Mind & Matter

• Cell Biology: Cytoskeleton, Self-Assembly & Self-Organization, Wound Healing | Bill Bement | 236

  Send us a textCellular self-organization, cytoskeleton dynamics, and membrane wound healing.Episode Summary: Cell Biologist Dr. Bill Bement explains the dynamic world of the cell cortex, discussing how actin filaments and microtubules drive processes like cell division and wound healing through self-assembly and self-organization; energy dynamics of these processes; the role of rho GTPases in patterning; the implications for diseases such as cancer and muscular dystrophy, using vivid analogies and video demonstrations to make complex concepts accessible.About the guest: Bill Bement, PhD is a cell biology professor at the University of Wisconsin-Madison, where he has studied cellular processes for over 30 years. He leads a lab focused on the cell cortex, investigating cell division and repair. His work emphasizes self-organization and cytoskeletal dynamics, contributing to insights into diseases like muscular dystrophy.Discussion Points:The cell cortex, the outer layer of a cell, includes the plasma membrane & underlying proteins like actin & myosin, which enable dynamic shape changes.Actin filaments self-assemble without energy input, growing & shrinking to facilitate cell movement and division, while microtubules, stiffer hollow tubes, aid in chromosome separation.Self-organization in cells, driven by energy-dependent feedback loops, creates complex patterns like mitotic spindles.Cellular wound healing involves concentric rings of rho GTPases and actin, closing wounds rapidly, a process critical for surviving natural damage from mechanical stress or toxins.Energy costs of cytoskeletal rearrangements are significant but likely less than protein synthesis, though precise measurements remain challenging.Cancer metastasis may rely on enhanced cell repair, allowing metastatic cells to survive mechanical damage while squeezing through tissues.Muscular dystrophy involves excessive damage or impaired repair, highlighting the importance of cell repair mechanisms.Bement’s lab is developing tools for synthetic self-organization, aiming to manipulate cellular processes to address repair deficits in diseases.Related episode:M&M 220: Cell Death, Oxidative Stress, PUFAs & Antioxidants | Pamela Support the showAll episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts

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• Computational Neuroscience, Machine Learning vs. Biological Learning, Large Language Models | Marius Pachitariu | 235

  Send us a textHow brains compute and learn, blending neuroscience with AI insights.Episode Summary: Dr. Marius Pachitariu discusses how the brain computes information across scales, from single neurons to complex networks, using mice to study visual learning. He explains the differences between supervised and unsupervised learning, the brain’s high-dimensional processing, and how it compares to artificial neural networks like large language models. The conversation also covers experimental techniques, such as calcium imaging, and the role of reward prediction errors in learning.About the guest: Marius Pachitariu, PhD is a group leader at the Janelia Research Campus, leading a lab focused on neuroscience with a blend of experimental and computational approaches.Discussion Points:The brain operates at multiple scales, with single neurons acting as computational units and networks creating complex, high-dimensional computations.Pachitariu’s lab uses advanced tools like calcium imaging to record from tens of thousands of neurons simultaneously in mice.Unsupervised learning allows mice to form visual memories of environments without rewards, speeding up task learning later.Brain activity during sleep or anesthesia is highly correlated, unlike the high-dimensional, less predictable patterns during wakefulness.The brain expands sensory input dimensionality (e.g., from retina to visual cortex) to simplify complex computations, a principle also seen in artificial neural networks.Reward prediction errors, driven by dopamine, signal when expectations are violated, aiding learning by updating internal models.Large language models rely on self-supervised learning, predicting next words, but lack the forward-modeling reasoning humans excel at.Related episode:M&M 44: Consciousness, Perception, Hallucinations, Selfhood, Neuroscience, Psychedelics & "Being You" | Anil Seth*Not medical advice.Support the showAll episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts

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• Brain Fat: Dietary PUFAs, Cannabinoids, Fatty Acid Binding Proteins, Anxiety & Mood | Steven Laviolette | 234

  Send us a textHow dietary fats and cannabinoids shape brain function and mental well-being.Episode Summary: Dr. Steven Laviolette discusses the role of lipids, particularly endocannabinoids and fatty acids, in brain signaling and mental health, discussing how dietary omega-3 and omega-6 imbalances, prenatal THC exposure, and fatty acid binding proteins (FABPs) impact mood, anxiety, and neuroinflammation, while highlighting potential dietary interventions to mitigate these effects.About the guest: Steven Laviolette, PhD is a professor at the University of Western Ontario, holding a PhD, and his lab focuses on the brain’s cannabinoid system and its role in mental health. He investigates how cannabinoids and fatty acids influence brain development and disorders like anxiety and schizophrenia.Discussion Points:The brain uses fats like endocannabinoids (e.g., anandamide, 2-AG) not just for structure but as signaling molecules to regulate emotional and cognitive processing.Prenatal THC exposure in rodents skews the omega-3/omega-6 balance toward pro-inflammatory omega-6, leading to cognitive and mood issues in offspring, but omega-3 supplementation can mitigate these effects.Fatty acid binding proteins (FABPs), especially FABP5, shuttle endocannabinoids like anandamide to degradation sites, and inhibiting FABP5 increases anandamide levels, reducing anxiety and depression without addictive side effects.FABP5 inhibitors show promise as safer alternatives to benzodiazepines.Both THC and CBD can induce problems during early development, challenging the notion that CBD is universally safe, especially during pregnancy.Dietary interventions, like omega-3 supplementation or antioxidants (e.g., L-theanine, N-acetylcysteine), may counteract the negative psychiatric effects of cannabinoid exposure, particularly during adolescence.The North American diet, high in omega-6, contributes to neuroinflammation and mental health issues, underscoring the need for nutritional neuroscience to address these imbalances.Related episode:M&M 165: PUFAs in Brain Health & Disease, Dietary Fats, Brain Lipids, Nutrition | Richard Bazinet*Not medical advice.Support the showAll episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts

