Podcasts about lysosomes

1er épisode / 5, de la série sur la maladie de Pompe. Episode 1 : Maladie rare – Qu'appelle-t-on maladie de Pompe ? Invité : Dr Emmanuelle Salort-Campana, neurologue, praticien hospitalier à l'hôpital de la Timone, à Marseille, clinicien du centre de référence des pathologies neuromusculaires PACA Réunion Rhône-Alpes de la filière Filnemus, membre du groupe de rédaction du PNDS sur la maladie de Pompe, réalisé avec les filières FILEMEMUS et G2M. http://fr.ap-hm.fr/service/maladies-neuromusculaires-et-sla-hopital-timone https://www.filnemus.fr/  https://www.filiere-g2m.fr/    1️⃣   Qu'appelle-t-on maladie de Pompe ? [0'34 – 1'30] ✔️ Glycogénose de type 2, maladie musculaire due à un déficit enzymatique. ✔️Parmi les premières maladies neuromusculaires à bénéficier d'un traitement. ✔️ Environ 290 cas recensés en France. Pour plus d'informations, retrouvez notre page article : https://rarealecoute.com/maladie-de-pompe-glycogenose-musculaire-de-type-ii/ 2️⃣   Quelle est la physiopathologie de cette maladie rare ? [1'30 – 2'49] ✔️ Maladie due à des mutations génétiques, entraînant un déficit en alpha-glucosidase acide. ✔️ L'enzyme déficiente empêche la dégradation du glycogène, qui s'accumule dans les lysosomes des muscles squelettiques, cardiaques et lisses. 3️⃣   Quel tableau clinique doit faire suspecter la maladie de Pompe ? [2'49 -4'05] ✔️ Forme infantile sévère : cardiomyopathie, hypotonie, détresse respiratoire. ✔️ Forme tardive variée (début après 1 an) : faiblesse musculaire des ceintures, atteinte des muscles respiratoire, avec sévérité variable. 4️⃣   Quel est le pronostic de la maladie de Pompe ? [4'05 – 5'44] ✔️ Pronostic révolutionné avec l'apparition de traitements 5️⃣   À qui adresser les patients en cas de suspicion de la maladie de Pompe ? [4'05 – 6'20] ✔️ Signes d'alerte : faiblesse musculaire, augmentation des CPK, atteinte respiratoire. ✔️ Dépistage par un test accessible. ✔️Orientation vers un centre de référence de la filière Filnemus.   L'équipe : Virginie Druenne – Ambassadrice RARE à l'écoute Cyril Cassard – Journaliste/Animation Hervé Guillot - Production Crédits : Sonacom ****************************** À propos : "RARE à l'écoute" est un podcast dédié à la sensibilisation aux maladies rares et au soutien des personnes touchées par ces affections. Créé par un groupe passionné de professionnels de la santé, le podcast vise à informer les professionnels de santé et fournissant des informations sur les dernières avancées médicales et scientifiques dans le domaine des maladies rares, et inspirer les patients et leurs proches en partageant des histoires de courage et de persévérance. Contenu :

Today, I am blessed to have Spencer Feldman here with me. Spencer is the founder of www.Remedylink.com — where for the last 20 years, he has been formulating and manufacturing detoxification products for doctors and their patients. His company specializes in helping support your body's natural responses to heavy metal toxins.  His background in Holistic Health and Chelation Therapy and passion for detoxification allows Spencer to do what he loves every day- make products that allow real detoxification to happen. Being the longest-running Suppository Company in the United States, Spencer has shared his passion for health for over 20 years with products that represent true craftsmanship and commitment to quality.  Spencer is now in his 50s and he lives with his partner completely off-grid on his 100-acre farm where he spends his time tending his orchard and garden while continuing to design new products to help detoxify people.  In this episode of Keto Kamp featuring guest Spencer Feldman, we deeply dive into the long-term effects of COVID-19 vaccines and the presence of spike proteins in the bloodstream. Spencer sheds light on the potential sources of these proteins and the need to address their continuous production within the body. We also explore whether spike proteins can be transferred from vaccine recipients to non-recipients through intimacy and the reported health implications.  Additionally, Spencer speaks about the influence of environmental factors on human behavior, drawing parallels to a study involving rodents in an enclosed environment. We discover how proteolytic enzymes, cyclodextrins, and lysosomes can be harnessed to break down harmful proteins and genetic material, ultimately optimizing our health. The conversation culminates in discussing digestion, fasting, kidney health, and protein intake, providing valuable insights for overall wellness. Join us on this enlightening journey as we uncover the secrets behind these vital health topics. Purchase Remedy Link products here: https://remedylink.com/ / / 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. [04:35] Long-Term Impact of COVID-19 Vaccines & Spike Proteins Researchers have identified the presence of spike proteins in the bloodstreams of individuals six months after receiving the COVID-19 vaccine. This finding raises questions about the source of these proteins and the body's ability to break them down or sequester them. One possibility is that these proteins are continuously produced due to a reservoir of viral infection in the body that was never fully eliminated. However, this scenario may not apply to most individuals, as typically, dormant infections only re-emerge when the immune system is weakened. Another potential explanation involves reverse transcriptase, where foreign genetic material from the vaccine may have integrated into the recipient's DNA. While this can be problematic, it doesn't necessarily lead to an increase in spike proteins unless the integrated genetic material affects actively expressed genes. Regardless of the source, addressing the presence of these spike proteins is crucial. However, a more comprehensive approach is needed to understand how to manage foreign genetic material and prevent the ongoing production of these toxins. [17:25] Can Spike Proteins Be Transferred from COVID Vaccine Recipients to Non-Recipients Through Intimacy? The theoretical possibility of individuals who did not receive a COVID vaccine acquiring spike proteins is a complex issue. The potential transfer of these proteins or foreign genetic material may occur through sexual activity with someone who received the COVID vaccine.  Reports of menstrual irregularities, blood clots, hemorrhages, and even miscarriages in individuals who were intimate with vaccinated partners suggest the need for further investigation into these possible connections. [21:20] The Influence of Environmental Factors on Human Behavior Spencer references a study involving rodents placed in an enclosed environment with an abundant food supply. As the rodent colony grew and outstripped its food source, various behaviors emerged, including increased homosexuality, infanticide, and murder, all contributing to a population decline. Spencer touches on the impact of environmental chemicals, such as Atrazine, which are known to affect gender identity and behavior. These chemicals are suggested to have contributed to changes in human behavior and choice, drawing parallels to the rodent study. Human choices and cultural shifts may be influenced by external factors that affect behavior, similar to how genetics and environmental influences affect rodents' choices and population dynamics. [35:00] Breaking Down Harmful Proteins and Genetic Material Spencer touches on the use of proteolytic enzymes, such as nattokinase, to break down spike proteins. These enzymes play a crucial role in addressing the presence of harmful proteins in the body. Cyclodextrins can effectively bind to prion fragments, helping to reduce their impact and minimize their spike effects. Enzymes, particularly pancreatic ribonuclease, have the potential to break down foreign genetic material. This approach may support the body in breaking down external genetic material, even if it's highly stable. Lysosomes, organelles within cells, are responsible for breaking down used proteins and certain toxins. Fasting can help clean up lysosomes, allowing them to function more efficiently in recycling and removing accumulated waste from the cells. [37:30] Cleaning Lysosomes and Securing Your Health Cyclodextrins are a powerful way to clean out lysosomes, even more effective than fasting, and can reach places that fasting cannot access. Cleaning out lysosomes using cyclodextrins creates space for other substances to be sequestered, such as foreign genetic material, which might otherwise continue to cause issues. [43:05] Unlocking the Link Between Spike Proteins and Allergies Spike proteins in the body can lead to various immune dysfunction reactions, including allergies, which can affect a wide range of tissues and systems. Allergies are often histamine-mediated reactions, and they can manifest in ways beyond the common symptoms like skin itching, watery eyes, or sneezing. Chronic conditions may have an allergic component, such as plaque in arteries or irritable bladder. Chronic allergic responses can lead to increased levels of immunoglobulins, which are responsible for targeting toxins and infections. The balance between immunoglobulins and albumin in the blood can influence overall health. Higher levels of albumin in the blood are associated with better health, longevity, intelligence, and physical beauty. It plays a vital role in detoxifying the body, and maintaining optimal albumin levels is crucial for overall well-being. [51:30] Optimizing Digestion, Fasting, Kidney Health, and Protein Intake for Wellness Pay attention to your enzyme levels and digestion efficiency. Digestive enzyme supplements may assist in breaking down proteins and aiding in better nutrient absorption. Intermittent fasting may not be the best choice for everyone. Instead, consider longer fasting periods, like 7 to 14 days, which can provide more significant metabolic benefits. Short-term fasts might stress your body without yielding the same advantages. Keep an eye on your kidney function, especially if you have high levels of blood urea nitrogen (BUN) and a high BUN-to-creatinine ratio. Elevated levels may indicate potential kidney stress, and you may need to adjust your protein intake to optimize kidney health. While protein is important for muscle, bone density, and overall health, consider spreading your protein consumption evenly throughout the day rather than in high doses all at once. This can help reduce the burden on your kidneys and maintain better overall health. AND MUCH MORE! Resources from this episode:  Remedylink: https://remedylink.com/ Email Spencer: info@remedylink.com Spencer Feldman | Is Histamine Intolerance The Cause Of Your Mysterious Symptoms? KKP: 630: https://ketokamp.libsyn.com/spencer-feldman-is-histamine-intolerance-the-cause-of-your-mysterious-symptoms-kkp-630 / / 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. // F O L L O W ▸ instagram | @thebenazadi | http://bit.ly/2B1NXKW ▸ facebook | /thebenazadi | http://bit.ly/2BVvvW6 ▸ twitter | @thebenazadi http://bit.ly/2USE0so ▸clubhouse | @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.

