 1994 – Dinosaur Island premiered in Japan - https://www.imdb.com/title/tt0109627/ On this day in 1994 in Japan, Dinosaur Island enjoyed its premiere on home video. The Fantasy/Comedy feature starred Griffin Drew and Michelle Bauer, and here's the premise: "An army captain is flying three misfit deserters home for a court martial when the plane has engine trouble and they must land on an uncharted island. There they find a primitive society of cave women who routinely sacrifice virgins to appease The Great One, the top dog dinosaur on the the island. Mistaken for gods, the men must destroy The Great One or face death, but meanwhile they fall in love."The cavewomen's ranch was constructed on a remote portion of David Carradine's ranch.Shot in 12 days.Almost every day was extremely hot during the shooting of this film except one.A sequence with a stop-motion animation dinosaur attacking people on the beach was changed to a hand puppet dinosaur in post-production.The filmmakers paid an additional four thousand dollars for the poster art used to advertise this film.Antonia Dorian said she was nervous filming her first love scene in this film, especially since she was going to be topless. She'd danced topless in Vegas shows and in videos, but that wasn't the same as being on a small set surrounded by male actors and crew just a few feet away, all staring at her. Jim Wynorski gave her wine to calm her nerves. He also limited how many people would be on set. That and the wine helped her finally get through the scene.When the female warriors are chasing the dinosaur towards the ocean, you can see Malibu homes in the background hills.Wynorski said that Roger Corman asked he and Fred Olen Ray to make the film after Jurassic Park came out. "It wasn't so much a Jurassic Park rip off as a cavewoman movie", Wynorski said.Wynorski and Ray said they rewrote the script entirely. They knew who they were going to cast, employing actors they had worked with before, and tailored the script accordingly. They based the characters of the soldiers on characters in Stripes. Another influence was The War that Time Forgot, part of the Star Spangled War Stories comic book series.The movie was shot at Vasquez Rocks and David Carradine's ranch at Sun Valley over ten days. Wynorski says he and Ray made it "on a wing and a prayer".Wynorski later said, "I'd never co-directed a movie before, but it was smooth sailing all the way. When one of us got tired, the other would take over. I'd usually go back to the comfort of the air-conditioned motor home and hang out with the girls. You really can't beat that."Wynorski says he was at a party when he met Joe Pesci who told him he loved the film, saying "everytime I watch it I feel like I want to go there."IntroArtist – Goblins from MarsSong Title – Super Mario - Overworld Theme (GFM Trap Remix)Song Link - https://www.youtube.com/watch?v=-GNMe6kF0j0&index=4&list=PLHmTsVREU3Ar1AJWkimkl6Pux3R5PB-QJFollow us onFacebook- Page - https://www.facebook.com/NerdsAmalgamated/- Group - https://www.facebook.com/groups/440485136816406/Twitter - https://twitter.com/NAmalgamatedSpotify - https://open.spotify.com/show/6Nux69rftdBeeEXwD8GXrSiTunes - https://itunes.apple.com/au/podcast/top-shelf-nerds/id1347661094Instagram - https://www.instagram.com/nerds_amalgamated/Email - Nerds.Amalgamated@gmail.comSupport via Podhero- https://podhero.com/podcast/449127/nerds-amalgamated See acast.com/privacy for privacy and opt-out information.
A group of aliens calling themeselves Axons land on Earth and offer technology in exchange for fuel. but The Doctor isn't fooled and must uncover the Axons' true nature all while once again facing his foe the Master this is the claws of axos welcome to regenerated why not take a look at our social media and give us a review on Apple Podcasts merchandise -https://teespring.com/en-GB/stores/regenerated facebook - www.facebook.com/regenerateddoctorwhopodcast/ twitter - twitter.com/Regenerated1963 website - regenerated1963.wixsite.com/regenerated patreon - patreon.com/regenerated buy me a coffee - https://www.buymeacoffee.com/regenerated
In this episode of Music Therapy, I talk with Chicago musician Adele Nicholas of Axons. Adele talks about her work as a lawyer, her active community involvement, her creative process, feeling anxious about releasing albums, her soon-to-be-released album about two creative bank robbers (based on true events!) and more! https://axons.bandcamp.com/ https://jessicarisker.com/
In this recording of a live-streamed training class from The Loving Awareness Meditation Course, I explain and demonstrate how modifying our optical focus can help us intervene really effectively in anxiety and stress.Check out my Classes and Courses online and in-person. The Meditation Course:https://www.meditationcourse.live/ The Loving Awareness Meditation Course:https://lovingawareness.fm/ Bromley Mindfulness:https://bromleymindfulness.org.uk The eyes are actually an extension of the brain. The cells in the retina are neurons that have been modified through evolution to process light.The connections between the eyes and the brain are not typical nerve fibres. They are axons. Axons are the fibres in the brain that pass messages from one neuron to another.The eyes are also involved in emotional memory processing during a phase of sleep known as rapid eye movement sleep.The early accounts of meditation, such as that found in the Bhagavad-Gita, an ancient Hindu spiritual text, instructs the meditation student to focus their eyes downwards past the tip of the nose.“With torso and head held straight, with posture steady and unmoving, gazing at the tip of his nose, not letting his eyes look elsewhere, the Yogi should sit there calm, fearless, firm in his vow to be chaste, his whole mind controlled, directed, focused."— The Bhagavad Gita by Stephen MitchellDownward gazing of the eyes can be seen in many ancient statues of meditators especially those in the Buddhist Tradition.This practice is taught in the Buddhist tradition as 'softening of the gaze' and 'adopting a downward gaze'.This can be experienced when practising the mirror meditation which I teach in this class.ReferencesRecent studies by Andrew D. Huberman of Stanford University and his research team have identified that softening the gaze and adopting a downward gaze, along with moving the eyes to the periphery of the vision significantly reduces anxiety and stress.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.21.349142v1?rss=1 Authors: Chong, Y., Cooper, E. Abstract: It is well accepted that refinement of converging presynaptic inputs depends on postsynaptic activity; however, it remains unclear how this developmental event is initiated. To address this, we developed a mosaic model where synaptically-active and synaptically-inactive sympathetic neurons develop side-by-side in the same ganglion. Surprisingly, we show that converging presynaptic inputs refine on neurons even without synaptic transmission as long as the synaptically-silent neurons share targets with synaptically-active neurons. In addition, our single-cell RNA sequencing experiments show that sympathetic ganglia contain at least 7 neuronal subtypes that decode the impact of synaptic activity differently, including their ability to maintain an adrenergic phenotype. Our results provide a new view on the roles that synaptic transmission and retrograde target activity have on developing circuits. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.12.336446v1?rss=1 Authors: Lucas, T. Abstract: Glia are known to play important roles in the brain, the gut, and around the sciatic nerve. While the gut has its own specialized nervous system, other viscera are innervated solely by autonomic nerves. The functions of glia that accompany autonomic innervation are not well known, even though they are one of the most abundant cell types in the peripheral nervous system. Here, we focused on non-myelinating Schwann Cells in the spleen, spleen glia. The spleen is a major immune organ innervated by the sympathetic nervous system, which modulates immune function. This interaction is known as neuroimmune communication. We establish that spleen glia can be visualized using both immunohistochemistry for S100B and GFAP and with a reporter mouse. Spleen glia ensheath sympathetic axons and are localized to the lymphocyte-rich white pulp areas of the spleen. We sequenced the spleen glia transcriptome and identified genes that are likely involved in axonal ensheathment and communication with both nerves and immune cells. Spleen glia express receptors for neurotransmitters made by sympathetic axons (adrenergic, purinergic, and Neuropeptide Y), and also cytokines, chemokines, and their receptors that may communicate with immune cells in the spleen. We also established similarities and differences between spleen glia and other glial types. While all glia share many genes in common, spleen glia differentially express immune genes, including genes involved in cytokine-cytokine receptor interactions, phagocytosis, and the complement cascade. Thus, spleen glia are a unique glial type, physically and transcriptionally poised to participate in neuroimmune communication in the spleen. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.10.334656v1?rss=1 Authors: Micheva, K. D., Kiraly, M., Perez, M. M., Madison, D. V. Abstract: Parvalbumin-containing (PV+) basket cells in mammalian neocortex are fast-spiking interneurons that regulate the activity of local neuronal circuits in multiple ways. Even though PV+ basket cells are locally projecting interneurons, their axons are myelinated. Can this myelination contribute in any significant way to the speed of action potential propagation along such short axons? We used dual whole cell recordings of synaptically connected PV+ interneurons and their postsynaptic target in acutely-prepared neocortical slices from adult mice to measure the amplitude and latency of single presynaptic action potential-evoked inhibitory postsynaptic currents (IPSCs). These same neurons were then imaged with immunofluorescent array tomography, the synaptic contacts between them identified and a precise map of the connections was generated, with the exact axonal length and extent of myelin coverage. Our results support that myelination of PV+ basket cells significantly increases conduction velocity, and does so to a degree that can be physiologically relevant. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.29.318881v1?rss=1 Authors: Wildenberg, G. A., Sorokina, A. M., Koranda, J., Monical, A., Heer, C., Sheffield, M., Zhuang, X., McGehee, D. S., Kasthuri, N. Abstract: Detailing the ways drugs of abuse physically change dopaminergic circuits would provide new mechanisms for explaining addictive behaviors, future targets for therapeutic intervention, and insights into the nature of synaptic plasticity. We combine recent advances in genetic labeling with large volume serial electron microscopy to detail how normal dopaminergic (DA) axons interact with putative targets and how those interactions change in mice briefly exposed to cocaine. We find that while most DA boutons are devoid of obvious signs of synapses (i.e. synaptic vesicles or synaptic densities) many DA boutons physically interdigitate with both dendrites and excitatory and inhibitory axons. After a brief exposure to cocaine, we find evidence of large-scale structural remodeling: extensive axonal branching and frequent occurrences of axonal blind-ended bulbs, filled with mitochondria, reminiscent of axonal retraction in the developing and damaged brain. The number of physical interdigitations and vesicle filled boutons between DA axons and targets scales linearly with the length of axon whether in controls or cocaine exposed animals and the size or the type of interaction (i.e. axo-axonic or axo-dendritic) does not change. Finally, we find significant cell-type and sub-cellular specific increases in mitochondrial length in response to cocaine. Specifically, mitochondria in dopamine axons and local Nucleus Accumbens (NAc) dendrites are ~3.5 times and 2 times longer, respectively, in cocaine treated mice than controls. These results show for the first time the effects of cocaine on remodeling of dopamine circuitry and reveal new details on how dopamine neurons physical associate with downstream targets. