Podcasts about Caenorhabditis

A l'occasion de la Journée Mondiale de la Vie Sauvage, le 3 mars, BSG rediffuse cette série avec Philippe Grandcolas. Philippe Grandcolas est biologiste, et l'auteur du “Sourire du pangolin” (CNRS Éditions / oct 2021), un ouvrage dans lequel il nous invite à méditer sur notre rapport au Vivant.Les sciences du vivant ont apporté quantité de connaissances extraordinaires grâce à l'étude de quelques organismes en laboratoire. Ce sont les “organismes modèles”, censés représenter l'ensemble du vivant. Ceux qui permettent de comprendre des lois générales de l'hérédité, du fonctionnement des organismes.  Environ 1000 espèces sont de tels modèles :Pour les vers, le favori des généticiens est Caenorhabditis elegans. Ce petit ver transparent d'1 mm, est un nématode mangeur de bactéries du sol. Il vit 20 jours, peut se reproduire 3 jours après son éclosion. Son corps comporte un nombre fixe de cellules, environ 1000. C'est le premier animal dont le génome a été entièrement séquencé en 1998.Pour les insectes, la superstar des labos est la Drosophile (Mouche du vinaigre) représentant les insectes.Pour les plantes, c'est l'Arabette des dames (une petite plante de la famille des Brassicacées, comme le Chou etc …).Le Poisson-zèbre et ses embryons transparents sont les favoris chez les poissons.Et vous connaissez tous Madame Souris blanche chez les mammifères.1000 espèces modèles seulement parmi plus de 2 millions d'espèces connues, c'est à la fois beaucoup et très peu. Beaucoup pour comprendre en profondeur les mécanismes généraux du Vivant et les transposer à l'espèce humaine. Trop peu pour gérer l'environnement et vivre en harmonie avec la nature. Que savons-nous des autres espèces au final, de toutes ces baleines sous les gravillons ?_______ 

BUFFALO, NY- January 7, 2025 – A new #research perspective was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 22 on December 9, 2024, entitled “Nuclear lipid droplets: a novel regulator of nuclear homeostasis and ageing.” In this article, Dr. Konstantinos Palikaras from the National and Kapodistrian University of Athens and Dr. Nektarios Tavernarakis from the University of Crete explore how tiny fat droplets, known as nuclear lipid droplets (nLDs), accumulate in the nucleus of cells as we age. Unlike regular lipid droplets, which store energy in the cytoplasm, these nuclear droplets may weaken the nucleus by disrupting critical cellular processes. The authors suggest that excessive buildup of nLDs could lead to nuclear instability and may be linked to metabolic conditions such as fatty liver disease, obesity-related disorders, and premature aging. This highlights the potential role of nLDs in cellular aging and age-related diseases. Previous research by the authors using Caenorhabditis elegans (C. elegans), a model organism commonly used to study aging, revealed the role of ATGL-1, an enzyme that regulates fat storage in the nucleus. When functioning properly, ATGL-1 helps maintain a healthy lipid balance. However, when it becomes inactive or overwhelmed, fat droplets build up around the nuclear lamina, making it more difficult for the cell to function properly. “These findings establish excessive nuclear lipid deposition as a key hallmark of aging, with profound implications for nuclear processes such as chromatin organization, DNA repair, and gene regulation.” The authors emphasize that lifestyle interventions, such as caloric restriction and better insulin regulation, can significantly reduce harmful nLD buildup, reinforcing the role of healthy metabolism in slowing cellular aging. They also call for further studies to understand how nLDs behave in human experimental models, particularly in patients with conditions like metabolic syndrome and progeria. A deeper understanding of these processes could lead to treatments designed to preserve cell health and delay age-related diseases. In summary, by presenting nuclear lipid droplets as potential therapeutic targets, this research perspective presents a new path for exploring treatments aimed at combating age-related diseases driven by lipid dysregulation. DOI - https://doi.org/10.18632/aging.206175 Corresponding authors - Konstantinos Palikaras - palikarask@med.uoa.gr, and Nektarios Tavernarakis - tavernarakis@imbb.forth.gr Video short - https://www.youtube.com/watch?v=vuSLuDk8Xjk Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206175 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, ATGL-1, HLH-30/TFEB, lipid droplet, non-linear optical phenomena, nucleus About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) Please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Hoy celebramos al gusano más famoso del mundo, la Beyonce del mundo de los gusanos: Caenorhabditis elegans. Este animalillo es uno de los modelos más usados en la ciencia, ha ayudado a muchos investigadores a ganar el premio Nobel y ha ido varias veces al espacio a ver qué onda por allá. Aquí les vamos a platicar por qué es tan buen animal modelo, sobre algunos de los avances de la ciencia relacionados con él, incluyendo el Nobel 2024 de los micro ARN y otros Nobel anteriores y sobre si sufren o no en algunos experimentos. En el pilón para nuestros Patreons hablaremos de los experimentos con proteína verde fluorescente y C. elegans que cambiaron el mundo de los diagnósticos. Visiten patreon.com/mandarax para poder escucharlo. Learn more about your ad choices. Visit megaphone.fm/adchoices

BUFFALO, NY- April 23, 2024 – A new #researchpaper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 7, entitled, “The coupling between healthspan and lifespan in Caenorhabditis depends on complex interactions between compound intervention and genetic background.” Aging is characterized by declining health that results in decreased cellular resilience and neuromuscular function. The relationship between lifespan and health, and the influence of genetic background on that relationship, has important implications in the development of pharmacological anti-aging interventions. In this new study, researchers Stephen A. Banse, E. Grace Jackson, Christine A. Sedore, Brian Onken, David Hall, Anna Coleman-Hulbert, Phu Huynh, Theo Garrett, Erik Johnson, Girish Harinath, Delaney Inman, Suzhen Guo, Mackenzie Morshead, Jian Xue, Ron Falkowski, Esteban Chen, Christopher Herrera, Allie J. Kirsch, Viviana I. Perez, Max Guo, Gordon J. Lithgow, Monica Driscoll, and Patrick C. Phillips from the University of Oregon, The State University of New Jersey (Rutgers), The Buck Institute for Research on Aging, and National Institute on Aging assessed swimming performance as well as survival under thermal and oxidative stress across a nematode genetic diversity test panel to evaluate health effects for three compounds previously studied in the Caenorhabditis Intervention Testing Program and thought to promote longevity in different ways – NP1 (nitrophenyl piperazine-containing compound 1), propyl gallate, and resveratrol. “Overall, we find the relationships among median lifespan, oxidative stress resistance, thermotolerance, and mobility vigor to be complex.” The researchers showed that oxidative stress resistance and thermotolerance vary with compound intervention, genetic background, and age. The effects of tested compounds on swimming locomotion, in contrast, are largely species-specific. In this study, thermotolerance, but not oxidative stress or swimming ability, correlates with lifespan. Notably, some compounds exert strong impact on some health measures without an equally strong impact on lifespan. “Our results demonstrate the importance of assessing health and lifespan across genetic backgrounds in the effort to identify reproducible anti-aging interventions, with data underscoring how personalized treatments might be required to optimize health benefits.” DOI - https://doi.org/10.18632/aging.205743 Corresponding authors - Gordon J. Lithgow - glithgow@buckinstitute.org, Monica Driscoll - driscoll@dls.rutgers.edu, and Patrick C. Phillips - pphil@uoregon.edu About Aging-US Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer's diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases. Please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

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  For the first time ever, parents going through IVF can use whole genome sequencing to screen their embryos for hundreds of conditions. Harness the power of genetics to keep your family safe, with Orchid. Check them out at orchidhealth.com. Today Razib talks to geneticist Erich Schwarz, a Research Professor in the Department of Molecular Biology and Genetics at Cornell University  since 2012. Schwarz has a molecular biology degree from Harvard and a Ph.D. from Caltech. After working with the fruit fly Drosophila melanogaster in graduate school, he switched to the nematode Caenorhabditis elegans, and has continued studying nematodes ever since. After helping to found the C. elegans genome database WormBase (wormbase.org) in the early 2000s, he began sequencing and characterizing the genomes of several nematode worms other than C. elegans, either because they are biologically informative or because they are worldwide parasites. His current work includes using the genome of Ancylostoma ceylanicum to help devise an anti-hookworm vaccine. Schwarz explains why C. elegans, often called “the worm,” has been so useful in developmental and molecular genetics, and its role in the career of the late Nobel laureate Sydney Brenner. With a simple anatomical structure, every single one of the 1,000 cells of  C. elegans has been mapped and detailed. Despite its small size, this organism has spawned a research community of thousands, documented in Andrew Brown's In the Beginning Was the Worm: Finding the Secrets of Life in a Tiny Hermaphrodite. In the age of hundreds of thousands of human genomes, Schwarz explains the decades-long period in the late 20th century when biological research was dominated by “model organisms,” simple and easy-to-experiment-on animals, plants and bacteria that could eloquently and plainly elucidate universal and essential mechanisms of function and structure.  Razib and Schwarz also discuss the future of model organisms in a genomic future, when high-throughput data analysis can supercharge decades-long experimental projects. Ultimately, the future is not likely to see model organisms set aside, but rather to witness them merged into the broader research community in human and medical genomics which has been driving technological changes in sppedspeed and volume of data collection.