Today, I am blessed to have here with me, Spencer Feldman. He founded Remedylink, where he has been formulating and manufacturing detoxification products for doctors and their patients. He was raised in New York where he spent most of his life before deciding the Pacific Northwest was where he belonged. Spencer can do what he loves daily by creating products that support natural detoxification, thanks to his training in holistic health, chelation therapy, and detoxification. Spencer has shared his love of health for over 20 years through his longest-running suppository company in the country, with goods that reflect proper workmanship and a commitment to quality. In this episode, Spencer discusses the importance of a balanced diet and its impact on microbiome health. The best way to improve our overall health is by detoxification. Spencer reveals the effective and convenient alternatives for detox. Tune in as we chat about long-term carnivore or high-fat diets, lysosomes' role, cyclodextrins and probiotics, and detoxification in maintaining overall health and promoting graceful aging. 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. [06:16] Histamine Receptors and Allergies: A New Perspective on Health Disorders Allergic reactions can be immediate or delayed. The latter, often called intolerances, can occur hours after exposure to an allergen and can be harder to identify due to this delay. Histamine receptors are found throughout the body, not only in typical locations like the skin, sinuses, and lungs. Therefore, allergic reactions can affect various bodily systems. Health issues like interstitial cystitis, plaque in the arteries, and neurological conditions may have allergic components, meaning they may be triggered or worsened by allergies or intolerances. It's crucial to identify and minimize exposure to allergens, which can come from various sources, such as food, to mitigate these adverse health effects. This can be done through allergy and intolerance tests. Understanding the broader impact of allergies can lead to better diagnoses and treatments for various health conditions that might have been previously unexplained.  [15:18] How Can You Manage Histamine Levels in Leftover Food? Check this out! Histamine, produced by bacteria, can accumulate in leftover food and may cause unpleasant reactions when consumed. This accumulation begins immediately after cooking and cannot be reversed by reheating. Refrigeration slows down histamine production by reducing bacterial activity. However, leftovers should be refrigerated immediately after cooking to limit histamine buildup effectively. Leftovers should be spread out rather than lumped in the fridge to speed up cooling and slow histamine buildup. This increases the surface area exposed to the cold temperature, helping the food cool down faster. Due to the potential histamine buildup in stored food, sensitive or reactive people may need to avoid leftovers until their condition is controlled. [17:37] What's the Effect of Vaccines on the Immune System that Makes a Significant Health Challenge? Long-term COVID-19 is linked to IgG4 disease, characterized by an immune system overreaction leading to tissue swelling and fibrosis. This previously rare condition is now seen more frequently due to the COVID-19 pandemic and related vaccines. Vaccines can trigger an immune response that produces spike proteins indefinitely, leading to continuous inflammation and fibrosis. This response lacks an "off switch," which presents a significant health challenge. To help manage this ongoing reaction, proteolytic enzymes, such as natto kinase and serrapeptase, may break down the spike proteins and fibrosis. Over time, lysosomes, the cellular "recycling centers," can become overwhelmed with proteins they cannot break down and gradually transform into "landfills." This shift may be a primary factor behind accelerated aging. The key to managing long-term health effects, particularly in COVID-19, is to support the body's protein digestion mechanisms and clean out lysosomes, potentially slowing the aging process.  [26:16] What Dietary Adaptation Techniques Are Useful Over the Long Term?  If you have a histamine problem, you can make significant improvements by modifying your environment and diet. Still, structural damage caused by inflammation from histamine may take longer to heal. Food reactivity is a spectrum, not a binary state. Some may be highly allergic to certain foods but only mildly reactive to others. Begin reintroduction with foods you are mildly reactive to. Over time, humans have selectively cultivated plants to have fewer toxins (anti-nutrients) and more desirable traits like sweetness. This has pros and cons, including the loss of some beneficial anti-nutrients. Some anti-nutrients can have medicinal value and defend against viruses, fungi, parasites, bacteria, and even cancer. Knowing which plants to avoid is crucial due to their high content of harmful anti-nutrients, like soy and spinach, which can harm our thyroid function and cause conditions such as kidney stones. A general guideline is to stay away from oxalates. [36:26] What's the Importance of Raw Meat and Protein? Raw meat contains a variety of proteins and peptides, which could be beneficial for anti-aging and overall health, which may be altered or reduced during the cooking process. Cooking meat releases glutamate, a flavor-enhancing amino acid, which can cause adverse reactions in some individuals, such as headaches or shaking. The cooking process can also lead to the creation of glycation products which can contribute to aging and other health issues. To mitigate the formation of glycation products during cooking, marinate your meat and cook with some acid, such as lemon juice. Recognize your sensitivity to glutamate. If you're not sensitive, you may only need to reduce your consumption of high-glutamate foods. If you are sensitive, more drastic dietary changes may be required for your well-being.  [42:10] What's the Role of Olive Oil in Nutrient Delivery and Fuel Source? While olive oil has many health benefits due to its oleocanthal and polyphenols content, it does not necessarily negate its glycation content. Olive oil should be used in moderation, not as a main fuel source but as a nutrient delivery mechanism. This supports the absorption of fat-soluble nutrients from other foods. Balancing the intake of different food groups like low glycemic grains, beans, and fats can provide a more balanced energy source. Individuals who consume large amounts of oil may need to increase their protein intake accordingly. It's important to protect the lysosomes, cellular components involved in waste disposal, especially when consuming large quantities of a particular food. [51:53] What Are the Benefits of The Carnivore Diet? The microbiome plays a significant role in overall health and requires prebiotics for optimal function, found primarily in plant-based foods. Carnivore diets may be short-term beneficial but can lead to a lack of necessary prebiotics over time. Introducing a range of plant-based foods gradually can maintain a healthy microbiome. Lysosomes, the organelles in cells responsible for digesting fats and proteins, can become overloaded by misfolded proteins and hydrogenated fats, leading to neurologic conditions. Regular detoxification of metals and minimizing intake of misfolded proteins and hydrogenated fats can help maintain lysosomal health and aid graceful aging. Introducing substances like cyclodextrins can help maintain lysosomal health by clearing out hydrogenated fats and misfolded proteins, especially for individuals following high-fat diets like keto or carnivore diets. AND MUCH MORE! Resources from this episode:  Website: https://remedylink.com/ 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 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. // 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.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.07.548108v1?rss=1 Authors: Jerabkova-Roda, K., Mousson, A., Peralta, M., Karali, R., Justiniano, H., Lisii, L.