Podcasts about homeostatic

In this episode of the Born to Thrive podcast, Alex and Luke Hanna explore the concept of "food noise," the persistent thoughts about food that can disrupt healthy eating habits. They discuss how dysregulation in the homeostatic and hedonic systems of appetite control contributes to this issue, with the homeostatic system driving hunger to maintain body weight and the hedonic system triggering eating for pleasure. The conversation covers practical strategies for managing food noise, including environmental adjustments, better sleep and stress management, and fostering a healthier relationship with food. Luke emphasizes the importance of self-compassion, realistic goal-setting, and understanding that everyone's journey with food and fitness is unique. Chapters 00:00 Introduction and Background 01:22 Defining Food Noise 04:04 Homeostatic and Hedonic Systems 05:21 Triggers and Cues 09:04 Role of New Weight Loss Drugs 13:18 Managing the Environment 19:41 Sleep and Stress Management 23:59 Building a Healthier Relationship with Food 24:29 Positive Mindset and Habits 25:19 Conclusion 29:46 Setting Realistic Goals and Removing Barriers 32:29 Practicing Self-Compassion 38:29 Navigating Social Settings and Food Noise 45:59 The Role of Education 46:24 Recognizing the Unique Journey and Being Kind to Yourself Find Luke here ------ Click Here to Purchase the Unposed Unbothered Journal! Click Here to Download LWA's Free Transformation Blueprint Save 10% with "alex" from Buffbunny: https://www.buffbunny.com/?rfsn=6261901.6ab300 Save 20% with alex from Legion: https://legionathletics.com/products/workout-supplements/?r=zrxnw&utm_source=bc_alex-allen_zrxnw&utm_campaign=bc Click Here to Apply for 1:1 Coaching with LWA Coaching

Take a ride through the neural pathways of hunger where we decode the complex signals your brain uses to determine when it's time to eat. This episode will not only explore the hormonal traffic lights of ghrelin and leptin that regulate our hunger signals but also illuminate the power of mindful eating as a practice to ensure that every meal fuels both body and mind optimally. Key Takeaways: ✅ Hedonic hunger drives us towards pleasurable, often less healthy foods. ✅ Homeostatic hunger signals the body's actual energy needs. ✅ Ghrelin is the 'start eating' hormone, while leptin is the 'stop eating' signal. ✅ Mindful eating helps distinguish between true hunger and emotional eating. ✅ Practicing mindful eating can improve mental clarity and foster a healthier relationship with food.

In this episode, Sam breaks down the different ways your body burns calories and why having a step goal can be so beneficial to weight loss.  She goes over several studies discussing the connection between daily movement and hunger management, fat loss, as well as weight loss maintenance.  You can find all the references below:•PMID: 29289613 Homeostatic and non-homeostatic appetite control along the spectrum of physical activity levels: An updated perspective•Burton, H.M. and E.F. Coyle, Daily Step Count and Postprandial Fat Metabolism. Med Sci Sports Exerc, 2021. 53(2): p. 333-340.•Sullivan Bisson, A.N., S.A. Robinson, and M.E. Lachman, Walk to a better night of sleep: testing the relationship between physical activity and sleep. Sleep Health, 2019. 5(5):•Foright, R., et al., Effects of Exercise during Weight Loss Maintenance on Appetite Regulation in Women. Transl J Am Coll Sports Med, 2020.•Foright, R.M., et al., Is regular exercise an effective strategy for weight loss maintenance?  Physiol Behav, 2018.•Mayer, J., P. Roy, and K.P. Mitra, Relation between caloric intake, body weight, and physical work: studies in an industrial male population in West Bengal.  Am J Clin Nutr, 1956.Follow Sam on IG at @fitfam_bysamLearn more about the Fitfam at www.fitfambysam.com

Dr Sarah Gilchrist from Gilchrist Performance, has a doctorate in sleep and athletic performance and an extensive background in the UK high performance sport industry. Sarah explains how exercise can impact sleep and support a better night's sleep for those with ADHD. The conversation with Sarah is followed by a beautiful, immersive musical soundscape, composed to help calm your mind. You will be immersed in frequencies proven to bring peace to busy brains. These soundscapes are most effective when listened to on headphones.

Today we welcome Dr. Antonio Damasio. He is an internationally recognized neuroscientist whose extensive research has shaped the understanding of neural systems and consciousness. With over a hundred journal articles and book chapters, he has earned many prestigious awards throughout his career. Currently, he serves as University Professor, the David Dornsife Professor of Neuroscience, Psychology, and Philosophy, and director of the Brain and Creativity Institute at the University of Southern California. His books Descartes' Error, Looking for Spinoza, Self Comes to Mind, The Strange Order of Things, and Feeling & Knowing, have been published in translation and are taught in universities throughout the world. In this episode, I talk to Antonio Damasio about consciousness. People often think that the mind and consciousness are the same thing, but Dr. Damasio disputes this notion. He argues that it's the complex relationship of both our brains and bodies that makes sentient thought possible. Homeostatic feelings like hunger and pain developed before emotions; and along with it came consciousness. We also touch on the topics of perception, mental illness, evolution, panpsychism, AI and machine learning. Website: dornsife.usc.edu/bc Twitter: @damasiouscSee omnystudio.com/listener for privacy information.

TWiV explains how immune profiling was used to identify distinguishing features of Long COVID, and how a co-opted feline endogenous retroviral envelope promotes cell survival by controlling copper transport and homeostasis in cats. Hosts: Vincent Racaniello, Alan Dove, Rich Condit, and Brianne Barker Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Become a patron of TWiV! Links for this episode MicrobeTV Discord Server MicrobeTV store at Cafepress Spike shirts at vaccinated.us (promo code Microbetv) Research assistant position in Rosenfeld Lab CBER/FDA (pdf) Features of Long COVID (Nature) ERV envelope mediates feline copper homeostasis (Cell Rep) Letters read on TWiV 1049 Timestamps by Jolene. Thanks! Weekly Picks Brianne – Webb spots a building block of life on Jupiter's moon Europa Rich – Are we really made of ‘star stuff?' Learn about your body's elements Alan – Avian flu has reached the Galàpagos Vincent – Why the US can't have nice things Listener Pick Az – Free solo Intro music is by Ronald Jenkees Send your virology questions and comments to twiv@microbe.tv

Discover the secret to youthful, radiant skin as we unpack our newest revolutionary product, Amplifying Essence, with Young Goose co-founder Anastasia. We reveal the synergy between internal cellular health and topical skincare, and how this harmony is embodied in Amplifying Essence.Welcome to another episode of the Biohacking Beauty podcast brought to you by Young Goose Skincare! In this episode, host Amitay Eshel, the CEO of Young Goose, is joined by Anastasia, Young Goose co-founder and the mastermind behind Young Goose's revolutionary newest product, Amplifying Essence. As we all strive for radiant, healthy skin, it's vital to understand the science behind the skincare products we use. In this episode, we discuss the key ingredients and benefits of the Amplifying Essence. These include Aerobic Complex, NAD+ Precursor Nicotinamide, Extremolyte Ection, and Jojoba Milk. The aerobic complex stimulates oxygen uptake in the skin, restoring its youthful processes and rebuilding its function. The NAD boosting properties of Nicotinamide improve the skin's cellular health, offering visible results. Extremolyte Ectoine offers protection against blue light emissions, toxins, and pollution while providing unparalleled hydration benefits.Visit www.younggoose.com and get 20% off your first purchase by using code PODCAST20. If you're a returning customer get 10% off your next purchase by using code PODCAST10. What we discuss:(0:04:07) - Exploring Young Goose's New Amplifying Essence(0:07:12) - What is an Essence(0:15:37) - The Importance of Oxygen in Skincare(0:21:00) - Aerobic Complex in Ampligying Essence(0:23:00) - Nicotinamide as a Precursor to NAD+(0:30:19) - Understanding NAD and Ectoine in Skincare(0:35:46) - Protecting your Skin from Blue Light(0:42:00) - What is Jojoba Milk(0:45:18) - Homeostatic versus Clean SkincareTo learn more about Young Goose:Website: https://www.younggoose.com/Instagram: @young_goose_skincareGet 20% off your first purchase by using code PODCAST20 at www.younggoose.com

Why do people settle into a homeostatic imbalance, leading to chronic illness? Why do people develop certain cancers while others don't? What are the contributing factors? Where does the line between the physical and emotional body ride? Answering these questions take a holistic approach to medicine, knowledge not just about the body but also the multiple factors that can affect it both inside and outside us. With over 45 years of experience in medicine and a focus on naturopathy and biological dentistry, Dr. Thom Dickson is joining us today to answer these questions and give us a more profound clarity into the inner workings of our bodies.HIGHLIGHTS [0:00:00] Introducing Dr. Thom Dixon and Biological Medicine[0:08:03] How Dr. Thom Would Treat Strep Throat[0:14:09] Dr. Thom's Start in Naturopathy and Biological Medicine and the Development in Dentistry[0:18:52] Genetics and How It's Affected By External Factors[0:28:20] Early Education on Holism[0:33:25] Dietary Temperament[0:38:13] How to Reprogram Your Body[0:48:36] How to Start Someone on Biological Medicine[1:00:25] Having Someone to Guide You to Better Your Health[1:07:30] Planning to Get a Whole Picture of Your Health at the Arizona BioMed Center[1:19:39] Getting Sick is a Process, Which Means Healing Should Be a Lifelong Journey[1:23:41] Being in the Mindset of Healing[1:26:36] Dr. Thom's Message to Everyone[1:30:00] Outro UPGRADE YOUR WELLNESSMarion Institute BioMed Courses:: https://www.marioninstitute.org/programs/biomed-network/biomed-courses/Code: beautifullybrokenGOT MOLD?:  https://www.gotmold.com/beautifullybroken/Code: beautifullybroken10CANCER/EVOLUTION World Premier Summit: https://cancerevolution.events/Code: freddie20Probiotics and Gut-Lining Restoration Kit: https://microbiomelabs.comCode: beautifullybrokenEnroll at Biological Medicine: biologicalmedicine.orgCode: beautifullybrokenLourdes Hydrofix Premium Edition https://holyhydrogen.com/?sca_ref=3008232.jSqidhzJ01Code: beautifullybrokenLightPathLED   https://lightpathled.com/?afmc=BEAUTIFULLYBROKENCode: beautifullybrokenFlowpresso 3-in-1 technology: https://www.beautifullybroken.world/flowpressoMedical grade Ozone Therapy: https://lddy.no/1djnhCode: BEAUTIFULLYBROKENAquaCure Machine + Molecular HydrogenWebsite:https://eagle-research.com?ref=24931Code: beautifullybrokenAMD Ionic Footbath: https://calendly.com/ioncleanse/detoxSilver Biotics Immune Support and toothpaste: https://bit.ly/3JnxyDDCode: BEAUTIFULLYBROKENDIY Home Cold Exposure: https://www.penguinchillers.com/product/beautifullybroken/Cellcore – https://www.beautifullybroken.world/affiliate-products My favorite BindersMy Favorite Sauna: Therasage https://bit.ly/39mTxwYCode: BEAUTIFULLYBROKENCONNECT WITH FREDDIE Check out my website and store:www.beautifullybroken.worldJoin my membership program –https://www.buymeacoffee.com/freddiesetgoInstagram – https://www.instagram.com/beautifullybroken.world/YouTube: https://www.youtube.com/@BeautifullyBrokenWorld

"No structure, even an artificial one, enjoys the process of entropy. It is the ultimate fate of everything, and everything resists it.' - Philip K. Dick Homeostasis refers to the maintenance of relatively constant internal conditions in an organism. For example, we maintain a body temperature of around 98.6°F (37°C). In a cold environment, we shiver to return to this temperature. In a warm climate, we cool ourselves down to restore balance. In our 9-part series on The Innovation Show, Mark Solms explains the relationship between homeostasis and entropy. Entropy is the natural tendency of things to lose order and fall into chaos. It's why ice melts; batteries lose charge, billiard balls stop, and hot water merges with cold. Homeostasis resists entropy. It keeps us in a limited range of ideal states, like a perfect body temperature. Our bodies need a constant energy supply to maintain homeostasis and resist entropy. Energy can be useful or useless, depending on its ability to work. As useful energy depletes, system entropy increases. This explains why our bodies eventually decline. We need to generate effort to counter entropy, like a balance. This includes exercising to prevent muscle loss, learning new skills for job relevance, and innovating to stay competitive. Like organisms, organisations are living entities that constantly need to reinvent and regenerate energy to maintain balance. Organisations can become stagnant, with experienced managers sometimes lacking the initiative to innovate or drive change. This can lead to inefficiencies and bureaucracy, causing the organisation to become less effective over time. If you think of people as molecules of energy, they dissipate and find areas of the business where they can do the least amount possible. Bureaucracy grows like a bacterial plaque throughout the organisation. The lifeblood of the organisation clogs up and becomes less effective. Information flows become inefficient, like varicose veins. In effect, the organisation atrophies. Injecting new energy into an organisation can revitalise it, realign its workforce, and increase efficiency. As discussed in my book "Undisruptable", this continuous revitalisation is essential for an organisation's health, especially during rapid technological change. Resisting entropy is a fundamental function of living things. Similarly, organisations that resist change become victims of entropy, disrupting the balance of their systems and tipping the scales towards entropy. Maintaining homeostasis is not an event. It is a continual process. Maintaining success requires effort, constant renewal and permanent reinvention.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.550767v1?rss=1 Authors: Martins-Ferreira, R., Calafell-Segura, J., Leal, B., Rodriguez-Ubreva, J., Mereu, E., Pinho e Costa, P., Ballestar, E. Abstract: Dysregulated microglia activation, leading to neuroinflammation, is currently considered to be of major relevance in the development and progression of neurodegenerative diseases. The initial M1/M2 dual activation classification for microglia is now considered outdated. Even the "disease-associated microglia" (DAM) phenotype, firstly described in mice, has proven insufficient to precisely represent the multitude of microglia phenotypes in pathology. In this study, we have constructed a transcriptomic atlas of human brain immune cells by integrating single-nucleus (sn)RNA-seq datasets from multiple neurodegenerative conditions. Sixteen datasets were included, comprising 295 samples from patients with Alzheimer's disease, autism spectrum disorder, epilepsy, multiple sclerosis, Lewy body diseases, COVID-19, and healthy controls. The integrated Human Microglia Atlas (HuMicA) dataset included 60,557 nuclei and revealed 11 microglial subpopulations distributed across all pathological and healthy conditions. Among these, we identified four different homeostatic clusters as well as pathological phenotypes. These included two stages of early and late activation of the DAM phenotype and the disease-inflammatory macrophage (DIM) phenotype, which was recently described in mice, and is also present in human microglia, as indicated by our analysis. The high versatility of microglia is evident through changes in subset distribution across various pathologies, suggesting their contribution to the establishment of pathological phenotypes. Our analysis showed overall depletion of four substates of homeostatic microglia, and expansion of niche subpopulations within the DAM and DIM spectrum across distinct neurodegenerative pathologies. The HuMicA is an invaluable resource tool used to support further advances in the study of microglia biology through healthy and disease settings. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.21.549845v1?rss=1 Authors: Jaulim, A., Cassidy, L. D., Young, A. R. J., Chan, A. S. L., Warren, A. Y., Taylor, A. E., Arlt, W., Lan, G., Blayney, M. L., Davidson, O., Barratt, C. L. R., Pacey, S., Narita, M. Abstract: Autophagy has been implicated in male fertility but its specific role in the post-testicular organs remains unclear. Here, we investigate this in mice expressing a doxycycline-inducible RNAi against Atg5 (Atg5i). Systemic autophagy inhibition in Atg5i mice resulted in the morphological and functional abrogation of the male accessory sex organs, leading to male subfertility. However, the testis was largely protected, likely due to the limited permeability of doxycycline through the blood-testis barrier. Interestingly, restoration of autophagy by doxycycline withdrawal in Atg5i mice led to substantial recovery of the phenotype in the accessory organs. This model offers a unique opportunity to dissect the pre- and post-testicular roles of autophagy, highlighting the non-autonomous impact of autophagy on male fertility. 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/2023.06.30.547251v1?rss=1 Authors: Strohman, A., Payne, B., In, A., Stebbins, K., Legon, W. Abstract: Homeostasis is the process of maintaining physiologic balance in the body that is critical for maintaining health and is dysfunctional in several disorders like chronic pain. The dorsal anterior cingulate cortex (dACC) is a critical brain area for homeostatic cardiovascular responses and pain processing, making it a promising non-invasive therapeutic target. We leverage the high spatial resolution and deep focal lengths of low-intensity focused ultrasound (LIFU) to non-invasively modulate the dACC for an effect on behavioral and cardiac autonomic responses using a transient heat pain stimulus. N = 16 healthy human volunteers (6M/10F) received transient contact heat pain during either LIFU to the dACC or Sham stimulation. Continuous electroencephalogram (EEG), electrocardiogram (ECG), and electrodermal response (EDR) were recorded. Outcome measures included perceived pain ratings, homeostatic measures including heart-rate variability, blood pressure, EDR response as well as the amplitude of the contact heat-evoked potential (CHEP). LIFU reduced pain ratings by 1.08 {+/-} 0.21 points relative to Sham. LIFU increased heart rate variability indexed by the standard deviation of normal sinus beats (SDNN), low frequency (LF) power, and the low-frequency/high-frequency (LF/HF) ratio. There were no effects on blood pressure or EDR. LIFU resulted in a 25.1% reduction in the N1-P1 CHEP amplitude driven primarily by effects on the P1 amplitude. Our results demonstrate LIFU to the dACC reduces perceived pain and alters homeostatic cardiovascular responses to a transient heat pain stimulus. These results have implications for the causal understanding of human pain and autonomic processing in the dACC and the potential for future therapeutics for pain relief and homeostatic modulation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