Rick Betzel is an Associate professor at India University Bloomington. We talk about his research on network neuroscience, how to find good collaborators, Rick's path to network neuroscience, and much more.Support the show: https://geni.us/bjks-patreonTimestamps0:00:00: What's the purpose of connectomics if understanding a species' entire connectome (as in C elegans) doesn't allow us to fully understand its behaviour?0:03:57: Rick's very very linear path to network neuroscience0:19:41: Multi-scale brain networks0:43:40: Collaborations (between people who collect data and people who analyse data)0:52:33: The future of network neuroscience: generative modeling, network control, and edge-centric connectomics1:13:15: A book or paper more people should read1:15:55: Something Rick wishes he'd learnt sooner1:18:01: Advice for PhD students/postdocsPodcast linksWebsite: https://geni.us/bjks-podTwitter: https://geni.us/bjks-pod-twtRick's linksWebsite: https://geni.us/betzel-webGoogle Scholar: https://geni.us/betzel-scholarTwitter: https://geni.us/betzel-twtBen's linksWebsite: https://geni.us/bjks-webGoogle Scholar: https://geni.us/bjks-scholarTwitter: https://geni.us/bjks-twtReferencesAkarca ... (2021). A generative network model of neurodevelopmental diversity in structural brain organization. Nat Comm.Barabási (2003). Linked.Barabási & Albert (1999). Emergence of scaling in random networks. Science.Betzel (2022). Network neuroscience and the connectomics revolution. In Connectomic deep brain stimulation.Betzel & Bassett (2017). Multi-scale brain networks. Neuroimage.Betzel & Bassett (2017). Generative models for network neuroscience: prospects and promise. Journal of The Royal Society Interface.Betzel ... (2012). Synchronization dynamics and evidence for a repertoire of network states in resting EEG. Front comp neuro.Bullmore & Sporns (2009). Complex brain networks: graph theoretical analysis of structural and functional systems. Nat Rev Neuro.Cook ... (2019). Whole-animal connectomes of both Caenorhabditis elegans sexes. Nature.Feltner & Dapena (1986). Dynamics of the shoulder and elbow joints of the throwing arm during a baseball pitch. J Appl Biomech.Lindsay (2021). Models of the mind.Nieminen ... (2022). Multi-locus transcranial magnetic stimulation system for electronically targeted brain stimulation. Brain stimulation.Oh ... (2014). A mesoscale connectome of the mouse brain. Nature.Rubinov & Sporns (2010). Complex network measures of brain connectivity: uses and interpretations. Neuroimage.Scheffer ... (2020). A connectome and analysis of the adult Drosophila central brain. Elife.Sporns (2016). Networks of the Brain.Van Den Heuvel & Sporns (2011). Rich-club organization of the human connectome. J Neuro.Watts & Strogatz (1998). Collective dynamics of ‘small-world'networks. Nature.White ... (1986). The structure of the nervous system of the nematode Caenorhabditis elegans. Philos Trans R Soc Lond B.Winding ... (2023). The connectome of an insect brain. Science.Yan ... (2017). Network control principles predict neuron function in the Caenorhabditis elegans connectome. Nature. 

BUFFALO, NY- November 22, 2023 – A new #researchpaper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 21, entitled, “Antibiotics that target mitochondria extend lifespan in C. elegans.” Aging is a continuous degenerative process caused by a progressive decline of cell and tissue functions in an organism. It is induced by the accumulation of damage that affects normal cellular processes, ultimately leading to cell death. It has been speculated for many years that mitochondria play a key role in the aging process. In this new study, researchers Gloria Bonuccelli, Darren R. Brooks, Sally Shepherd, Federica Sotgia, and Michael P. Lisanti from the University of Salford aimed to characterize the implications of mitochondria in aging using Caenorhabditis elegans (C. elegans) as an organismal model. The C. elegans were treated with a panel of mitochondrial inhibitors and assessed for survival. “In our study, we assessed survival by evaluating worm lifespan, and we assessed aging markers by evaluating the pharyngeal muscle contraction, the accumulation of lipofuscin pigment and ATP levels.” Their results show that treatment of worms with either doxycycline, azithromycin (inhibitors of the small and the large mitochondrial ribosomes, respectively), or a combination of both, significantly extended median lifespan of C. elegans, enhanced their pharyngeal pumping rate, reduced their lipofuscin content and their energy consumption (ATP levels), as compared to control untreated worms, suggesting an aging-abrogating effect for these drugs. Similarly, DPI, an inhibitor of mitochondrial complex I and II, was capable of prolonging the median lifespan of treated worms. On the other hand, subjecting worms to vitamin C, a pro-oxidant, failed to extend C. elegans lifespan and upregulated its energy consumption, revealing an increase in ATP level. “Therefore, our longevity study reveals that mitochondrial inhibitors (i.e., mitochondria-targeting antibiotics) could abrogate aging and extend lifespan in C. elegans.” DOI - https://doi.org/10.18632/aging.205229 Corresponding authors - Michael P. Lisanti - m.p.lisanti@salford.ac.uk, and Federica Sotgia - f.sotgia@salford.ac.uk Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205229 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, C. elegans, lifespan, lipofuscin, antibiotics, mitochondria, metabolism, DPI About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY- November 16, 2023 – A new #researchpaper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 21, entitled, “Parental age effect on the longevity and healthspan in Drosophila melanogaster and Caenorhabditis elegans.” Several studies have investigated the effect of parental age on biological parameters such as reproduction, lifespan, and health; however, the results have been inconclusive, largely due to inter-species variation and/or modest effect sizes. In their new study, researchers Camille Lenzi, Alexis Piat, Pascal Schlich, Judith Ducau, Jean-Claude Bregliano, Hugo Aguilaniu, and Anne Laurençon from the IM Projet, Caduceum, INRAE, IBDM, Instituto Serrapilheira, and Universite Claude Bernard-Lyon 1 examined the effect of parental age on the lifespan, reproductive capacity, and locomotor activity of genetic isogenic lines of the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster. “We decided to investigate parental age impact on the lifespan of their progeny on selected genomes of flies and worms to gain insights on the molecular mechanisms at work.” The researchers found that the progeny of successive generations of old parents had significantly shorter lifespans than the progeny of young parents in both species. Moreover, they investigated the fertility, fecundity, and locomotor activity of C. elegans. Interestingly, both the shorter lifespan and deteriorated healthspan of the progeny were significantly improved by switching to only one generation of younger parents. “Collectively, these data demonstrate that the detrimental effect of older parental age on the longevity of the progeny can be reversed, suggesting the existence of a beneficial non–genetic mechanism.” DOI - https://doi.org/10.18632/aging.205098 Corresponding author - Anne Laurençon - anne.laurencon@ens-lyon.fr Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205098 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, life span, intergenerational plasticity, maternal effect, nematode, drosophila About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

