Podcasts about molecular basis

------------------Support the channel------------ Patreon: https://www.patreon.com/thedissenter PayPal: paypal.me/thedissenter PayPal Subscription 3 Dollars: https://tinyurl.com/ybn6bg9l PayPal Subscription 5 Dollars: https://tinyurl.com/ycmr9gpz PayPal Subscription 10 Dollars: https://tinyurl.com/y9r3fc9m PayPal Subscription 20 Dollars: https://tinyurl.com/y95uvkao   ------------------Follow me on--------------------- Facebook: https://www.facebook.com/thedissenteryt/ Twitter: https://twitter.com/TheDissenterYT   This show is sponsored by Enlites, Learning & Development done differently. Check the website here: http://enlites.com/   Dr. Luis Favela is an Associate Professor of Philosophy and Cognitive Sciences (tenured) at the University of Central Florida. He is concurrently a Fellow in the Research Corporation for Science Advancement's Molecular Basis of Cognition Scialog program. His research attempts to understand mind (i.e., behavior, cognition, and consciousness) from a naturalistic and interdisciplinary perspective. He is the author of The Ecological Brain: Unifying the Sciences of Brain, Body, and Environment.   In this episode, we focus on The Ecological Brain. We first discuss ecological psychology and neuroscience, how they split historically, and why it seems hard to reconcile them. We talk about two traditions in neuroscience: one focusing on biological features of neurons, and the other focusing on abstract features of neurons. We discuss complexity science. We get into Dr. Favela's NExT (NeuroEcological Nexus Theory) framework, the hypotheses derived from it, and limitations of brain-centered approaches. We discuss what the ecological brain is. Finally, we talk about the main challenges to the NExT framework, non-mechanistic explanations, and the importance of interdisciplinarity. -- A HUGE THANK YOU TO MY PATRONS/SUPPORTERS: PER HELGE LARSEN, JERRY MULLER, HANS FREDRIK SUNDE, BERNARDO SEIXAS, OLAF ALEX, ADAM KESSEL, MATTHEW WHITINGBIRD, ARNAUD WOLFF, TIM HOLLOSY, HENRIK AHLENIUS, FILIP FORS CONNOLLY, DAN DEMETRIOU, ROBERT WINDHAGER, RUI INACIO, ZOOP, MARCO NEVES, COLIN HOLBROOK, PHIL KAVANAGH, SAMUEL ANDREEFF, FRANCIS FORDE, TIAGO NUNES, FERGAL CUSSEN, HAL HERZOG, NUNO MACHADO, JONATHAN LEIBRANT, JOÃO LINHARES, STANTON T, SAMUEL CORREA, ERIK HAINES, MARK SMITH, JOÃO EIRA, TOM HUMMEL, SARDUS FRANCE, DAVID SLOAN WILSON, YACILA DEZA-ARAUJO, ROMAIN ROCH, DIEGO LONDOÑO CORREA, YANICK PUNTER, ADANER USMANI, CHARLOTTE BLEASE, NICOLE BARBARO, ADAM HUNT, PAWEL OSTASZEWSKI, NELLEKE BAK, GUY MADISON, GARY G HELLMANN, SAIMA AFZAL, ADRIAN JAEGGI, PAULO TOLENTINO, JOÃO BARBOSA, JULIAN PRICE, EDWARD HALL, HEDIN BRØNNER, DOUGLAS FRY, FRANCA BORTOLOTTI, GABRIEL PONS CORTÈS, URSULA LITZCKE, SCOTT, ZACHARY FISH, TIM DUFFY, SUNNY SMITH, JON WISMAN, DANIEL FRIEDMAN, WILLIAM BUCKNER, PAUL-GEORGE ARNAUD, LUKE GLOWACKI, GEORGIOS THEOPHANOUS, CHRIS WILLIAMSON, PETER WOLOSZYN, DAVID WILLIAMS, DIOGO COSTA, ANTON ERIKSSON, CHARLES MOREY, ALEX CHAU, AMAURI MARTÍNEZ, CORALIE CHEVALLIER, BANGALORE ATHEISTS, LARRY D. LEE JR., OLD HERRINGBONE, MICHAEL BAILEY, DAN SPERBER, ROBERT GRESSIS, IGOR N, JEFF MCMAHAN, JAKE ZUEHL, BARNABAS RADICS, MARK CAMPBELL, TOMAS DAUBNER, LUKE NISSEN, KIMBERLY JOHNSON, JESSICA NOWICKI, LINDA BRANDIN, NIKLAS CARLSSON, GEORGE CHORIATIS, VALENTIN STEINMANN, PER KRAULIS, KATE VON GOELER, ALEXANDER HUBBARD, BR, MASOUD ALIMOHAMMADI, JONAS HERTNER, URSULA GOODENOUGH, DAVID PINSOF, SEAN NELSON, MIKE LAVIGNE, JOS KNECHT, ERIK ENGMAN, LUCY, YHONATAN SHEMESH, AND MANVIR SINGH! A SPECIAL THANKS TO MY PRODUCERS, YZAR WEHBE, JIM FRANK, ŁUKASZ STAFINIAK, TOM VANEGDOM, BERNARD HUGUENEY, CURTIS DIXON, BENEDIKT MUELLER, THOMAS TRUMBLE, KATHRINE AND PATRICK TOBIN, JONCARLO MONTENEGRO, AL NICK ORTIZ, AND NICK GOLDEN! AND TO MY EXECUTIVE PRODUCERS, MATTHEW LAVENDER, SERGIU CODREANU, BOGDAN KANIVETS, ROSEY, AND GREGORY HASTINGS!

