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Category: biotech/medical

Cell types: encoding the brain’s BIOS

Excellent Substack writeup by Patrick Mineault on how cell types may specify innate behaviors and why mapping regions of the brain specialized to steer innate behaviors (via lots of distinct cell types) could lead us to more aligned AI systems. Highly convincing and elegant arguments made here! [ https://substack.com/home/post/p-189321289](https://substack.com/home/post/p-189321289)

Dwarkesh seemed very confused by this, asking a few different times: “Why would each reward function need a different cell type?” I empathize with Dwarkesh here! It is mysterious that a cell type could represent something as abstract as a reward. As a computational neuroscientist who mostly worked at the representation level during my PhD, I’ve leaned historically towards thinking of cell types as a mere “implementation detail”. But over conversations with Adam, Steve Byrnes, Paul Cisek, Tony Zador, and a few others, I’ve started to become convinced that cell types are a really useful lens to think about innate behaviors and rewards.

In this essay, I’ll unpack the conversation and answer the question: what do cell types have to do with reward functions? To answer it, we’ll need to understand what kind of information can be encoded in the genome, and how that information ultimately relates to connectomes and to cell types. I’ll connect the answer to the central claim of Adam: that these connections matter for AI, and AI safety in particular.

Andrew Barto and colleagues make the point that all primary rewards are internal, and must be genetically encoded. In reinforcement learning, which Barto co-developed along with Rich Sutton, an agent learns by receiving reward signals that indicate what is good and bad. The critical insight is that for biological organisms, all of these reward signals are internal —they are generated by the organism’s own nervous system. It is not a chunk of steak that gives reward: it is circuitry inside the brain that assigns positive valence to fat, salt, umami, heat, and texture. Things like money—secondary rewards—must be bootstrapped off of the pre-existing primary rewards.

Life-changing drug identified for children with rare epilepsy

A new experimental treatment for children with a hard-to-treat form of epilepsy is safe and can reduce seizures dramatically, helping them lead much healthier and happier lives, according to the findings of a UCL (University College London) and Great Ormond Street Hospital-led international clinical trial. In a paper published in The New England Journal of Medicine, researchers found that children with Dravet syndrome had up to 91% fewer seizures while being regularly administered a new medication called zorevunersen.

The results also show, for the first time, the potential to reduce the impact of the condition on a child’s mental processes and behavior. The children’s quality of life improved over a three-year period and most of the treatment’s side effects were mild.

Dravet syndrome is a devastating genetic condition that causes frequent, hard-to-control seizures and long-term neurodevelopmental impairment. The condition also causes feeding difficulties, movement problems and has a high risk of premature death. Current treatments fail to control seizures in most patients and there are no approved medicines that address the condition’s devastating cognitive and behavioral impacts.

Abstract: This study is directly relevant to the clinical care of patients with the most common malignant tumor of the peripheral nervous system

While providing fundamental biological insight👇

Harish N. Vasudevan & team reveal transcriptional, functional genetic, and cellular mechanisms of interferon signaling that underlie radiotherapy response in people with MPNST.

Address correspondence to: Harish N. Vasudevan, Helen Diller Cancer Research Building, 1,450 3rd Street, Mail Box 520, San Francisco, California 94,158, USA. Phone: 415.502.4107; Email: [email protected].

Abstract: Molecular mechanisms regulating diabetic retinopathy

Vision loss from microvascular complication in patients with diabetes mellitus (DM) results in diabetic retinopathy (DR).

Recent evidence suggests that neurodegeneration occurs in parallel with or prior to vascular cell injury in the retina of patients with DM and thus DR is considered as a neurovascular disease.

The researchers in this review discuss how molecular stress (i.e., glucose dysregulation, dysmetabolism, oxidative stress, and inflammation) promote retinal vascular cell and neuronal injury in patients with DM.

The researchers also discuss how genes regulated by the HIF family of transcription factors in glial, vascular, neuronal, and inflammatory cells, control various pathways and identify new therapeutic avenues for the prevention or early treatment of patients with this vision-threating disease. sciencenewshighlights Science Mission https://sciencemission.com/diabetic-retina

Address correspondence to: Akrit Sodhi, Wilmer Eye Institute, Johns Hopkins School of Medicine, 400 N. Broadway St., Smith Building, 4,039, Baltimore, Maryland 21,287, USA. Email: [email protected].

