Podcasts about extracellular

South East Technological University (SETU) is thrilled to announce its role in the ambitious EVEREST project. Led by the University College Dublin (UCD), the project is a collaboration of 21 institutions from 11 countries, focused on harnessing the potential of extracellular vesicles (EVs) to transform biomedical research. With a €1.3 million budget funded through the prestigious Marie Sklodowska-Curie Actions (MSCA) programme under Horizon Europe, the project will commence in January 2025 and continue over a four-year period. Extracellular vesicles are small, cell-derived particles that serve as messengers between cells, carrying proteins, lipids, and nucleic acids essential for intercellular communication. By standardising methods for isolating and characterising these vesicles, EVEREST aims to leverage their potential for non-invasive diagnostics and personalised treatments, enabling more precise and effective interventions for complex diseases such as cancer and cardiovascular conditions. Prof Marie Claire Van Hout, Vice President for Research, Innovation and Impact at SETU, highlighted the significance of the project for the university: "The EVEREST project exemplifies SETU's commitment to advancing impactful research that can improve lives globally. Through collaboration with leading institutions and industry partners, we are contributing to innovative biomedical solutions that hold the potential to change the landscape of diagnostics and treatment. This is an exciting opportunity to showcase SETU's research capacity on an international stage." SETU's Ocular Therapeutics Research Group (OTRG), led by Dr Laurence Fitzhenry, is excited to contribute to this interdisciplinary initiative. Reflecting on the project, Dr Fitzhenry shared, "EVEREST provides a platform for researchers to develop valuable scientific skills while actively advancing transformative treatment options for those affected by challenging diseases. Our team is looking forward to expanding our expertise and collaborating with a consortium that spans multiple disciplines and industries." The EVEREST consortium unites leading academic and non-academic partners, with academic collaborators including University College Dublin, Trinity College Dublin, and Queen's University Belfast, among others across Europe. Industry partners such as SiriusXT, Bioreperia, and Fox Biosystems bring critical commercial perspectives, ensuring a robust approach from fundamental research to practical applications. Prof Breandan Kennedy and Dr Yolanda Alvarez, project leaders with significant experience managing European projects like CRYSTAL3 and 3D-NEO-NET, will ensure the project's effective progress. EVEREST will benefit greatly from the MSCA Staff Exchange programme, which promotes international collaboration, knowledge transfer, and innovation, with the goal of generating solutions to some of healthcare's most pressing global challenges. Through EVEREST, SETU and its partners are set to push the boundaries of biomedical science, leveraging extracellular vesicles to advance early diagnostics and pave the way for future treatment breakthroughs. More about Irish Tech News Irish Tech News are Ireland's No. 1 Online Tech Publication and often Ireland's No.1 Tech Podcast too. You can find hundreds of fantastic previous episodes and subscribe using whatever platform you like via our Anchor.fm page here: https://anchor.fm/irish-tech-news If you'd like to be featured in an upcoming Podcast email us at Simon@IrishTechNews.ie now to discuss. Irish Tech News have a range of services available to help promote your business. Why not drop us a line at Info@IrishTechNews.ie now to find out more about how we can help you reach our audience. You can also find and follow us on Twitter, LinkedIn, Facebook, Instagram, TikTok and Snapchat.

BUFFALO, NY - November 12, 2024 – A new #review was #published in Oncotarget's Volume 15 on November 7, 2024, entitled “Understanding the interplay between extracellular matrix topology and tumor-immune interactions: Challenges and opportunities.” This comprehensive review by researchers Yijia Fan, Alvis Chiu, Feng Zhao, and Jason T. George from Texas A&M University, Rice University, and MD Anderson Cancer Center sheds light on how the structural properties of the extracellular matrix (ECM) within tumors impact immune cell behavior and influence the effectiveness of cancer immunotherapies. The ECM, a network of proteins surrounding cells, often transforms in cancer, becoming denser and more aligned. These changes create physical barriers that can prevent immune cells, especially T cells, from effectively accessing and attacking tumors, thereby limiting the success of immunotherapies. The team emphasizes the role of specific ECM configurations, known as Tumor-Associated Collagen Signatures (TACS), in cancer progression and immune evasion. TACS1 and TACS2 patterns create "immune deserts" around tumors, limiting immune cell movement and preventing T cells from recognizing and attacking cancer cells, which is essential for successful immunotherapy. In advanced stages, TACS3 aligns ECM fibers in ways that both promote tumor spread and create additional barriers, further obstructing immune cell access to the tumor. These insights lead the way for ECM-targeted therapies designed to modify these barriers, potentially transforming “cold” (immune-non-responsive) tumors into “hot” (immune-responsive) ones, thereby improving immune cell infiltration and enhancing treatment outcomes. “Understanding the complex interplay is relevant for developing more accurate model of tumor evasion and the identification of corresponding therapeutic intervention.” The review highlights advanced computational models that simulate interactions between the ECM, immune cells, and tumors, offering valuable insights for developing ECM-targeted therapies. These models illustrate how modifying ECM properties could enhance immune cell migration and function, potentially overcoming immune resistance and expanding the effectiveness of immunotherapies. The authors also suggest that targeting ECM structure could significantly enhance the effectiveness of immunotherapy, especially for cancers like breast, pancreatic, and ovarian, which often feature dense ECM regions. By reshaping the ECM, such treatments could enable immune cells to access previously unreachable tumor areas, presenting a promising strategy to combat tumors that are resistant to standard therapies. In conclusion, the review underscores the need for continued research into ECM-focused strategies, which could support more integrated approaches to cancer treatment. By targeting the ECM's physical barriers and immune evasion mechanisms, these strategies hold promise for improving outcomes in difficult-to-treat cancers. DOI - https://doi.org/10.18632/oncotarget.28666 Correspondence to - Jason T. George - jason.george@tamu.edu Video short - https://www.youtube.com/watch?v=7Wm-SMLJadk Sign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28666 Subscribe for free publication alerts from Oncotarget: https://www.oncotarget.com/subscribe/ To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

Darshan H. Brahmbhatt, Podcast Editor of JACC: Advances, discusses a recently published original research paper on DPD quantification correlates with extracellular volume and disease severity in wild-type transthyretin cardiac amyloidosis.

Dr. Sherif Idriss is the CEO of Elastin Biosciences, a company focused on targeting aging-related diseases by restoring elastin, a key protein in the extracellular matrix that provides elasticity and resilience to organs and tissues. They are developing small molecule therapies for diseases linked to elastin deficiency, including Williams syndrome and abdominal aortic aneurysm. As elastin degrades over time due to aging, it leads to loss of tissue structural integrity and function, contributing to numerous age-related diseases.   Sherif explains, "One of the hallmarks of aging is the loss of the extracellular matrix, which is composed of several proteins. Collagen is quite famous, but also elastin is the other major protein that is responsible for the elasticity of the different organs. For example, in our skin, the loss of elastin is associated with us looking older and having all the aging signs and wrinkles on the skin. If you imagine that there are other organs inside that we don't visually see, then you have also the blood vessels, the lungs, a lot of the connective tissue. The extracellular matrix proteins and elastin itself are also aging in the same way and have their own form of damage one way or another. All of this contributes to aging and aging-related diseases as well." "Another kind of disease is the category of rare diseases. In this case, we aim to target Williams syndrome, a rare disease characterized by a genetic partial deletion of around 26 genes. One of these genes is elastin itself, so some genetic material is still there, but there is not enough. We would like to try to push the elastin production up in Williams syndrome, and this would help rectify a lot of the disease issues, particularly when it comes to the cardiovascular system because Williams syndrome patients have quite a lot of issues with the cardiovascular system from birth and all through life." #ElastinBiosciences #Aging #AgingRelatedDiseases #Elastin #WilliamsSyndrome  elastin-biosciences.com Download the transcript here

Dr. Sherif Idriss is the CEO of Elastin Biosciences, a company focused on targeting aging-related diseases by restoring elastin, a key protein in the extracellular matrix that provides elasticity and resilience to organs and tissues. They are developing small molecule therapies for diseases linked to elastin deficiency, including Williams syndrome and abdominal aortic aneurysm. As elastin degrades over time due to aging, it leads to loss of tissue structural integrity and function, contributing to numerous age-related diseases.   Sherif explains, "One of the hallmarks of aging is the loss of the extracellular matrix, which is composed of several proteins. Collagen is quite famous, but also elastin is the other major protein that is responsible for the elasticity of the different organs. For example, in our skin, the loss of elastin is associated with us looking older and having all the aging signs and wrinkles on the skin. If you imagine that there are other organs inside that we don't visually see, then you have also the blood vessels, the lungs, a lot of the connective tissue. The extracellular matrix proteins and elastin itself are also aging in the same way and have their own form of damage one way or another. All of this contributes to aging and aging-related diseases as well." "Another kind of disease is the category of rare diseases. In this case, we aim to target Williams syndrome, a rare disease characterized by a genetic partial deletion of around 26 genes. One of these genes is elastin itself, so some genetic material is still there, but there is not enough. We would like to try to push the elastin production up in Williams syndrome, and this would help rectify a lot of the disease issues, particularly when it comes to the cardiovascular system because Williams syndrome patients have quite a lot of issues with the cardiovascular system from birth and all through life." #ElastinBiosciences #Aging #AgingRelatedDiseases #Elastin #WilliamsSyndrome  elastin-biosciences.com Listen to the podcast here

Darshan H. Brahmbhatt, Podcast Editor of JACC: Advances discusses a recently published original research paper on neutrophil extracellular traps in ST-Segment elevation myocardial infarction.

