Podcasts about phagocytosis

Last week on the podcast, Jess spoke about the importance of building a healthy winter immune system in autumn. If you have not checked this episode yet, click here to listen. Today, on the podcast Jess is talking about the antibiotic cycle, how to break this cycle and help your child's immune system recover this winter. Nearly every child we see with immune issues or recurrent infections has had either a heavy use of antibiotics overall or exposure to antibiotics when very young. Although antibiotics have their place, they are often overused and can cause long-term effects on our health. In this episode, Jess discusses:The overuse of antibiotics and the negative long-term effects of antibiotics; Studies demonstrating the impact antibiotics have on the microbiome, atopic conditions, and metabolic disorders;The antibiotic cycle and how this cycle makes children more susceptible to infections;The effects of antibiotics on immune function;How to strengthen our children's ability to fight infections without the use of antibiotics.Episode Links:Study on the impact of early life antibiotic use on atopic and metabolic disorders;Research discussing the impact of antibiotics on the microbiome of children; Save your seat to our FREE on-demand Immunity Masterclass: 3 Simple Ways to Naturally Boost Your Kids Immunity to Avoid a Winter Full of Sickness. Click here to join us. Book a 1:1 consultation with our team.

Summary: Slime mold eats some pretty interesting stuff, but how it finds it's food is they really fascinating part. Join Kiersten as she talks about who slime mold eats.   For my hearing impaired listeners, a complete transcript of this podcast follows the show notes on Podbean   Show Notes:  “Slime Molds” by Dr. Sharon M. Douglas, Department of Plant Pathology and Ecology, The Connecticut Agricultural Experiment Station. https://portal.ct.gov “Slime Mould,” by Thomas J. Volk, in Encyclopedia of Biodiversity, 2001. https://www.sciencedirect.com “Slime Mold Nutrition” Brad Renner, University of Wisconsin-La Crosse. bioweb.uwlax.edu “Eight smart things slime molds can do without a brain,” by Alissa Greenberg, Nova, Monday, September 21, 2020. https://www.pbs.org   Slime Mold: Diet Transcript  (Piano music plays) Kiersten - This is Ten Things I Like About…a ten minute, ten episode podcast about unknown or misunderstood wildlife. (Piano music stops) Welcome to Ten Things I Like About… I'm Kiersten, your host, and this is a podcast about misunderstood or unknown creatures in nature. Some we'll find right out side our doors and some are continents away but all are fascinating.  This podcast will focus ten, ten minute episodes on different animals and their amazing characteristics. Please join me on this extraordinary journey, you won't regret it. On to number four, listeners, and we're talking diet. I'm learning so much researching this series and the fourth thing I like about slime mold is what it eats! Slime mold was thought to be a fungus for quite some time, so people were amazed to find out that it ingests it food, then digests. That doesn't sound so odd to me, since that's what I did with my breakfast this morning, but that's not how fungus does it. Fungus digests its food externally before absorbing it. So, this is what researchers expected when they looked at how slime mold eats. To say the least, they were surprised. Let's take a closer look at how slime mold eats. We're going to investigate how Myxomycota, the true slime molds, eat their food.  As a quick reminder, Myxomycota are the plasmodial slime molds. They exist as a plasmodium. A plasmodium is a blob of protoplasm without cell walls and only a cell membrane to keep everything together. (I see why this inspired a 1950s horror movie.) They are essentially an amoeba and amoebas eat their food well, like the Blob. They engulf their food and then digest it. By engulf I mean completely surround it with their amoeba body. This process is called pseudopodia. The definition of pseudopodia is a temporary protrusion of the surface of an amoeboid cell for movement and feeding. This is what slime mold does when it is preparing to eat. The next step is phagocytosis. Phagocytosis is the act of eating or damaging foreign components in cells. According to Science Direct phagocytosis is a universal cell function, which starts with the recognition and binding of a particle, generally in a receptor-dependent manner, and leads to its internalization and degradation. Sounds pretty complicated to me but, I guess it's essentially digestion. Some organisms may use it for other things besides digestion such as defending against invading pathogens, it is also important during development and in adulthood for normal turnover, remodeling, and disposal of tissues, but that's a whole other podcast. The important part of this definition is that this is the process that helps slime mold digest its food. Alright! We know how slime mold eats, let's look at what slime mold eats. Bacteria is a big favorite of slime mold, but they can also eat decaying leaves, decaying logs, yeasts, other protists, and poo.  Hey, somebody's gotta do it, right?! So far the diet and eating habits of slime molds don't seem too unusual compared to other creatures, expect for maybe the poo, but we're just getting to the really mind blowing part. First of all, slime mold can smell its food. I know what you're thinking, how can a blob of cells with no detectable olfactory system smell food? The answer is that they have olfactory receptors all over the cells connected into the amoeba. These receptors are similar to the receptors that mammals, including humans, have lining their nasal passages. I'll pause a moment while you let this information sink in… Hold on to your hat though, it's about to get even more amazing! Some mold actually shows preferences for food. That's right! If given the choice between two potential food sources they will chose the one that has the best nutritional value.  Ecologist and entomologist Tanya Latty has studied slime molds extensively and in her research she's discovered that slime molds make smart decisions about their nutritional needs. To be successful slime molds need sugars and proteins. In a laboratory setting, Latty and colleagues offered Physarum polycephalum, also know as the many-headed slime, 35 different recipes made of different ratios of the nutrients slime mold needs to survive. The slime mold chose to engulf the foods that offered the best balance of elements and avoided the recipes that would harm them or weren't worth the effort to ingest. You heard me correctly, they chose the food themselves. If nothing else blows your mind about slime mold, I just said a living entity that has no brain or any detectable ganglia is making a decision! Need another example? Latty also tested whether slime mold could make trade-offs between quality of food and risk. (I can't even believe I'm reporting this, it's so amazing!) The researchers set up an experiment where they put the preferred food under a bright light and less desirable food in the dark. Slime mold doesn't like bright light, so you'd expect it to stay in the dark and eat what it can get, right? But from what we've just learned you may be thinking it took the chance and ate the food in the light because it was worth the risk. The results were not this simple. What actually happened I that the slime mold only took the risk to enter the bright light to engulf the food if the food was fives times more nutritious than what was in the dark. That is crazy amazing! This entity that is a blob of simple cells kept together by a common wall is processing information from olfactory receptors and choosing to make a calculated trade-offs to ensure it's survival. Holy Cow!! Quoting from an article from PBS Nova Latty says, “If you're a basic system, you'd expect you always choose one. You have a simple rule that always works. If you're sophisticated, you get some information about quality of food and intensity of light and do some calculations to figure out if it's worth it.” End quote. Looks like slime mold is in the second category. Latty continues, “That implies some molds are able to process information between two different attributes of a food source, which seems pretty sophisticated thing for, well, mucus.” End quote. I have no words for this…it's truly amazing. Stick with me listeners because it only gets cooler from here. The diet and feeding behavior of slime mold is my fourth favorite thing about this mind-blowing creature. If you're enjoying this podcast please recommend me to friends and family and take a moment to give me a rating on whatever platform your listening. It will help me reach more listeners and give the animals I talk about an even better chance at change.    Join me next week for another episode about slime mold.       (Piano Music plays)  This has been an episode of Ten Things I like About with Kiersten and Company. Original music written and performed by Katherine Camp, piano extraordinaire.

Welcome to episode 101 of the official podcast of Your Unofficial Boys. Every week we review beers, talk sports and discuss funny current events. Please like and subscribe! Episode Guide: Beers of the Week: Hop Raider by New Belgium (Asheville, NC) - 3.50 Bigfoot by Sierra Nevada (Mills River, NC) - Rating: 2.50 Facts of the Week: Your brain is constantly eating itself. This process is called phagocytosis, where cells envelop and consume smaller cells or molecules to remove them from the system. Don't worry! Phagocytosis isn't harmful, but actually helps preserve your gray matter. The largest piece of fossilized dinosaur poop discovered is over 30cm long and over two liters in volume. Believed to be a Tyrannosaurus rex turd, the fossilized dung (also named a 'coprolite') is helping scientists better understand what the dinosaur ate. Animals can experience time differently from humans. To smaller animals, the world around them moves more slowly compared to humans. Salamanders and lizards, for example, experience time more slowly than cats and dogs. This is because the perception of time depends on how quickly the brain can process incoming information. The world's oldest dog lived to 29.5 years old. While the median age a dog reaches tends to be about 10-15 years, one Australian cattle dog, ‘Bluey', survived to the ripe old age of 29.5. The world's oldest cat lived to be 38 years and three days old. Creme Puff was the oldest cat to ever live. NASA genuinely faked part of the Moon landing. While Neil Armstrong's first steps on the lunar surface were categorically not faked, the astronaut quarantine protocol when the astronauts arrived back on Earth was largely just one big show. Platypuses sweat milk. This is because it doesn't have teats. Milk appears as sweat on a platypus, but it's an aquatic mammal so it doesn't actually sweat at all. Friendly Advice: The next time your significant other gets angry, drape a towel over her shoulders (like a cape) and say, “ now you're SUPER ANGRY!” Maybe she'll laugh. Maybe you'll die. My advice to anyone at an unpaid internship - steal from them. Big stuff too. Take the copier. Roll it right onto the elevator. Alcohol does not give you answers, but it certainly helps forget the question. If you swim with a friend, your chances of getting eaten by a shark will drop by 50%. Don't make snow angels in a dog park. My father once told me, "Son, if you want people to listen to what you have to say, claim it's something your father told you." Unofficial News 'Balls Out Bowling' event invites bowlers to roll in the nude Man arrested and accused of trying to steal a self-driving taxi in L.A. Billionaire Peter Thiel bankrolling ‘Olympics on steroids' event that allows athletes to dope. Unofficial Fanzone: MLB Spring Training. How are our teams doing? NFL Free Agents. NHL Standings. NBA Standings. Unofficial Thoughts: Worst injuries that we have had. We are proud to announce that Your Unofficial Boys has become Ambassadors for the ShankItGolf brand. Please use the following link and use promo code: “YourUnofficalBoys” to receive 15% off any purchases. ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://shankitgolf.com/?ref=yourunofficialboys⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Please go follow us on our social media and subscribe to our podcast on Spotify, Apple Podcast and Google Podcast. Also check out our website ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠www.yourunofficialboys.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠. --- Send in a voice message: https://podcasters.spotify.com/pod/show/your-unofficial-boys/message Support this podcast: https://podcasters.spotify.com/pod/show/your-unofficial-boys/support