-M., Carl, P., Asokan, N., Busnelli, I., Larnicol, A., Lefebvre, O., Lachuer, H., Pichot, A., Stemmelen, T., Molitor, A., Hirschler, A., Delalande, F., Sick, E., Carapito, R., Carapito, C., Hyenne, V., Schauer, K., Ronde, P., GOETZ, J. G. Abstract: Emerging evidences suggest that both function and position of organelles are pivotal for tumor cell dissemination. Among them, lysosomes stand out as they integrate metabolic sensing with gene regulation and secretion of proteases. Yet, how the function of lysosomes is linked to their position and how this controls metastatic progression remains elusive. Here, we analyzed lysosome subcellular distribution in micropatterned patient-derived melanoma cells and found that lysosome spreading scales with their aggressiveness. Peripheral lysosomes promote invadopodia-based matrix degradation and invasion of melanoma cells, which is directly linked to their lysosomal and cell transcriptional programs. When controlling lysosomal positioning using chemo-genetical heterodimerization in melanoma cells, we demonstrated that perinuclear clustering impairs lysosomal secretion, matrix degradation and invasion. Impairing lysosomal spreading in a zebrafish metastasis model significantly reduces invasive outgrowth. Our study provides a mechanistic demonstration that lysosomal positioning controls cell invasion, illustrating the importance of organelle adaptation in carcinogenesis. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.24.546289v1?rss=1 Authors: Wang, Y., Jefferson, M., Mccoll, J., Verkade, P., Mayer, U., Wileman, T. Abstract: Autophagosomes deliver cytosolic material to lysosomes to provide amino acids during starvation and to degrade damaged proteins and organelles to maintain tissue homeostasis. Delivery to lysosomes requires LC3/ATG8 (LC3), the major membrane protein of the autophagosome, that uses adaptor proteins to capture cargo and recruits tethering and SNARE proteins to promote fusion with lysosomes. LC3 is also recruited to endo-lysosome compartments in response to increases in vacuolar pH to facilitate degradation of material entering cells by endocytosis. A series of ubiquitin-like reactions conjugate LC3 to amino groups exposed by phosphatidylethanolamine (PE) or phosphatidylserine (PS) in target membranes. The E1 and E2-ubiquitin-like activities of ATG7 and ATG3 use thioester bonds to transfer LC3 to the ATG5-ATG12 conjugate. At the same time binding of ATG16L1 to ATG5-ATG12 provides the E3 ubiquitin-ligase like activity necessary to conjugate LC3 to PE or PS. The ATG5-ATG12 conjugate can also bind TECPR1 (tectonin beta propeller repeat-containing protein) which shares an ATG5 interaction (AIR) region with ATG16L1 and can binds LC3 directly through a LC3 interaction region (LIR). In this study we have used cells lacking ATG16L1 to determine if TECPR1 can substitute for ATG16L1 during LC3 conjugation. The results show that ATG16L1-/- MEFS can conjugate LC3 to lysosomes damaged by chloroquine or LLOMes and conjugation is dependent on the ubiquitin-like enzymes ATG3, ATG5 and ATG7 upstream of ATG16L1. TECPR1, ATG5 and galectin 3 are recruited to LAMP positive damaged lysosomes in the absence of ATG16L1 suggesting that TECPR-1 recruits ATG5-ATG12 to conjugate LC3 to damaged lysosomes. This was confirmed when truncation of TECPR1 at the central PH domain required for lysosome binding prevented LC3 conjugation, and LC3 conjugation could be restored by full length TECPR1. Recruitment of TECPR1 to damaged lysosomes required the N-terminal LIR motif and was partially dependent on the central PH domain that binds PI4P exposed during lysosome repair. TECPR1 can therefore conjugate LC3 to damaged lysosomes independently of ATG16L1 by providing E3 ligase-like activity to ATG5-ATG12. Direct conjugation of LC3 by TECPR1 may contribute to the autophagosome tethering functions reported for TECPR1 by increasing recruitment of cargo receptors, tethering proteins and SNARE proteins required for fusion with lysosomes and protein degradation. TECPR1-dependent conjugation of LC3 may also facilitate lysosome repair pathways involving autophagic lysosomal reformation and transcriptional activation of autophagy by TFEB. 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/2023.02.21.529466v1?rss=1 Authors: Bondar, V. V., Wang, X., Davis, O. B., Maloney, M. T., Agam, M., Chin, M. Y., Ho, A. C.-N., Joy, D., Lewcock, J. W., Di Paolo, G., Thorne, R. G., Sweeney, Z. K., Henry, A. G. Abstract: Leucine-rich repeat kinase 2 (LRRK2) variants associated with Parkinson's disease (PD) and Crohn's disease lead to increased phosphorylation of its Rab substrates. While it has been recently shown that perturbations in cellular homeostasis including lysosomal damage and stress can increase LRRK2 activity and localization to lysosomes, the molecular mechanisms by which LRRK2 activity is regulated have remained poorly defined. We performed a targeted siRNA screen to identify regulators of LRRK2 activity and identified Rab12 as a novel modulator of LRRK2-dependent phosphorylation of one of its substrates, Rab10. Using a combination of imaging and immunopurification methods to isolate lysosomes, we demonstrated that Rab12 is actively recruited to damaged lysosomes and leads to a local and LRRK2-dependent increase in Rab10 phosphorylation. PD-linked variants, including LRRK2 R1441G and VPS35 D620N, lead to increased recruitment of LRRK2 to the lysosome and a local elevation in lysosomal levels of pT73 Rab10. Together, these data suggest a conserved mechanism by which Rab12, in response to damage or expression of PD-associated variants, promotes the recruitment of LRRK2 and phosphorylation of its Rab substrate(s) at the lysosome. 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/2022.12.22.521712v1?rss=1 Authors: Mahanty, S., Bergam, P., Belapurkar, V., Eluvathingal, L., Gupta, N., Nair, D., Raposo, G., Gangi Setty, S. R. Abstract: Lysosomes, the major degradative compartments of the cell acquire unique properties upon receiving external signals. In the skin, epidermal keratinocytes follow a gradual differentiation process from the basal to the upper skin layers with consequent changes in cellular morphology and intracellular organelles. Previous studies show that keratinocyte differentiation relies on increased lysosome biogenesis. However, the mechanisms of the generation and maintenance of keratinocyte lysosomes remain unknown. Here, we show that dispersed Golgi stacks are distributed to the proximity of lysosomes in differentiated keratinocytes, facilitated by the Golgi tethering protein GRASP65 which associates with the lysosomes. Inhibition of GRASP65 results in the loss of Golgi-lysosome apposition. Further studies exploiting small molecule inhibition and gene modulation reveal a direct role of functional Golgi and its apposition in the generation and, maturation of keratinocyte lysosomes. Selective accumulation of secretory cargo and trans-Golgi enzyme in the lysosome lumen and, reversible dissociation in presence of brefeldin A or Golgicide-A suggests Golgi origin of keratinocyte lysosomes. Taken together, unique Golgi -lysosome apposition and the unconventional properties of keratinocyte lysosomes indicate their possible distinct roles in epidermis homeostasis. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Listen to a blog summary of a trending research paper published by Aging (Aging-US) in Volume 14, Issue 22, entitled, “Denervation induces mitochondrial decline and exacerbates lysosome dysfunction in middle-aged mice.” ________________________________________________________ A hallmark characteristic of aging is the progressive loss of skeletal muscle mass, known as sarcopenia. A process called motor neuron denervation (Den)—when nerve signals to muscles are blocked or reduced—leads to muscle atrophy, fatigue and eventually muscle loss. Determining how and when Den events influence older muscles is crucially important for developing interventions to stop or reverse age-related muscle wasting. “Further, aged muscle exhibits reduced plasticity to both enhanced and suppressed contractile activity. It remains unclear when the onset of this blunted response occurs, and how middle-aged muscle adapts to denervation.” Dysfunctional mitochondria in muscle tissue are known to increase with age. Lysosomes are responsible for the recycling of damaged mitochondria. However, as muscles age, lysosomal function in muscle tissue also declines. In a new study, researchers Matthew Triolo, Debasmita Bhattacharya and David A. Hood from York University in Toronto, Canada, aimed to characterize the time-dependent changes in denervated skeletal muscle from middle-aged mice. The team focussed on how mitochondrial turnover is impacted. On November 4, 2022, their research paper was published in Aging's Volume 14, Issue 