Podcasts about dendritic

In this episode, we dive into the interplay between the gut microbiota (their postbiotics) and the immune system. We will examine how gut microbiome-derived metabolites, such as short-chain fatty acids (SCFAs) and polyphenol metabolites, influence immune function by modulating key cellular and molecular pathways within the intestinal mucosa. Additionally, we discuss strategies for supporting butyrate production and optimizing microbiome health to foster a balanced and resilient gut-immune axis. Topics: 1. Introduction Overview of the gut-immune axis. Importance of gut microbiome-derived metabolites in supporting immune function. 2. The Intestinal Barrier Layers of the intestinal wall Focus on mucosa, specifically the epithelium and lamina propria. 3. Structure of the Intestinal Layers The intestinal lumen, mucus layer, epithelium (with tight junctions), and lamina propria. Importance of the lamina propria as a hub for immune responses and structural integrity. 4. Cellular and Structural Components of the Lamina Propria Extracellular matrix (ECM): structural support. Fibroblasts and myofibroblasts. Lymphatic vessels: immune cell transport, linking mucosal and systemic immune systems. 5. Immune Cells in the Lamina Propria T cells: immune tolerance, regulatory T cells (Tregs). B cells: Secretory immunoglobulin A (sIgA). Dendritic cells: antigen sampling and presentation. Macrophages: pathogen clearance. Mast cells 6. Role of Secretory Immunoglobulin A (sIgA) Functions as a first-line defense in the intestinal mucus layer. Neutralizes pathogens, prevents epithelial adhesion. 7. Postbiotics Overview Bioactive compounds produced by gut microbiota. Examples: short-chain fatty acids (SCFAs) 8. Short-Chain Fatty Acids (SCFAs) and Their Functions Influence on Treg cells in the lamina propria, promoting immune tolerance. Butyrate also as an energy source for epithelial cells. 9. Supporting Butyrate Production Microbiome optimization to enhance beneficial butyrate-producing microbes. Use of prebiotics: resistant starch, soluble fibers, and polyphenols. Supplementation with sodium butyrate as an additional tool. 10. Other Postbiotics Antimicrobial peptides produced by beneficial microbes. Complex carbohydrates produced by beneficial microbes and can act as prebiotics. Polyphenol metabolites: Gut microbiota biotransforms polyphenols into bioactive metabolites with increased bioavailability. 11. Specific Polyphenols Examples: resveratrol, quercetin, and ellagitannins. Effects on intestinal barrier function, inflammation, and immune cell populations. "⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠75 Gut-Healing Strategies & Biohacks⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠" Follow Chloe on Instagram ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠@synthesisofwellness⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Follow Chloe on TikTok @chloe_c_porter Visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠synthesisofwellness.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ --- Support this podcast: https://podcasters.spotify.com/pod/show/chloe-porter6/support

When patients with recurrent high-grade glioblastoma were treated with autologous myeloid dendritic cells, they had clinical responses described as “encouraging” in a Phase I clinical trial reported at the ESMO Congress 2024. Cells harvested from each patient were injected directly into the resection cavity brain tissue lining after surgery. Patients also received intracranial injections of the checkpoint inhibitor combination: nivolumab + ipilimumab. At the conference, Oncology Times reporter Peter Goodwin caught up with lead author of the study, Bart Neyns, MD, PhD, Head of Medical Oncology at the Vrije Universiteit Brussel in the University Hospital Brussels Faculty of Medicine & Pharmacy in Belgium.

In this episode, we dive into how short-chain fatty acids (SCFAs), particularly butyrate, and tryptophan metabolites support the gut-immune axis by promoting regulatory T cell differentiation, strengthening the intestinal barrier, and enhancing antimicrobial defenses through IL-22 signaling. We break down how butyrate can improve immune tolerance as well as epithelial integrity, aiding in the prevention of chronic inflammatory responses. We also detail practical ways to support butyrate levels and aid in strengthening both the epithelial barrier and gut-immune axis. Topics: 1. Introduction - Overview of the role of SCFAs and tryptophan metabolites in supporting the gut-immune axis. - Quick review of the location of immune cells in relation to the gut microbiota. 2. The Intestinal Barrier - Structure of the intestinal wall and layers - Focus on the mucosal layer, specifically epithelium and lamina propria. 3. The Lamina Propria - Structural elements: fibroblasts, extracellular matrix (ECM), and myofibroblasts. - Vascular components: endothelial cells, capillaries, and lymphatic vessels. - Importance of the lamina propria as a hub for immune responses. 4. Immune Cells in the Lamina Propria - T cells: Role of regulatory T cells (Tregs) in immune modulation. - B cells: Production of IgA, class switching, and plasma cells. - Dendritic cells: Sampling luminal antigens and initiating immune responses. - Macrophages: Phagocytic activity, pro-inflammatory (M1) vs. anti-inflammatory (M2) states. - Mast cells: Role in allergic responses, chronic inflammatory conditions, and MCAS. 5. Short-Chain Fatty Acids (SCFAs) - Production of SCFAs (acetate, propionate, butyrate) by gut microbiota. - Butyrate's role in supporting regulatory T cell (Treg) differentiation and immune tolerance. -Butyrate as fuel for epithelial cells and the production of tight junction proteins. 6. Mechanisms of Butyrate in Immune Modulation - Impact on Tregs through FoxP3 expression. - SCFA's role in maintaining immune balance. 7. Butyrate and Epithelial Integrity - Support for tight junction protein expression. - Prevention of translocation of harmful microbes and antigens. - Reduced systemic inflammation through a strengthened barrier. 8. Supporting Butyrate Production - Sodium butyrate supplementation and microbiome optimization. - Role of fiber, polyphenols, and probiotics. 9. Tryptophan Metabolites - Overview of tryptophan metabolism by gut bacteria into indoles. - Indoles' role in promoting IL-22 production, contributing to antimicrobial defense and immune tolerance. 10. IL-22 - IL-22's enhancement of antimicrobial peptides (AMPs) and mucin production. - Case Study: Role of Lactobacillus strains in restoring IL-22 and helping to mitigate colitis. 11. Conclusion - Recap of how SCFAs and tryptophan metabolites interact with the gut-immune axis. - Importance of gut microbiome support for maintaining immune balance. Thank you to our episode sponsor: 1. Check out ⁠⁠⁠⁠Daily Nouri⁠⁠⁠⁠ and use code ⁠⁠⁠⁠CHLOE20⁠⁠⁠⁠ for 20% off your order. Thanks for tuning in! Get Chloe's Book Today! "⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠75 Gut-Healing Strategies & Biohacks⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠" Follow Chloe on Instagram ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠@synthesisofwellness⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Follow Chloe on TikTok @chloe_c_porter Visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠synthesisofwellness.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ to purchase products, subscribe to our mailing list, and more! --- Support this podcast: https://podcasters.spotify.com/pod/show/chloe-porter6/support

The most prominent visual characteristic of neurons is their dendrites. Even more than 100 years after their first observation by Cajal, their function is not fully understood. Biophysical modeling based on cable theory is a key research tool for exploring putative functions, and today's guest is one the leading researchers in this field.   We talk about of passive and active dendrites, the kind of filtering of synaptic inputs they support, the key role of synapse placements, and how the inclusion of dendrites may facilitate AI.    

Seizure medication recalled due to wrong strength on carton; Gene therapy gains Fast Track status for Parkinson disease; Dendritic cell vaccine being developed for pancreatic cancer; Generic version of sickle cell disease treatment Endari is made available

Dr. Francisco Contreras serves as director, president and chairman of the Oasis of Hope Hospital. A distinguished oncologist and surgeon, Contreras is renowned for combining conventional and alternative medical treatments with emotional and spiritual support to provide patients with the most positive treatment experience possible. Oasis of Hope was founded by Contreras' father, Dr. Ernesto Contreras, Sr. in 1963, and since then the hospital has provided integrative cancer treatment for more than 100,000 patients. As director, Contreras continues the practice of his father's two fundamental principles – do no harm and treat the patient as yourself. Today, Contreras oversees the treatment of 800 cancer patients annually. After graduating with honors from medical school at the Autonomous University of Mexico in Toluca, Contreras studied alternative therapy at the Oasis of Hope Hospital. He then completed his specialty in surgical oncology at the University of Vienna in Austria, where he also graduated with honors. Contreras has authored and co-authored several books concerning integrative therapy, cancer and heart disease prevention and chronic illness, including “The Hope of Living Cancer Free,” “The Hope of Living Long and Well,” “Fighting Cancer 20 Different Ways” and “Dismantling Cancer.” His newest book The Art & Science of Undermining Cancer shares a revolutionary approach to cancer treatment that focuses on the patient, provides resources to the body, mind, and spirit, and leverages the metabolic traits of cancerous cells to undermine a tumor's strength. Topics covered in this episode:Artificial Intelligence in MedicineChallenges in Cancer TreatmentDendritic Cell VaccinesSuccess Rates With Patients Cancer Prevention MethodsImportance of DietExercise for Cancer PreventionBlue Zones and LongevityReferenced in the episode:The Lindsey Elmore Show Ep 265 | Antibiotics Unveiled: Impact on Gut Ecology |  Dr. Steven R. GundryTo learn more about Dr. Francisco Contreras and his work, head over to www.oasisofhope.com__________________________________________________________Somavedic is a device that can reliably mitigate unwanted influences of:EMF radiation (4G/5G, WiFi, phones)Geopathic stress, water crossesCurry and Hartmann linesOxidative stress / Free radicalsHead over to www.somavedic.com and use the code: LKE to save 10% off. __________________________________________________________We hope you enjoyed this episode. If you would like to be a supporter of the show, head to www.lindseyelmore.com/supporter Your contribution helps us to bring the best guests into our interview chair. Thank you for listening. Come check us out at www.spreaker.com/show/the-lindsey-elmore-showBecome a supporter of this podcast: https://www.spreaker.com/podcast/the-lindsey-elmore-show--5952903/support.