David Dalrymple, with a background from MIT and Harvard, is known for his study on Caenorhabditis elegans' nervous system, featured in Nature Methods. At Oxford University, his work spans neuroinformatics, machine learning, and software engineering. He is also a co-inventor of Filecoin.Key HighlightsA 10-year plan for brain uploading, dismissing certain techniques like neural dust, while highlighting expansion microscopy and immunofluorescence as promising.The use of AI for parameter estimation from destructive imaging, with a focus on automation for scalability.Validation techniques involving human brain slices and the application of advanced imaging and experimental methods.The challenges of dense brain data transfer and the potential solutions through mapping algorithms and axon tracing.Dive deeper into the session: Full SummaryAbout Foresight InstituteForesight Institute is a research organization and non-profit that supports the beneficial development of high-impact technologies. Since our founding in 1987 on a vision of guiding powerful technologies, we have continued to evolve into a many-armed organization that focuses on several fields of science and technology that are too ambitious for legacy institutions to support.Allison DuettmannThe President and CEO of Foresight Institute, Allison Duettmann directs the Intelligent Cooperation, Molecular Machines, Biotech & Health Extension, Neurotech, and Space Programs, alongside Fellowships, Prizes, and Tech Trees. She has also been pivotal in co-initiating the Longevity Prize, pioneering initiatives like Existentialhope.com, and contributing to notable works like "Superintelligence: Coordination & Strategy" and "Gaming the Future".Get Involved with Foresight:Apply: Virtual Salons & in-person WorkshopsDonate: Support Our Work – If you enjoy what we do, please consider this, as we are entirely funded by your donations!Follow Us: Twitter | Facebook | LinkedInNote: Explore every word spoken on this podcast through Fathom.fm, an innovative podcast search engine. Hosted on Acast. See acast.com/privacy for more information.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.21.549990v1?rss=1 Authors: Fujii, K., Kondo, T., Kimura, A. Abstract: The centrosome is a major microtubule-organizing center in animal cells. The intracellular positioning of the centrosomes is important for proper cellular function. One of the features of centrosome positioning is the spacing between centrosomes. The spacing activity is mediated by microtubules extending from the centrosomes; however, the underlying mechanisms are not fully understood. To characterize the spacing activity in the Caenorhabditis elegans embryo, a genetic setup was developed to produce enucleated embryos. The centrosome duplicated multiple times in the enucleated embryo, which enabled us to characterize the chromosome-independent spacing activity between sister and non-sister centrosome pairs. We knocked down genes in the enucleated embryo and found that the timely spacing was dependent on cytoplasmic dynein. Based on these results, we propose a stoichiometric model of cortical and cytoplasmic pulling forces for the spacing between centrosomes. We also found a dynein-independent but non-muscle myosin II-dependent movement of the centrosomes in a later cell cycle phase. The dynein-dependent spacing mechanisms for positioning the centrosomes revealed in this study is likely functioning in the cell with nucleus and chromosomes, including the processes of centrosome separation and spindle elongation. 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/2023.07.20.548338v1?rss=1 Authors: Li, M., Wang, Y., Wei, X., Cai, W.-F., Zhu, M., Yao, L., Wang, Y., Liu, Y.-H., Wu, J., Xiong, J., Tian, X., Qu, Q., Xie, R., Li, X., Chen, S., Huang, X., Zhang, C., Xie, C., Wu, Y., Xu, Z., Zhang, B., Jiang, B., Yu, Y., Wang, Z.-C., Li, Q., Li, G., Lin, S.-Y., Yu, L., Piao, H.-l., Deng, X., Zhang, C.-S., Lin, S.-C. Abstract: The shift of carbon utilisation from glucose to other nutrients is a fundamental metabolic adaptation to cope with the decreased glucose oxidation during fasting or starvation. AMP-activated protein kinase (AMPK) plays crucial roles in manifesting physiological benefits accompanying glucose starvation or calorie restriction. However, the underlying mechanisms are unclear. Here, we show that low glucose-induced activation of AMPK plays a decisive role in the shift of carbon utilisation from glucose to glutamine. We demonstrate that endoplasmic reticulum (ER)-localised PDZD8, which we identify to be a new substrate of AMPK, is required for the glucose starvation-promoted glutaminolysis. AMPK phosphorylates PDZD8 at threonine 527 (T527), and promotes it to interact with and activate the mitochondrial glutaminase 1 (GLS1), a rate-limiting enzyme of glutaminolysis, and as a result the ER-mitochondria contact is strengthened. In vivo, PDZD8 enhances glutaminolysis, and triggers mitohormesis that is required for extension of lifespan and healthspan in Caenorhabditis elegans subjected to glucose starvation or caloric restriction. Muscle-specific re-introduction of wildtype PDZD8, but not the AMPK-unphosphorylable PDZD8-T527A mutant, to PDZD8-/- mice is able to rescue the increase of glutaminolysis, and the rejuvenating effects of caloric restriction in aged mice, including grip strength and running capacity. Together, these findings reveal an AMPK-PDZD8-GLS1 axis that promotes glutaminolysis and executes the anti-ageing effects of calorie restriction by promoting inter-organelle crosstalk between ER and mitochondria. 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/2023.07.19.549777v1?rss=1 Authors: Parvand, M., Liang, J. J., Bozorgmehr, T., Born, D., Luna Cortes, A., Rankin, C. H. Abstract: Mutations in the presenilin (PS) genes are a predominant cause of familial Alzheimers disease (fAD). An ortholog of PS in the genetic model organism Caenorhabditis elegans (C. elegans) is sel-12. Mutations in the presenilin genes are commonly thought to lead to fAD by upregulating the expression of amyloid beta (Ab), however this hypothesis has been challenged by recent evidence. As C. elegans lack amyloid beta (Ab), the goal of this work was to examine Ab-independent effects of mutations in sel-12 and PS1/PS2 on behaviour and sensory neuron morphology across the lifespan in a C. elegans model. Olfactory chemotaxis experiments were conducted on sel-12(ok2078) loss-of-function mutant worms. Adult sel-12 mutant worms showed significantly lower levels of chemotaxis to odorants compared to wild-type worms throughout their lifespan, and this deficit increased with age. The chemotaxis phenotype in sel-12 mutant worms is rescued by transgenic over-expression of human wild-type PS1, but not the classic fAD-associated variant PS1C410Y, when expression was driven by either the endogenous sel-12 promoter (Psel-12), a pan-neuronal promoter (Primb-1), or by a promoter whose primary expression was in the sensory neurons responsible for the chemotaxis behavior (Psra-6, Podr-10). The behavioural phenotype was also rescued by over-expressing an atypical fAD-linked mutation in PS1 (PS1?S169) that has been reported to leave the Notch pathway intact. An examination of the morphology of polymodal nocieptive (ASH) neurons responsible for the chemotaxis behavior also showed increased neurodegeneration over time in sel-12 mutant worms that could be rescued by the same transgenes that rescued the behaviour, demonstrating a parallel with the observed behavioral deficits. Thus, we report an Ab-independent neurodegeneration in C. elegans that was rescued by cell specific over-expression of wild-type human presenilin. 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/2023.07.15.549072v1?rss=1 Authors: Boor, S. A., Meisel, J. D., Kim, D. H. Abstract: Animal internal state is modulated by nutrient intake, resulting in behavioral responses to changing food conditions. DAF-7 is a neuroendocrine TGF-beta ligand that regulates diverse food-related behaviors of Caenorhabditis elegans, including foraging behavior. Here, we show that in C. elegans, interoceptive cues from the ingestion of bacterial food inhibit the expression of DAF-7, a neuroendocrine TGF-beta ligand, from the ASJ pair of sensory neurons, whereas food deprivation in the presence of external chemosensory cues from bacteria promotes the expression of DAF-7 from the ASJ neurons. We show that SCD-2, the C. elegans ortholog of mammalian Anaplastic Lymphoma Kinase (ALK), which has been implicated in the central control of metabolism of mammals, functions in the AIA interneurons to regulate foraging behavior and cell-non-autonomously control the expression of DAF-7 from the ASJ neurons. Our data establish an SCD-2-dependent neuroendocrine DAF-7 gene expression feedback loop that couples the ingestion of bacterial food to foraging behavior. 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/2023.07.10.548405v1?rss=1 Authors: Schwartz, A. Z., Abdu, Y., Nance, J. Abstract: Rapid and conditional protein depletion is the gold standard genetic tool for deciphering the molecular basis of developmental processes. Previously, we showed that by conditionally expressing the E3 ligase substrate adaptor ZIF-1 in Caenorhabditis elegans somatic cells, proteins tagged with the first CCCH Zn finger (ZF1) domain from the germline regulator PIE-1 degrade rapidly, resulting in loss-of-function phenotypes. The described role of ZIF-1 is to clear PIE-1 and several other CCCH Zn finger proteins from early somatic cells, helping to enrich them in germline precursor cells. Here, we show that proteins tagged with the PIE-1 ZF1 domain are subsequently cleared from primordial germ cells in embryos and from undifferentiated germ cells in larvae and adults by ZIF-1. We harness germline ZIF-1 activity to degrade a ZF1-tagged heterologous protein from PGCs and show that its depletion produces phenotypes equivalent to those of a null mutation. Our findings reveal that ZIF-1 switches roles from degrading CCCH Zn finger proteins in somatic cells to clearing them from undifferentiated germ cells, and that ZIF-1 activity can be harnessed as a new genetic tool to study the early germ line. 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/2023.07.04.547647v1?rss=1 Authors: Amran, A., Pigatto, L., Farley, J., Godini, R., Pocock, R., Gopal, S. Abstract: The extracellular matrix (matrisome) provides chemical and mechanical cues to control the structure and function of cells and tissues. Yet, comprehensive understanding of how matrisome factors individually and collectively control cell and tissue behavior in vivo is lacking. Here, we systematically investigate the function of 443 conserved matrisome-coding genes in controlling germ cell behavior within a complex tissue - the Caenorhabditis elegans germline. Using high-content imaging, 3D reconstruction and cell behavior analysis of greater than 3500 germlines and greater than 7 million germ cells, we identify specific matrisome factors that regulate germline structure, protein distribution, germ cell cycle and fate, apoptosis, and oocyte health. These findings reveal matrisome networks acting autonomously and non-autonomously to coordinate germ cell behavior, providing new avenues to study and manipulate cell fates. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.28.546823v1?rss=1 Authors: Chauve, L., McLysaght, A., McGarry, A., Butler, L. Abstract: Gene duplications play a major evolutionary role by providing raw material for functional innovation. Whole Genome Duplication (WGD), or polyploidization, is a particular case of duplication encompassing the entire genome and has been implicated in evolutionary diversification. In plants, WGD is recognized as a major evolutionary force, and is linked to speciation and the ability to resist periods of stress and of environmental upheaval. In animals, examples of current polyploid species are rarer, but multiple ancient events are known, including the charismatic two rounds (2R) of WGD that occurred during early vertebrate evolution. The conditions favouring the success of polyploid lineages are unclear. One debated hypothesis states that polyploidy is adaptive in the short-term, however this has never been studied in animals. In this study, we investigated the consequences of polyploidy on physiology and stress resistance in Caenorhabditis elegans, where tetraploidy can be artificially constructed. Our results reveal that although tetraploidy reduces fitness by decreasing fertility and lifespan in regular conditions, tetraploid animals exhibit increased resilience under specific stress conditions related to temperature changes. While neotetraploid animals exhibit similar pathogen resistance, their response to heat stress is altered. They exhibit modest improvement in thermotolerance and prolonged hsp (heat shock protein) mRNA induction upon heat shock (HS) accompanied by altered hsp-16.2 nuclear localization upon HS. Most notably, under severe cold stress, gravid neotetraploids animals massively escape cold-induced death, and generate more progeny than diploid animals. These results suggest a potential adaptive value of tetraploidy under cold stress and might help explain recent correlations found between the frequency of extant animal polyploids and regions experiencing recent glaciation and large temperature variation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.25.546476v1?rss=1 Authors: Xie, Z., Chai, Y., Zhu, Z., Shen, Z., Zhao, Z., Xiao, L., Du, Z., Ou, G., Li, W. Abstract: Asymmetric cell divisions (ACDs) generate two daughter cells with identical genetic information but distinct cell fates through epigenetic mechanisms. However, the process of partitioning different epigenetic information into daughter cells remains unclear. Here, we demonstrate that the nucleosome remodeling and deacetylase (NuRD) complex is asymmetrically segregated into the surviving daughter cell rather than the apoptotic one during ACDs in Caenorhabditis elegans. The absence of NuRD triggers apoptosis via the EGL-1-CED-9-CED-4-CED-3 pathway, while an ectopic gain of NuRD enables apoptotic daughter cells to survive. We identify the vacuolar H+-adenosine triphosphatase (V-ATPase) complex as a crucial regulator of NuRD's asymmetric segregation. V-ATPase interacts with NuRD and is asymmetrically segregated into the surviving daughter cell. Inhibition of V-ATPase disrupts cytosolic pH asymmetry and NuRD asymmetry. We suggest that asymmetric segregation of V-ATPase may cause distinct acidification levels in the two daughter cells, enabling asymmetric epigenetic inheritance that specifies their respective life-versus-death fates. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Lead Story: The conserved endocannabinoid anandamide modulates olfactory sensitivity to induce hedonic feeding in C. elegans  Current Biology Laboratory worm Caenorhabditis elegans apparently gets the ‘munchies' when exposed to cannabis. After soaking in an endocannabinoid bath, worms preferred to eat nutrient-rich, rather than nutrient-poor, bacteria. They fed for longer than worms not exposed to endocannabinoid or worms without working endocannabinoid receptors. This shared trait points to the deep evolutionary origin of cannabinoid receptors and behaviors influenced by the molecules. Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