Immune reviews research showing that the migration of neutrophils between endothelial cells activates bactericidal function via mechanosensing. Hosts: Vincent Racaniello, Steph Langel, Cynthia Leifer, and Brianne Barker Subscribe (free): Apple Podcasts, Google Podcasts. RSS, email Become a patron of Immune! Links for this episode MicrobeTV Discord Server Trans endothelial migration activates neutrophil killing (Immunity) Time stamps by Jolene. Thanks! Music by Steve Neal. Immune logo image by Blausen Medical Send your immunology questions and comments to immune@microbe.tv

This episode gives new meaning to the phrase, "a nice light snack". A 360-second podcast that's full of the weird, the wonderful, the profound and the hilarious facts of life on earth.© 2024 Jonathan Clemson & Robin Crossman

In today's episode, we're exploring 3 different topics. First, we'll unravel the intriguing world of beta-glucans and their dual role in regulating the immune system. Then, we'll venture into the ancient practice of Agni Sara, a yoga exercise renowned for strengthening digestive organs. Finally, we'll unveil two unique methods to trigger the acute relaxation response, encouraging parasympathetic activity. Stay tuned for this 3-topic episode! Topics: 1. Agni Sara Exercise - Definition and Purpose - Origin and Traditional Yoga Practice - Physical and Energetic Benefits - Research Study on Agni Sara - Study Involving 12 Volunteers - Ultrasound Examination of Superior Mesenteric Artery - Increase in Blood Flow and Digestive Function Improvement - Traditional Agni Sara Exercise Instructions 2. Beta-Glucans - Definition and Classification - Interaction with the Immune System - Immune System Review - Role of Dectin-1 Receptors - Immune-Boosting Effects - Stimulation of Immune Cells, Phagocytosis, & Antibody Production - Modulation of Inflammation - Stimulation of Interleukin 10 - Balancing Immune Response - Food Sources of Beta-Glucans - Mushrooms Rich in Beta-Glucans - Mushroom Extract Supplements 3. Tibetan Singing Bowls and the Acute Stress Response - Introduction to Tibetan Singing Bowls - Composition and Original Use - Sound Characteristics - Benefits of Tibetan Singing Bowls (TSB) - Impact on Distress, Anxiety, Depression, and More - Physiological Effects on Heart Rate, Respiration, and More - Research Study on Acute Relaxation Response - Comparison of TSB and Progressive Muscle Relaxation (PMR) - Evaluation of HRV, Alpha Power Band (EEG), and Anxiety - Study Findings - Promotion of Acute Relaxation Response by TSB and PMR - TSB's Pronounced Effect on HRV Parameters and Alpha Band Activity - Acknowledgment of Individual Preferences for Relaxation Techniques - Emphasis on Research-Backed Tools for Stress Reduction 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

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.31.551329v1?rss=1 Authors: Imaz-Iruretagoyena, J., Blanco-Urrejola, M., de la Cruz-Gambra, A., Marquez, M., Sierra, A., Baleriola, J. Abstract: Polarized cells in the brain, such as neurons and glia, rely on the asymmetric distribution of their proteins compartmentalizing the function of dendrites, axons, glial projections and endfeet. Subcellular proteomes can be assembled either by the transport of proteins synthesized in the cell soma or by the delivery of mRNAs to target compartments where they are locally translated into protein. This latter mechanism is known as local protein synthesis or local translation, and it has been best studied in neurons. Increasing evidence suggest it is also required to maintain local protein homeostasis in glial cells, however, in microglia, local translation remains largely unexplored. Given the scant evidence, we aimed at exploring the existence of local translation in microglial peripheral processes (MPPs) and unravel its functional significance. We report that local translation indeed happens in MPPs and it is enhanced by triggering a microglial inflammatory response with bacterial lipopolysaccharides (LPS) suggesting a functional relevance of this molecular mechanism in response to inflammation. We found that Actb and Par3 mRNAs polarize to MMPs and are locally translated upon LPS exposure. Interestingly, downregulation of the Actb binding protein IMP1/ZBP1 impaired Actb mRNA polarization and its localized translation, leading to defects in filopodia distribution, lamellar directed migration and phagocytosis in microglia. Thus, our work contributes to recent findings that localized translation occurs in microglia and gives a mechanistic insight into the relevance of this molecular mechanism in fundamental microglial functions in response to LPS-induced inflammation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Overview White Blood Cells Normal Value Range Pathophysiology Special considerations Abnormal values (high) Abnormal values (low) Nursing Points General Normal value range WBC 4500-10000/mcL Differential Neutrophils 40-60% Bands 3-5% >8% indicates signal to WBC for more production Infection or inflammation is severe Eosinophils 1-4% Basophils 0.5-1% Lymphocytes 20-40% Monocytes 2-8% Pathophysiology WBC Formed in the bone marrow Responsible for responding to foreign invaders Creating antibodies (immunity) Phagocytosis (eating bacteria or fungi) Multiple types with different purposes Neutrophils – inflammation and first response to invader Eosinophils – Inflammation Allergic response Parasites Basophils Inflammation Allergic response Lymphocytes Create antibodies Recognize antigens Destroy cells T Cells B Cells Natural Killer cells Monocytes Macrophages Engulf and destroy invaders Indicative of infection Special considerations Lavender top tube Will commonly be submitted for Complete Blood Count with differential Abnormal lab values Increased White Blood Cell count (leukocytosis) Infection Inflammation Trauma/Stress Pregnancy Asthma Allergic Reaction Decreased lab values (leukopenia) Systemic Lupus Erythematosus (SLE)/Rheumatoid arthritis Cancers Chemotherapy/Radiation Medications Neutropenic precautions Masks Gloves Wash hands Consider yourself infectious Prevent spread of infection to the patient Assessment Consider the overall WBC count plus abnormalities in differential Evaluate patient Signs or symptoms of: Trauma Inflammation Infection Therapeutic Management Antibiotic therapies where indicated by infection (followed by cultures to determine efficacy of antibiotics) Anti-inflammatories for inflammation Provide neutropenic precautions when necessary Nursing Concepts Lab Values Infection Control Patient Education Educate patient on the finishing any antibiotics completely. Do not stop prior, even if the patient says they are feeling better.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.19.537577v1?rss=1 Authors: Laban, H., Froemel, T., Fleming, I., Benz, P. M. Abstract: Macrophage polarization plays an important role in tissue regeneration. Numerous factors and signaling molecules affect polarization processes. Here we investigated the consequences of the genetic deletion of vasodilator-stimulated phosphoprotein (VASP), which increases macrophage M1 polarization through augmented signal transducer and activator of transcription 1 (STAT1) signaling, and AMP-activated protein kinase (AMPK), which attenuates inflammation by inhibiting STAT1 expression and signaling. While a basal activity of AMPK (phosphorylation on Thr172) was detected in macrophages from wild-type mice, AMPK phosphorylation was significantly reduced in VASP-deficient M1 macrophages in vitro and the expression of the pro-inflammatory cytokines TNF and IL-1{beta} was increased in these cells. Consistent with the role of AMPK in macrophage phagocytosis, VASP-/- macrophage phagocytosis was also significantly impaired. Interestingly, impaired phagocytosis could be rescued by exogenous activation of AMPK. Mechanistically, we found that VASP binds directly to protein phosphatase 1 regulatory subunit 6 (PP1-R6) and we hypothesize that VASP-binding to PP1-R6/PP1 limits the PP1-dependent de-phosphorylation of AMPK in wild-type cells. Conversely, AMPK dephosphorylation by the PP1-R6/PP1 complex is enhanced in the absence of VASP. In summary, we have identified a link between VASP and AMP-activated protein kinase (AMPK) activity, which may contribute to the pro-inflammatory phenotype of VASP-deficient macrophages. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