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.15.297895v1?rss=1 Authors: Gonzalez Sabater, V., Rigby, M., Burrone, J. Abstract: The initiation and propagation of the action potential (AP) along an axon allows neurons to convey information rapidly and across distant sites. Although AP properties have typically been characterised at the soma and proximal axon, the propagation of APs towards distal axonal domains of mammalian neurons remains limited. We used Genetically Encoded Voltage Indicators (GEVIs) to image APs simultaneously at different locations along the long axons of dissociated hippocampal neurons with sub-millisecond temporal resolution. We found that APs became sharper and showed remarkable fidelity as they traveled towards distal axons, even during a high frequency train. Blocking voltage-gated potassium channels (Kv) with 4-AP resulted in an increase in AP width in all compartments, which was stronger at distal locations and exacerbated during AP trains. We conclude that the higher levels of Kv channel activity in distal axons serves to sustain AP fidelity, conveying a reliable digital signal to presynaptic boutons. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.09.288100v1?rss=1 Authors: Siddiqui, A. M., Islam, R., Cuellar, C. A., Silvernail, J. L., Knudsen, B., Curley, D. E., Strickland, T., Manske, E., T Suwan, P., Latypov, T., Akhmetov, N., Zhang, S., Summer, P., Nesbitt, J. J., Chen, B. K., Grahn, P. J., Madigan, N. N., Yaszemski, M. J., Windebank, A., Lavrov, I. Abstract: We report the effect of newly regenerated neural fibers via bioengineered scaffold on reorganization of spinal circuitry and restoration of motor functions with electrical epidural stimulation (EES) after spinal transection (ST). Restoration across multiple modalities was evaluated for 7 weeks after ST with implanted scaffold seeded with Schwann cells, producing neurotrophic factors and with rapamycin microspheres. Gradual improvement in EES-facilitated stepping was observed in animals with scaffolds, although, no significant difference in stepping ability was found between groups without EES. Similar number of regenerated axons through the scaffolds was found in rats with and without EES-enabled training. Re-transection through the scaffold at week 6, reduced EES-enabled motor function, remaining higher compared to rats without scaffolds. The combination of scaffolds and EES-enabled training demonstrated synaptic changes below the injury. These findings indicate that sub-functional connectivity with regenerated across injury fibers can reorganize of sub-lesional circuitry, facilitating motor functions recovery with EES. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.28.271593v1?rss=1 Authors: Almeida, R. G., Williamson, J. M., Madden, M. E., Early, J. J., Voas, M. G., Talbot, W. S., Bianco, I. H., Lyons, D. A. Abstract: To study activity-regulated myelination, we imaged synaptic vesicle fusion along single axons in living zebrafish, and found, surprisingly, that axonal synaptic vesicle fusion is driven by myelination. This myelin-induced axonal vesicle fusion was enriched along the unmyelinated domains into which newly-formed sheaths grew, and was promoted by neuronal activity, which in turn accelerated sheath growth. Our results indicate that neuronal activity consolidates sheath growth along axons already selected for myelination. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.22.262972v1?rss=1 Authors: Kimura, I., Matsumoto, H., Uchida, N., Watabe-Uchida, M. Abstract: Different regions of the striatum regulate different types of behavior. However, how dopamine signals differ across striatal regions and how dopamine regulates different behaviors remain unclear. Here, we compared dopamine axon activity in the ventral, dorsomedial, and dorsolateral striatum, while mice performed in a perceptual and value-based decision task. Surprisingly, dopamine axon activity was similar across all three areas. At a glance, the activity multiplexed different variables such as stimulus-associated values, confidence and reward feedback at different phases of the task. Our modeling demonstrates, however, that these modulations can be inclusively explained by moment-by-moment changes in the expected reward, i.e. the temporal difference error. A major difference between these areas was the overall activity level of reward responses: reward responses in dorsolateral striatum (DLS) were positively shifted, lacking inhibitory responses to negative prediction error. Tenets of habit and skill can be explained by this positively biased dopamine signal in DLS. Copy rights belong to original authors. Visit the link for more info
Apollo Moon Landing, Axons & Dendrites, Q&A
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.31.230250v1?rss=1 Authors: Matsumoto, N., Hori, I., Murase, T., Tsuji, T., Miyake, S., Inatani, M., Konishi, Y. Abstract: In the central nervous system, many neurons develop axonal arbors that are crucial for information processing. Previous studies have demonstrated that premature axons contain motile and stationary mitochondria, and their balance is important for axonal arborization. However, the mechanisms by which neurons determine the positions of stationary mitochondria as well as their turnover remain to be elucidated. In this study, we investigated the regulation of spatiotemporal group dynamics of stationary mitochondria. We observed that the distribution of stationary mitochondrial spots along the unmyelinated and nonsynaptic axons is not random but rather relatively uniform both in vitro and in vivo. Intriguingly, whereas the positions of each mitochondrial spot changed over time, the overall distribution remained uniform. In addition, local inactivation of mitochondria inhibited the translocation of mitochondrial spots in adjacent axonal regions, suggesting that functional mitochondria enhance the motility of neighboring mitochondria. Furthermore, we showed that the ATP concentration was relatively high around mitochondria, and treating axons with phosphocreatine, which supplies ATP, reduced the immobile mitochondria induced by local mitochondrial inhibition. These observations indicate that intermitochondrial interactions, mediated by ATP signaling, control the uniform distribution of axonal mitochondria. The present study reveals a novel cellular system that collectively regulates stationary mitochondria in axons. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.21.214908v1?rss=1 Authors: Steward, O., Yee, K. M., Metcalfe, M., Luo, J., Willenberg, R., Acevedo, R., Martin-Thompson, J., Gandhi, S. Abstract: Rostro-caudal specificity of corticospinal tract (CST) projections from different areas of the cortex was assessed by retrograde labeling with fluorogold and retrograde transfection following retro-AAV/Cre injection into the spinal cord of tdT-reporter mice. Injections at C5 led to retrograde labeling of neurons throughout forelimb area of the sensorimotor cortex, the rostral forebrain area (RFA), and a region in the lateral cortex near the barrel field. Injections at L2 led to retrograde labeling of neurons in the posterior sensorimotor cortex (hindlimb area) but not the RFA or lateral cortex. With BDA injections into the main sensorimotor cortex (forelimb region), labeled axons terminated selectively at cervical levels. With BDA injections into caudal sensorimotor cortex (hindlimb region), labeled axons passed through cervical levels without sending collaterals into the gray matter and then elaborated terminal arbors at thoracic-sacral levels. With BDA injections into the RFA and lateral cortex near the barrel field, labeled axons terminated at high cervical levels. Axons from medial sensorimotor cortex terminated primarily in intermediate laminae; Axons from lateral sensorimotor cortex terminated primarily in deep layers of the dorsal horn. One of the descending pathways seen in rats (the ventral CST) was not observed in most mice. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.16.207316v1?rss=1 Authors: Moss, M. M., Zatka-Haas, P., Harris, K. D., Carandini, M., Lak, A. Abstract: Midbrain dopamine neurons play key roles in decision-making by regulating reward valuation and actions. These roles are thought to depend on dopamine neurons innervating striatum. In addition to actions and rewards, however, efficient decisions often involve consideration of uncertain sensory signals. The functions of striatal dopamine during sensory decisions remains unknown. We trained mice in a task that probed decisions based on sensory evidence and reward value, and recorded the activity of striatal dopamine axons. Dopamine axons in ventral striatum (VS) responded to bilateral stimuli and trial outcomes, encoding prediction errors that scaled with decision confidence and reward value. By contrast, dopamine axons in dorsal striatum (DS) responded to contralateral stimuli and contralateral actions. Thus, during sensory decisions, striatal dopamine signals are anatomically organized. VS dopamine resembles prediction errors suitable for reward maximization under sensory uncertainty whereas DS dopamine encodes specific combinations of stimuli and actions in a lateralized fashion. Copy rights belong to original authors. Visit the link for more info
The Doctor his UNIT family must save the world from the Master and the Axons. Will they survive the onslaught of spaghetti monsters and interpretive dance under a duvet.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.27.119453v1?rss=1 Authors: Lavoie-Cardinal, F., Bilodeau, A., Lemieux, M., Gardner, M.-A., Wiesner, T., Laramee, G., Gagne, C., De Koninck, P. Abstract: The nanoscale organization of the F-actin cytoskeleton in neurons comprises membrane-associated periodical rings, bundles, and longitudinal fibers. The F-actin rings have been observed predominantly in axons but only sporadically in dendrites, where fluorescence nanoscopy reveals various patterns of F-actin arranged in mixed patches. These complex dendritic F-actin patterns pose a challenge for investigating quantitatively their regulatory mechanisms. We developed here a weakly supervised deep learning segmentation approach of fluorescence nanoscopy images of F-actin in cultured hippocampal neurons. This approach enabled the quantitative assessment of F-actin remodeling, revealing the disappearance of the rings during neuronal activity in dendrites, but not in axons. The dendritic F-actin cytoskeleton of activated neurons remodeled into longitudinal fibers. We show that this activity-dependent remodeling involves Ca2+ and NMDA-dependent mechanisms. This highly dynamic restructuring of dendritic F-actin based submembrane lattice into longitudinal fibers may serve to support activity-dependent membrane remodeling, protein trafficking and neuronal plasticity. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.28.122242v1?rss=1 Authors: Pederick, D. T., Lui, J. H., Gingrich, E. C., Xu, C., Liu, Y., He, Z., Quake, S. R., Luo, L. Abstract: Spatial- and object-related signals are preferentially processed through the medial and lateral hippocampal networks (MHN and LHN), respectively1,2. MHN comprises interconnected medial entorhinal cortex, proximal CA1 (pCA1), and distal subiculum (dSub), whereas the LHN comprises interconnected lateral entorhinal cortex, distal CA1, and proximal subiculum3,4. Previously, we showed that Teneurin-3 (Ten3) has matching expression in all interconnected regions of the MHN and is required in both CA1 and subiculum for the precise pCA1->dSub axon targeting through homophilic attraction5. Can matching gene expression in interconnected nodes of the LHN also contribute to hippocampal network assembly? Here, we discovered that latrophilin-2 (Lphn2), an adhesion GPCR known to bind teneurins6-8, has matching expression in the LHN that is complementary to Ten3. Viral-genetic perturbations in vivo revealed that Ten3+ pCA1 axons are repelled by ectopic expression of Lphn2 in dSub, and ectopically invade proximal subiculum deleted for Lphn2. Simultaneous subiculum deletion of Lphn2 and Ten3 causes Ten3+ pCA1 axon mistargeting reflecting loss of both repulsion and attraction. Our findings demonstrate that Lphn2 acts as a repulsive ligand for Ten3+ axons, identify Ten3 as a receptor for both repulsive and attractive ligands in the same axon during target choice, and reveal how a "Ten3->Ten3, Lphn2->Lphn2" rule directs the precise assembly of functional hippocampal networks. Copy rights belong to original authors. Visit the link for more info
Em The Claws of Axos, terceiro arco da 8ª temporada da série clássica, o Doutor se vê diante da ameaça dos Axons, que chegam à Terra com a desculpa de que precisam de combustível, e em troca oferecem um verdadeiro presente de grego: a axionita, uma fonte inesgotável de recursos. O Doutor se alia ao Mestre e tenta utilizar o mineral para tentar fugir da Terra - mas será que vai dar certo?