In today's episode, we go through the intricacies of lymphatic health in order to understand the mechanisms behind lymphatic congestion, fluid accumulation, and poor immune function. We highlight the pivotal role of white blood cells in orchestrating immune responses and emphasize diverse strategies for maintaining lymphatic flow. We go over herbal supplements, physical therapies, and peptide interventions, also evaluating whether or not they are research-backed. Topics: 1. Introduction to Lymphatic System and its Importance - Definition and Composition of Lymph - Functions of Lymphocytes (T cells, B cells, T cell types, and antibodies) 2. Components of the Lymphatic System - Lymphatic vessels - Lymph nodes - Bone marrow and thymus - Other lymphoid organs (Spleen, Tonsils, Adenoids, Peyer's patches) 3. Role of White Blood Cells (WBCs) in the Lymphatic System - Macrophages in innate immunity - Dendritic cells in antigen presentation - Adaptive immune response initiation 4. Causes and Effects of Lymphatic Congestion - Pathogen invasion and immune response - Inflammation and swelling of lymph nodes - Impaired lymphatic fluid flow and drainage 5. Strategies for Supporting Lymphatic Health - Herbal and Nutritional Support - Ginger, Ginseng, Cleavers, Red Clover, Echinacea, Burdock Root, Calendula - Physical Therapies - Exercise, Rebounding, Vibration Therapy, Manual Lymphatic Drainage - Peptide Therapies (Personal Thoughts & Use) - Thymosin alpha 1, Ovagen, Crystagen 6. Conclusion - Importance of holistic approach to lymphatic health - Always work with a licensed medical professional Thank you to our episode sponsor: Check out MoonBrew Here! Thanks for tuning in! Get Chloe's Book Today! "⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠75 Gut-Healing Strategies & Biohacks⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠" If you liked this episode, please leave a rating and review or share it to your stories over on Instagram. If you tag @synthesisofwellness, Chloe would love to personally thank you for listening! Follow Chloe on Instagram ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠@synthesisofwellness⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Follow Chloe on TikTok @chloe_c_porter Visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠synthesisofwellness.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ to purchase products, subscribe to our mailing list, and more! Or visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠linktr.ee/synthesisofwellness⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ to see all of Chloe's links, schedule a BioPhotonic Scanner consult with Chloe, or support the show! Thanks again for tuning in! --- Support this podcast: https://podcasters.spotify.com/pod/show/chloe-porter6/support

In this episode, we discuss common genetic and proteins implicated with Autism. This episode is all about preparing for a future episode about Excitation and Inhibition imbalance- a known phenomena with Autism. I play Tug-of-War with Barbed-Wire and talk about a critical factor of our environment implicating proteins and development- This is huge, and necessary. Genomic Architecture of Autism https://www.cell.com/cell/pdf/S0092-8674(22)01324-1.pdfPTEN and mTOR https://www.cell.com/cell-reports/fulltext/S2211-1247(22)01435-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124722014358%3Fshowall%3Dtrue16p11.2, Serotonin, and Possible Social Deficit Rescueshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824539/https://www.nature.com/articles/s41586-018-0416-4https://www.nature.com/articles/s41386-021-01091-6https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606557/Dr. Jack Kruse on Autism https://jackkruse.com/category/autism/Cullin 3 / Cul3 https://pubmed.ncbi.nlm.nih.gov/31455858/SHANK3 https://pubmed.ncbi.nlm.nih.gov/?term=shank3Neurexin and Neuroligin https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120877/https://www.sciencedirect.com/science/article/pii/S0092867414006734(0:00) Introduction; Excitation and Inhibition; (3:15) Phosphate and Tensin- Pten; Synapses, Soma Size, Migration, Cellular Spine Density, Dendritic Overgrowth, Myelination; mTOR (Rapamycin) and hope; Are cells doing what they should? (10:18) 16p11.2; Serotonin; Raphe and Nucleus Accumbens; Possible Therapeutic Help;(13:40) NEED TO KNOW INFORMATION; Tryptophan, Aromatic Amino Acids, UV-B Light and Proteins; Changes in our Light Environment and Implications to our Biology and Modern Health Concerns; Photoreceptors and Brain and Skin Connection- Neuroectoderm; Circadian Mismatch;(19:24) Back to 16p11.2 and Cortical Development;(22:00) Cullin 3 and Cul3 and Implications to Socialness and Sensory-Gating; Causes of Stereotypic Behaviors; Neuronal Excitability;(24:09) SHANK3; Tissues and Brain; Synaptic Implications; more Spine and Dendritic formation; Sensory Processing; Repetitive Behaviors; Anxiety; Social Deficits; Poor Motor Coordination;(25:59) Neurexin and Neuroligin; Synaptic development and action; Myelination; E/I and Spine; CNTNAP2 and mPFC(29:25) Wrap Up and Contact Informationemail: info.fromthespectrum@gmail.com

Today, I am blessed to have here with me Dr Matt Halpert. He has a doctorate in immunology, with a specific focus on inflammation and microbiology and the way the immune system operates and should operate. Dr Matt spent 10 years in the Texas Medical Center predominantly at Baylor College of Medicine, as an academic researcher, focused on cancer and cancer immunotherapy.  With regard to how the immune system functions, its physiology, how it goes about identifying a threat, whether that threat is a virus or cancer, and how that immune system can then be essentially reprogrammed or correctly directed toward fighting that threat, the research team Dr Matt was with made what we now know to be an extremely important discovery.  In this episode, Dr Matt speaks about immunotherapy to fight against cancer. He will also share about Immunocine Cancer Center, which provides one of the most advanced Cancer Immunotherapies available. They are supported by academic studies and several clinical studies which makes them unique from any other cancer treatment centre. Tune in as we chat about the difference in your immune system when you're younger and as an adult, using the immune system to fight off cancer, how stress can weaken your immune system, dendritic cells, and how can you support your immune system. Order Keto Flex: http://www.ketoflexbook.com -------------------------------------------------------- Download your FREE Vegetable Oil Allergy Card here: https://onlineoffer.lpages.co/vegetable-oil-allergy-card-download/ / / E P I S O D E   S P ON S O R S  ⭐ Biotiquest Sugar Shift product. Regulate glucose, reduce cravings, achieve deeper ketosis, and remove glyphosate. Head to https://bit.ly/47QZdbK , and use the coupon code KAMP10 for 10% off their products.  ⭐ Bioptimizers Magnesium Breakthrough. Get the best night of sleep ever. NO OTHER supplement on the market offers 7 types of magnesium in 1 bottle. Visit bioptimizers.com/ketokamp  and use promo code ketokamp10 for 10% off your first order.  ⭐ Upgraded Formulas | http://www.upgradedformulas.com Purchase Upgraded Formulas, Charge Electrolytes, and other products. GET 15% OFF with Coupon Code: KETOSIS Text me the words "Podcast" +1 (786) 364-5002 to be added to my contacts list.   [5:07] Strengthen your immune system to help fight cancer effectively. Chemotherapy would be analogous to putting a bomb on a building knowing there are bad guys (cancer) inside in the hopes of taking out all of the bad guys, but with the added risk of causing collateral damage. Even if it isn't shown on the scan, the bad guys are still there if you don't get them all. Relapse is undoubtedly a possibility in the future. Using the immune system and immunotherapy is a little more like using the Navy SEALs to go into the building and very specifically identify and eliminate those threats rather than the widespread destruction. If we're going to get to cures, it's going to be in the space of immunotherapy and rearming the immune system.  Our immune system, also known as our defense system, constantly guards against viruses, bacteria, and other pathogens, including cancer. Dendritic cells are a type of immune cell that runs the whole system. They are the generals of the immune system army.  [16:09] Why does the immune system lose its understanding? We tend to break down more frequently as we get older, our health tends to weaken, and we don't bounce back as quickly. That is a clear external reality, but there is also an inside reality. Mutations take longer to fix.  You need to have adequate movement each day. You need to exercise. When we are young, we are generally always on the move. As we age, we spend a lot more time sitting down and we don't try to exercise every day. Therefore, despite the immune system's potential strength, your body is no longer benefiting from it as quickly as it could.  [28:48] The First Cancer Treatment to Maximize the Immune System Immunocine Cancer Center send people a dozen or two dozen publications about dendritic cells and their role in cancer. That is their own science. They're not hiding from mainstream medicine, it just takes time.  They gathered the ideal group of medical professionals, including oncologists, radiologists, hematologists, and scientists. In addition, they have a cleanroom lab that complies with FDA regulations, where each patient's customized immunotherapy is created.  What they can do is reprogram your immune response to get going and get fighting. Instead of working in a lab, their scientists take a sample of the tumor and analyze it to find its protein library and very particular RNA components. The measures they followed to transform the blood cells into the appropriate type of dendritic cells over the course of a week are what make their technique so special.  They give you a legitimately unique, strong immune response that actually does ramp up and start fighting cancer. [58:36] Does immunotherapy works for all types of cancer? Here's what you need to know! As of today, Immunocine Cancer Center are not treating hematological malignancies, which are blood cancers, and heart cancers, and they're not treating brain cancers. They can treat a lot of cancers. It can be in conjunction with other treatment approaches.  AND MUCH MORE! Resources from this episode:  *Please note, the article Dr Matt Halpert & Ben Azadi wrote has not been published yet* Website: https://immunocine.com/  LinkedIn: https://www.linkedin.com/in/matthew-halpert-b4695174/  Facebook: https://m.facebook.com/people/Matt-Halpert/100079347564008/  Youtube: https://www.youtube.com/channel/UCWaOucdS32jADd-8JAVGh8w   Join the Keto Kamp Academy: https://ketokampacademy.com/7-day-trial-a  Watch Keto Kamp on YouTube: https://www.youtube.com/channel/UCUh_MOM621MvpW_HLtfkLyQ  Order Keto Flex: http://www.ketoflexbook.com -------------------------------------------------------- Download your FREE Vegetable Oil Allergy Card here: https://onlineoffer.lpages.co/vegetable-oil-allergy-card-download/ / / E P I S O D E   S P ON S O R S  ⭐ Biotiquest Sugar Shift product. Regulate glucose, reduce cravings, achieve deeper ketosis, and remove glyphosate. Head to https://bit.ly/47QZdbK , and use the coupon code KAMP10 for 10% off their products.  ⭐ Bioptimizers Magnesium Breakthrough. Get the best night of sleep ever. NO OTHER supplement on the market offers 7 types of magnesium in 1 bottle. Visit bioptimizers.com/ketokamp  and use promo code ketokamp10 for 10% off your first order.  ⭐ Upgraded Formulas | http://www.upgradedformulas.com Purchase Upgraded Formulas, Charge Electrolytes, and other products. GET 15% OFF with Coupon Code: KETOSIS Text me the words "Podcast" +1 (786) 364-5002 to be added to my contacts list.   Some links are affiliate links  // F O L L O W ▸ instagram | @thebenazadi | http://bit.ly/2B1NXKW ▸ facebook | /thebenazadi | http://bit.ly/2BVvvW6 ▸ twitter | @thebenazadi http://bit.ly/2USE0so ▸ tiktok | @thebenazadi https://www.tiktok.com/@thebenazadi Disclaimer: This podcast is for information purposes only. Statements and views expressed on this podcast are not medical advice. This podcast including Ben Azadi disclaim responsibility from any possible adverse effects from the use of information contained herein. Opinions of guests are their own, and this podcast does not accept responsibility of statements made by guests. This podcast does not make any representations or warranties about guests qualifications or credibility. Individuals on this podcast may have a direct or non-direct interest in products or services referred to herein. If you think you have a medical problem, consult a licensed physician.

Show notes and links: https://www.chrisbeatcancer.com/48-year-stage-iv-survivor-dr-robert-gorter-on-healing-cancer-with-mistletoe-dendritic-cell-therapy-hyperthermia-and-cannabinoids

References Front Immunol. 2019; 10: 14 Cancer Immunol Immunother. 2016 Apr;65(4):441-52 Anal Cell Pathol (Amst).2018; 2018: 787.1814. Molecular Cancer 2020. volume 19, Article number: 39 Cohan, G. 1917. "Over There" https://youtu.be/BYV044H5muI?si=LdANMG6dtXeC14tj --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

Featuring a slide presentation and related discussion from Prof Naveen Pemmaraju, including the following topics: Overview of blastic plasmacytoid dendritic cell neoplasms (0:00) Tagraxofusp: Development of the first FDA-approved targeted therapy for BPDCN (9:07) Integration of pivekimab sunirine into the management of BPDCN (20:31) Emerging novel therapies for patients with BPDCN and current role of chemotherapy-based regimens (26:02) Future directions in the management of BPDCN (33:26) CME information and select publications

Featuring an interview with Prof Naveen Pemmaraju, including the following topics: Case: A woman in her mid 20s with classic blastic plasmacytoid dendritic cell neoplasm (BPDCN) who responded to combination hyper-CVAD/venetoclax (0:00) Defining and diagnosing BPDCN (5:17) Presentation, prevention and management of capillary leak syndrome (7:56) Targeting CD123 in BPDCN (12:53) Case: A man in his early 70s with TET-mutated BPDCN who had a complete response to tagraxofusp (14:21) Selection of CD123-targeted therapy for patients with BPDCN (20:05) Case: A man in his mid 60s who had a complete response to pivekimab sunirine (27:04) Future directions in the treatment of BPDCN (28:55) CME information and select publications

Dr Naveen Pemmaraju from the University of Texas MD Anderson Cancer Center in Houston, Texas, discusses current and emerging management approaches for blastic plasmacytoid dendritic cell neoplasms.