Jean Claude Guimberteau is a French surgeon who specialises in endoscopic investigations of the human extracellular matrix, otherwise known as fascia. Over the span of several decades, Jean Claude has documented thousands of hours of footage of living tissue and the spaces between tissues. He has observed that the living extracellular matrix is a dynamic and fractal structure capable of absorbing stress and distributing it through the entire system in a non-linear manner. His work overlaps that of biotensegrity, systems biology and non-equilibrium thermodynamics, even extending to ideas of how posture influences cellular and even genomic processes.Follow Jean ClaudeBookDocumentaryFollow MeWebsiteSubstackConsultationInstagramYoutubeTwitter/XSpotifyAppleLinktree

Overcoming Confusion and Misinformation in Meeting the Needs of Children on the Spectrum While I'm used to guiding health-minded audiences deep down the Rabbit-Hole of water topics, today's discussion with Karen will be light on science and heavy on practicality. It aims to explain the challenging path for families who are intent on providing the safest and healthiest water for children on the Autism Spectrum and other Special Needs. Choosing water for consumption (drinking, beverages and food preparation) and water for bathing water for your family is daunting task because of the minefield of misinformation and hype that is associated with suppliers of water treatment for consumers. You cannot trust the Internet, your local water dealer, big-box stores or persuasive TV promotions. It is unconscionable and embarrassing to me – someone who spent the past 50+ years in the water industry that it has has not kept up with the current state of water contaminants AND the growing assaults on the declining state of health of humanity. Based on decades of observing homeowner's selection of water treatment technology, I conclude that more than 80-90% purchase and install inadequate systems for their and their children's health needs. Introduction The human body is 50% to over 90% water by weight depending on the stage of life. Not too long ago it was revealed that if we were to segregate all the types of molecules that make up the body, H2O would amount to 99% of them! An adult body contains roughly 40 liters of functional water derived from more than a billion years of evolution in the sea. No other single factor had such a profound influence on the animal kingdom's biological design and function. There are two primary compartments in the body: The Extracellular fluid (ECF) and the Intracellular Fluid. So, our 50+ trillion cells are floating in the Extracellular fluid (the Terrain) and contained within them is the Intracellular fluid where all the action is. It is the biochemical quality of the Terrain that governs overall health. Virtually all the great physiologists over the past 2 centuries agree one central concept – “The Terrain Is Everything” Understanding healthy hydration and how to maintain it Maintaining proper hydration is not only about consuming enough water. In fact, consuming an excessive amount of water can interfere with optimal hydration. Many factors can jeopardize the body's ability to maintain healthy hydration (illness, diarrhea, excessive work or exercise in hot climates, an imbalance in the quantity and variety of electrolytes). Key indicators of dehydration are varied and can include Lightheadedness or dizzy feeling Dry mouth and tongue and cracked lips Less frequent need to urinate Muscle cramps Thirst Frequent headaches Fatigue or drowsiness Urine has a darker color Eyes more sunken than usual The key physiological measure in achieving proper hydration is having sufficient water inside our cells – referred to as intracellular water. Sufficient pure water with the proper quantity and mix of electrolytes is key to achieving optimal hydration. A very rough daily guideline for those in good health is to consume – as water or sugar-free beverages (e.g. coffee, tea, vegetable juices, etc.)... Click Here or Click the link below for more details! https://naturallyrecoveringautism.com/199

Subscribe to Receive Venkat's Weekly Newsletter Rayyan was working 30 hour weeks while in High School. Outside of that, Rayyan was more likely to be playing basketball or video games. Then in his senior year he took some “sciency” classes, as he calls it, and did well and liked them! He felt Science might be his thing. Rayyan joins our podcast to share his UC Riverside undergraduate experience, UG Research, Winning the Goldwater Scholarship, Pursuing in Bioengineering, and his Advice for High Schoolers. In particular, we discuss the following with him:  Overall Undergraduate Experience UG Research in Tissue Engineering The Goldwater Scholarship Bioengineering Major Advice to High Schoolers Topics discussed in this episode: Introduction to Rayyan Ayoub, UCR [] Hi Fives - Podcast Highlights [] Overall Experience at UCR [] Why UCR? [] High School Interests [] Research Interest [] Starting UG Research [] The Research [] Impact of Research [] Goldwater Scholarship [] The GW Difference [] Challenges in School [] What's Next? [] Majoring in Bioengineering [] Advice for High Schoolers [] Memories [] Our Guests: Rayyan Ayoub is a Goldwater Scholar who is studying Bioengineering at the University of California Riverside. Memorable Quote: “If work is play, no one can beat you.” Rayyan Ayoub. Episode Transcript: Please visit Episode's Transcript. Similar Episodes: College Experiences , UG Research Calls-to-action: Follow us on Instagram. To Ask the Guest a question, or to comment on this episode, email podcast@almamatters.io. Subscribe or Follow our podcasts wherever you get your podcasts.

In this episode of the Critical Oxygen podcast, Dr. Robert Jacobs and I discuss how our bodies adapt to exercise. We explore the various cellular disturbances that are sensed by specific sensors and translate into intracellular signaling cascades that drive adaptation. The key themes covered include the importance of stress and adaptation, the specificity of exercise adaptations, energetic and mechanical signals, redox balance, decreased partial pressure of oxygen, mechanical tension, and extracellular signals. This conversation explores the signaling effects of various molecules and stimuli on muscle adaptation and overall health. Primary papers of discussion - https://pubmed.ncbi.nlm.nih.gov/23395166/ https://pubmed.ncbi.nlm.nih.gov/36395350/ TAKEAWAYS 1) Exercise imposes stress on the body, which leads to adaptations. The type and intensity of exercise determine the specific adaptations that occur. 2) Energetic and mechanical signals, redox balance, decreased partial pressure of oxygen, and mechanical tension are important cellular disturbances that drive adaptation. 3) Extracellular signals, such as hormones and proteins, also play a role in the adaptation process. Myokines, cytokines, and adipokines play important roles in signaling within different tissues. 4) Heat may act as a signaling agent and contribute to muscle and cardiovascular adaptations. 5) Exercise is a transient stress that promotes muscle adaptation. Disturbing cellular sensors through exercise and other means is important for overall health. Enjoy! Enjoying these podcasts? Don't forget to subscribe to get notified when new episodes are released. If you have a question or topic you want us to address, leave a comment! Follow Phil on Instagram - https://www.instagram.com/criticalo2 Interested in testing, courses, or other long form content check out the critical oxygen website - https://www.criticaloxygen.com CHAPTERS 00:00 Introduction 03:09 The Importance of Stress and Adaptation 10:10 Specificity of Exercise Adaptations 17:14 Energetic and Mechanical Signals 21:41 Redox Balance 25:28 Decreased Partial Pressure of Oxygen 31:26 Mechanical Tension 53:17 Extracellular Signals 56:39 Signaling Effects of Myokines and Cytokines 57:34 Heat as a Signaling Agent 58:28 Heat Shock Proteins as a Seventh Stimulus 59:32 Redundancy in Cellular Disturbances 01:00:30 The Importance of Redundancies in Human Robustness 01:01:25 Insulin Signaling and Non-Redundant Hormones 01:02:40 Exercise as a Transient Stress 01:03:30 Disturbing Cellular Sensors for Health

BUFFALO, NY- November 30, 2023 – A new #researchpaper was #published on the #cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 22, entitled, “Chronological aging impacts abundance, function and microRNA content of extracellular vesicles produced by human epidermal keratinocytes.” The disturbance of intercellular communication is one of the hallmarks of aging. In their new study, researchers Taku Nedachi, Christelle Bonod, Julie Rorteau, Wafae Chinoune, Yuri Ishiuchi, Sandrine Hughes, Benjamin Gillet, Nicolas Bechetoille, Dominique Sigaudo-Roussel, and Jérôme Lamartine from the University of Lyon, Toyo University and Gattefossé SAS aimed to clarify the impact of chronological aging on extracellular vesicles (EVs), a key mode of communication in mammalian tissues. “The present study was therefore conducted to elucidate whether the characteristics of EVs released from cultured human keratinocytes can be modulated during aging process.” The researchers focused on epidermal keratinocytes, the main cells of the outer protective layer of the skin which is strongly impaired in the skin of elderly. EVs were purified from conditioned medium of primary keratinocytes isolated from infant or aged adult skin. A significant increase of the relative number of EVs released from aged keratinocytes was observed whereas their size distribution was not modified. By small RNA sequencing, the researchers described a specific microRNA (miRNA) signature of aged EVs with an increase abundance of miR-30a, a key regulator of barrier function in human epidermis. EVs from aged keratinocytes were found to be able to reduce the proliferation of young keratinocytes, to impact their organogenesis properties in a reconstructed epidermis model and to slow down the early steps of skin wound healing in mice, three features observed in aged epidermis. This work reveals that intercellular communication mediated by EVs is modulated during aging process in keratinocytes and might be involved in the functional defects observed in aged skin. “To conclude, we have shown here that aging modulates EVs abundance, function and microRNA content in human keratinocytes.” DOI - https://doi.org/10.18632/aging.205245 Corresponding author - Jérôme Lamartine - jerome.lamartine@univ-lyon1.fr Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205245 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, keratinocytes, microRNA, senescence, exosomes 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

E.coli is one of the most studied and versatile bacteria, so how can we make it work for us? Bacteria's ability to generate electricity is well known, but often requires complex conditions. How can we use E.Coli to generate electricity without a complicated setup? Geothermal systems seem to promise unlimited power but sometimes a cold water 'short circuit' ruins the plan. How do you carefully control the efficiency of geothermal power in the extreme temperatures and pressures of the earth? References: Mohammed Mouhib, Melania Reggente, Lin Li, Nils Schuergers, Ardemis A. Boghossian. Extracellular electron transfer pathways to enhance the electroactivity of modified Escherichia coli. Joule, 2023; DOI: 10.1016/j.joule.2023.08.006 Qitao Zhang, Arash Dahi Taleghani. Autonomous fracture flow tunning to enhance efficiency of fractured geothermal systems. Energy, 2023; 281: 128163 DOI: 10.1016/j.energy.2023.128163  

The Doctor Dads are back!!! After a short hiatus Dr. David & Dr. Nick are back and bringing you some exciting content, guests, and conversations in the upcoming months. To kick off the return they will be doing a multiple part series breaking down the body ecosystem hierarchy. When looking at the body as a whole they is a hierarchy of the importance each system plays in coordination with all other systems. Each having their specific role and rhythm that plays out for the whole to be in coherence and harmony. In part one we begin with the extracellular matrix. Connecting every cell to every other cell, every system to every other system, and constantly moving energy and information through our body our fascial network is the most important system to keep the whole connected. Body Ecosystem Hierarchy The Extracellular Matrix Brain Lymphatic (Immune) Gut Vascular Nerves Organs Endocrine Musculoskeletal Local Tissue