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.20.093070v1?rss=1 Authors: Hayashi, S., Hoerder-Suabedissen, A., Kiyokage, E., Maclachlan, C., Toida, K., Knott, G. W., Molnar, Z. Abstract: Synapses are able to form in the absence of neuronal activity, but how is their subsequent maturation affected in the absence of regulated vesicular release? We explored this question using 3D electron microscopy and immuno electron microscopy analyses in the large, complex synapses formed between cortical sensory efferent axons and dendrites in the posterior thalamic nucleus. Using a Snap25 conditional knockout we found that during the first two postnatal weeks the axonal boutons emerge and increase in the size similar to the control animals. However, by P18, when an adult-like architecture should normally be established, axons were significantly smaller with 3D reconstructions showing that each Snap25-cko bouton only forms a single synapse with the connecting dendritic shaft. No excrescences from the dendrites were formed, and none of the normally large glomerular axon endings were seen. These results show that activity mediated through regulated vesicular release from the presynaptic terminal is not necessary for the formation of synapses, but it is required for the maturation of the specialised synaptic structures between layer 5 corticothalamic projections in Po. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.18.102582v1?rss=1 Authors: Lanfranchi, M., Meyer-Dilhet, G., Dos Reis, R., Garcia, A., Blondet, C., Javin, L., Amar, A., Courchet, J. Abstract: The precise regulation of the cellular mechanisms underlying axonal morphogenesis is essential to the formation of functional neuronal networks. We previously identified the autism-candidate kinase NUAK1 as a central regulator of axon branching in mouse cortical neurons through the control of mitochondria trafficking. How does local mitochondrial position or function regulate axon branching during development? Here, we characterized the metabolic regulation in the developing axon and report a marked metabolic decorrelation between axon elongation and collateral branching. We next solved the cascade of event leading to presynaptic clustering and mitochondria recruitment during spontaneous branch formation. Interestingly and contrary to peripheral neurons, mitochondria are recruited after but not prior to branch formation in cortical neurons. Using flux metabolomics and fluorescent biosensors, we observed that NUAK1 deficiency significantly impairs mitochondrial metabolism and axonal ATP concentration. Upregulation of mitochondrial function is sufficient to rescue axonal branching in NUAK1 null neurons in vitro and in vivo. Altogether, our results indicate that NUAK1 exerts a dual function during axon branching through its ability to control mitochondria distribution and activity, and suggest that a mitochondrial-dependent remodeling of local metabolic homeostasis plays a critical role during axon morphogenesis. Copy rights belong to original authors. Visit the link for more info
It’s all about maintaining homeostasis in Episode 36! Neurons are specialized cells for conducting electrical signals and releasing chemical neurotransmitters (2:02). Axons conduct an action potential through the movement of sodium and potassium ions (3:00). The message changes from electrical to chemical at a synapse (4:30). Neurotransmitters act as ligands, binding to the postsynaptic membrane (5:20).The Question of the Day asks (6:44) “Which autoimmune disorder degrades the myelin sheath of an axon? ”Thank you for listening to The APsolute RecAP: Biology Edition!(AP is a registered trademark of the College Board and is not affiliated with The APsolute RecAP. Copyright 2020 - The APsolute RecAP, LLC. All rights reserved.)Website:www.theapsoluterecap.comEMAIL:TheAPsoluteRecAP@gmail.comFollow Us:INSTAGRAMTWITTER
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.05.078642v1?rss=1 Authors: Mozafari, S., Starost, L., Manot-Saillet, B., Garcia-Diaz, B., Xu, Y. K. T., Roussel, D., Levy, M. J. F., Ottoboni, L., Kim, K.-P., Scholer, H. R., Kennedy, T. E., Antel, J. P., Martino, G., Angulo, M. C., Kuhlmann, T., Baron-Van Evercooren, A. Abstract: The remyelination failure in multiple sclerosis (MS) is associated with a migration/differentiation block of oligodendroglia. The reason for this block is highly debated. It could result from disease-related extrinsic regulators of the oligodendroglial biology or reflect MS oligodendrocyte intrinsic properties. To avoid confounding immune-mediated extrinsic effect, we used an immune-deficient, dysmyelinating mouse model, to compare side-by-side induced pluripotent stem-cell-derived O4+ oligodendroglia from MS and healthy donors following their engraftment in the developing CNS. We show that the MS-progeny survives, proliferates and differentiates into oligodendrocytes to the same extent as controls. Quantitative multi-parametric imaging indicates that MS and control oligodendrocytes generate equal amounts of myelin, with bona-fide nodes of Ranvier and promote equal restoration of their host slow conduction. Moreover, the MS-derived progeny expressed oligodendrocyte- and astrocyte-specific connexins and established functional connections with donor and host glial cells. Thus, MS pluripotent stem cell-derived progeny fully integrates into functional axo-glial and glial-glial components, reinforcing the view that the MS oligodendrocyte differentiation block is not due to intrinsic oligodendroglial deficits. These biological findings as well as the fully integrated human-murine chimeric model should facilitate the development of pharmacological or cell-based therapies to promote CNS remyelination. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.29.067629v1?rss=1 Authors: Jackson, J. S., Johnson, J. D., Meftah, S., Murray, T. K., Ahmed, Z., Fasiolo, M., Hutton, M. L., Isaac, J. T., O'Neill, M. J., Ashby, M. C. Abstract: Neurodegeneration driven by aberrant tau is a key feature of many dementias. Pathological stages of tauopathy are characterised by reduced synapse density and altered synapse function. Furthermore, changes in synaptic plasticity have been documented in the early stages of tauopathy suggesting that they may be a driver of later pathology. However, it remains unclear if synapse plasticity is specifically linked to the degeneration of neurons. This is partly because, in progressive dementias, pathology can vary widely from cell-to-cell along the prolonged disease time-course. To overcome this variability, we have taken a longitudinal experimental approach to track individual neurons through the progression of neurodegenerative tauopathy. Using repeated in vivo 2-photon imaging in rTg4510 transgenic mice, we have measured structural plasticity of presynaptic terminaux boutons and postsynaptic spines on individual axons and dendrites over long periods of time. By following individual neurons, we have measured synapse density across the neuronal population and tracked changes in synapse turnover in each neuron. We found that tauopathy drives a reduction in density of both presynaptic and postsynaptic structures and that this is partially driven by degeneration of individual axons and dendrites that are spread widely across the disease time-course. Both synaptic loss and neuronal degeneration was ameliorated by reduction in expression of the aberrant P301L transgene, but only if that reduction was initiated early in disease progression. Notably, neurite degeneration was preceded by alterations in synapse turnover that contrasted in axons and dendrites. In dendrites destined to die, there was a dramatic loss of spines in the week immediately before degeneration. In contrast, axonal degeneration was preceded by a progressive attenuation of presynaptic turnover that started many weeks before axon disappearance. Therefore, changes in synapse plasticity are harbingers of degeneration of individual neurites that occur at differing stages of tau-driven neurodegenerative disease, suggesting a cell or neurite autonomous process. Furthermore, the links between synapse plasticity and degeneration are distinct in axonal and dendritic compartments. Copy rights belong to original authors. Visit the link for more info
Its our first colour episode, as we take a look at the good and the bad of the Axons.
Its our first colour episode, as we take a look at the good and the bad of the Axons.