22, entitled, “Denervation induces mitochondrial decline and exacerbates lysosome dysfunction in middle-aged mice.” Full blog - https://aging-us.org/2022/12/new-insights-into-the-mechanisms-of-sarcopenia/ DOI - https://doi.org/10.18632/aging.204365 Corresponding author - David A. Hood - dhood@yorku.ca Video - https://www.youtube.com/watch?v=Vcrv4KeFvsY Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204365 Keywords - mitochondrial biogenesis, autophagy, mitophagy, lysosomes, muscle 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/agingus​ 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/2022.11.14.516427v1?rss=1 Authors: Li, T. Y., Wang, Q., Gao, A. W., Li, X., Mottis, A., Shong, M., Auwerx, J. Abstract: Lysosomes are central platforms for not only the degradation of macromolecules but also the integration of multiple signaling pathways. However, whether and how lysosomes mediate the mitochondrial stress response (MSR) remain largely unknown. Here, we demonstrate that lysosomal acidification via the vacuolar H+-ATPase (v-ATPase) is essential for the transcriptional activation of the mitochondrial unfolded protein response (UPRmt). Mitochondrial stress stimulates v-ATPase-mediated lysosomal activation of the mechanistic target of rapamycin complex 1 (mTORC1), which then directly phosphorylates the MSR transcription factor, activating transcription factor 4 (ATF4). Disruption of mTORC1-dependent ATF4 phosphorylation blocks the UPRmt, but not other similar stress responses, such as the UPRER. Finally, ATF4 phosphorylation downstream of the v-ATPase/mTORC1 signaling is indispensable for sustaining mitochondrial redox homeostasis and protecting cells from reactive oxygen species (ROS)-associated cell death upon mitochondrial stress. Thus, v-ATPase/mTORC1-mediated ATF4 phosphorylation via lysosomes links mitochondrial stress to UPRmt activation and mitochondrial function resilience. 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/2022.10.12.511921v1?rss=1 Authors: Burrinha, T., Cunha, C., Guimas Almeida, C. Abstract: Previously, we found that age-dependent beta-amyloid accumulation is not enough to cause synaptic decline. Here, we characterized endolysosomes (late-endosomes and lysosomes) in aged neurons and the aged brain, which might drive synaptic decline since lysosomes are a cellular aging target and relevant for synapses. Neuronal aging induces enlarged endolysosome accumulation in the aged neurons and brain, especially distally, related to the increased anterograde movement. Aged lysosomes abound in neurites but are less degradative due to deacidification despite cathepsin D buildup, leading to late-endosome accumulation. Increasing the acidification of aged lysosomes by ML-SA1 treatment increased degradation and reverted synaptic decline, while lysosome alkalinization by chloroquine treatment mimicked age-dependent lysosome dysfunction and synaptic decline. We identify the deacidification of distal lysosomes as a neuronal mechanism of age-dependent synapse loss. Our findings suggest that future therapeutic strategies to address lysosomal defects might be able to delay age-related synaptic decline. 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/2022.10.14.512269v1?rss=1 Authors: Zhu, X., Prakash, S. S., McAuliffe, G., Pan, P.-Y. Abstract: A major pathological hallmark of Parkinsons Disease (PD) is the manifestation of Lewy bodies comprised of alpha-synuclein (a-syn). The accumulation of a-syn enriched protein aggregates is thought to arise from dysfunction in degradation systems within the brain. Recently, missense mutations of SYNJ1 encoding the SAC1 and 5-phosphatase domains have been found in families with hereditary early-onset Parkinsonism. Previous studies showed that Synj1 haploinsufficiency (Synj1+/-) leads to PD-like behavioral and pathological changes in mice, including the accumulation of the autophagy substrate p62 and pathological a-syn proteins in the midbrain (MB) and striatum. In this study, we aim to investigate the neuronal degradation pathway using the Synj1+/- MB culture as a model. Our data suggests that autophagy flux and cumulative autophagosome formation is unaltered at baseline in Synj1+/- MB neurons. However, lysosome number is reduced with a similar decrease in lysosomal proteins, including LAMP1, LAMP2, and LAMP2A. Lysosomes are hyperacidified with enhanced enzymatic activity in Synj1+/- MB neurons. Using a combination of light and electron microscopy, we show that lysosomal changes are primarily associated with a lack of SAC1 activity. Consistently, expressing the SYNJ1 R258Q mutant in N2a cells reduces the lysosome number. Interestingly, the lysosomal defects in Synj1+/- neurons does not impact the clearance of exogenously expressed wild-type a-syn; however, the clearance of a-syn A53T was impaired in the axons of Synj1+/- MB neurons. Taken together, our results suggest axonal vulnerability to lysosomal defects in Synj1 deficient MB neurons. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Dr. Ana Maria Cuervo, M.D., Ph.D. (https://www.einsteinmed.edu/faculty/8784/ana-maria-cuervo/) is Co-Director of the Einstein Institute for Aging Research, and a member of the Einstein Liver Research Center and Cancer Center. She serves as a Professor in the Department of Developmental & Molecular Biology, and the Department of Medicine (Hepatology), and has the Robert and Renée Belfer Chair for the Study of Neurodegenerative Diseases. Dr. Cuervo studied medicine and pursued a Ph.D. in biochemistry and molecular biology at the University of Valencia, as well as post-doctoral work at Tufts, and in 2001 she started her laboratory at Einstein, where she studies the role of protein-degradation in aging and age-related disorders, with emphasis in neurodegeneration and metabolic disorders. Dr. Cuervo's group is interested in understanding how altered proteins can be eliminated from cells and their components recycled. Her group has linked alterations in lysosomal protein degradation (autophagy) with different neurodegenerative diseases including Parkinson's, Alzheimer's and Huntington's disease. They have also proven that restoration of normal lysosomal function prevents accumulation of damaged proteins with age, demonstrating this way that removal of these toxic products is possible. Her lab has also pioneered studies demonstrating a tight link between autophagy and cellular metabolism. They described how autophagy coordinates glucose and lipid metabolism and how failure of different autophagic pathways with age contribute to important metabolic disorders such as diabetes or obesity. Dr. Cuervo is considered a leader in the field of protein degradation in relation to biology of aging and has been invited to present her work in numerous national and international institutions, including name lectures as the Robert R. Konh Memorial Lecture, the NIH Director's, the Roy Walford, the Feodor Lynen, the Margaret Pittman, the IUBMB Award, the David H. Murdock, the Gerry Aurbach, the SEBBM L'Oreal-UNESCO for Women in Science, the C. Ronald Kahn Distinguished Lecture and the Harvey Society Lecture. She has organized and chaired international conferences on protein degradation and on aging, belongs to the editorial board of scientific journals in this topic, and is currently co-editor-in-chief of Aging Cell. Dr. Cuervo has served in NIH advisory panels, special emphasis panels, and study sections, the NIA Scientific Council and the NIH Council of Councils and has been recently elected member of the NIA Board of Scientific Counselors and member of the of the Advisory Committee to the NIH Deputy Director. She has received numerous awards for the pioneering work of her team such as the 2005 P. Benson Award in Cell Biology, the 2005/8 Keith Porter Fellow in Cell Biology, the 2006 Nathan Shock Memorial Lecture Award, the 2008 Vincent Cristofalo Rising Start in Aging Award, the 2010 Bennett J. Cohen Award in Aging Biology, the 2012 Marshall S. Horwitz, MD Faculty Prize for Research Excellence and the 2015 Saul Korey Prize in Translational Medicine Science. She has also received twice the LaDonne Schulman Teaching Award. In 2015 she was elected International Academic of the Royal Academy of Medicine of the Valencia Community and in 2017, she was elected member of the Real Academia de Ciencias Exactas, Fisicas y Naturales. She was elected member of the American Academy of Arts and Sciences in 2018 and member of the National Academy of Science in 2019.