------------------Support the channel------------ Patreon: https://www.patreon.com/thedissenter PayPal: paypal.me/thedissenter PayPal Subscription 1 Dollar: https://tinyurl.com/yb3acuuy PayPal Subscription 3 Dollars: https://tinyurl.com/ybn6bg9l PayPal Subscription 5 Dollars: https://tinyurl.com/ycmr9gpz PayPal Subscription 10 Dollars: https://tinyurl.com/y9r3fc9m PayPal Subscription 20 Dollars: https://tinyurl.com/y95uvkao   ------------------Follow me on--------------------- Facebook: https://www.facebook.com/thedissenteryt/ Twitter: https://twitter.com/TheDissenterYT Podcast: http://bit.ly/3FeSNqb   This show is sponsored by Enlites, Learning& Development done differently. Check the website here: http://enlites.com/   Dr. Luis Favela is an Associate Professor of Philosophy and Cognitive Sciences (tenured) at the University of Central Florida. He is concurrently a Fellow in the Research Corporation for Science Advancement's Molecular Basis of Cognition Scialog program. His research attempts to understand mind (i.e., behavior, cognition, and consciousness) from a naturalistic and interdisciplinary perspective.   In this episode, we start by talking about complexity science, and how it applies to the study of the mind, and the relationship between mind and brain. We then go through embodied cognition, distributed cognition, and extended cognition. We talk about computational-representational approaches in cognitive science and their limitations, and the computer metaphor of the mind. We discuss dynamical systems theory, what a dynamical system is, and a recent dynamical renaissance in neuroscience. Finally, we talk about mechanistic explanations in science, and explanatory pluralism. -- A HUGE THANK YOU TO MY PATRONS/SUPPORTERS: PER HELGE LARSEN, JERRY MULLER, HANS FREDRIK SUNDE, BERNARDO SEIXAS, OLAF ALEX, ADAM KESSEL, MATTHEW WHITINGBIRD, ARNAUD WOLFF, TIM HOLLOSY, HENRIK AHLENIUS, JOHN CONNORS, FILIP FORS CONNOLLY, DAN DEMETRIOU, ROBERT WINDHAGER, RUI INACIO, ZOOP, MARCO NEVES, COLIN HOLBROOK, PHIL KAVANAGH, SAMUEL ANDREEFF, FRANCIS FORDE, TIAGO NUNES, FERGAL CUSSEN, HAL HERZOG, NUNO MACHADO, JONATHAN LEIBRANT, JOÃO LINHARES, STANTON T, SAMUEL CORREA, ERIK HAINES, MARK SMITH, JOÃO EIRA, TOM HUMMEL, SARDUS FRANCE, DAVID SLOAN WILSON, YACILA DEZA-ARAUJO, ROMAIN ROCH, DIEGO LONDOÑO CORREA, YANICK PUNTER, ADANER USMANI, CHARLOTTE BLEASE, NICOLE BARBARO, ADAM HUNT, PAWEL OSTASZEWSKI, NELLEKE BAK, GUY MADISON, GARY G HELLMANN, SAIMA AFZAL, ADRIAN JAEGGI, PAULO TOLENTINO, JOÃO BARBOSA, JULIAN PRICE, EDWARD HALL, HEDIN BRØNNER, DOUGLAS FRY, FRANCA BORTOLOTTI, GABRIEL PONS CORTÈS, URSULA LITZCKE, SCOTT, ZACHARY FISH, TIM DUFFY, SUNNY SMITH, JON WISMAN, DANIEL FRIEDMAN, WILLIAM BUCKNER, PAUL-GEORGE ARNAUD, LUKE GLOWACKI, GEORGIOS THEOPHANOUS, CHRIS WILLIAMSON, PETER WOLOSZYN, DAVID WILLIAMS, DIOGO COSTA, ANTON ERIKSSON, CHARLES MOREY, ALEX CHAU, AMAURI MARTÍNEZ, CORALIE CHEVALLIER, BANGALORE ATHEISTS, LARRY D. LEE JR., OLD HERRINGBONE, MICHAEL BAILEY, DAN SPERBER, ROBERT GRESSIS, IGOR N, JEFF MCMAHAN, JAKE ZUEHL, BARNABAS RADICS, MARK CAMPBELL, TOMAS DAUBNER, LUKE NISSEN, KIMBERLY JOHNSON, BENJAMIN GELBART, JESSICA NOWICKI, LINDA BRANDIN, NIKLAS CARLSSON, ISMAËL BENSLIMANE, GEORGE CHORIATIS, VALENTIN STEINMANN, PER KRAULIS, KATE VON GOELER, ALEXANDER HUBBARD, LIAM DUNAWAY, BR, MASOUD ALIMOHAMMADI, JONAS HERTNER, URSULA GOODENOUGH, DAVID PINSOF, SEAN NELSON, MIKE LAVIGNE, JOS KNECHT, ERIK ENGMAN, LUCY, AND YHONATAN SHEMESH! A SPECIAL THANKS TO MY PRODUCERS, YZAR WEHBE, JIM FRANK, ŁUKASZ STAFINIAK, TOM VANEGDOM, BERNARD HUGUENEY, CURTIS DIXON, BENEDIKT MUELLER, THOMAS TRUMBLE, KATHRINE AND PATRICK TOBIN, JONCARLO MONTENEGRO, AL NICK ORTIZ, AND NICK GOLDEN! AND TO MY EXECUTIVE PRODUCERS, MATTHEW LAVENDER, SERGIU CODREANU, BOGDAN KANIVETS, ROSEY, AND GREGORY HASTINGS!