On this WSP, the boys watch as Cell reveals his origins and makes his escape, dead set on feeding on the local population. While the Z warriors decide on their next move, the androids arrive, and Piccolo steps up to fight 17. Note: Phagocytosis (fa·go·sai·tow·suhs) is the process through which a cell eats another cell. Thomas felt very clever with this one.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.03.531012v1?rss=1 Authors: Morrison, V. E., Houpert, M. G., Trapani, J. B., Brockman, A., Kingsley, P. J., Katdare, K. A., Layden, H. M., Nguena-Jones, G. N., Trevisan, A. J., Maguire-Zeiss, K. A., Marnett, L. J., Bix, G., Ihrie, R. A., Carter, B. D. Abstract: Microglia are the primary phagocytes in the central nervous system and are responsible for clearing dead cells generated during development or disease. The phagocytic process shapes the phenotype of the microglia, which affects the local environment. A unique population of microglia reside in the ventricular-subventricular zone (V-SVZ) of neonatal mice, but how they influence this neurogenic niche is not well-understood. Here, we demonstrate that phagocytosis creates a pro-neurogenic microglial phenotype in the V-SVZ and that these microglia phagocytose apoptotic cells via the engulfment receptor Jedi-1. Deletion of Jedi-1 decreases apoptotic cell clearance, triggering the development of a neuroinflammatory phenotype, reminiscent of neurodegenerative and-age-associated microglia, that reduces neural precursor proliferation via elevated interleukin (IL)-1{beta} signaling; inhibition of IL-1 receptor rescues precursor proliferation in vivo. Together, these results reveal a critical role for Jedi-1 in connecting microglial phagocytic activity to a phenotype that promotes neurogenesis in the developing V-SVZ. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.28.530395v1?rss=1 Authors: Marulanda-Gomez, A. M., Bayer, K., Pita, L., Hentschel, U. Abstract: Sponges harbor diverse, specific, and stable microbial communities, but at the same time, they efficiently feed on microbes from the surrounding water column. This filter-feeding lifestyle poses the need to distinguish between three categories of bacteria: food to digest, symbionts to incorporate, and pathogens to eliminate. How sponges discriminate between these categories is still largely unknown. Phagocytosis is conceivable as the cellular mechanism taking part in such discrimination, but experimental evidence is missing. We developed a quantitative in-vivo phagocytosis assay using an emerging experimental model, the sponge Halichondria panicea. We incubated whole sponge individuals with different particles, recovered the sponge (host) cells, and tracked the particles into the sponge cells to quantify the sponge phagocytic activity. Fluorescence-activated cell sorting (FACS) and fluorescent microscopy were used to quantify and verify phagocytic activity (i.e., the population of sponge cells with internalized particles). Sponges were incubated with a green microalgae to test the effect of particle concentration on the percentage of phagocytic activity, and to determine the timing where the maximum of phagocytic cells are captured in a pulse-chase experiment. Lastly, we investigated the application of our phagocytic assay with other particle types (i.e., bacteria and fluorescent beads). The percentage of phagocytic cells that had incorporated algae, bacteria, and beads ranged between 5 to 24 %. We observed that the population of phagocytic sponge cell exhibited different morphologies and sizes depending on the type of particle presented to the sponge. Phagocytosis was positively related to algal concentration suggesting that sponge cells adjust their phagocytic activity depending on the number of particles they encounter. Our results further revealed that sponge phagocytosis initiates within minutes after exposure to the particles. Fluorescent and TEM microscopy rectified algal internalization and potential digestion in sponge cells, and suggests translocation between choanocyte and archeocyte-like cells over time. To our knowledge, this is the first quantitative in-vivo phagocytosis assay established in sponges that could be used to further explore phagocytosis as a cellular mechanism for sponges to differentiate between different microorganisms. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

https://psychiatry.dev/wp-content/uploads/speaker/post-11896.mp3?cb=1676549964.mp3 Playback speed: 0.8x 1x 1.3x 1.6x 2x Download: Mitochondrial control of microglial phagocytosis by the translocator protein and hexokinase 2 in Alzheimer’s disease – PubMed Lauren H Fairley et al.Full EntryMitochondrial control of microglial phagocytosis by the translocator protein and hexokinase 2 in Alzheimer's disease – PubMed

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.16.528874v1?rss=1 Authors: Rijal, R., Ismail, I., Jing, S., Gomer, R. H. Abstract: Dictyostelium discoideum is a soil-dwelling unicellular eukaryote that accumulates extracellular polyphosphate (polyP). At high cell densities, when the cells are about to overgrow their food supply and starve, the corresponding high extracellular concentrations of polyP allow the cells to preemptively anticipate starvation, inhibit proliferation, and prime themselves to begin development. In this report, we show that starved D. discoideum cells accumulate cell surface and extracellular polyP. Starvation reduces macropinocytosis, exocytosis, and phagocytosis, and we find that these effects require the G protein-coupled polyP receptor (GrlD) and two enzymes, Polyphosphate kinase 1 (Ppk1), which is required for synthesizing intracellular polyP, cell surface polyP, and some of the extracellular polyP, and Inositol hexakisphosphate kinase (I6kA), which is required for cell surface polyP and polyP binding to cells, and some of the extracellular polyP. PolyP reduces membrane fluidity, and we find that starvation reduces membrane fluidity, and this effect requires GrlD and Ppk1 but not I6kA. Together, these data suggest that in starved cells, extracellular polyP decreases membrane fluidity, possibly as a protective measure. In the starved cells, sensing polyP appears to decrease energy expenditure from ingestion, and decrease exocytosis, to both decrease energy expenditures and retain nutrients. 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/2023.02.09.527850v1?rss=1 Authors: Fadjukov, J., Wienbar, S., Milicevic, N., Hakanen, S., Vihinen-Ranta, M., Ihalainen, T. O., Schwartz, G. W., Nymark, S. Abstract: Retinal pigment epithelium (RPE) at the back of the eye is a monolayer of cells with an extensive network of gap junctions that contributes to retinal health in a multitude of ways. One of those roles is the phagocytosis of photoreceptor outer segments. This renewal is under circadian regulation and peaks after light onset. Connexin 43 (Cx43) is the most predominantly expressed gap junction protein in RPE. In this study, we examine how gap junctions and specifically, Cx43 phosphorylation, contribute to phagocytosis in both human embryonic stem cell derived RPE and mouse RPE monolayers. We show that both Rac1 and CDK5 have differences in protein localization at different points in phagocytosis, and that by using their effectors, the capability of RPE for phagocytosis changes. CDK5 has not yet been reported in RPE tissue, and here we show that it likely regulates Cx43 localization and resulting electrical coupling. We find that gap junctions in RPE are temporally highly dynamic during phagocytosis and that regulation of gap junctions via phosphorylation is likely critical for maintaining eye health. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.29.525735v1?rss=1 Authors: Xu, Y., Moulding, D., Jin, W., Beggs, S. Abstract: Peripheral injury during the early postnatal period alters the somatosensory system, leading to behavioural hyperalgesia upon re-injury in adulthood. Spinal microglia have been implicated as the cellular mediators of this phenomenon, but the mechanism is unclear. We hypothesised that neonatal injury (1) alters microglial phagocytosis of synapses in the dorsal horn leading to long-term structural changes in neurons, and/or (2) trains microglia, leading to a stronger microglial response after re-injury in adulthood. Using hindpaw surgical incision as a model we showed that microglial density and phagocytosis increased in the dorsal horn region innervated by the hindpaw. Dorsal horn microglia increased engulfment of synapses following injury, with a preference for those expressing the vesicular GABA transporter VGAT and primary afferent A-fibre terminals in neonates. This led to a long-term reduction of VGAT density in the dorsal horn and reduced microglial phagocytosis of VGLUT2 terminals. We also saw an increase in apoptosis following neonatal injury, which was not limited to the dorsal horn suggesting that larger circuit wide changes are happening. In adults, hindpaw incision increased microglial engulfment of predominantly VGAT synapses but did not alter the engulfment of A-fibres. This engulfment was not affected by prior neonatal injury, suggesting that microglial phagocytosis was not trained. These results highlight microglial phagocytosis in the dorsal horn as an important physiological response towards peripheral injury with potential long-term consequences and reveals differences in microglial responses between neonates and adults. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.08.523170v1?rss=1 Authors: Elguero, J. E., Liu, G., Tiemeyer, K., Gandevia, H., Duro, L., McCall, K. Abstract: In nervous system development, disease and injury, neurons undergo programmed cell death, leaving behind cell corpses that are removed by phagocytic glia. Altered glial phagocytosis has been implicated in several neurological diseases including Alzheimer's disease, Parkinson's disease, and traumatic brain injury. To untangle the links between glial phagocytosis and neurodegeneration, we investigated Drosophila mutants lacking the phagocytic receptor Draper. Loss of Draper leads to persistent neuronal cell corpses and age-dependent neurodegeneration. Here we investigate whether the phagocytic defects observed in draper mutants lead to chronic increased immune activation that promotes neurodegeneration. A major immune response in Drosophila is the activation of two NF{kappa}B signaling pathways that produce antimicrobial peptides, primarily in the fat body. We found that the antimicrobial peptide Attacin-A is highly upregulated in the fat body of aged draper mutants and that inhibition of the Immune deficiency (Imd) pathway in the glia and fat body of draper mutants led to reduced neurodegeneration, indicating that immune activation promotes neurodegeneration in draper mutants. Taken together, these findings indicate that phagocytic defects lead to neurodegeneration via increased immune signaling, both systemically and locally in the brain. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.21.521447v1?rss=1 Authors: Kaba, M., Carreras-Sureda, A., Nunes-Hasler, P., Demaurex, N. Abstract: Changes in membrane phosphoinositides and local Ca2+ elevations at sites of particle capture coordinate the dynamic remodeling of the actin cytoskeleton during phagocytosis. Here, we show that the phosphatidylinositol (PI) transfer proteins PITPNM1 (Nir2) and PITPNM2 (Nir3) maintain PI(4,5)P2 homeostasis at phagocytic cups, thereby promoting actin contractility and the sealing of phagosomes. Nir3 and to a lesser extent Nir2 accumulated in ER cisternae juxtaposed to phagocytic cups when expressed in phagocytic mouse fibroblasts. CRISPR-Cas9 editing of Nir2 and Nir3 genes decreased plasma membrane PI(4,5)P2 levels, store-operated Ca2+ entry (SOCE), and receptor-mediated phagocytosis, stalling particle capture at cup stage. Re-expression of either Nir2 or Nir3 restored phagocytosis, but not SOCE, proportionally to the PM PI(4,5)P2 levels. Phagosomes forming in Nir2/3-edited cells had decreased overall PI(4,5)P2 levels but normal periphagosomal Ca2+ signals. Nir2/3 editing reduced the density of contractile actin rings at sites of particle capture, causing repetitive low-intensity contractile events indicative of abortive phagosome closure. We conclude that Nir-mediated lipid transfer maintains phosphoinositide homeostasis at phagocytic cups, thereby sustaining the signals that initiate the remodeling of the actin cytoskeleton during phagocytosis. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