ReferencesWe considered the complexity of the machinery to excrete ammonium in the context of research on dietary protein and how high protein intake may increase glomerular pressure and contribute to progressive renal disease (many refer to this as the “Brenner hypothesis”). Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal diseaseA trial that studied low protein and progression of CKD The Effects of Dietary Protein Restriction and Blood-Pressure Control on the Progression of Chronic Renal Disease(and famously provided data for the MDRD eGFR equation A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study GroupWe wondered about dietary recommendations in CKD. of note, this is best done in the DKD guidelines from KDIGO Executive summary of the 2020 KDIGO Diabetes Management in CKD Guideline: evidence-based advances in monitoring and treatment.Joel mentioned this study on red meat and risk of ESKD. Red Meat Intake and Risk of ESRDWe referenced the notion of a plant-based diet. This is an excellent review by Deborah Clegg and Kathleen Hill Gallant. Plant-Based Diets in CKD : Clinical Journal of the American Society of NephrologyHere's the review that Josh mentioned on how the kidney appears to sense pH Molecular mechanisms of acid-base sensing by the kidneyRemarkably, Dr. Dale Dubin put a prize in his ECG book Free Car Prize Hidden in Textbook Read the fine print: Student wins T-birdA review of the role of the kidney in DKA: Diabetic ketoacidosis: Role of the kidney in the acid-base homeostasis re-evaluatedJosh mentioned the effects of infusing large amounts of bicarbonate The effect of prolonged administration of large doses of sodium bicarbonate in man and this study on the respiratory response to a bicarbonate infusion: The Acute Effects In Man Of A Rapid Intravenous Infusion Of Hypertonic Sodium Bicarbonate Solution. Ii. Changes In Respiration And Output Of Carbon DioxideThis is the study of acute respiratory alkalosis in dogs: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC293311/?page=1And this is the study of medical students who went to the High Alpine Research Station on the Jungfraujoch in the Swiss Alps https://www.nejm.org/doi/full/10.1056/nejm199105163242003Self explanatory! A group favorite! It Is Chloride Depletion Alkalosis, Not Contraction AlkalosisEffects of chloride and extracellular fluid volume on bicarbonate reabsorption along the nephron in metabolic alkalosis in the rat. Reassessment of the classical hypothesis of the pathogenesis of metabolic alkalosisA review of pendrin's role in volume homeostasis: The role of pendrin in blood pressure regulation | American Journal of Physiology-Renal PhysiologyInfusion of bicarbonate may lead to a decrease in respiratory stimulation but the shift of bicarbonate to the CSF may lag. Check out this review Neural Control of Breathing and CO2 Homeostasis and this classic paper Spinal-Fluid pH and Neurologic Symptoms in Systemic Acidosis.OutlineOutline: Chapter 11- Regulation of Acid-Base Balance- Introduction - Bicarb plus a proton in equilibrium with CO2 and water - Can be rearranged to HH - Importance of regulating pCO2 and HCO3 outside of this equation - Metabolism of carbs and fats results in the production of 15,000 mmol of CO2 per day - Metabolism of protein and other “substances” generates non-carbonic acids and bases - Mostly from sulfur containing methionine and cysteine - And cationic arginine and lysine - Hydrolysis of dietary phosphate that exists and H2PO4– - Source of base/alkali - Metabolism of an ionic amino acids - Glutamate and asparatate - Organic anions going through gluconeogenesis - Glutamate, Citrate and lactate - Net effect on a normal western diet 50-100 mEq of H+ per day - Homeostatic response to these acid-base loads has three stages: - Chemical buffering - Changes in ventilation - Changes in H+ excretion - Example of H2SO4 from oxidation of sulfur containing AA - Drop in bicarb will stimulate renal acid secretion - Nice table of normal cid-base values, arterial and venous- Great 6 bullet points of acid-base on page 328 - Kidneys must excrete 50-100 of non-carbonic acid daily - This occurs by H secretion, but mechanisms change by area of nephron - Not excreted as free H+ due to minimal urine pH being equivalent to 0.05 mmol/L - No H+ can be excreted until virtually all of th filtered bicarb is reabsorbed - Secreted H+ must bind buffers (phosphate, NH3, cr) - PH is main stimulus for H secretion, though K, aldo and volume can affect this.- Renal Hydrogen excretion - Critical to understand that loss of bicarb is like addition of hydrogen to the body - So all bicarb must be reabsorbed before dietary H load can be secreted - GFR of 125 and bicarb of 24 results in 4300 mEq of bicarb to be reabsorbed daily - Reabsorption of bicarb and secretion of H involve H secretion from tubular cells into the lumen. - Thee initial points need to be emphasized - Secreted H+ ion are generated from dissociation of H2O - Also creates OH ion - Which combine with CO2 to form HCO3 with the help of zinc containing intracellular carbonic anhydrase. - This is how the secretion of H+ which creates an OH ultimately produces HCO3 - Different mechanisms for proximal and distal acidification - NET ACID EXCRETION - Free H+ is negligible - So net H+ is TA + NH4 – HCO3 loss - Unusually equal to net H+ load, 50-100 mEq/day - Can bump up to 300 mEq/day if acid production is increased - Net acid excretion can go negative following a bicarb or citrate load - Proximal Acidification - Na-H antiporter (or exchanger) in luminal membrane - Basolateral membrane has a 3 HCO3 Na cotransporter - This is electrogenic with 3 anions going out and only one cation - The Na-H antiporter also works in the thick ascending limb of LOH - How about this, there is also a H-ATPase just like found in the intercalated cells in the proximal tubule and is responsible for about a third of H secretion - And similarly there is also. HCO3 Cl exchanger (pendrin-like) in the proximal tubule - Footnote says the Na- 3HCO3 cotransporter (which moves sodium against chemical gradient NS uses negative charge inside cell to power it) is important for sensing acid-base changes in the cell. - Distal acidification - Occurs in intercalated cells of of cortical and medullary collecting tubule - Three main characteristics - H secretion via active secretory pumps in the luminal membrane - Both H-ATPase and H-K ATPase - H- K ATPase is an exchange pump, k reabsorption - H-K exchange may be more important in hypokalemia rather than in acid-base balance - Whole paragraph on how a Na-H exchanger couldn't work because the gradient that H has to be pumped up is too big. - H-ATPase work like vasopressin with premise H-ATPase sitting on endocarditis vesicles a=which are then inserted into the membrane. Alkalosis causes them to be recycled out of the membrane. - H secretory cells do not transport Na since they have few luminal Na channels, but are assisted by the lumen negative tubule from eNaC. - Minimizes back diffusion of H+ and promotes bicarb resorption - Bicarbonate leaves the cell through HCO3-Cl exchanger which uses the low intracellular Cl concentration to power this process. - Same molecule is found on RBC where it is called band 3 protein - Figure 11-5 is interesting - Bicarbonate resorption - 90% in the first 1-22 mm of the proximal tubule (how long is the proximal tubule?) - Lots of Na-H exchangers and I handed permeability to HCO3 (permeability where?) - Last 10% happens distally mostly TAL LOH via Na-H exchange - And the last little bit int he outer medullary collecting duct. - Carbonic anhydrase and disequilibrium pH - CA plays central role in HCO3 reabsorption - After H is secreted in the proximal tubule it combines with HCO# to form carbonic acid. CA then dehydrates it to CO2 and H2O. (Step 2) - Constantly moving carbonic acid to CO2 and H2O keeps hydrogen combining with HCO3 since the product is rapidly consumed. - This can be demonstrated by the minimal fall in luminal pH - That is important so there is not a luminal gradient for H to overcome in the Na-H exchanger (this is why we need a H-ATPase later) - CA inhibitors that are limited tot he extracellular compartment can impair HCO3 reabsorption by 80%. - CA is found in S1, S2 but not S3 segment. See consequence in figure 11-6. - The disequilibrium comes from areas where there is no CA, the HH formula falls down because one of the assumptions of that formula is that H2CO3 (carbonic acid) is a transient actor, but without CA it is not and can accumulate, so the pKa is not 6.1. - Bicarbonate secretion - Type B intercalated cells - H-ATPase polarity reversed - HCO3 Cl exchanger faces the apical rather than basolateral membrane- Titratable acidity - Weak acids are filtered at the glom and act as buffers in the urine. - HPO4 has PKA of 6.8 making it ideal - Creatinine (pKa 4.97) and uric acid (pKa 5.75) also contribute - Under normal cinditions TA buffers 10-40 mEa of H per day - Does an example of HPO4(2-):H2PO4 (1-) which exists 4:1 at pH of 7.4 (glomerular filtrate) - So for 50 mEq of Phos 40 is HPO4 and 10 is H2PO4 - When pH drops to 6.8 then the ratio is 1:1 so for 50 - So the 50 mEq is 25 and 25, so this buffered an additional 15 mEq of H while the free H+ concentration increased from 40 to 160 nanomol/L so over 99.99% of secreted H was buffered - When pH drops to 4.8 ratio is 1:100 so almost all 50 mEq of phos is H2PO4 and 39.5 mEq of H are buffered. - Acid loading decreases phosphate reabsorption so more is there to act as TA. - Decreases activity of Na-phosphate cotransporter - DKA provides a novel weak acid/buffer beta-hydroxybutyrate (pKa 4.8) which buffers significant amount of acid (50 mEq/d).- Ammonium Excretion - Ability to excrete H+ as ammonium ions adds an important amount of flexibility to renal acid-base regulation - NH3 and NH4 production and excretion can be varied according to physiologic need. - Starts with NH3 production in tubular cells - NH3, since it is neutral then diffuses into the tubule where it is acidified by the low pH to NH4+ - NH4+ is ionized and cannot cross back into the tubule cells(it is trapped in the tubular fluid) - This is important for it acting as an important buffer eve though the pKa is 9.0 - At pH of 6.0 the ratio of NH3 to NH4 is 1:1000 - As the neutral NH3 is converted to NH4 more NH3 from theintracellular compartment flows into the tubular fluid replacing the lost NH3. Rinse wash repeat. - This is an over simplification and that there are threemajor steps - NH4 is produced in early proximal tubular cells - Luminal NH4 is partially reabsorbed in the TAL and theNH3 is then recycled within the renal medulla - The medullary interstitial NH3 reaches highconcentrations that allow NH3 to diffuse into the tubular lumen in the medullary collecting tubule where it is trapped as NH4 by secreted H+ - NH4 production from Glutamine which converts to NH4 and glutamate - Glutamate is converted to alpha-ketoglutarate - Alpha ketoglutarate is converted to 2 HCO3 ions - HCO3 sent to systemic circulation by Na-3 HCO3 transporter - NH4 then secreted via Na-H exchanger into the lumen - NH4 is then reabsorbed by NaK2Cl transporter in TAL - NH4 substitutes for K - Once reabsorbed the higher intracellular pH causes NH4 to convert to NH3 and the H that is removed is secreted through Na-H exchanger to scavenge the last of the filtered bicarb. - NH3 diffuses out of the tubular cells into the interstitium - NH4 reabsorption in the TAL is suppressed by hyperkalemia and stimulated by chronic metabolic acidosis - NH4 recycling promotes acid clearance - The collecting tubule has a very low NH3 concentration - This promotes diffusion of NH3 into the collecting duct - NH3 that goes there is rapidly converted to NH4 allowing more NH3 to diffuse in. - Response to changes in pH - Increased ammonium excretion with two processes - Increased proximal NH4 production - This is delayed 24 hours to 2-3 days depending on which enzyme you look at - Decreased urine pH increases diffusion of ammonia into the MCD - Occurs with in hours of an acid load - Peak ammonium excretion takes 5-6 days! (Fig 11-10) - Glutamine is picked up from tubular fluid but with acidosis get Na dependent peritublar capillary glutamine scavenging too - Glutamine metabolism is pH dependent with increase with academia and decrease with alkalemia - NH4 excretion can go from 30-40 mEq/day to > 300 with severe metabolic acidosis (38 NaBicarb tabs) - Says each NH4 produces equimolar generation of HCO3 but I thought it was two bicarb for every alpha ketoglutarate?- The importance of urine pH - Though the total amount of hydrogren cleared by urine pH is insignificant, an acidic urine pH is essential for driving the reactions of TA and NH4 forward.- Regulation of renal hydrogen excretion - Net acid excretion vary inverse with extracellular pH - Academia triggers proximal and distal acidification - Proximally this: - Increased Na-H exchange - Increased luminal H-ATPase activity - Increased Na:3HCO3 cotransporter on the basolateral membrane - Increased NH4 production from glutamine - In the collecting tubules - Increased H-ATPase - Reduction of tubular pH promotes diffusion of NH3 which gets converted to NH4…ION TRAPPING - Extracellular pH affects net acid excretion through its affect on intracellular pH - This happens directly with respiratory disorders due to movement of CO2 through the lipid bilayer - In metabolic disorders a low extracellular bicarb with cause bicarb to diffuse out of the cell passively, this lowers intracellular pH - If you manipulate both low pCO2 and low Bicarb to keep pH stable there will be no change in the intracellular pH and there is no change in renal handling of acid. It is intracellular pH dependent - Metabolic acidosis - Ramps up net acid secretion - Starts within 24 hours and peaks after 5-6 days - Increase net secretion comes from NH4 - Phosphate is generally limited by diet - in DKA titratable acid can be ramped up - Metabolic alkalosis - Alkaline extracellular pH - Increased bicarb excretion - Decrease reabsorption - HCO3 secretion (pendrin) in cortical collecting tubule - Occurs in cortical intercalated cells able to insert H-ATPase in basolateral cells (rather than luminal membrane) - Normal subjects are able to secrete 1000 mmol/day of bicarb - Maintenance of metabolic alkalosis requires a defect which forces the renal resorption of bicarb - This can be chloride/volume deficiency - Hypokalemia - Hyperaldosteronism - Respiratory acidosis and alkalosis - PCO2 via its effect on intracellular pH is an important determinant of renal acid handling - Ratios he uses: - 3.5 per 10 for respiratory acidosis - 5 per 10 for respiratory alkalosis - Interesting paragraph contrasting the response to chronic metabolic acidosis vs chronic respiratory acidosis - Less urinary ammonium in respiratory acidosis - Major differences in proximal tubule cell pH - In metabolic acidosis there is decreased bicarb load so less to be reabsorbed proximally - In respiratory acidosis the increased serum bicarb increases the amount of bicarb that must be reabsorbed proximally - The increased activity of Na-H antiporter returns tubular cell pH to normal and prevents it from creating increased urinary ammonium - Mentions that weirdly more mRNA for H-Na antiporter in metabolic acidosis than in respiratory acidosis - Net hydrogen excretion varies with effective circulating volume - Starts with bicarb infusions - Normally Tm at 26 - But if you volume deplete the patient with diuretics first this increases to 35+ - Four factors explain this increased Tm for bicarb with volume deficiency - Reduced GFR - Activation of RAAS - Ang2 stim H-Na antiporter proximally - Ang2 also stimulates Na-3HCO3 cotransporter on basolateral membrane - Aldosterone stimulates H-ATPase in distal nephron - ALdo stimulates Cl HCO3 exchanger on basolateral membrane - Aldo stimulates eNaC producing tubular lumen negative charge to allow H secretion to occur and prevents back diffusion - Hypochloremia - Increases H secretion by both Na-dependent and Na-independent methods - If Na is 140 and Cl is 115, only 115 of Na can be reabsorbed as NaCl, the remainder must be reabsorbed with HCO3 or associated with secretion of K or H to maintained electro neutrality - This is enhanced with hypochloridemia - Concurrent hypokalemia - Changes in K lead to trans cellular shifts that affect inctracellular pH - Hypokalemia causes K out, H in and in the tubular cell the cell acts if there is systemic acidosis and increases H secretion (and bicarbonate resorption) - PTH - Decreases proximal HCO3 resorption - Primary HyperCard as cause of type 2 RTA - Does acidosis stim PTH or does PTH stim net acid excretion

Episode #260. Are you struggling to maintain a healthy weight and navigate the confusing world of diets and weight loss solutions? In this episode, join me as I dive into the science behind eating behaviours, obesity, and the challenges of losing weight with renowned researcher Dr Stephan Guyenet. Discover the different types of eating, the importance of controlling our food environment, and various evidence-based strategies for weight loss. With practical advice and insights from Dr Guyenet, you'll gain a better understanding of the complexities of weight management and how to make informed choices for your health. Don't miss this eye-opening conversation about the widespread issue of obesity and our brain's role in eating behaviours. Specifically, we discuss: Intro (00:00) From neurodegenerative disease to obesity neuroscience (01:36) The holiday weight gain (10:38) The problem with excess fat (14:37) 'Personal fat threshold' and diabetes (26:06) Main drivers of type 2 diabetes (31:26) The role of the hypothalamus in weight gain (38:55) Homeostatic vs. non-homeostatic eating (47:29) Genetics and the obesity epidemic (56:50) Models of obesity: carbohydrate -insulin vs. energy balance (1:00:21) The brain and obesity (1:10:34) The protein-leverage hypothesis (1:19:39) Carbohydrates, fat, and the Mediterranean diet (1:24:08) The weight loss puzzle: low carb vs. low fat diet (1:30:10) Foods that promote satiety on fewer calories (1:38:25) GLP-1 agonists (1:43:08) Is weight loss largely dependent on exercise? (1:55:06) Physical activity vs sedentary lifestyle (1:58:40) Mental health and sleep (2:00:28) Expert advice on how to stop overeating (2:05:11) Outro (2:05:59) To connect with Dr Stephan Guyenet, you can find him on Twitter or visit his website, https://www.stephanguyenet.com/. You can also purchase Dr Guyenet's widely acclaimed book, The Hungry Brain, to learn more about why we overeat and how to overcome this issue. Make sure to also check out Red Pen Reviews, where you can access free expert reviews on nutrition books. Discover more insights and supporting resources in the full show notes. Enjoy, friends. Simon Want to support the show? The best way to support the show is to use the products and services offered by our sponsors. To check them out, and enjoy great savings, visit theproof.com/friends. You can also show your support by leaving a review on the Apple Podcast app and/or sharing your favourite episodes with your friends and family. Simon Hill, MSc, BSc (Hons) Creator of theproof.com and host of The Proof with Simon Hill Author of The Proof is in the Plants Watch the episodes on YouTube or listen on Apple/Spotify Connect with me on Instagram, Twitter, and Facebook Nourish your gut with my Plant-Based Ferments Guide Download my complimentary two-week meal plan and high protein Plant Performance recipe book

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.04.539450v1?rss=1 Authors: Niraula, S., Yan, S. S., Subramanian, J. Abstract: Alzheimer's disease is associated with altered neuronal activity, presumably due to impairments in homeostatic synaptic plasticity. Neuronal hyper and hypoactivity are also observed in mouse models of amyloid pathology. Using multicolor two-photon microscopy, we test how amyloid pathology alters the structural dynamics of excitatory and inhibitory synapses and their homeostatic adaptation to altered experience-evoked activity in vivo in a mouse model. The baseline dynamics of mature excitatory synapses and their adaptation to visual deprivation are not altered in amyloidosis. Likewise, the baseline dynamics of inhibitory synapses are not affected. In contrast, despite unaltered neuronal activity patterns, amyloid pathology leads to a selective disruption of homeostatic structural disinhibition on the dendritic shaft. We show that excitatory and inhibitory synapse loss is locally clustered under the nonpathological state, but amyloid pathology disrupts it, indicating impaired communication of changes in excitability to inhibitory synapses. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.29.537929v1?rss=1 Authors: Kon, K., Ode, K. L., Mano, T., Fujishima, H., Tone, D., Shimizu, C., Shiono, S., Yada, S., Garcon, J. Y., Kaneko, M., Shinohara, Y., Takahashi, R. R., Yamada, R. G., Shi, S., Sumiyama, K., Kiyonari, H., Susaki, E. A., Ueda, H. R. Abstract: Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.27.538634v1?rss=1 Authors: Murao, N., Matsuda, T., Kadowaki, H., Matsushita, Y., Tanimoto, K., Katagiri, T., Nakashima, K., Nishitoh, H. Abstract: Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.14.536851v1?rss=1 Authors: Yuan, X., Puvogel, S., van Rhijn, J.-R., Esteve-Codina, A., Meijer, M., Rouschop, S., J.H. van Hugte, E., Oudakker, A., Schoenmaker, C., Schubert, D., Franke, B., Nadif Kasri, N. Abstract: Mechanisms that underlie homeostatic plasticity have been extensively investigated at single-cell levels in animal models, but are less well understood at the network level. Here, we used microelectrode arrays to characterize neuronal networks following induction of homeostatic plasticity in human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons co-cultured with rat astrocytes. Chronic suppression of neuronal activity through tetrodotoxin (TTX) elicited a time-dependent network re-arrangement. Increased expression of AMPA receptors and the elongation of axon initial segments were associated with increased network excitability following TTX treatment. Transcriptomic profiling of TTX-treated neurons revealed up-regulated genes related to extracellular matrix organization, while down-regulated genes related to cell communication; also astrocytic gene expression was found altered. Overall, our study shows that hiPSC-derived neuronal networks provide a reliable in vitro platform to measure and characterize homeostatic plasticity at network and single-cell level; this platform can be extended to investigate altered homeostatic plasticity in brain disorders. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.27.534486v1?rss=1 Authors: Saha, S., Chakraborty, P., Naskar, A., Roy, D., Banerjee, A. Abstract: Ageing brain is associated with a slow drift in structural network properties over the lifespan accompanied by reorganization in neuromolecular interactions giving rise to changes in global functional markers. What are the guiding principles of the homeostatic mechanisms that maintain the desired performance of functional neural circuits and preserve brain health during healthy ageing? We hypothesize that an ageing brain alters two primary neurotransmitters, glutamate and {gamma} -aminobutyric acid (GABA), responsible for excitation-inhibition regulation, concomitant with anatomical demyelination to preserve critical neural dynamics that are necessary to uphold optimal network performance. Thus, often observed reorganized functional connectivity with age by several investigations is a byproduct of this adaptive process. We demonstrate that the adaptive mechanism is driven by the tuning of glutamate and GABA concentration over a very slow time scale (lifespan) that can be estimated by tracking criticality from coordinated neural dynamics at a resting state via a biophysically driven computational framework, introduced as a computational microscope. We validate several empirical observations and model predictions across three independent aging cohorts using this computational microscope. One of the key mechanisms we discover is the reduction in local glutamate levels employed by brain regions to maintain a homeostatic balance with aging. This is further supported by the invariance of measures of global functional integration during the healthy ageing process. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.20.533396v1?rss=1 Authors: Anil, S., Lu, H., Rotter, S., Vlachos, A. Abstract: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique used to induce neuronal plasticity in healthy individuals and patients. Designing effective and reproducible rTMS protocols poses a major challenge in the field as the underlying biomechanisms remain elusive. Current clinical protocol designs are often based on studies reporting rTMS-induced long-term potentiation or depression of synaptic transmission. Herein, we employed computational modeling to explore the effects of rTMS on long-term structural plasticity and changes in network connectivity. We simulated a recurrent neuronal network with homeostatic structural plasticity between excitatory neurons, and demonstrated that this mechanism was sensitive to specific parameters of the stimulation protocol (i.e., frequency, intensity, and duration of stimulation). The feedback-inhibition initiated by network stimulation influenced the net stimulation outcome and hindered the rTMS-induced homeostatic structural plasticity, highlighting the role of inhibitory networks. These findings suggest a novel mechanism for the lasting effects of rTMS, i.e., rTMS-induced homeostatic structural plasticity, and highlight the importance of network inhibition in careful protocol design, standardization, and optimization of stimulation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

You may think you understand the important of steps as far as energy out goes, but there is SO MUCH MORE to it than that!!! Today's Episode we are breaking down WHY we track steps, and what the research shows about different step averages in regards to your overall health and hitting your fitness goals.Topics: (00:24) - Mesocycle and Microcycle (01:57) - Versa Gripps (04:44) - Steps challenge and step knowledge (05:54) - Don't get weird about steps (07:35) - Step levels explained (10:31) - Why 8,000 steps? (13:15) - Benefits that are often overlooked (18:41) - What about 12,000? (22:21) - Does cardio count towards steps? (24:29) - Movement builds momentum (27:58) - Changing the story you tell about yourself (33:33) - Doing all or something (34:24) - It willl look different for everybody (37:46) - Suggestions from recent steps challenge (45:17) - Habit stacking (47:52) - Recapping the benefits of movement Sign up HERE for the LiftingLindsay Newsletter so you never miss out on fitness and health brain gains!Want optimized training programs? You have enough to think about, let me do all your training programming for you. Sign up HERE for optimized training, no matter the goal. Training programs include home alternatives. I have 3,4 & 5 day programs. You can also upload videos for form reviews done by me in the VIP Facebook group Facebook group includes monthly challenges to take your health to the next level and have a chance to win prizes too! Studies sited PMID: 29289613 Homeostatic and non-homeostatic appetite control along the spectrum of physical activity levels: An updated perspective Burton, H.M. and E.F. Coyle, Daily Step Count and Postprandial Fat Metabolism. Med Sci Sports Exerc, 2021. 53(2): p. 333-340. Sullivan Bisson, A.N., S.A. Robinson, and M.E. Lachman, Walk to a better night of sleep: testing the relationship between physical activity and sleep. Sleep Health, 2019. 5(5): Foright, R., et al., Effects of Exercise during Weight Loss Maintenance on Appetite Regulation in Women. Transl J Am Coll Sports Med, 2020. Foright, R.M., et al., Is regular exercise an effective strategy for weight loss maintenance?  Physiol Behav, 2018. Mayer, J., P. Roy, and K.P. Mitra, Relation between caloric intake, body weight, and physical work: studies in an industrial male population in West Bengal.  Am J Clin Nutr, 1956.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.05.530392v1?rss=1 Authors: Mayzel, J., Schneidman, E. Abstract: Studying and understanding the code of large neural populations hinge on learning accurate statistical models of population activity. A new class of such models, based on learning to weigh sparse nonlinear Random Projections (RP) of the population, was recently shown to be highly accurate, efficient, and scalable. Moreover, RP models have a clear biologically-plausible implementation as a shallow neural circuit. Here we extend these models and present RP models that are learned by optimizing the randomly selected sparse projections. This "reshaping" of projections is akin to changing synaptic connections in the corresponding neural circuit model. When we applied these Reshaped RP models to recordings of tens of cortical neurons from behaving monkeys, we found them to be more accurate and efficient than the previous class of RP models and on par with backpropagation models. Our exploration of the effect of adding biological features to these circuit models revealed that learning reshaped RP models with homeostatic synaptic scaling yields even more efficient and accurate models. We further show that homeostatic reshaped RP models, which rely on sparse and random connectivity, are superior to fully connected network models. Our results thus suggest a key functional role for homeostatic scaling in neural circuits, beyond regulating network activity, namely - optimizing performance and efficiency. 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/2023.02.20.529310v1?rss=1 Authors: Berecki, G., Bryson, A., Polster, T., Petrou, S. Abstract: SCN1A gain-of-function variants are associated with early onset developmental and epileptic encephalopathies (DEEs) that possess distinct clinical features compared to Dravet syndrome caused by SCN1A loss-of-function. However, it is unclear how SCN1A gain-of-function may predispose to cortical hyper-excitability and seizures. Here, we first report the clinical features of a patient carrying a de novo SCN1A variant (T162I) associated with neonatal-onset DEE, and then characterize the biophysical properties of T162I and three other SCN1A variants associated with neonatal-onset or early infantile DEE (I236V, P1345S, R1636Q). In voltage clamp experiments, three variants (T162I, P1345S and R1636Q) exhibited changes in activation and inactivation properties that enhanced window current, consistent with gain-of-function. Dynamic action potential clamp experiments utilising model neurons incorporating Nav1.1. channels supported a gain-of-function mechanism for all four variants. Here, the T162I, I236V, P1345S, and R1636Q variants exhibited higher peak firing rates relative to wild type and the T162I and R1636Q variants produced a hyperpolarized threshold and reduced neuronal rheobase. To explore the impact of these variants upon cortical excitability, we used a spiking network model containing an excitatory pyramidal cell (PC) and parvalbumin positive (PV) interneuron population. SCN1A gain-of-function was modeled by enhancing the excitability of PV interneurons and then incorporating three simple forms of homeostatic plasticity that restored pyramidal cell firing rates. We found that homeostatic plasticity mechanisms exerted differential impact upon network function, with changes to PV-to-PC and PC-to-PC synaptic strength predisposing to network instability. Overall, our findings support a role for SCN1A gain-of-function and inhibitory interneuron hyperexcitability in early onset DEE. We propose a mechanism through which homeostatic plasticity pathways can predispose to pathological excitatory activity and contribute to phenotypic variability in SCN1A disorders. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