Dr Naveen Pemmaraju from the University of Texas MD Anderson Cancer Center in Houston, Texas, discusses current and emerging management approaches for blastic plasmacytoid dendritic cell neoplasms moderated by Dr Neil Love. CME information and select publications here (https://www.researchtopractice.com/OncologyTodayBPDCN23)

Dr. Iyad Alnahhas interviews Drs. Kelly Hotchkiss and Mustafa Khasraw about their recently published review entitled: "Dendritic cell vaccine trials in gliomas: untangling the lines", published online in Neuro-Oncology in June 2023. Read Paper

A new research paper 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 16, entitled, “Dectin-1 stimulation promotes a distinct inflammatory signature in the setting of HIV-infection and aging.” Dectin-1 is an innate immune receptor that recognizes and binds β-1, 3/1, 6 glucans on fungi. In this new study, researchers Archit Kumar, Jiawei Wang, Allen Esterly, Chris Radcliffe, Haowen Zhou, Brent Vander Wyk, Heather G. Allore, Sui Tsang, Lydia Barakat, Subhasis Mohanty, Hongyu Zhao, Albert C. Shaw, and Heidi J. Zapata evaluated Dectin-1 function in myeloid cells in a cohort of HIV-positive and HIV-negative young and older adults. “The HIV-positive and HIV-negative groups were comparable in age and gender distribution, incidence of comorbidities such as diabetes, metabolic syndrome, cardiovascular disease and pulmonary disease.” Stimulation of monocytes with β-D-glucans induced a pro-inflammatory phenotype in monocytes of HIV-infected individuals that was characterized by increased levels of IL-12, TNF-α, and IL-6, with some age-associated cytokine increases also noted. Dendritic cells showed a striking HIV-associated increase in IFN-α production. These increases in cytokine production paralleled increases in Dectin-1 surface expression in both monocytes and dendritic cells that were noted with both HIV and aging. Differential gene expression analysis showed that HIV-positive older adults had a distinct gene signature compared to other cohorts characterized by a robust TNF-α and coagulation response (increased at baseline), a persistent IFN-α and IFN-γ response, and an activated dendritic cell signature/M1 macrophage signature upon Dectin-1 stimulation. Dectin-1 stimulation induced a strong upregulation of MTORC1 signaling in all cohorts, although increased in the HIV-Older cohort (stimulation and baseline). In sum, this study demonstrates that the HIV Aging population has a distinct immune signature in response to Dectin-1 stimulation. This signature may contribute to the pro-inflammatory environment that is associated with HIV and aging. “Overall, this study demonstrates that age, HIV-infection and co-morbidities can alter the individual immune response. In particular our study showed a unique immune signature in the setting of both HIV and aging in response to Dectin-1 stimulation.” DOI - https://doi.org/10.18632/aging.204927 Corresponding author - Heidi J. Zapata - heidi.zapata@yale.edu Video short - https://www.youtube.com/watch?v=MpMBDvv0dDI Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204927 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, immune response, innate immune cells, HIV-infection, dectin-1 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

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.03.551788v1?rss=1 Authors: Eberhardt, F. Abstract: The cable equation is key for understanding the electrical potential along dendrites or axons, but its application to dendritic spines remains limited. Their volume is extremely small so that moderate ionic currents suffice to alter ionic concentrations. The resulting chemical-potential gradients between dendrite and spine head lead to measurable electrical currents. The cable equation, however, considers electrical currents only as result of gradients in the electrical potential. The Poisson-Nernst-Planck (PNP) equations allow a more accurate description, as they include both types of currents. Previous PNP simulations predict a considerable change of ionic concentrations in spines during an excitatory postsynaptic potential (EPSP). However, solving PNP-equations is computationally expensive, limiting their applicability for complex structures. Here, we present a system of equations that generalizes the cable equation and considers both, electrical potentials and time-dependent concentrations of ion species with individual diffusion constants. Still, basic numerical algorithms can be employed to solve such systems. Based on simulations, we confirm that ion concentrations in dendritic spines are changing significantly during current injections that are comparable to synaptic events. Electrical currents reflecting ion diffusion through the spine neck increase voltage depolarizations in the spine head. Based on this effect, we identify a mechanism that affects the influx of Ca2+ in sequences of pre- and postsynaptic action potentials. Taken together, the diffusion of individual ion species need to be taken into account to accurately model electrical currents in dendritic spines. In the future the presented equations can be used to accurately integrate dendritic spines into multicompartment models to study synatptic integration. 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/2023.07.31.551324v1?rss=1 Authors: Lottes, E. N., Ciger, F. H., Bhattacharjee, S., Timmins-Wilde, E. A., Tete, B., Tran, T., Matta, J., Patel, A. A., Cox, D. N. Abstract: The development of cell-type-specific dendritic arbors is integral to the proper functioning of neurons within their circuit networks. In this study, we examine the regulatory relationship between the cytosolic chaperonin CCT, key insulin pathway genes, and an E3 ubiquitin ligase (Cullin1) in homeostatic dendritic development. CCT loss of function (LOF) results in dendritic hypotrophy in Drosophila Class IV (CIV) multidendritic larval sensory neurons, and CCT has recently been shown to fold components of the TOR (Target of Rapamycin) complex 1 (TORC1), in vitro. Through targeted genetic manipulations, we have confirmed that LOF of CCT and the TORC1 pathway reduces dendritic complexity, while overexpression of key TORC1 pathway genes increases dendritic complexity in CIV neurons. Both CCT and TORC1 LOF significantly reduce microtubule (MT) stability. CCT has been previously implicated in regulating proteinopathic aggregation, thus we examined CIV dendritic development in disease conditions as well. Expression of mutant Huntingtin leads to dendritic hypotrophy in a repeat-length-dependent manner, which can be rescued by TORC1 disinhibition via Cullin1 LOF. Together, our data suggest that Cullin1 and CCT influence dendritic arborization through regulation of TORC1 in both health and disease. 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/2023.08.01.549180v1?rss=1 Authors: Jain, A., Nakahata, Y., Watabe, T., Rusina, P., South, K. E., Adachi, K., Yan, L., Simorowski, N., Furukawa, H., Yasuda, R. Abstract: Behavioral time scale plasticity (BTSP), is a form of non-Hebbian plasticity induced by integrating pre- and postsynaptic components separated by behavioral time scale (seconds). BTSP in the hippocampal CA1 neurons underlies place cell formation. However, the molecular mechanisms underlying this behavioral time scale (eligibility trace) and synapse specificity are unknown. CaMKII can be activated in a synapse-specific manner and remain active for a few seconds, making it a compelling candidate for the eligibility trace during BTSP. Here, we show that BTSP can be induced in a single dendritic spine using 2-photon glutamate uncaging paired with postsynaptic current injection temporally separated by behavioral time scale. Using an improved CaMKII sensor, we saw no detectable CaMKII activation during this BTSP induction. Instead, we observed a dendritic, delayed, and stochastic CaMKII activation (DDSC) associated with Ca2+ influx and plateau 20-40 s after BTSP induction. DDSC requires both pre-and postsynaptic activity, suggesting that CaMKII can integrate these two signals. Also, optogenetically blocking CaMKII 30 s after the BTSP protocol inhibited synaptic potentiation, indicating that DDSC is an essential mechanism of BTSP. IP3-dependent intracellular Ca2+ release facilitates both DDSC and BTSP. Thus, our study suggests that the non-synapse specific CaMKII activation provides an instructive signal with an extensive time window over tens of seconds during BTSP. 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/2023.07.27.550829v1?rss=1 Authors: Rovira, M., Ferrero, G., Miserocchi, M., Montanari, A., Wittamer, V. Abstract: Recent studies have highlighted the heterogeneity of the immune cell compartment within the steady-state murine and human CNS. However it is not known whether this diversity is conserved among non mammalian vertebrates, especially in the zebrafish, a model system with increasing translational value. Here, we reveal the complexity of the immune landscape of the adult zebrafish brain. Using single-cell transcriptomics, we characterized these different immune cell subpopulations, including cell types that have not been -or have been poorly- characterized in zebrafish so far. By histology, we found that, despite microglia being the main immune cell type in the parenchyma, the zebrafish brain is also populated by a distinct myeloid population that shares a gene signature with mammalian dendritic cells (DC). Notably, zebrafish DC-like cells rely on batf3, a gene essential for the development of conventional DC1 in the mouse. Using specific fluorescent reporter lines that allowed us to reliably discriminate DC-like cells from microglia, we quantified brain myeloid cell defects in commonly used irf8-/-, csf1ra-/- and csf1rb-/- mutant fish, revealing previously unappreciated distinct microglia and DC-like phenotypes. Overall, our results suggest a conserved heterogeneity of brain immune cells across vertebrate evolution and also highlights zebrafish-specific brain immunity characteristics. 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/2023.07.21.550095v1?rss=1 Authors: Kruessel, S., Deb, I., Son, S., Ewall, G., Chang, M., Lee, H.-K., Heo, W. D., Kwon, H.-B. Abstract: Dendritic spines are structural correlates of excitatory synapses maintaining stable synaptic communications. However, this strong spine-synapse relationship was mainly characterized in excitatory pyramidal neurons (PyNs), raising a possibility that inferring synaptic density from dendritic spine number may not be universally applied to all neuronal types. Here we found that the ectopic expression of H-Ras increased dendritic spine numbers regardless of cortical cell types such as layer 2/3 pyramidal neurons (PyNs), parvalbumin (PV)- and vasoactive intestinal peptide (VIP)-positive interneurons (INs) in the primary motor cortex (M1). The probability of detecting dendritic spines was positively correlated with the magnitude of H-Ras activity, suggesting elevated local H-Ras activity is involved in the process of dendritic spine formation. H-Ras overexpression caused high spine turnover rate via adding more spines rather than eliminating them. Two-photon photolysis of glutamate triggered de novo dendritic spine formation in mature neurons, suggesting H-Ras induced spine formation is not restricted to the early development. In PyNs and PV-INs, but not VIP-INs, we observed a shift in average spine neck length towards longer filopodia-like phenotypes. The portion of dendritic spines lacking key excitatory synaptic proteins were significantly increased in H-Ras transfected neurons, suggesting that these increased spines have other distinct functions. High spine density caused by H-Ras did not result in change in the frequency or the amplitude of miniature excitatory postsynaptic currents (mEPSCs). Thus, our results propose that dendritic spines possess more multifaceted functions beyond the morphological proxy of excitatory synapse. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.19.549725v1?rss=1 Authors: Parkins, E. V., Brager, D. H., Rymer, J. K., Burwinkel, J. M., Rojas, D., Tiwari, D., Hu, Y.-C., Gross, C. Abstract: MicroRNAs are an emerging class of synaptic regulators. These small noncoding RNAs post-transcriptionally regulate gene expression, thereby altering neuronal pathways and shaping cell-to-cell communication. Their ability to rapidly alter gene expression and target multiple pathways makes them interesting candidates in the study of synaptic plasticity. Here, we demonstrate that the proconvulsive microRNA miR-324-5p regulates excitatory synapse structure and function in the hippocampus of mice. Both Mir324 knockout (KO) and miR-324-5p antagomir treatment significantly reduce dendritic spine density in the hippocampal CA1 subregion, and Mir324 KO, but not miR-324-5p antagomir treatment, shift dendritic spine morphology, reducing the proportion of thin, 'unstable' spines. Western blot and quantitative Real-Time PCR revealed changes in protein and mRNA levels for potassium channels, cytoskeletal components, and synaptic markers, including MAP2 and Kv4.2, which are essential for long-term potentiation (LTP). In line with these findings, slice electrophysiology revealed that LTP is severely impaired in Mir324 KO mice, while baseline excitatory activity remains unchanged. Overall, this study demonstrates that miR-324-5p regulates dendritic spine density, morphology, and plasticity in the hippocampus, potentially via multiple cytoskeletal and synaptic modulators. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