A group of gold-skinned aliens land on Earth and offer wondrous technology in exchange for fuel, while the Third Doctor isn’t easily convinced. But while uncovering the Axons’ true nature, the Doctor must once again face his arch enemy, the … Continue reading →
In 1495, a mysterious and deadly plague struck the city of Naples. Over the next 500 years, the medical attempts to understand and treat this new disease -- syphilis -- would mold and shape medicine in surprising ways. In this episode, Tony Breu and I will perform an historical and physiological biography of syphilis, covering the development of germ theory, epic poetry, mercury saunas, intentionally infecting patients with malaria, magic bullets, and lots and lots of experiments on poor rabbits. This presentation was performed live at the American College of Physicians’ national meeting in Philadelphia on April 11, 2019. Sources (WARNING -- LONG LIST): Swain, K. ‘Extraordinarily arduous and fraught with danger’: syphilis, Salvarsan, and general paresis of the insane. Lancet Psychiatry 5, (2018). Kępa, M. et al. Analysis of mercury levels in historical bone material from syphilitic subjects – pilot studies (short report). Kępa Małgorzata 69, 367-377(11) (2012). Forrai, J. Syphilis - Recognition, Description and Diagnosis. (2011). doi:10.5772/24205 Parascandola, J. From mercury to miracle drugs: syphilis therapy over the centuries. Pharm Hist 51, 14–23 (2009). Eisler, C. Who Is Dürer’s ‘Syphilitic Man’? Perspect Biol Med 52, 48–60 (2009). Rothschild, B. M. History of Syphilis. Clin Infect Dis 40, 1454–1463 (2005). Schwartz, R. S. Paul Ehrlich’s Magic Bullets. New Engl J Medicine 350, 1079–1080 (2004). Fee, E. The wages of sin. Lancet 354, SIV61 (1999). O’Shea, J. ‘Two Minutes with Venus, Two Years with Mercury’-Mercury as an Antisyphilitic Chemotherapeutic Agent. J Roy Soc Med 83, 392–395 (1989). Mahoney, J., Arnold, R., Sterner, B. L., Harris, A. & Zwally, M. Penicillin Treatment of Early Syphilis: II. Jama 251, 2005–2010 (1984). Waugh, M. Role played by Italy in the history of syphilis. Sex Transm Infect 58, 92–95 (1982). Thorburn, A. Fritz Richard Schaudinn, 1871-1906: protozoologist of syphilis. Sex Transm Infect 47, 459–461 (1971). CROSBY, A. W. The Early History of Syphilis: A Reappraisal. Am Anthropol 71, 218–227 (1969). Clark, E. G. & Danbolt, N. The Oslo study of the natural history of untreated syphilis An epidemiologic investigation based on a restudy of the Boeck-Bruusgaard material a review and appraisal. J Chron Dis 2, 311–344 (1955). MUNGER, R. S. Guaiacum, the Holy Wood from the New World. J Hist Med All Sci IV, 196–229 (1949). Thomas, E. & r, W. Rapid Treatment of Early Syphilis with Multiple Injections of Mapharsen. J Nerv Ment Dis 99, 88 (1944). WIEDER, L., FOERSTER, O. & FOERSTER, H. MAPHARSEN IN THE TREATMENT OF SYPHILIS: FURTHER EXPERIENCES. Arch Dermatol Syph 35, 402–413 (1937). THON, L. SHOULD THE INTERNIST KNOW SYPHILIS? J Amer Med Assoc 97, 994–996 (1931). Sarton, G. The Earliest Printed Literature on Syphilis, being Ten Tractates from the Years 1495-1498. Karl Sudhoff , Charles Singer , Henry E. Sigerist. Isis 8, 351–354 (1926). COLE, H., GERICKE, A. & SOLLMANN, T. THE TREATMENT OF SYPHILIS BY MERCURY INHALATIONS: HISTORY, METHOD AND RESULTS. Arch Dermatol Syph 5, 18–33 (1922). Mason, U. Observation: Use and Abuse of Salvarsan. J Natl Med Assoc 3, 340–3 (1911). Fleming, A. & Colebrook, L. ON THE USE OF SALVARSAN IN THE TREATMENT OF SYPHILIS. Lancet 177, 1631–1634 (1911). Evans, A. The Treatment of Syphilis by Salvarsan (Dioxy-diamido-arseno-benzol). Brit Med J 1, 617 (1911). Boeck, W. History, Theory and Practice of Syphilisation. New Engl J Medicine 73, 20–25 (1865). Veale, H. Remarks on Syphilis and Its Treatment. Edinb Medical J 10, 10–26 (1864). LaFond RE and Lukehart SA, Biological Basis for Syphilis. Clinical Microbiology Reviews 2006. Secher L et al, Treponema pallidum in peripheral nerve tissue of syphilitic chancres. Acta dermato-venereologica 1982. Hollander DH, Turner TB, The role of temperature in experimental treponemal infection. American journal of syphilis, gonorrhea, and venereal diseases, 1954 Eagle H, et al. The effect of hyperpyrexia on the therapeutic efficacy of penicillin in experimental syphilis. American journal of syphilis, gonorrhea, and venereal diseases, 1947. Kampmeier RH, Syphilis therapy: an historical perspective. Journal of the American Venereal Disease Association 1976. Pachner AR, Spirochetal Diseases of the CNS. Neurologic clinics, 1986. Sell S et al, Experimental syphilitic orchitis in rabbits: ultrastructural appearance of Treponema pallidum during phagocytosis and dissolution by macrophages in vivo. Laboratory investigation; a journal of technical methods and pathology, 1982. Taylor SH, Diuretics in cardiovascular therapy. Perusing the past, practising in the present, preparing for the future. Zeitschrift für Kardiologie, 1985. Ovchinnikov NM, [Treponema pallidum in peripheral nerves of rabbit syphiloma]. Vestnik dermatologii i venerologii, 1975. Cheek DB, Wu F, The Effect of Calomel on Plasma Epinephrine in the Rat and the Relationship to Mechanisms in Pink Disease, Archives of Disease in Childhood, 1959 Vogl A, The discovery of the organic mercurial diuretics, American Heart Journal, 1950 Schwemlein GX et al, Penicillin and fever therapy in early syphilis, Journal of the American Medical Association, 1948. Stringham JS, On the Diuretic Effects of Mercury in a Case of Syphilis. The Medical and physical journal, 1807 Evanson RL et al, Effect of mercurial diuretics on tubular sodium and potassium transport in the dog. The American journal of physiology, 1972 Sell S and Salman J, Demonstration of Treponema pallidum in Axons of Cutaneous Nerves in Experimental Chancres of Rabbits, Sexually Transmitted Diseases, 1992 Penn CW, Avoidance of Host Defences by Treponema pallidum in Situ and on Extraction from Infected Rabbit Testes, Microbiology 1981. Beutler B and Munford RS, Tumor Necrosis Factor and the Jarisch–Herxheimer Reaction, The New England Journal of Medicine 1996. Radolf JD et al, Treponema pallidum: doing a remarkable job with what it's got. Trends in Microbiology, 1999 Tight RR, Perkins RL, Treponema pallidum infection in subcutaneous polyethylene chambers in rabbits. Infection and immunity, 1976 Salazar JC et al, Treponema pallidum Elicits Innate and Adaptive Cellular Immune Responses in Skin and Blood during Secondary Syphilis: A Flow-Cytometric Analysis. The Journal of Infectious Diseases, 2007 Azevedo BF et al, Toxic Effects of Mercury on the Cardiovascular and Central Nervous Systems. Journal of Biomedicine and Biotechnology 2012, Clarkson TW and Magos L, The Toxicology of Mercury and Its Chemical Compounds, Critical Reviews in Toxicology 2008. Fitzgerald TJ, The Th1/Th2-like switch in syphilitic infection: is it detrimental? Infection and immunity, 1992 Batterman RC et al, THE SUBCUTANEOUS ADMINISTRATION OF MERCAPTOMERIN (THIOMERIN®): Effective Mercurial Diuretic for the Treatment of Congestive Heart Failure. Journal of the American Medical Association, 1949 Batterman RC, The status of mercurial diuretics for the treatment of congestive heart failure. American Heart Journal, 1951 Bleich HL et al, The Role of Regional Body Temperature in the Pathogenesis of Disease, The New England Journal of Medicine, 1981 Vander Veer JB et al, The Prolonged Use of an Oral Mercurial Diuretic in Ambulatory Patients with Congestive Heart Failure. Circulation 1950 Cox DL et al, The outer membrane, not a coat of host proteins, limits antigenicity of virulent Treponema pallidum. Infection and immunity, 1992. Fildes P, The Mechanism of the Anti-bacterial Action of Mercury. Br J Exp Pathol, 1940 Clarkson TW, THE MECHANISM OF ACTION OF MERCURIAL DIURETICS IN RATS; THE METABOLISM OF 203Hg‐LABELLED CHLORMERODRIN. British Journal of Pharmacology and Chemotherapy, 1965 Engelkens HJ et al, The localisation of treponemes and characterisation of the inflammatory infiltrate in skin biopsies from patients with primary or secondary syphilis, or early infectious yaws. Genitourinary Medicine, 1993 Belum GR et al, The Jarisch–Herxheimer reaction: Revisited. Travel Medicine and Infectious Disease, 2013 Arando M et al, The Jarisch–Herxheimer reaction in syphilis: could molecular typing help to understand it better? Journal of the European Academy of Dermatology and Venereology, 2018. Butler T, The Jarisch–Herxheimer Reaction After Antibiotic Treatment of Spirochetal Infections: A Review of Recent Cases and Our Understanding of Pathogenesis. The American Journal of Tropical Medicine and Hygiene, 2016 Carlson JA et al, The Immunopathobiology of Syphilis: The Manifestations and Course of Syphilis Are Determined by the Level of Delayed-Type Hypersensitivity. The American Journal of Dermatopathology 2011. Aronson IK and Soltani K, The enigma of the pathogenesis of the Jarisch-Herxheimer reaction. The British Journal of Venereal Diseases, 1976 Sellato TJ et al, The Cutaneous Response in Humans to Treponema pallidum Lipoprotein Analogues Involves Cellular Elements of Both Innate and Adaptive Immunity, The Journal of Immunology 2001 Spiller HA, Rethinking mercury: the role of selenium in the pathophysiology of mercury toxicity. Clinical Toxicology 2017 Sell S et al, Reinfection of chancre-immune rabbits with Treponema pallidum. I. Light and immunofluorescence studies. The American journal of pathology 1985. Grant SS and Hung DT, Persistent bacterial infections, antibiotic tolerance, and the oxidative stress response, Virulence 2013 Lant AF, Modern diuretics and the kidney. Journal of Clinical Pathology, 1981 Kamath SU et al, Mercury-based traditional herbo-metallic preparations: a toxicological perspective, Archives of Toxicology 2012. Yeter et al, Mercury Promotes Catecholamines Which Potentiate Mercurial Autoimmunity and Vasodilation: Implications for Inositol 1,4,5-Triphosphate 3-Kinase C Susceptibility in Kawasaki Syndrome. Korean Circulation Journal 2013 Wöβmann W et al, Mercury intoxication presenting with hypertension and tachycardia. Archives of Disease in Childhood, 1999 Giacani L et al, Identification of the Treponema pallidum subsp. pallidum TP0092 (RpoE) Regulon and Its Implications for Pathogen Persistence in the Host and Syphilis Pathogenesis. Journal of Bacteriology 2013. Edwards AM, From tooth to hoof: treponemes in tissue‐destructive diseases. Journal of Applied Microbiology, 2003 Wolgemuth CW, Flagellar motility of the pathogenic spirochetes. Seminars in Cell & Developmental Biology 2015. Solomon HC and Kopp I, Fever Therapy. The New England Journal of Medicine 1937. Rice KM et al, Environmental Mercury and Its Toxic Effects. Journal of Preventive Medicine and Public Health 2014. Drusin LM, Electron microscopy of Treponema pallidum occurring in a human primary lesion. Journal of bacteriology 1969. McNeely MC et al, Cutaneous secondary syphilis: Preliminary immunohistopathologic support for a role for immune complexes in lesion pathogenesis. Journal of the American Academy of Dermatology 1986. Borenstein LA et al, Contribution of rabbit leukocyte defensins to the host response in experimental syphilis. Infection and immunity 1991. Cabot RC et al, Case 51-1976 — Bicentennial CPC — Syphilis, Diarrhea and Death in the 1820's. The New England Journal of Medicine 1976. Hobman JL and Crossman LC, Bacterial antimicrobial metal ion resistance. Journal of Medical Microbiology 2015 Gelpi A and Tucker JD, After Venus, mercury: syphilis treatment in the UK before Salvarsan. Sexually Transmitted Infections 2015. MacHaffie et al, A study of the effectiveness of mercurial diuretics in treatment of cardiac decompensation. The American Journal of Cardiology 1958 Aberer W et al, Ammoniated mercury ointment: outdated but still in use. Contact Dermatitis 1990 Farhi D, Dupin N, Origins of syphilis and management in the immunocompetent patient: Facts and controversies. Clinics in Dermatology (2010) 28, 533–538 Frith J, “Syphilis – Its early history and Treatment until Penicillin and the Debate on its Origins,” Journal of Military and Veterans’ Health, 20(4), retrieved online at: http://jmvh.org/article/syphilis-its-early-history-and-treatment-until-penicillin-and-the-debate-on-its-origins/ Howes OD et al, “Julius Wagner-Jauregg, 1857-1940,” American Journal of Psychiatry, April 2009 Volume 166 Number 4, Volume 166, Issue 4, April, 2009, pp. 409-409. Karamanou M et al, “Julius Wagner-Jauregg (1857-1940): Introducing fever therapy in the treatment of neurosyphilis.” Psychiatriki. 2013 Jul-Sep;24(3):208-12. Simpson WM, “Artificial fever therapy of syphilis,” JAMA. 1935;105(26):2132-2140. Tsay CJ, “Julius Wagner-Jauregg and the Legacy of Malarial Therapy for the Treatment of General Paresis of the Insane,” Yale J Biol Med. 2013;86(2): 245–254 Wagner-Jauregg J, “The history of malaria treatment of general paralysis.” Am J Psychiatry. 1946;02: 577-582 Shafer JK et al, Untreated syphilis in the male Negro: A prospective study of the effect on life expectancy. Public Health Rep. 1954 Jul; 69(7): 684–690. Abara WE et al, Syphilis Trends among Men Who Have Sex with Men in the United States and Western Europe: A Systematic Review of Trend Studies Published between 2004 and 2015. PLoS One. 2016; 11(7): e0159309. Nutton V, The Reception of Fracastoro's Theory of Contagion: The Seed That Fell among Thorns? Osiris, Vol. 6, Renaissance Medical Learning: Evolution of a Tradition (1990) Tsaraklis A, Preventing syphilis in the 16th century: the distinguished Italian anatomist Gabriele Falloppio (1523-1562) and the invention of the condom. 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In this episode of LIGHT TALK, the Lumen Brothers discuss everything from Dangerous Tools to Stan's Buddha. Join Steve, David, and Stan, as they pontificate about: Lighting designers' responsibilities when it comes to flashing lights, Alice Cooper, New LED strobe lights, Neurons, Axons, and electrical charges, When you look into her eyes you are looking at her brain, Refresh rates, Hertz, What makes a good Road Case, Gorilla Tests, Do lighting designers intensionally (or unintentionally) discriminate against black and Asian actors?, Techniques to light darker skin-tones, Dancing Desdemonas, How to pick a Master Electrician, and a Shout-Out to Toby the Dog! Nothing is Taboo, Nothing is Sacred, and Very Little Makes Sense.