https://psychiatry.dev/wp-content/uploads/speaker/post-11235.mp3?cb=1671346136.mp3 Playback speed: 0.8x 1x 1.3x 1.6x 2x Download: Altered expression of microglial markers of phagocytosis in schizophrenia – Aaron K Jenkins et al. Schizophrenia Research. 2022. Cognitive disturbances in schizophreniaFull EntryAltered expression of microglial markers of phagocytosis in schizophrenia –

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.15.516591v1?rss=1 Authors: Lieberman, R., Elnaggar, K., Jesseman, K., DeFrancisco, S., Degouveia, K., Suneby, E., Wu, H., Rojas, L. A., Graef, J. D. Abstract: Synucleinopathies such as Parkinson's disease (PD) are characterized by pathologic production, aggregation, and cell-to-cell transmission of alpha-synuclein (alpha-syn) protein that results in impaired cellular function. While neurons of the substantia nigra pars compacta express high levels of alpha-synuclein and are highly vulnerable to its aberrant expression or conformation, brain-resident macrophages (microglia) are also sensitive to abnormal alpha-synuclein, with recent reports indicating that elevated levels impair phagocytic ability in vivo and in vitro. To explore the impact of elevated alpha-syn on microglial function we employed a co-culture model containing iPSC-derived neurons and microglia-like cells. iPSCs from healthy control donors and a Parkinson's donor with an allelic triplication of the SNCA gene locus were differentiated into neurons and microglia-like cells. In monoculture, neurons and microglia generated from the SNCA triplication donor expressed higher levels of SNCA transcript and protein. Neurons were found to have significantly greater expression of SNCA compared to microglia, regardless of donor genotype. Co-cultures of neurons and microglia revealed that microglia cultured with SNCA triplication neurons displayed reduction in phagocytosis of fluorescent E. coli, irrespective of microglia donor genotype. SNCA mRNA and protein expression could be reduced with treatment with an antisense oligonucleotide (ASO) targeting SNCA. ASO treatment partially rescued microglia phagocytosis in SNCA triplication co-cultures and in co-cultures containing SNCA triplication neurons and healthy control microglia. Our results complement and extend previous findings of impaired microglial function in the presence of elevated alpha-synuclein in a novel patient-derived co-culture model that utilizes more disease-relevant conditions rather than the relaying on the addition of exogenous alpha-synuclein. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.10.515919v1?rss=1 Authors: Savulescu, A. F., Peton, N., Oosthuizen, D., Hazra, R., Mhlanga, M. M., Coussens, A. K. Abstract: Macrophages provide a first line of defense against invading pathogens, including the leading cause of bacterial mortality, Mycobacterium tuberculosis (Mtb). Phagocytosing extracellular organisms mediate pathogen clearance via a multitude of antimicrobial mechanisms, uniquely designed against an array of pathogens. Macrophages are able to execute different programs of activation in response to pathogenic challenge with host mediators, polarizing them to a variety of differentiation states, including the pro-inflammatory M1 and anti-inflammatory M2 states. The functional polarization of a macrophage prior to infection, thus impacts the outcome of host-pathogen interaction. One of the limitations when using in vitro differentiated human primary monocyte-derived macrophages (MDMs) is the heterogeneous nature of the mature population, which presents a challenge for quantitative characterization of various host-pathogen processes. Here, we describe an approach to minimize this heterogeneity, based on micropatterning of cells to reintroduce aspects of cellular homogeneity lost in a 2D tissue culture. Micropatterning consists of growing cells at the single cell level on microfabricated patterns, to constrain the size and shape of the cell, reducing cell-to-cell variation and mimicking the physiological spatial confinement that cells experience in tissues. We infected micropatterned GM-CSF- (M1) and M-CSF- (M2) derived human MDMs with Mtb, which allowed us to study host-pathogen interactions at a single cell level, at high resolution and in a quantitative manner, across tens to hundreds of cells in parallel. Using our approach, we were able to quantify phagocytosis of Mtb in MDMs, finding phagocytic contraction is increased by interferon-gamma stimulation, whilst contraction and bacterial uptake is decreased following silencing of phagocytosis regulator NHLRC2 or Tween80 removal of bacterial surface lipids. We also identify alterations in host organelle position within Mtb infected MDMs, as well as identifying differences in Mtb subcellular localization in relation to the microtubule organizing center (MTOC) and in line with the cellular polarity in M1 and M2 MDMs. Our approach described here can be adapted to study other host-pathogen interactions and co-infections in MDMs and can be coupled with downstream automated analytical approaches. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.19.512953v1?rss=1 Authors: Zhu, K., He, Q., Tsai, S.-F., Mudalige, D. M., Tang, A., Henrion, M. Y. R., Liu, Y., Vijayan, R., Zaidi, S. S. A., Branden, L., Cadiz, M. P., Hodos-Nkhereanye, R., Moein, S., Alamprese, M. L., Bennett, D. A., De Jager, P., Kuo, Y.-M., Ronaldson, P. T., Chang, R. Abstract: Microglia, the innate immune cells of the brain, are essential determinants of late-onset Alzheimer Disease (LOAD) neuropathology. Here, we developed an integrative computational systems biology approach to construct causal network models of genetic regulatory programs for microglia in Alzheimer Disease (AD). This model enabled us to identify novel key driver (KDs) genes for microglial functions that can be targeted for AD pharmacotherapy. We prioritized FCER1G, HCK, LAPTM5, ITGB2, SLC1A2, PAPLN, GSAP, NTRK2, and CIRBP as KDs of microglial phagocytosis promoting neuroprotection and/or neural repair. In vitro, shRNA knockdown of each KD significantly reduced microglial phagocytosis. We repurposed riluzole, an FDA-approved ALS drug that upregulates SLC1A2 activity, and discovered that it stimulated phagocytosis of A{beta}1-42 in human primary microglia and decreased hippocampal amyloid plaque burden/phosphorylated tau levels in the brain of aged 3xTg-AD mice. Taken together, these data emphasize the utlility of our integrative approach for repurposing drugs for AD therapy. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.03.510683v1?rss=1 Authors: King'uyu, D., Nti-Kyemereh, L., Tram, M., Kopec, A. M. Abstract: Opioids have long been used for clinical pain management, but also have addictive properties that have contributed to the ongoing opioid epidemic. While opioid activation of opioid receptors is well known to contribute to reward and reinforcement, data now also suggest that opioid activation of immune signaling via toll-like receptor 4 (TLR4) may also play a role in addiction-like processes. TLR4 expression is enriched in immune cells in peripheral organs and blood and in the nervous system is primarily expressed in microglia, the resident immune cells of the central nervous system. In peripheral immune cells, morphine is repeatedly shown to decreases immune activation and phagocytosis in vivo and in vitro. Phagocytosis is an important immune effector that serves to clear damage, debris, and infection. Unlike peripheral immune cells, the effect of morphine on microglia is less well studied. Morphine is reported to both increase and decrease microglial phagocytosis. Several different factors contribute to microglial phagocytic activity, including sex, region, and local microglial density. We hypothesized that morphine increases phagocytic activity in microglia, but in a density-, dose-, region-, and sex-dependent manner ex vivo. To test this, we isolated microglia from adult male and female rat cortex and striatum and plated them ex vivo at a relatively low or high density. Microglia were incubated with neutral fluorescent microbeads to stimulate phagocytosis in the presence of one of four morphine doses. We found that brain region of origination and plating density, but not sex, impacted microglial phagocytosis at baseline. These heterogenous properties further diverge when morphine is applied causing emergence of effects not observed at baseline, maintenance of some baseline effects, and disappearance of effects observed at baseline. Further work is necessary to identify the precise interactions and signaling that is dominant in different sex, region, and density contexts to better understand the complex effects of opioids on microglial immunoregulation. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Dr. Linden Hu, Vice Dean for Research at Tufts University in Boston Massachusetts and Paul and Elaine Chervinsky Professor in Immunology, discusses new and ongoing research pertaining to the prevention, treatment and diagnosis of human Lyme disease. He also discusses some of the key unanswered questions about Lyme, such as how B. burgdorferi adapts to different hosts and environments and why some patients have been known to exhibit persistent symptoms even after treatment.   Links mentioned: Webinar - Vector-Borne Disease in a Changing Climate https://asm.org/Webinars/Vector-Borne-Disease-in-a-Changing-Climate The Bulls-Eye Rash of Lyme Disease: https://asm.org/Articles/2018/April/going-skin-deep-investigating-the-cutaneous-host-p Pfizer and Valneva Initiate Phase 3 Study of Lyme Disease Vaccine Candidate VLA15 https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-valneva-initiate-phase-3-study-lyme-disease Could This Treatment Prevent Chronic Lyme Disease? https://news.northeastern.edu/2021/10/06/preventing-chronic-lyme-disease/ Promising New Drug Would Eradicate Lyme While Leaving Gut Microbes Alone: https://www.lymedisease.org/members/lyme-times/2022-spring-news/targeted-lyme-disease-drug/ A Tick's Meal: https://asm.org/Podcasts/TWiM/Episodes/A-Tick-s-Meal-TWiM-258 Evidence That the Variable Regions of the Central Domain of VlsE Are Antigenic during Infection with Lyme Disease Spirochetes https://journals.asm.org/doi/10.1128/IAI.70.8.4196-4203.2002 Distinct Roles for MyD88 and Toll-Like Receptors 2, 5, and 9 in Phagocytosis of Borrelia burgdorferi and Cytokine Induction https://journals.asm.org/doi/10.1128/IAI.01600-07