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.04.551608v1?rss=1 Authors: Gomez-Ferrer, M., Amaro-Prellezo, E., Albiach-Delgado, A., Ten-Domenech, I., Kuligowski, J., Sepulveda, P. Abstract: Premature infants (PIs) are at risk of suffering necrotizing enterocolitis (NEC), and infants consuming human milk (HM) show a lower incidence than infants receiving formula. The composition of HM has been studied in depth, but the lipid content of HM-derived small extracellular vesicles (HM sEVs) remains unexplored. We isolated HM sEVs from HM samples and analyzed their oxylipin content using liquid chromatography coupled to mass spectrometry, which revealed the presence of anti-inflammatory oxylipins. We then examined the efficacy of a mixture of these oxylipins in combating inflammation and fibrosis, in vitro and and in a murine model of inflammatory bowel disease (IBD). HM-related sEVs contained higher concentrations of oxylipins derived from docosahexaenoic acid, an omega-3 fatty acid. Three anti-inflammatory oxylipins, 14-HDHA, 17-HDHA, and 19,20-DiHDPA ({omega}3 OXLP), demonstrated similar efficacy to HM sEVs in preventing cell injury, inducing re-epithelialization, mitigating fibrosis, and modulating immune responses. Both {omega}3 OXLP and HM sEVs effectively reduced inflammation in IBD-model mice, preventing colon shortening, infiltration of inflammatory cells and tissue fibrosis. Incorporating this unique cocktail of oxylipins into fortified milk formulas might reduce the risk of NEC in PIs and also provide immunological and neurodevelopmental support. 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/2023.07.28.551012v1?rss=1 Authors: Santiago, J. V., Natu, A., Ramelow, C. C., Rayaprolu, S., Xiao, H., Kumar, V., Seyfried, N., Rangaraju, S. Abstract: Microglia are resident immune cells of the brain that play important roles in mediating inflammatory responses in several neurological diseases via direct and indirect mechanisms. One indirect mechanism may involve extracellular vesicle (EV) release, so that the molecular cargo transported by microglia-derived EVs can have functional effects by facilitating intercellular communication. The molecular composition of microglia-derived EVs, and how microglial activation states impacts EV composition and EV-mediated effects in neuroinflammation, remain poorly understood. We hypothesize that microglia-derived EVs have unique molecular profiles that are determined by microglial activation state. Using size-exclusion chromatography to purify EVs from BV2 microglia, combined with proteomic (label-free quantitative mass spectrometry or LFQ-MS) and transcriptomic (mRNA and non-coding RNA seq) methods, we obtained comprehensive molecular profiles of microglia-derived EVs. LFQ-MS identified several classic EV proteins (tetraspanins, ESCRT machinery, and heat shock proteins), in addition to over 200 proteins not previously reported in the literature. Unique mRNA and microRNA signatures of microglia-derived EVs were also identified. After treating BV2 microglia with lipopolysaccharide (LPS), interleukin-10, or transforming growth factor beta, to mimic pro-inflammatory, anti-inflammatory, or homeostatic states, respectively, LFQ-MS and RNA seq revealed novel state-specific proteomic and transcriptomic signatures of microglia-derived EVs. Particularly, LPS treatment had the most profound impact on proteomic and transcriptomic compositions of microglia-derived EVs. Furthermore, we found that EVs derived from LPS-activated microglia were able to induce pro-inflammatory transcriptomic changes in resting responder microglia, confirming the ability of microglia-derived EVs to relay functionally-relevant inflammatory signals. These comprehensive microglia-EV molecular datasets represent important resources for the neuroscience and glial communities, and provide novel insights into the role of microglia-derived EVs in neuroinflammation. 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/2023.07.23.550166v1?rss=1 Authors: Newman, B. T., Jacokes, Z., Venkadesh, S. T., Webb, S. J., Kleinhans, N. M., McPartland, J. C., Druzgal, T. J., Pelphrey, K. A., Van Horn, J. D., For the GENDAAR Research Consortium Abstract: The neuronal differences contributing to the etiology of autism spectrum disorder (ASD) are still not well defined. Previous studies have suggested that myelin and axons are disrupted during development in ASD. By combining structural and diffusion MRI techniques, myelin and axons can be assessed using extracellular water, aggregate g-ratio, and a novel metric termed aggregate conduction velocity, which is related to the capacity of the axon to carry information. In this study, several innovative cellular microstructural methods, as measured from magnetic resonance imaging (MRI), are combined to characterize differences between ASD and typically developing adolescent participants in a large cohort. We first examine the relationship between each metric, including microstructural measurements of axonal and intracellular diffusion and the T1/T2 ratio. We then demonstrate the sensitivity of these metrics by characterizing differences between ASD and neurotypical participants, finding widespread increases in extracellular water in the cortex and decreases in aggregate g-ratio and aggregate conduction velocity throughout the cortex, subcortex, and white matter skeleton. This study is the first to reveal that ASD involves differences of myelin and axonal development with implications for neuronal function. We also introduce a novel neuroimaging metric, aggregate conduction velocity, that is highly sensitive to these changes. We conclude that ASD may be characterized by otherwise intact structural connectivity but that functional connectivity may be attenuated by network properties affecting neural transmission speed. This effect may explain the putative reliance on local connectivity in contrast to more distal connectivity observed in ASD. 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/2023.07.14.549082v1?rss=1 Authors: Brahmer, A., Geiss, C., Lygeraki, A., Neuberger, E., Tzaridis, T., Nguyen, T. T., Luessi, F., Regnier-Vigouroux, A., Hartmann, G., Simon, P., Endres, K., Bittner, S., Reiners, K. S., Kramer-Albers, E.-M. Abstract: Extracellular vesicles (EVs) derived from the CNS are potential liquid-biopsy markers for early detection and monitoring of neurodegenerative diseases and brain tumors. This study assessed the performance of a bead-based flow cytometry assay (EV Neuro) for multiparametric detection of CNS-derived EVs and identification of disease-specific markers. Different sample materials and EV isolation methods were compared. Glioblastoma- and primary human astrocyte-derived EVs exhibited distinct EV profiles, with signal intensities increasing with higher EV input. Analysis of serum or plasma from glioblastoma, multiple sclerosis, Alzheimers Disease patients and healthy controls showed varying marker signal intensities. Notably, data normalization improved marker identification. Specific EV populations, such as CD36+EVs in glioblastoma and GALC+EVs in multiple sclerosis, were significantly elevated in disease compared to controls. Clustering analysis techniques effectively differentiated glioblastoma patients from controls. A potential correlation between CD107a+EVs and neurofilament levels in the blood was identified in multiple sclerosis patients. Together, the semi-quantitative EV Neuro assay demonstrated its utility for EV profiling in complex samples. However, reliable statistical results in biomarker studies require large sample cohorts and high effect sizes. Nonetheless, this exploratory trial confirmed the feasibility of discovering EV-associated biomarkers and monitoring circulating EV profiles in CNS diseases using the EV Neuro assay. 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/2023.07.17.549331v1?rss=1 Authors: Milioto, C., Carcole, M., Giblin, A., Coneys, R., Attrebi, O., Ahmed, M., Harris, S. S., Lee, B. I., Yang, M., Nirujogi, R. S., Biggs, D., Salomonsson, S., Zanovello, M., De Oliveira, P., Katona, E., Glaria, I., Mikheenko, A., Geary, B., Udine, E., Vaizoglu, D., Rademakers, R., van Blitterswijk, M., Devoy, A., Hong, S., Partridge, L., Fratta, P., Alessi, D., Davies, B., Busche, M. A., Greensmith, L., Fisher, E. M., Isaacs, A. M. Abstract: A GGGGCC repeat expansion in C9orf72 is the most common genetic cause of ALS and FTD (C9ALS/FTD). The presence of dipeptide repeat (DPR) proteins, generated by translation of the expanded repeat, is a major pathogenic feature of C9ALS/FTD pathology, but their most relevant effects in a physiological context are not known. Here, we generated C9orf72 DPR knock-in mouse models characterised by physiological expression of 400 codon-optimised polyGR or polyPR repeats, and heterozygous C9orf72 reduction. (GR)400 and (PR)400 knock-in mice exhibit cortical neuronal hyperexcitability, age-dependent spinal motor neuron loss and progressive motor dysfunction, showing that they recapitulate key features of C9FTD/ALS. Quantitative proteomics revealed an increase in extracellular matrix (ECM) proteins in (GR)400 and (PR)400 spinal cord, with the collagen COL6A1 the most increased protein. This signature of increased ECM proteins was also present in C9ALS patient iPSC-motor neurons indicating it is a conserved feature of C9ALS/FTD. TGF-{beta}1 was one of the top predicted regulators of this ECM signature and polyGR expression in human iPSC-neurons was sufficient to induce TGF-{beta}1 followed by COL6A1, indicating TGF-{beta}1 is one driver of the ECM signature. Knockdown of the TGF-{beta}1 or COL6A1 orthologue in Drosophila dramatically and specifically exacerbated neurodegeneration in polyGR flies, showing that TGF-{beta}1 and COL6A1 protect against polyGR toxicity. Altogether, our physiological C9orf72 DPR knock-in mice have revealed a neuroprotective and conserved ECM signature in C9FTD/ALS. 