Concussion Corner is your trusted resource for interdisciplinary conversations related to all things concussion-related in healthcare, advocacy, and sport. *This podcast is for entertainment purposes only and should not be confused for medical advice. Please reach out to your medical team or call 911 if this is an emergency*Check us out on Facebook, Instagram, Twitter, & YouTube
Concussion Corner is your trusted resource for interdisciplinary conversations related to all things concussion-related in healthcare, advocacy, and sport. *This podcast is for entertainment purposes only and should not be confused for medical advice. Please reach out to your medical team or call 911 if this is an emergency*Check us out on Facebook, Instagram, Twitter, & YouTube
Straight from a Scientist Medical Research Education and Discussion Podcast
This interview podcast features Maya Gosztyla, an undergraduate researcher at THE Ohio State University. Maya researches the genetics of axon guidance, or brain wiring in fruit flies, and runs her own Alzheimer's Disease learning blog called AlzScience. We discuss her research, how she balances work with free time, and how she worked her way into her first research lab without hands-on experience. Here's a great post by Maya on AlzScience describing Alzheimer's Disease Here are her latest posts. Highly recommend for those looking to learn more about Alzheimer's Disease! @AlzScience Facebook @AlzScience Twitter Stay tuned for a special Alzheimer's Disease roundtable podcast with Maya and Connor, releasing later this week! We'll discuss the idea that Amyloid Beta may not be simply a villain... Any other questions? Let us know! We appreciate your feedback. You can now support the podcast at https://www.patreon.com/sfspodcast. Many thanks to our past and present supporters! Thanks to Plant Warrior for their support. Use discount code SFS10 at checkout for 10% off your purchase of plant-based protein.
Lo, the (almost) end has come, and the Three Who Rule have thoughts, feels and comments about “The Doctor Falls,” the penultimate episode for both director Rachel Talalay and showrunner/writer Steven Moffat. What did the three scoundrels think of this stew of Masters and Mondasians? More to the point, what’s going on with the First Doctor and the upcoming Xmas special? So many questions! Next week, the return of Fluid Links, but only pertaining to Series 10, so no questions about Nimons and Axons! Links: – The Doctor Falls review – Christmas Special press release – Christmas Special promo pic – Doctor Who Fan Show interviews Moffat & Talalay – Moffat homage to RTD as mentioned in the Fan Show – Matt Lucas says goodbye – Michelle Gomez says goodbye – The Doctor Falls BBC One overnight viewing figures – The Eaters of Light final BBC One viewing figures – World Enough and Time Appreciation Index – The Thirteenth Doctor’s actor should be known soon – Gallifrey One guest announcement – Peter Capaldi and Doctor Who at San Diego Comic-Con – LI Who guests – Voord and Tetrap figurines – Planet 14 Information
Basic Brain Biology Your brain is made of cells. Those cells are called neurons. Neurons transmit signals in the form of electricity (aka .positive and negative charges). One end of a neuron will build a signal or charge, and once it reaches a certain threshold, then a signal is send down the axons. Most of the cells in your body touch and transmit signals and pass chemicals through their membranes. Neurons do not touch. The terminals of one will get really really close to the dendrites of another. They're really good at the telephone game - mostly because the body tries to minimize the number of neurons involved in passing a signal. Axons are coated in myelin. Myelin insulates the axon that helps the signal being sent travel faster, and prevents it from getting lost to something else touching it. You want the signal to have to same strength when it reaches its destination as it did when it left its source. Parts of a neuron Dendrites: receives signals from previous neuron Cell body: contains the nucleus and creates and translates signals Axon: the "wire" that transmits signals Terminals: sends signals to the next neuron Grey matter - cell bodies, dendrites, and terminals White matter - axons wrapped in myelin Grey matter - information storage and translation White matter - information transmission Brain: grey matter is on the outside, white matter is on the inside Spinal cord: grey matter is on the inside, white matter is on the outside. PS. Grey? Gray? IDK!!! Connect with me Support us on Patreon *NEW* Join the Pharmacist Answers Podcast Community on Facebook Subscribe: iTunes, Stitcher, GooglePlay, TuneIn Radio Like the Facebook page Music Credits: “Radio Martini” Kevin MacLeod (incompetech.com) Licensed under Creative Commons: By Attribution 3.0 http://creativecommons.org/licenses/by/3.0/
Wanderers in the 4th Dimension: A Journey Through Doctor Who
This week we cover story #57, The Claws of Axos! The Master is at it again, trying to trade the nutrient value of all life on Earth to the Axons in exchange for his freedom, his TARDIS, and the death of the Doctor! Question of the Week/Listener Mailbag Discussion of "The Claws of Axos" (Trevor 8, Charlie 8, David 8) Connor's Corner Big Finish audio adventure: Prison in Space (Trevor 6.5, Charlie 6, David 6.75) May Comics Roundup: Tenth Doctor #9: The Weeping Angels of Mons part 4 Eleventh Doctor #11: Four Dimensions Twelfth Doctor #7: The Fractures part 2 Hosts: Trevor Twitter: @WhovianTrev Tumblr: http://trevsplace.tumblr.com/ Charlie Twitter: @insanityinchaos Infinite Longbox Podcast Comic Conspiracy Podcast David Twitter: @gwythinn WWW: http://www.davidsafar.com/ Tumblr: http://maroonedwhovian.tumblr.com/ Join us next week for our review of Doctor Who story #58, Colony in Space! You can stream the serial from Hulu Plus, rent the DVD from Netflix, or buy the DVD from Amazon.com, or many other fine retailers.
Anthony and Dr. David Linden (Professor, Johns Hopkins University School of Medicine) talked this week about David’s neuroscience research and how he gets inspiration in and out of lab. Anthony also asked David about his journey to becoming a successful scientist and best-selling author. This episode of Brain Matters was brought to you be Audible.com. To get a free audiobook go to audiblepodcast.com/brainmatters
Anthony and Dr. David Linden (Professor, Johns Hopkins University School of Medicine) talked this week about David’s neuroscience research and how he gets inspiration in and out of lab. Anthony also asked David about his journey to becoming a successful scientist and best-selling author. This episode of Brain Matters was brought to you be Audible.com. To get a free audiobook go to audiblepodcast.com/brainmatters
In PleasureTown's third "minisode," we flash forward to the present, where we meet young Mason Bowen, a student at Enid State University. As part of his college thesis, he interviews Mr. Johnstone, an elderly man who visited the fabled PleasureTown as a boy. But is Mr. Johnstone's account as credible as he'd like Mason to believe? Written by Richard Izzo, this is part of our "Write an Episode" contest and features music by the band Axons.