ReferencesWe considered the effect of a high protein diet and potential metabolic acidosis on kidney function. This review is of interest by Donald Wesson, a champion for addressing this issue and limiting animal protein: Mechanisms of Metabolic Acidosis-Induced Kidney Injury in Chronic Kidney DiseaseHostetter explored the effect of a high protein diet in the remnant kidney model with 1 ¾ nephrectomy. Rats with reduced dietary acid load (by bicarbonate supplementation) had less tubular damage. Chronic effects of dietary protein in the rat with intact and reduced renal massWesson explored treatment of metabolic acidosis in humans with stage 3 CKD in this study. Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rateIn addition to the effect of metabolic acidosis from a diet high in animal protein, this diet also leads to hyperfiltration. This was demonstrated in normal subjects; ingesting a protein diet had a significantly higher creatinine clearance than a comparable group of normal subjects ingesting a vegetarian diet. Renal functional reserve in humans: Effect of protein intake on glomerular filtration rate.This finding has been implicated in Brenner's theory regarding hyperfiltration: The hyperfiltration theory: a paradigm shift in nephrologyOne of multiple publications from Dr. Nimrat Goraya whom Joel mentioned in the voice over: Dietary Protein as Kidney Protection: Quality or Quantity?We wondered about the time course in buffering a high protein meal (and its subsequent acid load on ventilation) and Amy found this report:Effect of Protein Intake on Ventilatory Drive | Anesthesiology | American Society of Anesthesiologists Roger mentioned that the need for acetate to balance the acid from amino acids in parenteral nutrition was identified in pediatrics perhaps because infants may have reduced ability to generate acid. Randomised controlled trial of acetate in preterm neonates receiving parenteral nutrition - PMCHe also recommended an excellent review on the complications of parenteral nutrition by Knochel https://www.kidney-international.org/action/showPdf?pii=S0085-2538%2815%2933384-6 which explained that when the infused amino acids disproportionately include cationic amino acids, metabolism led to H+ production. This is typically mitigated by preparing a solution that is balanced by acetate. Amy mentioned this study that explored the effect of protein intake on ventilation: Effect of Protein Intake on Ventilatory Drive | Anesthesiology | American Society of AnesthesiologistsAnna and Amy reminisced about a Skeleton Key Group Case from the renal fellow network Skeleton Key Group: Electrolyte Case #7JC wondered about isolated defects in the proximal tubule and an example is found here: Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalitiesAnna's Voiceover re: Gastric neobladder → metabolic alkalosis and yes, dysuria. The physiology of gastrocystoplasty: once a stomach, always a stomach but not as common as you might think Gastrocystoplasty: long-term complications in 22 patientsSjögren's syndrome has been associated with acquired distal RTA and in some cases, an absence of the H+ ATPase, presumably from autoantibodies to this transporter. Here's a case report: Absence of H(+)-ATPase in cortical collecting tubules of a patient with Sjogren's syndrome and distal renal tubular acidosisCan't get enough disequilibrium pH? Check this out- Spontaneous luminal disequilibrium pH in S3 proximal tubules. Role in ammonia and bicarbonate transport.Acetazolamide secretion was studied in this report Concentration-dependent tubular secretion of acetazolamide and its inhibition by salicylic acid in the isolated perfused rat kidney. | Drug Metabolism & DispositionIn this excellent review, David Goldfarb tackles the challenging case of a A Woman with Recurrent Calcium Phosphate Kidney Stones (spoiler alert, many of these patients have incomplete distal RTA and this problem is hard to treat). Molecular mechanisms of renal ammonia transport excellent review from David Winer and Lee Hamm. OutlineOutline: Chapter 11- Regulation of Acid-Base Balance- Introduction - Bicarb plus a proton in equilibrium with CO2 and water - Can be rearranged to HH - Importance of regulating pCO2 and HCO3 outside of this equation - Metabolism of carbs and fats results in the production of 15,000 mmol of CO2 per day - Metabolism of protein and other “substances” generates non-carbonic acids and bases - Mostly from sulfur containing methionine and cysteine - And cationic arginine and lysine - Hydrolysis of dietary phosphate that exists and H2PO4– - Source of base/alkali - Metabolism of an ionic amino acids - Glutamate and asparatate - Organic anions going through gluconeogenesis - Glutamate, Citrate and lactate - Net effect on a normal western diet 50-100 mEq of H+ per day - Homeostatic response to these acid-base loads has three stages: - Chemical buffering - Changes in ventilation - Changes in H+ excretion - Example of H2SO4 from oxidation of sulfur containing AA - Drop in bicarb will stimulate renal acid secretion - Nice table of normal cid-base values, arterial and venous- Great 6 bullet points of acid-base on page 328 - Kidneys must excrete 50-100 of non-carbonic acid daily - This occurs by H secretion, but mechanisms change by area of nephron - Not excreted as free H+ due to minimal urine pH being equivalent to 0.05 mmol/L - No H+ can be excreted until virtually all of th filtered bicarb is reabsorbed - Secreted H+ must bind buffers (phosphate, NH3, cr) - PH is main stimulus for H secretion, though K, aldo and volume can affect this.- Renal Hydrogen excretion - Critical to understand that loss of bicarb is like addition of hydrogen to the body - So all bicarb must be reabsorbed before dietary H load can be secreted - GFR of 125 and bicarb of 24 results in 4300 mEq of bicarb to be reabsorbed daily - Reabsorption of bicarb and secretion of H involve H secretion from tubular cells into the lumen. - Thee initial points need to be emphasized - Secreted H+ ion are generated from dissociation of H2O - Also creates OH ion - Which combine with CO2 to form HCO3 with the help of zinc containing intracellular carbonic anhydrase. - This is how the secretion of H+ which creates an OH ultimately produces HCO3 - Different mechanisms for proximal and distal acidification - NET ACID EXCRETION - Free H+ is negligible - So net H+ is TA + NH4 – HCO3 loss - Unusually equal to net H+ load, 50-100 mEq/day - Can bump up to 300 mEq/day if acid production is increased - Net acid excretion can go negative following a bicarb or citrate load - Proximal Acidification - Na-H antiporter (or exchanger) in luminal membrane - Basolateral membrane has a 3 HCO3 Na cotransporter - This is electrogenic with 3 anions going out and only one cation - The Na-H antiporter also works in the thick ascending limb of LOH - How about this, there is also a H-ATPase just like found in the intercalated cells in the proximal tubule and is responsible for about a third of H secretion - And similarly there is also. HCO3 Cl exchanger (pendrin-like) in the proximal tubule - Footnote says the Na- 3HCO3 cotransporter (which moves sodium against chemical gradient NS uses negative charge inside cell to power it) is important for sensing acid-base changes in the cell. - Distal acidification - Occurs in intercalated cells of of cortical and medullary collecting tubule - Three main characteristics - H secretion via active secretory pumps in the luminal membrane - Both H-ATPase and H-K ATPase - H- K ATPase is an exchange pump, k reabsorption - H-K exchange may be more important in hypokalemia rather than in acid-base balance - Whole paragraph on how a Na-H exchanger couldn't work because the gradient that H has to be pumped up is too big. - H-ATPase work like vasopressin with premise H-ATPase sitting on endocarditis vesicles a=which are then inserted into the membrane. Alkalosis causes them to be recycled out of the membrane. - H secretory cells do not transport Na since they have few luminal Na channels, but are assisted by the lumen negative tubule from eNaC. - Minimizes back diffusion of H+ and promotes bicarb resorption - Bicarbonate leaves the cell through HCO3-Cl exchanger which uses the low intracellular Cl concentration to power this process. - Same molecule is found on RBC where it is called band 3 protein - Figure 11-5 is interesting - Bicarbonate resorption - 90% in the first 1-22 mm of the proximal tubule (how long is the proximal tubule?) - Lots of Na-H exchangers and I handed permeability to HCO3 (permeability where?) - Last 10% happens distally mostly TAL LOH via Na-H exchange - And the last little bit int he outer medullary collecting duct. - Carbonic anhydrase and disequilibrium pH - CA plays central role in HCO3 reabsorption - After H is secreted in the proximal tubule it combines with HCO# to form carbonic acid. CA then dehydrates it to CO2 and H2O. (Step 2) - Constantly moving carbonic acid to CO2 and H2O keeps hydrogen combining with HCO3 since the product is rapidly consumed. - This can be demonstrated by the minimal fall in luminal pH - That is important so there is not a luminal gradient for H to overcome in the Na-H exchanger (this is why we need a H-ATPase later) - CA inhibitors that are limited tot he extracellular compartment can impair HCO3 reabsorption by 80%. - CA is found in S1, S2 but not S3 segment. See consequence in figure 11-6. - The disequilibrium comes from areas where there is no CA, the HH formula falls down because one of the assumptions of that formula is that H2CO3 (carbonic acid) is a transient actor, but without CA it is not and can accumulate, so the pKa is not 6.1. - Bicarbonate secretion - Type B intercalated cells - H-ATPase polarity reversed - HCO3 Cl exchanger faces the apical rather than basolateral membrane- Titratable acidity - Weak acids are filtered at the glom and act as buffers in the urine. - HPO4 has PKA of 6.8 making it ideal - Creatinine (pKa 4.97) and uric acid (pKa 5.75) also contribute - Under normal cinditions TA buffers 10-40 mEa of H per day - Does an example of HPO4(2-):H2PO4 (1-) which exists 4:1 at pH of 7.4 (glomerular filtrate) - So for 50 mEq of Phos 40 is HPO4 and 10 is H2PO4 - When pH drops to 6.8 then the ratio is 1:1 so for 50 - So the 50 mEq is 25 and 25, so this buffered an additional 15 mEq of H while the free H+ concentration increased from 40 to 160 nanomol/L so over 99.99% of secreted H was buffered - When pH drops to 4.8 ratio is 1:100 so almost all 50 mEq of phos is H2PO4 and 39.5 mEq of H are buffered. - Acid loading decreases phosphate reabsorption so more is there to act as TA. - Decreases activity of Na-phosphate cotransporter - DKA provides a novel weak acid/buffer beta-hydroxybutyrate (pKa 4.8) which buffers significant amount of acid (50 mEq/d).- Ammonium Excretion - Ability to excrete H+ as ammonium ions adds an important amount of flexibility to renal acid-base regulation - NH3 and NH4 production and excretion can be varied according to physiologic need. - Starts with NH3 production in tubular cells - NH3, since it is neutral then diffuses into the tubule where it is acidified by the low pH to NH4+ - NH4+ is ionized and cannot cross back into the tubule cells(it is trapped in the tubular fluid) - This is important for it acting as an important buffer eve though the pKa is 9.0 - At pH of 6.0 the ratio of NH3 to NH4 is 1:1000 - As the neutral NH3 is converted to NH4 more NH3 from theintracellular compartment flows into the tubular fluid replacing the lost NH3. Rinse wash repeat. - This is an over simplification and that there are threemajor steps - NH4 is produced in early proximal tubular cells - Luminal NH4 is partially reabsorbed in the TAL and theNH3 is then recycled within the renal medulla - The medullary interstitial NH3 reaches highconcentrations that allow NH3 to diffuse into the tubular lumen in the medullary collecting tubule where it is trapped as NH4 by secreted H+ - NH4 production from Glutamine which converts to NH4 and glutamate - Glutamate is converted to alpha-ketoglutarate - Alpha ketoglutarate is converted to 2 HCO3 ions - HCO3 sent to systemic circulation by Na-3 HCO3 transporter - NH4 then secreted via Na-H exchanger into the lumen - NH4 is then reabsorbed by NaK2Cl transporter in TAL - NH4 substitutes for K - Once reabsorbed the higher intracellular pH causes NH4 to convert to NH3 and the H that is removed is secreted through Na-H exchanger to scavenge the last of the filtered bicarb. - NH3 diffuses out of the tubular cells into the interstitium - NH4 reabsorption in the TAL is suppressed by hyperkalemia and stimulated by chronic metabolic acidosis - NH4 recycling promotes acid clearance - The collecting tubule has a very low NH3 concentration - This promotes diffusion of NH3 into the collecting duct - NH3 that goes there is rapidly converted to NH4 allowing more NH3 to diffuse in. - Response to changes in pH - Increased ammonium excretion with two processes - Increased proximal NH4 production - This is delayed 24 hours to 2-3 days depending on which enzyme you look at - Decreased urine pH increases diffusion of ammonia into the MCD - Occurs with in hours of an acid load - Peak ammonium excretion takes 5-6 days! (Fig 11-10) - Glutamine is picked up from tubular fluid but with acidosis get Na dependent peritublar capillary glutamine scavenging too - Glutamine metabolism is pH dependent with increase with academia and decrease with alkalemia - NH4 excretion can go from 30-40 mEq/day to > 300 with severe metabolic acidosis (38 NaBicarb tabs) - Says each NH4 produces equimolar generation of HCO3 but I thought it was two bicarb for every alpha ketoglutarate?- The importance of urine pH - Though the total amount of hydrogren cleared by urine pH is insignificant, an acidic urine pH is essential for driving the reactions of TA and NH4 forward.- Regulation of renal hydrogen excretion - Net acid excretion vary inverse with extracellular pH - Academia triggers proximal and distal acidification - Proximally this: - Increased Na-H exchange - Increased luminal H-ATPase activity - Increased Na:3HCO3 cotransporter on the basolateral membrane - Increased NH4 production from glutamine - In the collecting tubules - Increased H-ATPase - Reduction of tubular pH promotes diffusion of NH3 which gets converted to NH4…ION TRAPPING - Extracellular pH affects net acid excretion through its affect on intracellular pH - This happens directly with respiratory disorders due to movement of CO2 through the lipid bilayer - In metabolic disorders a low extracellular bicarb with cause bicarb to diffuse out of the cell passively, this lowers intracellular pH - If you manipulate both low pCO2 and low Bicarb to keep pH stable there will be no change in the intracellular pH and there is no change in renal handling of acid. It is intracellular pH dependent - Metabolic acidosis - Ramps up net acid secretion - Starts within 24 hours and peaks after 5-6 days - Increase net secretion comes from NH4 - Phosphate is generally limited by diet - in DKA titratable acid can be ramped up - Metabolic alkalosis - Alkaline extracellular pH - Increased bicarb excretion - Decrease reabsorption - HCO3 secretion (pendrin) in cortical collecting tubule - Occurs in cortical intercalated cells able to insert H-ATPase in basolateral cells (rather than luminal membrane) - Normal subjects are able to secrete 1000 mmol/day of bicarb - Maintenance of metabolic alkalosis requires a defect which forces the renal resorption of bicarb - This can be chloride/volume deficiency - Hypokalemia - Hyperaldosteronism - Respiratory acidosis and alkalosis - PCO2 via its effect on intracellular pH is an important determinant of renal acid handling - Ratios he uses: - 3.5 per 10 for respiratory acidosis - 5 per 10 for respiratory alkalosis - Interesting paragraph contrasting the response to chronic metabolic acidosis vs chronic respiratory acidosis - Less urinary ammonium in respiratory acidosis - Major differences in proximal tubule cell pH - In metabolic acidosis there is decreased bicarb load so less to be reabsorbed proximally - In respiratory acidosis the increased serum bicarb increases the amount of bicarb that must be reabsorbed proximally - The increased activity of Na-H antiporter returns tubular cell pH to normal and prevents it from creating increased urinary ammonium - Mentions that weirdly more mRNA for H-Na antiporter in metabolic acidosis than in respiratory acidosis - Net hydrogen excretion varies with effective circulating volume - Starts with bicarb infusions - Normally Tm at 26 - But if you volume deplete the patient with diuretics first this increases to 35+ - Four factors explain this increased Tm for bicarb with volume deficiency - Reduced GFR - Activation of RAAS - Ang2 stim H-Na antiporter proximally - Ang2 also stimulates Na-3HCO3 cotransporter on basolateral membrane - Aldosterone stimulates H-ATPase in distal nephron - ALdo stimulates Cl HCO3 exchanger on basolateral membrane - Aldo stimulates eNaC producing tubular lumen negative charge to allow H secretion to occur and prevents back diffusion - Hypochloremia - Increases H secretion by both Na-dependent and Na-independent methods - If Na is 140 and Cl is 115, only 115 of Na can be reabsorbed as NaCl, the remainder must be reabsorbed with HCO3 or associated with secretion of K or H to maintained electro neutrality - This is enhanced with hypochloridemia - Concurrent hypokalemia - Changes in K lead to trans cellular shifts that affect inctracellular pH - Hypokalemia causes K out, H in and in the tubular cell the cell acts if there is systemic acidosis and increases H secretion (and bicarbonate resorption) - PTH - Decreases proximal HCO3 resorption - Primary HyperCard as cause of type 2 RTA - Does acidosis stim PTH or does PTH stim net acid excretion

In the 142nd episode of The Strength Connection Podcast, Mike and our special guest, Professor at the Carrick Institute in Rocky Mountain University and Researcher, Dr. Mike T Nelson, will talk about heat transfer experiment, the metabolic flexibility project, ways to check metabolic flexibility at home, homeostatic regulators, and more.Join us in this insightful and captivating talk! In this chapter, you will discover:(0:45) Welcome to our special guest Professor at the Carrick Institute in Rocky Mountain University and Researcher, Dr. Mike T Nelson @drmiketnelson(2:15) Dr. Mike's origin story(2:20) Interest in science(3:05) Starting lifting early(3:40) Undergrad psychology class (4:50) Heat transfer experiment(6:10) Presentation for DARPA(8:10) New psychology class(9:00) Working in a cube environment(9:20) NSCA CSCS(10:00) Training people(10:15) Ph.D. work in biomechanical engineering(11:00) What does Dr. Mike currently do?(11:45) About metabolic flexibility(13:10) Lack of choice for projects(14:00) The Metabolic Flexibility project(16:20) Metabolic inflexibility(19:50) From inflexible to flexible(20:40) Insulin-dependent and insulin-independent(23:10) Ways to check metabolic flexibility at home(25:35) Fasted cardio(27:00) Why is fasted cardio easier in practice?(28:05) Opposite data(28:10) Shout out to Dr. Jeff Rothschild @eatsleep.fit(28:25) Shout out to Ryan Baxter @ryanjasonbaxtor(28:40) Is fasted cardio magical?(30:15) Should you do fasted cardio?(32:15) The flexibility levels(33:30) Dr. Mike's pet peeve(33:50) Homeostatic regulators(34:50) Steps to become more resilient(35:10) Heat acclimation(36:00) “The greater your buffer zone is in temperature, pH level, that's the key to advanced recovery, longevity, and being more robust antifragile.” - Dr. Mike T Nelson @drmiketnelson(37:10) Sauna village(37:10) Shout out to Krista Scott-Dixon @stumptuous(37:30) Shout out to Thadius Owen @primalhacker(38:25) Shout out to Laird Hamilton @lairdhamilton(39:20) Benefits of cold showers(39:40) At home cold immersion(42:50) Voluntarily suffering(43:50) Stress-related thoughts(44:50) “You have to pick some stressors in your life.” - Dr. Mike T Nelson @drmiketnelson(45:20) “You have to pick what stressors you want to expose yourself to and if you do that in an intelligent manner your body rewards you by getting better at those things via adaptation.” - Dr. Mike T Nelson @drmiketnelson(45:45) Meditative practice(46:15) Shout out to John Danaher @danaherjohn(46:30) Stress lessen(47:25) Shout out to Brian Mackenzie @_brianmackenzie(47:25) Shout out to Rob Wilson @preparetoperform(48:40) Mike and Chris' nose breathing experiment(49:30) One of Dr. Mike's training methods(51:20) What's next with Dr. Mike?Where to find Dr. Mike T Nelson? @drmiketnelsonwww.flexdiet.com www.physiologicflexibility.com 