My AP Biology Thoughts  Unit 2 Cell Structure and FunctionWelcome to My AP Biology Thoughts podcast, my name is Shriya and I am your host for episode #53 called Unit 2 Cell Structure and Function: Lysosomes and Vacuoles. Today we will be discussing the importance of each in regards to the cells and our bodies, and how they fit into the overarching topic of Cell Structure and Function.  Segment 1: Introduction to Lysosomes and VacuolesWe will begin by discussing what exactly lysosomes and vacuoles are and why they are so important for our cells to contain Both of these are essential organelles, and organelles are subcellular structures with specific jobs to perform in the cell, much like an organ does in the body  Lysosomes are membrane-bound sacs of enzymes which digest cellular macromolecules  They are made by proteins from the ER and enclosed in vesicles by the Golgi apparatus and are formed by budding from the Golgi apparatus  They break down excess cell parts, and can be used to destroy invading viruses and bacteria so if the cell is damaged beyond repair, lysosomes can help it self-destruct through a process called apoptosis  Lysosomes also play a role in phagocytosis which is when a cell engulfs a molecule to break it down which is known as “cell eating” White blood cells have more lysosomes than other cells because they destroy bacteria, dead cells, cancerous cells, and foreign matter through disgestion  Vacuoles are fluid-filled enclosed structures separated from the cytoplasm by a single membrane which are found mostly in plant cells and fungi  They have a less prominent role in some protists, animal cells, and bacteria and in animal cells they function to sequester waste products; in plant cells, they help maintain water balance Overall, they function to provide nutrient storage, detoxification, and as waste exportation  Vacuoles are also known as “specialized lysosomes” because both function to get rid of waste products, but when that product is water, the vacuole activates its function to balance water inside and outside a cell Segment 2: More About Structure/Function of Lysosomes and Vacuoles Above is a picture of the structure of lysosomes which are generally known to be very acidic meaning it has to be protected from the rest of the inside of the cell The membrane around it stores the digestive enzymes that require the acidic, low-pH environment, also known as hydrolytic enzymes  Hydrolytic enzymes break down large molecules into smaller ones such as large amino acids into smaller proteins and by doing so they provide necessary nutrients to the rest of the cell  Storing the large molecules is detrimental to your health and can cause disease  Another type of lysosome storage disease is where the small molecules that are produced from those large molecules can't get out of the lysosome They're stored there because the transporters for moving these small molecules out are missing genetically Above, is a picture of the vacuole which is similar to vesicles, another organelle, because both are membrane-bound sacs, but vacuoles are significantly larger than vesicles and are formed when multiple vesicles fuse together Filled tight with water, the vacuole pushes the cytoplasm into a thin strip adjacent to the membrane and pushes outwards like a water filled balloon; it is this turgor pressure that holds the cell firm and provides the characteristic shape of plant structures such as leaves. So when the plant has been without water for a long time, the central vacuoles lose water, the cells lose shape, and the whole leaf wilts Segment 3: Connection to the CourseLysosomes and vacuoles fit into the bigger picture of cell structure and function because they contribute to supporting the origin of eukaryotic cells, one of the big ideas of Unit 2 Eukaryotic cells arose through endosymbiotic events that which rise to the...

