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Category: genetics – Page 19

How the brain suppresses itch during stress

The researchers then tested whether these stress-activated neurons directly influence itch. “We ran some pilot experiments, and we saw that surprisingly, acute stress was able to suppress acute itching,” says the first author of the study.

When the team artificially activated the stress neurons, scratching behaviour decreased in both short-term chemically induced itch and a psoriasis-like chronic itch model. Conversely, when these neurons were silenced, stress no longer reduced scratching. These results showed that these neurons are both necessary and sufficient for stress-induced suppression of itch.

“We show that a specific circuit in the lateral hypothalamus can suppress itch during acute stress, revealing how the brain directly links emotional states to sensory perception,” says the corresponding author. “By identifying the specific neural circuit that links stress to itch, we are opening the possibility of targeting these brain mechanisms to better manage chronic stress-induced worsening of itch.” ScienceMission sciencenewshighlights.

Researchers have mapped a neural circuit in the brain involved in the complex relationship between itch and stress. Their findings, published in Cell Reports, reveal how specific neurons activated during stress can directly regulate itch.

Itch and pain are both unpleasant sensations triggered by harmful or irritating stimuli, but they lead to different behavioural responses. While pain typically causes us to withdraw (such as pulling our hand away from a fire), itch drives scratching. Scientists have long known that emotional states such as stress and anxiety can influence the intensity of these sensations. While the neural mechanisms linking stress and pain have been studied extensively, the effect of stress on itch has remained poorly understood.

In the new study, the team focused on the lateral hypothalamic area (LHA), a brain region known to regulate stress, motivation, and emotional states. Using genetically engineered mouse models, the researchers identified a specific population of neurons in the LHA that become active during acute stress.

Continue reading “How the brain suppresses itch during stress” | >

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].

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.

Utility of Targeted RNA Analysis in Neurogenetic Disorders

Anti-CASPR2 encephalitis on EEG

Many patients show (DSWA) and IED, reflecting widespread cortical dysfunction.

Importantly, diffuse slowing and absence of deep (N3) sleep may signal a worse prognosis. — @Natalia Olaru.

CLICK THIS TO READ LINK

Objective The clinical manifestations of autoimmune encephalitis associated with contactin-associated protein-like 2 (CASPR2) were atypical and progressed slowly. We aimed to summarize the characteristics of video-electroencephalography (V-EEG) and video-polysomnography (V-PSG) to achieve early recognition and assess long-term outcomes.

Abstract: The changing landscape of urothelial carcinoma: on the edge of paradigm shift

In this Review Joshua J. Meeks discusses advancements in biomarkers and novel therapeutics that are likely to dramatically improve survival of patients with Bladder Cancer.

1Departments of Urology and.

2Biochemistry and Molecular Genetics, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA.

3Jesse Brown VA Medical Center, Department of Veterans Affairs, Chicago, Illinois, USA.

Address correspondence to: Joshua J. Meeks, Department of Urology, Biochemistry and Molecular Genetics, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA. Phone: 312.695.8146; Email: [email protected].

Challenges and opportunities in adapting high-throughput functional assays for in vivo neuroscience

High-throughput functional assays such as CRISPR screens and massively parallel reporter assays have transformed studies of gene regulation in cultured cells, but their translation to neuroscience remains limited.

The brain presents unique barriers to scaling these assays, including delivery bottlenecks, low recovery, and the complexity of cellular diversity and spatial architecture.

Emerging strategies—ranging from optimized viral vectors and streamlined library design to integration with singlecell and spatial transcriptomics—offer paths to overcome these limitations.

Together, these innovations are paving the way toward in vivo functional genomics approaches that can bridge the gap between genetic variation, regulatory logic, and brain function. sciencenewshighlights ScienceMission https://sciencemission.com/high-throughput-functional-assays

Genetic sequencing has aided in the discovery of novel mutations in inborn errors of immunity, but their clinical relevance often remains unclear

In this Research Article, Marcus Altfeld & team identify a TLR8 gene mutation causing immune overactivation and inflammation in two siblings, linking genetic change to immune system dysfunction and disease: Immunology.

14 Hamburg Center for Translational Immunology;

15 German Center for Child and Adolescent Health (DZKJ), partner site Hamburg; and.

16 Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Structures of hantavirus glycoprotein tetramers

This surface protein complex for the Andes virus is a mushroom-shaped structure called a Gn-Gc tetramer. To map the 3D structures, the team first produced virus-like particles that mimic a real virus, but without the genome that makes a virus infectious. They then used a cryo-electron microscope—which shines an electron beam through a frozen sample and detects the shadows created by molecules—to reconstruct the three-dimensional structures of the Gn-Gc tetramers on the surface of the virus-like particles.

But there was a twist: To obtain extremely high-resolution structures, the researchers painstakingly identified and isolated shadows from only the tetramers that were pointing sidewise relative to the electron beam and ignored those pointing in other directions. This allowed them to borrow a reconstruction method typically used on individual proteins.

The resulting structures have an extremely high resolution of 2.3 angstroms, meaning details the size of just a couple of atoms were effectively captured. That’s enough to represent a transformational improvement over another team’s model of the tetramer from a few years ago, at a resolution of 12 angstroms, still tiny but large enough to produce some key inaccuracies – ones effectively corrected with the newer method and resulting structure.

These latest structures show the Gn-Gc tetramer in a particular state before it has infected a cell. For vaccines or antibody therapies to be most effective against a hantavirus, mimicking surface proteins at this pre-infection stage is essential. ScienceMission sciencenewshighlights.

Hantaviruses, transmitted from rodents to people, have a death rate approaching 40%. They’re found around the world, and because there are no approved vaccines or treatments, they’re among the pathogens of highest concern for future pandemics. They made news in the United States last year when Betsy Arakawa, the wife of actor Gene Hackman, died from a hantavirus infection in New Mexico in March.

New findings published in the journal Cell about the Andes virus, a hantavirus endemic to the southwestern U.S. and other parts of North and South America, represent a crucial first step towards much-needed vaccines and antibody therapies for this and other hantaviruses.

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MDSGene Systematic Review of Common Forms of Dominant Hereditary Spastic Paraplegia: Novel Insights

Hereditary spastic paraplegia refers to a group of disorders characterized by progressive spasticity of lower extremities. The Genetic Nomenclature Study Group found differing frequency of variant types across 3 HSP genes: ATL1, SPAST and REEP1.

The PubMed literature search and articles obtained through additional sources yielded a total of 239 articles for HSP–ATL1, of which 70 were eligible, 531 articles for HSP–SPAST, for which 187 were eligible, and 334 articles for HSP–REEP1, of which 31 were eligible (Fig. 1, Supplementary File_HSP Article Screening Log).

By classifying these articles according to study type, we found that the most common were genetic screening studies (36.3%), family studies (30.4%), followed by, case reports/series (23.2%), and other/mixed-type studies (10.0%). While genetic screening studies were the most common study type for HSP–SPAST and HSP–REEP1, family studies were the most common study type for HSP–ATL1 (Table S2).

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