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Category: biotech/medical

Grant supports research into how microglia may spread toxic tau in Alzheimer’s

A paper describing Hopp’s upcoming study published on the CureAlz website, titled, “How Do Microglia Contribute to the Spread of Tau Pathology in Alzheimer’s Disease?”, says that while tau aggregates are a defining feature of Alzheimer’s disease and closely track with brain cell loss, memory problems and cognitive decline, much still isn’t known about how it spreads or what role the brain’s immune system plays in the process.

There is evidence, it says, that toxic forms of tau, which have become “misfolded” or dysfunctional, act like a “bad influence.”

“When they encounter nearby healthy tau proteins, they cause them to misfold as well, triggering a chain reaction that spreads from one brain region to another,” according to the paper. “Microglia … are among the first to encounter these toxic tau ‘seeds.’ Normally, microglia protect the brain by clearing debris and helping repair damage. But growing evidence suggests that microglia may also contribute to tau’s spread by engulfing misfolded tau and inadvertently releasing it, thereby amplifying its harmful effects.”

A researcher with the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at UT Health San Antonio has received a two-year, $402,500 grant award from the Cure Alzheimer’s Fund to study how microglia, the brain’s resident immune cells, paradoxically might contribute to the spread of toxic forms of tau protein in the disease.

Sarah C. Hopp, PhD, associate professor of pharmacology with the Biggs Institute and the South Texas Alzheimer’s Disease Research Center, along with her lab have been instrumental in uncovering the behavior of microglia. UT Health San Antonio is the academic health center of The University of Texas at San Antonio.

Starting this month, Hopp’s lab will test the hypothesis that microglial uptake of tau is a key mechanism driving its spread through the brain, and that specific molecular pathways determine whether this process protects or harms neurons. The Cure Alzheimer’s Fund, also known as CureAlz, is a nonprofit organization that funds research “with the highest probability of preventing, slowing or reversing Alzheimer’s disease.”

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DeepRare AI helps shorten the rare disease diagnostic journey with evidence-linked predictions

Researchers developed DeepRare, an LLM-driven multi-agent diagnostic system that integrates clinical descriptions, phenotype data, and genomic information to improve rare disease identification. Across thousands of cases, the system showed higher diagnostic recall than existing AI tools and clinicians in benchmark testing, while providing traceable reasoning linked to medical evidence.

By 2050 we could get “10,000 years of technological progress”

Every major AI company has the same safety plan: when AI gets crazy powerful and really dangerous, they’ll use the AI itself to figure out how to make AI safe and beneficial. It sounds circular, almost satirical. But is it actually a bad plan? Today’s guest, Ajeya Cotra, recently placed 3rd out of 413 participants forecasting AI developments and is among the most thoughtful and respected commentators on where the technology is going.

She thinks there’s a meaningful chance we’ll see as much change in the next 23 years as humanity faced in the last 10,000, thanks to the arrival of artificial general intelligence. Ajeya doesn’t reach this conclusion lightly: she’s had a ring-side seat to the growth of all the major AI companies for 10 years — first as a researcher and grantmaker for technical AI safety at Coefficient Giving (formerly known as Open Philanthropy), and now as a member of technical staff at METR.

So host Rob Wiblin asked her: is this plan to use AI to save us from AI a reasonable one?

Ajeya agrees that humanity has repeatedly used technologies that create new problems to help solve those problems. After all:
• Cars enabled carjackings and drive-by shootings, but also faster police pursuits.
• Microbiology enabled bioweapons, but also faster vaccine development.
• The internet allowed lies to disseminate faster, but had exactly the same impact for fact checks.

But she also thinks this will be a much harder case. In her view, the window between AI automating AI research and the arrival of uncontrollably powerful superintelligence could be quite brief — perhaps a year or less. In that narrow window, we’d need to redirect enormous amounts of AI labour away from making AI smarter and towards alignment research, biodefence, cyberdefence, adapting our political structures, and improving our collective decision-making.

The plan might fail just because the idea is flawed at conception: it does sound a bit crazy to use an AI you don’t trust to make sure that same AI benefits humanity.

Continue reading “By 2050 we could get “10,000 years of technological progress”” | >

Key alterations discovered in the cerebral cortex of people with psychosis

Researchers at the University of Seville have analyzed alterations in the cerebral cortex in people suffering from psychosis. Their findings show that psychosis does not follow a single trajectory, but rather its evolution depends on a complex interaction between brain development, symptoms, cognition and treatment. The authors therefore emphasize the need to adopt more personalized approaches that take individual differences into account in order to better understand the disease and optimize long-term therapeutic strategies.

Psychosis is a set of symptoms—such as hallucinations and delusions—that are common in schizophrenia and involve a loss of contact with reality. From their first manifestation, known as the first psychotic episode, these symptoms can appear and evolve in very different ways between individuals, thus making schizophrenia a particularly complex disorder.