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.01.526708v1?rss=1 Authors: Makarava, N., Mychko, O., Molesworth, K., Chang, J. C.-Y., Henry, R. J., Tsymbalyuk, N., Gerzanich, V., Simard, J. M., Loane, D., Baskakov, I. V. Abstract: The transformation of astrocytes into reactive states constitutes a biological response of the central nervous system under a variety of pathological insults. Astrocytes display diverse homeostatic identities, which are developmentally predetermined and regionally specified. Upon transformation into reactive states associated with neurodegenerative diseases and other neurological disorders, astrocytes acquire diverse reactive phenotypes. However, it is not clear whether their reactive phenotypes are dictated by region-specific homeostatic identity or, alternatively, by the nature of an insult. To address this question, region-specific gene expression profiling was performed for four brain regions (cortex, hippocampus, thalamus and hypothalamus) in mice using a custom Nanostring panel consisting of selected sets of genes that report on astrocyte functions and their reactivity for five conditions: prion disease, traumatic brain injury, brain ischemia, 5XFAD Alzheimer's disease model and normal aging. Upon transformation into reactive states, genes that are associated predominantly with astrocytes were found to preserve region-specific signatures suggesting that they respond to insults in a region-specific manner. A common gene set was found to be involved in astrocyte remodeling across insults and normal aging. Regardless of the nature of an insult or insult-specificity of astrocyte response, strong correlations between the degree of astrocyte reactivity and perturbations in their homeostasis-associated genes were observed within each individual brain region. The insult-specific populations did not separate well from each other and instead partially overlapped, forming continuums of phenotypes. The current study demonstrates that astrocytes acquire their reactive phenotypes according to their region-specific homeostatic identities. Within these region-specified identities, reactive phenotypes show continuums of states, partially overlapping between individual insults. 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/2023.01.26.525642v1?rss=1 Authors: Duriez, A., Bergerot, C., Cone, J. J., Roitman, M. F., Gutkin, B. Abstract: Seeking and consuming nutrients is essential to survival and maintenance of life. Dynamic and volatile environments require that animals learn complex behavioral strategies to obtain the necessary nutritive substances. While this has been classically viewed in terms of homeostatic regulation, where complex nutrient seeking behaviors are triggered by physiological need, recent theoretical work proposed that such strategies are a result of reinforcement learning processes. This theory also proposed that phasic dopamine (DA) signals play a key role in signaling potentially need-fulfilling outcomes. To examine potential links between homeostatic and reinforcement learning processes, we focus on sodium appetite as sodium depletion triggers state and taste dependent changes in behavior and DA signaling evoked by sodium-related stimuli. We find that both the behavior and the dynamics of DA signaling underlying sodium appetite can be accounted for by extending principles of homeostatic regulation into a reinforcement learning framework (HRRL). We first optimized HRRL-based agents to model sodium-seeking behavior measured in rats. Agents successfully reproduced the state and the taste dependence of behavioral responding for sodium as well as for lithium and potassium salts. We then show that these same agents can account for the regulation of DA signals evoked by sodium tastants in a taste and state dependent manner. Our models quantitatively describe how DA signals evoked by sodium decrease with satiety and increase with deprivation suggesting that phasic DA signals and sodium consumption are down regulated prior to animals reaching satiety. Lastly, our HRRL agents also account for the behavioral and neurophysiological observations that suggest mice cannot distinguish between sodium and lithium containing salts. Our HRRL agents exhibited an equal preference for sodium versus lithium containing solutions, and underestimated the nutritional value of sodium when lithium was concurrently available. We propose that animals use orosensory signals as predictors of the internal impact of the consumed good and our results pose clear targets for future experiments. In sum, this work suggests that appetite-dirven behavior may be driven by reinforcement learning mechanisms that are dynamically tuned by homeostatic need. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Changes in reindeer sleep regulation across the year: a central role for rumination? In this episode, I am joined by Melanie Furrer, who recently presented her study on sleep in reindeer. Most non-hibernating animals maintain daily “circadian ”rhythms of sleep across the year, as well as “homeostatic” sleep-wake patterns in which increasing time awake is followed by increased sleep amount or intensity. Strikingly, ruminant reindeer in the Arctic show 24-h rhythmicity at the equinoxes but none at either solstice; summertime activity greatly exceeds wintertime activity. So far, nothing is known about their sleep or how it might be seasonally modulated. Methods: We simultaneously recorded non-invasive electroencephalography EEG in four adult female reindeer for four days at The Arctic University of Norway in Tromsø, Norway in July, September, and December. Rapid eye movement, REM sleep, non-REM NREM sleep, and rumination were visually identified from the EEG, and slow-wave activity SWA, EEG power 1–18 4.5 Hz during NREM sleep, the classic marker for homeostatic changes in sleep pressure, was calculated. Results: Although sleep in reindeer generally resembled that of other mammals, key novel adaptations were observed in July/September: n=4, December: n=3. Like most species, sleep-wake distribution paralleled daily activity during seasonally changing light-dark conditions and SWA during NREM sleep increased after prolonged wake periods. Surprisingly, total sleep duration was roughly equal across seasons, and prolonged waking produced a lower SWA response in summer than in winter. As reported for some domestic ruminants, EEG during rumination showed typical characteristics of NREM sleep. Furthermore, rumination appeared to substitute for sleep under all observed conditions. Accordingly, SWA decreased across rumination, and total rumination and NREM sleep durations were negatively correlated. Homeostatic modelling of SWA further suggested that rumination was equivalent to sleep. Conclusions: We suggest that less pronounced SWA increases across waking in summer might indicate higher baseline sleep pressure during this season, possibly resulting from increased activity, food intake and light exposure. Within this context, rumination might partially substitute conventional sleep, permitting near-constant feeding in the arctic summer while compensating for increased sleep pressure. Contact or follow Melanie https://www.kispi.uzh.ch/forschungszentrum/person/furrer-melanie. https://www.researchgate.net/profile/Melanie-Furrer-2   Contact me at iandunican@sleep4performance.com.au or www.sleep4performance.com.au and check out the YouTube channel. Check out our sponsor LMNT. Click on the link to order and get a free LMNT Sample Pack when you order through the custom link below. Key details: • The LMNT Sample Pack includes 1 packet of every flavour. This is the perfect offer for anyone interested in trying all of our flavours or who wants to introduce a friend to LMNT. • This offer is exclusively available through VIP LMNT Partners – you won't find this offer publicly available. • This offer is available for new and returning customers • They offer refunds on all orders with no questions – you don't even have to send it back! DrinkLMNT.com/sleep4performance

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.11.519940v1?rss=1 Authors: Theret, M., Messing, M., White, Z., Henry, L. W., Rempel, L., Hamer, M., Hashimoto, J., Li, F. F., Brassard, J., Li, Y., Sauge, E., Shin, S., Day, K., Uppal, M., Low, M., Eisner, C., Sato, S., Akira, S., Bernatchez, P., McNagny, K., Rossi, F. M. V. Abstract: The ability of mesenchymal stromal cells to modulate inflammation is at the basis of the ongoing interest in their therapeutic potential. Yet, reliable success in clinical trials is limited, possibly due to a limited understanding of their impact on the inflammatory milieu in physiological conditions. Here we show that, at steady state, mesenchymal progenitors regulate the balance between type 1 and type 2 inflammatory milieus by acting on innate immune cells through the TAK1-NFkB pathway. Suppressing the constitutive activity of this pathway in MPs leads to skewing of the immune system toward systemic Type 2 inflammation (Th2). These changes have significant effects on diseases with an important inflammatory component, leading to a worsening of disease in a preclinical model of Th2-dependent Asthma, and a reduction of symptoms associated with Th1/Th17-dependent experimental autoimmune encephalitis. 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/2022.11.16.516613v1?rss=1 Authors: Jusyte, M., Blaum, N., Boehme, M. A., Berns, M. M., Bonard, A. E., Kobbersmed, J. R., Walter, A. M. Abstract: Chemical synaptic transmission relies on neurotransmitter release from presynaptic release sites and on transmitter-sensing by the postsynaptic cell. Presynaptic plasticity increasing neurotransmitter release achieves two fundamental nervous system functions: It tunes some synapses to be more responsive to millisecond repetitive activation and it maintains signals when postsynaptic transmitter sensitivity is reduced. How enhanced neurotransmitter release is achieved in these phenomena, termed short-term facilitation and homeostatic potentiation, remains unknown. We combine mathematical modeling and experimental analysis of Drosophila neuromuscular junction model synapses to elucidate the molecular mechanisms underlying these forms of plasticity. Our results indicate that both phenomena depend on a rapid increase in the participation of neurotransmitter release sites which is controlled by the regulatory domains of the evolutionarily conserved (M)Unc13A protein that bind Ca2+/Calmodulin and diacylglycerol. Mutation of the Calmodulin binding (CaM) domain increased baseline transmission and impaired both short-term facilitation and acute homeostatic potentiation. Mathematical modeling indicated that these defects result from too many release sites participating at rest combined with the inability to plastically further increase their number. Super-resolution microscopy revealed that this coincided with a redistribution of Unc13A`s functionally essential MUN domain closer to the synaptic plasma membrane, which may constitute the molecular switch to increase release site participation. Similar consequences (enhanced baseline transmission, block of both short-term facilitation and homeostatic potentiation) were caused by the acute pharmacological activation of the C1 domain of wildtype Unc13A using phorbol esters. This treatment had no effect on Unc13A CaM domain mutants, indicating that both the CaM and C1 domains activate a binary release site switch. Thus, our findings indicate that Unc13A regulatory domains are tuned to integrate a multitude of signals on various timescales to switch release site participation for synaptic plasticity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Guest Name: Pedro Caceres, Leading expert in supply chain, Language: English, Publication date: Nov, 01. 2022 Pedro J. Caceres is an American business executive that has held executive positions in several global corporations, such as Hasbro (Senior VP Operations - Hasbro Games), Newell Rubbermaid (Global VP Operations & Supply Chain - Lenox Division), and Petmate (Chief Operating Officer).As a published author, he released “The Thundering Voice" (2009) a book that introduces a moral approach to Corporate Social Responsibility, and “Operational Success” (2012) to introduce practical operational models to drive Lean Transformation. He is also the creator of "MyInventory.AI” a System of Intelligence to optimize global supply chains. Pedro is also involved in community activities and has been Chairman of the Board of Advisors of the Division of Business Excellence (Affiliated Chambers of Commerce of Greater Springfield in Massachusetts), member of the Advisory Board for the National Ergonomic Conference and Exposition (NECE), and Vice-Chairman of the Board of Directors of Junior Achievement of Western Massachusetts. Visit his website www.operationalsuccess.com. Some of the questions we asked Pedro during our conversation: What is the primary distinction between the Homeostatic value chain and other approaches? How can we use these value chain models to respond to recent supply chain challenges where there has been a lot of uncertainty, complexity, and ambiguity in various aspects of SCM? How do you see technological advancements like the Internet of Things, Smart factories, Intregated cloud-systems, and others playing a role in improving supply chains? --- Send in a voice message: https://anchor.fm/bicarasupplychain/message

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.31.514538v1?rss=1 Authors: Muller, S. Z., Abbott, L. F., Sawtell, N. B. Abstract: Homeostatic (anti-Hebbian) forms of synaptic are effective at eliminating "prediction errors" that signal the differences between predicted and actual sensory input. However, such mechanisms appear to preclude the possibility of transmitting the resulting predictions to downstream circuits, severely limiting their utility. Using modeling and recordings from the electrosensory lobe of mormyrid fish, we reveal interactions between axonal and dendritic spikes that support both the learning and transmission of predictions. We find that sensory input modulates the rate of dendritic spikes by adjusting the amplitude of backpropagating axonal action potentials. Homeostatic plasticity counteracts these effects through changes in the underlying membrane potential, allowing the dendritic spike rate to be restored to equilibrium while simultaneously transmitting predictions through modulation of the axonal spike rate. These results reveal how two types of spikes dramatically enhance the computational power of single neurons in support of an ethologically relevant multi-layer computation. 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/2022.10.23.513396v1?rss=1 Authors: Kruse, P., Vlachos, A., Lenz, M. Abstract: Neurological diseases can lead to the denervation of brain regions caused by demyelination, traumatic injury or cell death. Nevertheless, the molecular and structural mechanisms underlying the lesion-induced reorganization of denervated brain regions are a matter of ongoing investigation. In order to address this issue, we performed an entorhinal cortex lesion (ECL) in organotypic entorhinal-hippocampal tissue cultures and studied denervation-induced homeostatic plasticity of mossy fiber synapses, which connect dentate granule cells with CA3 pyramidal neurons and play important roles in spatial learning. Partial denervation caused a homeostatic strengthening of excitatory neurotransmission in dentate granule cells (GC), in CA3 pyramidal neurons, and their direct synaptic connections as revealed by paired recordings (GC-to-CA3). These functional changes were accompanied by ultrastructural reorganization of mossy fiber synapses, which regularly contain the plasticity-related protein synaptopodin and the spine apparatus organelle. We demonstrate that the spine apparatus organelle and its associated protein synaptopodin assemble ribosomes in close proximity to synaptic sites and moreover we unravel synaptopodin-related transcriptome, which can be linked to the expression of homeostatic synaptic plasticity. Notably, synaptopodin-deficient tissue preparations that lack the spine apparatus organelle, failed to express homeostatic adjustments of both excitatory neurotransmission and the region-specific transcriptome. Hence, synaptopodin and the spine apparatus organelle form local protein synthesis hubs that are essential for mediating lesion-induced homeostatic synaptic plasticity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Our topic today is very scientific, heavy, and wonderful. It's something that I think, as we go through, it's clearly going to open your eyes to understanding the immune system, how the immune system has been misunderstood for quite some time, and the cells that are actually required for our homeostatic optimal function.So today, we're going to dig into macrophages and all the different types of macrophages within the body. We are analyzing their role in development, homeostasis, and in inflammation. We are also explaining why these cells function the way they do, and why they're super important! Rate and review before the next episode. If you want to know more about us and what we do, go to www.healthupgradepodcast.com.Contact info:Navaz HabibEmail: podcast@healthupgraded.comFacebook: https://www.facebook.com/DrNavazHabib/Instagram: https://www.instagram.com/drnavazhabib/LinkedIn: https://ca.linkedin.com/in/drnavazhabibJP ErricoLinkedIn: https://www.linkedin.com/in/jp-errico-097629aa 

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.12.507667v1?rss=1 Authors: Schultheiss, H., Zulfiqar, I., Moerel, M. Abstract: Tinnitus is a clinical condition where a sound is perceived without external sound source. Homeostatic plasticity (HSP), serving to increase neural activity as compensation for the reduced input to the auditory pathway after hearing loss, has been proposed as causal mechanism underlying tinnitus. In support, animal models of tinnitus show evidence of increased neural activity after hearing loss, including increased spontaneous and sound-driven firing rate, as well as increased neural noise throughout the auditory processing pathway. Bridging these findings to human tinnitus, however, has proven to be challenging. Here we implement hearing loss-induced HSP in a Wilson-Cowan Cortical Model of the auditory cortex to predict how homeostatic principles operating at the microscale translate to the meso- to macroscale accessible through human neuroimaging. We observed HSP-induced response changes in the model that were previously proposed as neural signatures of tinnitus. As expected, HSP increased spontaneous and sound-driven responsiveness in hearing-loss affected frequency channels of the model. We furthermore observed evidence of increased neural noise and the appearance of spatiotemporal modulations in neural activity, which we discuss in light of recent human neuroimaging findings. Our computational model makes quantitative predictions that require experimental validation, and may thereby serve as the basis of future human tinnitus studies. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.08.31.506141v1?rss=1 Authors: Dannhäuser, S., Mrestani, A., Gundelach, F., Pauli, M., Komma, F., Kollmannsberger, P., Sauer, M., Heckmann, M., Paul, M. Abstract: Neurotransmitter release at presynaptic active zones (AZs) requires concerted protein interactions within a dense 3D nano-hemisphere. Among the complex protein mesh- work the (M)unc-13 family member Unc-13 of Drosophila melanogaster is essential for docking of synaptic vesicles and transmitter release. We employ MiMIC-based gene editing using GFSTF (EGFP-FlAsH-StrepII-TEV- 3xFlag) to endogenously tag all annotated Drosophila Unc-13 isoforms enabling visualization of endogenous Unc-13 expression within the central and peripheral nervous system. Electrophysiological characterization using two-electrode voltage clamp (TEVC) reveals that evoked and spontaneous synaptic transmission remain unaffected in unc-13 GFSTF 3 rd instar larvae and acute presynaptic homeostatic potentiation (PHP) can be induced at control levels. Furthermore, multi-color structured-illumination shows precise co-localization of Unc-13 GFSTF , Bruchpilot and GluRIIA-receptor subunits within the synaptic mesoscale. Localization microscopy in combination with HDBSCAN algorithms detect Unc-13 GFSTF nanoclusters that move towards the AZ center during PHP with unaltered Unc-13 GFSTF protein levels. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.08.31.506100v1?rss=1 Authors: Armstrong, N. S., Frank, C. A. Abstract: The ability of synapses to maintain physiological levels of evoked neurotransmission is essential for neuronal stability. A variety of perturbations can disrupt neurotransmission, but synapses often compensate for disruptions and work to stabilize activity levels, using forms of homeostatic synaptic plasticity. Presynaptic homeostatic potentiation (PHP) is one such mechanism that is expressed at the model Drosophila melanogaster larval neuromuscular junction (NMJ) synapse. In PHP, neurotransmitter release increases in response to challenges to the synapse, resulting in the maintenance of evoked neurotransmission. Prior work separated PHP into two temporal phases, acute and chronic. Those data suggested that cytoplasmic calcium signaling was important for a long-term maintenance of PHP. Here we used a combination of transgenic Drosophila RNA interference and overexpression lines, along with NMJ electrophysiology, synapse imaging, and pharmacology to test if regulators of the calcium/calmodulin-dependent protein phosphatase calcineurin are necessary for the normal expression of acute or chronic forms of PHP. We found that either pre- or postsynaptic dysregulation of a Drosophila gene regulating calcineurin, sarah (sra), blocks PHP. Examination of tissue-specific data showed that increases and decreases in sra expression are both detrimental to PHP. Additionally, the acute and chronic phases of PHP are functionally separable depending entirely upon which sra genetic manipulation is used. Surprisingly, concurrent pre- and postsynaptic sra knockdown or overexpression ameliorated PHP blocks revealed in single tissue experiments. Pharmacological inhibition of calcineurin corroborated this latter finding. Our results suggest that a discrete balance of calcineurin signaling is needed across multiple synapse tissue types and over different temporal phases to stabilize peripheral synaptic outputs. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Today on the show is Dr Mike T. Nelson. Mike has a Ph.D. in Exercise Physiology, a BA in Natural Science, and an MS in Biomechanics. He is also an adjunct professor and a member of the American College of Sports Medicine. Dr. Mike T. Nelson has spent 18 years of his life learning how the human body works, specifically focusing on how to properly condition it to burn fat and become stronger, more flexible, and healthier. He's been called in to share his techniques with top government agencies, universities and colleges, fitness organizations and fanatics. The techniques he's developed, and the results Mike gets for his clients have been featured in international magazines, in scientific publications, and on websites across the globe. Links to Dr. MikeInstagram: https://www.instagram.com/drmiketnelson/?hl=en Twitter: https://twitter.com/miketnelson Physiological Flexibility Course: https://miketnelsons.samcart.com/products/physflex/Metabolic Flexibility Course: https://flexdiet.com/Oxidative Potential Podcast LinksMoxy Monitor Discount:For a 5% discount on a Moxy Monitor purchase use promocode: OXPOhttps://www.moxymonitor.com/Instagram Links:https://www.instagram.com/criticalo2/?hl=enhttps://www.instagram.com/resiliencehpc/?hl=enYoutube Links:https://www.youtube.com/channel/UCfkBVklDMTPMbaPw0ikG2tgWebsite Links:https://www.resiliencehpc.ca/

Sarah welcomes Austin Stout back to the Beyond Condition Podcast and they talk about female health as a bodybuilder.Austin has a wealth of knowledge when it comes to physique development. Through his experience as a coach and competitor he is able to share valuable information on the effects bodybuilding has on the body and mind.Discussions include:*Homeostatic adaptations*Cortisol*Hormonal changes when dieting*Bloodwork*Menstrual cycles*Effects of dieting*Estrogen*GI health*Common environmental contributions that effect health during a dieting phase*Acute and chronic effects*Multiple preps and diet phases*Looking at the bigger picture*Emotional attachments to bodybuilding*Age considerations*Competition aspirations*Prep start point*Picking a show*Stress*Reverse dieting and recovery after a prep*Diet and training fatigue*Levels of leanest*Social media*Off season*Practical advice to considerAnd now it's over to you!!! We want to hear from our listeners, send us your topic suggestions and questions!Get in touch via Instagram@austinst8@sarahparker_bbRemember to follow us and share our episodes on your Instagram stories.Watch it here: https://youtu.be/DqMrHUv8SSoGet in touch and share this episode @sarahparker_bb

Doce é muito bom, né? Infelizmente, a vontade de doces é o que impede muitas pessoas de conseguir seguir uma alimentação saudável e emagrecer. Veja o que estes dois estudos revelaram sobre a vontade de doces, e qual o método para você parar de ser "escravo" dos doces - e poder degustá-los com prazer e calma, sem desespero. Você encontra receitas deliciosas e baixas em carboidratos estão disponíveis no nosso Livro Físico 120 Receitas Low-Carb De Sucesso (receba em casa com frete grátis): http://bit.ly/120-receitas-tanquinho Outros de nossos livros, cursos e treinamentos: https://landing.senhortanquinho.com/ ------------ * Dicas E Comentários Sobre Como Diminuir A Vontade de Doces * Existem algumas medidas práticas para acabar com a #vontade de doces. Como falamos, a vontade de #doces, ou de carboidratos, não é uma questão de "força ou fraqueza". Por exemplo, você sabia que algumas desregulações hormonais estão intimamente ligadas à vontade de comer carboidratos a noite? Falamos sobre isso aqui https://www.youtube.com/watch?v=wag8oD-hQhk E o estudo 1 mostrou que o "consumo cronicamente alto de carboidratos pode afetar os sistemas de recompensa do cérebro, de maneiras que pode impedir a manutenção da perda de peso". Ou seja: coma muitos carboidratos, e pode ser mais difícil para você se manter magra. Já o estudo 2 mostrou que as pessoas que faziam um café da manhã mais rico em carboidratos tinha maiores oscilações na glicemia, e tiveram mais fome, e comeram mais calorias. Ou seja: mais um ponto para a dieta #lowcarb. (Entenda as diferenças e semelhanças entre low-carb, paleo, cetogênica, primal, aqui: https://www.youtube.com/watch?v=IMDMteQg8N8 ) E veja como fazer um café da manhã low-carb aqui: https://www.youtube.com/watch?v=w0ie_q52mFY Estudos citados: 1 - Laura M Holsen, W Scott Hoge, Belinda S Lennerz, Hilâl Cerit, Taryn Hye, Priyanka Moondra, Jill M Goldstein, Cara B Ebbeling, David S Ludwig, Diets Varying in Carbohydrate Content Differentially Alter Brain Activity in Homeostatic and Reward Regions in Adults, The Journal of Nutrition, Volume 151, Issue 8, August 2021, Pages 2465–2476 2 - Wyatt, P., Berry, S.E., Finlayson, G. et al. Postprandial glycaemic dips predict appetite and energy intake in healthy individuals. Nat Metab 3, 523–529 (2021). Mas note que o *grau de processamento* dos alimentos é importante. Neste aspecto, prefira sempre a comida de verdade - explicamos o porquê aqui: https://www.youtube.com/watch?v=Wh5z_aC7YnQ --- Support this podcast: https://anchor.fm/senhortanquinho/support

References Dr Guerra lecture notes Endocr Rev. 2020 Aug; 41(4): 594–609 Alzheimer's & Dementia: Translational Research & Clinical Interventions (TRCI) 2021 Volume7, Issue1 e12217 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Today we welcome Dr. Antonio Damasio. He is an internationally recognized neuroscientist whose extensive research has shaped the understanding of neural systems and consciousness. With over a hundred journal articles and book chapters, he has earned many prestigious awards throughout his career. Currently, he serves as University Professor, the David Dornsife Professor of Neuroscience, Psychology, and Philosophy, and director of the Brain and Creativity Institute at the University of Southern California. His books Descartes' Error, Looking for Spinoza, Self Comes to Mind, The Strange Order of Things, and Feeling & Knowing, have been published in translation and are taught in universities throughout the world.In this episode, I talk to Antonio Damasio about consciousness. People often think that the mind and consciousness are the same thing, but Dr. Damasio disputes this notion. He argues that it's the complex relationship of both our brains and bodies that makes sentient thought possible. Homeostatic feelings like hunger and pain developed before emotions; and along with it came consciousness. We also touch on the topics of perception, mental illness, evolution, panpsychism, AI and machine learning. Website: dornsife.usc.edu/bcTwitter: @damasiousc Topics02:17 Time-locked multiregional retroactivation11:32 The difference between the mind, intelligence, and consciousness18:37 Panpsychism is an escape22:50 AIs can replicate minds but not consciousness 25:42 Feeling gave way to consciousness30:59 The purpose of emotions33:25 The evolution of feelings and emotions38:28 The interoceptive nervous system44:23 Does mental illness disrupt consciousness?49:51 Creativity as a bottom-up process54:38 Consciousness can hinder creativity58:09 Scott's interest in panpsychism59:18 Can we ever make feeling machines?

