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SCFFBXW11 Complex Targets Interleukin-17 Receptor A for Ubiquitin–Proteasome-Mediated Degradation

Interleukin-17 (IL-17) is a pro-inflammatory cytokine that participates in innate and adaptive immune responses and plays an important role in host defense, autoimmune diseases, tissue regeneration, metabolic regulation, and tumor progression. Post-translational modifications (PTMs) are crucial for protein function, stability, cellular localization, cellular transduction, and cell death. However, PTMs of IL-17 receptor A (IL-17RA) have not been investigated. Here, we show that human IL-17RA was targeted by F-box and WD repeat domain-containing 11 (FBXW11) for ubiquitination, followed by proteasome-mediated degradation. We used bioinformatics tools and biochemical techniques to determine that FBXW11 ubiquitinated IL-17RA through a lysine 27-linked polyubiquitin chain, targeting IL-17RA for proteasomal degradation.

Neuralink Patient Controls a Robotic Arm Telepathically! (Interview w/ Nick Wray)

Follow Nick on X: https://twitter.com/Telepath_8

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Neura Pod is a series covering topics related to Neuralink, Inc. Topics such as brain-machine interfaces, brain injuries, and artificial intelligence will be explored. Host Ryan Tanaka synthesizes information, shares the latest updates, and conducts interviews to easily learn about Neuralink and its future.

Sign up for Neuralink’s Patient Registry: https://neuralink.com/trials/

Join the Neuralink team: https://neuralink.com/careers/

For those living with dementia, new study suggests shingles vaccine could slow the disease

An unusual public health policy in Wales may have produced the strongest evidence yet that a vaccine can reduce the risk of dementia. In a new study led by Stanford Medicine, researchers analyzing the health records of Welsh older adults discovered that those who received the shingles vaccine were 20% less likely to develop dementia over the next seven years than those who did not receive the vaccine.

The remarkable findings, published April 2 in Nature, support an emerging theory that viruses that affect the nervous system can increase the risk of dementia. If further confirmed, the new findings suggest that a preventive intervention for dementia is already close at hand.

In a follow-up study published Dec. 2 in Cell, the researchers found that the vaccine may also benefit those already diagnosed with dementia by slowing the progress of the disease.

DAP12 deletion reduces neuronal SLIT2 and demyelination and enhances brain resilience in female tauopathy mice

How DAP12 deletion enhances brain resilience in female tauopathy mice.

Microglia selectively expresses DAP12 (DNAX-activation protein 12), which, plays a crucial role in microglial immune responses.

Previously, it was show that tauopathy mice lacking DAP12 exhibit higher tau pathology but are protected from tau pathology-induced cognitive deficits but the mechanism remains elusive.

The authors in this study show that tau processing in primary microglia is reduced by Dap12 deletion, while, tau pathology increased in female tauopathy mice, with minimal effects on males. However, brain inflammation, synapse loss, and demyelination are reduced by Dap12 deletion indicating enhanced resilience to tau toxicity.

The authors also show that elevated SLIT2 levels and demyelination in tauopathy and is reversed by Dap12 deletion. The author s also found correlation of SLIT2 expression and tau pathology in AD brain tissue. https://sciencemission.com/DAP12-deletion-reduces-neuronal-SLIT2


Background Pathogenic tau accumulation drives neurodegeneration in Alzheimer’s disease (AD). Enhancing the aging brain’s resilience to tau pathology would lead to novel therapeutic strategies. DAP12 (DNAX-activation protein 12), highly and selectively expressed by microglia, plays a crucial role in microglial immune responses. Previous studies have shown that tauopathy mice lacking DAP12 exhibit higher tau pathology but are protected from tau pathology-induced cognitive deficits. However, the exact mechanism behind this resilience remains elusive. Methods We investigated the effects of DAP12 deletion on tau pathology, as well as tau-induced brain inflammation and neurodegeneration, in homozygous human Tau P301S transgenic mice. In addition, we conducted single-nucleus RNA sequencing of hippocampal tissues to examine cell type-specific transcriptomic changes at the single-cell level.

A Fentanyl Vaccine Is About to Get Its First Major Test

ARMR’s experimental vaccine is designed to neutralize fentanyl in the bloodstream before it reaches the brain. Keeping fentanyl out of the brain would prevent the respiratory failure that comes with overdose, which causes death, as well as the euphoric high people get while taking fentanyl.

The basic idea behind ARMR’s shot is the same as any other vaccine. It trains the body’s immune system to make antibodies that recognize a foreign invader. But since fentanyl is much smaller than the pathogens our current vaccines target, it doesn’t trigger a natural antibody response on its own. To stimulate antibody production, ARMR has paired a fentanyl-like molecule with a ‘carrier’ protein—a deactivated diphtheria toxin that’s already used in several approved medical products…

…If a vaccinated person encounters fentanyl, antibodies in the blood would then bind to the drug and prevent it from traveling to the brain. Normally, fentanyl molecules can pass through the blood-brain barrier with ease, in part because of their small size. But fentanyl molecules with antibodies attached would be too big to get through. The result? No high and no overdose. The antibody-bound fentanyl molecules would eventually be passed in the urine.

The vaccine is based on work from the University of Houston, with collaborators at Tulane University designing an adjuvant derived from E.coli bacteria to boost the immune response to the vaccine. In rats, the shot blocked 92 to 98 percent of fentanyl from entering the brain and prevented the behavioral effects of the drug. The effects lasted for at least 20 weeks in the rats, which Gage thinks could translate to a year of protection in people.


ARMR Sciences of New York is trialing a vaccine in the Netherlands to protect against fentanyl-related overdose and death.

Science history: Female chemist initially barred from research helps helps develop drug for remarkable-but-short-lived recovery in children with leukemia — Dec. 6, 1954

In December 1954, Gertrude Elion and colleagues described a new compound they had developed that sent children with leukemia into remission. It would guide a new approach to “rational drug design.”

Taxonomy of Bacteria: Identification and Classification

We’ve been looking at bacteria for a few centuries now, so how do we categorize them? We love to classify things and put them in groups, so how does that work for bacteria? Well let’s learn about Gram-staining, antigens, other phenotypic and genotypic properties, and we will be well on our way to understanding this process!

Script by Kellie Vinal.

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The Genius Spiders Changing How We Think About Brains

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Despite having a brain the size of a pinhead, jumping spiders in the genus Portia can plan ahead, learn through trial and error, and even lie. How are they so smart? They’re changing what we know about cognition.

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Phages Carrying Silver Nanoparticles Could Combat Antibiotic Resistance

In a recent study, Bagchi and her colleagues discovered that together, silver nanoparticles scaffolded onto phages killed bacteria more potently than either component alone.

This suggests that the conjugates may be a new, promising weapon in the fight against antibiotic resistance.

Read more: https://bit.ly/3KKm5D4


In a recent study, researchers wanted to “take advantage of both worlds,” said Damayanti Bagchi, a material chemist who led the work as a postdoctoral researcher in Irene Chen’s laboratory at the University of California, Los Angeles.1 For the first time, Bagchi and her colleagues synthesized silver nanoparticles using phages called M13, which they also used as a scaffold for the nanoparticles. The silver particle and M13 phage conjugate killed bacteria more effectively than each component alone. The conjugate also slowed down the development of bacterial resistance. This work, published in Langmuir, expands researchers’ arsenal of weapons in their fight against antibiotic resistance.

“This is quite new, using phages as scaffolds [for silver nanoparticles]. I find it very exciting,” said Timea Fernandez, a biochemist at Winthrop University who was not involved in the study.

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