What does symmetry and self-similarity between life and intelligence mean for the nature of reality? How are neurones like genes?  Today we have the extraordinary Fractal Brain Theory to discuss. After episode #38 about the World as a Neural Network, with Russian physicist and computer scientist Vitaly Vanchurin, i've become more open to a unified theory of universe that reconciles quantum mechanics with general relativity, as Vanchurin's equations seem to offer. So when I was recommended today's guest's Fractal Brain Theory by one of the wonderful listeners, I was curious if a little sceptical given all the psychedelic hype about fractal geometry. So a symmetrical theory of repeating self-similar, self-modifying behaviour in the universe is not so far from the vision of the universe as a thriving, adaptable neural network. And according to today's guest the symmetry directly connects the often divorced worlds of neurones, brains and intelligence with the world of genes, evolution and life.  He is multi-disciplinary researcher, computer scientist, musician and author Wai H Tsang. A self-taught thinker in the world of neurology, evolutionary biology, consciousness and philosophy of mind, Tsang is in the unique position of combining these traditions into a single theory of brain, that promises to solve even the hard problem of consciousness. Trained in computer science at Imperial college, he wrote the first version of his Fractal Brain Theory in 2016, in his book of the same name, and it was picked up by quantum consciousness theorist Stuart Hameroff, who invited him to the Science of Consciousness Conference, alongside heavy weights in the field like David Chalmers, Roger Penrose, Sue Blackmore,  Donald Hoffman - many who've been on this show already. This recognition catapulted his theory into the field, so it's with great pleasure that I include it on the show for us to compare alongside the theories of many of the giants. What we discuss: 00:00 Intro 07:10 Symmetry explained: Variance and non-variance; change and resistance to change 11:00 Genomes work like tiny fractal brains 12:30 The symmetry between intelligence and life, neurones and genes 13:00 Junk DNA, neurones and boolean algebra 17:45 Dendritic structure, processing and artificial intelligence 19:00 Self-similarity and recursively nested symmetry 21:30 Evolution and ontogenesis algorithm: differentiate, select, amplify  22:15 Fractal Mathematics and Benoit Mandelbrot: Approximate self-similarity 25:45 Binary trees generating life and intelligence 29:00 Mitosis and progenator fields 30:00 Allocentric and egocentric mapping (Nobel prize) 34:40 Goodwin and cell division VS epigenetic mutation/adaptation 36:00 Recursive modification IS intelligence; evolving evolvability 40:15 A new calculus: analytic geometry  47:00 The soft and hard problem of consciousness  51:00 Time symmetric quantum mechanics and problems with causal chains  58:00 David Chalmers: Identity cosmo-psychism critique 01:11:00 Is self-reflective conscious Ai possible? 01:19:30 Penrose: Quantum mechanics is incomplete until we understand the collapse of the wave function 01:21:00 The ethical debate about the future of Ai References: ‘The Fractal Brain Theory' Wai Tsang Wai Tsang You Tube Channel  Boolean Algebra David Chalmers, “Idealism and the mind body problem” paper

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.14.549063v1?rss=1 Authors: Thomas, C., Ryan, M., Kamasawa, N., Scholl, B. Abstract: Postsynaptic mitochondria are critical to the development, plasticity, and maintenance of synaptic inputs. However, their relationship to synaptic structure and functional activity is unknown. We examined a correlative dataset from ferret visual cortex with in vivo two-photon calcium imaging of dendritic spines during visual stimulation and electron microscopy (EM) reconstructions of spine ultrastructure, investigating mitochondrial abundance near functionally- and structurally-characterized spines. Surprisingly, we found no correlation to structural measures of synaptic strength. Instead, we found that mitochondria are positioned near spines with orientation preferences that are dissimilar to the somatic preference. Additionally, we found that mitochondria are positioned near groups of spines with heterogeneous orientation preferences. For a subset of spines with a mitochondrion in the head or neck, synapses were larger and exhibited greater selectivity to visual stimuli than those without a mitochondrion. Our data suggest mitochondria are not necessarily positioned to support the energy needs of strong spines, but rather support the structurally and functionally diverse inputs innervating the basal dendrites of cortical neurons. 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/2023.07.13.548819v1?rss=1 Authors: Warner, H. M., Chen, T., Mahajan, S., ter Beest, M., Linders, P., Franciosa, G., Bianchi, F., van den Bogaart, G. Abstract: The mounting of an adaptive immune response is critical for removing pathogens from the body and generating immunological memory. Central to this process are myeloid cells, which sense pathogens through a variety of cell surface receptors, engulf and destroy pathogens and become activated. Activation is essential for the release of cytokines as well as the cell-surface presentation of pathogen-derived-antigens. Activation-induced cytokine release by myeloid cells requires a complex series of molecular events to facilitate cytokine expression. However, although the transcriptional machinery regulating cytokine expression is well defined, it is becoming increasingly clear that trafficking machinery has to be re-programmed through post-translational modifications to dynamically regulate cytokine secretory events. We demonstrate through quantitative total internal-resonance fluorescence (TIRF) microscopy that short-term stimulation with the pathogenic stimulus lipopolysaccharide (LPS) is sufficient to up-regulate IL-6 secretion rates in human blood monocyte-derived dendritic cells and that this secretion is asymmetric and thus polarised. Using bioinformatics analysis of our phosphoproteomic data, we demonstrate that LPS stimulation of monocyte-derived dendritic cells rapidly reprograms SNARE-associated membrane trafficking machinery, through phosphorylation/dephosphorylation events. Finally, we link this enhanced rate of secretion to the phosphorylation of the SNARE protein VAMP3 at serine 44 (48 in mice), by showing that this phosphorylation drives the release of VAMP3 by its chaperone WDFY2 and the complexing of VAMP3 with STX4 at the plasma membrane. 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

In Episode 139, we explore a new discovery in nerve signaling in the brain called a dendritic action potential (dCaAP), we look at a whacky proposed model of brain function, and we share some ideas about how we can help our students understand the core concepts of chemical signaling and signal transduction in different contexts. Put on your thinking caps and jump into this fresh episode now. 00:00 | Introduction 00:50 | Dendritic Action Potentials 12:16 | Transducer Model of the Brain 21:43 | Chemical Signals & Signal Transduction 35:09 | Staying Connected   ★ If you cannot see or activate the audio player, go to: theAPprofessor.org/podcast-episode-139.html

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.06.539205v1?rss=1 Authors: Nordentoft, M. S., Papoutsi, A., Takahashi, N., Heltberg, M. S., Jensen, M. H., Rasmussen, R. N. Abstract: During neuronal activity the extracellular concentration of potassium ions ([K+]o) increases substantially above resting levels, but it remains unclear what role these [K+]o changes play in dendritic integration of synaptic inputs. In this work, we used mathematical formulations and biophysical modeling to explore the role of activity-dependent [K+]o changes near dendritic segments of a visual cortex pyramidal neuron, receiving synaptic inputs tuned to stimulus orientation. We found that the fine-scale spatial arrangement of inputs determines the magnitude of [K+]o changes around the dendrites: Dendritic segments with similarly-tuned inputs can attain substantially higher [K+]o increases than segments with diversely-tuned inputs. These [K+]o elevations in turn increase dendritic excitability, leading to more robust and prolonged dendritic spikes. Ultimately, these local effects amplify the gain of neuronal input-output transformations, causing higher orientation-tuned somatic firing rates without compromising orientation selectivity. Our results thus suggest that local activity-dependent [K+]o changes around dendrites may act as a "volume knob" that determines the impact of synaptic inputs on feature-tuned neuronal firing. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

References Current Oncology Reports. 2020. 1534-6269, May 15, Vol. 22, Issue 6. Cell. 2021 Dec 9; 184(25):6081–6100.e26. --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

References Autoimmunity. 2012 Aug;45(5):333-47 Clinical and Experimental Rheumatology 2019: One year in review 2019: systemic lupus erythematosus Trends in Immunology, 2021-01-01, Volume 42, Issue 1, Pages 59-75 Annu. Rev. Immunol. 2000. 18:767–811 --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