Find articles by Guo, C. in: | Google Scholar |

Continue reading “Abstract: Molecular mechanisms regulating diabetic retinopathy” | >

Introduction: The Parkinson’s pandemic: prioritizing environmental policy and biological resilience

Via the gut.

Bianca Palushaj & Robin M Voigt puts forward a strategy for altering the trajectory of this modern epidemic.

1Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.

2Rush Center for Integrated Microbiome and Chronobiology Research.

3Department of Internal Medicine, and.

4Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, Illinois, USA.

Continue reading “Introduction: The Parkinson’s pandemic: prioritizing environmental policy and biological resilience” | >

Ctenophore research points to earlier origins of brain-like structures

New 3D reconstructions of a key sensory organ in ctenophores reveal an unexpected structural and functional complexity. The findings suggest that an elementary brain may have already appeared in our most ancient relatives, reshaping our understanding of nervous system evolution in animals. The work is published in Science Advances.

Ctenophores (comb jellies) are gelatinous animals that appeared in the ocean an estimated 550 million years ago. The delicate animals possess a specialized sensory structure called the aboral organ (AO), which allows them to sense gravity, pressure, and light. The new morphological study reveals that this organ is far more complex than previously thought.

“We show that the AO is a complex and functionally unique sensory system,” said Pawel Burkhardt, group leader at the Michael SARS Centre, University of Bergen. “Our study profoundly enhances our understanding of the evolution of behavioral coordination in animals.”

One-of-a-kind microscope reveals living cells in unprecedented detail

Stanford researchers have combined two microscopy techniques to create a one-of-a-kind instrument that can show cell structures interacting in real time at an unprecedented 120-nanometer resolution—the highest achieved without the use of fluorescent labels. This new “label-free” technology, called Interferometric Image Scanning Microscopy, or iISM, will allow scientists to observe cellular structures in their wider context, including their responses to intrusions, such as pathogens or drugs.

The advance is detailed in Light: Science and Applications. “This new microscope provides a fantastic new view into the cell, where you can see the tiny structures and machines in the cell moving, changing, and interacting without having to add fluorescence to observe them,” said senior author W.E. Moerner, the Harry S. Mosher Professor of Chemistry in Stanford’s School of Humanities and Sciences.

“It’s a wonderful look into these complex little cellular boxes that drive our life.”

Frontiers: Dietary restriction (DR)

Defined as reduced caloric intake or selective limitation of specific nutrients without malnutrition, is one of the most robust interventions known to extend lifespan and healthspan across species. Studies from yeast to mammals demonstrate that DR elicits conserved genetic, transcriptional, and epigenetic programs that promote cellular maintenance and stress resistance. At the molecular level, DR engages evolutionarily conserved nutrient-sensing pathways, including insulin/IGF-1 signaling (IIS), the mechanistic target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), and NAD+-dependent sirtuins, which converge on key transcription factors (TFs) and transcriptional coactivators (TCs) to coordinate metabolic and longevity-associated gene expression. Downstream, these pathways enhance autophagy and proteostasis, remodel mitochondrial function and redox balance, reshape immune and inflammatory networks, and induce epigenetic and transcriptional reprogramming. Recent work further highlights amino acid–specific sensing mechanisms, endocrine mediators such as fibroblast growth factor 21 (FGF21), the gut microbiome, circadian regulators, and nuclear pore–associated transcriptional plasticity as integral components of DR responses. Importantly, the physiological outcomes of DR are context dependent and influenced by genetic background, sex, age at intervention, and the type and duration of restriction. In this review, we summarize current knowledge on the genetic and molecular architecture underlying DR-induced longevity and health benefits across species, discuss implications for aging-related diseases, and outline future directions toward precision nutrition and safe translational strategies.

Aging is characterized by a progressive decline in physiological integrity, reduced stress resilience, and increased susceptibility to chronic diseases (Lopez-Otin et al., 2023). Among numerous genetic, pharmacological, and lifestyle interventions examined over the past decades, dietary restriction (DR) remains the most robust and evolutionarily conserved strategy for extending lifespan and improving healthspan. Originally described in rodents nearly a century ago, the beneficial effects of reduced nutrient intake have since been validated in a wide range of organisms, including yeast, nematodes, flies, and mammals (Wu et al., 2022). While often used interchangeably, it is critical to distinguish between different nutritional interventions to avoid conceptual overlap. Caloric restriction (CR) typically refers to a chronic reduction in total calorie intake (usually 20%–40%) without malnutrition.

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