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/2023.07.10.548429v1?rss=1 Authors: Warner, H., Franciosa, G., van der Borg, G., Faas, F., Koenig, C., de Boer, R., Classens, R., Maassen, S., Baranov, M., Mahajan, S., Dabral, D. D., Coenen, B., Bianchi, F., van Hilten, N., Risselada, H. J., Roos, W. H., Olsen, J., Querol Cano, L., van den Bogaart, G. V. Abstract: To mount an adaptive immune response, dendritic cells must process antigens, migrate to lymph nodes and form synapses with T cells. Critical to 3D migration and mechanosensing is the nucleus, which is the size-limiting barrier for navigation through gaps in the extracellular matrix. Here, we show that inflammatory activation of dendritic cells leads to the nucleus becoming spherically deformed, and enables dendritic cells to overcome the typical 2 to 3 micron pore limit for 3D migration. We show that the nuclear shape-change is partially attained through reduced cell adhesion, whereas improved migration through extracellular matrix is achieved through reprogramming of the actin cytoskeleton. Specifically we show that phosphorylation of cofilin-1 at serine 41 drives the assembly of a CofilinActoMyosin (CAM)ring proximal to the nucleus and enhances migration through 3D collagen gels. In summary, these data describe novel signaling events through which dendritic cells simultaneously deform their nucleus and enhance their migratory capacity; molecular events that may be recapitulated in other contexts such as wound healing and cancer. 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/2023.07.06.547926v1?rss=1 Authors: Pauwels, J., Van de Steene, T., Van de Velde, J., Eyckerman, S., Gevaert, K. Abstract: Extracellular vesicles (EVs), membrane-delimited nanovesicles that are secreted by cells into the extracellular environment, are gaining substantial interest due to their involvement in cellular homeostasis and their contribution to disease pathology. The latter in particular has led to an exponential increase in interest in EVs as they are considered to be circulating packages containing potential biomarkers and are also a possible biological means to deliver drugs in a cell-specific manner. However, several challenges hamper straightforward analysis of EVs as they are generally low abundant and reside in complex biological matrices. These matrices typically contain protein concentrations that vastly exceed those of the EV proteome and contain particles in the same size and density range (e.g. protein aggregates and apolipoprotein particles). Therefore, extensive EV isolation and purification protocols are imperative and many have been developed, including (density) ultracentrifugation, size-exclusion and precipitation methods. Here, we describe an approach based on 300 kDa MWCO filtration, which allows processing of multiple samples in parallel within a reasonable timeframe and at moderate cost. We demonstrate that our strategy is capable of quantitatively retaining EV particles on filters, whilst allowing extensive washing with relatively high percentages of the mild detergent TWEEN-20. In addition, we provide evidence that the retained EVs can be recuperated from the filter for qualitative studies or can be directly lysed on the filter for the recovery of the EV protein cargo for proteome analysis. Applying this strategy on MCF7 conditioned medium using different percentages of serum, we observed dramatic changes in the EV proteome. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.03.547488v1?rss=1 Authors: Romenskaja, D., Jonavice, U., Pivoriunas, A. Abstract: Autophagy dysfunction has been closely related with pathogenesis of many neurodegenerative diseases and therefore represents a potential therapeutic target. Extracellular vesicles (EVs) may act as a potent anti-inflammatory agents and also modulators of autophagy in target cells. However, the molecular mechanisms by which EVs modulate autophagy flux in human microglia remain largely unexplored. In the present study we investigated the effects of EVs derived from human oral mucosa stem cells on the autophagy in human microglia. We demonstrate that EVs promoted autophagy and autophagic flux in human microglia and that this process was dependent on the integrity of lipid rafts. LPS also activated autophagy, but combined treatment with EVs and LPS suppressed autophagy response indicating interference between these signalling pathways. Blockage of Toll-like receptor 4 (TLR4) with anti-TLR4 antibody suppressed EV-induced autophagy. Furthermore, blockage of EV- asscoiated HSP70 chaperone which is one of the endogenous ligands of the TLR4 also suppressed EV- induced lipid raft formation and autophagy. Pre-treatment of microglia with selective inhibitor of v{beta}3/v{beta}5 integrins cilengitide inhibited EV-induced autophagy. Finally, blockage of purinergic P2X4 receptor (P2X4R) with selective inhibitor 5-BDBD also suppressed of EV-induced autophagy. In conclusion, we demonstrate that EVs activate autophagy in human microglia through interaction with HSP70/TLR4, V{beta}3/V{beta}5, and P2X4R signalling pathways and that these effects depend on the integrity of lipid rafts. Our findings could be used for development of new therapeutic strategies targeting disease-associated microglia. 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/2023.06.29.547098v1?rss=1 Authors: O'Brien, J. G., Willis, A. B., Long, A. M., Kwon, J., Lee, G., Li, F., Page, P. G., Vo, A. H., Hadhazy, M., Crosbie, R. H., Demonbreun, A. R., McNally, E. M. Abstract: Genetic background shifts the severity of muscular dystrophy. In mice, the DBA/2J strain confers a more severe muscular dystrophy phenotype, whereas the Murphys Roth Large (MRL) strain has super-healing properties that reduce fibrosis. A comparative analysis of the Sgcg null model of Limb Girdle Muscular Dystrophy in the DBA/2J versus MRL strain showed the MRL background was associated with greater myofiber regeneration and reduced structural degradation of muscle. Transcriptomic profiling of dystrophic muscle in the DBA/2J and MRL strains indicated strain-dependent expression of the extracellular matrix (ECM) and TGF-b signaling genes. To investigate the MRL ECM, cellular components were removed from dystrophic muscle sections to generate decellularized myoscaffolds. Decellularized myoscaffolds from dystrophic mice in the protective MRL strain had significantly less deposition of collagen and matrix-bound TGF-b1 and TGF-b3 throughout the matrix, and dystrophic myoscaffolds from the MRL background were enriched in myokines. C2C12 myoblasts were seeded onto decellularized matrices from Sgcg-/- MRL and Sgcg-/- DBA/2J matrices. Acellular myoscaffolds from the dystrophic MRL background induced myoblast differentiation and growth compared to dystrophic myoscaffolds from the DBA/2J matrices. These studies establish that the MRL background also generates its effect through a highly regenerative ECM, which is active even in muscular dystrophy. 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/2023.06.29.546882v1?rss=1 Authors: Garcia, S., Windolf, C., Boussard, J., Dichter, B., Buccino, A. P., Yger, P. Abstract: High-density neural devices are now offering the possibility to record from neuronal populations in-vivo at unprecedented scale. However, the mechanical drifts often observed in these recordings are currently a major issue for "spike sorting", an essential analysis step to identify the activity of single neurons from extracellular signals. Although several strategies have been proposed to compensate for such drifts, the lack of proper benchmarks makes it hard to assess the quality and effectiveness of motion correction. In this paper, we present an exhaustive benchmark study to precisely and quantitatively evaluate the performance of several state-of-the-art motion correction algorithms introduced in literature. Using simulated recordings with induced drifts, we dissect the origins of the errors performed while applying motion-correction algorithm as a preprocessing step in the spike sorting pipeline. We show how important it is to properly estimate the positions of the neurons from extracellular traces in order to correctly estimate the probe motion, compare several interpolation procedures, and highlight what are the current limits for motion correction approaches. 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/2023.06.18.545506v1?rss=1 Authors: McNeill, M. C., Chee, F. L., Ebrhimighaei, R., Sala Newby, G. B., Newby, A. C., Hathway, T., Annaiah, A. S., Joseph, S., Carrabba, M., Bond, M. Abstract: 1.0BackgroundVascular calcification (VC) is a prevalent independent risk factor for adverse cardiovascular events and is associated with diabetes, hypertension, chronic kidney disease, and atherosclerosis. However, the mechanisms regulating the osteogenic differentiation of vascular smooth muscle cells (VSMC) are not fully understood. MethodsUsing hydrogels of tuneable stiffness and lysyl oxidase-mediated stiffening of human saphenous vein ex vivo,we investigated the role of extracellular matrix (ECM) stiffness in the regulation of VSMC calcification ResultsWe demonstrate that increased ECM stiffness enhances VSMC osteogenic differentiation and VSMC calcification. We show that the effects of ECM stiffness are mediated via a reduction in the level of actin monomer within the nucleus. We show that in cells interacting with soft ECM, elevated levels of nuclear actin monomer repress osteogenic differentiation and calcification by repressing YAP-mediated activation of both TEA Domain transcription factor (TEAD) and RUNX Family Transcription factor 2 (RUNX2). ConclusionThis work highlights for the first time the role of nuclear actin in mediating ECM stiffness-dependent VSMC calcification and the dual role of YAP-TEAD and YAP-RUNX2 transcriptional complexes. 2.0 GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/545506v1_ufig1.gif" ALT="Figure 1" greater than View larger version (24K): org.highwire.dtl.DTLVardef@10b52aforg.highwire.dtl.DTLVardef@619f4borg.highwire.dtl.DTLVardef@1212f97org.highwire.dtl.DTLVardef@1bb9766_HPS_FORMAT_FIGEXP M_FIG C_FIG 9.0 HIGHLIGHTSO_LIIncreased ECM stiffness promotes VSMC calcification. C_LIO_LIIncreased ECM stiffness reduces levels of nuclear actin monomer. C_LIO_LIOn physiological soft ECM, high levels of nuclear actin monomer inhibits calcification by repressing YAP activation. C_LIO_LIYAP activation promotes calcification by stimulating the activity of TEAD and RUNX2. C_LI Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Collin Yvès Ewald is a Swiss scientist investigating the molecular mechanisms of healthy aging. He is a molecular biologist and a professor at ETH Zurich, where he leads the Laboratory of Extracellular Matrix Regeneration The post Extracellular Matrix, Machine Learning, & Longevity Research Collin Ewald -Learning with Lowell 185 first appeared on Learning with Lowell.