Dr. Björn Schumacher is the Principal Investigator and Chair for Genome Stability in Ageing and Disease at the Institute for Genome Stability in Aging and Disease. His research group uses the nematode worm Caenorhabditis elegans to understand the causal role of DNA damage in aging and disease. The post Dr. Bjorn Schumacher – DNA Repair Mechanisms, Longevity, & DREAM complex – Learning with Lowell 180 first appeared on Learning with Lowell.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.23.537987v1?rss=1 Authors: Bardozzo, F., Terlizzi, A., Lio, P., Tagliaferri, R. Abstract: This research report introduces ElegansNet, a neural network that mimics real-world neuronal network circuitry, with the goal of better understanding the interplay between connectome topology and deep learning systems. The proposed approach utilizes the powerful representational capabilities of living beings' neuronal circuitry to design and generate improved deep learning systems with a topology similar to natural networks. The Caenorhabditis elegans connectome is used as a reference due to its completeness, reasonable size, and functional neuron classes annotations. It is demonstrated that the connectome of simple organisms exhibits specific functional relationships between neurons, and once transformed into learnable tensor networks and integrated into modern architectures, it offers bio-plausible structures that efficiently solve complex tasks. The performance of the models is demonstrated against randomly wired networks and compared to artificial networks ranked on global benchmarks. In the first case, ElegansNet outperforms randomly wired networks. Interestingly, ElegansNet models show slightly similar performance with only those based on the Watts-Strogatz small-world property. When compared to state-of-the-art artificial neural networks, such as transformers or attention-based autoencoders, ElegansNet outperforms well-known deep learning and traditional models in both supervised image classification tasks and unsupervised hand-written digits reconstruction, achieving top-1 accuracy of 99.99% on Cifar10 and 99.84% on MNIST Unsup on the validation sets. 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/2023.04.18.537280v1?rss=1 Authors: Kita, T., Chiba, K., Wang, J., Nakagawa, A., Niwa, S. Abstract: Kinesin-3 is a family of microtubule-dependent motor proteins that transport various cargos within the cell. However, the mechanism underlying kinesin-3 activations remains largely elusive. In this study, we compared the biochemical properties of two Caenorhabditis elegans kinesin-3 family proteins, KLP-6 and UNC-104. Both KLP-6 and UNC-104 are predominantly monomeric in solution. As previously shown for UNC-104, non-processive KLP-6 monomer is converted to a processive motor when artificially dimerized. We present evidence that releasing the autoinhibition is sufficient to trigger dimerization of monomeric UNC-104 at nanomolar concentrations, which results in processive movement of UNC-104 on microtubules, although it has long been thought that enrichment in the phospholipid microdomain on cargo vesicles is required for the dimerization and processive movement of UNC-104. In contrast, KLP-6 remains to be a non-processive monomer even when its autoinhibition is unlocked, suggesting a requirement of other factors for full activation. By examining the differences between KLP-6 and UNC-104, we identified a coiled-coil domain called CC2 that is required for the dimerization and processive movement of UNC-104. Our results suggest a common activation mechanism for kinesin-3 family members, while also highlighting their diversification. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In which Martin Chalfie, a professor of Biological Sciences at Columbia University and Nobel laureate recognized for his contribution to the development of green fluorescent protein (GFP), and Sophia discuss the applications of GFP and his current research on the development and function of touch receptor neurons (TRNs) using the nematode Caenorhabditis elegans. Dr. Chalfie highlights the versatility of GFP as a tool for studying biological processes, including the development and function of neurons. He explains the regulation of TRNs by transcription factors and transduction channels and how studying their development and function can provide insights into sensory perception.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.14.536929v1?rss=1 Authors: Scheer, E., Bargmann, C. Abstract: Foraging animals optimize feeding decisions by adjusting both common and rare behavioral patterns. Here, we characterize the relationship between an animal's arousal state and a rare decision to leave a patch of bacterial food. Using long-term tracking and behavioral state classification, we find that food leaving decisions in Caenorhabditis elegans are coupled to arousal states across multiple timescales. Leaving emerges probabilistically over minutes from the high arousal roaming state, but is suppressed during the low arousal dwelling state. Immediately before leaving, animals have a brief acceleration in speed that appears as a characteristic signature of this behavioral motif. Neuromodulatory mutants and optogenetic manipulations that increase roaming have a coupled increase in leaving rates, and similarly acute manipulations that inhibit feeding induce both roaming and leaving. By contrast, inactivating a set of chemosensory neurons that depend on the cGMP-gated transduction channel TAX-4 uncouples roaming and leaving dynamics. In addition, tax-4-expressing sensory neurons promote leaving behaviors that are elicited by feeding inhibition. Our results indicate that sensory neurons responsive to both internal and external cues play an integrative role in arousal and foraging decisions. 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/2023.04.13.536481v1?rss=1 Authors: Lamberti, M. L., Spangler, R. K., Cerdeira, V., Ares, M., Rivollet, L., Ashley, G. E., Coronado, A. R., Tripathi, S., Spiousas, I., Ward, J. D., Partch, C. L., Benard, C. Y., Goya, M. E., Golombek, D. A. Abstract: Circadian rhythms are endogenous oscillations present in nearly all organisms from prokaryotes to humans, allowing them to adapt to cyclical environments close to 24 hours. Circadian rhythms are regulated by a central clock, which is based on a transcription-translation feedback loop. One important protein in the central loop in metazoan clocks is PERIOD, which is regulated in part by Casein kinase 1{varepsilon}/{delta} (CK1{varepsilon}/{delta}) phosphorylation. In the nematode Caenorhabditis elegans, period and casein kinase 1{varepsilon}/{delta} are conserved as lin-42 and kin-20, respectively. Here we studied the involvement of lin-42 and kin-20 in circadian rhythms of the adult nematode using a bioluminescence-based circadian transcriptional reporter. We show that mutations of lin-42 and kin-20 generate a significantly longer endogenous period, suggesting a role for both genes in the nematode circadian clock, as in other organisms. These phenotypes can be partially rescued by overexpression of either gene under their native promoter. Both proteins are expressed in neurons and seam cells, a population of epidermal stem cells in C. elegans that undergo multiple divisions during development. Depletion of LIN-42 and KIN-20 specifically in neuronal cells after development was sufficient to lengthen the period of oscillating sur-5 expression. Therefore, we conclude that LIN-42 and KIN-20 are critical regulators of the adult nematode circadian clock through neuronal cells. 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/2023.04.09.536174v1?rss=1 Authors: Gregory, E. F., Kalra, S., Brock, T., Bonne, G., Luxton, G. G., Hopkins, C., Starr, D. A. Abstract: Striated muscle laminopathies caused by missense mutations in the nuclear lamin gene LMNA are characterized by cardiac dysfunction and often skeletal muscle defects. Attempts to predict which LMNA variants are pathogenic and to understand their physiological effects lags behind variant discovery. We created Caenorhabditis elegans models for striated muscle laminopathies by introducing pathogenic human LMNA variants and variants of unknown significance at conserved residues within the lmn-1 gene. Severe missense variants reduced fertility and/or motility in C. elegans. Nuclear morphology defects were evident in the hypodermal nuclei of many lamin variant strains, indicating a loss of nuclear envelope integrity. Phenotypic severity varied within the two classes of missense mutations involved in striated muscle disease, but overall, variants associated with both skeletal and cardiac muscle defects in humans lead to more severe phenotypes in our model than variants predicted to disrupt cardiac function alone. We also identified a separation of function allele, lmn-1(R204W), that exhibited normal viability and swimming behavior but had a severe nuclear migration defect. Thus, we established C. elegans avatars for striated muscle laminopathies and identified LMNA variants that offer insight into lamin mechanisms during normal development. 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/2023.04.04.535547v1?rss=1 Authors: Adamo, G., Santonicola, P., Picciotto, S., Gargano, P., Nicosia, A., Longo, V., Aloi, N., Romancino, D. P., Paterna, A., Rao, E., Raccosta, S., Noto, R., Salamone, M., Costa, S., Alfano, C., Zampi, G., Colombo, P., Wei, M., Touzet, N., Manno, M., Di Schiavi, E., Bongiovanni, A. Abstract: Nanoalgosomes are extracellular vesicles (EVs) released by microalgal cells that can mediate intercellular and cross-kingdom communication. In the present study, the optimization of high quality nanoalgosome manufacturing from cultures of the marine microalgae Tetraselmis chuii has been enhanced by quality control procedures, applying robust biophysical and biochemical characterizations. Then, we evaluated the biological properties of nanoalgosomes in pre-clinical models. Our investigation of nanoalgosome biocompatibility included toxicological and genetic analyses, starting from studies on the invertebrate model organism Caenorhabditis elegans and proceeding to hematological and immunological evaluations in mice and human cells. Nanoalgosome biodistribution was evaluated in mice with accurate space-time resolution, and in C. elegans at cellular and subcellular levels. Further examination highlighted the antioxidant and anti-inflammatory bioactivities of nanoalgosomes. This holistic approach to nanoalgosome characterization showcases that nanoalgosomes are innate effectors for novel cosmetic formulations and EV-based therapies. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.02.535296v1?rss=1 Authors: Lee, Y.-T., Savini, M., Chen, T., Yang, J., Zhao, Q., Ding, L., Gao, S. M., Senturk, M., Sowa, J., Wang, J. D., Wang, M. C. Abstract: Healthy mitochondria are critical for reproduction. During aging, both reproductive fitness and mitochondrial homeostasis decline. Mitochondrial metabolism and dynamics are key factors in supporting mitochondrial homeostasis. However, how they are coupled to control reproductive health remains unclear. We report that mitochondrial GTP metabolism acts through mitochondrial dynamics factors to regulate reproductive aging. We discovered that germline-only inactivation of GTP- but not ATP-specific succinyl-CoA synthetase (SCS), promotes reproductive longevity in Caenorhabditis elegans. We further revealed an age-associated increase in mitochondrial clustering surrounding oocyte nuclei, which is attenuated by the GTP-specific SCS inactivation. Germline-only induction of mitochondrial fission factors sufficiently promotes mitochondrial dispersion and reproductive longevity. Moreover, we discovered that bacterial inputs affect mitochondrial GTP and dynamics factors to modulate reproductive aging. These results demonstrate the significance of mitochondrial GTP metabolism in regulating oocyte mitochondrial homeostasis and reproductive longevity and reveal mitochondrial fission induction as an effective strategy to improve reproductive health. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Welcome back to Neurotech Pub! In this first installment of two episodes on Connectomics, host and Paradromics CEO Matt Angle kicks off a lively discussion on the rapidly accelerating research in the mapping, preservation, and reconstruction of the human connectome. We explore the ethical and legal ramifications of disruptive technology, and some of the unique challenges faced when driving innovation in emerging industries. Our guests are:  Nita Faraheny, JD, PhD, Everett Distinguished Professor of Law & Philosophy at Duke Law School, the Founding Director of Duke Science & Society, the Faculty Chair of the Duke MA in Bioethics & Science Policy, and principal investigator of SLAP Lab.  Kenneth Hayworth, PhD, President and Co-Founder of the Brain Preservation Foundation, Senior Scientist at the Howard Hughes Medical Institute's Janelia Farm Research Campus (JFRC) Robert McIntyre, CEO at Nectome As an exciting new development since the recording of this episode, Nita recently published a book, The Battle for Your Brain, which examines many topics in neuroethics, from Connectomics to Brain-Computer Interfaces. It is currently available on Amazon.Keep an eye out for part two in this series, which will take a deep dive into the latest technical and engineering innovations in the connectomics ecosystem. Coming soon!Please be advised that this episode contains a brief discussion of assisted suicide in a medical setting.Show Notes: 0:00 | Episode Intro 1:16 | Nita A. Farahany, JD, PhD1:21 | Kenneth Hayworth, PhD1:27 | Robert McKintyre, CEO, Nectome1:56 | Meeting of the minds 2:53 | Aldehyde-stabilized cryopreservation wins final phase of brain preservation prize3:56 | The Brain Preservation Foundation4:09 | Documentary series on the Brain Preservation Foundation5:21 | Letter of Support for Aldehyde Stabilized Cryopreservation (and ‘next steps' caveats)5:51 | Nita's 2018 Neuroethics Ted Talk 5:54 | International Neuroethics Society6:25 | Connectomics & new paths in neuroscience 8:10 | Allen Institute for Brain Science8:47 | A connectome and analysis of the adult Drosophila central brain9:33 | A visual intro to synaptic imaging in connectomics10:28 | The structure of the nervous system of the nematode Caenorhabditis elegans 11:16 | Mouse Connectome Project at CIC14:59 | Cryonics controversy 19:00 | Death, taxes, and synapses 20:51 | Uniform Law Commission21:08 | The Uniform Determination of Death Act24:25 | Watch Altered Carbon on Netflix25:49 | Understanding the “Loss of Chance” Doctrine 37:13 | Understanding Physician-Assisted Death, or ‘Death with Dignity' 40:21 | Euthanasia in the Netherlands46:01 | Autonomy, Dignity, and Consent to Harm, Rutgers Law Review Want More?Follow Neurotech Pub on TwitterFollow Paradromics on Twitter, LinkedIn, and InstagramFollow Matt on LinkedIn and Twitter