Multiple Sclerosis Discovery: The Podcast of the MS Discovery Forum
[intro music] Hello, and welcome to Episode Twenty-Five of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller. This week’s podcast features a special interview with actor and science advocate, Alan Alda, whom you may remember as Hawkeye Pierce in M*A*S*H. But to begin, here’s a brief summary of some of the latest developments on the MS Discovery Forum at msdiscovery.org. Positive thinking may lead to positive clinical outcomes, according to a new meta-analysis. The investigators found that interventions such as cognitive behavioral therapy helped patients deal with physical symptoms like fatigue and pain. They suggested that psychological well-being should be assessed and treated along with physical disability in people with MS. The researchers also called for studies that examined the connection between the psychological and the physical more directly. Moving from the macro to the micro, we recently published an article about axonal transport. Axons rely on motor proteins to carry cargo across long tracks of microtubules in order to survive. A disruption in this process is associated with neurodegeneration. Recently a team of researchers discovered that axonal transport is disrupted in mice with EAE. In this animal model of MS, even normal-appearing axons failed to transport organelles as quickly or as effectively as healthy axons. But the researchers were able to reverse the process, suggesting a potential new therapeutic target for drug development. [transition music] Now to the interview. Alan Alda is an actor known for his television roles in M*A*S*H and The West Wing. But he’s also a longtime advocate of science and scientific literacy and the founder of the Alan Alda Center for Communicating Science at Stony Brook University. He met with MSDF recently to talk about the art of good science communication. [Interview] Interviewer – Dan Keller What, at this point, would you say are the one or two biggest pieces of advice you could give to any technical person or a scientist trying to get his point across to the general public? Interviewee – Alan Alda I think the most important thing to remember is that it’s not nearly so important to worry about what you have to say to the other person, as it is to think about how the other person is receiving what you have to say. We know this intellectually because everybody knows that you want to know your audience, everybody knows you want to start where the student is, you know, find out what they know and build on that, that kind of thing. We all know that. But one of the things that I think that we’ve found at the Center for Communicating Science that I helped start is that you need to get in the habit of doing that; you need to really go through the experience of actually opening up to other people, getting their feedback, being able to read from the signals that they give you on their face and their body language – all the various signals you can get – whether or not they’re really paying attention and really following you. If you miss one of the crucial words I say at the beginning of a paragraph, the rest of the paragraph is dead; you’re spending most of your time trying to figure out what I’m talking about. MSDF As an example, say, in Scientific American Frontiers, you elicited great storytelling; I mean, I assume part of that was picking the right speakers, but how do you coax it out of them in an understandable way? I mean can you essentially guide people without saying, “Hey, come on, bring it down, bring it down.”? Mr. Alda I think Scientific American Frontiers worked as well as it did because in a way it was a rare thing – I hadn’t seen it done before and so maybe it has, but I hadn’t seen it – where you had a naïve person – ignorant, played by me – and I wasn’t acting. I made use of the natural fund of ignorance that I came in with. I didn’t aspire to an ignorance I didn’t possess, it was real; I really didn’t know what these people did in the laboratory, and I really did want to know what it was. And I wanted to understand it, so I badgered them until I understood it, and I didn’t pretend I understood it if I didn’t. That step where they actually had to come to terms with this person standing right next to them looking up in their faces where they had to actually make it clear to this one person, that changed them in some way, that brought out the human being in them. And they forgot about the camera, they forgot about the millions of people that they might have gone into lecture mode to explain this to. They were talking to one individual and that made a big difference, because they became much more human. So, yeah, I think that we had people who were comfortable being in front of a camera, but regardless of how comfortable they were in making their language plain-spoken, they had to get even more so when they talked to me because I really, I just tugged at their coat until I understood it. And something happened between us, there was some kind of connection between us that was very watchable, very interesting. I think that helped draw other people in. After we did that, I really wondered if a scientist didn’t have this person dogging him or her to get the information out, but to get it out understandably, what would do it? How could they get accustomed to speaking as though they’re talking to another person who really wants to know? And that’s when it occurred to me that I bet we could teach them improvising and that would help them get more personal, and it has. MSDF To envision one person. Mr. Alda Well, when you improvise, at least the way we improvise with scientists, it’s not for the purpose of getting them to be comical, or to make things up on the spot, or to be clever. The whole thing is designed to get the scientists to be accustomed to observing the person they’re talking to, because you can’t play these improvising games unless you’re tuned into the other person in a very powerful way. Once they get used to that and when they turn and talk to an audience, they carry with them that same ability to talk to the people and not over their heads and not at them. They don’t spray information at them anymore, they actually engage the audience, and that’s a tremendous difference. MSDF Let me switch gears a little bit. I don’t know if you’ve ever noticed it, I’ve certainly noticed it, between different closely related scientific disciplines – I mean, I cover medicine mostly – and people in just very closely related things, there’s no cross-pollination. They’re surprised when they hear something that’s going on. Oh, you know, that could be applicable to me. And I think there’s even a lack of communication between the disciplines between scientists. They can certainly speak in the same jargon, but I don’t know if there’s a barrier or if they’re just so wrapped up in their own stuff. Mr. Alda It seems to be a really serious problem that scientists need more and more to collaborate across disciplines, and the problem is that they often – I think I could say often – don’t understand one another much better than a layperson understands a scientist in a specialized field. So at a certain level, at a certain distance from one another’s work, they’re really in the position of an interested layperson rather than a collaborator, rather than a colleague. And we have to bridge that gap if we’re going to get the benefits of collaboration. And I’ve heard some horror stories of scientists getting together and not understanding one another. And on the other hand, I’ve heard these really heartbreakingly wonderful stories. When we have a workshop with a range of scientists, scientists from several different fields, one of the wonderful things they say is this has been great, I got to understand, I got to hear about this guy’s work and I never knew anything about it before. They’re hearing an explanation of another person’s work in terms that they might say it to the lay public. It’s acceptable to the other scientists because we don’t ask them to dumb it down, we ask them NOT to dumb it down just to make it clear. So they’re getting a clear version of somebody else’s work that doesn’t include the jargon of that specialized field. It’s stripped of its jargon, it’s spoken in plain language. And the emotion, the passion that the scientist feels about it is allowed to come out because that’s part of the human story that science is. Science, rather than being passionless, is generated by passion. So it’s great that that comes out in this work. MSDF In the training, obviously you can tell if there’s a difference between before and after. But have you ever been able to test the durability of this, that these people retaining these? Or do they lapse back? Or can you tell? Mr. Alda It’s hard to get measurements on the success of this, but we’re beginning to get some early results because we’ve been working with teaching assistants. And teaching assistants are graduate students who are asked to give courses to undergraduates to see if the undergraduates want to go into science. And one of the problems has been that a lot of them drop out because they can’t get interested in the science partly because the teaching assistants don’t have any training in communication or in education; they know the material but they’re not really experienced at communicating. So we put them through a course of communication, and then we find some of the numbers we’re getting back are that the students are rating them as highly or higher than people who have been doing this for five years, and these are first-time teaching assistants. Next thing we’ll check on is are their grades getting better and other things you can measure. But so far, the acceptance of the teachers is already better because there’s an attempt to personalize the experience. And so the students are accepting the teachers more, and by the same token, I assume they’re accepting the science more. MSDF Have you ever thought of designing a curriculum that could be put into the science graduate programs, because these people are going to become scientists? Mr. Alda What we’ve actually done is introduced a curriculum into Stony Brook University where I helped the Center for Communicating Science. And there are courses for credit taught to graduate students, and in addition there’s even at least one department that requires that the students take these communication courses. So it’s beginning to be seen as an essential element of the science education. And it’s a small beginning. But my feeling has always been isn’t communication essential to science itself, don’t we need to communicate science in order for it to take place or for the benefits of science to come to the surface? And not only that, that’s practical, but for the beauty of science to be enjoyed by the whole world, you definitely need communication. And that will help more science get done, and better science get done. More people entering science, if they understand how beautiful and engrossing it is – exciting. So it seems to me that since communication is such an important part of science, shouldn’t it be taught as part of a science education so that when you graduate as a capable scientist, you’re also a capable communicator? MSDF Maybe you don’t even have an idea of this answer, but what got you into this passion for science? Mr. Alda I’ve always been curious and that made me want to know more. I started reading Scientific American in my early 20s and since then I’ve read almost every article in almost every issue. And I love it, I just love it! I mean, I put the magazine down and I read other science magazines – I read Science & Nature and Science News, which I think does a very good job. Just the other day, I just slammed it down on the table and I said to my wife, “Arlene, you won’t believe this, listen to this.” You hear these wonderful stories of things you never imagined. MSDF No, I agree. I mean, some people get turned off by it, some people get turned on by it. Mr. Alda Well, it’s hard to believe anybody would get turned off by it unless they’re not hearing it the right way. MSDF I think that a lot of people are turned off early because they weren’t encouraged or they were led to believe they couldn’t understand it. Mr. Alda Yeah, it’s true. MSDF I appreciate it. Thanks. Mr. Alda Well, thank you very much. [transition music] Thank you for listening to Episode Twenty-Five of Multiple Sclerosis Discovery, our final episode for 2014. We’ll be taking a two-week hiatus for the holidays, but we’ll be back with new weekly episodes starting on January fifth. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations. Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances. We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org. [outro music]
Tamler and David leech off of their listeners and dedicate an episode to their favorite comments, questions, and criticisms from the past few weeks (but not before Tamler goes on a rant about bicycle helmets). Included in this episode: Does doing research on hypothetical moral dilemmas actually say anything about how people would act in real life? Do people make different moral judgments in their native language than in a more recently acquired language? Do Tamler and David only appeal to intuitions when it's convenient for the view they are defending? Do they hold "barbaric" views about justice and revenge? Does doing philosophy make your life better? And, perhaps most importantly, why do we seem to mention porn on every episode? LinksBicycle helmet effectiveness [wikipedia.org]Tamler's appearance on The Partially Examined Life podcast [partiallyexaminedlife.com]Axons and Axioms podcast [axonsandaxioms.com]Spacetime Mind podcast [spacetimemind.com]A valuable site if you're interested in putting together your own podcast: Dan Benjamin's Podcasting Handbook [podcastinghandbook.co]If you like the music we use, you can listen/download here: soundcloud.com/peezismynamePea Soup Blog [peasoup.typepad.com]Qualia [wikipedia.org]Judith Jarvis Thomson's "A Defense of Abortion" [wikipedia.org]Entranced by Reality by Ian Corbin (Review of "A Life Worth Living: Albert Camus and the Quest for Meaning" by Robert Zaretsky). [theamericanconservative.com]Iranian killer's execution halted at last minute by victim's parents by Saeed Kamali Dehghan [theguardian.com]Academic Articles MentionedBartels, Daniel M. (2008), "Principled Moral Sentiment and the Flexibility of Moral Judgment and Decision Making," Cognition, 108, 381-417. [uchicago.edu]Costa, A., Foucart, A., Hayakawa, S., Aparici, M., Apesteguia, J., Heafner, J., & Keysar, B. (2014). Your Morals Depend on Language. PloS one, 9(4), e94842. [plosone.org]Gold, N., Colman, A. M., & Pulford, B. D. (2014). Cultural differences in responses to real-life and hypothetical trolley problems. Judgment and Decision Making, 9, 65-76. [sjdm.org]Special thanks to listeners (in order of question-appearance) Jakub Maly, Mark Ellis, Derek Leben, Jennifer Cohen, Rob Sica, Larson Landes, Billie Pritchett, Dave Herman, Otakar Horak, Monique Oliveira, Paul Bello, and Dag Soras.
Hank Thompson is a comedian and producer at The Young Turks (youtube.com/TYTComedy), and his brother Dr. Chris Thompson is a post-doctoral fellow at Scripps Research Institute in the Department of Cellular and Molecular Neuroscience. This powerful comedy/science sibling duo join Matt and Andy this week to discuss: Sibling rivalry! Vocal communication in animals! Learned vocalization! Dolphins who know their own names! Inverted commas! Everything you ever wanted to know about songbirds! Chicago ladies! 3D syrinx models! Burning out parts of bird brains! Terrible Hunger Games writing! Taxi drivers' enlarged hippocampi! Axons, neurons, dendrites and synapses! The effect of Prozac on birds' songs! Getting harrassed by amateur birders! Albino African clawed frogs! Inheriting the chess team captain crown! Andy's upcoming 1,000-mile road trip with a Belgian stranger! The Jimmy Dore Show on TYT Comedy!
