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A brain reward circuit inhibited by next-generation weight-loss drugs in mice

New research using humanized mouse models has finally pulled back the curtain on how these small-molecule drugs work in the brain, revealing that they don’t just tell the body it’s full—they actually change how we perceive “treats.”

1. The Homeostatic Circuit: This is the body’s fuel gauge. It involves the hypothalamus and hindbrain, which manage basic hunger and energy levels. It’s the circuit that tells you, “I’ve had enough calories for today.”

These new weight-loss pills do more than just settle your stomach; they speak directly to the brain’s reward center to help quiet the “food noise” that leads to overeating.

This is a “proof of concept” study. It proves the mechanism exists, but it doesn’t yet guarantee that a pill will be a side-effect-free “cure” for overeating in humans.

Humanized glucagon-like peptide 1 receptor (GLP1R) mouse models are used to investigate the neural circuitry through which small-molecule GLP1R agonists modulate feeding, with implications for how these orally delivered weight-loss drugs engage brain reward circuits.

Nanotechnology-Driven Therapeutic Innovations in Neurodegenerative Disorders: A Focus on Alzheimer’s and Parkinson’s Disease

Neurodegenerative disorders entail a progressive loss of neurons in cerebral and peripheral tissues, coupled with the aggregation of proteins exhibiting altered physicochemical properties. Crucial to these conditions is the gradual degradation of the central nervous system, manifesting as impairments in mobility, aberrant behaviors, and cognitive deficits. Mechanisms such as proteotoxic stress, neuroinflammation, oxidative stress, and programmed cell death contribute to the ongoing dysfunction and demise of neurons. Presently, neurodegenerative diseases lack definitive cures, and available therapies primarily offer palliative relief. The integration of nanotechnology into medical practices has significantly augmented both treatment efficacy and diagnostic capabilities.

Researchers discover advanced language processing in the unconscious human brain

Baylor College of Medicine researchers have found that the human brain is capable of sophisticated language processing while in an unconscious state from general anesthesia. The findings, published in the latest edition of Nature, challenge what we know about the role of consciousness and cognition, and could open new ways of understanding memory, language and brain-computer interfaces.

“Our findings show that the brain is far more active and capable during unconsciousness than previously thought,” said Dr. Sameer Sheth, professor and Cullen Foundation Endowed chair of neurosurgery and a McNair Scholar at Baylor. “Even when patients are fully anesthetized, their brains continue to analyze the world around them.”

Sheth, who is also a neurosurgeon at Baylor St. Luke’s Medical Center, and his collaborators first recorded neural activity from hundreds of individual neurons in the hippocampus, a part of the brain associated with memory, while patients were under general anesthesia during epilepsy surgery. Patients undergoing this type of surgery were sought after because it allowed researchers access to this particular part of the brain.

A new way coronaviruses can get into human cells

CcCoV-KY43 is found in heart-nosed bats, or Cardioderma cor, an ecologically important species found mainly in eastern Africa, including eastern Sudan and northern Tanzania.

The researchers say the zoonotic (animal-to-human) and pandemic potential of alphaCoVs has remained relatively unchartered – to date, only two cellular receptors have been characterized for alphaCoVs.

They screened the CcCoV-KY43 spike against a panel of human receptors, identified direct interactions with the human CEACAM proteins CEACAM3, CEACAM5 and CEACAM6. Overexpression of human CEACAM6—a protein widely expressed in the human lung—conferred permissivity to otherwise refractory human cells.

During the study, partners provided specific expertise. They identified CcCoV-KY43’s ability to infect human cells and confirmed CEACAM6 supports human cell entry.

They measured how strongly CEACAM6 binds to the spike, and solved the spike structure and receptor binding in atomic detail. They showed that the RBD binds the amino-terminal IgV-like domain of human CEACAM6.

They also made initial CcCov detection in bats and mapped it across Kenya, and showed where CEACAM6s is expressed in the human body, testing serum from people living in CcCoV areas to see if they might have previously been infected by CcCoV-KY43.

Continue reading “A new way coronaviruses can get into human cells” | >

Efficacy and Safety of Amifampridine in Myasthenia GravisA Randomized, Double-Blind, Placebo-Controlled Crossover Trial

Class I evidence that in patients with AChRAb+ myasthenia gravis, the addition of amifampridine to pyridostigmine was not superior to treatment with pyridostigmine alone and was associated with a higher incidence of adverse events.

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Teaching NeuroImage: Bilateral Posterior Limb Internal Capsule T2 Hyperintensity and Severe Cerebellar Atrophy in 2 Lifelong Friends

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First Images From the Pandora Exoplanet Mission

A new mission promises to ‘open the box’ on exoplanet science. Scientists and engineers recently released the first engineering images from the Pandora exoplanet survey mission. The pictures represent the first ever images from a NASA Astrophysics Pioneers Program mission. Established in 2020, the program looks to test the feasibility of small low cost missions designed to address key questions in astronomy and astrophysics.

Cellular and subcellular specialization enables biology-constrained deep learning

Galloni et al. introduce “dendritic target propagation”: a Dale’s law-compliant learning algorithm for cortical microcircuits with soma-and dendrite-targeting inhibition and realistic connectivity constraints. By combining experimentally derived BTSP and Hebbian rules, dendrites compute local error proxies via E/I mismatch, supporting gradient-based deep learning during simultaneous bottom-up and top-down signaling.

Older people with HIV are especially vulnerable to influenza, yet this group remains understudied

https://doi.org/10.1172/jci.insight.199232 Here, Savita G. Pahwa & team demonstrate high-dose vaccination for influenza strengthens immunity in older adults with HIV after prior standard dosing, but not all strain-specific weaknesses were overcome.

1Department of Microbiology and Immunology.

2Division of Biostatistics, Department of Public Health Sciences; and.

3Division of Infectious Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.

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