In this episode, we review the high-yield topic of Extracellular Matrix⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠from the Biochemistry section. Follow ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Medbullets⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbullets --- Send in a voice message: https://podcasters.spotify.com/pod/show/medbulletsstep1/message

It's been 40 years since extracellular vesicles, or exosomes, were first connected to the way cells communicate and transfer information. Since then, researchers have studied what part they play in the normal physiology of a cell. There has also been an expanding amount of work in the role that exosomes can play in therapeutics and diagnostics of a wide range of diseases.  Jim West, CEO of Clara Biotech, joins us to share his perspective on research and innovation using exosomes as well as life in a biotech startup. He provides great insights into where this technology is today, the challenges being experienced in the field, and the potential and opportunity that the field of applied exosome research represents in the future. Tune in today. Subscribe to get future episodes. Share with a friend or colleague that might enjoy too! Visit https://thermofisher.com/molbioschool to access molecular biology resources and educational content. Experience the Speaking of Mol Bio podcast in its extended video format for a more immersive journey, while also ensuring accessibility with downloadable transcripts for each episode.Watch now at thermofisher.com/podcast-video

A new editorial paper was published in Aging (Aging-US) Volume 15, Issue 5, entitled, “Senescence and extracellular vesicles: novel partners in vascular amyloidosis.” In their editorial, researchers Meredith Whitehead, Marco Antonazzi and Catherine M. Shanahan from King's College London discussed amyloidosis—a prevalent age-associated pathology caused by the accumulation of fibrous, insoluble protein fibrils in tissues. The most common human amyloid is aortic medial amyloid (AMA), caused by aggregation of a 50-amino acid peptide called medin, which is cleaved by an unknown mechanism from its parent protein, milk fat globulin EGF-factor 8 (MFGE8). Medin is present in the vessel wall of 97% of Caucasians aged over 50- years ,yet despite its prevalence in the ageing population there is a very limited understanding of the mechanisms driving AMA. “Despite several forms of amyloidosis, including AMA and Alzheimer's disease (AD), being frequently associated with ageing, there has been limited research to date on the effect of cellular ‘ageing', termed senescence, on amyloidosis.” The novel data presented in the paper by Whitehead et al. provides evidence that vascular smooth muscle cell (VSMC)-derived small extracellular vesicles (sEVs) are key mediators of medin accumulation in the vessel wall. In addition, the authors identify, for the first time, a role for cellular senescence in triggering amyloidosis via changes in sEVs and extracellular matrix (ECM) composition. Thus, this study not only advances our understanding of how AMA is formed but uncovers potential therapeutic targets for mitigating the detrimental effects of amyloidosis on tissue function. “Further work is now required to understand the relationships between cellular ageing pathways, different forms of amyloidosis and potentially other ageing pathologies with shared mechanisms, such as vascular calcification, that often occur concomitantly within the aged ECM.” Full Editorial: DOI: https://doi.org/10.18632/aging.204571 Corresponding Author: Catherine M. Shanahan -cathy.shanahan@kcl.ac.uk Keywords: amyloid, smooth muscle cells, senescence, extracellular vesicles, medin Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204571 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

Video for this podcast: https://mehlmanmedical.com/hy-usmle-q-641-extracellular-matrix-proteins Main website: https://mehlmanmedical.com/ Instagram: https://www.instagram.com/mehlman_medical/ Telegram private group: https://mehlmanmedical.com/subscribe/ Telegram public channel: https://t.me/mehlmanmedical Facebook: https://www.facebook.com/mehlmanmedical Podcast: https://anchor.fm/mehlmanmedical Patreon: https://www.patreon.com/mehlmanmedical

Will Milligan, Founder of Extracellular.com, talks to Andrew Ive from Big Ideas Ventures. Extracellular is based in Bristol and is the very first partner in the cellular agriculture space. They are there to help accelerate media development able to screen thousands of formulations and produce quantities for larger scale-up runs.

Dr. Refky Nicola discusses the role of Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumor (VERDICT) MRI analysis in improving the classification of clinically significant prostate cancer with Dr. Valdair Muglia.  Avoiding Unnecessary Biopsy after Multiparametric Prostate MRI with VERDICT Analysis: The INNOVATE Study. Singh et al. Radiology 2022; 305:623–630

Listen to a blog summary of an editorial perspective published in Volume 13, entitled, "The future of bioorthogonal-chemistry for targeting of exosomes in precision medicine." ____________________________________________________________ Extracellular vesicles are membrane-bound vehicles released by cells into the extracellular environment. There are three known types of extracellular vesicles: microvesicles, apoptotic bodies and exosomes. Discovered in 1983, exosomes can be defined as packets of bio-nanoparticles released by cells containing bioactive molecules such as proteins, lipids and nucleic acids. Exosomes can deliver their payload to other cells and are now also recognized for their role in cell-to-cell communication. This makes exosomes attractive targets for precision medicine tactics. However, targeting exosomes is challenging due to their nano-size and reactive contents. Bioorthogonal-chemistry may provide a new approach for targeting exosomes in precision medicine. “Bioorthogonal is the name of a chemical reaction that can occur inside of living cells without interfering the naïve biological process [1, 2].” Bioorthogonal-chemistry allows for the attachment of bioactive molecules to the surface of exosomes without disturbing the native environment. Developed in the early 2000s, this strategy could potentially be used to deliver therapeutic drugs or bioactive molecules directly to the target site with high precision. Bioorthogonal-chemistry is still at an early stage of development, but it holds promise in precision medicine for the treatment of cancer and other illnesses. By providing a way to target exosomes with bioactive molecules, bioorthogonal-chemistry could help to significantly improve the efficacy of medical treatments. It could also reduce the side effects of current treatments and increase safety for patients. “The concept of bioorthogonal chemistry has inspired a generation of biologists to think about RNA editing and bioengineering of exosomes [3, 4].” Full blog - https://www.oncotarget.org/2022/12/20/a-new-method-of-targeting-exosomes-in-precision-medicine/ DOI - https://doi.org/10.18632/oncotarget.28323 Correspondence to - Mujib Ullah - ullah@stanford.edu About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ For media inquiries, please contact: media@impactjournals.com

In this podcast, Dr Luca Roz and Dr Luca Varinelli discuss about the usefulness of decellularized extracellular matrix obtained from cell cultures or cancer patients-derived tissue fragments for investigating the cross-talk between cancer cells and microenvironment niches in basic and translational research.