We have all attempted to change how we feel and think about food and our bodies and continuously wind up in a yo-yo type cycle. In this episode Lisa discusses what we have to change about our approach in order to truly achieve a true, deep and profound lifestyle change. Topics Include: Taking healing our relationship to food, eating and our body from the physical to spiritual dimension Being the observer and how it's the true lifestyle change we've been looking for Food's innate emotional component What it means to be healthy from a holistic point of view Focusing on health vs weight [2:30] What spirituality has to do with all of this, regardless of how you identify on the spirituality spectrum, how are we in relationship the thinking, feeling, the connected, loving being inside of us [6:30] Swinging “the pendulum” of food and eating to overeating, mindless eating, feeling out of control around food to being restrictive, counting, weight points, etc vs being still in mindfulness, aware of our emotions and stressors [13:19] What it means to be in alignment with yourself [16:30] Becoming a conscious observer of your thoughts, feelings, and behaviors [21:00] Homeostatic and hedonic hunger [26:45] Getting back to your factory settings and being able to get your needs met appropriately [30:10] Clues that hunger is physical rather than emotional and vice versa [33:20] How being hyper focused on weight can take us further from holistic health and defining what it means to be healthy, beyond physical health and health Next Cycle of Group Coaching begins January 2022 - Reserve Your Spot https://www.outofthecave.health/work-with-me Become a Member of the Out of the Cave Online Community - Includes Two Live Coaching Calls Monthly https://www.outofthecave.health/membership EMail Lisa - We welcome questions, comments and feedback lisa@lisaschlosberg.com Out of the Cave Merch - For 10% off use code SCHLOS10 https://www.outofthecave.health/shop Socials Instagram: www.instagram.com/lisa.schlosberg Facebook: https://www.facebook.com/outofthecavellc YouTube: https://www.youtube.com/user/lees325/videos

Weight gain during the holidaysIs it real?Discussion of the researchEat more protein4x40 or 4x30 approachRelax on the big dayHedonic and homeostatic reasons to eatGo moveWalk or exerciseDaily body weight measurementsResearchMore water and electrolytesRelationship between hunger and thirstGetting salt is mainly done via eatingCraving salty foodsResearchAffiliate link: Drink LMNT | Paleo-Keto Friendly Hydration | Zero Sugar Electrolytes – Drink The Flex Diet Podcast is brought to you by the Flex Diet Certification. Go to https://flexdiet.com/ for 8 interventions on nutrition and recovery. If you're outside the enrollment window, sign up for my free newsletter, and you'll be notified when it opens!ReferencesHoliday Weight Gain?Díaz-Zavala, R. G., Castro-Cantú, M. F., Valencia, M. E., Álvarez-Hernández, G., Haby, M. M., & Esparza-Romero, J. (2017). Effect of the Holiday Season on Weight Gain: A Narrative Review. Journal of obesity, 2017, 2085136. https://doi.org/10.1155/2017/2085136https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514330/Roberts SB, Mayer J. Holiday weight gain: fact or fiction? Nutr Rev. 2000 Dec;58(12):378-9. doi: 10.1111/j.1753-4887.2000.tb01839.x. PMID: 11206847.https://pubmed.ncbi.nlm.nih.gov/11206847/Kaviani S, vanDellen M, Cooper JA. Daily Self-Weighing to Prevent Holiday-Associated Weight Gain in Adults. Obesity (Silver Spring). 2019 Jun;27(6):908-916. doi: 10.1002/oby.22454. PMID: 31119881.https://pubmed.ncbi.nlm.nih.gov/31119881/Protein EffectsWesterterp-Plantenga MS, Lemmens SG, Westerterp KR. Dietary protein - its role in satiety, energetics, weight loss and health. Br J Nutr. 2012 Aug;108 Suppl 2:S105-12. doi: 10.1017/S0007114512002589. PMID: 23107521.https://pubmed.ncbi.nlm.nih.gov/23107521/Cuenca-Sánchez M, Navas-Carrillo D, Orenes-Piñero E. Controversies surrounding high-protein diet intake: satiating effect and kidney and bone health. Adv Nutr. 2015 May 15;6(3):260-6. doi: 10.3945/an.114.007716. PMID: 25979491; PMCID: PMC4424780.https://pubmed.ncbi.nlm.nih.gov/25979491/Phillips SM, Chevalier S, Leidy HJ. Protein "requirements" beyond the RDA: implications for optimizing health. Appl Physiol Nutr Metab. 2016 May;41(5):565-72. doi: 10.1139/apnm-2015-0550. Epub 2016 Feb 9. PMID: 26960445.https://pubmed.ncbi.nlm.nih.gov/26960445/Non-exercise activity thermogenesisLevine JA. Non-exercise activity thermogenesis (NEAT). Best Pract Res Clin Endocrinol Metab. 2002 Dec;16(4):679-702. doi: 10.1053/beem.2002.0227. PMID: 12468415.https://pubmed.ncbi.nlm.nih.gov/30370831/Malaeb S, Perez-Leighton CE, Noble EE, Billington C. A "NEAT" Approach to Obesity Prevention in the Modern Work Environment. Workplace Health Saf. 2019 Mar;67(3):102-110. doi: 10.1177/2165079918790980. Epub 2018 Oct 29. PMID: 30370831.https://pubmed.ncbi.nlm.nih.gov/12468415/Hunger and ThirstAugustine V, Lee S, Oka Y. Neural Control and Modulation of Thirst, Sodium Appetite, and Hunger. Cell. 2020 Jan 9;180(1):25-32. doi: 10.1016/j.cell.2019.11.040. PMID: 31923398; PMCID: PMC7406138.https://pubmed.ncbi.nlm.nih.gov/31923398/Bray N. A taste for hunger and thirst. Nat Rev Neurosci. 2020 Nov;21(11):592-593. doi: 10.1038/s41583-020-00380-1. PMID: 32913320.https://pubmed.ncbi.nlm.nih.gov/32913320/Mattes RD. Hunger and thirst: issues in measurement and prediction of eating and drinking. Physiol Behav. 2010 Apr 26;100(1):22-32. doi: 10.1016/j.physbeh.2009.12.026. Epub 2010 Jan 11. PMID: 20060847; PMCID: PMC2849909.https://pubmed.ncbi.nlm.nih.gov/20060847/McKiernan F, Houchins JA, Mattes RD. Relationships between human thirst, hunger, drinking, and feeding. Physiol Behav. 2008 Aug 6;94(5):700-8. doi: 10.1016/j.physbeh.2008.04.007. Epub 2008 Apr 13. PMID: 18499200; PMCID: PMC2467458.https://pubmed.ncbi.nlm.nih.gov/18499200/McKiernan F, Hollis JH, McCabe GP, Mattes RD. Thirst-drinking, hunger-eating; tight coupling? J Am Diet Assoc. 2009 Mar;109(3):486-90. doi: 10.1016/j.jada.2008.11.027. PMID: 19248867; PMCID: PMC2671201.https://pubmed.ncbi.nlm.nih.gov/19248867/ 

Calcula tus calorías, proteínas, grasas y carbohidratos según tu objetivo, totalmente GRATIS 👉 https://fullmusculo.com/calculadora-de-calorias/ Únete a nuestra comunidad fitness y recibe cada semana emails con los mejores tips en entrenamiento, nutrición, psicología y suplementación, siempre basado en la última evidencia científica. 👉 https://fullmusculo.com Síguenos también en instagram donde estamos aportando contenido cada día. 👉 https://www.instagram.com/fullmusculo/ Y sigue nuestro Podcast en Spotify donde puedes escuchar esta y muchas entrevistas más con los mejores profesionales cada semana. 👉 https://open.spotify.com/show/3Zb1EtDKEPX50TyKGqfD3R Referencias bibliográficas 🔬 Beaulieu, K., et al., Homeostatic and non-homeostatic appetite control along the spectrum of physical activity levels: An updated perspective. Physiology & Behavior, 2017.

Keno Juechems is a Junior Research Fellow at St John's College in Oxford. He studies how humans make decisions, using computational modelling, behavioural tasks, and fMRI. In this conversation, we talk about his papers  "Optimal utility and probability functions for agents with finite computational precision" and  "Where does value come from?", and various related topics.BJKS Podcast is a podcast about neuroscience, psychology, and anything vaguely related, hosted by Benjamin James Kuper-Smith. New episodes every Friday. You can find the podcast on all podcasting platforms (e.g., Spotify, Apple/Google Podcasts, etc.).Timestamps0:00:05: Where does the name "Keno" come from?0:01:47: How Keno got into his current research area0:14:09: Start discussing Keno's paper "Optimal utility and probability functions for agents with finite computational precision"0:26:46: Rationality and optimality0:38:58: Losses, gains, and how much does a paper need to include?0:51:04: Start discussing Keno's paper "Where does value come from?"1:10:28: How does a PhD student learn all this stuff?1:19:56: Resources for learning behavioural economics and reinforcement learning1:25:42: What's next for Keno Juechems?Podcast linksWebsite: https://bjks.buzzsprout.com/Twitter: https://twitter.com/BjksPodcastKeno's linksWebsite: https://www.sjc.ox.ac.uk/discover/people/keno-juchems/Google Scholar: https://scholar.google.de/citations?user=tereY1oAAAAJTwitter: https://twitter.com/kjuechemsBen's linksWebsite: www.bjks.blog/Google Scholar: https://scholar.google.co.uk/citations?user=-nWNfvcAAAAJTwitter:  https://twitter.com/bjks_tweetsReferencesJuechems, K., & Summerfield, C. (2019). Where does value come from?. Trends in cognitive sciences.Juechems, K., Balaguer, J., Spitzer, B., & Summerfield, C. (2021). Optimal utility and probability functions for agents with finite computational precision. Proceedings of the National Academy of Sciences.Kahneman, D., & Tversky, A. (1979). Prospect theory: An analysis of decision under risk. Econometrica.Keramati, M., & Gutkin, B. (2014). Homeostatic reinforcement learning for integrating reward collection and physiological stability. Elife.Lewis, M. (2016). The undoing project: A friendship that changed the world. Penguin UK.Sutton, R. S., & Barto, A. G. (2018). Reinforcement learning: An introduction. MIT press.Thaler, R. H. (2015). Misbehaving: The making of behavioral economics.Trepte, S., Reinecke, L., & Juechems, K. (2012). The social side of gaming: How playing online computer games creates online and offline social support. Computers in Human behavior.https://en.wikipedia.org/wiki/Indifference_curveDavid Silver's reinforcement learning course on YouTube: https://www.youtube.com/watch?v=2pWv7GOvuf0&list=PLqYmG7hTraZDM-OYHWgPebj2MfCFzFObQChris Summerfield's course How to Build a Brain: https://humaninformationprocessing.com/teaching/

Neste episódio: O que acontece quando uma personalidade famosa (e magra) aconselha as pessoas a fazer como ela e comer sorvete pois, afinal, a vida é curta para fazer low-carb e comer alface? Artigo da semana - Diets Varying in Carbohydrate Content Differentially Alter Brain Activity in Homeostatic and Reward Regions in Adults | The Journal of Nutrition | Oxford Academic (oup.com) - diferentes alimentos têm diferentes impactos sobre o centro do prazer e recompensa no cérebro. Inscreva-se e siga esse podcast para não perder nenhum episódio (e deixe 5 estrelinhas) ;-) Conheça também o Podcurso Low-Carb da Teoria à Prática em http://drsouto.com.br/podcurso

Please support this podcast by checking out our sponsor: - Strength Coach Network: https://strengthcoachnetwork.com/upside/?orid=15781 to get 50% off your first month GUEST: Mike T. Nelson, PhD, MSME, CSCS, CISSN, is a research fanatic who specializes in metabolic flexibility and heart rate variability, as well as an online trainer, adjunct professor, faculty member at the Carrick Institute, presenter, creator of the Flex Diet Cert, kiteboarder, and (somewhat incongruously) heavy-metal enthusiast. The techniques he's developed, and the results Mike gets for his clients have been featured in international magazines, in scientific publications, and on websites across the globe. In his free time, he enjoys spending time with his wife, lifting odd objects, reading research, and kiteboarding as much as possible. You can find out more about him at his website at www.miketnelson.com EPISODE LINKS: ► IG: https://www.instagram.com/drmiketnelson ► Twitter: https://twitter.com/miketnelson ► Website: https://flexdiet.com ► Full Videl Episode: https://youtu.be/LRQ3j79JvQ4 PODCAST INFO: ► Podcast website: https://upsidestrength.podbean.com/ ► Apple Podcasts: http://apple.co/3mroiB4 ► Spotify: http://spoti.fi/34jJtyX PODCAST PLAYLISTS: ► Full episodes playlist: http://bit.ly/3oSCkxe ► English Clips playlist: http://bit.ly/3gRmAry ► French Clips playlist: http://bit.ly/2K1IoVK TOPICS: 0:00 - Intro 1:01 - Start 1:07 - Background 2:09 - Moxy Monitor 29:46 - PNOE Analytics 39:37 - Respiratory Limitations & Training 55:57 - Homeostatic Regulators 1:03:22 INTRO 1:03:42 - Physiologic Flexibility 1:10:03 - Current Interests CONNECT: ► Subscribe for more videos here: http://bit.ly/1Xgr5y5 ► Twitter: https://twitter.com/seanseale ► LinkedIn: https://www.linkedin.com/in/seanseale/ ► Facebook: https://www.facebook.com/upsidestrength ► Instagram: https://www.instagram.com/upsidestrength ► Tik Tok: https://vm.tiktok.com/ZSgNAPQF/ EQUIPMENT: ▶︎ Spirometer: http://ebay.to/2YCcSBj ▶︎ Idiag P-100: https://www.idiag.ch/en/idiag-p100-en/ (email me at info@upsidestrength.com for a 20% discount code) ▶︎ Moxy Monitor (email me at info@upsidestrength.com for a 20% discount code) DISCLAIMER:  ► These descriptions usually contain affiliate links. If you decide to purchase a product through one of them, I receive a small commission at no cost to you. I never endorse products that I have not personally used myself or not found to be beneficial in my life.

A fancy word for balance is homeostasis. It means to be "at ease". A body in this state experiences optimal health. Let's look at what looks like. --- Send in a voice message: https://anchor.fm/drjeni/message

www.kaiehnes.com Ep38 Living…Normal Hello and Welcome to the Way of the Emotional Warrior Podcast. My name is Kai Ehnes and today we will be answering the question of: How can one live this thing called normal?   So the main issue we need to look at is the notion of what is normal? You hear this all the time. Normal this or hey, that's not normal. Somewhere out there I think most people believe that there is a normal or point of reference. Then it is believed that the closer you are to it the more normal or right you are in your thoughts and actions. If this were really all so simple why is normal such an elusive mistress? When I was little I never fully understood what this normal life actually was. Think about it, we are born, not really by choice, (well…mostly) into a family we didn't have a choice over, (mostly) and into a time and place outside of our control. Talk about not having a center. On top of being cast into a life without an operator's manual, we are supposed to act normal, when essentially few people can agree on what that actually is or means? Let's look a bit deeper into normal. The Cambridge definition says that normal is ordinary or usual, the same as would be expected. So we can already see that normal is pretty bland, the same old same old. Sure it is consistent and that is good for a while but it will pretty quickly get challenged by novelty and variety. To me normal would be good as a point of reference but not really of value to living an authentic vivacious, dynamic life. One way to look at normal is through the lens of neuroscience. The term in this field for normal is homeostasis. This helps animals maintain stable internal and external environments with the best conditions for it to operate. So if we use normal and homeostasis interchangeably you can see that it is no longer bland.  Homeostatic balance means that you can have your own being interact with the world around you in the best overall fashion.  This is what I would call a sustainable state of being. IS there more? According to Donald Riggles, our brains process a staggering 11 million bits of information per second, of that 50 bits per second are conscious. Neuroscience shows that survival and pleasure reactions are the main task of our unconscious mind and are directly involved with our health and well being. Consider this for a second. Our health and well being are being handled by our unconscious mind and mainly work on our interaction with pleasure and pain. There is a secretion of adrenaline, dopamine and oxytocin, all which maintain our balanced state. These bookends or guardrails keep us in check and balanced. So…tieing this together, Our brains are hard wired to consistently bring us back into a state of balance which means that we have an internal sense of normal. We know what normal is at all times. However, with our lifestyles, we spend a lot of time and effort on being out of balance, consider diet and exercise. So if we know what normal is internally and by design, why do we have such a hard time with it? Let's look at this from the perspective of an Emotional Warrior. What is clear from this viewpoint is that the heart controls the show. Resilience and love are the tools for emotional balance and vibrational consciousness. This means that the Emotional Warrior spends their time actualizing their natural, authentic, normal state and then navigates their external world to find places and activities where that normalcy can be lived. Simply put, an Emotional Warrior lives an authentic heart based life on the inside and the outside. Confusion and chaos begin to fade away allowing for growth, fulfilment and actualization. Consider how wonderful this lived life is and can be. In the next episode we look at life within these guardrails. I look forward to seeing you there.   Support this podcast

Homeostatic chronic low stress results in low to moderate levels of CRF in the LC in association with enhanced Extra-Dimensional Shifting and optimal executive decision making. However, acute or chronic severe stress is linked to high levels of CRF in the LC and this may contribute to a shift from optimal executive function necessary for goal-directed behavior toward an iterative decision response. In healthy environments, this variable tonicity is a readout for adaptation when goal-oriented behavior is relaxed so that the individual uses pro-forma decisions even when novel environmental stimuli are encountered. During aging these pathways lose flexibility due to a decrease in executive decision making linked to the senescence phenotype that may impair neural circuitry via inflammation, over or under activation and lack of control over immune cell responses. J Neurosci. 2008 Nov 5; 28(45): 11517–11525. GeroScience. 2017 Feb; 39(1): 61–72. Neuroscience. 2017 Mar 14; 345: 12–26. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.02.365130v1?rss=1 Authors: Bhandari, A., Smith, J., Van Hook, M. Abstract: Within the nervous system, homeostatic mechanisms stabilize network activity following disruption by injury, disease, or degeneration. Vision loss and optic nerve injury in age-related diseases such as glaucoma might trigger homeostatic responses in direct retinal projection targets in the brain in adulthood. We tested this possibility using patch-clamp electrophysiology, optogenetics, and single-cell dendritic analysis to probe the effects of optic nerve injury and vision loss on dLGN thalamocortical (TC) relay neurons and their synaptic inputs following bilateral enucleation. Using vGlut2 immunostaining, we found that retinal axon terminals in the dLGN degenerated over several days post-enucleation, which corresponded with the loss of retinogeniculate (RG) synaptic function as assessed with optogenetic stimulation of ganglion cell axons in acute brain slices. Analysis of TC neuron dendritic structure from single-cell dye fills revealed a gradual loss of dendrites proximal to the soma, where TC neurons receive the bulk of RG inputs. Surprisingly, there was little change to the frequency of miniature post-synaptic currents (mEPSCs), even two weeks post-enucleation, although we did find an increase in the relative proportion of mEPSCs with slower kinetics, hinting at a possible enhancement of corticogeniculate input. Whole-cell current clamp recordings showed that enucleation enhanced TC neuron action potential firing and input resistance, consistent with homeostatic scaling of intrinsic neuronal excitability following perturbation of synaptic inputs. Our findings show that degeneration of the retinal axons/optic nerve and loss of RG synaptic inputs induces structural and functional changes in TC neurons consistent with compensatory homeostatic plasticity in the dLGN. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.02.363440v1?rss=1 Authors: Wieser, B. I., Pena de la Sancha, P., Schauer, S., Reicher, H., Sattler, W., Breinbauer, R., Schweiger, M., Espenshade, P. J., Zechner, R., Hoefler, G., Vesely, P. W. Abstract: Sterol Regulatory Element-Binding Protein-1c (SREBP-1c) is translated as an inactive precursor-protein that is proteolytically activated to promote fatty-acid (FA) biosynthesis, when unsaturated (u)FAs are scarce. During fasting, however, lipogenesis is low, and adipose-tissue lipolysis supplies the organism with FAs. Adipose TriGlyceride Lipase (ATGL) is the rate-limiting enzyme for lipolysis, and it preferentially hydrolyzes uFAs. Therefore, we hypothesized that ATGL-derived FAs may suppress the proteolytic activation of SREBP-1c in the liver. Here we show that (i) SREBP-1c is inactive during fasting but active after refeeding, (ii) uFA species liberated by ATGL suppress SREBP-1c activation in vitro, (iii) SREBP-1c is hyperactivated in livers of mice lacking ATGL, and (iv) pharmacological inhibition of ATGL selectively activates SREBP-1c in hepatocytes. Our findings highlight an ATGL/SREBP-1c axis, instrumental to coordinate lipogenesis and lipolysis, whose homeostatic regulation is crucial to avoid severe diseases including diabetes, cardiomyopathy, and even cancer. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.12.336883v1?rss=1 Authors: Yeates, C. J., Frank, C. A. Abstract: Synapses and circuits rely on homeostatic forms of regulation in order to transmit meaningful information. The Drosophila melanogaster neuromuscular junction (NMJ) is a well-studied synapse that shows robust homeostatic control of function. Most prior studies of homeostatic plasticity at the NMJ have centered on presynaptic homeostatic potentiation (PHP). PHP happens when postsynaptic muscle neurotransmitter receptors are impaired, triggering retrograde signaling that causes an increase in presynaptic neurotransmitter release. As a result, normal levels of evoked excitation are maintained. The counterpart to PHP at the NMJ is presynaptic homeostatic depression (PHD). Overexpression of the Drosophila vesicular glutamate transporter (VGlut) causes an increase in the amplitude of spontaneous events. PHD happens when the synapse responds to the challenge by decreasing quantal content during evoked neurotransmission, again, resulting in normal levels of postsynaptic excitation. We hypothesized that there may exist a class of molecules that affects both PHP and PHD. Impairment of any such molecule could hurt the ability of a synapse to respond to any significant homeostatic challenge. We conducted an electrophysiology-based screen for blocks of PHD. While we did not observe a block of PHD in the genetic conditions screened, we instead found loss-of-function conditions that led to excess depression, i.e., a substantial deficit in evoked amplitude when combined with VGlut overexpression. The conditions causing this phenotype included a double heterozygous loss-of-function condition for genes encoding the inositol trisphosphate receptor (IP3R, itpr) and ryanodine receptor (RyR). IP3Rs and RyRs gate calcium release from intracellular stores. Pharmacological agents targeting IP3R and RyR recapitulated the genetic losses of these factors, as did lowering calcium levels from other sources. Our data are consistent with the idea that some factors required for homeostatic potentiation are also required for the synapse to achieve appropriate levels of homeostatic depression. Loss of such factors may disorient compensatory plasticity signals. Copy rights belong to original authors. Visit the link for more info