We have been receiving a lot of questions on social media and via our email in regards to winter illness this year. Especially because the last two winters have been spent mostly indoors thanks to the pandemic, parents are finding there is a dramatic increase in illness this season. Popular questions from parents include what they can do to boost their child's immune system, but we also have to consider what we might be doing that is depleting their immune system as well. As parents, we can be providing our children with all the right nutrients to increase their immunity, but if they're still exposed to things that are weakening their immune system at the same time, it might not work in your favour.In this podcast episode, I go over the 3 things that weaken your child's immune system, including:1: Sugar: Studies show that a high sugar intake can suppress the immune system by up to 45% for up to 5 hours after consuming it. If your child is having big doses of sugar regularly, their immune system will keep getting suppressed. In this episode, I share the best ways to reduce sugar intake in your children's diet. 2: Stress: When we are stressed, there is a boost in cortisol, a stress hormone. Cortisol prepares the body for fight or flight. But the body only has limited resources and will prioritise where those go. So when stress hits, it will pull nutrients from the immune system and digestion. Find out the common causes of stress in children and what we can do to reduce our child's stress. 3: Too much time spent indoors: Kids are spending more time indoors than ever before, and it is having a negative impact on overall wellbeing. There are two major concerns with so much indoor time including reduced vitamin D exposure, and the lack of microbes generated from nature. In this episode, I give you some ideas and inspiration for getting your children outside during winter. These three factors might just be the missing piece as to why your children can't fight off the winter illness.  Episode Links:Check out this blog post - 3 Things That Weaken Your Child's Immune System. Break the winter sickness cycle and learn how to keep your family healthy this winter.Get access to our on-demand masterclass (to watch at your convenience) 3 SIMPLE Ways To NATURALLY BOOST Your Kids' IMMUNITY to Avoid A Winter Full Of Sickness. Sign up here

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay. In today's episode, a little brushing before I take a deep dive in true and exact process of Pharmacokinetics, let the oven preheat before true baking starts!! The heads covered are Vesicular transport and Filtration. As I solve the puzzle of tangled and knotty wool yarn of the day's talk, the beginnings of conversation are marked by definitions and explanations of Pinocytosis and Phagocytosis, two types of Endocytosis. Its own description is as simple as simplicity.After covering details along with examples for this heads mentioned, i will shift the tides of my talk towards Exocytosis, another good simple talk unfolds in words and this is followed by something too simple equalling to 2+2 addition in mathematics, which never turns greater as 5 , or less as 3, but exactly as equal to 4. Decorated with classical antique examples, I will pull down the curtains for today's talk while slowly curbing the pace and volume of my verbal proceedings, a quick tip to revise and learn better!Just grab it hard, and make a difference in your performance, nothing left untold.......... For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!!

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay.In today's episode, a little brushing before I take a deep dive in true and exact process of Pharmacokinetics, let the oven preheat before true baking starts!!The heads covered are Vesicular transport and Filtration. As I solve the puzzle of tangled and knotty wool yarn of the day's talk, the beginnings of conversation are marked by definitions and explanations of Pinocytosis and Phagocytosis, two types of Endocytosis. Its own description is as simple as simplicity.After covering details along with examples for this heads mentioned, i will shift the tides of my talk towards Exocytosis, another good simple talk unfolds in words and this is followed by something too simple equalling to 2+2 addition in mathematics, which never turns greater as 5 , or less as 3, but exactly as equal to 4. Decorated with classical antique examples, I will pull down the curtains for today's talk while slowly curbing the pace and volume of my verbal proceedings, a quick tip to revise and learn better!Just grab it hard, and make a difference in your performance, nothing  left  untold.......... For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!!

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay.In today's episode, a little brushing before I take a deep dive in true and exact process of Pharmacokinetics, let the oven preheat before true baking starts!!The heads covered are Vesicular transport and Filtration. As I solve the puzzle of tangled and knotty wool yarn of the day's talk, the beginnings of conversation are marked by definitions and explanations of Pinocytosis and Phagocytosis, two types of Endocytosis. Its own description is as simple as simplicity.After covering details along with examples for this heads mentioned, i will shift the tides of my talk towards Exocytosis, another good simple talk unfolds in words and this is followed by something too simple equalling to 2+2 addition in mathematics, which never turns greater as 5 , or less as 3, but exactly as equal to 4. Decorated with classical antique examples, I will pull down the curtains for today's talk while slowly curbing the pace and volume of my verbal proceedings, a quick tip to revise and learn better!Just grab it hard, and make a difference in your performance, nothing left untold.......... For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!!

Welcome to Immunity Week! Five episodes in Five days all on the topic of Immunity. Today we kick off with an episode all about Pathogens, Antigens and Phagocytosis!Find us on the internet!Our website - Teachmescience.co.ukEmail - teachmebiologycast@gmail.comTwitter - twitter.com/teachmebiocastInstagram - @teachmebiologycast