Our experts providing you with the best Biology assignment help Australia are capable of assisting with the terms and terminologies such as Ribosomes, RNA, Lysosomes. Chloroplasts, Vacuoles, Endoplasmic Reticulum, and much more. We have more than 400 Biology assignment help experts who are there with us and have more than 12 experience in the corresponding discipline.

Sciencing from Home episode 17 introduces us to Eddie, a member of Dr. Swetha Gowrishankar's lab. In Dr. Gowrishankar's lab he investigates lysosome formation using mice as the model. Lysosome function is associated with Alzheimer's disease and other neurological disorders. Eddie graduated from UIC in Fall 2020 and will begin pharmacy school in Fall 2021. You can subscribe and listen to "Sciencing from Home" at https://anchor.fm/uiclasganas/ https://go.uic.edu/lasganaspodcast-apple https://go.uic.edu/lasganaspodcast-spotify

Give all your Biology assignment help online queries a strategic direction by diverting your problems to My Assignment Services. Our experts providing you with the best Biology assignment help Australia are capable of assisting with the terms and terminologies such as Ribosomes, RNA, Lysosomes. Chloroplasts, Vacuoles, Endoplasmic Reticulum, and much more. We have more than 400 Biology assignment help experts who are there with us and have more than 12 experience in the corresponding discipline. By choosing our assignment help experts, you get a chance to prepare a 100% original and plagiarism free assessment tasks at a minimal price.

Lysosomes, an essential part of the endomembrane system, are reviewed in this episode. The podcast opens by discussing the structure and then transitions into a thorough explanation of the functions of a lysosome. Finally, the episode quickly gives a short review on Tay-Sachs disease. If you have any questions, feel free to send them to https://anchor.fm/christopher-jang/message or https://2255christopher.wixsite.com/biotime/questions

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.27.316133v1?rss=1 Authors: Yellajoshyula, D., Pappas, S. S., Rogers, A., Choudhury, B., Cookson, M., Reed, X., Shakkottai, V., Giger, R., Dauer, W. T. Abstract: Mechanisms controlling myelination during CNS maturation play a pivotal role in the development and refinement of CNS circuits. The transcription factor THAP1 is essential for timing the inception of myelination during CNS maturation through a cell-autonomous role in the oligodendrocyte lineage. Here, we demonstrate that THAP1 modulates ECM composition by regulating glycosaminoglycan (GAG) catabolism within oligodendrocyte progenitor cells (OPCs). Thap1-/- OPCs accumulate and secrete excess GAGs, inhibiting their maturation through an auto-inhibitory mechanism. THAP1 controls GAG metabolism by binding to and regulating the GusB gene encoding {beta}-glucuronidase, a GAG-catabolic lysosomal enzyme. Applying GAG-degrading enzymes or overexpressing {beta}-glucuronidase rescues Thap1-/- OL maturation deficits in vitro and in vivo. Our studies establish lysosomal GAG catabolism within OPCs as a critical mechanism regulating oligodendrocyte development. Copy rights belong to original authors. Visit the link for more info

Dr. Aimee Kao looks at recent news in Alzheimer's Disease therapeutics including drugs in development and the potential of stem cells and genome editing. Series: "Mini Medical School for the Public" [Show ID: 35238]

Dr. Aimee Kao looks at recent news in Alzheimer's Disease therapeutics including drugs in development and the potential of stem cells and genome editing. Series: "Mini Medical School for the Public" [Show ID: 35238]

Dr. Aimee Kao looks at recent news in Alzheimer's Disease therapeutics including drugs in development and the potential of stem cells and genome editing. Series: "Mini Medical School for the Public" [Health and Medicine] [Show ID: 35238]

Dr. Aimee Kao looks at recent news in Alzheimer's Disease therapeutics including drugs in development and the potential of stem cells and genome editing. Series: "Mini Medical School for the Public" [Show ID: 35238]

Dr. Aimee Kao looks at recent news in Alzheimer's Disease therapeutics including drugs in development and the potential of stem cells and genome editing. Series: "Mini Medical School for the Public" [Health and Medicine] [Show ID: 35238]

Dr. Aimee Kao looks at recent news in Alzheimer's Disease therapeutics including drugs in development and the potential of stem cells and genome editing. Series: "Mini Medical School for the Public" [Show ID: 35238]

Dr. Aimee Kao looks at recent news in Alzheimer's Disease therapeutics including drugs in development and the potential of stem cells and genome editing. Series: "Mini Medical School for the Public" [Show ID: 35238]

Dr. Aimee Kao looks at recent news in Alzheimer's Disease therapeutics including drugs in development and the potential of stem cells and genome editing. Series: "Mini Medical School for the Public" [Show ID: 35238]

Dr. Aimee Kao looks at recent news in Alzheimer's Disease therapeutics including drugs in development and the potential of stem cells and genome editing. Series: "Mini Medical School for the Public" [Show ID: 35238]

Dr. Aimee Kao looks at recent news in Alzheimer's Disease therapeutics including drugs in development and the potential of stem cells and genome editing. Series: "Mini Medical School for the Public" [Show ID: 35238]