Dr. Joon Yun is President and Managing Partner of Palo Alto Investors LP, a healthcare hedge fund founded in 1989. Board certified in radiology, Joon served on the clinical faculty at Stanford from 2000-2006. Joon has served on numerous boards, and he is currently a trustee of the Salk Institute. Joon is a member of the President's Circle of the National Academies of Sciences, Engineering, and Medicine. Joon has published dozens of patents and scientific articles. Joon and his wife Kimberly launched the $1 million Palo Alto Longevity Prize in 2013 to reverse the aging process and recently donated $2 million to launch the National Academy of Medicine Aging and Longevity Grand Challenge. Fun fact: Joon has been going to Burning Man consecutively for the past 18 years. Show Notes 00:03 - Dr. Joon: A quick biography 04:45 - The aging process 09:26 - The Fractal nature of biology and the plasticity of aging 11:10 - Homeostatic capacity defined 21:22 - Why we should (occasionally) eat junk food 22:19 - Regaining lost resilience 27:55 - The multidimensional nature of capacity building 34:10 - Psychological deconditioning 40:59 - Four-dimensional science and four-dimensional data 48:36 - Improve your health doing things you love 57:51 - How HRV is aiding studies of homeostatic capacity 1:01:12 - Conclusion

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.21.301325v1?rss=1 Authors: Cousins, J. N., Leong, R. L. F., Jamaluddin, S. A., Ng, A. S. C., Ong, J. L., Chee, M. W. L. Abstract: Daytime naps have been linked with enhanced memory encoding and consolidation. It remains unclear how a daily napping schedule impacts learning throughout the day, and whether these effects are the same for well-rested and sleep restricted individuals. We compared memory in 112 adolescents who underwent two simulated school weeks containing 8 or 6.5 hour sleep opportunities each day. Sleep episodes were nocturnal or split between nocturnal sleep and a 90-min afternoon nap, creating four experimental groups: 8h-continuous, 8h-split, 6.5h-continuous and 6.5h-split. Declarative memory was assessed with picture encoding and an educationally realistic factual knowledge task. Splitting sleep significantly enhanced afternoon picture encoding and factual knowledge under both 6.5h and 8h durations. Splitting sleep also significantly reduced slow-wave activity during nocturnal sleep, suggesting lower homeostatic sleep pressure during the day. There was no negative impact of the split sleep schedule on morning performance, despite a reduction in nocturnal sleep duration. These findings suggest that naps could be incorporated into a daily sleep schedule that provides sufficient sleep and benefits learning. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.16.297606v1?rss=1 Authors: Lu, H., Gallinaro, J. V., Normann, C., Rotter, S., Yalcin, I. Abstract: Synapse formation and network rewiring is key to build neural circuits during development and has been widely observed in adult brains. Maintaining neural activity with the help of synaptic plasticity is essential to enable normal brain function. The model of homeostatic structural plasticity (HSP) was proposed to reflect the homeostatic regulation of neural activity and explain structural changes seen after perturbations. However, the specific temporal profile of such plastic responses has not yet been elucidated in experiments. To address this issue, we combined computational modeling and mouse optogenetic stimulation experiments. Our model predicted that within 48h post-stimulation, neural activity returns to baseline, while the connectivity among stimulated neurons follows a very specific transient increase and decrease. To capture such dynamics experimentally in vivo, we activated the pyramidal neurons in the anterior cingulate cortex of mice and harvested their brains at 1.5h, 24h, and 48h post-stimulation. Cortical hyperactivity as demonstrated by robust c-Fos expression persisted up to 1.5h and decayed to baseline after 24h. However, spine density and spine head volume were increased at 24h and decreased at 48h. Synaptic proteins VGLUT1 and PSD-95 were also upregulated and downregulated at 24h and 48h, respectively, while the calmodulin-binding protein neurogranin was translocated from the soma to the dendrite. Additionally, lasting astrocyte reactivation and microglia proliferation were observed, suggesting a role of neuron-glia interaction. All this corroborates the interpretation of our experimental results in terms of homeostatic structural plasticity. Our results bring important insights of how external stimulation modulates synaptic plasticity and behaviors. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.02.276071v1?rss=1 Authors: Mukherjee, A., Singh, S. S., Ray, D., Raghunathan, P., Banerjee, A. Abstract: In daily lives, speech perception requires binding of spatiotemporally disjoint auditory and visual cues. On the other hand, functional segregation and integration are the two complementary mechanisms that capture brain information processing. Here, we demonstrate using fMRI recordings that subjective perceptual experience of multisensory speech stimuli is dependent on a homeostatic balance of segregation and integration mechanisms. Previous reports conceptualized posterior superior temporal sulcus as the key brain region for binding signals from multiple sensory streams. However, we report an enhancement of segregated information processing in distributed brain regions, defined as the perceptual binding network. The seed-based whole brain functional connectivity of each node in this network was anti-correlated with higher propensity for illusory perception. Interestingly, the perceptual binding network was anti-correlated with other intrinsic brain networks, such as dorsal attention and default mode networks during cross-modal perception. The pattern disappeared for people who rarely reported the illusory perception, further strengthening the hypothesis of homeostatic balance. The cognitive theories of Bayesian causal inference and predictive coding hypothesis could explain the balance of segregative and integrative mechanisms during cross-modal perception. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.31.274993v1?rss=1 Authors: Colameo, D., Soutschek, M., Rajman, M., Bicker, S., von Ziegler, L., Bohacek, J., Germain, P.-L., Dieterich, C., Schratt, G. Abstract: Synaptic scaling is a form of homeostatic plasticity which allows neurons to adjust their action potential firing rate in response to chronic alterations in neural activity. Synaptic scaling requires profound changes in gene expression, but the relative contribution of local and cell-wide mechanisms is controversial. Here we performed a comprehensive multi-omics characterization of the somatic and process compartments of primary rat hippocampal neurons during synaptic scaling. Thereby, we uncovered both highly compartment-specific and correlated changes in the neuronal transcriptome and proteome. Whereas downregulation of crucial regulators of neuronal excitability occurred primarily in the somatic compartment, structural components of excitatory postsynapses were mostly downregulated in processes. Motif analysis further suggests an important role for trans-acting post-transcriptional regulators, including RNA-binding proteins and microRNAs, in the local regulation of the corresponding mRNAs. Altogether, our study indicates that compartmentalized gene expression changes are widespread in synaptic scaling and might co-exist with neuron-wide mechanisms to allow synaptic computation and homeostasis. Copy rights belong to original authors. Visit the link for more info

The Gary Null Show is here to inform you on the best news in health, healing, the environment. Multivitamin, mineral supplement linked to less-severe, shorter-lasting illness symptoms Oregon State University, August 18, 2020   Older adults who took a daily multivitamin and mineral supplement with zinc and high amounts of vitamin C in a 12-week study experienced sickness for shorter periods and with less severe symptoms than counterparts in a control group receiving a placebo. The findings by Oregon State University researchers were published in the journal Nutrients. The research by scientists at OSU's Linus Pauling Institute involved 42 healthy people ages 55 to 75 and was designed to measure the supplement's effects on certain immune system indicators. It also looked at bloodstream levels of zinc and vitamins C and D while taking the supplement, as these micronutrients are important for proper immune function. The immune indicators, including white blood cells' ability to kill incoming pathogens, were unaltered in the group receiving the supplement.  The multivitamin group showedimproved vitamin C and zinc status in the blood. Most intriguingly, illness symptoms reported by this group were less severe and went away faster than those experienced by the placebo group.  The same percentage of participants in each group reported symptoms, but days of sickness in the supplement group averaged fewer than three compared to more than six for the placebo group.  "The observed illness differences were striking," said corresponding author Adrian Gombart, professor of biochemistry and biophysics in the OSU College of Science and a principal investigator at the Linus Pauling Institute. "While the study was limited to self-reported illness data and we did not design the study to answer this question, the observed differences suggest that additional larger studies designed for these outcomes are warranted - and, frankly, overdue." As people get older, the risk of vitamin and mineral deficiencies that contribute to age-related immune system deficiencies rises. Across the United States, Canada and Europe, research suggests more than one-third of older adults are deficient in at least one micronutrient, often more than one. "That likely contributes to a decline in the immune system, most often characterized by increased levels of inflammation, reduced innate immune function and reduced T-cell function," Gombart said. "Since multiple nutrients support immune function, older adults often benefit from multivitamin and mineral supplements. These are readily available, inexpensive and generally regarded as safe." The multivitamin supplement used in the study focused on vitamins and minerals typically thought to help immunity. It contained 700 micrograms of vitamin A; 400 international units of vitamin D; 45 milligrams of vitamin E; 6.6 milligrams of vitamin B6; 400 micrograms of folate; 9.6 micrograms of vitamin B12; 1,000 milligrams of vitamin C; 5 milligrams of iron; 0.9 milligrams of copper; 10 milligrams of zinc; and 110 micrograms of selenium. "Supplementation was associated with significantly increased circulating levels of zinc and vitamin C, and with illness symptoms that were less severe and shorter lasting," Gombart said. "This supports findings that stretch back decades, even to the days of Linus Pauling's work with vitamin C. Our results suggest more and better designed research studies are needed to explore the positive role multivitamin and mineral supplementation might play in bolstering the immune system of older adults."     Honey found to be a better treatment for upper respiratory tract infections than traditional remedies Oxford University, August 19, 2020 A trio of researchers at Oxford University has found that honey is a better treatment for upper respiratory tract infections (URTIs) than traditional remedies. In their paper published in BMJ Evidence-based Medicine, Hibatullah Abuelgasim, Charlotte Albury, and Joseph Lee describe their study of the results of multiple clinical trials that involved testing of treatments for upper respiratory tract infections (URTIs) and what they learned from the data. Over the past several years, the medical community has grown alarmed as bacteria have developed resistance to antibacterial agents. Some studies have found that over-prescription of such remedies is hastening the pace. Of particular concern are antibacterial prescriptions written for maladies that they are not likely to help, simply due to demands from patients. One such case is often URTIs, the vast majority of which are caused by viruses, not bacteria. Because of such cases, scientists have been looking for other remedies for these infections, and one therapy in particular has begun to stand out: honey. Anecdotal evidence has suggested that honey can be used to treat colds in general and coughs in particular—people have been using it as a therapy for thousands of years. In this new effort, the researchers looked at the results of multiple clinical trials testing the effectiveness of therapies against URTIs. In all, the team looked at data from 14 clinical trials involving 1,761 patients. In analyzing the data from all of the trials combined, the researchers found that the trials had included studies of virtually all of the traditional remedies such as over-the-counter cold and sinus medicines as well as antibiotics—and honey. They found that honey proved to be the best therapy among all of those tested. In addition to proving more effective in treating coughing (36 percent better at reducing the amount of coughing and 44 percent better at reducing coughing severity), it also led to a reduction in average duration of infection by two days. The researchers note that the reason honey works as a treatment for URTIs is because it contains hydrogen peroxide—a known bacteria killer—which also makes it useful as a topical treatment for cuts and scrapes. Honey is also of the right consistency—its thickness works to coat the mouth and throat, soothing irritation.   High intensity physical activity in early life could lead to stronger bones in adulthood University of Bristol (UK), August 17 2020   The research, which analysed data from 2,569 participants of the Children of the 90s health study, found that more time spent doing moderate-to-vigorous intensity physical activity (MVPA) from age 12 years was associated with stronger hips at age 25 years, whereas time spent in light intensity activity was less clearly associated with adult hip strength. Peak bone mass occurs in young adulthood and is considered to be a marker of the risk of fracture and osteoporosis in later life. Hip fractures make up a large proportion of the osteoporosis disease burden.  Researchers looked at data from healthy individuals who had physical activity measured up to 4 times using accelerometers worn as part of clinical assessments at age 12, 14, 16 and 25 years. This is a device that measures a person's movement for the whole time they wear it. Researchers also found evidence to suggest that adolescent MVPA was more important than MVPA in adulthood, and that MVPA in early adolescence may be more important than in later adolescence. There was also some evidence that higher impact activity (consistent with jumping; assessed once in a subsample in late adolescence using custom accelerometer) was related to stronger hips at age 25. Dr Ahmed Elhakeem, lead author and Senior Research Associate in Epidemiology, said: "The unique availability of repeated accelerometer assessments over many years beginning at age 12 within the Children of the 90s cohort, allowed us to describe the trajectory of time spent in different physical activity intensities through early life and to examine how this might relate to adult hip strength. The results highlight adolescence as a potentially important period for bone development through high intensity exercise, which could benefit future bone health and prevent osteoporosis in later life. We have also confirmed other studies showing that levels of MVPA decline through adolescence. Our findings show it is really important to support young people to remain active at this age"  Francesca Thompson, Clinical and Operations Director at the Royal Osteoporosis Society (ROS), said: "The ROS is working closely at the moment with Public Health England to review the importance of exercise for bone health in children. The findings from this study are welcome as they provide further evidence that children need to be doing moderate to vigorous intensity physical activity during their early adolescence to maximise bone strength in later life and reduce the risk of painful fractures. Supporting and encouraging young people to be more physically active needs to be a priority for bone as well as general health."   Magnesium supplementation associated with improved vitamin D status in postmenopausal women University of Granada (Spain), August 17, 2020   According to news originating from Granada, Spain,  the research stated, “Menopause is a stage of hormonal imbalance in women which, in addition to other physiopathological consequences, poses a risk of deficiency of key micronutrients such as magnesium and vitamin D.” Our news editors obtained a quote from the research from University of Granada: “A study was made of the influence of a magnesium intervention upon vitamin D status in a postmenopausal population from the province of Granada (Spain). Fifty-two healthy postmenopausal women between 44-76 years of age were included. Two randomized groups-placebo and magnesium (500 mg/day)-were treated during eight weeks. Nutrient intake was assessed using questionnaires based on 72-h recall. Vitamin D was analyzed by liquid chromatography-tandem mass spectrometry. Baseline vitamin D proved deficient in over 80% of the subjects.” According to the news editors, the research concluded: “The administration of magnesium resulted in significantly increased vitamin D levels in the intervention group versus the controls (* * p* * < 0.05). Magnesium supplementation improved vitamin D status in the studied postmenopausal women.”     High fructose diet in pregnancy impacts metabolism of offspring, study finds University of Otago (New Zealand), August 18, 2020   An increased level of fructose intake during pregnancy can cause significant changes in maternal metabolic function and milk composition and alter the metabolism of their offspring, researchers from the University of Otago, Wellington, have found. The research, which was led by Dr Clint Gray, a Research Fellow in the Department of Paediatrics and Child Health, found increasing the fructose in the diets of female guinea pigs led to highly significant and consistent changes in the free fatty acids circulating in the blood of their offspring. This was despite the offspring consuming no fructose themselves.  The research is published in the international journal Frontiers in Endocrinology.  First author, PhD student Erin Smith, says "previous research has shown poor quality nutrition during pregnancy can predispose offspring to long-term consequences, including the development of obesity, diabetes and cardiovascular disease later in life".  "However, there has been a lack of data examining the impact of increased fructose intake before and during pregnancy and subsequent adverse effects on lactation, foetal development and offspring metabolic function." The two experimental groups were fed either a control diet or a fructose diet prior to and during pregnancy. The fructose group was given supplementary fructose water to replicate increased sugar-sweetened beverage intake 60 days prior to mating and until the delivery of their offspring. Fructose made up 16.5 per cent of their diets, closely resembling the average human consumption of fructose/sugar in Western countries, which is estimated at about 14 per cent of average daily caloric intake.  "We found fructose had a significant impact on a pregnant females' metabolic status and the free fatty acid content of their milk. We also provide the first evidence that offspring born from fructose-fed mothers display a very specific pattern of increased free fatty acids and altered lipid metabolism that persists throughout early life." Ms Smith says it is well known that increased levels of circulating free fatty acids increases the risk of obesity, insulin resistance, type 2 diabetes and cardiovascular disease - with increased fatty acid synthesis shown to occur following fructose consumption. She says the evidence suggests suboptimal maternal diets, such as diets high in fructose and refined sugars, may be contributing to the rise in metabolic diseases in humans observed during the past 40 to 50 years. "Our study emphasises the importance of limiting added refined fructose, such as sugar-sweetened beverages, and striving for a more nutritionally balanced diet in women prior to and during pregnancy and lactation."       Sleep makes relearning faster and longer-lasting University of Lyon (France). August 14, 2020   Getting some sleep in between study sessions may make it easier to recall what you studied and relearn what you've forgotten, even 6 months later, according to new findings from Psychological Science, a journal of the Association for Psychological Science.   "Our results suggest that interleaving sleep between practice sessions leads to a twofold advantage, reducing the time spent relearning and ensuring a much better long-term retention than practice alone," explains psychological scientist Stephanie Mazza of the University of Lyon. "Previous research suggested that sleeping after learning is definitely a good strategy, but now we show that sleeping between two learning sessions greatly improves such a strategy."   While studies have shown that both repeated practice and sleep can help improve memory, there is little research investigating how repetition and sleep influence memory when they are combined. Mazza and colleagues hypothesized that sleeping in between study sessions might make the relearning process more efficient, reducing the effort needed to commit information to memory.   A total of 40 French adults were randomly assigned to either a "sleep" group or a "wake" group. At the first session, all participants were presented with 16 French-Swahili word pairs in random order. After studying a pair for 7 seconds, the Swahili word appeared and participants were prompted to type the French translation. The correct word pair was then shown for 4 seconds. Any words that were not correctly translated were presented again, until each word pair had been correctly translated.   Twelve hours after the initial session, the participants completed the recall task again, practicing the whole list of words until all 16 words were correctly translated.   Importantly, some participants completed the first session in the morning and the second session in the evening of the same day ("wake" group); others completed the first session in the evening, slept, and completed the second session the following morning ("sleep" group).   In the first session, the two groups showed no difference in how many words they could initially recall or in the number of trials they needed to be able to remember all 16 word pairs.   But after 12 hours, the data told another story: Participants who had slept between sessions recalled about 10 of the 16 words, on average, while those who hadn't slept recalled only about 7.5 words. And when it came to relearning, those who had slept needed only about 3 trials to be able to recall all 16 words, while those who had stayed awake needed about 6 trials.   Ultimately, both groups were able to learn all 16 word pairs, but sleeping in between sessions seemed to allow participants to do so in less time and with less effort.   "Memories that were not explicitly accessible at the beginning of relearning appeared to have been transformed by sleep in some way," says Mazza. "Such transformation allowed subjects to re-encode information faster and to save time during the relearning session."   The memory boost that participants got from sleeping between sessions seemed to last over time. Follow-up data showed that participants in the sleep group outperformed their peers on the recall test 1 week later. The sleep group showed very little forgetting, recalling about 15 word pairs, compared to the wake group, who were able to recall about 11 word pairs. This benefit was still noticeable 6 months later.   The benefits of sleep could not be ascribed to participants' sleep quality or sleepiness, or to their short-term or long-term memory capacity, as the two groups showed no differences on these measures.   The results suggest that alternating study sessions with sleep might be an easy and effective way to remember information over longer periods of time with less study, Mazza and colleagues conclude.       Meta-analysis adds evidence to chromium supplementation's glucose control benefits in diabetics Lorestan University of Medical Sciences (Iran), August 15, 2020   A systematic review and meta-analysis published on July 27, 2020 in Pharmacological Research found reductions in fasting plasma glucose, insulin, hemoglobin A1c (HbA1c, a marker of long term glucose control) and insulin resistance in men and women with type 2 diabetes who supplemented with the mineral chromium.  For their analysis, Omid Asbaghi of Lorestan University of Medical Sciences and colleagues selected 23 randomized, controlled trials that evaluated the effects of supplementing with chromium on various glycemic control indexes. Doses used in the studies ranged between 50 micrograms (mcg) and 1,000 mcg per day consumed from four to 25 weeks. Eleven of the trials evaluated a chromium dosage within a 400 to 600 mcg range.  Analysis of 22 trials that reported fasting plasma glucose levels concluded that chromium supplementation was associated with an average reduction of 19.0 milligrams per deciliter (mg/dL) in comparison with the placebo. Trials of at least 12 weeks duration were associated with a far greater average decrease of 58.74 mg/dL in association with chromium.  Of the 14 trials that reported insulin levels, levels declined by an average of 1.7784 µIU/mL among subjects who received chromium compared to the placebo, with trials that lasted 12 weeks or longer associated with a decrease of 3.47 µIU/mL.  For the 22 trials that reported HbA1c, supplementation with chromium was associated with an average decrease of 0.71%, which improved to a significant 1.70% reduction when trials of 12 weeks duration or more were examined. Homeostatic model assessment for insulin resistance (HOMA-IR) also decreased significantly among participants who received chromium.  The authors observed that chromium plays a role in carbohydrate and lipid metabolism and may enhance insulin sensitivity. Other nutrients that have been associated with a lower risk of type 2 diabetes include vitamins A, C, D and E, beta-carotene, calcium, magnesium, potassium and zinc. “Present systematic review and meta-analysis of all available published randomized trials up to 2020 found a significant reduction in all glycemic control indices such as fasting plasma glucose, insulin, HbA1c and HOMA-IR levels after chromium supplementation,” they wrote. “Furthermore, long term intervention contributed to greater reduction of all mentioned indices.” “The results of the current meta‐analysis study might support the use of chromium supplementation for the improvement of glycemic control indices in T2DM patients,” they concluded.       Mangiferin: The Health-Boosting Antioxidant in Mangos GreenMedInfo, August 12th 2020    Mangiferin, a polyphenol found in mango fruit and plant extracts, possesses potent antioxidant and anti-inflammatory properties. Mangiferin has been shown to have beneficial effects on gastrointestinal health, Type 2 diabetes and cardiovascular health, and may have anticancer properties Mango, a type of juicy stone fruit native to eastern Asia and India, is rich in omega-3 and omega-6 fatty acids, fiber, antioxidants, micronutrients and minerals, and a unique polyphenol called mangiferin.[i] While mango itself has long been touted for its health benefits, researchers are becoming increasingly interested in mangiferin, which can be found in the leaves, fruit, stone, kernel and stems of the mango plant.[ii] Studies show that mangiferin extracts may have beneficial effects on lifestyle-related disorders and degenerative diseases, and researchers are eager to understand and utilize this potent polyphenol. Antioxidant and Anti-Inflammatory Potential of Mangiferin Mangiferin is a powerful antioxidant that modulates glucose metabolism and shows enhanced antioxidant capabilities in both inflammatory and pro-inflammatory conditions.[iii] Mangiferin antioxidants have also been shown to protect against liver damage and lower peroxidation in human peripheral blood lymphocytes, and mangiferin may have radioprotective properties thanks to its ability to suppress free radicals in cells.[iv],[v] Additionally, mangiferin's anti-inflammatory benefits have been demonstrated in both the liver and heart, and researchers have discovered that mangiferin can protect against lipid peroxidation and oxidative stress by up-regulating the expression of Nrf2, a transcription factor responsible for the regulation of protective antioxidants and detoxification responses.[vi],[vii] Mangiferin's anti-inflammatory effects have also been demonstrated in the lungs, where it can improve acute lung injury by reducing systemic and pulmonary inflammationresponses.[viii] Overall, mangiferin's anti-inflammatory properties have been demonstrated to reduce both macro and microscopic damage in various organs and tissues, making it a potential preventative therapy for a variety of disorders.[ix] Many of the benefits of mangiferin come from these strong antioxidant and anti-inflammatory properties. Researched benefits of mangiferin include: Mangiferin Extract May Protect Against Diabetes More than 80% of all diabetes cases are Type 2, which is associated with a lowered ability to increase glucose utilization in skeletal muscle tissue and adipose tissue.[x] This decrease in glucose metabolism and increased insulin increases the risk for disorders like cardiovascular disease, fatty liver and renal diseases.[xi] In one study, researchers demonstrated that mangiferin extract significantly reduced kidney weight while enhancing enzymatic activity and protein expression after just nine weeks.[xii] Other studies have shown that mangiferin extract can also reduce low-density lipoprotein (LDL) cholesterol and improve oral-glucose tolerance after just 28 days.[xiii] Mangiferin Boosts Gastrointestinal Health Mangiferin has gastroprotective effects, leading researchers to believe it could be a useful therapeutic measure against gastric complications including diarrhea, abdominal pain, weight loss and anemia associated with Crohn's disease and ulcerative colitis.[xiv] These effects are likely due to mangiferin's antioxidant and anti-inflammatory properties, which both contribute to the development of gastrointestinal disorders.[xv] In other studies, researchers have found that mangiferin improves postoperative ileus, a short-term disturbance of gastrointestinal motility after surgery.[xvi] Mangiferin improves intestinal transit by reducing the intestinal inflammatory response and decreasing pro-inflammatory cytokine levels in the plasma, improving gastrointestinal transit in both normal and constipated subjects.[xvii],[xviii] Mangiferin Has Anticancer Properties Researchers believe that one root cause of carcinogenesis is oxidative stress and have long searched for natural, polyphenolic antioxidant compounds that could mediate oxidative damage in the body. One study found that mangiferin's antioxidant capabilities may stall the progression of carcinogenesis and induce apoptosis (cell death) on cancer cells.[xix] Mangiferin is demonstrated to have protective effects against several cancers, including breast, colon, neural, skin and cervical cancers, by lowering oxidative stress and suppressing DNA damage in cells in various studies.[xx] Mangiferin Has Immunomodulatory Properties Mangiferin's strong immunomodulatory characteristics come from its ability to both reduce oxidative stress in lymphocytes, neutrophils and macrophages, and also enhance the number and activity of immune cells in your body.[xxi],[xxii] Additionally, mangiferin inhibits lipid peroxidation, which researchers believe may account for the reduction of radiation-induced DNA damage to immune cells and explain mangiferin's strong immune-stimulating and anticancer effects.[xxiii] Mangiferin Protects Against Cardiovascular Disease Mangiferin may play a significant cardiovascular-protective role by decreasing fatty acids, cholesterol and triglycerides and decreasing the inflammatory process in heart tissue.[xxiv] Mangiferin treatment is also shown to increase enzymatic activity and reduce the formation of lipid peroxides, which researchers use as a marker for cardiovascular disease risk and vascular cognitive impairment disorders.[xxv] Given that mangiferin exhibits little to no toxicity and has anti-inflammatory and antioxidant benefits, there is strong evidence that mangiferin can be used as an alternative or preventive therapy against a variety of illnesses.[xxvi] However, it has a low water solubility and oral bioavailability and researchers must find an effective dosage and enhance its absorption rate before it can effectively be used in clinical settings.  