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.06.531342v1?rss=1 Authors: Ding, J., Peng, L., Moon, S., Lee, H. J., Patel, D. S., Lu, H. Abstract: In living organisms, changes in calcium flux are integral to many different cellular functions and are especially critical for the activity of neurons and myocytes. Genetically encoded calcium indicators (GECIs) have been popular tools for reporting changes in calcium levels in vivo. In particular, GCaMP, derived from GFP, are the most widely used GECIs and have become an invaluable toolkit for neurophysiological studies. Recently, new variants of GCaMP, which offer a greater variety of temporal dynamics and improved brightness, have been developed. However, these variants are not readily available to the Caenorhabditis elegans research community. This work reports a set of GCaMP6 and jGCaMP7 reporters optimized for C. elegans studies. Our toolkit provides reporters with improved dynamic range, varied kinetics, and targeted subcellular localizations. Besides optimized routine uses, this set of reporters are also well-suited for studies requiring fast imaging speeds and low magnification or low-cost platforms. 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/2023.03.05.531166v1?rss=1 Authors: Yadav, D. K., Chang, A. C., Gabel, C. V. Abstract: Cellular metabolism plays an essential role in the regrowth and regeneration of a neuron following physical injury. Yet, our knowledge of the specific metabolic pathways that are beneficial to neuron regeneration remains sparse. Previously, we have shown that modulation of O-linked {beta}- N-acetylglucosamine (O-GlcNAc), a ubiquitous post-translational modification that acts as a cellular nutrient sensor, can significantly enhance in vivo neuron regeneration. Here we define the specific metabolic pathway by which mutation of the O-GlcNAc transferase (ogt-1) increases regenerative outgrowth. Performing in vivo laser axotomy and measuring subsequent regeneration of individual neurons in C. elegans, we find that the ogt-1 mutation increases regeneration by diverting the metabolic flux of enhanced glycolysis towards one carbon metabolism (OCM) and the downstream transsulfuration metabolic pathway (TSP). These effects are abrogated by genetic and/or pharmacological disruption of OCM or the serine synthesis pathway (SSP) that links OCM to glycolysis. Testing downstream branches of this pathway, we find that enhanced regeneration is dependent only on the vitamin B12 24 independent shunt pathway. These results are further supported by RNA-sequencing that reveals dramatic transcriptional changes, by the ogt-1 mutation, in the genes involved in glycolysis, OCM, TSP and ATP metabolism. Strikingly, the beneficial effects of the ogt-1 mutation can be recapitulated by simple metabolic supplementation of the OCM metabolite methionine in wild-type animals. Taken together, these data unearth the metabolic pathways involved in the increased regenerative capacity of a damaged neuron in ogt-1 animals and highlight the therapeutic possibilities of OCM and its related pathways in the treatment of neuronal injury. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Listen to a blog summary of a trending research paper published in Volume 15, Issue 3 of Aging (Aging-US), entitled, "The lipidomes of C. elegans with mutations in asm-3/acid sphingomyelinase and hyl-2/ceramide synthase show distinct lipid profiles during aging." __________________________________________________ Lipids are a diverse group of biomolecules that are essential for life, including fats, oils, waxes, and steroids, and play crucial roles in cell membrane structure, energy storage and signaling. Lipidomics is the comprehensive analysis of lipids and their interactions in biological systems, with an aim to understand the role of lipids in cellular processes and their association with diseases. As we age, our cells undergo complex changes, including alterations in cellular lipid profiles. These changes are not only confined to humans; organisms such as the nematode Caenorhabditis elegans (C. elegans) are also subject to changes in lipid composition during aging. “For example, lipid classes including fatty acids (FA), triacylglycerols (TAG), sphingolipids (SL), and phospholipids (PL) have been identified as targets in lipid signatures related to aging [2, 3]. Furthermore, specific signatures are detected in the lipid profiles of those with age-related diseases, such as Alzheimer's Disease [4–9]. In addition, the abundance of many fatty acid subtypes differs between the youth, elderly, and centenarians [10, 11].” In a recent study, researchers Trisha A. Staab, Grace McIntyre, Lu Wang, Joycelyn Radeny, Lisa Bettcher, Melissa Guillen, Margaret P. Peck, Azia P. Kalil, Samantha P. Bromley, Daniel Raftery, and Jason P. Chan from Marian University, the University of Washington and Juniata College investigate the lipid profiles of C. elegans with mutations in the genes asm-3/acid sphingomyelinase and hyl-2/ceramide synthase during aging. On February 13, 2023, their research paper was published in Aging's Volume 15, Issue 3, entitled, “The lipidomes of C. elegans with mutations in asm-3/acid sphingomyelinase and hyl-2/ceramide synthase show distinct lipid profiles during aging.” Full blog - https://aging-us.org/2023/02/the-role-of-lipids-in-aging-insights-from-c-elegans/ DOI - https://doi.org/10.18632/aging.204515 Corresponding author - Jason P. Chan - jpchan@me.com Keywords - lipidomics, aging, sphingolipid metabolism, C. elegans, fatty acid metabolism About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

In this episode of the Epigenetics Podcast, we caught up with Peter Sarkies from University of Oxford Biochemistry to talk about his work on Transgenerational Inheritance of Epimutations. The team in the Sarkies lab focuses on investigating the connections between epigenetic gene regulation and evolution. The lab performs evolution experiments in the nematode C. elegans to determine if evolution can be influenced by epigenetic differences between individuals in a given population when no changes in the underlying DNA sequence are observed. A second area of interest of the team is evolution of piRNAs, which are present in metazoans but have been lost in nematodes during evolution.   References The Selfish Gene Sarkies, P., & Miska, E. A. (2013). Is There Social RNA? Science, 341(6145), 467–468. https://doi.org/10.1126/science.1243175 Beltran, T., Shahrezaei, V., Katju, V., & Sarkies, P. (2020). Epimutations driven by small RNAs arise frequently but most have limited duration in Caenorhabditis elegans. Nature ecology & evolution, 4(11), 1539–1548. https://doi.org/10.1038/s41559-020-01293-z Beltran, T., Pahita, E., Ghosh, S., Lenhard, B., & Sarkies, P. (2021). Integrator is recruited to promoter-proximally paused RNA Pol II to generate Caenorhabditis elegans piRNA precursors. The EMBO journal, 40(5), e105564. https://doi.org/10.15252/embj.2020105564   Related Episodes The Role of Small RNAs in Transgenerational Inheritance in C. elegans (Oded Rechavi) Epigenetic Influence on Memory Formation and Inheritance (Isabelle Mansuy)   Contact Epigenetics Podcast on Twitter Epigenetics Podcast on Instagram Epigenetics Podcast on Mastodon Active Motif on Twitter Active Motif on LinkedIn Email: podcast@activemotif.com

This episode contains: Devon, Ben and Steven all record in the same room again! It's crazy! Devon tells us about his travels, and Ben tries to QA a Tesla. It's a whole thing. Only one Science and no Big Question this week because we have Sci-Fi to talk about.  Robot Overlords: Researchers Discover a More Flexible Approach to Machine Learning. Liquid neural nets can transform their underlying algorithms on the fly. They are based on the Caenorhabditis elegans nervous system. Nonlinear equations, worm nervous systems, and liquid neural nets are all here.  https://www.quantamagazine.org/researchers-discover-a-more-flexible-approach-to-machine-learning-20230207/  Picard: We talk about the first episode of the third season of Star Trek Picard. There are a lot of nits to pick, but we are generally optimistic about this final season. We start off with some complaints about seasons 1 and 2, but it seems season 3 has rectified some of those. We have deep discussions about Captain Shaw, The Orville, and ship refits.  Ant-Man and The Wasp: Quantumania: SPOILERS. Devon and Steven just watched it, Ben watched it a few days before and we do a deep dive. We talk about plot, characters, editing, Kang and how there was a bit of dissappointment in all of those things. Steven attempts to explain Kang, and we all try and figure out M.O.D.O.K. In there end, there was little consistancy, which is consistant with other Ant-Man movies.   