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.24.550266v1?rss=1 Authors: Ramirez-Franco, J., Debreux, K., Sangiardi, M., Belghazi, M., Kim, Y., Lee, S.-H., Leveque, C., Seagar, M., El Far, O. Abstract: The Kv1 members (KCNA, Shaker) of the voltage-gated potassium channels are implicated in determining key functional neuronal properties from spike generation at axonal initial segments to the control of synaptic strength at nerve terminals. In animal models of LGI1-dependent autosomal dominant lateral temporal lobe epilepsy (ADTLE), Kv1 channels are downregulated, suggesting their crucial involvement in epileptogenesis. The molecular basis of Kv1 channel-downregulation in LGI1 knock-out mice has not been elucidated and how the absence of this extracellular protein induces an important modification in the expression of Kv1 remains unknown. In this study we analyse by immunofluorescence the detailed modifications in neuronal Kv1.1 and Kv1.2 distribution throughout the hippocampal formation of LGI1 knock-out mice. We show that Kv1 downregulation is not restricted to the axonal compartment, but also takes place in the somatodendritic region and is accompanied by a drastic decrease in Kv2 expression levels. Moreover, we find that the downregulation of these Kv channels is associated with an important increase in bursting patterns. Finally, mass spectrometry uncovered key important modifications in the Kv1 interactome that highlight the epileptogenic implication of Kv1 downregulation in LGI1 knock-out animals. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.20.549895v1?rss=1 Authors: Ng, B., Tasaki, S., Greathouse, K., Walker, C., Zhang, A., Covitz, S., Cieslak, M., Adamson, A., Andrade, J., Poovey, E., Curtis, K., Muhammad, H., Seidlitz, J., Satterthwaite, T., Bennett, D., Seyfried, N., Vogel, J., Gaiteri, C., Herskowitz, J. Abstract: Neuroimaging is commonly used to infer human brain connectivity, but those measurements are far-removed from the molecular underpinnings at synapses. To uncover the molecular basis of human brain connectivity, we analyzed a unique cohort of 98 individuals who provided neuroimaging and genetic data contemporaneous with dendritic spine morphometric, proteomic, and gene expression data from the superior frontal and inferior temporal gyri. Through cellular contextualization of the molecular data with dendritic spine morphology, we identified hundreds of proteins related to synapses, energy metabolism, and RNA processing that explain between-individual differences in functional connectivity and structural covariation. By integrating data at the genetic, molecular, subcellular, and tissue levels, we bridged the divergent fields of molecular biology and neuroimaging to identify a molecular basis of brain connectivity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In this episode of Health411, Dr. Jonathan Karp and producer Daniel Geller explore the molecular basis and effects of the circadian rhythm. They unravel the internal body clock's intricate mechanisms and its impact on sleep-wake cycles, hormone production, metabolism, and cognitive function. External factors like light exposure, social cues, and daily routines also influence the circadian rhythm. We delve into the consequences of disruptions, including sleep disorders, metabolic disorders, and mood disorders. Practical tips for optimizing the circadian rhythm are shared, promoting consistent sleep schedules, sleep-friendly environments, and healthy habits for overall well-being.

How do scientists collaborate when writing? In this episode, Ralph Panstruga and Matthew Moscou discuss how they wrote a review paper together while residing in two different countries, working at two different institutions, and living through a pandemic.The editorial, titled "What is the Molecular Basis of Nonhost Resistance?" can be found here:https://apsjournals.apsnet.org/doi/10.1094/MPMI-06-20-0161-CR

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.20.513066v1?rss=1 Authors: Mikaeili, H., Habib, A. M., Yeung, C., Santana-Varela, S., Luiz, A. P., Panteleeva, K., Zuberi, S., Athanasiou-Fragkouli, A., Houlden, H., Wood, J. N., Okorokov, A. L., Cox, J. J. Abstract: Chronic pain affects millions of people worldwide. Studying pain insensitive individuals helps to identify novel analgesic strategies. Here we report how the recently discovered FAAH-OUT lncRNA-encoding gene, which was found from studying a pain insensitive patient with reduced anxiety and fast wound healing, regulates the adjacent key endocannabinoid system gene FAAH, which encodes the anandamide-degrading fatty acid amide hydrolase enzyme. We demonstrate that the disruption in FAAH-OUT lncRNA transcription leads to DNMT1-dependent DNA methylation within the FAAH promoter. In addition, FAAH-OUT contains a conserved regulatory element, FAAH-AMP, that acts as an enhancer for FAAH expression. Furthermore, using transcriptomic analyses we have uncovered a network of genes that are dysregulated from disruption of the FAAH-FAAH-OUT axis, thus providing a coherent mechanistic basis to understand the human phenotype observed and a platform for development of future gene and small molecule therapies. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Britt is a postdoc in Erik Jorgensen's lab at the University of Utah after joining in October 2021. The lab studies the molecular basis of synaptic transmission, focusing on the mechanisms of synaptic vesicle fusion and synaptic vesicle regeneration, her research uses C. elegans. Britt earned her PhD in May 2020 from the University of Leeds which focussed on modeling single amino acid variants in the ryanodine receptor in C. elegans.

One of the top 10 unanswered questions in molecular plant-microbe interactions asks  "What is the molecular basis of nonhost resistance?"  But answering this question may be impossible. Ralph Panstruga and Matthew Moscou consider how to re-frame it. The editorial, titled "What is the Molecular Basis of Nonhost Resistance?" can be found here:https://apsjournals.apsnet.org/doi/10.1094/MPMI-06-20-0161-CR

In this episode I do my best to provide an objective, science-based mechanism for how plant-based and paleo-type diets can be effective in reversing insulin resistance.  I cover the following: Molecular overview of insulin resistance Case descriptions of how plant-based and paleo-type diets can reverse insulin resistance Critical role of mitochondrial horsepower Overlap areas with plant-based and paleo-type diets Key concepts behind dietary personalization