The results of the study show that, at the time of the first episode, people with psychosis present a reduction in cortical volume, which is particularly marked in regions with a high density of serotonin and dopamine receptors, key neurotransmitters in both the pathophysiology of psychosis and the mechanism of action of antipsychotics. The data also suggest that both neurons and other brain cells involved in inflammatory and immunological processes may play an important role in the disease.

One stem cell generates 14 million tumor-killing NK cells in major cancer breakthrough

Scientists in China have unveiled a breakthrough way to mass-produce powerful cancer-fighting immune cells in the lab. By engineering early-stage stem cells from cord blood—rather than trying to modify mature natural killer (NK) cells—they created a streamlined process that generates enormous numbers of highly potent NK cells, including CAR-equipped versions designed to hunt specific cancers.

Symbiotic bacteria in planthoppers break record for smallest non-organelle genome ever found

Many insects rely on heritable bacterial endosymbionts for essential nutrients that they cannot get through their diet. A new study, published in Nature Communications, indicates that the genomes of these symbiotic bacteria often shrink over time. Some of these bacteria, which live inside certain insect cells, have lost so many genes that they have broken the record for the tiniest genome ever found—almost blurring the lines between organelle and bacteria.

Endosymbiotic relationships are common in many insects, and in sap-sucking insects, like planthoppers and cicadas, they are essential for the insect’s survival. Because the sap of plants does not typically contain certain amino acids or vitamins, the insect must get them another way. Over hundreds of millions of years, these insects have co-evolved with bacteria that provide these additional nutrients.

Sulcia and Vidania are two examples of bacterial endosymbionts, which have co-evolved with planthoppers for more than 260 million years. These bacteria live in specialized cells within the planthopper abdomen. The new study has found that, along with their hosts, these endosymbionts have evolved—or devolved—in some unexpected ways.

Scientists find hundreds of genes that behave like light switches

If cancer’s genetic off switch is found then even Covid 19s off switch could essentially be found aswell.

Gene expression, where cells use the genetic information encoded in DNA to produce proteins, has been thought of as a dimmer light.

How much a particular gene gets expressed continually rises and falls, depending on the needs of a cell at any given time. It’s like adjusting the lighting of a room until it’s just right for your mood.

But University at Buffalo researchers have shown that a considerable portion of a human’s roughly 20,000 genes express more like your standard light switch — fully on or fully off.

Anti-aging effect of Hedgehog signaling

Aging weakens the body’s ability to maintain balance and repair damage, increasing vulnerability to disease. This study reveals that the Hedgehog (Hh) signaling pathway plays a crucial role in preserving tissue integrity and regenerative capacity. Using animal models, researchers found that activating Hh signaling in multiple tissues such as the liver and brain enhances tissue repair and mitigates age-related functional decline. These findings suggest that targeting Hh signaling could be a promising strategy to promote healthy aging by enhancing regeneration and alleviating age-related dysfunction.

This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

A PI3Kδ-Foxo1-FasL signaling amplification loop rewires CD4+ T cell signaling and differentiation

Dominic P. Golec, Pamela L. Schwartzberg and colleagues (National Institute of Allergy and Infectious Diseases (NIAID)) describe a PI3 Kinase-Foxo1-FasL signaling circuit that promotes amplified signaling and rewires transcriptional and epigenetic programs driving IFN-γ and altered T helper cell differentiation in CD4+ T cells from mice expressing an activating mutant of phosphoinositide 3-kinase delta.

Immunodeficiency LymphocyteBiology

While inputs regulating CD4+ T helper (Th) cell differentiation are well defined, the integration of downstream signaling with transcriptional and epigenetic programs that define Th lineage identity remains incompletely resolved. PI3K signaling is a critical regulator of T cell function; activating mutations affecting PI3Kδ result in an immunodeficiency with multiple T cell defects. Using mice expressing activated PI3Kδ, we found aberrant expression of proinflammatory Th1 signature genes under Th2-inducing conditions, both in vivo and in vitro. This dysregulation was driven by a PI3Kδ-IL-2-Foxo1 signaling amplification loop, fueling Foxo1 inactivation, loss of Th2 lineage restriction, and extensive epigenetic reprogramming. Surprisingly, ablation of Fasl, a Foxo1-repressed gene, normalized both Th2 differentiation and TCR signaling. BioID and imaging revealed Fas interactions with TCR signaling components, which were supported by Fas-mediated potentiation of TCR signaling that could occur in the absence of FADD. Our results highlight Fas-FasL signaling as a critical intermediate in phenotypes driven by activated PI3Kδ, thereby linking two key pathways of immune dysregulation.

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