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.22.529281v1?rss=1 Authors: Merritt, D. M., Udachina, A., Freidel, N., Almeida, S. M. T., Lau, Y. M. A., van der Kooy, D. Abstract: Memories are often categorized into types, reflecting their behavioural, anatomical and molecular diversity: these classifications both aid understanding of the differences among varieties of memory and help delineate the unifying cross-species principles underlying them. In the nematode worm Caenorhabditis elegans, we find that an associative memory of the pairing of the normally attractive odorant benzaldehyde and starvation depends on de novo transcription and translation, is independent of CREB, and is produced by massed training: a pattern which does not correspond to any of the well-characterized molecular categories of invertebrate memory. Further, as has been shown for many memories in vertebrates, but not previously in nematodes, we find that formation of this memory continues after removal of the stimuli initially causing it, and that it is labile to disruption through protein synthesis inhibition following training, but that inhibition of proteasomal activity does not extend the duration of the memory. Previous findings have implicated insulin pathway signalling as a key component of this benzaldehyde/starvation memory, however we find that the transcriptional activity required for the memory is likely to be independent of the transcription factors that function at the terminus of this pathway. These findings better characterize this model associative memory in relation to other invertebrate memory types and identify ways in which it both shares their traits and differs from them. 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/2023.02.16.528858v1?rss=1 Authors: Kenis, S., Istiban, M. N., Van Damme, S., Vandewyer, E., Watteyne, J., Schoofs, L., Beets, I. Abstract: In vertebrates, thyrostimulin is a highly conserved glycoprotein hormone that, besides thyroid stimulating hormone (TSH), is a potent ligand of the TSH receptor. Thyrostimulin is considered the most ancestral glycoprotein hormone and orthologs of its subunits, GPA2 and GPB5, are widely conserved across vertebrate and invertebrate animals. Unlike TSH, however, the functions of the thyrostimulin neuroendocrine system remain largely unexplored. Here, we identify a functional thyrostimulin-like signaling system in Caenorhabditis elegans. We show that orthologs of GPA2 and GPB5, together with thyrotropin-releasing hormone (TRH) related neuropeptides, constitute a neuroendocrine pathway that promotes growth in C. elegans. GPA2/GPB5 signaling is required for normal body size and acts through activation of the glycoprotein hormone receptor ortholog FSHR-1. C. elegans GPA2 and GPB5 increase cAMP signaling by FSHR-1 in vitro. Both subunits are expressed in enteric neurons and promote growth by signaling to their receptor in glial cells and the intestine. Impaired GPA2/GPB5 signaling causes bloating of the intestinal lumen. In addition, mutants lacking thyrostimulin-like signaling are defective in defecation behavior. Our study suggests that the thyrostimulin GPA2/GPB5 pathway is an ancient enteric neuroendocrine system that regulates intestinal function in ecdysozoans, and may ancestrally have been involved in the control of organismal growth. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Dr. Adriana San Miguel is an Assistant Professor in the Department of Chemical and Biomolecular Engineering at North Carolina State University. Adriana conducts research using a small roundworm called Caenorhabditis elegans (C. elegans). They use this model organism to better understand processes such as aging, neurodegeneration, and stress. In particular, Adriana's lab uses engineering tools and approaches to try to conduct research that is highly efficient and quantitative. In her free time, Adriana enjoys exercising, swimming, and spending quality time with her family. She received her BSc. in chemical engineering from ITESM, a technological institute in Monterrey, Mexico. As an undergraduate, she received the Frisa Entrepreneurship Award from ITESM as well as the Craig P. Dunn Award for Social Innovations in Entrepreneurship from the San Diego State University Venture challenge. Prior to starting graduate school, Adriana worked in the cement and water-treatment industries. She was awarded her PhD in chemical engineering from Georgia Tech, and during her PhD, she was recognized with the Exemplary Academic Achievement Award and the Ziegler Award for Best PhD Thesis Proposal from the School of Chemical and Biomolecular Engineering at Georgia Tech. Afterwards, Adriana worked as a Postdoctoral Fellow at Georgia Tech and at the Dana-Farber Cancer Institute. As a postdoc she received an NIH K99 Pathway to Independence Award. In our interview, she shares more about her life and science.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.28.526030v1?rss=1 Authors: Schwartz, A. Z., Nance, J. Abstract: The mitochondrial genome (mtDNA) is packaged into discrete protein-DNA complexes called nucleoids. mtDNA packaging factor TFAM (mitochondrial transcription factor-A) promotes nucleoid compaction and is required for mtDNA replication. Here, we investigate how changing TFAM levels affects mtDNA in the Caenorhabditis elegans germ line. We show that increasing germline TFAM activity boosts mtDNA number and significantly increases the relative proportion of a selfish mtDNA mutant, uaDf5. We conclude that TFAM levels must be tightly controlled to ensure appropriate mtDNA composition in the germ line. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.25.525622v1?rss=1 Authors: Tomioka, M., Umemura, Y., Ueoka, Y., Chin, R., Katae, K., Uchiyama, C., Ike, Y., Iino, Y. Abstract: The nematode Caenorhabditis elegans memorizes various external chemicals, such as ions and odorants, during feeding. Here we find that C. elegans is attracted to the monosaccharides glucose and fructose after exposure to these monosaccharides in the presence of food; however, it avoids them without conditioning. The attraction to glucose requires a left-sided ASE gustatory neuron called ASEL. ASEL activity increases when glucose concentration decreases. Optogenetic ASEL stimulation promotes forward movements; however, after glucose conditioning, it promotes turning, suggesting that after glucose conditioning, the behavioral output of ASEL activation switches toward glucose. We previously reported that chemotaxis toward sodium ion (Na+), which is sensed by ASEL, increases after Na+ conditioning in the presence of food. Interestingly, glucose conditioning decreases Na+ chemotaxis, and conversely, Na+ conditioning decreases glucose chemotaxis, suggesting the reciprocal inhibition of learned chemotaxis to distinct chemicals. The activation of PKC-1, an nPKC {varepsilon}/{eta} ortholog, in ASEL promotes glucose chemotaxis and decreases Na+ chemotaxis after glucose conditioning. Furthermore, genetic screening identified ENSA-1, an ortholog of the protein phosphatase inhibitor ARPP-16/19, which functions in parallel with PKC-1 in glucose-induced chemotactic learning toward distinct chemicals. These findings suggest that kinase-phosphatase signaling regulates the balance between learned behaviors based on glucose conditioning in ASEL, which might contribute to migration toward chemical compositions where the animals were previously fed. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

A new research paper was published in Aging (listed as "Aging (Albany NY)" by MEDLINE/PubMed and "Aging-US" by Web of Science) Volume 15, Issue 1, entitled, “The innate immune signaling component FBXC-58 mediates dietary restriction effects on healthy aging in Caenorhabditis elegans.” Dietary restriction (DR) is a highly effective and reproducible intervention that prolongs longevity in many organisms. The molecular mechanism of action of DR is tightly connected with the immune system; however, the detailed mechanisms and effective downstream factors of immunity that mediate the beneficial effects of DR on aging remain unknown. In this new study, researchers Jeong-Hoon Hahm, Farida S. Nirmala, Pyeong Geun Choi, Hyo-Deok Seo, Tae Youl Ha, Chang Hwa Jung, and Jiyun Ahn from the Korea Food Research Institute and the University of Science and Technology (in Daejeon, South Korea) investigated the immune signaling that mediates DR effects. The team used Caenorhabditis elegans (C. elegans) to understand the underlying molecular mechanisms of aging and immunity. “We found that the F-box gene, fbxc-58, a regulator of the innate immune response, is a novel mediator of DR effects on extending the health span of C. elegans.” Fbxc-58 is upregulated by DR and is necessary for DR-induced lifespan extension and physical health improvement in C. elegans. Furthermore, through DR, fbxc-58 prevents disintegration of the mitochondrial network in body wall muscle during aging. The researchers found that fbxc-58 is a downstream target of the ZIP-2 and PHA-4 transcription factors, the well-known DR mediator, and fbxc-58 extends longevity in DR through an S6 kinase-dependent pathway. Thus, the team proposed that fbxc-58 may provide a new mechanistic understanding of the effects of DR on healthy aging and elucidate the signaling mechanisms that link immunity and DR effects with aging. “Thus, we propose that investigating the molecular mechanism of action of F-box proteins, including fbxc-58, in DR will shed light on means to prevent sarcopenia and offer a potentially practical means of encouraging healthy aging via DR.” DOI: https://doi.org/10.18632/aging.204477 Corresponding Authors: Jeong-Hoon Hahm - hahmjh@kfri.re.kr, Jiyun Ahn - jyan@kfri.re.kr Keywords: dietary restriction, aging, innate immunity, F-box protein, Caenorhabditis elegans Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204477 About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://youtube.com/Aging-US LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ For media inquiries, please contact: media@impactjournals.com

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.12.523604v1?rss=1 Authors: Tang, L. T. H., Lee, G. A., Cook, S. J., Ho, J., Potter, C. C., Buelow, H. E. Abstract: Asymmetric brain function is common across the animal kingdom and involved in language processing, and likely in learning and memory. What regulates asymmetric brain function remains elusive. Here, we show that the nematode Caenorhabditis elegans restructures an asymmetric salt sensing neural circuit during associative learning. Worms memorize and prefer the salt concentration at which they were raised in the presence of food through a left- biased network architecture. When conditioned at elevated salt concentrations, animals change the left-biased to a right-biased network, which explains the changed salt-seeking behavior. The changes in circuit architecture require new synapse formation induced through asymmetric, paracrine insulin-signaling. Therefore, experience-dependent changes in asymmetric network architecture rely on paracrine insulin signaling and are fundamental to learning and behavior. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In Episode 2, Dr. Nally addresses the cowboys perception of vegetarians and vegans, presents a little cowboy poetry (you don't want to miss this) and discusses lectins. Cowboy Poetry by Baxter Black, "Vegetarians Nightmare" Show Notes: https://www.researchgate.net/publication/343273411_Do_Plants_Feel_Pain? https://ndpr.nd.edu/reviews/plant-minds-a-philosophical-defense/ https://www.um.es/web/minimal-intelligence-lab/ Wang Q, et al. Identification of intact peanut lectin in peripheral venous blood. Lancet. Dec 5 1998. Vol 352;1943. p1831-1832. DOI:https://doi.org/10.1016/S0140-6736(05)79894-9. Shechter Y. Bound lectins that mimic insulin produce persistent insulin-like activities. Endocrinology. 1983 Dec;113(6):1921-6. doi: 10.1210/endo-113-6-1921. PMID: 6357762. Zheng J, Wang M, Wei W, Keller JN, Adhikari B, King JF, King ML, Peng N, Laine RA. Dietary Plant Lectins Appear to Be Transported from the Gut to Gain Access to and Alter Dopaminergic Neurons of Caenorhabditis elegans, a Potential Etiology of Parkinson's Disease. Front Nutr. 2016 Mar 7;3:7. doi: 10.3389/fnut.2016.00007. PMID: 27014695; PMCID: PMC4780318.