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• Feel the Burn: Seed Oils, Memes & Oxidative Stress | Brian Kerley | 233

  Send us a textAre seed oils really driving chronic disease (and sunburns), or is it hype?Episode Summary: Dr. Brian Kerley talks about the health impacts of seed oils, their high omega-6 fatty acid content, and their role in chronic diseases through mechanisms like lipid peroxidation and oxidative stress. They explore how these industrially processed oils may contribute to conditions like heart disease and obesity, discuss the challenges of studying their long-term effects, and highlight the cultural and political dimensions of dietary trends.About the guest: Brian Kerley, MD is a family medicine-trained hospitalist physician who gained online prominence as the "Seed Oil Disrespecter" through his meme account, raising awareness about the health risks of seed oils.Discussion Points:Seed Oils & Health Risks: Seed oils (e.g., soybean, corn, etc.) are high in omega-6 polyunsaturated fatty acids (PUFAs), linked to oxidative stress and lipid peroxidation, producing toxic compounds like 4-HNE and acrolein that damage cells.Evolutionary Perspective: The high omega-6 levels in modern diets are evolutionarily novel, deviating from natural omega-6 to omega-3 ratios found in traditional diets, potentially exacerbating health issues across diverse populations.Challenges with RCTs: Randomized controlled trials (RCTs) often fail to capture the long-term effects of seed oils due to the need for extended washout periods (up to 8 years) and the pervasive presence of omega-6 in modern food environments.Cultural & Political Coding: Dietary trends like seed oil avoidance have become politically charged, with Kerley noting the polarization between institutional health narratives and alternative health communities, complicating public health discussions.Personal Impact: Dr. Kerley’s focus on seed oils stems from personal experiences, including managing his daughter’s mitochondrial disorder, highlighting the personal stakes in dietary choices.Related episode:M&M 192: Seed Oils, Chronic Disease, Diet & Religious Cults, Mainstream Medicine vs. Independent Research | Tucker Goodrich*Not medical advice.Support the showAll episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts

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• SSRIs, Sexual Dysfunction, Suicide & Mass Shootings, How FDA Works | David Healy | 232

  Send us a textA critique of SSRIs and pharma’s influence on medicine, including SSRI-induced sexual dysfunction, suicidality, and violence. Long Summary: Dr. David Healy critiques modern medicine, focusing on SSRIs and psychiatric medicine, including: how pharmaceutical companies manipulate clinical trial data, ghostwrite studies, and influence medical practice, often ignoring patient experiences; highlighting issues like post-SSRI sexual dysfunction (PSSD), the immediate sensory effects of SSRIs, and their potential to induce suicidal or violent behavior; challenging the reliance on randomized controlled trials (RCTs) over individual patient reports; and more.About the guest: David Healy, MD, PhD, a psychiatrist and pharmacologist, has decades of experience researching the serotonin system and SSRIs, working across Ireland, the UK, Canada, and the US. He is a professor at McMaster University and a vocal critic of pharmaceutical industry practices.Discussion Points:SSRIs cause near-immediate sensory effects, like genital numbing, in most people.Post-SSRI sexual dysfunction (PSSD) can persist for years or decades after stopping the drug, affecting many long-term users.Healy argues RCTs prioritize averages over individual experiences, often missing serious side effects like suicidality.Pharmaceutical companies ghostwrite studies and manipulate data, with journals like the New England Journal of Medicine publishing misleading articles.Serotonin theory of depression lacks evidence.Industry tactics include dismissing patient reports as anecdotes and using high doses in trials to mask weak efficacy.SSRIs can increase suicide risk, not just during initiation but also when adjusting doses or withdrawing, as seen in cases like the Aurora movie theater shooting.Regulatory bodies like the FDA often fail to investigate adverse effects due to bureaucratic processes and lack of follow-up.Healy emphasizes doctors’ failure to prioritize patient observations, driven by industry-influenced standards of care.Related episode:M&M 88: Depression, Serotonin, SSRIs, Psychiatry & Social Media | Joanna Moncrieff*Not medical advice.Support the showAll episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts

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