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.04.236042v1?rss=1 Authors: Kaleb, K., Pedrosa, V., Clopath, C. Abstract: Despite ongoing experiential change, neural activity maintains remarkable stability. Such stability is thought to be mediated by homeostatic plasticity and is deemed to be critical for normal neural function. However, what aspect of neural activity does homeostatic plasticity conserve, and how it still maintains the exibility necessary for learning and memory, is not fully understood. Homeostatic plasticity is often studied in the context of neuron-centered control, where the deviations from the target activity for each individual neuron are suppressed. However, experimental studies suggest that there are additional, network-centered mechanisms. These may act through the inhibitory neurons, due to their dense network connectivity. Here we use a computational framework to study a potential mechanism for such homeostasis, using experimentally inspired, input-dependent inhibitory plasticity (IDIP). In a hippocampal CA1 spiking model, we show that IDIP in combination with place tuned input can explain the formation of active and silent place cells, as well as place cells remapping following optogenetic silencing of active place cells. Furthermore, we show that IDIP can also stabilise recurrent network dynamics, as well as preserve network firing rate heterogeneity and stimulus representation. Interestingly, in an associative memory task, IDIP facilitates persistent activity after memory encoding, in line with some experimental data. Hence, the establishment of global network balance with IDIP has diverse functional implications and may be able to explain experimental phenomena across different brain areas. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.03.233833v1?rss=1 Authors: Luque, N. R., Naveros, F., Ros, E., Arleo, A. Abstract: The vestibulo-ocular reflex (VOR) stabilises vision during head motion. Age-related structural changes predict a linear VOR decay, whereas epidemiological data show a non-linear temporal profile. Here, we model cerebellar-dependent VOR adaptation to link structural and functional changes throughout ageing. We posit that three neurosynaptic factors codetermine VOR ageing patterns: electrical coupling between inferior olive neurons, intrinsic plasticity at Purkinje cell synapses, and long-term spike timing dependent plasticity at parallel fibre - Purkinje cell synapses as well as mossy fibre - medial vestibular nuclei synapses. Our cross-sectional simulations show that long-term plasticity acts as a global homeostatic mechanism mediating the non-linear temporal profile of VOR. Our results also suggest that intrinsic plasticity at Purkinje cells acts as a local homeostatic mechanism sustaining VOR at old ages. Importantly, longitudinal simulations show that residual fibres coding for the peak and trough of the VOR cycle constitute a predictive hallmark of VOR ageing trajectories. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.21.213660v1?rss=1 Authors: Schubert, F., Gros, C. Abstract: Recurrent cortical network dynamics plays a crucial role for sequential information processing in the brain. While the theoretical framework of reservoir computing provides a conceptual basis for the understanding of recurrent neural computation, it often requires manual adjustments of global network parameters, in particular of the spectral radius of the recurrent synaptic weight matrix. Being a mathematical and relatively complex quantity, the spectral radius is not readily accessible to biological neural networks, which generally adhere to the principle that information about the network state should either be encoded in local intrinsic dynamical quantities (e.g. membrane potentials), or transmitted via synaptic connectivity. We present two synaptic scaling rules for echo state networks that solely rely on locally accessible variables. Both rules work online, in the presence of a continuous stream of input signals. The first rule, termed flow control, is based on a local comparison between the mean squared recurrent membrane potential and the mean squared activity of the neuron itself. It is derived from a global scaling condition on the dynamic flow of neural activities and requires the separability of external and recurrent input currents. We gained further insight into the adaptation dynamics of flow control by using a mean field approximation on the variances of neural activities that allowed us to describe the interplay between network activity and adaptation as a two-dimensional dynamical system. The second rule that we considered, variance control, directly regulates the variance of neural activities by locally scaling the recurrent synaptic weights. The target set point of this homeostatic mechanism is dynamically determined as a function of the variance of the locally measured external input. This functional relation was derived from the same mean-field approach that was used to describe the approximate dynamics of flow control. The effectiveness of the presented mechanisms was tested numerically using different external input protocols. The network performance after adaptation was evaluated by training the network to perform a time delayed XOR operation on binary sequences. As our main result, we found that flow control can reliably regulate the spectral radius under different input statistics, but precise tuning is negatively affected by interneural correlations. Furthermore, flow control showed a consistent task performance over a wide range of input strengths/variances. Variance control, on the other side, did not yield the desired spectral radii with the same precision. Moreover, task performance was less consistent across different input strengths. Given the better performance and simpler mathematical form of flow control, we concluded that a local control of the spectral radius via an implicit adaptation scheme is a realistic alternative to approaches using classical "set point" homeostatic feedback controls of neural firing. Copy rights belong to original authors. Visit the link for more info

In this conversation I talk with Tim Archer. Tim is a former Group Captain, he held a number of senior appointments in the RAF during which time he gained an MA in Leadership Studies from the Centre for Leadership Studies at Exeter University, a Post Grad Certificate in Executive Coaching from Lancaster University Business School and was awarded a full-time 12-month Fellowship back at the Centre for Leadership Studies. After a spell as Director Public Sector at the Leadership Trust in the UK, he moved to the United Arab Emirates for 8 years where he was a government advisor during which time he developed, designed and taught experiential leadership development and coaching programmes. He currently works for Cardiff University developing their leadership modules for the MSc in Public Health. We have a wide ranging conversation that touches on: The definition of leadership Mission command - military doctrine (what to do, not how to do it - no disseminated responsibility) myth of military leadership - Constructive decent Vs destructive concept The OODA loop (Observe, Orient, Decide, Act) Leadership Vs Management (Kotter) Trust and cohesion – Peak rapport Homeostatic leadership Compassionate Leadership Situational leadership Leadership in conflict Leader as a coach Systems leadership - NHS Model - leading when not in charge I hope you enjoy this episode with a fascinating guest and friend.

In this conversation I talk with Tim Archer. Tim is a former Group Captain, he held a number of senior appointments in the RAF during which time he gained an MA in Leadership Studies from the Centre for Leadership Studies at Exeter University, a Post Grad Certificate in Executive Coaching from Lancaster University Business School and was awarded a full-time 12-month Fellowship back at the Centre for Leadership Studies. After a spell as Director Public Sector at the Leadership Trust in the UK, he moved to the United Arab Emirates for 8 years where he was a government advisor during which time he developed, designed and taught experiential leadership development and coaching programmes. He currently works for Cardiff University developing their leadership modules for the MSc in Public Health. We have a wide ranging conversation that touches on: The definition of leadership Mission command - military doctrine (what to do, not how to do it - no disseminated responsibility) myth of military leadership - Constructive decent Vs destructive concept The OODA loop (Observe, Orient, Decide, Act) Leadership Vs Management (Kotter) Trust and cohesion – Peak rapport Homeostatic leadership Compassionate Leadership Situational leadership Leadership in conflict Leader as a coach Systems leadership - NHS Model - leading when not in charge I hope you enjoy this episode with a fascinating guest and friend.

Best Old Time Radio Podcast with Bob Bro Wednesday Mysteries for July 1, 2020 The Line Up: The Hiccuping Hamster Homeostatic Case Who are the two hit-men who murdered Luther Griswold, the mob lawyer? One suspect, Benny Samson, is identified in the police line-up. Then an informant known as "The Hamster" (played by Howard McNear) points his finger at George Vincente, a man he saw in the company of Benny on the night of the murder. As the investigation gets closer to Max Ragillo, the mob boss, Ragillo begins to retaliate: Word on the street is there is a hit out on Lt. Guthrie. Featuring: Bill Johnstone, Wally Maher, Howard McNear. Written by Blake Edwards and Dick Klein. Original Broadcast date: May 29, 1951 on CBS

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.22.152066v1?rss=1 Authors: Galanis, C., Fellenz, M., Becker, D., Bold, C., Lichtenthaler, S. F., Mueller, U. C., Deller, T., Vlachos, A. Abstract: The physiological role of the amyloid-precursor protein (APP) is insufficiently understood. Recent work has implicated APP in the regulation of synaptic plasticity. Substantial evidence exists for a role of APP and its secreted ectodomain APPs in Hebbian plasticity. Here, we addressed the relevance of APP in homeostatic synaptic plasticity using organotypic tissue cultures of APP-/- mice. In the absence of APP, dentate granule cells failed to strengthen their excitatory synapses homeostatically. Homeostatic plasticity is rescued by amyloid-{beta} (A{beta} and not by APPs, and it is neither observed in APP+/+ tissue treated with {beta}- or {gamma}-secretase inhibitors nor in synaptopodin-deficient cultures lacking the Ca2+-dependent molecular machinery of the spine apparatus. Together, these results suggest a role of APP processing via the amyloidogenic pathway in homeostatic synaptic plasticity, representing a function of relevance for brain physiology as well as for brain states associated with increased A{beta} levels. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.28.121673v1?rss=1 Authors: Leinonen, H., Pham, N. C., Boyd, T., Santoso, J., Palczewski, K., Vinberg, F. Abstract: Neuronal plasticity of the inner retina has been observed in response to photoreceptor degeneration. Typically, this phenomenon has been considered maladaptive and may preclude vision restoration in the blind. However, several recent studies utilizing triggered photoreceptor ablation have shown adaptive responses in bipolar cell dendrites expected to support normal vision. Whether such homeostatic plasticity occurs during progressive photoreceptor degenerative disease to help maintain normal visual behavior is unknown. We addressed these issues in an established mouse model of Retinitis Pigmentosa caused by the P23H mutation in rhodopsin. We show robust modulation of the retinal transcriptomic network reminiscent of the neurodevelopmental state as well as potentiation of rod - rod bipolar cell signaling following rod photoreceptor degeneration. Additionally, we found highly sensitive night vision in P23H mice even when more than half of the rod photoreceptors were lost. The results implicate retinal adaptation leading to persistent visual function during photoreceptor degenerative disease. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.13.094680v1?rss=1 Authors: Tanvir, Z., Rivera, D., Severi, K., Haspel, G., Soares, D. Abstract: Mauthner cells are the largest neurons in the hindbrain of teleost fish and most amphibians. Each cell has two major dendrites thought to receive segregated streams of sensory input: the lateral dendrite receives mechanosensory input while the ventral dendrite receives visual input. These inputs, which mediate escape responses to sudden stimuli, may be modulated by the availability of sensory information to the animal. To understand the impacts of absence of visual information on the morphologies of Mauthner cells during development and evolutionary time scales, we examined Astyanax mexicanus. This species of tetra is found in two morphs: a seeing surface fish and blind cavefish. We compared the structure of Mauthner cells in surface fish raised in daily light conditions, surface fish that raised in constant darkness, and two independent lineages of cave populations. The length of ventral dendrites of Mauthner cells in dark raised surface larvae were longer and more branched, while in both cave morphs the ventral dendrites were smaller or absent. The absence of visual input in surface fish with normal eye development leads to a homeostatic increase in dendrite size, whereas over evolution the absence of light led to the loss of eyes and a phylogenetic reduction in dendrite size. Consequently, homeostatic mechanisms are under natural selection that provide adaptation to constant darkness. Copy rights belong to original authors. Visit the link for more info

Have you ever thought about brains? Our brains are seriously important, that's not news, but how do they actually work? There is a delicate balance between order and chaos. RadioBio this week is all about stability in the brain. Hopefully by the end you'll know a little bit more about how your brain works!

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.14.093187v1?rss=1 Authors: Ellingford, R. A., Rabeshala de Meritens, E., Shaunak, R., Naybour, L., Basson, M. A., Andreae, L. C. Abstract: Heterozygous mutation of chromodomain helicase DNA binding protein 8 (CHD8) is strongly associated with autism spectrum disorder (ASD) and results in dysregulated expression of neurodevelopmental and synaptic genes during brain development. To reveal how these changes affect ASD-associated cortical circuits, we studied synaptic transmission in the prefrontal cortex of a haploinsufficient Chd8 mouse model. We report profound alterations to both excitatory and inhibitory synaptic transmission onto deep layer projection neurons, resulting in a reduced excitatory:inhibitory balance, which were found to vary dynamically across neurodevelopment and result from distinct effects of reduced Chd8 expression within individual neuronal subtypes. These changes were associated with disrupted regulation of homeostatic plasticity mechanisms operating via spontaneous neurotransmission. These findings therefore directly implicate CHD8 mutation in the disruption of ASD-relevant circuits in the cortex. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.29.068627v1?rss=1 Authors: King, A. N., Schwarz, J. E., Hsu, C. T., Barber, A. F., Sehgal, A. Abstract: Sleep is controlled by homeostatic mechanisms, which drive sleep following periods of wakefulness, and a circadian clock, which regulates sleep timing in a daily cycle. Homeostatic sleep drive sometimes overrides the clock, such that recovery sleep after deprivation occurs outside the normal circadian rest period. However, mechanisms underlying this effect are unknown. We find that sleep-promoting dorsal fan-shaped body (dFB) neurons, effectors of homeostatic sleep in Drosophila, are presynaptic to hugin+ neurons, previously identified as circadian output neurons regulating locomotor activity rhythms. Sleep deprivation decreases hugin+ neuronal activity, which likely suppresses circadian control to promote recovery sleep driven by dFB neurons. Indeed, removal of hugin+ neurons increases sleep-promoting effects of dFB neurons. Trans-synaptic mapping reveals that hugin+ neurons feed back onto s-LNv central clock neurons, which also show Hugin-dependent decreased activity upon sleep loss. These findings identify a circuit-based mechanism through which sleep drive modulates the circadian system to promote recovery sleep following deprivation. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.29.068833v1?rss=1 Authors: Sun, C., Nold, A., Tchumatchenko, T., Heilemann, M., Schuman, E. Abstract: An individual neuron hosts up to 10,000 individual synapses that can be made stronger or weaker by local and cell-wide plasticity mechanisms, both of which require protein synthesis. To address over what spatial scale a neuron allocates synaptic resources, we quantified the distribution of newly synthesized proteins after global homeostatic upscaling using metabolic labeling and single-molecule localization (DNA-PAINT). Following upscaling, we observed a global increase in locally synthesized nascent protein in synapses and at dendrites, with a high degree of variability between individual synapses. We determined the smallest spatial scale over which nascent proteins were evenly distributed and found that it is best described by synaptic neighborhoods (~ 10 microns in length)- smaller than a dendritic branch and larger than an individual synapse. Protein allocation at the level of neighborhoods thus represents a solution to the problem of protein allocation within a neuron that balances local autonomy and global homeostasis. Copy rights belong to original authors. Visit the link for more info

Getting distracted is a huge time stealer. You plan to accomplish one task, but along the way, you see something interesting while scrolling the Internet. By the time you look at the clock, you'll realize you've been scrolling mindlessly for hours. How can we remove these distractions that take us away from our plans and goals? In today's episode, Nir Eyal, the author of the book "Indistractable," joins us to talk about the motivation and strategies that can help us minimize and manage distractions from our lives. Nir is an active angel investor and is an expert in behavioural engineering, where he incorporates elements of behavioural science in software design to develop habit-forming products for businesses.  You'll surely be a changed person after this episode. So sit back and indulge in all the tips and tricks while tuning in to the show, and become inDISTRACTable! How To Control Your Attention And Choose Your Life (02:36) The world is going to become more distracting as technology becomes more pervasive and more persuasive. The bifurcation between people: Those who control their time, attention, and their lives, and those who allow their time and attention to be controlled by other people Focusing on our relationships is a critical macro skill in all facets of life. Even if we go on a digital detox, we'll still find ways to get distracted. We can only get the best out of tools and technology if we know how to use them correctly. What Is Distraction? (06:18) Etymology: Traction and distraction came from the same Latin root "trahere" which means to pull. They end in the same six letters, which is "action." A traction is any action that you take that pulls you towards things that you do with intent. The opposite of traction is distraction. It is anything that pulls you away from what you plan to do with intent. Anything can be a distraction or traction, whether we plan it or whether it's something we do impulsively. Something is going to eat up your time and attention unless you decide in advance how you want to spend your time. The Root Cause (08:27) The question is not "What do we do?" The question is "Why don't we do the things we know we should?" Homeostatic response: Everything we do is about the desire to escape discomfort. The root cause of all distractions is uncomfortable emotional states or "internal triggers." Motivation And Satisfaction (11:48) Hedonic adaptation: Even when something good or bad happens to us, we gravitate towards our baseline level of happiness. In some way, Nir says the self-help industry perpetuates this myth to our detriment by feeding the message that we're supposed to be happy all the time. Feeling bad is part of the human condition.  "If satisfaction and pleasure were permanent, there might be little incentive to continue seeking benefits or advancement." Four Strategies To Become Indistractable (15:33) The first step is to master the internal triggers, to understand what is driving us towards distraction. Second, make time for traction. Timeboxing or making an implementation intention is planning in advance what you're going to do and when you're going to do it. Third, hack back the external triggers. Lastly, prevent distractions with pacts or precommitments that we can make with ourselves or with other people to avoid temptation. Three Types Of Pact (20:40) Effort pact: A friction that prevents us from doing something we later regret Prize pact: Monetary disincentive to getting distracted Identity pact: Self-image can help us stay true to what we say we're going to do The Pattern Of Distraction: Liminal Moments (25:42) The three potential causes of distraction: planning problem, external trigger, or internal trigger. Distraction tricks you into thinking that what you're doing is what you intend to do. If you accomplish something, but it's not what you were initially planning to do for that given time, that is still a distraction. Managing Self-Talk (29:06) Utilize self-compassion. More self-compassionate people are much more likely to achieve long-term goals. Don't be a shamer. Negative self-talk stirs up more internal triggers. Don't be a blamer. Blamers blame something outside themselves. Be a claimer. Claim responsibility for all of your actions. You can't affect how you feel; you can only change how you respond to those situations. Resources Get a copy of Nir Eyal's book, "Indistractable: How To Control Your Attention And Choose Your Life." Indistractable Tools Nir's Free Schedule Maker Indistractable Supplementary Workbook Connect with Nir through his website—NirAndFar, and get all the tools and resources that can help you manage your time and attention. You can download a copy of my ebook 10 Key Traits of Top Business Leaders here. For more podcast episodes and other resources, visit my website at John Murphy International. Thanks for tuning in!