Graduate School of Systemic Neurosciences - Digitale Hochschulschriften der LMU
Thu, 20 Dec 2012 12:00:00 +0100 http://edoc.ub.uni-muenchen.de/15183/ http://edoc.ub.uni-muenchen.de/15183/1/Schuemann_Anne.pdf Schümann, Anne Graduate School of Systemic Neuroscien
Plot The Axons land on Earth, desperately in need of fuel. They propose to exchange the miracle substance they call Axonite for some much needed energy. Axonite is a "thinking" molecule that can replicate any substance... or so they claim. As it turns out, the ship is a single organism called Axos whose purpose is to feed itself by draining all energy through the Axonite (which is just a part of itself), including the energy of every life form on Earth. The deception about the Axonite's beneficial properties was to facilitate the distribution of Axonite across the globe. Meanwhile, the , who was captured by Axos and used his knowledge of Earth as a bargaining chip for his life and freedom, escapes Axos and makes his way to the Doctor's — his own having been seized by Axos. He plans to repair it to escape from Earth. Axos itself becomes interested in the Doctor's knowledge of . It now plans to broaden its feeding base by travelling through time as well as space. The Doctor, realising this, plans to trick Axos into linking up its drive unit to his TARDIS so that he can send Axos into a perpetual . After tricking the Master into completing the repairs on his TARDIS, the Doctor does just that. This results in every part of Axos dematerialising from Earth, including the Axon automatons and the Axonite. At the end, with the Master having escaped in his own TARDIS during the confusion aboard Axos, the Doctor returns to Earth, but not of his own volition. The have programmed the TARDIS to always return to Earth, the Doctor states that he is a "galactic yo-yo!". Continuity Both the Doctor and the Master refer to the events of this serial in "". "", a with the , tells the subsequent story of astronauts visiting Axos, still imprisoned in the time loop. The Axons reappear in the comic strip "The Golden Ones", beginning in issue #425. In this story they are behind a brain-enhancing drink and associated show in . The drink transforms children into Axons by "increasing the links between in the brain" - in other words, the .
A proportion of small diameter primary sensory neurones innervating human skin are chemosensitive. They respond in a receptor dependent manner to chemical mediators of inflammation as well as naturally occurring algogens, thermogens and pruritogens. The neurotransmitter GABA is interesting in this respect because in animal models of neuropathic pain GABA pre-synaptically regulates nociceptive input to the spinal cord. However, the effect of GABA on human peripheral unmyelinated axons has not been established.
The Doctor, newly rejuvenated, shows the Master the power of the human race. A year after the events of "The Sound of Drums", Earth has been closed to all species and labelled as in "terminal extinction". Martha returns to , having travelled the world since teleporting away from the Valiant at the moment of the Master's triumph. Her TARDIS key, still generating a , has kept her hidden all this time. She meets Thomas Milligan, a doctor-turned-freedom-fighter, who can lead her to one Professor Docherty. Martha herself has become a figure of hope against the Master, rumoured to be the only one capable of killing him. Meanwhile, on the , is keeping the aged Doctor in a 'dog-kennel' tent as his humiliated prisoner, Martha's family as his servants, and in chains. is still his companion, but shows evidence of physical and emotional abuse. The Master shows the Doctor the world he has created: the new Time Lord Empire. Across the planet, warships are being built to wage war on the rest of the universe. The Doctor has "only one thing to say", but the Master doesn't want to hear it. After a failed attempt by the Jones family, Jack, and the Doctor to gain control by stealing the Master's , the Master sends out a transmission intended for Martha. Watching in Docherty's lab, she sees the Master suspend the Doctor's capacity to and age him by a further nine hundred years, shrinking him into a tiny, frail creature. Instead of being dismayed, Martha draws hope from the Doctor's continued survival. Though the have proven to be virtually invincible, Martha reveals that she stumbled upon one that was struck by lightning, and with the data gathered from the incident Docherty is able to replicate the required conditions. Upon examining the sphere thus captured, they make a horrifying discovery: the Toclafane contain the conscious remains of . There was no Utopia, only more darkness, and with everything dying around them the humans cannibalised and regressed themselves, becoming the child-like Toclafane. The Master brought them back in time using the TARDIS, which could only travel between Utopia and present-day Earth. The contradiction of the Toclafane is made possible by the built by the Master. Martha is horrified when the Toclafane quotes young Creet that she met on , telling her that the Toclafane have of the last of humanity. When questioned as to why it wishes to kill its own ancestors, the Toclafane responds, "Because it's fun" followed by maniacal laughter. Tom subsequently shoots it dead. When Docherty asks if the rumours about Martha are true, Martha reveals a gun, developed by and , purportedly able to kill a Time Lord and prevent the ensuing . Martha has retrieved three of the four chemicals needed for the gun from their hiding places around the world, and has returned to to find the fourth. After Martha and Thomas depart for a shelter in to hide, Docherty (who is desperate for information regarding her missing son) reveals their whereabouts to the Master. The Master thus comes to Earth's surface to capture Martha, killing Tom, destroying the special gun and taking her back to the Valiant. He intends to execute her before the Doctor and her family, at the moment his fleet is launched. As the clock counts down, Martha reveals the real reason she travelled the globe. It wasn't for a fictional anti-regeneration gun, or to fight back, but merely to talk. She told everyone about the Doctor; specifically, she told everyone to think of the Doctor at the same time the Master plans to launch his fleet. Docherty's betrayal was expected, engineered by Martha so that she would be brought on board the Valiant to rejoin the Doctor. Combined with the Master's , which the Doctor has had an entire year to get in tune with, this has the effect of charging the Doctor with the combined psychic energy of the people of Earth. This enables the Doctor to restore his youthful physiognomy and end the Master's control. As the Master cowers, the Doctor says the words the Master was afraid to hear: "I forgive you." With the Master out of the picture, Jack rounds up some soldiers to destroy the paradox machine, but is delayed by the Toclafane. The Master, using Jack's , teleports himself and the Doctor to Earth, threatening to detonate his fleet and take the Earth with it. The Doctor knows that the Master can't kill himself, and manages to teleport both himself and the Master back to the Valiant just as Jack destroys the paradox machine, rewinding time to just after the US President is killed and just before the Toclafane arrive. All those on the Valiant remember the events due to being at "the eye of the storm", but nobody else will know of the Master's reign of terror in "the year that never happened". The Master, now defenceless, is handcuffed and stands before the Doctor. The Doctor announces that, since the Master is a Time Lord, he is the Doctor's responsibility and will be imprisoned on board the TARDIS. Francine Jones is talked out of shooting the Master, but Lucy Saxon, with a glazed expression, seizes a gun herself and shoots him. Rather than be a prisoner for the rest of his lives, the Master lets himself die, refusing to regenerate despite the Doctor's desperate pleas. Just before dying in his opponent's arms, the Master muses on the constant drumming in his head, wondering if it will finally stop, and with a smile says, "I win", leaving the Doctor to weep for his lost adversary and fellow Time Lord. The Doctor the Master's body on a . However, after he leaves, a female hand wearing red nail polish is seen taking the Master's ring from the burnt-out pyre, with malevolent laughter echoing in the background. In Cardiff, Jack decides to remain behind to look after his , "defending the Earth". The Doctor disables Jack's vortex manipulator to keep him from jumping through time unsupervised. The Doctor then tells Jack there's nothing that can be done about his immortality: it seems likely he'll never be able to die — though he isn't sure about aging. Thinking about what he might look like millions of years from now, Jack confesses his vanity and recalls how, as the first person from the Boeshane Peninsula to join the Time Agency, his good looks earned him the nickname "the ". With the TARDIS repaired, the Doctor is ready to move on. Martha, however, has decided to stay so she can look after her family and finally qualify as a medical doctor. She gives the Doctor her phone so they can keep in touch and says she will see him again, but when someone is in love and it's unrequited, they have to get out: "this is me getting out". Leaving in the TARDIS, the Doctor begins to relax in the console room chair — until the ship is suddenly shaken with great force, and the bow of a ship smashes through the TARDIS' wall. Picking up a , he finds "" written on it, to which he can only respond, "What?!" [] Cast — — — — — — — — Thomas Milligan — Professor Docherty — Lad — Woman — voices — Zoe Thorne, Gerard Logan, and Johnnie Lyne-Pirkis [] Cast Notes Reggie Yates is credited as playing Leo Jones; however, the character Leo only appears in this episode as background. The audio commentary for the episode mentions that Leo was originally scheduled to appear, but Yates was double-booked. [] Continuity In the episode's commentary, writer called the implication of Jack's nickname ("the ") "a theory" as to the Face of Boe's origins, prompting Executive Producer Julie Gardner to urge him to "stop backpedaling" about the two characters being the same. There was much laughter. Davies also mentioned the addition of a line in "Gridlock" in which the Face of Boe calls the Doctor "old friend", suggesting a strong connection between him and the Doctor.The Master makes reference to the and the . The Doctor also makes references to the Axons and the .Earth is referred to as Sol 3, the third planet from the star , as it was in . Sol is the Latin name for the Sun, and is often used in science fiction.The Master's laser screwdriver is said to be isomorphically controlled, a property the Doctor attributed to the TARDIS in ; although other characters, such as , have operated the TARDIS.Clips from "", "" and "" are used in this episode.After receiving a great amount of psychic energy, and rejuvenating himself, the Doctor says the line: "", a frequently used catchphrase of his.Martha mentions that she once met ("").When the Master is shot by he says, "It's always the women." He was previously shot by in "Utopia".The Doctor's severed hand from "", "Utopia", "The Sound of Drums" and various episodes can be seen at the end of the episode inside the .At the end of the episode, the Doctor says "What?!" three times, after the crashed through the wall, which was his response to Donna at the end of "", when she appeared onboard the TARDIS.This does not appear to be the Doctor's first encounter with the Titanic. In "" the stated that he had been onboard an "unsinkable" ship and that he "ended up clinging to an iceberg". In "", Clive shows Rose evidence that someone that looked like the Ninth Doctor prevented a family from boarding the ship. The Doctor has also been on the Titanic in novels (for example, the in the ), but the of the novels is in question.The hand seen picking up the Master's ring leaves open the possibility of reintroducing the character at a later date, although Russell T Davies stated in the podcast for this episode that this would not occur in the 2008 series.