You all Know, This chapter is something exotic and needs a proper study. We have brought you the Summary of it! Plug in at your leisure and get productive, listening to our Podcasts! If you like the work we do, Do Share and Support us. Happy Listening! --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.13.337386v1?rss=1 Authors: Auhim, H., Grigorenko, B., Harris, T., Polyakov, I., Berry, C., dos Passos Gomes, G., Alabugin, I., Rizkallah, P., Nemukhin, A. V., Jones, D. Abstract: Fluorescent proteins (FPs) have revolutionised the life sciences but the mechanism of chromophore maturation is still not fully understood. Incorporation of a photo-responsive non-canonical amino acid within the chromophore stalls maturation of Venus, a yellow FP, at an intermediate stage; the crystal structure reveals the presence of O2 located above a dehydrated enolate imidazolone (I) ring, close to the strictly conserved Gly67 that occupies a twisted conformation. His148 adopts an open conformation, potentially allowing O2 access to the chromophore. Absorption spectroscopy supported by QM/MM simulations suggest that the first oxidation step involves formation of a hydroperoxyl intermediate in conjunction with dehydrogenation of the methylene bridge. A fully conjugated mature chromophore is formed through release of H2O2 upon irradiation of this intermediate, both in vitro and in vivo. The possibility of interrupting and photochemically restarting chromophore maturation, and the mechanistic insights opens up new approaches for engineering optically controlled fluorescent proteins. Copy rights belong to original authors. Visit the link for more info

Jan explains how dendrite morphology relates to the function of neurons. For example, class IV da neurons are photoreceptors and their dendrites form a regular array in the fruit fly larvae to enable the avoidance of noxious signals, like light. On the other hand, class III da neurons are mechanosensors, and they use no mechanoreceptor potential C (NompC) protein to detect gentle touch. Jan and collaborators showed that NompC works by tethering ankyrin repeats to microtubules, providing evidence for the first time that this type of gating mechanosensor mechanism is possible.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.10.291757v1?rss=1 Authors: Delgado, J. M., Duro, N., Rogers, D. M., Tkatchenko, A., Pandit, S. A., Varma, S. Abstract: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused substantially more infections, deaths, and economic disruptions than the 2002-2003 SARS-CoV. The key to understanding SARS-CoV-2's higher infectivity may lie in its host receptor recognition mechanism. This is because experiments show that the human ACE2 protein, which serves as the primary receptor for both CoVs, binds to CoV-2's spike protein 5-20 fold stronger than SARS-CoV's spike protein. The molecular basis for this difference in binding affinity, however, remains unexplained and, in fact, a comparison of X-ray structures leads to an opposite proposition. To gain insight, we use all-atom molecular dynamics simulations. Free energy calculations indicate that CoV-2's higher affinity is due primarily to differences in specific spike residues that are local to the spike-ACE2 interface, although there are allosteric effects in binding. Comparative analysis of equilibrium simulations reveals that while both CoV and CoV-2 spike-ACE2 complexes have similar interfacial topologies, CoV-2's spike protein engages in greater numbers, combinatorics and probabilities of hydrogen bonds and salt bridges with ACE2. We attribute CoV-2's higher affinity to these differences in polar contacts, and these findings also highlight the importance of thermal structural fluctuations in spike-ACE2 complexation. We anticipate that these findings will also inform the design of spike-ACE2 peptide blockers that, like in the cases of HIV and Influenza, can serve as antivirals. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.21.260745v1?rss=1 Authors: Pontes, C., Ruiz-Serra, V. I., Lepore, R., Valencia, A. Abstract: The recent emergence of the novel SARS-CoV-2 in China and its rapid spread in the human population has led to a public health crisis worldwide. Like in SARS-CoV, horseshoe bats currently represent the most likely candidate animal source for SARS-CoV-2. Yet, the specific mechanisms of cross-species transmission and adaptation to the human host remain unknown. Here we show that the unsupervised analysis of conservation patterns across the {beta}-CoV spike protein family, using sequence information alone, can provide rich information on the molecular basis of the specificity of {beta}-CoVs to different host cell receptors. More precisely, our results indicate that host cell receptor usage is encoded in the amino acid sequences of different CoV spike proteins in the form of a set of specificity determining positions (SDPs). Furthermore, by integrating structural data, in silico mutagenesis and coevolution analysis we could elucidate the role of SDPs in mediating ACE2 binding across the Sarbecovirus lineage, either by engaging the receptor through direct intermolecular interactions or by affecting the local environment of the receptor binding motif. Finally, by the analysis of coevolving mutations across a paired MSA we were able to identify key intermolecular contacts occurring at the spike-ACE2 interface. These results show that effective mining of the evolutionary records held in the sequence of the spike protein family can help tracing the molecular mechanisms behind the evolution and host-receptors adaptation of circulating and future novel {beta}-CoVs. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.10.144097v1?rss=1 Authors: Das, T., Soren, K., Yerasi, M., Kamle, A., Kumar, A., Chakravarty, S. Abstract: Hypoxia the major cause of ischemia leads to debilitating disease in infants via birth asphyxia and cerebral palsy whereas in adults via heart attack and stroke. A widespread natural protective phenomenon termed Hypoxic Preconditioning occurs when prior exposures to hypoxia eventually results in robust hypoxia resistance. Accordingly we have developed a novel model of sex-specific hypoxic preconditioning in adult zebrafish to mimic the tolerance of mini strokes in human which appears to protect against the severe damage inflicted by a major stroke event. Remarkable difference in the progression pattern of neuroprotection between preconditioning hypoxia followed by acute hypoxia (PH) group, and acute hypoxia (AH) group were observed with noticeable sex difference. Since gender difference has been reported in stroke it was pertinent to investigate whether any such sex difference also exists in PHs protective mechanism against acute ischemic stroke. In order to elucidate the neural molecular mechanisms behind sex difference in neuroprotection induced by PH, a high throughput proteomics approach utilizing iTRAQ was performed, followed by protein enrichment analysis using Ingenuity Pathway Analysis. Out of thousands of altered proteins in zebrafish brain the ones having critical role either in neuroglial proliferation/differentiation or neurotrophic functions, were validated by analyzing their expression levels in PH, AH and normoxia groups. Results indicate that female zebrafish brains are more protected against the severity of AH. The study also sheds light on the involvement of many signaling pathways underlying sex difference in pre-conditioning induced neuroprotective mechanism, which can be further validated for the therapeutic approach. Copy rights belong to original authors. Visit the link for more info