Today, I am blessed to have here with me Dr Matt Halpert. He has a doctorate in immunology, with a specific focus on inflammation and microbiology and the way the immune system operates and should operate. Dr Matt spent 10 years in the Texas Medical Center predominantly at Baylor College of Medicine, as an academic researcher, focused on cancer and cancer immunotherapy.  With regard to how the immune system functions, its physiology, how it goes about identifying a threat, whether that threat is a virus or cancer, and how that immune system can then be essentially reprogrammed or correctly directed toward fighting that threat, the research team Dr Matt was with made what we now know to be an extremely important discovery.  In this episode, Dr Matt speaks about immunotherapy to fight against cancer. He will also share about Immunocine Cancer Center, which provides one of the most advanced Cancer Immunotherapies available. They are supported by academic studies and several clinical studies which makes them unique from any other cancer treatment centre. Tune in as we chat about the difference in your immune system when you're younger and as an adult, using the immune system to fight off cancer, how stress can weaken your immune system, dendritic cells, and how can you support your immune system. Register your FREE spot for the next 7 day keto kickstart challenge with Dr Jason Fung, Dr Ken Berry, Dr Annette Boz and many others: http://www.ketokampchallenge.com  Order Keto Flex: http://www.ketoflexbook.com -------------------------------------------------------- Download your FREE Vegetable Oil Allergy Card here: https://onlineoffer.lpages.co/vegetable-oil-allergy-card-download/ / / E P I S O D E   S P ON S O R S  Wild Pastures: $20 OFF per Box for Life + Free Shipping for Life + $15 OFF your 1st Box! https://wildpastures.com/promos/save-20-for-life-lf?oid=6&affid=132&source_id=podcast&sub1=ad BonCharge: Blue light Blocking Glasses, Red Light Therapy, Sauna Blankets & More. Visit https://boncharge.com/pages/ketokamp and use the coupon code KETOKAMP for 15% off your order.  Text me the words "Podcast" +1 (786) 364-5002 to be added to my contacts list.   [5:07] Strengthen your immune system to help fight cancer effectively. Chemotherapy would be analogous to putting a bomb on a building knowing there are bad guys (cancer) inside in the hopes of taking out all of the bad guys, but with the added risk of causing collateral damage. Even if it isn't shown on the scan, the bad guys are still there if you don't get them all. Relapse is undoubtedly a possibility in the future. Using the immune system and immunotherapy is a little more like using the Navy SEALs to go into the building and very specifically identify and eliminate those threats rather than the widespread destruction. If we're going to get to cures, it's going to be in the space of immunotherapy and rearming the immune system.  Our immune system, also known as our defense system, constantly guards against viruses, bacteria, and other pathogens, including cancer. Dendritic cells are a type of immune cell that runs the whole system. They are the generals of the immune system army.  [16:09] Why does the immune system lose its understanding? We tend to break down more frequently as we get older, our health tends to weaken, and we don't bounce back as quickly. That is a clear external reality, but there is also an inside reality. Mutations take longer to fix.  You need to have adequate movement each day. You need to exercise. When we are young, we are generally always on the move. As we age, we spend a lot more time sitting down and we don't try to exercise every day. Therefore, despite the immune system's potential strength, your body is no longer benefiting from it as quickly as it could.  [28:48] The First Cancer Treatment to Maximize the Immune System Immunocine Cancer Center send people a dozen or two dozen publications about dendritic cells and their role in cancer. That is their own science. They're not hiding from mainstream medicine, it just takes time.  They gathered the ideal group of medical professionals, including oncologists, radiologists, hematologists, and scientists. In addition, they have a cleanroom lab that complies with FDA regulations, where each patient's customized immunotherapy is created.  What they can do is reprogram your immune response to get going and get fighting. Instead of working in a lab, their scientists take a sample of the tumor and analyze it to find its protein library and very particular RNA components. The measures they followed to transform the blood cells into the appropriate type of dendritic cells over the course of a week are what make their technique so special.  They give you a legitimately unique, strong immune response that actually does ramp up and start fighting cancer. [58:36] Does immunotherapy works for all types of cancer? Here's what you need to know! As of today, Immunocine Cancer Center are not treating hematological malignancies, which are blood cancers, and heart cancers, and they're not treating brain cancers. They can treat a lot of cancers. It can be in conjunction with other treatment approaches.  AND MUCH MORE! Resources from this episode:  *Please note, the article Dr Matt Halpert & Ben Azadi wrote has not been published yet* Website: https://immunocine.com/  LinkedIn: https://www.linkedin.com/in/matthew-halpert-b4695174/  Facebook: https://m.facebook.com/people/Matt-Halpert/100079347564008/  Youtube: https://www.youtube.com/channel/UCWaOucdS32jADd-8JAVGh8w   Join the Keto Kamp Academy: https://ketokampacademy.com/7-day-trial-a  Watch Keto Kamp on YouTube: https://www.youtube.com/channel/UCUh_MOM621MvpW_HLtfkLyQ  Register your FREE spot for the next 7 day keto kickstart challenge with Dr Jason Fung, Dr Ken Berry, Dr Annette Boz and many others: http://www.ketokampchallenge.com  Order Keto Flex: http://www.ketoflexbook.com -------------------------------------------------------- Download your FREE Vegetable Oil Allergy Card here: https://onlineoffer.lpages.co/vegetable-oil-allergy-card-download/ / / E P I S O D E   S P ON S O R S  Wild Pastures: $20 OFF per Box for Life + Free Shipping for Life + $15 OFF your 1st Box! https://wildpastures.com/promos/save-20-for-life-lf?oid=6&affid=132&source_id=podcast&sub1=ad BonCharge: Blue light Blocking Glasses, Red Light Therapy, Sauna Blankets & More. Visit https://boncharge.com/pages/ketokamp and use the coupon code KETOKAMP for 15% off your order.  Text me the words "Podcast" +1 (786) 364-5002 to be added to my contacts list.   Some links are affiliate links  // F O L L O W ▸ instagram | @thebenazadi | http://bit.ly/2B1NXKW ▸ facebook | /thebenazadi | http://bit.ly/2BVvvW6 ▸ twitter | @thebenazadi http://bit.ly/2USE0so ▸ tiktok | @thebenazadi https://www.tiktok.com/@thebenazadi Disclaimer: This podcast is for information purposes only. Statements and views expressed on this podcast are not medical advice. This podcast including Ben Azadi disclaim responsibility from any possible adverse effects from the use of information contained herein. Opinions of guests are their own, and this podcast does not accept responsibility of statements made by guests. This podcast does not make any representations or warranties about guests qualifications or credibility. 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Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.27.534425v1?rss=1 Authors: Busch, S. E., Hansel, C. Abstract: In rodents, most Purkinje cells in the adult cerebellum receive one climbing fiber from the inferior olive. In postnatal competition for innervation of the growing primary dendrite, one "winner" climbing fiber prevails, while surplus fibers are eliminated. It is unknown if the presence of multiple primary dendrites - which we describe as nearly universal in human - might allow multiple climbing fibers to survive. Mouse cerebellum provides a useful model for investigation as a minority of Purkinje cells exhibit polydendritic architecture. Among mature cells with multiple primary dendrites, ~25% are indeed innervated by multiple climbing fibers. Two-photon calcium imaging in vivo demonstrates that separate primary dendrites can have distinct response properties to sensory stimulation, suggesting that polydendritic Purkinje cells integrate functionally independent climbing fiber receptive fields. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.25.534233v1?rss=1 Authors: Virga, D. M., Hamilton, S., Osei, B., Morgan, A., Zamponi, E., Park, N. J., Hewitt, V. L., Zhang, D., Gonzalez, K. C., Bloss, E., Polleux, F., Lewis, T. L. Abstract: Neuronal mitochondria play important roles beyond ATP generation, including Ca2+ uptake, and therefore have instructive roles in synaptic function and neuronal response properties. Mitochondrial morphology differs significantly in the axon and dendrites of a given neuronal subtype, but in CA1 pyramidal neurons (PNs) of the hippocampus, mitochondria within the dendritic arbor also display a remarkable degree of subcellular, layer-specific compartmentalization. In the dendrites of these neurons, mitochondria morphology ranges from highly fused and elongated in the apical tuft, to more fragmented in the apical oblique and basal dendritic compartments, and thus occupy a smaller fraction of dendritic volume than in the apical tuft. However, the molecular mechanisms underlying this striking degree of subcellular compartmentalization of mitochondria morphology are unknown, precluding the assessment of its impact on neuronal function. Here, we demonstrate that this compartment-specific morphology of dendritic mitochondria requires activity-dependent, Camkk2-dependent activation of AMPK and its ability to phosphorylate two direct effectors: the pro-fission Drp1 receptor Mff and the recently identified anti-fusion, Opa1-inhibiting protein, Mtfr1l. Our study uncovers a new activity-dependent molecular mechanism underlying the extreme subcellular compartmentalization of mitochondrial morphology in dendrites of neurons in vivo through spatially precise regulation of mitochondria fission/fusion balance. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.08.531672v1?rss=1 Authors: Masoli, S., Sanchez-Ponce, D., Vrieler, N., Abu-Haya, K., Lerner, V., Shahar, T., Nedelescu, H., Rizza, M. F., Benavides-Piccione, R., DeFelipe, J., Yarom, Y., Munoz, A., D'Angelo, E. Abstract: Purkinje cells (PC) of the cerebellum are amongst the largest neurons of the brain and have been extensively investigated in rodents. However, their morphological and physiological properties in humans are still poorly understood. Here, we have taken advantage of high-resolution morphological reconstructions and of unique electrophysiological recordings of human PCs ex vivo to generate computational models and estimate computational capacity. An inter-species comparison showed that human PCs had similar fractal structure but were bigger than mouse PCs. Consequently, given a similar spine density (2/micrometer), human PCs hosted about 5 times more dendritic spines. Moreover, human had higher dendritic complexity than mouse PCs and usually emitted 2-3 main dendritic trunks instead than 1. Intrinsic electroresponsiveness was similar in the two species but model simulations revealed that the dendrites generated ~6.5 times (n=51 vs. n=8) more combinations of independent input patterns in human than mouse PCs leading to an exponential 2n increase in Shannon information. Thus, while during evolution human PCs maintained similar patterns of spike discharge as in rodents, they developed more complex dendrites enhancing computational capacity up to the limit of 10 billion times. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.02.530772v1?rss=1 Authors: Leighton, A. H., Cheyne, J. E., Lohmann, C. Abstract: Synaptic inputs to cortical neurons are highly structured in adult sensory systems, such that neighboring synapses along dendrites are activated by similar stimuli. This organization of synaptic inputs, called synaptic clustering, is required for high-fidelity signal processing, and clustered synapses can already be observed before eye opening. However, how clustered inputs emerge during development is unknown. Here, we employed concurrent in vivo whole-cell patch clamp and dendritic calcium imaging to map spontaneous synaptic inputs to dendrites of layer 2/3 neurons in the mouse primary visual cortex during the second postnatal week until eye opening. We find that the number of functional synapses and the frequency of transmission events increase several fold during this developmental period. At the beginning of the second postnatal week, synapses assemble specifically in confined dendritic segments, whereas other segments are devoid of synapses. By the end of the second postnatal week, just before eye-opening, dendrites are almost entirely covered by domains of co-active synapses. Finally, co-activity with their neighbor synapses correlates with synaptic stabilization and potentiation. Thus, clustered synapses form in distinct functional domains presumably to equip dendrites with computational modules for high-capacity sensory processing when the eyes open. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.24.529978v1?rss=1 Authors: Nanda, S., Bhattacharjee, S., Cox, D. N., Ascoli, G. A. Abstract: Dendritic morphology underlies the source and processing of neuronal signal inputs. Morphology can be broadly described by two types of geometric characteristics. The first is dendrogram topology, defined by the length and frequency of the arbor branches; the second is spatial embedding, mainly determined by branch angles and tortuosity. We have previously demonstrated that microtubules and actin filaments are associated with arbor elongation and branching, fully constraining dendrogram topology. Here we relate the local distribution of these two primary cytoskeletal components with dendritic spatial embedding. We first reconstruct and analyze 167 sensory neurons from the Drosophila larva encompassing multiple cell classes and genotypes. We observe that branches with higher microtubule concentration are overall straighter and tend to deviate less from the direction of their parent branch. F-actin displays a similar effect on the angular deviation from the parent branch direction, but its influence on branch tortuosity varies by class and genotype. We then create a computational model of dendritic morphology purely constrained by the cytoskeletal composition imaged from real neurons. The model quantitatively captures both spatial embedding and dendrogram topology across all tested neuron groups. These results suggest a common developmental mechanism regulating diverse morphologies, where the local cytoskeletal distribution can fully specify the overall emergent geometry of dendritic arbors. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.17.528927v1?rss=1 Authors: Piers, T. M., Namboori, S. C., Bhinge, A., Killick, R., Scholpp, S. Abstract: Neuronal circuits evolve as a precisely patterned network. In this context, a growing neuron must locate the appropriate target area on a neurite of a neighbouring cell with which to connect. Controlled target selection involves dendritic filopodial contacts and requires the exact apposition of synaptic components. Calcium signalling has been postulated to trigger the transformation from dendritic filopodia into functional synapses. However, calcium is a rather unspecific signalling system, and it needs to be clarified how the exact development of synaptic connections is controlled. Similarly, Wnt/beta-catenin signalling promotes synapse formation; however, how secreted Wnts induce and maintain synapses on neuronal dendrites is not well understood. Here, we show that Wnt-7a is tethered to the tips of dynamic dendritic filopodia during spine formation in human cortical neurons. These filopodia can activate Wnt signalling precisely at the contact sites on the dendrites of an adjacent neuron. Subsequently, local calcium transients can be observed at these Wnt-positive contact sites. Depleting either the filopodial-loaded Wnt or the extracellular calcium pool blocks the clustering of pre- and post-synaptic markers, hence the establishment of stable connections. Therefore, we postulate that local Wnt-7a signalling from the tip of the dendritic filopodia, verified by simultaneous calcium signalling, provides an elegant mechanism for orchestrating focal synapse maturation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.15.528686v1?rss=1 Authors: Bhattacharjee, S., Iyer, E. P. R., Iyer, S. C., Nanda, S., Rubaharan, M., Ascoli, G. A., Cox, D. N. Abstract: Dendrites are the primary points of sensory or synaptic inputs to a neuron and play an essential role in synaptic integration and neural function. Despite the functional importance of dendrites, relatively less is known about the underlying mechanisms regulating cell-type specific dendritic patterning. Herein, we have dissected functional roles of a previously uncharacterized gene, CG3995, in cell-type specific dendritic development in Drosophila melanogaster. CG3995, which we have named bedwarfed (bdwf), encodes a zinc-finger BED-type protein which is required for proportional growth and branching of dendritic arbors, exhibits nucleocytoplasmic expression, and functions in both transcriptional and translational cellular pathways. At the transcriptional level, we demonstrate a reciprocal regulatory relationship between Bdwf and the homeodomain transcription factor (TF) Cut. We show that Cut positively regulates Bdwf expression and that Bdwf acts as a downstream effector of Cut-mediated dendritic development, whereas overexpression of Bdwf negatively regulates Cut expression in multidendritic sensory neurons. Proteomic analyses revealed that Bdwf interacts with ribosomal proteins and disruption of these proteins produced phenotypically similar dendritic hypotrophy defects as observed in bdwf mutant neurons. We further demonstrate that Bdwf and its ribosomal protein interactors are required for normal microtubule and F-actin cytoskeletal architecture. Finally, our findings reveal that Bdwf is required to promote protein translation and ribosome trafficking along the dendritic arbor. Taken together, these results provide new insights into the complex, combinatorial and multi-functional roles of transcription factors (TFs) in directing diversification of cell-type specific dendritic development. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.14.528554v1?rss=1 Authors: Jin, S., Chen, X., Tian, Y., Jarvis, R., Promes, V., Yang, Y. Abstract: Developing astroglia play important roles in regulating synaptogenesis through secreted and contact signals. Whether they regulate postnatal axon growth is unknown. By selectively isolating exosomes using size-exclusion chromatography (SEC) and employing cell-type specific exosome reporter mice, our current results define a secreted astroglial exosome pathway that can spread long-range in vivo and stimulate axon growth of cortical pyramidal neurons. Subsequent biochemical and genetic studies found that surface expression of glial HepaCAM protein essentially and sufficiently mediates the axon-stimulating effect of astroglial exosomes. Interestingly, apolipoprotein E (ApoE), a major astroglia-secreted cholesterol carrier to promote synaptogenesis, strongly inhibits the stimulatory effect of astroglial exosomes on axon growth. Developmental ApoE deficiency also significantly reduces spine density of cortical pyramidal neurons. Together, our study suggests a surface contact mechanism of astroglial exosomes in regulating axon growth and its antagonization by ApoE, which collectively coordinates early postnatal pyramidal neuronal axon growth and dendritic spine formation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