Dr Guerra of Authentic Biochemistry provides his third discussion of adipokine-mediated control over obesity and associated disease from animal models to clinical disease. 02 October 2019. --- Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Carolyn Barron is more than a healer practicing Chinese Medicine here in LA...Her website says this and it doesn't even begin to encapsulate her work:  CHINESE MEDICAL POETICS + HOLISTIC PRIMARY CARE ☯ EMBRACING THE CYCLES OF NATURE TO WORK IN SYNC WITH THE UNIVERSAL FLOW We get into ALL OF IT. Carolyn has been working on me for the past few months and to be frank, mostly during a moment of crisis. Her full body/soul/psyche resets have been truly life changing.  Hope you enjoy our chat!! _________________________________________ Today's episode is brought to you by: - Prolon - the Fasting Mimicking Diet - Use GROOMEDLA2 at checkout and THIS LINK here for $25 off your order!!   - OBE FITNESS! Super cool at home workouts that are COOL TO LOOK AT, GUYS! Get 30% off Your first month with the code : EMILY30 https://www.obefitness.com/ __________________________________________     I am obsessed with this below: T H E  B O T A N A R C H Y   M A N I F E S T A   o n  R A D I C A L  F E M I N I S T  H E A L T H C A R E    Botanarchy’s model of Radical Feminist Healthcare is oriented towards freeing us from a reliance upon medicines + institutions that are exploitive of natural resources and the body en masse. The rich, expansive palate of nature, Taoism, and Traditional Chinese Medicine provide a path that engenders a true state of bodily autonomy, reacquainting us with the rhythms and cycles of our bodies and liberating us from a dependence on healthcare practices that undermine its intelligence and flow.  Botanarchy as a concept hearkens to the idea that medicine can be both a form of resistance and a reclamation of original, authentic nature. Botanarchy offers a vision of radical feminist healthcare that is built on humanism, integrity, and respect for the flow of the natural world. Botanarchists are committed to ending the corporate co-option of the body, supporting the democratization of medicine, and empowering others to think and feel for themselves. Every gender expression benefits from radical feminist health care. We are all suffering from being underserved in a for-profit, disease-driven model that has taken power and autonomy out of the hands of the people and put it into the hands of corporations and politicians. As shepherds of this radical feminist healthcare, we aim to rescue medicine from the patriarchy by means of the following core principles: *Radical feminist healthcare is rooted in natural models that do not suppress the true nature of the body, enhancing connection to both the microcosm of the body and the macrocosm of the earth. *Radical feminist healthcare is based on thousands of years of observing and revering nature, not heterosexual cis white male bodies. *Radical feminist healthcare is tethered to natural rhythms and embraces the cycles of change.  *Radical feminist healthcare honors both light and shadow, recognizing each phase of the creative cycle as medicine — birth, growth, harvest, death, and renewal.  *Radical feminist healthcare is not based on an unattainable goal of ‘healing’, valuing the full spectrum of human experience instead. *Radical feminist healthcare is age-positive, committed to providing compassionate healthcare for all stages of personhood, exulting the menstrual cycle and menopause equally as sacred passages.  *Radical feminist healthcare refuses to industrialize the rhythms and cycles of the body. *Radical feminist healthcare will never measure health by our ability to work harder, work longer, make more money, increase our sexual potency, feel better with less sleep, compete with each other, push beyond our means and capacity.  *Radical feminist healthcare is against positing ‘wellness’ as maximizing our output in a capitalist labor market by increasing motivation and productivity. *Radical feminist healthcare allows every body to define ‘wellness’ on their own terms. *Radical feminist healthcare supports people in finding their own Tao, recovering the self not corrupted by culture.  *Radical feminist healthcare individualizes treatment for every body as a unique emanation of the Tao, recognizing that our Tao can be thwarted by multiple forms of systemic discrimination that may block us from thriving in our personhood. *Radical feminist healthcare is pro-autonomy, helping us recover the capacity to taste and feel and sense for ourselves.  *Radical feminist healthcare is insistent on inner authority, and never shaming of choice. *Radical feminist healthcare recognizes a non-binary gender spectrum beyond male and female, and is focused on balancing the masculine + feminine polarity inside all of us regardless of biological sex or gender. *Radical feminist healthcare sees masculine + feminine as principles existing in a relationship, interdependent, working together, flowing back and forth into each other. *Radical feminist healthcare acknowledges the emotions as aspects of disease, and is non-shaming of emotional states. *Radical feminist healthcare is against the immediate medicating of emotions that don’t fit the dominant narratives of ‘health’ and ‘wellness’. *Radical feminist healthcare is not fear-based and disease-driven. *Radical feminist healthcare cultivates and value receptivity, gentleness, and subtlety.  *Radical feminist healthcare empowers mothers and working families with the tools to take care of ourselves and our communities where the system has failed to protect and sustain us. *Radical feminist healthcare is oriented towards freeing us from a reliance upon privatized healthcare and allopathic methods that often harm the body and undermine its innate, elegant intelligence. *Radical feminist healthcare transmutes the darkness and discomfort of our bodies and society en masse into something new, in the alchemy of turning lead into gold.   If this manifesta speaks to you, I urge you to share it freely and wantonly! Distribute it in your communities. Demand your doctors treat you in accordance with its precepts. Love your body through the medicine of its message! In health and solidarity,  Carolyn      

Commentary by Dr. Valentin Fuster

Today we’re talking to Stephan Guyenet who has a degree in biochemistry and a PhD in neuroscience. He’s spent over 12 years in the neuroscience research world studying neurodegenerative disease and the neuroscience of body fatness. He wrote a great book called The Hungry Brain, speaks at conferences, is a Senior Fellow at GiveWell and scientific reviewer for the Examine.com Research Digest. He is definitely not a low carb person which is why I had him on. He has a lot of great ideas and is a great mind in the space of nutrition. It was very interesting to hear him talk about all the great benefits he did see when he ate a low carb diet 11 years ago. Make sure to listen until the end when he talks about this. He has some problems with certain people and aspects of the low carb community and is going on Joe Rogan’s podcast soon to debate Gary Taubes on his views of the Carbohydrate Insulin theory of obesity and sugar being uniquely toxic We had some disagreement on the recommended daily allowance of nutrients - he thinks what’s recommended is all you need and getting more than that is pointless. I think this is wrong. I think he’s basing it on studies of worthless, non-bioavailable vitamin C pills that in excess do nothing. So in that - I agree. I don’t think there’s any benefit to popping a bunch of these and think we’re going to cure a cold. I do know that our ancestors got estimates of 10-20 times the amount of nutrients we get today, so there’s a lot more to this discussion that we didn’t have time to get into. We also disagreed on fiber which led to some carnivore talk. He got some things wrong about the member of the Grateful Dead who was a carnivore. He said he died at a young age of a heart attack. I looked into it and it turns out he was carnivore for 48 years and was in excellent health and died in a car accident at 72.  He also says we don’t have longterm studies on the safety of low carb diets at the end. This isn’t exactly true and furthermore, we have hundreds of thousands of years of human populations living on low carb diets to prove its safety and efficacy. He additionally mentions the low carb community makes crazy claims that aren’t based on science. I’m not sure what he’s referring to. Not everything can be measured anyway. If tens of thousands of people report to their doctor they aren’t hungry anymore, their energy is stable, their brain is working better, they aren’t addicted to sugar, they finally have control of their food intake, etc. then this is some great clinical observations and patient anecdotes that add up to a lot. I think everyone has their own ideas about things and collects info to support their opinion. It’s only natural, and I’m sure I’m doing it to, even though I’m trying not to. Everyone has to be in their camp and collect data and narratives to support their theories. He seemed to do this as you’ll see throughout the episode.  I agreed with a lot of his points though, especially that humans didn’t evolve to eat based on tracking macros and calories and using an excel spreadsheet to figure out what to eat. He’s doing great work and looking at this from a different angle which is important. A lot of interesting stuff here so let’s get to it. But first I gotta mention the Food Lies film which is in the last stretch of crowdfunding on Indiegogo. We really need your help to finish it. We have a bunch of cool perks like the Eat Meat T-shirt, the movie poster, bonus features, and more. Find it through FoodLies.org or by clicking through this link in the show notes. I really appreciate it - and now here’s Stephan Guyenet. http://indiegogo.com/projects/food-lies-post   Show Notes  I’m obsessed with why we get fat and what to do about it and you’ve been researching this for a long time Why the brain is the most important place to focus on The brain regulates how much we eat, our food choices, and our exercise There’s also non conscious processes the brain regulates that influence caloric expenditure, etc. We also study the human genome to find how that plays a role in body fatness When it comes to body weight, the genes that relate the most are in the brain Nobody wants to overeat, but we end up doing it anyway We need to look at our past to understand why we are wired to seek excess calories Animals and hunter gatherers we’ve studied follow the Optimum Foraging Theory when they acquire food. It’s all about the calories per the amount of effort Because we were eating whole foods from nature, if we got enough calories, we by default we’re getting all the vitamins and minerals needed They didn’t have white flour, sugar, or refined oils We only have receptors for fat, sugar, salt, and glutamate  Apparently those are the nutrients that natural selection cared about most to create reward systems for The Hadza people went mainly for meat, tubers, and honey and didn’t go for leafy greens  The brain is motivated to pursue calorie containing foods, not vitamins and minerals Combining bliss points make certain foods almost irresistible You need to control your food environment  Not only don’t have it sitting out so you can see certain foods, don’t even have them in the house How do genetics play a role? We know it’s way more to do with the type of foods eaten  About 70% of people in countries like the US are genetically susceptible to become obese when eating the bad diet that exists there. The remaining percent just aren’t as susceptible and can get away with it Energy balance while always be a fact, but there’s a lot more to it Eat less, move more may work for some people, but it’s not how we evolved. It’s not a natural way to regulate body weight You can set up a food environment to allow your body to naturally eat the right amount You’d have to be hungry all the time to continue eating processed foods and try to lose weight His definition and thoughts on nutrient density Questioning the necessity of fiber His views on the carnivore diet - he thinks a big factor is becoming lean and it certainly does that He questions if there’s long term chronic disease problems that we don’t know about Inuit seek some plant matter Sound engineer from the Grateful Dead who was carnivore for 48 years - Stephan said he died of a heart attack at a young age. Turns out he was super healthy and died of a car accident at 72. His book https://justmeat.co/docs/the-bear.pdf They call him “Bear” https://dangerousminds.net/comments/uncle_johns_ham_the_grateful_deads_all-meat_diet Wikipedia on him: https://en.wikipedia.org/wiki/Owsley_Stanley Stephan agrees with what I always say about going to either end of the extreme with super low carb or super low fat you have great benefits He’s going on Joe Rogan’s podcast to debate Gary Taubes on his views of the Carbohydrate Insulin theory of obesity and sugar being uniquely toxic What happened with Gary Taubes and Dr. Peter Attia’s non profit venture NuSI - the Nutritional Science Initiative? What Stephan got wrong in his blog posts Why he thinks Gary Taubes is wrong and what is the evidence  He doesn’t like the fact that Gary is calling out scientists  Exercise and weight loss The model of obesity he subscribes to is that it’s all regulated by the brain Homeostatic regulation - hypothalamus controls body fatness like a thermostat The hormone leptin sends feedback to your brain regarding body fat levels Personal fat threshold, how someone can be skinny on the outside but fat on the inside, people can be obese but metabolically healthy, and insulin as a dam holding back fat in the cells He doesn’t think that eating an insulin lowering diet like low carb allows you to lose weight because of the lowered insulin He thinks low carb diets and low fat diets work merely because you’re taking away the extreme motivation to overeat the foods, AKA hyperplatability  Potato hack Metabolic flexibility He thinks being metabolically inflexible is more a sign of insulin resistance than anything He eats about 50% carb, 18% protein, 32% fat He ate a low carb diet after reading Taubes’ book Good Calories, Bad Calories 11 years ago He said it was about the same but one benefit was that he wasn’t tied to meal times. Eating high carb he definitely knew when it was time to eat. Easier to fast He was easily doing 24 hour fasts. Now on high carb it’s way harder and he experiences brain fog Why are low carb diets so maligned in the mainstream media and medical system? What are his solutions for fixing the nation’s health problems? His book The Hungry Brain http://www.stephanguyenet.com/thehungrybrain/ His website http://www.stephanguyenet.com His Twitter https://twitter.com/whsource   Preorder the film here: http://indiegogo.com/projects/food-lies-post   Film site: http://FoodLies.org YouTube: https://www.youtube.com/c/FoodLies Sapien Movement: http://SapienMovement.com   Follow along: http://twitter.com/FoodLiesOrg http://instagram.com/food.lies http://facebook.com/FoodLiesOrg   Theme music by https://kylewardmusic.com/

"Инээгээрэй, эгэл биш юм шүү энэ инээд" гээд дуу байдаг. Инээд үнэхээр эгэл биш эмчилгээ болдогийг шинжлэх ухаан тайлсаар байна. Дэлгэрэнгүйг:Noureldein, M. H., & Eid, A. A. (2017). Homeostatic effect of laughter on diabetic cardiovascular complications: The myth turned to fact. diabetes research and clinical practice.

"Инээгээрэй, эгэл биш юм шүү энэ инээд" гээд дуу байдаг. Инээд үнэхээр эгэл биш эмчилгээ болдогийг шинжлэх ухаан тайлсаар байна. Дэлгэрэнгүйг:Noureldein, M. H., & Eid, A. A. (2017). Homeostatic effect of laughter on diabetic cardiovascular complications: The myth turned to fact. diabetes research and clinical practice.

How is stress really affecting us? And what stress is the worst for us? The author of The Warrior Diet joins me on the show to discuss stress and it's dynamics, how it is really affecting us, why, and whether our biological systems are handling what we are throwing at it in this modern age. A fascinating show from one of life true health intellects. Check out Ori's work here: http://www.orihofmekler.com 

Check out IFPodcast.com/Episode33 for shownotes and references, and IFPodcast.com/StuffWeLike for all the stuff we like! You can support us at Patreon.com/IFpodcast - It would mean the world!! We LOVE putting time into this podcast, and every dollar can help us continue to make that possible! Get Melanie's Book What When Wine: Lose Weight and Feel Great with Paleo-Style Meals, Intermittent Fasting, and Wine, on Amazon and Barnes & Noble! Get Gin's Books' Feast Without Fear: Food and the Delay, Don't Deny Lifestyle SHOW NOTES 4:15 - Gin's Dry Farm Wines Review 6:50 - Listener Feedback: Rosie - Victory: Preparing Meals In The Fasted State!  11:25 - Listener Q&A: Kathi  - What Minerals And Vitamins Do Melanie And Gin Take During IF? 12:50 - Prebiotics/ Probiotics  18:35 - What Does Gin Take Now? 20:25 - Types of Magnesium (Magnesium Citrate) 22:50 - Melanie's Routine 24:45 - Low Dose Naltrexone 28:10 - Our Thoughts On Melatonin 32:30 - Cilantro 34:30 - Listener Q&A: Heidi  - Can You Differentiate Between Actual Hunger And Habitual Eating By The Source Of The Thought?  35:45 - Listener Q&A: Alexis  - How Do You Stop Eating Out Of Boredom? 36:45 - The Four Tendencies 36:45 - Homeostatic vs Traditional Hunger  41:50 - Artificial Sweeteners And Cravings  47:15 - Elaborates Intrusion Theory 48:44 - Rational Reasoning  55:05 - Tips To Deal With Eating Out Of Boredom  55:35 - Pavlok For information regarding your data privacy, visit acast.com/privacy

Vladyslav Vyazovskiy from the Department of Physiology, Anatomy and Genetics gives this Nuffield Department of Clinical Neurosciences seminar

Summary and hypothesis Role of pro-inflammatory chemokines in diabetic nephropathy Beyond hemodynamic and metabolic abnormalities associated with diabetes, the role of inflammation in development and progression of diabetic nephropathy is well accepted. Recruitment and activation of macrophages in different renal compartment is considered to be hallmark of all inflammation in diabetic nephropathy. Although recruitment of macrophages to the renal compartment has been extensively studied, the exact mechanisms involved are still to be explored. The chemokine-chemokine receptor interactions are implicated to be mainly responsible for trafficking and infiltration of different monocytes and macrophages. Contribution of macrophages to the development of DN can be addressed in either by inhibiting chemokines or chemokine receptor associated with diabetes. We hypothesized that inhibition of CCL2 may inhibit macrophages infiltrating into different compartments in kidney and inhibition started at earlier stage of disease progression may show more beneficial effects than CCL2 blockade at late stage of DN. To address the involvement of additional chemokine receptors we hypothesized that blocking CCR5 and CCR2 simultaneously might have some additive or synergistic effects. Role of homeostatic chemokines in diabetic nephropathy Homeostatic chemokies are mainly involved in hematopoeisis, immune cell survival and adaptive immune responses. CXCL12 attracted our attention as it is being extensively studied and reported to be responsible for different functions like stem cell survival and homing and trafficking to different compartments. The role of CXCL12 in diabetic nephropathy has not been explored yet. CXCL12 is constitutively expressed by different renal cells. It may contribute to tissue repair and inhibit disease progression by stem cell recruitment or may cause increased tissue fibrosis and aggravate the disease. We hypothesized that CXCL12 plays role in development and progression of diabetic nephropathy. In order to address this question we used CXCL12 blocker in a mouse model of diabetic nephropathy.

Enhanced Audio PodcastAired date: 9/25/2006 12:00:00 PM Eastern Time

Enhanced Video PodcastAired date: 9/25/2006 12:00:00 PM Eastern Time Institute: NINDS

Enhanced Audio PodcastAired date: 9/25/2006 12:00:00 PM Eastern Time Institute: NINDS

Enhanced Video PodcastAired date: 9/25/2006 12:00:00 PM Eastern Time

Homeostasis is a key concept in biology. It enables ecosystems, organisms, organs and cells to adjust their operating range to values that ensure optimal performance. Homeostatic regulation of synaptic activity has been shown to play an important role during development. Here I investigated whether also mature neurons possess mechanisms to prevent the strengthening of input synapses once the limit of their ‘operating range’ has been reached. Using electrophysiological recordings in hippocampal slices, I showed that such a mechanism indeed exists but only comes into play after a considerable number of synapses has been potentiated. Thus, adult neurons can sustain a substantial amount of synaptic strengthening but, once a certain threshold of potentiation is exceeded, homeostatic regulation ensures that no further strengthening occurs.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.17.047423v1?rss=1 Authors: Lok, R., Woelders, T., van Koningsveld, M. J., Oberman, K., Fuhler, S. G., Beersma, D. G. M., Hut, R. A. Abstract: Light induced improvements in alertness are more prominent during night-time than during the day, indicating circadian regulation or wake duration related dependence. Relative contributions of both factors can be quantified using a forced desynchrony (FD) designs. Here we investigate alerting effects of light in a novel 4x18 hours FD protocol (5h sleep, 13h wake) under dim (6 mlux) and bright light (1159 mlux) conditions. Hourly saliva samples (melatonin and cortisol assessment) and 2-hourly test-sessions were used to assess effects of bright light on subjective and objective alertness (electroencephalography and performance). Results reveal (1) stable free-running cortisol rhythms with uniform phase progression under both light conditions, indicating that FD designs can be conducted under high intensity lighting, (2) subjective alerting effects of light depend on elapsed time awake, while (3) light consistently improves objective alertness independent of time awake. Three dimensional graphs reflecting light induced alertness improvements depending on wake duration related variation and circadian clock phase suggest that performance is improved during daytime, while subjective alertness remains unchanged. This suggests that light during office hours might be beneficial for performance, even though this may not be perceived as such. Copy rights belong to original authors. Visit the link for more info