In this episode, Alan Cash talks about oxaloacetate and the beginning of his journey in developing it as a nutritional supplement. He shares the ongoing research on oxaloacetate's benefits, especially for patients suffering from brain damage. He also dives into oxaloacetate's ability to increase muscle use before fatigue and reduce anxiety and depression levels in women experiencing PMS. If you want to learn more about oxaloacetate's many benefits and applications, then this episode is for you! Here are three reasons why you should listen to this episode: Learn what oxaloacetate is and how it can help slow the biological effects of ageing. Discover the numerous potential health benefits of oxaloacetate. Get to know Alan's journey in developing and manufacturing oxaloacetate as a nutritional supplement. Get Customised Guidance for Your Genetic Make-Up For our epigenetics health programme, all about optimising your fitness, lifestyle, nutrition and mind performance to your particular genes, go to  https://www.lisatamati.com/page/epigenetics-and-health-coaching/. Customised Online Coaching for Runners CUSTOMISED RUN COACHING PLANS — How to Run Faster, Be Stronger, Run Longer  Without Burnout & Injuries Have you struggled to fit in training in your busy life? Maybe you don't know where to start, or perhaps you have done a few races but keep having motivation or injury troubles? Do you want to beat last year's time or finish at the front of the pack? Want to run your first 5-km or run a 100-miler? ​​Do you want a holistic programme that is personalised & customised to your ability, goals, and lifestyle?  Go to www.runninghotcoaching.com for our online run training coaching. Health Optimisation and Life Coaching Are you struggling with a health issue and need people who look outside the square and are connected to some of the world's greatest science and health minds? Then reach out to us at support@lisatamati.com, and we can jump on a call to see if we are a good fit for you. If you have a big challenge ahead, are dealing with adversity or want to take your performance to the next level and want to learn how to increase your mental toughness, emotional resilience, foundational health, and more, contact us at support@lisatamati.com. Order My Books My latest book, Relentless, chronicles the inspiring journey of how my mother and I defied the odds after an aneurysm left my mum, Isobel, with massive brain damage at age 74. The medical professionals told me there was absolutely no hope of any quality of life again. Still, I used every mindset tool, years of research and incredible tenacity to prove them wrong and bring my mother back to full health within three years. Get your copy here: https://shop.lisatamati.com/collections/books/products/relentless. For my other two best-selling books Running Hot and Running to Extremes, chronicling my ultrarunning adventures and expeditions worldwide, go to https://shop.lisatamati.com/collections/books. Lisa's Anti-Ageing and Longevity Supplements  NMN: Nicotinamide Mononucleotide, an NAD+ precursor Quercetin and Trimethylglycine by NMN Bio Benagene, an oxaloacetate supplement by benaGene Feel Healthier and Younger* Researchers have found that Nicotinamide Adenine Dinucleotide or NAD+, a master regulator of metabolism and a molecule essential for the functionality of all human cells, is being dramatically decreased over time. What is NMN? NMN Bio offers a cutting edge Vitamin B3 derivative named NMN (beta Nicotinamide Mononucleotide) that can boost the levels of NAD+ in muscle tissue and liver. Take charge of your energy levels, focus, metabolism and overall health to live a happy, fulfilling life. Founded by scientists, NMN Bio offers supplements of the highest purity and are rigorously tested by an independent, third-party lab. Start your cellular rejuvenation journey today. Support Your Healthy Ageing We offer powerful third-party tested NAD+ boosting supplements so you can start your healthy ageing journey today. Shop now: https://nmnbio.nz/collections/all NMN (beta Nicotinamide Mononucleotide) 250mg | 30 capsules NMN (beta Nicotinamide Mononucleotide) 500mg | 30 capsules 6 Bottles | NMN (beta Nicotinamide Mononucleotide) 250mg | 30 Capsules 6 Bottles | NMN (beta Nicotinamide Mononucleotide) 500mg | 30 Capsules Quality You Can Trust — NMN Our premium range of anti-ageing nutraceuticals (supplements that combine Mother Nature with cutting edge science) combats the effects of aging while designed to boost NAD+ levels. Manufactured in an ISO9001 certified facility Boost Your NAD+ Levels — Healthy Ageing: Redefined Cellular Health Energy & Focus Bone Density Skin Elasticity DNA Repair Cardiovascular Health Brain Health  Metabolic Health Perfect Amino Supplement by Dr David Minkoff Introducing PerfectAmino PerfectAmino is an amino acid supplement that is 99% utilized by the body to make protein. PerfectAmino is 3-6x the protein of other sources with almost no calories. ​100% vegan and non-GMO. ​The coated PerfectAmino tablets are a slightly different shape and have a natural, non-GMO, certified organic vegan coating on them so they will glide down your throat easily. Fully absorbed within 20-30 minutes! ​No other form of protein comes close to PerfectAminos Ketone Products by Keto-Pro Exogenous Ketones developed by Nutritionist and Body Building champion Richard Smith. Keto-Pro BHB Exogenous Ketones –  250g   MORE BHB per gram than other MARKET LEADERS. During In-house testing, Keto-Pro BHB raised ketones quicker, higher and for longer than other market leaders. Ketones My  ‘Fierce' Sports Jewellery Collection For my gorgeous and inspiring sports jewellery collection, 'Fierce', go to https://shop.lisatamati.com/collections/lisa-tamati-bespoke-jewellery-collection. Episode Highlights [09:36] How Alan Found Out About Oxaloacetate Alan got sick and needed to undergo brain surgery. He found out that his pain and illness were related to ageing. As Alan researched more about ageing, he discovered calorie restriction, wherein organisms tend to live longer when they eat less. Increasing the ratio of Nicotinamide Adenine Dinucleotide (NAD) to NADH helps fight off ageing. Alan started looking into biomechanical pathways and found that oxaloacetate that can change the ratio of NAD from NADH to 900% in just two minutes. He started testing oxaloacetate using worms and realised that the activated pathway was the same as calorie restriction. [21:53] What is Oxaloacetate? Oxaloacetate is a naturally occurring molecule in our bodies during metabolism. It exists in every cell of the body and, therefore, is non-toxic. Oxaloacetate is considered a hot molecule right now, given how it can help moderate metabolism on a cell-by-cell basis. Increasing oxaloacetate affects metabolism, which is vital to some people. [25:38] Patenting Oxaloacetate  Tohoku University in Sendai, Japan, conducted research in the 1960s which found how oxaloacetate reduced fasting glucose levels in type one and type two diabetics.  At first, Alan ran into the problem of being unable to get a patent for oxaloacetate, a naturally occurring compound in the human body. He persevered and eventually was able to own patent rights based on how oxaloacetate can maintain its stable form of enol-oxaloacetate.  After rigorous testing, their products now have a shelf life of two to three years or more. [31:00] Oxaloacetate and the Warburg Effect Oxaloacetate is a potential drug for brain cancer such as glioblastoma. It also has the potential to reverse the Warburg effect, in which fermented glucose turns into lactate that a tumour feeds off. Giving Oxaloacetate to cancer cells changes the cancer metabolism cell by cell. There's a specific dosage where cancer cells stop reproducing. [38:03] Oxaloacetate and Glutamate Glutamate is a compound that fires off the neutrons in the brain. Excessive glutamate excites the neurons until they die, a process known as excitotoxicity. Many studies describe how we may reduce the risk of excitotoxicity.  Alan is looking into cognition through clinical trials with Alzheimer's disease patients. The study showed how oxaloacetate reduced glutamate levels. In the same clinical trial, they also found how oxaloacetate increased the amount of glucose the brain can take in. The brain can take in more glucose due to the signalling protein PGC-1 Alpha enabling the production of more mitochondria. [38:03] Oxaloacetate Can Improve Muscle Use Oxaloacetate also improves muscle use by 10% more before it goes into fatigue. 10% is a significant improvement for both top-end athletes and daily living. Alan has done a clinical trial that showed a 25% to 30% drop in fatigue levels within six weeks, even for people with chronic fatigue syndrome or ME/CFS for up to 30 years. NF-κB turns on genes that release a cytokine storm, which at high levels can lead to chronic inflammation seen in arthritis or long COVID patients. Animal models show that oxaloacetate led to a reduction of NF-κB's translocation to the nucleus by 70%, which turns off the cytokine storm.  People experiencing chronic fatigue can benefit from oxaloacetate's mechanism of producing new mitochondria.  [51:34] Increase Focus and Attention Using Oxaloacetate In animal models, oxaloacetate turns on the mechanism to increase the number of neurons in the brain and increase the length of the axons, the little tendrils that connect neurons. Alan did a critical trial on the effect of oxaloacetate on premenstrual syndrome (PMS), wherein he found a 50% drop in anxiety, depression and suicide ideation. Drugs have an immediate pharmacological effect. Another is the genomic effect with a cumulative property that takes about a month or more to see. Even after getting better from your illnesses, keep the ball rolling and don't stop intaking your medicine and supplements. 7 Powerful Quotes ‘We could see when we gave the oxaloacetate to them if they live longer, or if they didn't, so we could eliminate what were the critical genes. And, we were able to follow along with a pathway, and it turned out to be the exact same pathway as calorie restriction, which is really exciting.' ‘First of all, is oxaloacetate toxic? Well, it turns out it's a human molecule. It's in metabolism. It's in practically every cell of your body.' ‘Experiment and see what works and understanding some of these mechanisms is really important because then we can actually start to connect the dots of cells.' ‘The reality is most people are not going to have the perfect diet, not going to be in a perfect environment, can't maybe even afford to have great food, or organic food, or all of these things that restrict us from having the ideal.' ‘None of us are going to know what's around the corner for us but, if we can be in that preventative space and be understanding this more and more, then that is to me the most fascinating conversation we can have.' ‘What happens then is that they stop all their protocol, and the thing that they were doing and, “Now I'm fixed. I don't need it anymore.” And I'm like, “Hang on a minute, you don't drop the ball now. You're already underway. You got to stay underway. You got to keep it going.”' ‘You want that cumulative, and those epigenetic changes, and those long term changes.' Resources Gain exclusive access and bonuses to Pushing the Limits Podcast by becoming a patron!  Oxaloacetate supplementation increases lifespan in Caenorhabditis elegans through an AMPK/FOXO-dependent pathway. Studies on Anti-diabetic Effect of Sodium Oxalcacetate Get benaGene Capsules containing oxaloacetate  Get TMG (Trimethylglycine) as the ultimate anti-aging combination with NMN  PerfectAmino Tablets by Bodyhealth Keto-Pro's D-BHB Exogenous Ketones - Chocolate Flavour Keto-Pro's Keto Bar - Chocolate Almond Brownie Colloidal Health's Colloidal Silver Black Cumin Seed Oil Connect with Alan Cash: LinkedIn About Alan Alan Cash is a physicist, biologist and geologist. He's also a professional entrepreneur and the CEO and Founder of Terra Biological LLC and MetVital, Inc.  Alan is also the clinical trials supervisor and medical researcher. He's currently pursuing the advancement and development of nutritional supplements containing oxaloacetate, which is known as a caloric-restriction mimetic compound. His research has brought profound breakthroughs addressing cognitive decline and anti-aging. If you want to reach out, you may connect with Alan via LinkedIn. Enjoyed This Podcast? If you did, be sure to subscribe and share it with your friends! Post a review and share it! If you enjoyed tuning in, then leave us a review. You can also share this with your family and friends so they can know how to optimise sleep.  Have any questions? You can contact me through email (support@lisatamati.com) or find me on Facebook, Twitter, Instagram and YouTube. For more episode updates, visit my website. You may also tune in on Apple Podcasts. To pushing the limits, Lisa