I read from den to dendritic cell.     The Key and Peele College Football sketches are classic. https://youtu.be/gRhB2Oiy0Nc     I sure wish I had some denarius coins: https://en.wikipedia.org/wiki/Denarius     The word of the episode is "denazify".     Theme music from Tom Maslowski https://zestysol.com/     Merchandising! https://www.teepublic.com/user/spejampar     "The Dictionary - Letter A" on YouTube   "The Dictionary - Letter B" on YouTube   "The Dictionary - Letter C" on YouTube   "The Dictionary - Letter D" on YouTube     Featured in a Top 10 Dictionary Podcasts list! https://blog.feedspot.com/dictionary_podcasts/     Backwards Talking on YouTube: https://www.youtube.com/playlist?list=PLmIujMwEDbgZUexyR90jaTEEVmAYcCzuq     dictionarypod@gmail.com https://www.facebook.com/thedictionarypod/ https://twitter.com/dictionarypod https://www.instagram.com/dictionarypod/ https://www.patreon.com/spejampar https://www.tiktok.com/@spejampar 917-727-5757

We talk to Naveen Pemmaraju, MD, about the results of the largest prospective BPDCN trial evaluating the CD123-targeted therapy tagraxofusp in adults with treatment-naive and relapsed/refractory blastic plasmacytoid dendritic cell neoplasm (BPDCN). BPDCN is a rare and aggressive myeloid malignancy of the dendritic cell lineage which can affect other organs such as the lymph nodes, spleen, central nervous system, and skin. The disease carries a poor prognosis, and although it has been treated with combination leukemia or lymphoma chemotherapy regimens, these often result in nondurable responses with high rates of relapse. Oncology Times journalist Catlin Nalley sat down with Pemmaraju to discuss his most recent study titled “Long-Term Benefits of Tagraxofusp for Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm,” recently published in the Journal of Clinical Oncology (2022; doi: 10.1200/JCO.22.00034). Pemmaraju is Associate Professor in the Department of Leukemia at the University of Texas MD Anderson Cancer Center and has dedicated his career to the study of rare and ultra-rare cancers.

Check out my short video series about what's missing in AI and Neuroscience. Support the show to get full episodes and join the Discord community. Matthew Larkum runs his lab at Humboldt University of Berlin, where his group studies how dendrites contribute to computations within and across layers of the neocortex. Since the late 1990s, Matthew has continued to uncover key properties of the way pyramidal neurons stretch across layers of the cortex, their dendrites receiving inputs from those different layers - and thus different brain areas. For example, layer 5 pyramidal neurons have a set of basal dendrites near the cell body that receives feedforward-like input, and a set of apical dendrites all the way up in layer 1 that receives feedback--like input. Depending on which set of dendrites is receiving input, or neither or both, the neuron's output functions in different modes- silent, regular spiking, or burst spiking. Matthew realized the different sets of dendritic inputs could signal different operations, often pairing feedforward sensory--like signals and feedback context-like signals. His research has shown this kind of coincidence detection is important for cognitive functions like perception, memory, learning, and even wakefulness. We discuss many of his ideas and research findings, why dendrites have long been neglected in favor of neuron cell bodies, the possibility of learning about computations by studying implementation-level phenomena, and much more. Larkum Lab.Twitter: @mattlark.Related papersCellular Mechanisms of Conscious Processing.Perirhinal input to neocortical layer 1 controls learning. (bioRxiv link: https://www.biorxiv.org/content/10.1101/713883v1)Are dendrites conceptually useful?Memories off the top of your head.Do Action Potentials Cause Consciousness?Blake Richard's episode discussing back-propagation in the brain (based on Matthew's experiments) 0:00 - Intro 5:31 - Background: Dendrites 23:20 - Cortical neuron bodies vs. branches 25:47 - Theories of cortex 30:49 - Feedforward and feedback hierarchy 37:40 - Dendritic integration hypothesis 44:32 - DIT vs. other consciousness theories 51:30 - Mac Shine Q1 1:04:38 - Are dendrites conceptually useful? 1:09:15 - Insights from implementation level 1:24:44 - How detailed to model? 1:28:15 - Do action potentials cause consciousness? 1:40:33 - Mac Shine Q2