The Latest Malaria News, in 60 Seconds. Scientists identify the process by which the malaria parasite imports sugar, a potential target for inhibiting parasitic development. More: www.fightmalaria.uk/MalariaMinute

Listen to this week's podcast to hear Professor Louise Serpell and Dr Karen Marshall from the University of Sussex talk Biochemistry and drug development. Learn about what amyloid fibrils actually are, their structure, other diseases that are caused by them and ultimately what we can do with this knowledge. You can find out more about our panellists, and their work on our website www.dementiaresearcher.nihr.ac.uk. A transcript of this podcast is also available on here https://www.dementiaresearcher.nihr.ac.uk/podcast-molecular-basis-of-alzheimers-disease Like what you hear? Please review, like, and share our podcast - and don't forget to subscribe to ensure you never miss an episode. We encourage all of our listeners to visit our website, it doesn’t matter if you are in the UK or elsewhere in the world as there is something there for everyone. We add new content every day, from blogs discussing peoples research and their careers, a full dementia and research events planner, details of all upcoming funding opportunities + lots more. Register today, and you’ll receive a short weekly news round-up email each Friday, to ensure you don't miss a think. Finally, we are now hosting a bi-weekly Whatsapp discussion (the week after each new podcast is released) which includes the panellists from this podcast. To talk to the panellists. ask questions and to chat about the 'Molecular Basis of Alzheimer's Disease' with the rest of our community join our Whatsapp group using this link: https://chat.whatsapp.com/BqxaDYhdjsML7doT6Qmbyd _________________________ If you would like to share your own experiences or discuss your research in a blog or on a podcast, drop us a line to dementiaresearcher@nihr.ac.uk or find us on twitter @dem_researcher

Reviewing everything DNA-related For detailed notes (PowerPoints) visit www.BiologyForBastards.com --- Send in a voice message: https://anchor.fm/bioforbastards/message

DNA! DNA! DEAD MICE! DNA! Also, other shit, like replication. For detailed notes (PowerPoints) visit www.BiologyForBastards.com --- Send in a voice message: https://anchor.fm/bioforbastards/message

In this episode, we talk about salt, electrolytes, and why you should be taking a serious look at your daily levels. We also address the endurance myth of salt consumption, the history,the genes associated with sodium, and why certain demographics need to pay more attention to their levels than others. Try one of our online programs: Here! Contact us: faqfitnesspodcast@gmail.com Add us on IG Parker Chuck   Show notes   Yanonami Indians in Brazillian rainforests still maintain ancient dietary patterns and consume less than 500mg/day The CDC estimates that the average American consumes 3,436 milligrams (mg) of sodium a day - far more than the maximum recommendation of 2,300 mg Salt became important when humans transitioned from eating, plants, fruits, bugs to using tools to hunt. Salt was important in the preservation of food. In modern times salt in higher concentration suppresses the bitterness of processed foods. 70%-80% of the sodium in U.S. diets comes not from the salt shaker but from packaged, processed, restaurant, and store-bought foods. In May, the Center for Science in the Public Interest released a report that found 85 out of 102 restaurant meals from 17 popular chains had more than a full day's worth of sodium. Some had more than four days’ worth. Clinical studies have indicated that the effect of sodium intake on blood pressure is influenced by a gene called the angiotensin-converting enzyme (ACE). GA and AA variants of this gene increase your likeliness to having elevated blood pressure when consuming salt.     Ways to reduce salt intake:   Eat MORE fresh minimally processed foods. Read the nutrition labels on packaged foods. When eating out at restaurants ask for low salt preparation. Avoid high sodium sauces like Soy, ketchup, mustard, and some salad dressings. Use sodium-free spices or fresh herbs to flavor foods.   Sources: Poch et al. “Molecular Basis of Salt Sensitivity in Human Hypertension. Evaluation of Renin-Angiotensin-Aldos-terone System Gene Polymorphisms,” Hypertension 38, no, 5 (2001): 1204-1209 https://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_sodium.htm PAUL, SHARAD P. GENETICS OF HEALTH: Understand Your Genes for Better Health. ATRIA Books, 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622706/ https://www.outsideonline.com/2010476/truth-about-endurance-athletes-and-salt

2015 Osborne Lecture Award Winner Marie-Catherine Vozenin: Understand the Cellular and Molecular Basis of Normal Tissues Toxicity to Define New Therapeutic Strategies and Improve Radiation Therapy Outcome

Today on Mission Supercritical our host Andy Joseph is joined by Paul Muchowski Dr. Paul received a PhD in Biological Structure from the University of Washington and performed post-doctoral training at the Max Planck Institute for Biochemistry. Dr. Muchowski worked as a professor in the medical schools at the University of Washington and the University of California San Francisco, and subsequently in drug development in the pharmaceutical and biotech industries. Dr. Muchowski's research focuses on the molecular basis of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Huntington's disease. He has published >60 highly cited research papers. His lab also published research on the role of the endocannabinoid system in neurodegeneration, showing that it is a critical determinant of the onset and severity of disease in animal models of chronic neurodegeneration.

Steve Brown, MRC, Harwell, UK speaks on "Mouse models for otitis media: dissecting the molecular basis of middle ear disease". This movie has been recorded at ICGEB Trieste.