The arms race against antibiotic resistant bacteria continues. As the world faces down this challenge, we turn to stranger and stranger places for treatment. So how can you turn ancient druidic treatments into modern new antibiotics? How do you make wasp venom actually a useful treatment? Can you trap bacteria inside a cage and just starve them to this? This week we find out about the fight back against bacteria. References: Luciana Terra, Paul J. Dyson, Matthew D. Hitchings, Liam Thomas, Alyaa Abdelhameed, Ibrahim M. Banat, Salvatore A. Gazze, Dušica Vujaklija, Paul D. Facey, Lewis W. Francis, Gerry A. Quinn. A Novel Alkaliphilic Streptomyces Inhibits ESKAPE Pathogens. Frontiers in Microbiology, 2018; 9 DOI: 10.3389/fmicb.2018.02458 Sina Krokowski, Damián Lobato-Márquez, Arnaud Chastanet, Pedro Matos Pereira, Dimitrios Angelis, Dieter Galea, Gerald Larrouy-Maumus, Ricardo Henriques, Elias T. Spiliotis, Rut Carballido-López, Serge Mostowy. Septins Recognize and Entrap Dividing Bacterial Cells for Delivery to Lysosomes. Cell Host & Microbe, 2018; 24 (6): 866 DOI: 10.1016/j.chom.2018.11.005 Massachusetts Institute of Technology. (2018, December 7). Engineers repurpose wasp venom as an antibiotic drug. ScienceDaily. Retrieved December 29, 2018 from www.sciencedaily.com/releases/2018/12/181207112651.htm   Antibiotics from druidic recipes in the Irish countryside.

More than half a million people in the UK suffer from Alzheimer's disease. Symptoms of this disease, including memory loss and communication problems, are due to sticky protein build ups within the brain, called amyloid plaques. These plaques cause damage to nerve cells and are a hallmark feature of the disease. Currently, there is no cure for Alzheimer's disease. However, researchers at Yale University School of Medicine have made a striking discovery about the role of cellular garbage disposal units, called lysosomes, in the formation of these plaques. Lead researcher on the study, Shawn... Like this podcast? Please help us by supporting the Naked Scientists

More than half a million people in the UK suffer from Alzheimer's disease. Symptoms of this disease, including memory loss and communication problems, are due to sticky protein build ups within the brain, called amyloid plaques. These plaques cause damage to nerve cells and are a hallmark feature of the disease. Currently, there is no cure for Alzheimer's disease. However, researchers at Yale University School of Medicine have made a striking discovery about the role of cellular garbage disposal units, called lysosomes, in the formation of these plaques. Lead researcher on the study, Shawn... Like this podcast? Please help us by supporting the Naked Scientists

Synaptic activity shifts dendritic lysosomes Lysosomes are known to exist in both the cell body and axon of neurons, but whether they also localize to dendrites is unclear. Goo et al. reveal that lysosomes do exist in dendrites and dendritic spines, and that their trafficking in this region of neurons is regulated by synaptic activity. This biosights episode presents the paper by Goo et al. from the August 7th, 2017, issue of The Journal of Cell Biology and includes an interview with the paper's senior author, Gentry Patrick (University of California, San Diego). 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

Peter H Backx, PhD is a senior scientist at Toronto General Hospital Research Institute and also at York University. Dr Backx is a recognised expert in cardiac mechanics, heart failure and arrhythmias. His research focuses on the role of ion transport, ion channels and myocardial signalling in the initiation and progression of heart disease with a particular interest in atrial fibrillation. He holds a patent on tissue-specific drug delivery and has published over 190 peer-reviewed articles, many in the top tier journals like Cell, Nature, Nature Medicine, Journal of Clinical Investigation and Circulation Research. His work has been cited over 12,900 times, with over 5600 in the last 5 years. Dr Backx has delivered over 150 distinguished invited lectures at the national and international level. You could listen to this podcast to learn more about the causes of arrhythmias in endurance athletes. Special thanks to Mark Featherman for the introduction to Dr Backx and also some excellent questions. Sign up for our Highlights email and every week we’ll send you a short (but sweet) email containing the following: One piece of simple, actionable advice to improve your health and performance, including the reference(s) to back it up. One item we read or saw in the health and fitness world recently that we would like to give a different perspective on, and why. One remarkable thing that we think you’ll enjoy! Here’s the outline with Peter H Backx, PhD: [00:00:06] Book: The Haywire Heart: How too much exercise can kill you, and what you can do to protect your heart. [00:00:21] PHAT FIBRE MCT oil powder. [00:01:27] Toronto General Hospital Research Institute (TGHRI). [00:01:50] Atrial arrhythmias. [00:03:23] The electrical system of the heart. [00:04:04] SA node. [00:07:30] Main symptoms: fatigue, dizziness. [00:09:02] Peter is trained as a cardiac electrophysiologist. [00:09:18] Sudden cardiac death. [00:09:43] Ventricular tachycardia. [00:10:23] The dangers of afib. [00:11:03] Paroxysmal (acute) afib. [00:12:07] Tommy and Mark Cucuzzella podcast: greatest risk endurance athletes doing more than an hour per day for 20 years. [00:13:01] Biggest risk factor is ageing. [00:13:36] CVD risk factors are also predictive of afib. [00:14:39] Is there a threshold? [00:15:25] Athletes may be at great risk for vfib. [00:17:30] Genetic predisposition. [00:18:33] Exosome (genetic) testing. [00:19:15] Ion channels. [00:20:17] Ablation. [00:22:24] Mark Featherman, you rock! [00:22:55] If you continue doing the same thing, will you develop another arrhythmia? [00:24:44] Finding the sweet spot of exercise. [00:25:36] Exercise intensity. [00:26:20] Polarised training. See Hydren, Jay R., and Bruce S. Cohen. "Current scientific evidence for a polarized cardiovascular endurance training model." The Journal of Strength & Conditioning Research 29.12 (2015): 3523-3530. [00:27:00] Rodent studies. [00:28:18] Only the mice running on weighted wheels developed pathological changes. [00:32:13] Chronic inflammation. [00:32:41] Rheumatoid arthritis. [00:34:05] TNF-a is a mechanosensor. [00:34:58] TNF-a inhibitors. [00:35:51] Etanercept. [00:36:09] XPro®1595. [00:37:02] Blood testing for TNF-a. [00:37:41] Kroetsch, Jeffrey T., et al. "Constitutive smooth muscle tumour necrosis factor regulates microvascular myogenic responsiveness and systemic blood pressure." Nature Communications 8 (2017). [00:39:01] Sebastian Bolz, PhD. See Hui, Sonya, et al. "Sphingosine-1-phosphate signaling regulates myogenic responsiveness in human resistance arteries." PloS one 10.9 (2015): e0138142. [00:41:11] The atria as an endocrine organ, see atrial natriuretic factor. [00:42:36] Stretching the atria. [00:42:46] Alcohol. [00:43:54] Increased parasympathetic activity. [00:45:43] Low-dose alcohol is a stimulant, at higher doses, it's a depressant. [00:47:31] Caffeine. [00:50:12] Acid reflux. [00:50:37] Vagus nerve. [00:51:54] A hiatal hernia. [00:52:37] Proton pump inhibitors and dementia. [00:53:21] The 2016 Nobel Prize in Physiology or Medicine to Yoshinori Ohsumi for his discoveries of mechanisms for autophagy. [00:53:54] Lysosomes. [00:55:03] The vulnerability period increases the chances of a “false start”. [00:58:18] Vagus nerve releases acetylcholine. [01:00:34] Are ablation procedures overperformed? [01:01:14] Stroke. [01:03:16] Increased back pressure “volume overload” models. [01:05:03] Heart & Stroke/Richard Lewar Centre of Excellence. [01:05:39] York University, Canada. [01:05:56] MRI on cyclists. [01:06:39] PubMed author search for Peter H. Backx. [01:07:34] Developing methods for producing atrial cardiomyocytes from stem cells.