Thanks for joining us, today we welcome Dr. Fatma Kaplan. She is the co-founder, CEO, and CSO of Pheronym. Not only is she an entrepreneur and accomplished scientist with experience in biology and chemistry, but she also has a passion for understanding the intricacies and behaviors of both parasitic and beneficial nematodes. Monte and Fatma explore everything from nematodes in agriculture to nematodes in space, yes space! Dr. Kaplan conducted the first agricultural biocontrol experiment in Space at the International Space Station in 2020. Dr. Kaplan has a Ph.D. in Plant Molecular and Cellular Biology and postdoctoral training in Natural Product Chemistry with a focus on isolating biologically active compounds. She discovered the first sex pheromone of the nematode Caenorhabditis elegans and published in Nature in 2008. Then she discovered pheromones regulate other behaviors in both parasitic and beneficial nematodes. Dr. Kaplan conducted the first agricultural biocontrol experiment in Space at the International Space Station in 2020. She has very high impact publications and her dissertation was cited in textbooks within 5 years of publication. Dr. Kaplan worked as a scientist at NASA, the National Magnetic Field Laboratory and the US Department of Agriculture – Agricultural Research Service. Dr. Kaplan co-founded Pheronym to bring nematode pheromone technology to the market. Dr. Kaplan believes that nematode pheromone technology will provide effective, non-toxic pest control for farmers and gardeners. https://www.pheronym.com/ https://www.ars.usda.gov/news-events/news/research-news/2019/starship-nematode/ https://www.sciencedirect.com/science/article/abs/pii/S0022201119300503 Got questions you want answered? Send them our way and we'll do our best to research and find answers. Know someone you think would be great on the AgEmerge stage or podcast? Send your questions or suggestions to kim@asn.farm we'd love to hear from you.

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: We Haven't Uploaded Worms, published by jefftk on the LessWrong. In theory you can upload someone's mind onto a computer, allowing them to live forever as a digital form of consciousness, just like in the Johnny Depp film Transcendence. But it's not just science fiction. Sure, scientists aren't anywhere near close to achieving such feat with humans (and even if they could, the ethics would be pretty fraught), but now an international team of researchers have managed to do just that with the roundworm Caenorhabditis elegans. Science Alert Uploading an animal, even one as simple as c. elegans would be very impressive. Unfortunately, we're not there yet. What the people working on Open Worm have done instead is to build a working robot based on the c. elegans and show that it can do some things that the worm can do. The c. elegans nematode has only 302 neurons, and each nematode has the same fixed pattern. We've known this pattern, or connectome, since 1986. [1] In a simple model, each neuron has a threshold and will fire if the weighted sum of its inputs is greater than that threshold. Which means knowing the connections isn't enough: we also need to know the weights and thresholds. Unfortunately, we haven't figured out a way to read these values off of real worms. Suzuki et. al. (2005) [2] ran a genetic algorithm to learn values for these parameters that would give a somewhat realistic worm and showed various wormlike behaviors in software. The recent stories about the Open Worm project have been for them doing something similar in hardware. [3] To see why this isn't enough, consider that nematodes are capable of learning. Sasakura and Mori (2013) [5] provide a reasonable overview. For example, nematodes can learn that a certain temperature indicates food, and then seek out that temperature. They don't do this by growing new neurons or connections, they have to be updating their connection weights. All the existing worm simulations treat weights as fixed, which means they can't learn. They also don't read weights off of any individual worm, which means we can't talk about any specific worm as being uploaded. If this doesn't count as uploading a worm, however, what would? Consider an experiment where someone trains one group of worms to respond to stimulus one way and another group to respond the other way. Both groups are then scanned and simulated on the computer. If the simulated worms responded to simulated stimulus the same way their physical versions had, that would be good progress. Additionally you would want to demonstrate that similar learning was possible in the simulated environment. (In a 2011 post on what progress with nematodes might tell us about uploading humans I looked at some of this research before. Since then not much has changed with nematode simulation. Moore's law looks to be doing much worse in 2014 than it did in 2011, however, which makes the prospects for whole brain emulation substantially worse.) I also posted this on my blog. [1] The Structure of the Nervous System of the Nematode Caenorhabditis elegans, White et. al. (1986). [2] A Model of Motor Control of the Nematode C. Elegans With Neuronal Circuits, Suzuki et. al. (2005). [3] It looks like instead of learning weights Busbice just set them all to +1 (excitatory) and -1 (inhibitory). It's not clear to me how they knew which connections were which; my best guess is that they're using the "what happens to work" details from [2]. Their full writeup is [4]. [4] The Robotic Worm, Busbice (2014). [5] Behavioral Plasticity, Learning, and Memory in C. Elegans, Sasakura and Mori (2013). Thanks for listening. To help us out with The Nonlinear Library or to learn more, please visit nonlinear.org.

Many aging-associated neurodegenerative disorders, including Alzheimer's disease, involve the aggregation of abnormal tau in nerve cells (neurons). Normally, tau proteins function to stabilize microtubules in the brain. Tauopathy occurs when tau proteins become misfolded and misshapen (which turns tau into toxic tau). They then continue to proliferate and bind to each other, forming tau oligomers. These tau oligomers are more toxic and have a greater potential to spread tau pathology. Before toxic tau snowballs into neurodegenerative disorders, the events that lead up to abnormal tau have remained elusive to researchers. “While the association between tau levels and energy metabolism is established, it is not clear whether mitochondrial dysfunction is an early pathological feature of high levels of tau or a consequence of its excessive formation of protein aggregates.” Previous studies have demonstrated an association between tau levels and mitochondrial metabolism, however, determining which one proceeds the other has yet to be fully illuminated. Shedding light on this subject, researchers—from the University of Copenhagen, National and Kapodistrian University of Athens and the National Institutes of Health's National Institute on Aging—used a Caenorhabditis elegans (C. elegans; roundworm/nematode) model of tau to examine mitochondrial changes over time. Their paper was chosen as the cover of Aging (Aging-US) Volume 13, Issue 21, published in November of 2021 and entitled, “Alteration of mitochondrial homeostasis is an early event in a C. elegans model of human tauopathy”. Full blog - https://www.impactjournals.com/journals/blog/aging/trending-with-impact-worms-reveal-early-event-in-neurodegeneration/ Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.203683 DOI - https://doi.org/10.18632/aging.203683 Full Text - https://www.aging-us.com/article/203683/text Correspondence to: Konstantinos Palikaras email: palikarask@med.uoa.gr, Mansour Akbari email: akbari@sund.ku.dk and Vilhelm A. Bohr email: bohrv@grc.nia.nih.gov Keywords: aging, Alzheimer's disease, C. elegans, energy metabolism, mitochondria, tau, tauopathy About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at http://www.Aging-US.com​​ or connect with us on: SoundCloud - https://soundcloud.com/aging-us​ Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging​ Pinterest - https://www.pinterest.com/AgingUS/ Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Boiled or iced with water or milk, blended in smoothies, condensed into shots or even baked into pastries—humans are infatuated with green tea. Today, green tea is one of the most widely consumed beverages in the world. Molecules found in this plant, named catechins, are known to have numerous evidence-based health benefits, including weight loss and age delaying properties. However, the mechanism by which these effects take place have yet to be fully elucidated. “The popularity of green tea makes it crucial to study its impact on health and aging.” Researchers from Friedrich Schiller University Jena, Huazhong Agricultural University, ETH Zurich, and the Medical University of Graz investigated green tea catechins and their effects in roundworms, known as Caenorhabditis elegans (C. elegans), and isolated rodent mitochondria. Their trending paper was published in October of 2021 by Aging (Aging-US), and entitled, “Green tea catechins EGCG and ECG enhance the fitness and lifespan of Caenorhabditis elegans by complex I inhibition.” “We have designed the current study to investigate the impact and to unveil the target of the most abundant green tea catechins, epigallocatechin gallate (EGCG) and epicatechin gallate (ECG).” Full blog - https://www.impactjournals.com/journals/blog/aging/trending-with-impact-green-tea-enhances-fitness-and-lifespan-in-worms/ Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.203597 DOI - https://doi.org/10.18632/aging.203597 Full text - https://www.aging-us.com/article/203597/text Correspondence to: Corina T. Madreiter-Sokolowski email: corina.madreiter@medunigraz.at and Michael Ristow email: michael-ristow@ethz.ch Keywords: aging, reactive oxygen species, mitochondria, polyphenols, C. elegans About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at http://www.Aging-US.com​​ or connect with us on: Twitter - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ SoundCloud - https://soundcloud.com/aging-us​ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging​ Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Make sure to check out this paper—Sperm fate is promoted by the mir-44 microRNA family in the Caenorhabditis elegans hermaphrodite germline—that was published in Genetics in Jan 2021.

Science's Online News Editor David Grimm joins host Sarah Crespi to talk about a 2000-year-old pet cemetery found in the Egyptian city of Berenice and what it can tell us about the history of human-animal relationships. Also this week, Dipon Ghosh, a postdoctoral fellow at the Massachusetts Institute of Technology, talks about how scientists missed that the tiny eyeless roundworm Caenorhabditis elegans, which has been intensively studied from top to bottom for decades, somehow has the ability to detect colors. This week's episode was produced with help from Podigy. Listen to previous podcasts About the Science Podcast Download a transcript (PDF) [Image: HINRICH SCHULENBURG; Music: Jeffrey Cook] Authors: Sarah Crespi; David Grimm   See omnystudio.com/listener for privacy information.

Dr. Fatma Kaplan (@KaplanSchiller) is the co-founder and CEO/CSO of Pheronym, a company trying to help solve world food crisis and feed the growing world population, farmers need for a non-toxic way to control pests.Fatma's an accomplished scientist with experience in both biology and chemistry focused on isolating biologically active compounds. She discovered the first sex pheromone of the nematode Caenorhabditis elegans and published in Nature and discovered that pheromones regulate other behaviors in both parasitic and beneficial nematodes.To listen to the entire episode, visit: https://disruptors.fm/110-a-biotech-solution-to-pesticide-free-food-to-feed-the-world-and-mars-colonies-fatma-kaplan/