This week, please join author Trisha Singh as she discusses her article "Manganese-Enhanced Magnetic Resonance Imaging in Takotsubo Syndrome." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass for the journal and its editors. We're your co-hosts. I'm Dr. Carolyn Nam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, Associate Editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Carolyn, very interesting feature discussion this week. Many times we hear in magnetic resonance imaging the use of gadolinium contrast. And remember, gadolinium is an extracellular agent. And when we apply it in the heart, we look for infarcts, or areas of the heart that are perhaps dead, or scarred over. This week's feature discusses manganese as a contrast agent and it is an intracellular contrast agent. And very interestingly, it identifies calcium handling, so it's a marker of viability. And these authors are going to apply manganese as well as gadolinium in trying to understand mechanisms behind Takotsubo cardiomyopathy. But before we get to that, how about we grab a cup of coffee and jump into some of the other articles in the issue? Dr. Carolyn Lam: Oh, I'd love to tell you about the other articles. But just have to first say, I loved your description of the feature paper. It's right up your alley and I can't wait to learn more. But my first paper today I want to talk about pulse field ablation. Now, what is that? Pulse field ablation, or PFA, is a unique and novel technique to treat atrial fibrillation. It has a unique safety profile largely related to its preferentially for myocardial tissue ablation. And thus, sparing the esophagus and thus, deemed to have a unique safety profile. Now, a pentaspline catheter was the first such PFA system studied for AF ablation. And in the initial trials the catheter was used for pulmonary vein isolation and left atrial posterior wall ablation. However, following its regulatory approval in Europe, in clinical practice, physicians have ablated both these locations and expanded lesions that could be in closer proximity to the coronary arteries. Now, this is an unstudied important issue since preclinical and maybe some clinical data have raised the potential for coronary arterial spasm. Hence, the investigators led by Dr. Vivek Reddy from Icahn School of Medicine at Mount Sinai and colleagues studied the vasal spastic potential of PFA lesion sets, both remote from and adjacent to coronary arteries. Dr. Greg Hundley: Wow, Carolyn, this is a really interesting question. So what did they find? Dr. Carolyn Lam: In this retrospective analysis of a series of 25 patients undergoing PFA for atrial fibrillation in whom coronary angiography was performed pre, during and post ablation, they found that during pulmonary vein isolation and left atrial posterior wall ablation, coronary spasm did not occur. However, cavotricuspid isthmus ablation provoked severe subtotal vasospasm in five out of five consecutive patients. And this was relieved by in coronary nitroglycerin. ST elevation was not observed. No patient had severe spasm if first pretreated with parenteral nitroglycerin, either intracoronary or intravenous. And so in summary, coronary vasospasm was not provoked during PFA at locations remote from the coronary arteries. But when the energy is delivered adjacent to a coronary artery, like in cavotricuspid isthmus ablation, PFA did provoke subclinical vasospasm. And the phenomenon was attenuated by nitroglycerine administered either post hoc to treat spasm or as prophylaxis. And this is discussed in accompanying editorial, I like it, “Coronary Vasospasm in PFA Primum Non Nocere” by Drs. Estes and Sundeep and Saba. Dr. Greg Hundley: Very nice Carolyn. Very important research in this area using that particular methodology. Well Carolyn, my next study comes to us again from preclinical science. And Carolyn, this study evaluated mechanisms responsible for pulmonary hypertension. So as background, pulmonary hypertension is associated with increased expression of VEGFA and it's receptor VEGFR-2. But whether and how activation of VEGFA signal participates in the pathogenesis of pulmonary hypertension, that's unclear. And so these authors led by Dr. Yangxin Chen from Sun Yat-Sen Memorial Hospital and Sun Yat-Sen University evaluated VEGFA, VEGFR-2 signal activation and VEGFR-2 Y949 dependent vascular leak in lung samples from patients with pulmonary hypertension as well as in mice exposed to hypoxia. Dr. Carolyn Lam: Another one of those excellent translational pieces, isn't it Greg? So what did they find? Dr. Greg Hundley: Right Carolyn. So these authors found that pulmonary hypertension led to excessive pulmonary vascular leak in both patients and hypoxic mice. And this was owing to over activated VEGFA and VEGFR-2 Y949 signaling axis. Abolishing VEGFR-2 Y949 signaling via a specific point mutation was sufficient to prevent pulmonary vascular permeability and inhibit macrophage infiltration and Rac1 activation in smooth muscle cells under hypoxia exposure. This, in turn, led to alleviation of pulmonary hypertension manifestations including muscularization of distal pulmonary arterials, elevation of right ventricular systolic pressure and right ventricular hypertrophy. And so Carolyn, in summary, these results suggest that VEGFA, VEGFR-2 Y949 dependent vascular permeability is an important determinant in the pathogenesis of pulmonary hypertension and might serve as an attractive therapeutic target pathway for this disease. Dr. Carolyn Lam: Aw, thanks Greg for explaining that so well. The next paper talks about transcatheter aortic valve replacement of TAVR, recognizing that it is a well established treatment now for high and intermediate risk patients with severe symptomatic aortic stenosis. However, the question asked here is what makes some, but not all patients improve their left ventricular ejection fraction following TAVR associated after load reduction? Now, hypothesizing that circulating microRNAs may play a role here, the authors led by corresponding authors, Dr. Hosen and Jansen from University of Bonn and their colleagues profiled the differential expression of microRNAs in circulating extracellular vesicles in patients after TAVR. And in particular, the novel role of circulating microRNA 1225p in cardiomyocytes. Dr. Greg Hundley: Oh wow. So Carolyn, important study. So what did they find? Dr. Carolyn Lam: Well, first aortic stenosis increases circulating microRNA 1225p, which correlated with a lack of improvement of the EF in patients after TAVR. Extracellular vesicles harbored microRNA 1225p and facilitated its startling into the cardiomyocytes. Vesicular shuttling of this particular microRNA was regulated by a direct interaction with a multifunctional RNA binding protein called heterogeneous nuclear ribonucleoprotein U in a sequence specific manner. Extracellular vesicles containing the specific microRNA post transcriptionally repressed BCL2 an anti-apoptotic gene, which is central to cell viability and apoptosis. So in summary, Greg, an increase in extracellular vesicle microRNA 1225p in patients with aortic stenosis represents a novel mechanism for the deterioration of cardiac function in patients following TAVR. And pharmacological manipulation of this axis may improve ejection fraction and cardiac function in patients with aortic stenosis by improving the viability of cardiomyocytes, which opens the door to a potential therapeutic approach in patients with limited EF improvement following TAVR. Dr. Greg Hundley: Oh Carolyn, beautiful, beautiful description of that wonderful preclinical science. Well, let's reach into the mail bag and see what else is in the issue. And first, there's a research letter by Professor van Raalte entitled “Kidney Hemodynamic Effects of Angiotensin Receptor Blockades Sodium Glucose Co-transporter 2 Inhibition Alone and in Their Combination: A Crossover Randomized Trial in People with Type 2 Diabetes.” And Carolyn, there's also an In Depth piece from Dr. Marx entitled “GLP1 Receptor Agonist for the Reduction of Atherosclerotic Cardiovascular Risk in Patients with Type 2 Diabetes.” Dr. Carolyn Lam: Very, very nice papers, those two. There's also an exchange of letters between Drs. Hou and Sedej regarding the article, “Fine Tuning Cardiac Insulin Like Growth Factor 1 Receptor Signaling to Promote Health and Longevity.” As well as a Perspective by Dr. Eagle, “Comments on the 2022 Aortic Guidelines: Seeking More Precision in Aortic Care.” Now, let's go onto the feature discussion of all things MRI, shall we? Dr. Greg Hundley: You bet. More on manganese. Welcome listeners to this very interesting feature discussion on December 13th. And we have with us Dr. Trisha Singh from the University of Edinburgh in Edinburgh, Scotland. Welcome, Trisha. This is a fascinating study incorporating manganese cardiovascular magnetic resonance to study some of the mechanistic underpinnings of hypokinesis left ventricular hypokinesis in patients with Takotsubo syndrome. So maybe just describe for us some of the background information that went into the preparation of your study, and what was the hypothesis that you wanted to address? Dr. Trisha Singh: Yes, of course. So we know with patients with Takotsubo syndrome, it predominantly affects middle aged women, patients present with a degree of left ventricular dysfunction, which is transient. And, unfortunately, it can be quite difficult to diagnose because it can phenotypically present very similar to an acute coronary syndrome. We know from previous studies that these patients do have ongoing symptoms despite normalization of their LV function. And actually their outcomes are not as benign as previously thought. In terms of manganese enhanced MRI imaging, we at Edinburgh University have imaged patients with other cardiac conditions such as hypertrophic cardiomyopathy, and dilated cardiomyopathy. And have established that it can be used as a surrogate marker of myocardial calcium uptake and handling. So we were very interested to see whether or not patients with acute Takotsubo syndrome have got a myocardial calcium dysfunction and more importantly whether or not this translates into long-term dysfunction and perhaps could explain their symptoms and worse prognosis in long-term. Dr. Greg Hundley: Trisha, manganese MRI. Now, we hear about gadolinium MRI, how is manganese different? You mentioned it's a nice marker for calcium handling. Is this widely used clinically? What kind of contrast does it provide? Dr. Trisha Singh: So manganese was actually one of the first contrast agents to be used with magnetic resonance imaging. It kind of came about in the 1970s and 1980s. And previous animal models have looked at how it is essentially an intracellular contrast agent. And what I mean by that is manganese is a calcium analog and therefore, in cells where they are viable and there's intact cell function, they will be taken up through a voltage gated calcium channels. So, for example, in the heart. So the theory is that manganese, when you've got normal viability, manganese is taken up into the myocardium via voltage gate calcium channels. And several studies have shown that if you then have disease myocardium, these tissues do not take up the manganese as normal tissue would. And the main difference between manganese and gadolinium is they are both paramagnetic, which is why they're helpful and useful in MRI. But gadolinium, as a compound, is too big and it cannot cross an intact cell membrane and therefore, gadolinium is more extracellular. And as, we know, accumulates in tissues where there is increased edema, or water content. So gadolinium, for all intents and purposes, is incredibly useful contrast agent, certainly what we use predominantly at the moment in clinical practice, but it is extracellular. So the theory behind manganese is that it is an intracellular contrast agent as opposed to gadolinium. And where gadolinium accumulates in disease tissue, manganese accumulates in viable tissue. So they behave almost kind of in contrast to each other. And currently, manganese is not used in clinical practice. I think the only clinical compound contrast agent utilizing manganese was mangafodipir, otherwise known as Teslascan, which I believe came off the market in 2012 and that was predominantly used for imaging liver metastasis. Dr. Greg Hundley: Well Trisha, thank you for clarifying for us the difference between manganese, the intracellular contrast agent, and gadolinium, the extracellular contrast agent, that's so widely used clinically. Well, with that description, can you describe for us now, your study population and your study design? Dr. Trisha Singh: Perfect. So the study population was we aimed to recruit 20 patients with acute Takotsubo syndrome. The diagnosis of Takotsubo syndrome was based on a clinical diagnosis, so all our patients underwent a baseline echocardiography and invasive coronary angiography. Now, for us, the coronary angiography was quite important because we wanted to ensure we ruled out anyone with an acute myocardial infarction, which can often be tricky in this cohort of patients. So after recruiting 20 patients during the acute phase of Takotsubo, they all underwent a baseline gadolinium enhanced MRI scan followed by a manganese enhanced MRI scan. And these were done at least 48 hours a part. And then about three months roughly after the acute index, they were all invited to participate in a second manganese enhanced MRI scan. Dr. Greg Hundley: Very good. So two exams separated longitudinally over time. What were your study results? Dr. Trisha Singh: Our results demonstrated that during the acute phase as one would expect, patients had a degree of left ventricular dysfunction. The majority of our patients had afibrillar Takotsubo, so had afibrillar ballooning with preservation of the basal segments. With this, we also noted that in the areas that were affected by Takotsubo, so kind of the mid ventricular wall and the apex that all patients had significantly elevated native T1 and associated T2 as well. And as we expected there was reduced uptake of manganese and therefore kind of reduced calcium uptake in the myocardium in the area affected by Takotsubo syndrome. Interesting, what we also noticed was that all these patients had significantly elevated LV mass, which has been described in previous Takotsubo papers, certainly by Professor Dawson. And when you measured the left ventricular wall thickness, the LV wall thickness is elevated in the affected and actually not even in the non-affected areas, which I suspect explains why in the acute phase people almost doubles up which kind I guess fit with kind of acute myocardial edema and intense water content. And then, three months later when these patients returned for their follow-up scan, a lot of the acute changes had resolved. So native T2 values had improved and gone back to baseline. Native T1 and post contrast T1 values had remained elevated compared to the control population. And what we found was that manganese uptake, though it had improved, it still remained abnormal and reduced compared to the control population, which is a finding that we weren't expecting to find. Dr. Greg Hundley: Very interesting. So acutely we've got extracellular water there, elevation of myocardial T2, and also impaired manganese uptake. So intracellular abnormalities with calcium handling. Then later, so three months later, we have restoration of myocardial T2 so the extra water content is absent, but we have impaired manganese uptake indicating an abnormality with calcium handling. So how do we put this all together mechanistically? What does this tell us about the pathophysiology of Takotsubo syndrome? Dr. Trisha Singh: For one thing, I think we can say that there is, as described before, there is obviously intense myocardial edema present in patients with acute Takotsubo. And I think the significant elevation in T2 and LV mass kind of all fits together. Actually interestingly, as native T2 improves in their follow-up scans, the LV mass actually all return back to normal baseline. So I think the acute edema does resolve. And as you said, interestingly, despite all of these patients, their LV function completely recover. And despite that their myocardial calcium uptake, or handling remain normal. And I think that's not been demonstrated before. And I think it just points to that there is obviously, still something going on in the myocardium and it's not behaving completely normally despite completely normal kind of gross LV function. And potentially, this might point in the direction of why these patients have ongoing symptoms. So, certainly, from our observational cohort group, about 70% of patients had ongoing symptoms and this was predominantly breathlessness and palpitations. And potentially, might be related to why patients have worse outcomes compared to the general population. Dr. Greg Hundley: Very nice. And Trisha, can you describe, was there a therapeutic intervention between the acute and then the three month later measurements? Were these patients administered any type of medical therapy and were there differences in what those therapies may have been between different patients in your study? Dr. Trisha Singh: So predominantly, most of the patient population that were started on some combination of heart treatment due to the baseline LV dysfunction. And this kind of was a combination of most of them were on Ramipril, a few of them were also on spironolactone or eplerenone. And then, every single one was on furosemide. And interestingly, I mean I appreciate, I think the population group was quite small, so it's very difficult to compare those that were on kind of full heart failure treatment versus those who were just on beta blocker and ramipril therapy. But even in that cohort there was a split of about, I think predominantly, I think 17, 16 patients were on kind just beta blockers and ramipril as opposed to beta blocker, ramipril, spironolactone. And there was no difference kind of in the recovery in manganese uptake in that cohort. But, again, the numbers are quite small, so I think it's difficult to extrapolate any kind of true meaning in that. Of course, we know there's a lack of randomized control trial data looking at how to best treat patients with acute Takotsubo syndrome and certainly, what treatment may prevent these patients from having a recurrence of Takotsubo. And I know some of the TACA registry data has looked at actually despite the fact patients of being on beta blocker, or ramipril therapy, they still go having recurrence of Takotsubo and certainly of our cohort, one of our patients went on having a recurrent episode of Takotsubo within a year of her index event and she was on aspirin, beta blocker, spironolactone as well. Dr. Greg Hundley: Very nice. And then lastly, when you made these measurements looking at the manganese uptake or lack thereof, were these in the regions of myocardium where you mentioned many had apical LV wall motion abnormalities, were they in those regions or did you also measure regions remote to where the wall motion abnormality occurred? Dr. Trisha Singh: Of course. So we took measurements in the affected regions of the heart that kind of demonstrated spironolactone syndrome. And we also took measurements in kind of, so to speak, the remote segments of the heart. Now, for the remote segments of the heart, we could only measure native T1 and post contrast T1 at 30 minutes and to measure manganese uptake well, unfortunately, what we have to do is take a measurement over time, so we'd do every two and a half minutes for 30 minutes after the manganese contrast. So we weren't able to calculate manganese uptake in the remote regions. But what we could do was measure the native T1 in the remote region, and then the post contrast T1 and see how it differed with the region of interest in the affected portion of the heart, so to speak. Dr. Greg Hundley: Very good. Well, Trisha, with this really exciting research and very nice methodology, what do you see as the next study to be performed in patients with Takotsubo? Dr. Trisha Singh: So I think, in terms of manganese enhanced imaging, I think it'd be really interesting to re-scan these patients at one year or at two years. And the question there is whether or not their manganese uptake ever recovers really. I know we previously talked about this and thought about whether or not these patients who go onto developing Takotsubo syndrome might actually have a kind of an underlying cardiomyopathy that puts them at risk of developing Takotsubo with stress. So it'd be interesting to see whether or not actually their calcium uptake ever recovers in the long-term, or whether actually they have more of a chronic heart failure type like picture. And I think another area of interest would be to see potentially using manganese imaging as a noninvasive measure of kind of myocardial calcium activity and to see whether or there's any changes with therapy over the course of months to years or so. Dr. Greg Hundley: Very nice. Well listeners, we want to thank Dr. Trisha Singh from University of Edinburgh in Edinburgh, Scotland for bringing us this really interesting article in patients with Takotsubo syndrome demonstrating that there is a marked perturbation of myocardial manganese uptake, which is most evident in the acute phase of Takotsubo presentation, but also persists for at least three months despite apparent restoration of normal left ventricular ejection fraction and resolution of myocardial edema. All of this suggesting that abnormal myocardial calcium handling may be implicated in the pathophysiology of Takotsubo syndrome. Well, on behalf of Carolyn and myself, we want to wish you a great week. And we will catch you next week on the run. This program is copyright of the American Heart Association 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ajjournals.org.