This episode: Algae surviving impact that killed the dinosaurs seem to have consumed other organisms to make it through the dark times! Download Episode (7.1 MB, 10.3 minutes) Show notes: Microbe of the episode: Chaetoceros tenuissimus RNA virus 01 News item Takeaways Being able to look through time and learn about what might have happened to creatures throughout Earth's history is what makes paleontology great. Everyone knows about dinosaurs and what happened to them at the end of the Cretaceous period thanks to science. But what we can learn is not limited just to large organisms; there are ways to learn about microorganisms of the past as well, including by looking at fossils!   In this study, fossils of hard-shelled algae from around the end of the dinosaurs show that many of these microbes in the oceans went extinct at the same time due to the massive space impact. Debris blocked out sunlight for years, making it difficult for photosynthetic organisms to survive. So some of these algae appear to have survived by preying on smaller organisms, pulling them in through a hole in their shell.   Journal Paper: Gibbs SJ, Bown PR, Ward BA, Alvarez SA, Kim H, Archontikis OA, Sauterey B, Poulton AJ, Wilson J, Ridgwell A. 2020. Algal plankton turn to hunting to survive and recover from end-Cretaceous impact darkness. Sci Adv 6:eabc9123. Other interesting stories: Phages could help treat diabetic wound infections without harming microbiota (paper)   Email questions or comments to bacteriofiles at gmail dot com. Thanks for listening! Subscribe: Apple Podcasts, Google Podcasts, Android, or RSS. Support the show at Patreon, or check out the show at Twitter or Facebook.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.11.378893v1?rss=1 Authors: Raiders, S., Black, E. C., Bae, A., MacFarlane, S., Shaham, S., Singhvi, A. Abstract: Glia in the central nervous system engulf neuron fragments during synapse remodeling and recycling of photo-receptor outer-segments. Whether glia passively clear shed neuronal debris, or actively remove neuron fragments is unknown. How pruning of single-neuron endings impacts animal behavior is also unclear. Here we report that adult C. elegans AMsh glia engulf sensory endings of the AFD thermosensory neuron. Engulfment is regulated by temperature, AFD sensory input, and tracks AFD activity. Phosphatidylserine (PS) flippase TAT-1/ATP8A, functions with glial PS-receptor PSR-1/PSR and PAT-2/-integrin to initiate engulfment. Glial CED-10/Rac1 GTPase, acting through a conserved GEF complex, executes phagocytosis using the actin-remodeler WSP-1/nWASp and the membrane-sealing factor EFF-1 fusogen. CED-10 levels determine engulfment rates, and engulfment-defective mutants exhibit altered AFD-ending shape and thermosensory behavior. Our findings reveal a molecular pathway underpinning glia-dependent phagocytosis in a peripheral sense-organ, and demonstrate that glia actively engulf neuron-fragments, with profound consequences on neuron shape and animal behavior. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.04.368977v1?rss=1 Authors: Takuwa, H., Orihara, A., Takado, Y., Shimojo, M., Ishikawa, A., Takahash, M., Barron, A. M., Ono, M., Maeda, J., Masamoto, K., Akatsu, H., Tolkovsky, A. M., Ji, B., Tomita, Y., Ito, H., Zhang, M.-R., Goedert, M., Spillantini, M. G., Lee, V. M.-Y., Trojanowski, J. Q., Maehara, T., Suhara, T., Sahara, N., Higuchi, M. Abstract: Fibrillary tau pathologies have been implicated in Alzheimer's and allied neurodegenerative diseases, while mechanisms by which neurons bearing tau tangles die remain enigmatic. To address this issue, we pursued tau and related key pathologies macroscopically by PET and MRI and microscopically by intravital two-photon laser optics. Time-course macroscopic assays of tau transgenic mice demonstrated intimate associations of tau deposition and increase of an inflammatory microglial marker, translocator protein (TSPO), with regional brain atrophy. Longitudinal microscopy of these mice revealed a rapid turnover of tau lesions resulting from continuous generation of new tau aggregates followed by loss of neurons and their fibrillar contents. This technology also allowed the capturing of the disappearance of tangle-bearing neurons several days after being engulfed by activated microglia. Notably, a therapeutic TSPO ligand profoundly suppressed the mobility and phagocytotic activity of microglia and improved neuronal survival in this model, supporting the involvement of primary phagocytosis of viable neurons by microglia in tau-primed neuronal death. Finally, partial depletion of microglia revealed roles of immune factors, MFG-E8 and C1q, as 'eat-me' signals for an immediate attraction of phagocytic microglia towards the elimination of tangle-loaded neurons. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.25.354399v1?rss=1 Authors: Quek, H., Cuni-Lopez, C., Stewart, R., Colletti, T., Notaro, A., Sun, Y., Guo, C. C., Lupton, M. K., Nguyen, T. H., Oikari, L. E., Roberts, T. L., Lim, Y. C., La Bella, V., White, A. R. Abstract: Aims: Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease characterised by the loss of upper and lower motor neurons. Neuroinflammation mediated by microglial activation is evident in post-mortem brain tissues, and in brain imaging of patients with ALS. However, the exact role of microglia in ALS remains to be elucidated partly due to the lack of an accurate microglial model system that is able to recapitulate the clinical pathology of ALS. Moreover, direct sampling of microglia from patients with ALS is not feasible, further limiting the study of microglial function in ALS. To address this shortcoming, we describe an approach that generates monocyte-derived microglia (MDMi) that are capable of expressing molecular markers, and functional characteristics similar to resident human brain microglia. Importantly, MDMi can be routinely and reproducibly generated from ALS patient blood, and reveal patient heterogeneity associated with age, sex and disease subgroup. Methods: MDMi were successfully established from all 30 ALS patients, including 15 patients with slow disease progression, 6 with intermediate progression, and 9 with rapid progression, together with 20 non-affected heathy controls (HC). Results: Our ALS MDMi model recapitulated canonical pathological features of ALS including non-phosphorylated and phosphorylated-TDP-43-positive pathological inclusions. We further observed significantly impaired phagocytosis, altered cytokine expression and microglial morphology, as well as elevated DNA damage in ALS compared to HC MDMi. Abnormal phagocytosis was observed in all ALS cases, and was correlated to the progression of disease. Moreover, in-depth analysis of individual microglia revealed cell-specific variation in phagocytic function that was significantly altered, and exacerbated in rapid disease progression. Conclusions: Our approach enabled us to generate ALS patient microglia from peripheral blood samples using a rapid, robust, cost-effective, and reproducible protocol. We have shown that ALS monocyte-derived microglia have significantly altered functional behaviour compared to age-matched HCs, with a major deficit in phagocytic activity. This is also the first demonstration of abnormal TDP-43 localisation in microglia grown from ALS patients. Overall, this approach is highly applicable to monitor disease progression and can be applied as a functional readout in clinical trials for anti-neuroinflammatory agents. Additionally, this model system can be used as a basis for personalised therapeutic treatment for ALS, as well as other neurodegenerative diseases. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.22.296376v1?rss=1 Authors: Illouz, T., Nicola, R., Ben-Shushan, L., Madar, R., Biragyn, A., Okun, E. Abstract: Down Syndrome (DS) features a life-long overexpression of the APP and DYRK1A genes, leading to a cognitive decline mediated by Amyloid-{beta} (A{beta}) overproduction and tau hyper-phosphorylation. As DS can be diagnosed in utero, maternally transferred anti-A{beta} antibodies might promote removal of early accumulation of A{beta} from the CNS. A DNA-vaccine expressing A{beta}1-11 was delivered to wild-type female mice, followed by mating with 5xFAD males, which exhibit early A{beta} plaque formation, similar to individuals with DS. Maternal A{beta}-specific antibodies provided transgenic offspring with passive immunization against A{beta} via the placental and subsequently lactation. Maternal antibodies reduced cortical A{beta} levels 4 months after antibodies were undetectable, along with alleviating short-term memory deficits and activation of the FcR1/Syk/Cofilin pathway in microglia. Sera from immunized dams facilitated A{beta} clearance by microglia in a Syk-dependent manner. These data suggest that maternal anti-A{beta} immunization is a potential strategy to alleviate cognitive decline in individuals with DS. Copy rights belong to original authors. Visit the link for more info

A vaccine is a biological preparation that provides active acquired immunity to a particular infectious disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. Vaccination comes from the Latin word “Vacca” meaning cow. First used to eradicate smallpox estimated to have killed about 300-500 million people. Vaccination is different from inoculation in that inoculation is a process where the actual pathogen itself is injected and in some cases, the person inoculated may catch the disease and infection can become serious as well. Variolation: Practised in Ottoman Empire for immunity against smallpox, brought to England by lady Lady Mary Wortley Montagu. Required quarantine. Milk Maids rejected the procedure claiming they had cowpox.  Immune cells start as stem cells within the bone marrow. Lymph nods store immune cells to be released during pathogen infection and swell during infection as a result. Antigen Presenting Cells (APC) monitors blood for pathogens and on finding them start the process of Phagocytosis where the pathogens are ingested and broken down to be presented to the nearest lymph nodes which start the immune response. These pieces of pathogens are called antigens. APC activates the T cells which oversee the cytokine proteins. These proteins of the immune system help regulate immunity. B cells multiply and generate antibodies that can kill the pathogens. After the first infection, these T and B cells remain in the system preparing for future pathogen invasions. Two types of vaccines: Live attenuated vaccines: a mild version of the pathogen is used. Effective for a long time but the risk of being infected. Inactivated vaccine: Dead pathogens or parts of pathogens are used. It is effective for a short term and repeated booster shots might be essential. Safer. Herd Immunity: When a majority of people in the society get immunity which slows down the spread. Immunological memory: Ability of an immune system to quickly and specifically recognise an antigen the body has previously seen and then initiate an immune response. Acquired Immune System: It is a subsystem of the immune system that consists of specialised cells and processes that eliminate pathogens by limiting their growth. Vaccination can fail due to difference in immunity amongst people. Usually has side effects and no vaccine is 100% effective Source: Infographic Show video: How Are Vaccines Actually Made Reddit post on Rabies: What's a scary or disturbing fact that would probably keep most people awake at night? Image by cottonbro from Pexels