Review Disease like Alzheimer's and dementia are grey matter issues - the creation and translation of messages are interrupted or dysfunctional.  White matter is like the power cords that are responsible for sending the signals. White matter diseases Hypomylenation - cells are created with a low amount of myelin; premature, chromosome-linked defects Cell Biology review:  animal cells have a membrane and a nucleus that holds all the DNA, and cytoplasm, and then all the organelles that have different jobs - just like a self-contained factory.  Some systems can be dysfunctional and the cell still live and replicate. Dysmylenation - neurodystrophy (a huge list based on what's broken) Lysosomes - stores enzymes for breakdown Perioxosomes - stores enzymes for energy metabolism Mitochondrial - dysfunction of energy usage Amino acid metabolism dysfunction Demylenation Inflammatory: Multiple Sclerosis = autoimmune disease.  The brain wants the body to do something but the message doesn't make it to the body, so the body doesn't move or has very jerky, irregular movements.  Tests for antibodies can identify MS.  Available treatment is mostly immune suppressants. Huntington's is a genetic disease that presents in the same way.  It has a very sad prognosis and presents in females starting between the ages of 30 and 50.  Thus they have already planned a life and possibly had kids who now may have the same disease.  Genetic testing can identify Huntington's. Viral - PML (Progressive Multifocal Leukoencephalopathy); J-virus a typical virus that may mutate and go dormant in the brain.  If the immune system is lowered drastically - due to suppression or immunodeficiency diseases, this virus will wake up and attack the myelin of the neurons. Acquired metabolism demyleniation (being exposed to chemicals) - “Chasing the Dragon” - refers to a technique used to keep melted pills from burning in a container (usually a spoon) while it's being heated by a flame from underneath and the vapors are inhaled.  Drug of choice: heroin.  **DON'T DO DRUGS** Hypoxic ischemic - loss of oxygen.  Examples:  asphyxiation, drowning, ischemic stroke. Mechanical - compression due to injury or swelling Call Back Migraines are not a white matter issue, they are a brain chemistry issue.  Learn more on the Headache episode Connect with me Support us on Patreon *NEW* Join the Pharmacist Answers Podcast Community on Facebook Subscribe: iTunes, Stitcher, GooglePlay, TuneIn Radio Like the Facebook page Music Credits:  “Radio Martini” Kevin MacLeod (incompetech.com)  Licensed under Creative Commons: By Attribution 3.0  http://creativecommons.org/licenses/by/3.0/

Septins step in to promote macropinosome fusion After they are formed by the closure of membrane ruffles, macropinosomes mature by fusing with each other and with endosomes, before eventually delivering their fluid phase cargo to lysosomes. Dolat and Spiliotis reveal that septin filaments promote macropinosome maturation and lysosomal delivery by facilitating macropinosome/endosome fusion. This biosights episode presents the paper by Dolat and Spiliotis from the August 29th, 2016, issue of The Journal of Cell Biology and includes an interview with the paper's senior author, Elias Spiliotis (Drexel University, Philadelphia, PA). 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

Deploying exosomes in a battle of the sexes The paired accessory glands of male Drosophila secrete multiple signaling factors into the seminal fluid that promote reproductive success by altering the recipient female's physiology and behavior. This biosights episode presents the paper by Corrigan et al. from the September 1, 2014, issue of The Journal of Cell Biology and includes an interview with corresponding author Alexander Bershadsky (Weizmann Institute, Israel, and Mechanobiology Institute, National University of Singapore). 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

Aneuploidy is a change in number or structure of one or more chromosomes that are not a multiple of the whole chromosome set. One of the best known pathological aneuploidies is trisomy 21 (Down syndrome), with chromosome 21 present in three instead of two copies. Patients with Down syndrome display severe mental retardation and growth defects. In fact, most abnormal aneuploid karyotypes lead to spontaneous abortions during embryogenesis, indicating that aneuploidy is not well tolerated in humans. Aneuploidy was also shown to be a common hallmark of cancer tissues; however, the debate is ongoing whether aneuploidy is rather a by-product or a trigger of tumorigenesis. Even though aneuploid karyotypes were already identified more than 100 years ago little is understood about cellular physiology of aneuploidy cells, especially in humans. To uncover the consequences of numerical aneuploidy in human cells, I generated aneuploid cell lines derived from the human cell lines HCT116 and RPE-1 hTERT. First, we showed that aneuploid cells proliferate slower compared to their disomic counterparts. A detailed cell cycle analysis revealed that this delay was due to a prolonged G1 and S phase, whereas G2 and M phase remained unperturbed. Furthermore, we conducted an in depth genome wide comparison of DNA, mRNA and protein levels in aneuploid cells. Using CGH, mRNA array and SILAC technology, we quantified the changes in DNA, mRNA and protein abundance. We revealed that extra chromosomes are actively transcribed and translated. However, the abundance of some proteins, particularly subunits of protein complexes and protein kinases, are adjusted towards disomic levels. Additionally, we asked how the cellular physiology is affected by the addition of a specific chromosome. Two scenarios are possible: either the cellular response depends on the additional chromosomes or all aneuploid cells show the same changes of cellular physiology. Indeed, we found that all aneuploid cell lines show similar physiological responses, irrespective of the type of additional chromosome. All aneuploid cell lines down-regulate DNA and RNA metabolism and up-regulate among others energy metabolism, lysosome function and membrane biosynthesis pathways. Lysosomes which are involved in autophagy are besides the ubiquitin-proteasome system important for cellular protein turn over. We found p62-dependent selective autophagy increased in all analyzed cell lines with extra chromosomes suggesting a role of p62-dependent selective autophagy in maintenance of protein homeostasis upon expression of extra protein in these cell lines.

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