Extracellular vesicles, or small balloon like structures, are released from both maternal and fetal cells during pregnancy, where they serve a communication function between mom and baby. Sarven Sabunciyan and colleagues at Johns Hopkins have also found they're associated with … Variations in levels of messenger RNA may help predict postpartum depression, Elizabeth Tracey reports Read More »

Show Notes Radioactive implant wipes tumors in unprecedented pre-clinical success | New Atlas (00:52) Pancreatic cancer is notoriously difficult to diagnose and treat, with tumor cells of this type highly evasive and loaded with mutations that make them resistant to many drugs.  3.2 percent of all cancers, yet is the third leading cause of cancer-related death Engineers at Duke University have developed a novel delivery system for cancer treatment and demonstrated its potential against one of the disease's most troublesome forms A radioactive implant completely eliminated tumors in the majority of the rodents The team wanted to figure out a way to implant into the tumor without causing damage to the surrounding tissue. Created one from more biocompatible materials (instead of titanium)  that wouldn't post the same risks to the human body. Synthetic chains of amino acids known as elastin-like polypeptides (ELPs), which form a stable gel-like material in the warmer environment of the body. This substance was injected into tumors in various mouse models of pancreatic cancer along with a radioactive element called iodine-131. ELP entombs the iodine-131 and prevents it from leaking into the body. Allows it to emit beta radiation that penetrates into the surrounding tumor. Once the radiation is spent, the ELP biogel safely degrades into harmless amino acids. The treatment was tested in combination with a common chemotherapy drug called paclitaxel. Across all the models tested, the scientists report a 100% response rate to the treatment.  In three quarters of the models, the dual treatment completely eliminated the tumors 80% of the time. The scientists deployed the novel treatment against pancreatic cancer because they wanted to explore its potential against one of the trickiest forms of the disease, but believe these results bode well for its wider application. Study author Jeff Schaal, explains the significance of their finding: “We did a deep dive through over 1,100 treatments across preclinical models and never found results where the tumors shrank away and disappeared like ours did … When the rest of the literature is saying that what we're seeing doesn't happen, that's when we knew we had something extremely interesting." In a first, scientists grow fully mature hair follicles in cultures | Interesting Engineering (07:12) According to a press release, researchers from Japan generated hair follicles in cultures while working on the processes of hair follicle growth and hair pigmentation.  Could contribute to the development of different applications such as hair loss treatment, animal testing and drug screenings. Scientists have been trying to understand the essential mechanisms of hair follicle development through animal models for a long while. Hair follicle morphogenesis wasn't something that could be reproduced in a culture dish until now. Morphogenesis is the process when the outer layer of skin and the connective tissue interacts while the embryo develops. Researchers built hair follicle organoids by controlling the structure generated from the two types of embryonic cells tapping into a low concentration of extracellular matrices. Extracellular matrix is a network that supplies structure for cells and tissue in the body. These matrices change the spacing between the two types of embryonic cells from a dumbbell-shape to core-shell configuration.  Fully mature hair follicles with approximately 3 millimeter (mm)-long hair shafts were produced by the hair follicle organoids on the 23rd day of being cultured. Researchers included a melanocyte-stimulating drug that helps produce hair color pigmentation in the culture medium.  The findings could help understand how physiological and pathological processes develop in relation to other organ systems as well.  Junji Fukuda, a professor with the faculty of engineering at Yokohama National University, speaks on next steps: “Our next step is to use cells from human origin, and apply for drug development and regenerative medicine.” Team uses live plant cells in 3D printing | Futurity (11:35) Researchers have developed a reproducible way of studying cellular communication among varied types of plant cells by “bioprinting” those cells with a 3D printer. Communication is key to understanding more about plant cell functions. Could ultimately lead to creating better crop varieties and optimal growing environments. They bioprinted cells from the model plant Arabidopsis thaliana and from soybeans to study not just whether plant cells would live after being bioprinted but also how they acquire and change their identity and function.  Lisa Van den Broeck, first author of a paper, describes the work: “A plant root has a lot of different cell types with specialized functions … There are also different sets of genes being expressed; some are cell-specific. We wanted to know what happens after you bioprint live cells and place them into an environment that you design. Are they alive and doing what they should be doing?” Live plant cells without cell walls, or protoplasts, were bioprinted along with nutrients, growth hormones, and a thickening agent called agarose. Agarose helps provide cells strength and scaffolding “When you print the bioink, you need it to be liquid, but when it comes out, it needs to be solid. Mimicking the natural environment helps keep cellular signals and cues occurring as they would in soil,” explained  Professor Ross Sozzani, co-corresponding author of the paper. The research showed that more than half of the 3D bioprinted cells were viable and divided over time to form microcalli, or small colonies of cells. Also bioprinted individual cells to test whether they could regenerate, or divide and multiply, which showed that Arabidopsis root and shoot cells needed different combinations of nutrients and scaffolding for optimal viability. More than 40% of individual soybean embryonic cells remained viable two weeks after bioprinting and also divided over time to form microcalli. End off with Professor Sozzani: “All told, this study shows the powerful potential of using 3D bioprinting to identify the optimal compounds needed to support plant cell viability and communication in a controlled environment,”  IKEA Is Using Driverless Trucks to Move Its Furniture in Texas | SIngularity Hub (18:49) Thanks to its mild climate, expansive highway network, and lax regulations, Texas has become the country's proving ground for driverless trucks. traveling the state's highways partially driver-free for a couple of years already autonomous mode on highways, but safety drivers take over to navigate city streets This week Kodiak Robotics announced a partnership to transport IKEA products using a heavy-duty self-driving truck. The route runs from an IKEA distribution center in Baytown, east of Houstin, to a store in Frisco, 290 miles away just north of Dallas. Kodiak has been around since 2018, and is focused on building a technology stack specifically for long-haul trucks.  Use a modular hardware approach that includes easy-to-install “mirror pods” with lidar and cameras. Seems like this company is on the rise with self driving trucks partnerships in place with CEVA Logistics and U.S. Express In August announced an agreement with Pilot Companies to develop services for self-driving trucks at Pilot and Flying J travel centers.  Kodiak's founder and CEO Don Burnette hopes the IKEA pilot will lead to a long-term relationship between the two companies, and an expansion of delivery routes for the furniture store.  Burnette told Forbes: “Up until now we've primarily been working with other carriers who work on behalf of shippers as their customers, and this is the first time we're working with a shipper directly … It was a really good opportunity to build that relationship and understand their operational needs.” New VR app lets you step inside your smartphone videos | Freethink (24:40) Startup Wist Labs is developing a VR app that converts your smartphone clips into 3D videos — giving you a chance to walk inside your memories using a VR headset. To create a memory with Wist, a user opens the app and records a video.  The app collects the information it needs to make the 2D clip look three-dimensional. Co-founder Andrew McHugh explained to Freethink: “During capture, we save color, depth, device pose, audio, and scene information … Depth is captured using the LiDAR sensors on the Pro model iPhones and iPads.” Once the app processes the video, the user can play it back using mobile AR or a VR headset. Video example of how it works  The next steps for Wist Labs are to close pre-seed funding, launch a beta, and then roll out features to fill in those gaps and improve the app.  McHugh plans to continue using it to capture and share memories of his first child McHugh explaining how the experience has been using it: “I loaded [an ultrasound video] into our VR app, shared it with my mom who lives halfway across the country, and we were able to both walk around that moment together … It's better than a video because it feels like you're actually there.”