Talk to a Dr. Berg Keto Consultant today and get the help you need on your journey (free consultation). Call 1-540-299-1557 with your questions about Keto, Intermittent Fasting, or the use of Dr. Berg products. Consultants are available Monday through Friday from 8 AM to 10 PM EST. Saturday & Sunday from 9 AM to 6 PM EST. USA Only. Get Dr. Berg's Veggie Solution today! • Flavored (Sweetened) - https://shop.drberg.com/veggie-solution-flavored-sweetened?utm_source=Podcast&utm_medium=AGM(Anchor) • Plain (Unflavored) - https://shop.drberg.com/veggie-solution-plain?utm_source=Podcast&utm_medium=AGM(Anchor) Take Dr. Berg's Free Keto Mini-Course! Today we're going to talk about apple cider vinegar and the coronavirus. Apple cider vinegar is very anti-microbial. It has been known to kill: • E. coli • Staph • Candida Apple cider vinegar also has the ability to downregulate cytokines. A cytokine is involved in the immune process and inflammation. Apple cider vinegar may be able to help decrease inflammation by downregulating cytokines. Apple cider could also impair cell membranes in certain pathogens. Apple cider vinegar and other kinds of vinegar can stimulate phagocytosis. Phagocytosis is a condition where you have this immune cell eating the pathogen. It eats the bacteria or virus and kills it. Vinegar, being an acid, can stimulate the activity of that process. DATA: https://www.ncbi.nlm.nih.gov/pmc/arti... https://journals.plos.org/plosone/art... Dr. Eric Berg DC Bio: Dr. Berg, 51 years of age is a chiropractor who specializes in weight loss through nutritional & natural methods. His private practice is located in Alexandria, Virginia. His clients include senior officials in the U.S. government & the Justice Department, ambassadors, medical doctors, high-level executives of prominent corporations, scientists, engineers, professors, and other clients from all walks of life. He is the author of The 7 Principles of Fat Burning. FACEBOOK: fb.me/DrEricBerg?utm_source=Podcast&utm_medium=Anchor TWITTER: http://twitter.com/DrBergDC?utm_source=Podcast&utm_medium=Post&utm_campaign=Daily%20Post YOUTUBE: http://www.youtube.com/user/drericberg123?utm_source=Podcast&utm_medium=Anchor DR. BERG'S SHOP: https://shop.drberg.com/?utm_source=Podcast&utm_medium=Anchor MESSENGER: https://www.messenger.com/t/drericberg?utm_source=Podcast&utm_medium=Anchor

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.11.088443v1?rss=1 Authors: Griffin, P., Sheehan, P. W., Dimitry, J. M., Guo, C., Kanan, M. F., Lee, J., Zhang, J., Musiek, E. S. Abstract: The circadian clock has been shown to regulate various aspects of brain health including microglial and astrocyte activation. Here we report that deletion of the master clock protein BMAL1 induces robust increases in the expression of complement genes such as C3, C4b and C1q in the hippocampus. Loss of downstream REV-ERBalpha-mediated transcriptional repression led to increases in C4b in neurons and astrocytes as well as C3 protein in microglia and astrocytes. REV-ERBalpha deletion induced complement C3/C4b gene expression and increased microglial phagocytosis of synapses in the CA3 region of the hippocampus. Finally, we observed diurnal variation in the degree of microglial synaptic phagocytosis in wild type mice which was abrogated by REV-ERBalpha deletion. This work uncovers the BMAL1-REV-ERBalpha axis as a regulator of complement expression and synaptic phagocytosis in the brain, thereby illuminating a novel mechanism of synaptic regulation by the circadian clock. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.06.075903v1?rss=1 Authors: Sierra-Torre, V., Plaza-Zabala, A., Bonifazi, P., Abiega, O., Diaz-Aparicio, I., Tegelberg, S., Lehesjoki, A.-E., Valero, J., Sierra, A. Abstract: Microglial phagocytosis of apoptotic cells is an essential component of the brain regenerative response in neurodegenerative diseases. Phagocytosis is very efficient in physiological conditions, as well as during apoptotic challenge induced by excitotoxicity or inflammation, but is impaired in mouse and human mesial temporal lobe epilepsy (MTLE). Here we extend our studies to a genetic model of progressive myoclonus epilepsy type 1 (EPM1) in mice lacking cystatin B (CSTB), an inhibitor of cysteine proteases involved in lysosomal proteolysis. We first demonstrated that microglial phagocytosis was impaired in the hippocampus in Cstb knock-out (KO) mice when seizures arise and hippocampal atrophy begins, at 1 month of age. To test if this blockage was related to the lack of Cstb in microglia, we used an in vitro model of phagocytosis and siRNAs to acutely reduce Cstb expression but we found no significant effect in the phagocytosis of apoptotic cells. We then tested whether seizures were involved in the phagocytosis impairment, similar to MTLE, and analyzed Cstb KO mice before seizures begin, at postnatal day 14. Here, phagocytosis impairment was restricted to the granule neuron layer but not to the subgranular zone, where there are no active neurons. Furthermore, we observed apoptotic cells (both phagocytosed and not phagocytosed) in Cstb deficient mice at close proximity to active, cFos+ neurons and used mathematical modeling to demonstrate that the physical relationship between apoptotic cells and cFos+ neurons was specific for Cstb KO mice. These results suggest a complex crosstalk between apoptosis, phagocytosis and neuronal activity, hinting that local neuronal activity could be related to phagocytosis dysfunction in Cstb KO mice. Overall, this data suggest that phagocytosis impairment is an early feature of hippocampal damage in epilepsy and opens novel therapeutic approaches for epileptic patients based on targeting microglial phagocytosis. Copy rights belong to original authors. Visit the link for more info

This episode: A newly discovered species of bacteria consumes other bacteria as prey by engulfing them! Download Episode (8.7 MB, 12.6 minutes) Show notes: Microbe of the episode: SARS-CoV-2! This is the coronavirus responsible for COVID-19, the current pandemic. For more up-to-date information, please refer to the American Society for Microbiology, This Week in Virology, and other reputable sources. Stay healthy! Takeaways There are bacteria living almost every different lifestyle you can think of, including predatory, preying on other bacteria. Since bacterial cells are usually quite rigid, bacterial predators usually consume others either by burrowing inside them or digesting them from outside, rather than engulfing prey like eukaryotes often do. The study here discovers a new kind of bacteria, in the group called Planctomycetes, known for having unusually flexible cells and internal compartments like eukaryotes. This new species does engulf its prey, including bacteria and even tiny algae, and digests them inside itself. It possesses multiple adaptations that suit it for this lifestyle. Journal Paper: Shiratori T, Suzuki S, Kakizawa Y, Ishida K. 2019. Phagocytosis-like cell engulfment by a planctomycete bacterium. Nat Commun 10:1–11. Other interesting stories: Engineering a common industrial yeast strain to fix carbon dioxide (paper) Lake microbes convert microplastics into essential fatty acids   Email questions or comments to bacteriofiles at gmail dot com. Thanks for listening! Subscribe: Apple Podcasts, Google Podcasts, Android, or RSS. Support the show at Patreon, or check out the show at Twitter or Facebook.

Emma looks at the process of phagocytosis in dealing with pathogens. She looks at the role of T cytotoxic and T helper cells. Perfect for AQA, Edexcel and OCR exam boards. Ideal for preparing you for your A Level Biology exam. Click here for the full course, or visit this link: http://bit.ly/2TaDFD8

Active Transport, Endocytosis, Phagocytosis, Pinocytosis, and Exocytosis are discussed during this segment.

The TWiM team presents an extracellular bacterium associated with Paramecium, and induction of antiviral immunity by a bacteriophage that prevents bacterial clearance. Subscribe to TWiM (free) on iTunes, Google Podcasts, Stitcher, Android, RSS, or by email. You can also listen on your mobile device with the Microbeworld app. Become a Patron of TWiM! Bacteria on the outside of paramecia (ISME) Phage trigger antiviral immunity (Science) Image credit Letters read on TWiM 198 Music used on TWiM is composed and performed by Ronald Jenkees and used with permission. Send your microbiology questions and comments to twim@microbe.tv

Norris Cotton Cancer Center Grand Rounds presented on October 24, 2017 by Douglas R. Green, PhD Chair, Department of Immunology St. Jude Children’s Research Hospital

Synaptic activity shifts dendritic lysosomes Invading pathogens or other toxic agents can trigger the assembly of the inflammasome adaptor ASC into large, intracellular specks that activate caspase-1 to initiate a proinflammatory cell death called pyroptosis. Kuri et al. follow the dynamics of ASC speck formation in live zebrafish, revealing their lethal effects on epidermal keratinocytes and their subsequent engulfment and degradation by macrophages. This biosights episode presents the paper by Kuri et al. from the September 4th, 2017, issue of The Journal of Cell Biology and includes an interview with two of the paper's authors, Paola Kuri and Maria Leptin (EMBL). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research.