This month on Episode 36 of Discover CircRes, host Cynthia St. Hilaire highlights original research articles featured in the April 29 and May 13 issues of Circulation Research. This episode also features a conversation with Dr Patricia Nguyen and Jessica D'Addabbo from Stanford University about their study, Human Coronary Plaque T-cells are Clonal and Cross-React to Virus and Self.   Article highlights:   Zanoli, et al. COVID-19 and Vascular Aging   Wang, et al. JP2NT Gene Therapy in a Mouse Heart Failure Mode   Harraz, et al. Piezo1 Is a Mechanosensor in CNS Capillaries   Zhao, et al. BAT sEVs in Exercise Cardioprotection   Cindy St. Hilaire:        Hi, and welcome to Discover CircRes, the podcast of the American Heart Association's journal, Circulation Research. I'm your host, Dr Cyndy St. Hilaire, from the Vascular Medicine Institute at the University of Pittsburgh. And today, I'll be highlighting the articles from our April 29th and May 13th issues of Circulation Research. I also will speak with Dr Patricia Nguyen and Jessica D'Addabbo from Stanford University about their study, Human Coronary Plaque T-cells are Clonal and Cross-React to Virus and Self.   Cindy St. Hilaire:        The first article I want to share is titled Vascular Dysfunction of COVID 19 Is Partially Reverted in the Long-Term. The first author is Agostino Gaudio and the corresponding author is Luca Zanoli. And they're from the University of Catania. Cardiovascular complications, such as endothelial dysfunction, arterial stiffness, thrombosis and heart disease are common in COVID 19. But how quickly such issues resolve, once the acute phase of the illness has passed, remains unclear. To find out, this group examined aortic and brachial pulse wave velocity, and other measures of arterial stiffness in 90 people who, several months earlier, had been hospitalized with COVID 19. These measurements were compared with data from 180 controls, matched for age, sex, ethnicity and body mass index, whose arterial stiffness had been assessed prior to the pandemic. 41 of the COVID patients were also examined 27 weeks later to assess any changes in arterial stiffness over time. Together, the data showed arterial stiffness was higher in COVID patients than in controls. And though it improved over time, it tended to remain higher than normal for almost a year after COVID.   Cindy St. Hilaire:        This finding could suggest residual structural damage to the arterial walls or possibly, persistent low-grade inflammation in COVID patients. Either way, since arterial stiffness is a predictor of cardiovascular health, its potential longterm effects in COVID patients deserves further longitudinal studies.   Cindy St. Hilaire:        The second article I want to share is titled Gene Therapy with the N-Terminus of Junctophilin-2 Improves Heart Failure in Mice. The first author is Jinxi Wang and the corresponding author is Long-Sheng Song from the University of Iowa. Junctophilin-2 is a protein with a split personality. Normally, it forms part of the heart's excitation contraction coupling machinery. But when the heart is stressed, JP2 literally splits in two, and sends its N-terminal domain, JP2NT, to the nucleus, where it suppresses transcription of genes involved in fibrosis, hypertrophy, inflammation and other heart failure related processes. However, if this stress is severe or sustained, the protective action of JP2NT is insufficient to halt the progressive failure. This group asked. "What if this N-terminal domain could be ramped up using gene therapy to aid a failing mouse heart?"   Cindy St. Hilaire:        To answer this question, they injected adenoviral vectors encoding JP2NT into mice either before or soon after transaortic constriction, or TAC, tack, which is a method of experimentally inducing heart failure. They found, in both cases, that the injected animals fared better than the controls. Animals injected before TAC showed less severe cardiac remodeling than control mice, while those treated soon after TAC exhibited slower loss of heart function with reduced ventricle dilation and fibrosis. These data suggest that supplementing JP2NT, via gene therapy or other means, could be a promising strategy for treating heart failure. And this data provides a basis for future translational studies.   Cindy St. Hilaire:        The third article I want to share is titled Piezo1 Is a Mechanosensor Channel in Central Nervous System Capillaries. The first and corresponding author is Osama Harraz from the University of Vermont. Neurovascular coupling is the process whereby transient activation of neurons leads to an upsurge in local blood flow to accommodate the increased metabolic needs of the cell. It's known that agents released from active neurons trigger changes in local capillaries that prompt vasodilation, but how these hemodynamic changes are sensed and controlled is not entirely clear. This group suspected that the mechanosensory protein Piezo1, a calcium channel that regulates dilation and constriction of other blood vessels, may be involved. But whether Piezo1 is even found in the microcirculation of the CNS was unknown. This group shows that Piezo1 is present in cortical capillaries of the brain and the retina of the mouse, and that it responds to changes in blood pressure and flow.   Cindy St. Hilaire:        Ex vivo preparations of mouse retina showed that experimentally induced changes in hemodynamics caused calcium transients and related currents within capillary endothelial cells, and that these were dependent on the presence of Piezo1. While it is not entirely clear how Piezo1 influences cerebral blood flow, its pressure induced activation of CNS capillary endothelial cells suggest a critical role in neurovascular coupling.   Cindy St. Hilaire:        The last article I want to share is titled Small Extracellular Vesicles from Brown Adipose Tissue Mediate Exercise Cardioprotection. The first authors are Hang Zhao and Xiyao Chen. And the corresponding authors are Fuyang Zhang and Ling Tao from the Fourth Military Medical University. Regular aerobic exercise is good for the heart and it increases the body's proportion of brown adipose tissue relative to white adipose tissue. This link has led to the idea that brown fat, possibly via its endocrinal activity, might somehow contribute to exercise related cardioprotection. Zhao and colleagues now show that, indeed, brown fat produces extracellular vesicles that are key to preserving heart health. While mice subjected to four weeks of aerobic exercise were better protected against subsequent heart injury than their sedentary counterparts, blocking the production of EVs prior to exercise significantly impaired this protection. Furthermore, injection of brown fat derived EVs into the hearts of mice lessened the impact of subsequent cardiac injury.   Cindy St. Hilaire:        The team went on to identify micro RNAs within the vesicles responsible for this protection, showing that the micro RNAs suppressed an apoptosis pathway in cardiomyocytes. In identifying mechanisms and molecules involved in exercise related cardio protection, the work will inform the development of exercise mimicking treatments for people at risk of heart disease or who are intolerant to exercise.   Cindy St. Hilaire:        Lastly, I want to bring up that the April 29th issue of Circulation Research also contains a short Review Series on pulmonary hypertension, with articles on: The Latest in Animal Models of Pulmonary Hypertension and Right Ventricular Failure, by Olivier Boucherat; Harnessing Big Data to Advance Treatment and Understanding of Pulmonary Hypertension, by Christopher Rhodes and colleagues; New Mutations and Pathogenesis of Pulmonary Hypertension: Progress and Puzzles in Disease Pathogenesis, by Christophe Guignabert and colleagues; Group 3 Pulmonary Hypertension From Bench to Bedside, by Corey Ventetuolo and colleagues; and Novel Approaches to Imaging the Pulmonary Vasculature and Right Heart, by Sudarshan Rajagopal and colleagues; and Understanding the Pathobiology of Pulmonary Hypertension Due to Left Heart Disease, by Jessica Huston and colleagues.   Cindy St. Hilaire:        Today, Dr Patricia Nguyen and Jessica D'Addabbo, from Sanford University, are with me to discuss their study, Human Coronary Plaque T-cells are Clonal and Cross-React to Virus and Self. And this article is in our May 13th issue of Circulation Research. So, Trisha and Jessica, thank you so much for joining me today.   Jessica D'Addabbo:    Thank you for having us.   Patricia Nguyen:         Yes. Thank you for inviting us to your podcast. We're very excited to be here.   Cindy St. Hilaire:        Yeah. And I know there's lots of authors involved in this study, so unfortunately we can't have everyone join us, but I appreciate you all taking the time.   Patricia Nguyen:         This is like a humongous effort by many people in the group, including Roshni Roy Chowdhury, and Xianxi Huang, as well as Charles Chan and Mark Davis. So, we thank you.   Cindy St. Hilaire:        So atherosclerosis, it stems from lipid deposition in the vascular wall. And that lipid deposition causes a whole bunch of things to happen that lead to a chronic inflammatory state. And there's many cells that can be inflammatory. And this study, your study, is really focusing on the role of T-cells in the atherosclerotic plaque. So, before we get into the nitty gritty details of your study, can you share with us, what is it that a T-cell does normally and what is it doing in a plaque? Or rather, let me rephrase that as, what did we know a T-cell was doing in a plaque before your study?   Patricia Nguyen:         So, T-cells, as you know, are members of the adaptive immune system. They are the master regulators of the entire immune system, secreting cytokines and other proteins to attract immune cells to a diseased portion of the body, for example. T-cells have been characterized in plaque previously, mainly with immunohisto chemistry. And their characterization has also been recently performed using single cell technologies. Those studies have been restricted to mainly mirroring studies, studies in mice in their aortic walls, in addition to human carotid arteries. So, it is well known that T cells are found in plaque and a lot of attention has been given to the macrophage subset as the innate immune D. But let's not forget the T-cell because they're actually composed about... 50% in the plaque are T-cells.   Patricia Nguyen:         And we were particularly interested in the T-cell population because we have a strong collaboration with Dr Mark Davis, who's actually the pioneer of T-cell biology and was the first to describe the T-cell receptor alpha beta receptor in his lab in the 1970s. So, he has developed many techniques to interrogate T-cell biology. And our collaboration with him has allowed us and enabled us to perform many of these single cell technologies. In addition, his colleague, Dr Chen, also was pivotal in helping us with the interrogation and understanding of the T-cells in plaque.   Cindy St. Hilaire:        And I think one of the really neat strengths of your study is that you used human coronary artery plaques. So, could you walk us through? What was that like? I collect a lot of human tissue in my lab. I get a lot of aortic valves from the clinic. And it's a lot of logistics. And a lot of times, we're just fixing them, but you are not just fixing them. So, can you walk us through? What was that experimental process from the patient to the Petri dish? And also, could you tell us a little bit about your patient population that you sampled from?   Jessica D'Addabbo:    So, these were coronary arteries that we got from patients receiving a heart transplant. So, they were getting a heart transplant for various reasons, and we would receive their old heart, and someone would help us dissect out the coronary arteries from these. And then, we would process each of these coronary arteries separately. And this happened at whatever hour the hearts came out of the patient.   Jessica D'Addabbo:    So sometime, I was coming in at 3:00 AM with Dr Nguyen and we would be working on these hearts then, because we wanted the samples to be as fresh as possible. So, we would get the arteries. We would digest out the tissue. And then, we would have certain staining profiles that we wanted to look at so that we could put the cells on fax to be able to sort the cells, and then do all the downstream sequencing from there.   Cindy St. Hilaire:        So, in terms of, I don't know, the time when you get that phone call that a heart's coming in to actually getting those single cells that you can either send a fax or send a sequencing, how long did that take, on a good day? Let's talk only about good days.   Jessica D'Addabbo:    Yeah. A lot of factors went into that, sometimes depending on availability of things. But usually, we were ready with all of the materials in advance. So, I'd say it could be anywhere from six to 12 hours, it would take, to get everything sorted. Then, everything after that would happen. But that was just that critical period of making sure we got the cells fresh.   Patricia Nguyen:         So we have to credit the CT surgeons at Stanford for setting up the program or the structure, infrastructure, that enables us to obtain this precious tissue. That is Jack Boyd and Joseph Woo of CT surgery. So, they have enabled human research on hearts by making these tissues available. Because as you know, a transplant... They can say the transplant's happening at 12:00 AM, but it actually doesn't happen until 4:00 AM. And I think it's very difficult for a lab to make that happen all the time. And I think having their support in this paper was critical. And this has allowed us, enabled us, to interrogate kind of the spectrum of disease, especially focusing on T-cells, which are... They make a portion of the plaque, but the plaque itself has not like a million cells that are immune. A lot of them are not immune. So, enabling us to get the tissue in a timely fashion where they're not out of the body for more than 30 minutes enables us to interrogate these small populations of cells.   Cindy St. Hilaire:        That's actually the perfect segue to my next question, which is, how many cells in a plaque were you able to investigate with the single cell analysis? And what was the percentage again of the T-cells in those plaques or in... I guess you looked at different phases of plaque. So, what was that spectrum for the percentage of T-cells?   Patricia Nguyen:         So, for 10X, for example, you need a minimum of 10,000 captured cells. You could do less, but the utility of the 10X is maximized with 10,000. So, many times before the ability to multiplex these tissues, we were doing like capturing 5,000 for example. And the number of cells follows kind of the disease progression, in the sense that as a disease is more severe, you have more immune cells, in general. And it kind of decreases as it becomes more fibrotic and scarred, like calcified. So, it was a bit challenging to get very early just lipid-only cells. And a lot of those, we captured like 3000 or something like that. And efficiency is like 80% perhaps. So, you kind of capture…   Cindy St. Hilaire:        And also, how many excised hearts are going to have early athero? So, it's...   Patricia Nguyen:         Well, there are... nonischemics will have...   Cindy St. Hilaire:        Oh, okay. Okay.   Patricia Nguyen:         So, the range was nonischemic to ischemic.   Cindy St. Hilaire:        Oh great.   Patricia Nguyen:         So, about a portion... I would say one third of the total heart transplants were ischemic. And a lot of them were non ischemic. But as you know, the nonischemic can mix with ischemia. And so, they could have mild to moderate disease in the other arteries, for example, but not severe like 70%/90% obstruction.   Cindy St. Hilaire:        Wow. That's so great. That's amazing. Amazing sample size you have. So T-cell, it's kind of an umbrella term, right? There's many different types of T-cells. And when you start to get in the nitty gritty, they really do have distinct functions. So, what types of T-cells did you see and did you focus on in this study?   Jessica D'Addabbo:    So, the two main types of T-cells are CD4 positive T-cells and CD8 positive T-cells. And we looked at both of these T-cells from patients. We usually sorted multiple plates from each. And then, with 10X, we captured both. But our major finding was actually that the CD8 positive t-cell population was more clonally expanded than the CD4 population, which led us to believe that these cells were more important in the coronary artery disease progression and in the study that we were doing because for a cell to be clonally expanded, it means it was previously exposed to an antigen. And so, if we're finding these T-cells that are clonally expanded in our plaques, then we're hypothesizing that they were likely exposed to some sort of antigen, and then expanded, and then settled into the plaque.   Cindy St. Hilaire:        And when you're saying expansion, are you talking about them being exposed to the antigen in the plaque and expanding there? Or do you think they're being triggered in the periphery and then honing in as a more clonal population?   Patricia Nguyen:         So, that's a great question. And unfortunately, I don't have the answer to that. So basically-   Jessica D'Addabbo:    Next paper, next paper.   Patricia Nguyen:         Exactly. So, we... Interesting to expand on Jessica's answer. Predominantly what was found, as you said, was memory T-cells, so memory T-cells expressing specific markers, so memory versus naive. And these were effector T-cells. And memory meaning they were previously expanded by antigen engagement, and just happened to be in the plaque for whatever reason. We do not know why T-cells specifically are attracted to the plaque, but they are obviously there. And they're in a memory state, if you will. And some of them did display activation markers, which suggested that they clonally expanded to an antigen. What that antigen is, is the topic of another paper. But certainly, it is important to understand that these patients that we recruit, because they were transplant patients, they're not actively infected, right? That is a exclusionary criteria for transplants, right?   Patricia Nguyen:         So, that means these T-cells were there for unclear reasons. Why they're there is unclear. Whether they are your resident T-cells also is unclear, because the definition of resident T-cell still remains controversial. And you actually have to do lineage tracking studies to find out, "Okay, where... Did they come from the bone marrow? Did they come from the periphery? How did they get there?" Versus, "Okay. They were already there and they just expanded, for whatever reason, inside the plaque."   Cindy St. Hilaire:        So, your title... It was a great title, with this provocative statement, "T-cells are clonal and cross react to virus and self." So, tell us a little bit more about this react to virus and self bit. What did your data show?   Jessica D'Addabbo:    So, because of the way we sequenced the T-cell receptor, we were able to have paired alpha and beta chains. And because we knew the HLA type of the patients, we were able to put the sequences that we got out after we sequenced these through an algorithm called GLIPH, which allows us to look at the CDR3 region of the T cell receptor, which is the epitope binding region. And there are certain peptide. They're about anywhere from three to four amino acids long. These are mapped to certain binding specificities to known peptides. And so, basically, we were able to look at which epitopes were most common in our plaques. And we found that after comparing these to other epitopes, that these were actually more binding to virus. Patricia Nguyen:         So let me add to what Jessica stated, and kind of emphasize the value of the data set, if you will. So, this is, I believe, the first study that provides the complete TCR repertoire of coronary plaque, and actually any plaque that I know of, which is special because we know that there is specificity of TCR binding. It's more complicated than the antibody that binds directly from B cells to the antigen, because the T-cells bind processed antigen. So, the antigens are processed by antigen presenting cells like Dendritic cells and macrophages. And they have a specific HLA MHC class that they need to present to. And they need both arms, the antigen epitope and the MHC, to activate the T-cell. So unfortunately, it's not very direct to find the antigen that is actually activating the T-cell because we're only given a piece of it. Right?            Patricia Nguyen:         But we have provided a comprehensive map of all the TCRs that we find in the plaque. And these TCRs have a sequence, an immuno acid sequence. And luckily, in the literature, there is a database of all TCR specificities. Okay. So, armed with our TCR repertoire, we can then match our TCR repertoire with an existing database of known TCR specificities. Surprisingly, the matching TCRs are specific to virus, like flu, EBV and CMB. And also, because this was done in the era of COVID, we thought it would be important to look at the coronavirus database. We did find that there were matches to the coronavirus database. Even though our finding is not specific to SARS, it does lend to some potential mechanistic link there as well.   So, because this is all computational, it is important to validate. So, the importance of validation requires us to put the TCR alpha beta chain into a Jurkat cell, which is a T-cell line that does not have alpha beta chains on it, and then expose it to what we think is the cognate antigen epitote, with the corresponding HLA MHC APC. Because you don't have all those pieces, it will not work. Yes. So importantly, we did find that what we predicted to have the specificity of a flu peptide had specificity to a flu peptide.   Patricia Nguyen:         So then, the important question was, "Okay, these patients aren't infected, right? Why are these things here? Is there a potential cross reactivity with self peptides?"   Patricia Nguyen:         So luckily, our collaborator, Dr Charles Chan, was able to connect us with another computational algorithm that he was familiar with, whereby we were able to take the peptide sequences from the flu and match them with peptide sequencing from proteins that are self and ubiquitous. And we demonstrated, again, these T-cells were activated in vitro. That is why we concluded that there's a potential cross reactivity between self and virus that can potentially lead to thrombosis associated with viral infections. Of course, this all needs to be proved in vivo.   Cindy St. Hilaire:        Sure, sure.   Patricia Nguyen:         It's that first step for other things.   Cindy St. Hilaire:        The other big immune cell that we know is in atherosclerotic plaques and that's macrophages. And they can help to present antigens and things like that. And they also help to chew up the necrotic bits. And so, do you think that this T-cell component is an earlier, maybe disease driving, process or an adaptive process that goes awry as a secondary event? Patricia Nguyen:         So, I'm a fan of the T-cell. So... I'm with team T cell. I would like to think that it is playing an active role in pathology in this case and not a reactive role, in the sense of just being there. I think that the T-cell is actively communicating with other cells within the plaque, and promoting pro fibrotic and pro inflammatory reactions, depending on the T-cell. So, a subset of this paper was looking at kind of the interactions between the T-cell and other cells within the plaque, like macrophages and smooth muscle cells. And as we know, T-cells are activated and they produce cytokines. Those cytokines then communicate to other cells. And we found that, computationally, when you look at the transcriptome, there is a pro-inflammatory signature of the T-cell that resides in the more complex stage. And then, there's an anti-inflammatory signature that kind of resides in the transition between lipid and fibro atheroma, if you will.   Cindy St. Hilaire:        So, do you know, or is it known, how dynamic these populations are? Obviously, the hearts that you got, the samples you got, didn't have active infections. But do you know perhaps even how long ago they happened, or even how soon after there might be an infection or an antigen presented that you could get this expansion? And could that be a real driver of rupture or thrombosis?   Patricia Nguyen:         So, in theory, you would suppose that T-cells expanding and dividing and producing more and more cytokines would then lead to more macrophages coming, more of their production of proteinases that destroy the plaque. Right? So yes, in theory, yes. I think it's very difficult to kind of map the progression of T cell clonality in the current model that we have, because we're just collecting tissues. However, in the future, as organoids become more in science and kind of a primary tissue, where we can... For example, Mark Davis is making organoids with spleen, and also introducing skin to that.   Patricia Nguyen:         And certainly, we could think of an organoid involving the vasculature with immune cells introduced. And so, I think, in the next phase, project 2.0, we can investigate what... like over time, if you could model atherosclerosis and the immune system contribution, T-cells as well as macrophages and other immune cells, you can then kind of map how it happens in humans. Because obviously, mice are different. We know that mice... Actually, the models of transgenic mice do not rupture. It's very hard to make them rupture. Right?   Cindy St. Hilaire:        Well, if you stop feeding them high fat diet, the plaque goes away.   Patricia Nguyen:         For sure, for sure. So I think.. I mean, Mark Davis is a huge proponent of human based research, like research on human tissue. And as a physician scientist, obviously I'm more inclined to do human based research. And Jessica's going to be a physician someday soon. And I'm sure she's more inclined to do human based research. And certainly, the mouse model and in vitro models are great because you can manipulate them. But ultimately, we are trying to cure human diseases.   Cindy St. Hilaire:        Mice are not little humans. That's what we say in my lab. I similarly do a lot of human based stuff and it's amazing how great mice are for certain things, but still how much is not there when we need to really fully recapitulate a disease model.   So, my last question is kind of regarding this autoimmune angle of your findings. And that is, women tend to have more autoimmune diseases than men, but due to the fact that you are getting heart transplants, you've got a whole lot more men in your study than women. I think it was like 31 men to four women. But, I mean, what can you do? It's the nature of heart transplants. But I'm wondering, did you happen to notice...Maybe the sample size perhaps is too small, but were there any differences in the populations of these cells between women and men? And do you think there could be any differences regarding this more prevalence of autoimmune like reactions in women?   Patricia Nguyen:         So, that's an interesting question, but you hit it on the nose when you said "Your sample is defined mainly by men." And in addition, the samples that were women tend to have less disease. And they tend to be nonischemic in etiology. So, I think that kind of restricts our analysis. And perhaps, I guess, future studies could model using female tissues, for example, instead of only male. But the limitation of all human studies is sample availability. And perhaps, human organoid research can be less limited by that. And certainly, mouse research has become more evenly distributed of male and female mice.   Cindy St. Hilaire:        Yeah. Suffice it to say, human research is hard, but you managed to do an amazing and really important study. It was really elegant and well done. Congratulations on what is an epic amount of time. 12-hour experiments are no joke, and really beautiful data. So, thank you so much for joining me today, Dr Nguyen and Miss almost Dr D'Addabbo. Congrats and I'm really looking forward to seeing your future work.   Jessica D'Addabbo:    Thank you so much.   Patricia Nguyen:         Thanks so much.   Jessica D'Addabbo:    Thank you for having us. This is wonderful.   Cindy St. Hilaire:        That's it for the highlights from the April 29th and May 13th issues of Circulation Research. Thank you so much for listening. Please check out the Circ Res Facebook page and follow us on Twitter and Instagram with the handle @Circres and #Discover CircRes. Thank you to our guests: Dr Patricia Nguyen, and soon to be Doctor, Jessica D'Addabbo, from Stanford University.   This podcast was produced by Ishara Ratnayaka, edited by Melissa Stoner, and supported by the editorial team of Circulation Research. Copy text for the highlighted articles was provided by Ruth Williams. I'm your host, Dr Cindy St. Haler. And this is Discover CircRes, you're on the go source for the most exciting discoveries in basic cardiovascular research. This program is copyright of the American Heart Association 2022. The opinions expressed by the speakers of this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more information, visit aha journals.org.  