SUNY Downstate

Moderator: Shivakumar Vignesh

Moderator: Shivakumar Vignesh

SUNY Downstate

This is the audio recording of the study guide Molecular basis of carcinogenesis, available here -> http://www.letstalkmed.com/molecular-basis-of-carcinogenesis.html . Facilitated and organized by Jinan AlRashoud

Paolo Golino, Department of Cardio-Thoracic and Respiratory Sciences, Section of Cardiology, Second University of Naples, Naples - ITALY speaks on "New Insights into the Pathophysiology of Acute Coronary Syndromes: From Molecular Basis to Clinical Manifestations". This seminar has been recorded by ICGEB Trieste

Molecular Basis of Colon Cancer - Panel Discussion

Molecular Basis of Colon Cancer - Panel Discussion

Five articles from the October 2015 issue summarized in five minutes, with the addition of a brief editorial commentary. The 5-in-5 feature is designed to give readers an overview of articles that may pique their interest and encourage more detailed reading. It may also be used by busy readers who would prefer a brief audio summary in order to select the articles they want to read in full. The featured articles for this month are  “Novel Application of Magnetic Resonance Imaging Demonstrates Characteristic Differences in Vasculature at Predilection Sites of Osteochondritis Dissecans,” “Why Do Osteochondral Allografts Survive?: Comparative Analysis of Cartilage Biochemical Properties Unveils a Molecular Basis for Durability,” “Autograft Versus Allograft Anterior Cruciate Ligament Reconstruction: A Prospective, Randomized Clinical Study With a Minimum 10-Year Follow-up,” “Deficits in Glenohumeral Passive Range of Motion Increase Risk of Shoulder Injury in Professional Baseball Pitchers: A Prospective Study,” and “Knee Kinematics During Noncontact Anterior Cruciate Ligament Injury as Determined From Bone Bruise Location.”     Click here to read the articles. 

Dr. Stephen Curry is a Professor of Structural Biology and Director of Undergraduate Studies in the Department of Life Sciences at Imperial College London. He received his PhD from Imperial College London. Stephen is a Fellow of the Society of Biology and was recently awarded the Peter Wildy Prize for Microbiology Education from the Society for General Microbiology. Stephen is here with us today to tell us all about his journey through life and science.

Dr Gerard Evan talks to ecancer at the 2013 NCRI Cancer Conference in Liverpool about methods for discovering new targets for treating cancer and the continuing move towards a more personalised approach to treatment.

Primary Progressive Aphasia is a language disorder that occurs when the language areas of the brain deteriorate due to a number of different neurodegenerative diseases (e.g. Frontotemporal Lobar Degeneration, Alzheimer’s Disease). Over time there is gradual loss of language abilities (speaking, understanding spoken language, reading, writing), but other mental abilities may be relatively unaffected for many years. This talk will review language and communication interventions that have been used in this population, and discuss additional services to support quality of life that should be considered and researched. | Center for Advanced Studies: 17.01.2013 | Speaker: Dr. Karen Croot | Moderation: Prof. Dr. Adrian Danek

Mehr als zwei Drittel der Demenzkranken werden zu Hause gepflegt. Für die Familienangehörigen ist dies oft mit einer hohen Belastung verbunden. Daher muss über das Leben mit den an Demenz Erkrankten offen gesprochen werden, statt sie und ihre Betreuer von der Gesellschaft zu isolieren. Die Zukunft der Betreuung liegt nicht in Heimen, sondern in einer Gemeinschaft, in der sich die Menschen für einander verantwortlich fühlen. | Center for Advanced Studies: 11.07.2012 | Referent: Prof. Thomas Klie | Moderation: Dr. Lena Bouman

Neuere Forschungen geben Anlass zu der Annahme, dass Ludwig II. an einer beginnenden präsenilen Demenz litt. Ein Podium mit Vertretern aus Medizin, Jurisprudenz und Geschichtswissenschaft wird der Frage nachgehen, inwiefern diese Diagnose dazu beiträgt, das Bild des Herrschers ebenso wie die Umstände seiner Entmachtung neu zu deuten. | Center for Advanced Studies: 14.05.2012 | Referenten: Prof. Hans Förstl, Dr. Katharina Weigand, Dr. Peter Gauweiler | Moderation: Prof. Hans-Michael Körner

Am Anfang der Diagnose Demenz stehen das Erleben und die Bedürfnisse der Betroffenen selbst. Die Angehörigen hingegen nehmen die Symptome ganz anders wahr, alle Akteure im Versorgungsnetz haben also ihren eigenen Blickwinkel. Im Bereich der Selbsthilfe werden sowohl die Bedürfnisse der Betroffenen aufgezeigt als auch die Hilfen und Möglichkeiten dargelegt, mit der Krankheit umzugehen. | Center for Advanced Studies: 17.01.2012 | Referentin: Heike von Lützau-Hohlbein | Moderation: Prof. Christian Haass

Wolfgang Enard, a junior group leader at the Max-Planck Institute for Evolutionary Anthropology in Leipzig, Germany, investigates the genetic and molecular basis of human speech. He uses a mouse model to explore language evolution in humans. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 23226]

Wolfgang Enard, a junior group leader at the Max-Planck Institute for Evolutionary Anthropology in Leipzig, Germany, investigates the genetic and molecular basis of human speech. He uses a mouse model to explore language evolution in humans. Series: "CARTA - Center for Academic Research and Training in Anthropogeny" [Science] [Show ID: 23226]