1. Electrotonic responses to 150 ms current pulses were recorded from isolated rat dorsal roots incubated for at least 3 h with either normal (5 mM) or high (25 mM) D-glucose solutions, and with either normal (25 mM) or low (5 mM) bicarbonate concentrations. 2. On replacement of O2 by N2 for 50 min, all the roots depolarized, but the changes in electrotonus differed systematically. With normal glucose, the depolarization was accompanied by an increase in input conductance. In contrast, for the hyperglycaemic roots the depolarization was slower and accompanied by a fall in input conductance which was exacerbated in low bicarbonate concentrations. 3. The changes induced by hyperglycaemic hypoxia in low bicarbonate could be mimicked by exposure of the roots either to 100% CO2 or to a combination of 3 mM tetraethylammonium chloride and 3 mM 4-aminopyridine, to block both fast and slow potassium channels. 4. These results indicate that the primary mechanism of hypoxic depolarization of these sensory axons is altered by hyperglycaemia. In normoglycaemia, the changes in electrotonus are consistent with an increase in axonal potassium conductance. The block of potassium channels seen in hyperglycaemic hypoxia is attributed to intra-axonal acidification by anaerobic glycolysis and may contribute to the pathogenesis of diabetic neuropathy.
The functional anatomy of motor recovery was studied by assessing motor function quantitatively in 23 patients following capsular or striatocapsular stroke. While selective basal ganglia lesions (caudate and/or putamen exclusively) did not affect voluntary movements of the extremities, lesions of the anterior (plus caudate/putamen) or posterior limb of the internal capsule led to an initially severe motor impairment followed by excellent recovery, hand function included. In contrast, lesions of the posterior limb of the internal capsule in combination with damage to lateral thalamus compromised motor outcome. In experimental tracing of the topography of the internal capsule in macaque monkeys, we found axons of primary motor cortex passing through the middle third of the posterior limb of the internal capsule. Axons of premotor cortex (dorsolateral and post-arcuate area 6) passed through the capsular genu, and those of supplementary motor area (mesial area 6) through the anterior limb. Small capsular lesion can therefore disrupt the output of functionally and anatomically distinct motor areas selectively. The clinically similar motor deficits with a similar course of functional restitution following disruption of these different descending motor pathways indicate a parallel operation of cortical motor areas. They may have the further capability of substituting each other functionally in the process of recovery from hemiparesis.
1. The mechanism of post-ischaemic ectopic impulse generation in nerve is not known, and previous measurements of excitability changes in human motor axons have appeared to conflict. We have used automatic threshold tracking and different stimulus-response combinations to follow the effects on excitability of brief (5-10 min) periods of ischaemia, too short to induce motor fasciculations. Excitability changes have been compared at different sites in axons innervating hand, arm and foot muscles. 2. Threshold was determined as the percutaneous stimulus current required to excite a single motor unit, or to evoke a constant multiunit response, after rectifying and integrating the electromyogram (EMG). Three different waveforms of stimulus current were compared: short (less than or equal to 2 ms) pulses, long (100-200 ms) pulses to measure rheobase, and 100 ms current ramps. We also measured accommodation by recording the effects of subthreshold depolarizing currents on excitability. 3. Ischaemic and post-ischaemic excitability changes were greatest in the proximal parts of the longest motor axons, and greater if the sphygmomanometer cuff was inflated over, rather than proximal to, the stimulating site. 4. Using integrated EMG responses from abductor digiti minimi, the ulnar nerve stimulated above the elbow became rapidly much less excitable after ischaemia when tested with short pulses, but more excitable when tested with current ramps. The rheobase rose briefly, but then fell, often below resting level, always staying below the pulse and ramp thresholds. 5. The latency of the response to a rheobasic stimulus altered in parallel with the threshold to short current pulses, and increased dramatically after ischaemia. This latency increase was associated with a prolonged phase of 'negative accommodation', i.e. the continued increase in excitability to a maintained subthreshold depolarizing current. 6. Changes in excitability and accommodation similar to those occurring after ischaemia were recorded following high frequency trains of stimuli. They were attributed primarily to hyperpolarization by the electrogenic sodium pump, since comparable changes could be induced by passing a steady hyperpolarizing current through the stimulating electrode. 7. Threshold and latency recordings from single motor units during and after ischaemia resembled in most respects the multiunit responses, but single unit rheobase did not show a post-ischaemic fall below the resting level. Repetitive firing contributed to the low multiunit thresholds recorded with long current pulses during the post-ischaemic period. 8. We conclude that human motor nerves become simultaneously both more and less excitable than normal after 10 min of ischaemia, depending on the choice of stimulus and response.
Current recordings from single chloride channels were obtained from excised and cell-attached patches of rat and human axons. In rat axons the channels showed an outwardly rectifying current-voltage relationship with a slope conductance of 33 pS at negative membrane potentials and 65 pS at positive potentials (symmetrical 150 mM CsCl). They were measurably for cations (PNa/PCs/PCl=0.1/0.2/1). Channel currents were independent of cytoplasmatic calcium concentration. Inactivation was not observed and gating was weakly voltage dependent. Cl− channels in human axons showed similar gating behavior but had a lower conductance.
The reasons for the resistance to ischaemia of peripheral nerves in diabetics are not well understood. We have now explored whether axonal depolarization underlies this phenomenon, as has previously been proposed. Resistance to ischaemia was determined by the new method of “threshold tracking”. This method revealed an increase in excitability of the peroneal nerve at the popliteal fossa during ischaemia, and a decrease in excitability in the post-ischaemic period. The extent of these alterations in 28 type 1 diabetics without peripheral neuropathy showed a strong correlation with the mean blood glucose concentrations during the last 24 h before examination. To test whether the ischaemic resistance was related to membrane potential, we also measured axonal superexcitability in 11 selected diabetics, since it has been shown that post-spike changes in excitability depend on membrane potential. Changes in excitability of the peroneal nerve were measured in the period between 10 and 30 msec following a conditioning supramaximal compound action potential. Under resting conditions, no differences in the post-spike superexcitability were found between controls and diabetics, despite striking differences in their responses to a 10-min pressure cuff. These observations indicate that membrane depolarization is not involved in the resistance to ischaemia of motor axons in diabetic subjects.
1. The nature, distribution and function of rectifying channels in rat spinal root myelinated axons has been assessed with selective blocking agents and a variety of intracellular and extracellular recording techniques. 2. The electrotonic responses of roots poisoned with tetrodotoxin (TTX) to constant current pulses had fast (rise time much less than 1 ms) and slow components, which were interpreted in terms of Barrett & Barrett's (1982) revised cable model for myelinated nerve. Depolarization evoked a rapid outward rectification (time constant, tau approximately 0.5 ms), selectively blocked by 4-aminopyridine (4AP, 1 mM), and a slow outward rectification (tau approximately 15 ms), selectively blocked by tetraethylammonium (TEA, 1 mM) or Ba2+ (0.5 mM). Hyperpolarization evoked an even slower inward rectification, selectively blocked by Cs+ (3 mM) but not by Ba2+. 3. From the different effects of the blocking agents on the fast and slow components of electrotonus, it was deduced (a) that the inward rectification is a property of the internodal axon, (b) that the slow outward rectifier is present at the nodes, and probably the internodes as well, and (c) that the 4AP-sensitive channels have a minor nodal and a major internodal representation. 4. TEA and Ba2+ reduced the accommodation of roots and fibres not poisoned with TTX to long current pulses, whereas 4AP facilitated short bursts of impulses in response to a single brief stimulus. 5. TEA and Ba2+ also abolished a late hyperpolarizing after-potential (peaking at 20-80 ms), while 4AP enhanced the depolarizing after-potential in normal fibres, and abolished an early hyperpolarizing after-potential (peaking at 1-3 ms) in depolarized fibres. Corresponding to the later after-potentials were post-spike changes in excitability and conduction velocity, which were affected similarly by the blocking agents. Cs+ increased the post-tetanic depression attributable to electrogenic hyperpolarization. 6. The physiological roles of the three different rectifying conductances are discussed. It is also argued that the prominent ohmic 'leak conductance', usually ascribed to the nodal axon, must arise in an extracellular pathway in series with the rectifying internodal axon.
Myelinated nerve fibres with a reduced safety factor for conduction due to demyelination are easily blocked by trains of impulses. To find out why, in vivo recordings from rat ventral root fibres demyelinated with diphtheria toxin have been supplemented with in vivo and in vitro recordings from normal fibres. Despite a small rise in extracellular potassium activity, normal fibres were invariably hyperpolarized by intermittent trains of impulses. This hyperpolarization resulted in an increase in threshold and also in an enhancement of the depolarizing after-potential and the superexcitable period. Replacement of NaCl in the extracellular solution by LiCl completely blocked both the membrane hyperpolarization and the threshold increase which were normally observed during intermittent trains of impulses. At demyelinated nodes which were blocked by trains of impulses (10-50 Hz), conduction block was preceded by a rise in threshold current and in an increase in internodal conduction time, but by no detectable reduction in the outward current generated by the preceding node. It was found possible to prevent the threshold from changing during a train by automatic adjustment of a d.c. polarizing current. This 'threshold clamp' prevented the conduction failure and virtually abolished the changes in internodal conduction time. The threshold changes were attributed to hyperpolarization, as in normal fibres, since (a) the polarizing current required to prevent them was always a depolarizing current, and (b) they were accompanied by an increase in superexcitability. The post-tetanic depression that can follow continuous trains of impulses was attributed to the combination of increased threshold and enhanced superexcitable period due to hyperpolarization. It is concluded that the susceptibility of these demyelinated fibres to impulse trains is not due to a membrane depolarization induced by extracellular potassium accumulation but to a membrane hyperpolarization as a consequence of electrogenic sodium pumping.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.16.044818v1?rss=1 Authors: Birdsall, V., Imoto, Y., Waites, C., Watanabe, S. Abstract: Turnover of synaptic vesicle (SV) proteins is vital for the maintenance of healthy, functional synapses in neurons. Our previous work showed that the degradation of SV proteins is mediated by the endosomal sorting complex required for transport (ESCRT) pathway in an activity-dependent manner. Here, we characterize the axonal transport dynamics of ESCRT-0 proteins Hrs and STAM1, the first components of the ESCRT pathway critical for initiating SV protein degradation. Hrs- and STAM1-positive transport vesicles exhibit increased anterograde and bidirectional motility in response to neuronal firing, and frequent colocalization with SV pools. These ESCRT-0 vesicles are a subset of Rab5-positive structures in axons, likely representing pro-degradative early endosomes. Further, we identify kinesin motor protein KIF13A as essential for the activity-dependent transport of ESCRT-0 vesicles as well as the degradation of SV membrane proteins. Together, these data demonstrate a novel KIF13A-dependent mechanism for mobilizing axonal transport of ESCRT machinery to facilitate the degradation of SV proteins. Copy rights belong to original authors. Visit the link for more info
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