We've been hearing a lot about immunology the past two years since the outbreak of the Covid-19 pandemic. But can you explain how our immune system works? 2007 Lasker Laureate Ralph Steinman discovered dendritic cells, the preeminent component of the immune system that initiates and regulates the body's response to foreign antigens. He discusses how he got interested in science, what it felt like to receive a Lasker Award, and eloquently explains how dendritic cells protect us from pathogens.   Read more about Steinman's Award-winning work: http://ow.ly/UH7R50J0C5R

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This episode covers dendritic cells!

Do you have ongoing gut issues but have never tried to eliminate gluten? Lindsey discusses whether this step is necessary, how to do it properly and why gluten is problematic, especially in autoimmune disease. She discusses the symptoms of celiac disease, non-celiac gluten sensitivity and SIBO and how to test for them. She also delves into the issue of loss of oral tolerance, when you become sensitive to almost all foods, and how to regain it so you can expand your diet.   Lindsey Parsons, EdD, the host, helps clients solve gut issues, reverse autoimmune disease and type 2 diabetes naturally and lose weight without cutting calories or cutting out major food groups. She's a Certified Health Coach at High Desert Health in Tucson, Arizona. She coaches clients locally and nationwide. You can also follow Lindsey on Facebook, Twitter, Instagram or Pinterest or reach her via email at lindsey@highdeserthealthcoaching.com to set up a free 1-hour Healthy and Sustainable Weight Loss/Health Restoration Breakthrough Session. Functional Health and Nutrition Review with Lindsey: http://highdeserthealthcoaching.com/functional-health-and-nutrition-review/ Health Coaching Breakthrough Session with Lindsey: http://highdeserthealthcoaching.com/healthcoaching/ Lindsey's Gut Healing Facebook Group: https://www.facebook.com/groups/gut.healing.for.you/ Betaine HCl (to supplement stomach acid for meals with meat): https://amzn.to/2GwIFKI Digestive enzymes:  https://amzn.to/38PF7Q6 DPP-IV enzymes (to digest gluten and dairy): https://amzn.to/2vx0YNT Luteolin: https://amzn.to/30YQ7YA Querticin: https://amzn.to/37xR2Sk Lindsey's Healthy and Sustainable Weight Loss Tucson Facebook Group: https://www.facebook.com/groups/614864552264400/ Tucson Reversing Autoimmune Disease Together Meetup: https://www.meetup.com/Tucson-paleo-Meetup-Group/ Lindsey Parsons' Fullscript Dispensary: https://us.fullscript.com/welcome/highdeserthealth Links to Lindsey's affiliate shops, lab tests and recommended products: http://highdeserthealthcoaching.com/supplements-and-lab-tests/ Lindsey Parsons' web site: High Desert Health: http://highdeserthealthcoaching.com and email: lindsey@highdeserthealthcoaching.com High Desert Health on Pinterest: https://www.pinterest.com/highdeserthealth/ High Desert Health on Facebook: https://www.facebook.com/HighDesertHealth/ High Desert Health on Twitter: https://twitter.com/HDesertHealth or @HDesertHealth High Desert Health on Instagram: https://www.instagram.com/high.desert.health/ or @high.desert.health Credits:   Thank you to SoundDot for the music on the podcast: Royalty Free Music: www.soundotcom.com