Eukaryotic nuclear transcription is carried out by three different Polymerases (Pol), Pol I, Pol II and Pol III. Among these, Pol I is dedicated to transcription of the rRNA, which is the first step of ribosome biogenesis, and cell growth is regulated during Pol I transcription initiation by the conserved factor Rrn3/TIF-IA in yeast/human. A wealth of structural information is available on Pol II and its general transcription factors (GTFs). Recently, also the architectures of Pol I and Pol III have been described by electron microscopy and the additional subunits that are specific to Pol I and Pol III have been identified as orthologs of the Pol II transcription factors TFIIF and TFIIE. Nevertheless, we still lack information about the architecture of the Pol I initiation complex and structural data is missing explaining the regulation of Pol I initiation mediated by its central transcription initiation factor Rrn3. The Rrn3 structure solved in this study reveals a unique HEAT repeat fold and indicates dimerization of Rrn3 in solution. However, the Rrn3-dimer is disrupted upon Pol I binding. The Rrn3 structure further displays a surface serine patch. Phosphorylation of this patch represses human Pol I transcription (Mayer et al, 2005; Mayer et al, 2004), and a phospho-mimetic patch mutation prevents Rrn3 binding to Pol I in vitro, and reduces S. cerevisiae cell growth and Pol I gene occupancy in vivo. This demonstrates a conserved regulation mechanism of the Pol I-Rrn3 interaction. Crosslinking indicates that Rrn3 does not only interact with Pol I subunits A43/14, but the interface further extends past the RNA exit tunnel and dock domain to AC40/19. The corresponding region of Pol II binds the Mediator head (Soutourina et al., 2011) that co-operates with TFIIB (Baek et al, 2006). Consistent with this, the Rrn3 binding partner, core factor subunit Rrn7, is predicted to be a TFIIB homologue. Taken together, our results provide the molecular basis of Rrn3-regulated Pol I initiation and cell growth and indicate a universally conserved architecture of eukaryotic transcription initiation complexes.

The recent advances in our understanding of the molecular biology of neurodegenerative diseases have been paralleled (and indeed preceded) by a growing recognition that different forms of neurodegeneration are associated with characteristic patterns of cognitive dysfunction. In his presentation Thomas Bak will focus on different types of language impairment seen in neurodegeneration and its relationship not only to other cognitive but also motor functions. He will argue that a more subtle analysis of language deficits is not only essential for diagnosis and treatment, but can also offer insights into the very nature of neurodegenerative processes. | Center for Advanced Studies: 02.11.2011 | Speaker: Dr. Thomas Bak | Moderation: Prof. Adrian Danek

Topic I Molecular basis of RNA polymerase III transcription repression by Maf1 RNA polymerase III (RNAP III) is a conserved 17-subunit enzyme that transcribes genes encoding short untranslated RNAs such as transfer RNAs (tRNAs) and 5S ribosomal RNA (rRNA). These genes are essential and involved in fundamental processes like protein biogenesis; hence RNAP III activity needs to be tightly regulated. RNAP III is repressed upon stress and this is regulated by Maf1, a protein conserved from yeast to humans. Many stress pathways were shown to converge on Maf1 and result in its phosphorylation, followed by its nuclear import and eventual repression of RNAP III activity. However, the molecular mechanisms of this repression activity were not known at the beginning of these studies. This work establishes the mechanism of RNAP III specific transcription repression by Maf1. The crystal structure of Maf1 was solved. It has a globular fold with surface accessible NLS sequences, which sheds new light on already published results and explains how stress-induced phopshorylation leads to import of Maf1 into the nucleus. Additionally, cryo EM studies and competition assays show that Maf1 binds RNAP III at its clamp domain and thereby induces structural rearrangements of RNAP III, which inhibits the interaction with Brf1, a subunit of the transcription initiation factor TFIIIB. This specifically impairs recruitment of RNAP III to its promoters and implies that Maf1 is a repressor of transcription initiation. Competition and transcription assays show that Maf1 also binds RNAP III that is engaged in transcription, leaving RNAP III activity intact but preventing re-initiation. Topic II Structure of human mitochondrial RNA polymerase The nuclear-encoded human mitochondrial RNAP (mitoRNAP) transcribes the mitochondrial genome, which encodes rRNA, tRNAs and mRNAs. MitoRNAP is a single subunit (ss) polymerase, related to T7 bacteriophage and chloroplast polymerases. All share a conserved C-terminal core, whereas the N-terminal parts of mitoRNAP do not show any homology to other ss RNAPs. Unlike phage RNAPs, which are self-sufficient, human mitoRNAP needs two essential transcription factors for initiation, TFAM and TFB2M. Both of these factors are likely to control the major steps of transcription initiation, promoter binding and melting. Thus human mitoRNAP has evolved a different mechanism for transcription initiation and exhibits a unique transcription system. Structural studies thus far concentrated on the nuclear enzymes or phage RNAPs, whereas the structure of mitochondrial RNA polymerase remained unknown. The structural organization of human mitoRNAP and the molecular mechanisms of promoter recognition, binding and melting were subject of interest in these studies. In this work the crystal structure of human mitoRNAP was solved at 2.4 Å resolution and reveals a T7-like C-terminal catalytic domain, a N-terminal domain that remotely resembles the T7 promoter-binding domain (PBD), a novel pentatricopeptide repeat (PPR) domain, and a flexible N-terminal extension. MitoRNAP specific adaptions in the N-terminus include the sequestering of one of the key promoter binding elements in T7 RNAP, the AT-rich recognition loop, by the PPR domain. This sequestration and repositioning of the N-terminal domain explain the need for the additional initiation factor TFAM. The highly conserved active site within the C-terminal core was observed to bind a sulphate ion, a well known phosphate mimic, and thereby suggests conserved substrate binding and selection mechanisms between ss RNAPs. However, conformational changes of the active site were observed due to a movement of the adjacent fingers subdomain. The structure reveals a clenching of the active site by a repositioned fingers subdomain and an alternative position of the intercalating -hairpin. This explains why the conserved transcription factor TFB2M is required for promoter melting and initiation. A model of the mitochondrial initiation complex was build to further explore the initiation mechanism, and to rationalize the available biochemical and genetic data. The structure of mitoRNAP shows how this enzyme uses mechanisms for transcription initiation that differ from those used by phage and cellular RNAPs, and which may have enabled regulation of mitochondrial gene transcription and adaptation of mitochondrial function to changes in the environment.