Them TWiM team discusses the importance of neutrophils in microbial infections, and evidence that ancient bacteria had two cell walls. Hosts: Vincent Racaniello, Elio Schaechter, Michael Schmidt, and Michele Swanson. Subscribe to TWiM (free) on iTunes, Stitcher, RSS, or by email. You can also listen on your mobile device with the Microbeworld app. Links for this episode Conquering neutrophils (PLoS Path) Ancestral outer membrane in firmicutes (eLife ) Were gram positive rods the first bacteria? (Cell) Image credit Letters read on TWiM 136 This episode is brought to you by CuriosityStream, a subscription streaming service that offers over 1,400 documentaries and non­fiction series from the world's best filmmakers. Get unlimited access starting at just $2.99 a month, and for our audience, the first two months are completely free if you sign up at curiositystream.com/m​icrobe ​and use the promo code MICROBE​. This episode is also brought to you by Drobo, a family of safe, expandable, yet simple to use storage arrays. Drobos are designed to protect your important data forever. Visit www.drobo.com to learn more. Listeners can save $100 on a Drobo system at drobostore.com by using the discount code Microbe100. Send your microbiology questions and comments (email or mp3 file) to twim@microbe.tv 

Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin The case of the Man from Assam is solved, and phagocytosis of Leishmania by B-1 cells is brought to you by the Three Twipeteers on this episode of TWiP.   Subscribe to TWiP (free) in iTunes, Google Play Music, by the RSS feed or by email Links for this episode: Kalazar detect (pdf) Phagocytosis of Leishmania promastigotes by B-1 cells (Parasite Immunol) Image credit Letters read on TWiP 108 This episode is sponsored by ASM Agar Art Contest and ASM Microbe 2016 Case study for TWiP 108 Todays case is a 26 yo male longhaul truck driver from northern tiger country of India. Comes into hospital at end of rainy season with 6 days of fever, chills, muscle aches, small loose stools, vomiting, trouble breathing, cough, decreased urine output. Lives in mud hut with coconut leaf roof. No one else in family  is sick (wife, two children). Significant animal and insect exposure (dogs, cows, monkeys). Got sick after coming home from a trip up north. No significant medical probs, no surgery. Really sick. Pain everywhere. Occasionally drinks palm wine. Some yellowing of eyes. Has lost a little weight. Ketonic breath. Exam: 39 fever, bp 100/71, 126 heart rate, 24 resp rate. Looks distressed, not fully sharp. Nothing focal on lung exam. Belly tender, esp upper right, spleen enlarged. Liver is tender but not enlarged. Some labs: bun elevated 102, creatinine elevated, Hg decreased 11, platelets 9000 (down), white count 10.3 no eosinophils. LDH 8000 AST/ALT normal, bilirubin 21. Never been this sick. Send your diagnosis to twip@microbe.tv Send your questions and comments to twip@microbe.tv

Ivan Bogeski explains how redox-insensitive ORAI calcium channels enable monocytes to sustain calcium signaling while still producing bactericidal reactive oxygen species.

Jim Casanova describes how a macrophage adhesion receptor both mediates phagocytosis of bacteria and triggers the generation of reactive oxygen species to kill them.

Background: Dictyostelium harbors several paralogous Sec7 genes that encode members of three subfamilies of the Sec7 superfamily of guanine nucleotide exchange factors. One of them is the cytohesin family represented by three members in D. discoideum, SecG, Sec7 and a further protein distinguished by several transmembrane domains. Cytohesins are characterized by a Sec7-PH tandem domain and have roles in cell adhesion and migration. Results: We study here Sec7. In vitro its PH domain bound preferentially to phosphatidylinositol 3,4-bisphosphate (PI(3,4) P-2), phosphatidylinositol 4,5-bisphosphate (PI(4,5)P-2) and phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P-3). When following the distribution of GFP-Sec7 in vivo we observed the protein in the cytosol and at the plasma membrane. Strikingly, when cells formed pseudopods, macropinosomes or phagosomes, GFP-Sec7 was conspicuously absent from areas of the plasma membrane which were involved in these processes. Mutant cells lacking Sec7 exhibited an impaired phagocytosis and showed significantly reduced speed and less persistence during migration. Cellular properties associated with mammalian cytohesins like cell-cell and cell-substratum adhesion were not altered. Proteins with roles in membrane trafficking and signal transduction have been identified as putative interaction partners consistent with the data obtained from mutant analysis. Conclusions: Sec7 is a cytosolic component and is associated with the plasma membrane in a pattern distinctly different from the accumulation of PI(3,4,5)P-3. Mutant analysis reveals that loss of the protein affects cellular processes that involve membrane flow and the actin cytoskeleton.

At the end of cytokinesis, the microtubule-rich midbody connecting the daughter cells is either shed into the extracellular space or retained by one of the daughters. Chai et al. find that the midbodies released from C. elegans Q neuroblasts are cleared via a pathway that closely mimics the removal of apoptotic cell corpses. This biosights episode presents the paper by Chai et al. from the December 24, 2012 issue of the Journal of Cell Biology and includes an interview with senior author Guangshuo Ou (Institute of Biophysics, Chinese Academy of Sciences, Beijing, China). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research. Subscribe to biosights via iTunes or RSS View biosights archive The Rockefeller University Press biosights@rockefeller.edu

The protein phosphatase activity of PTEN impairs macrophage phagocytosis of a fungal pathogen by promoting actin depolymerization.

Mon, 1 Jan 1990 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9801/1/9801.pdf Kortmann, H.; Jochum, Marianne; Fröhlich, D.; Billing, A. ddc:610, Medizin

Fri, 1 Jan 1988 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9337/1/9337.pdf Kortmann, H.; Jochum, Marianne; Fröhlich, D.; Billing, A.

Fri, 1 Jan 1988 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9498/1/9498.pdf Kortmann, H.; Jochum, Marianne; Fröhlich, D.; Billing, A. ddc:

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.15.042143v1?rss=1 Authors: Desale, S. E., Chinnathambi, S. Abstract: Background: Seeding effect of extracellular Tau species is an emerging aspect to study the Tauopathies in Alzheimers disease. Tau seeds enhance the propagation of disease along with its contribution to microglia-mediated inflammation. Omega-3 fatty acids are known to exert the anti-inflammatory property to microglia by modulating cell membrane compositions. The immunomodulatory function of omega-3 fatty acids exerts anti-inflammatory property to microglia. Owing to the imparted anti-inflammatory nature enhance phagocytosis and increased migration property has been observed in microglia. The dietary omega-3 fatty acids are found to change the lipid composition of the cell membrane that predominated many signaling cascade and by modulating specific receptor response. Thus the omega-3 fatty acids influence microglial response in Tauopathy. Methods: N9 microglia cells were exposed to extracellular full-length Tau monomer and aggregates along with ALA (alpha Linolenic acid) to study the internalization of exposed Tau. The degradation of internalized Tau studied with the endosomal markers Rab5 and Rab7. The final degradation step in phagocytosis has been studied with LAMP-2A as lysosomal markers. The changes in the rate of migration of microglia were assessed by wound-scratch assay along with Microtubule organizing center (MTOC) reorientation were studied after exposure of Tau and ALA as the property of highly migratory microglia. The role of actin in phagocytosis and migration was observed with the study of actin structures lamellipodia, filopodia, and membrane ruffling. The formation of extensive actin branching in lamellipodia and membrane ruffling was studied with the help of ARP2/3 complex for nucleating actin network. Results: The increased phagocytosis of extracellular Tau monomer and aggregates has been observed upon ALA exposure to microglia cells. The intracellular degradation of internalized Tau species was targeted by early and late endosomal markers Rab5 and Rab7. The increase levels of LAMP-2A and colocalization with internalized Tau indicated the degradation via lysosome. These results indicate the degradation of internalized Tau species in the presence of ALA instead of getting accumulated in the cell. The enhanced migratory ability of microglia in the presence of ALA induces the MTOC repolarization and reduces the nuclear-centrosomal axis polarity and favorable anterior positioning of MTOC. The increased migration also complemented with the enhance actin remodeling through lamellipodia, filopodia and membrane ruffles formation along with Iba-1 protein. The high density of ARP2/3 complex at the leading ends of migratory microglia confirmed the extensive branching of actin filaments on ALA exposure. Conclusions: Tau seeds greatly contributes to the spread of disease, one way to reduce the spreading is to reduce the presence of extracellular Tau seed. Microglia could be influenced to reduce extracellular Tau seed with dietary fatty acids. Our results suggest that dietary fatty acids ALA significantly enhance phagocytosis and intracellular degradation of internalized Tau. The actin dynamics and enhanced migration supports the phagocytosis process. Our approach provides the insights of beneficial role of ALA as anti-inflammatory dietary supplement to treat AD. Copy rights belong to original authors. Visit the link for more info