Aetna Wun Trombley, CEO of Lycia Therapeutics, on extracellular protein degraders.

Dr. Henrique Borges da Silva is an Assistant Professor at the Mayo Clinic in Arizona. His main research focus is determining how extracellular nucleotides affect transcriptional, metabolic, and functional mechanisms of CD8+ T cells in response to viral infections and cancer. He talks about where extracellular ATP comes from, and how there could be a link between ATP and ADP immunological signaling and the powers of caffeine.

Veterinary surgical oncologist Dr. Nicole Ehrhart, one of the authors of “Regenerative medicine 2.0: Extracellular vesicle–based therapeutics for musculoskeletal tissue regeneration,” talks about translational and regenerative medicine, including how she discovered her passion for this field of inquiry through an unplanned volunteer experience early in her career. She also shares details of how she came to drive the process of implementing surveillance testing for COVID-19 in her state of Colorado. Hosted by Associate Editor, Dr. Sarah Wright, and Editor-in-Chief, Dr. Lisa Fortier. INTERESTED IN SUBMITTING YOUR MANUSCRIPT TO JAVMA OR AJVR?JAVMA: https://avma.org/JAVMAAuthorsAJVR: https://avma.org/AJVRAuthorsFOLLOW US:JAVMA:Facebook: Journal of the American Veterinary Medical Association - JAVMA | FacebookInstagram: JAVMA (@avma_javma) • Instagram photos and videosTwitter: JAVMA (@AVMAJAVMA) / Twitter AJVR: Facebook: American Journal of Veterinary Research - AJVR | FacebookInstagram: AJVR (@ajvroa) • Instagram photos and videosTwitter: AJVR (@AJVROA) / TwitterJAVMA and AJVR LinkedIn: https://linkedin.com/company/avma-journals#VeterinaryVertexPodcast #JAVMA #AJVR INTERESTED IN SUBMITTING YOUR MANUSCRIPT TO JAVMA ® OR AJVR ® ? JAVMA ® : https://avma.org/JAVMAAuthors AJVR ® : https://avma.org/AJVRAuthorsFOLLOW US:JAVMA ® : Facebook: Journal of the American Veterinary Medical Association - JAVMA | Facebook Instagram: JAVMA (@avma_javma) • Instagram photos and videos Twitter: JAVMA (@AVMAJAVMA) / Twitter AJVR ® : Facebook: American Journal of Veterinary Research - AJVR | Facebook Instagram: AJVR (@ajvroa) • Instagram photos and videos Twitter: AJVR (@AJVROA) / Twitter JAVMA ® and AJVR ® LinkedIn: https://linkedin.com/company/avma-journals

A new research paper was published on the cover of Aging (Aging-US) Volume 14, Issue 17, entitled, “Extracellular microRNA and cognitive function in a prospective cohort of older men: The Veterans Affairs Normative Aging Study.” Aging-related cognitive decline is an early symptom of Alzheimer's disease and other dementias, and on its own can have substantial consequences on an individual's ability to perform important everyday functions. Despite increasing interest in the potential roles of extracellular microRNAs (miRNAs) in central nervous system (CNS) pathologies, there has been little research on extracellular miRNAs in early stages of cognitive decline. In a new study, researchers Nicole Comfort, Haotian Wu, Peter De Hoff, Aishwarya Vuppala, Pantel S. Vokonas, Avron Spiro, Marc Weisskopf, Brent A. Coull, Louise C. Laurent, Andrea A. Baccarelli, and Joel Schwartz from Columbia University Mailman School of Public Health, University of California San Diego, VA Boston Healthcare System, Boston University School of Medicine, and Harvard TH Chan School of Public Health leveraged the longitudinal Normative Aging Study (NAS) cohort to investigate associations between plasma miRNAs and cognitive function among cognitively normal men. “In a cohort of older men from Massachusetts, we investigated associations between plasma miRNAs and global cognition and rate of global cognitive decline measured by the MMSE.” Full press release - https://aging-us.net/2022/09/15/aging-extracellular-microrna-and-cognitive-function-in-a-prospective-cohort-of-older-men-the-veterans-affairs-normative-aging-study/ DOI: https://doi.org/10.18632/aging.204268 Corresponding Author: Nicole Comfort – nicole.comfort@columbia.edu Keywords: plasma, extracellular RNA, RNA-seq, microRNA, cognitive decline, cognitive impairment Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204268 About Aging-US: Launched in 2009, Aging (Aging-US) publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at www.Aging-US.com​​ and connect with us: SoundCloud – https://soundcloud.com/Aging-Us Facebook – https://www.facebook.com/AgingUS/ Twitter – https://twitter.com/AgingJrnl Instagram – https://www.instagram.com/agingjrnl/ YouTube – https://www.youtube.com/agingus​ LinkedIn – https://www.linkedin.com/company/aging/ Reddit – https://www.reddit.com/user/AgingUS Pinterest – https://www.pinterest.com/AgingUS/ For media inquiries, contact media@impactjournals.com.

Osteochondral autograft transplant (OAT) is often used to treat large osteochondral lesions of the talus and is generally associated with good outcomes. The addition of adjuncts such as cartilage extracellular matrix with bone marrow aspirate concentrate (ECM-BMAC) may further improve the OAT procedure but have not been thoroughly studied. We hypothesized that the placement of ECM-BMAC around the OAT graft would improve radiographic and patient-reported outcomes following OAT. In conclusion, the addition of ECM-BMAC to OAT was associated with improved imaging and clinical outcomes compared to OAT with BMAC alone.   To view the article click here.

https://medicienterprises.com/2022/07/01/show-580/

Cellular agriculture or cultivated meat - often mistakenly called "lab-grown meat" - is now coming into its own with the first products nearing market readiness. Many of these companies now face the daunting task of scaling their innovation. Because most CDMOs for animal cell growth are geared toward the health sector, costs are much higher for bioprocessing than they need to be for the relatively less-stringent food sector when it comes to regulatory needs. Will Milligan founded https://www.extracellular.com/ (Extracellular), based in Bristol in the UK, as the first CDMO and innovation partner for cellular agriculture. With a background in mechanical engineering - and coming from a family of farmers - Will believes the solution to making cellular agriculture affordable, sustainable, and available requires innovation partnership for scaling up product development within the sector. In this episode of BioInnovation Spotlight, Will discusses the unmet needs underlying the cellular agriculture sector and the challenges faced by cultivated meat products in scaling up and getting to the market. Extracellular is based at and supported by https://sciencecreates.co.uk/ventures/ (Science Creates) in Bristol.

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Dr. Inti Zlobec, professor of digital pathology at the Institute of Pathology in the University of Bern, discusses her team's recent publication in Modern Pathology on the role of image analysis in assessing area of extracellular mucin and predicting consensus molecular subtypes (CMS) in colorectal carcinoma. The utilized deep learning algorithm had an excellent agreement with pathologists' estimates of mucin areas. Coupled with MSI, mucinous area estimates may predict CMS classification using only histopathology. This highlights the great potential of Image based classifier of molecular subtypes of colon cancer. Study by Nguyen, HG., Lundström, O., Blank, A. et al. Image-based assessment of extracellular mucin-to-tumor area predicts consensus molecular subtypes (CMS) in colorectal cancer. Mod Pathol 35, 240–248 (2022) See acast.com/privacy for privacy and opt-out information.

Welcome to another episode of the I3 podcast where you'll hear two after parties for the price of one! First up, you'll hear what happened after the More or Less webinar, which was all about timings of lab events and how important they are. Speakers who joined the I3 team were: Dr. Jason Swain and Dr. Rebecca Holmes with Dr. Chelsey Leisinger, Dr. Denny Sakkas, Hubert Joris, Dr. Alessandra Alteri, Tricia AdamsWatch the full webinar: What was discussed: Witnessing and time stamp accessHow time stamps are controversial - some people want to see it and some don't How ideas are presented to the team Using timestamp with difficult sperm cases - measuring the time to search for sperm FET's - time issues and the impact it has on the embryology The impact of the traffic light system in the UKThe Use of ‘add on's' and whether there should be a cost? Blastocyst debateDo they run shifts in the lab? In the second after party speakers included Dr. Pierre Comizzoli, Professor Marc Antoine Driancourt, Dr. Alison Bartolucci. Dr. Daniel Le Bourhis, Professor Islam M. Saadeldin, Dr. Eli Sellem and Dr. Antonio CapalboInternational Society for Extracellular vesicles Standards and oprations proceducres devleopd Extracting extracellular vesicles in the Giant Panda and discussion about artificial insemination. Discussions about life of Panda's how they live in China and other countries have to pay rent to get to work with them. Working with Panda's is very stressful as any mistakes, cause issuesWatch the Might Molecules webinar here Follow us on our socials: TwitterFacebook InstagramYou Tube

KSQD 3-30-2022: Ironically, some allergic asthma sufferers have less severe COVID-19 symptoms! More COVID news. mRNA vaccines are easier to revise for new variants. Extracellular vesicles and a new signaling pathway based on RNA found in round worms. How to protect against side effects of long-term proton pump inhibitor use. Fighting diabetes and cancer with microRNA, which regulates protein production. Acoustic shaping of cells in solution. Adverse childhood experiences affect how one deals with stress and is treatable with acupuncture

This episode describes how the nonliving connective tissues surrounding and connecting cells are also important in understanding Nexus Theory by the theoretical ability of collagen fibers to guide biophotons throughout your body and brain. The results of the two experiments described in this Episode are published here: Simanonok, K.E. Elastooptic photon signal modulation in collagenic fiber optics of tendon. Biomaterials, Medical Devices, and Artificial Organs  11:83-92, 1983.