Die höhere Lebenserwartung der Menschen in Industrieländern geht mit einem Anstieg altersbedingter Krankheiten einher. Hierbei spielen neurodegenerative Erkrankungen wie Alzheimer, Parkinson, Frontotemporale Demenz, Chorea Huntington und Prionerkrankungen eine große Rolle. Dies hat sowohl wirtschaftliche als auch soziale Folgen für die Gesellschaft und ist schon jetzt eine große Belastung für die Gesundheitssysteme. Im Forschungsschwerpunkt "Dementia in Society" sollen die Erkenntnisse der Grundlagen- und klinischen Forschung zu neurodegenerativen Erkrankungen mit sozial- und geisteswissenschaftlichen Analysen einer zunehmend alternden Gesellschaft vermittelt werden. An den Schnittstellen üblicherweise separierter fachwissenschaftlicher Debatten sollen interdisziplinäre Gespräche geführt werden und so nicht nur der Austausch zwischen den Natur- bzw. Sozial- und Geisteswissenschaften, sondern auch der Austausch zwischen Grundlagen-forschung und angewandter Medizin in diesem Feld gefördert und gestärkt werden. | Center for Advanced Studies: 04.07.2011 | Referenten: Prof. Christian Haass, Prof. Hans Förstl, Prof. Monika Reichert | Moderation: Dr. Jeanne Rubner

Wed, 12 May 2010 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/11520/ https://edoc.ub.uni-muenchen.de/11520/1/Wenter_Roland.pdf Wenter, Roland ddc:570, ddc:500, Fakultät für Biol

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RNA polymerase II (Pol II) is the eukaryotic enzyme responsible for transcribing all protein-coding genes into messenger RNA (mRNA). This thesis describes studies on the molecular mechanisms of Pol II translocation, alpha-amanitin inhibition and DNA lesion recognition by Pol II. To study how Pol II translocates after nucleotide incorporation, we prepared elongation complex (EC) crystals in which pre- and post-translocation states interconvert. Crystal soaking with the inhibitor alpha-amanitin locked the EC in a new state that we identified as a translocation intermediate at 3.4 Å resolution. The DNA base entering the active site occupies a “pre-templating” position above the central bridge helix, which is shifted and occludes the standard templating position. A leucine residue in the trigger loop forms a wedge next to the shifted bridge helix, but moves by 13 Å to close the active site for nucleotide incorporation. Our results support a Brownian ratchet mechanism of elongation that involves swinging of the trigger loop between open, wedged, and closed positions, and suggest that alpha-amanitin impairs nucleotide incorporation and translocation by trapping the trigger loop and bridge helix in a translocation intermediate. Cells use transcription-coupled repair (TCR) to efficiently eliminate DNA lesions such as UV-induced cyclobutane pyrimidine dimers (CPDs). Here we present the structure-based mechanism for the first step in eukaryotic TCR, CPD-induced stalling of Pol II. A CPD in the transcribed strand slowly passes a translocation barrier, and enters the polymerase active site. The CPD 5’-thymine then directs uridine monophosphate (UMP) misincorporation into mRNA, which blocks translocation. Artificial replacement of the UMP by adenosine monophosphate (AMP) enables CPD bypass, thus Pol II stalling requires CPD-directed misincorporation. In the stalled complex, the lesion is inaccessible, and the polymerase conformation is unchanged. This is consistent with non-allosteric recruitment of repair factors and excision of a lesion-containing DNA fragment in the presence of Pol II. CPD recognition is compared with the recognition of a cisplatin-induced guanine-guanine intrastrand crosslink. Similarities and differences in the detailed mechanism of transcriptional stalling at the two different dinucleotide lesions are discussed.

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Sun, 1 Jan 1989 12:00:00 +0100 https://epub.ub.uni-muenchen.de/8584/1/8584.pdf Scriba, Peter Christian; Heesemann, Jürgen; Franke, T. F.; Wenzel, B. E.

The murine cytomegalovirus protein pp89, which is encoded by gene ieI, is a nonstructural regulatory protein expressed in the immediate-early phase of the viral replication cycle and located mainly in the nucleus of infected cells. Protection of BALB/c (H-2d) mice against a lethal murine cytomegalovirus challenge infection is achieved by vaccination with a recombinant vaccinia virus, MCMV-ieI-VAC, expressing pp89 as the only murine cytomegalovirus gene product. The protection is entirely mediated by T lymphocytes of the CD8+ subset. In the present report, we analyzed the molecular basis of the recognition of pp89 by BALB/c CD8+ cytolytic T lymphocytes. A series of internal and terminal deletion mutants of gene ieI was constructed and cloned in vaccinia virus, and the antigenicity and immunogenicity of the fragments of pp89 expressed by the recombinants were studied. A region of only one-sixth of the protein, from amino acids 154 to 249 and encoded by the fourth exon of gene ieI, was sufficient for both the recognition in vitro of the protein by pp89-specific cytotoxic T lymphocytes and the induction in vivo of pp89-specific cytotoxic T lymphocytes. By using synthetic peptides, the sequence between residues 161 and 179, which is located within the defined domain, was identified as an epitope presented to BALB/C cytotoxic T lymphocytes by the class I major histocompatibility antigen Ld.

Wed, 1 Jan 1986 12:00:00 +0100 http://epub.ub.uni-muenchen.de/3220/ http://epub.ub.uni-muenchen.de/3220/1/3220.pdf Schütz, Günther; Schmid, Wolfgang; Jantzen, M.; Danesch, U.; Gloss, Bernd; Strähle, Uwe; Becker, Peter B.; Boshart, Michael Schütz, Günther; Schmid, Wolfgang; Jantzen, M.; Danesch, U.; Gloss, Bernd; Strähle, Uwe; Becker, Peter B. und Boshart, Michael (1986): Molecular basis for the hormonal regulation of the tyrosine aminotransferase and tryptophane oxygenase genes. In: ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, Vol. 478: pp. 93-10.

Wed, 1 Jan 1986 12:00:00 +0100 https://epub.ub.uni-muenchen.de/7529/1/Peter_becker_7529.pdf Boshart, Michael; Becker, Peter B.; Strähle, Uwe; Gloss, Bernd; Danesch, U.; Schmid, Wolfgang; Schütz, Günther

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