Science, Volume 392, Issue 6797, Page 471-471, April 2026.
Disordered protein LAT encodes relative levels of signaling pathways in T cell activation
Science, Volume 392, Issue 6797, April 2026.
Lymphoid tissue chemokines limit priming duration to preserve CD8+ T cell functionality
Science, Volume 392, Issue 6797, April 2026.
Facilitating Thought Progression: A Neurocognitive Framework Linking Thought Dynamics and Mood Disorders
Mood and thought are tightly coupled, but the mechanisms linking them are not understood. This link is particularly important when considering mood disorders such as depression. We propose the Facilitating Thought Progression (FTP) framework, which characterizes depression as a disorder of thought dynamics, encompassing both the temporal evolution and semantic expanse of mental activity. Five parameters jointly determine the fluency of thought progression: breadth, speed, flexibility, novelty, and scope.
Implications of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) for Mood Disorders and Suicide Risk
A strategic imperative in mood disorders is to identify innovative mechanisms that translate into improved therapeutics when compared to the extant options. More specifically, there is a need for treatments with greater efficacy, shorter time-to-peak efficacy, greater durability of effect as well as improved tolerability profiles. Moreover, priority has also shifted towards identifying mood disorder therapeutics capable of targeting domains of psychopathology that are most pervasive, debilitating and inadequately treated by conventional pharmacology (e.g., anhedonia, cognitive impairment).
Current Landscape of Mental Health Conversational Agents From a Trauma-Informed Care Lens: Scoping Review
Background: Conversational agents (CAs) are increasingly used in mental health care to enhance access and engagement. However, their safe, ethical, and user-sensitive design remains a challenge. Despite growing attention to trauma-informed approaches in human-computer interaction, there is limited work on how the trauma-informed care (TIC) framework could be applied in the design of mental health CAs and no comprehensive synthesis to date. Objective: Guided by the Substance Abuse and Mental Health Services Administration’s TIC framework, this scoping review explored how TIC principles (safety; trustworthiness and transparency; collaboration and mutuality; empowerment, voice, and choice; peer support; and cultural, historical, and gender issues) are currently represented in the design and evaluation of mental health conversational agents (MHCAs) and identified gaps and opportunities to promote more trauma-informed design practices. Methods: Online databases, as well as a secondary survey of citation lists from an initial search, were used to identify English-language journal articles and conference proceedings from 2000 to 2024 that empirically evaluated an independent, web- or app-based, unassisted CA used for mental health and included concepts from TIC. Results: Our analysis included 38 publications (n=28, 73.7%, published in 2020 or later) covering 28 distinct MHCAs. Most studies used experimental methods (n=23, 60.6%) or user studies (n=11, 28.9%), with samples skewed toward female (men: mean 34.92%, SD 18.64%), young in age (mean 32.52, SD 14.6 y), and predominantly nonclinical (n=29, 76.3%). MHCAs were largely rule-based prototypes. No studies explicitly referenced the TIC framework as a guiding lens for MHCA design or evaluation. A total of 26 studies referenced terminology from TIC core principles but rarely defined them, while all 38 included language that could be linked to one or more principles. Overall, TIC-related concepts appeared most often within intervention design descriptions, qualitative assessments, or as items embedded in questionnaires evaluating broader constructs. Trustworthiness and transparency, safety, empowerment, voice and choice, and collaboration and mutuality were comparatively well addressed, while peer support and cultural, historical, and gender issues were largely absent. Design recommendations, where present, were relatively broad and emphasized secure, customizable, reliable, human-like, and context-sensitive MHCAs that offered multimodal interaction, goal setting and tracking, and transparency. Conclusions: Studies did not self-identify as using Substance Abuse and Mental Health Services Administration’s framework for TIC, making it more difficult to identify its elements. The fragmented terms, disciplines, and metrics used make it difficult to draw more systematic conclusions about the current research landscape related to TIC, but our analysis indicates TIC to be a descriptive and potentially unifying framework and provides a starting point for the explicit trauma-informed MHCA research and design.
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Brain Glucose Levels Act as a Metabolic Switch for Myelin Formation
Scientists have long known that myelin doesn’t appear everywhere in the brain at once. Some regions myelinate early, others much later, and the timing shapes everything from motor development to cognitive maturation. What has remained elusive is why these regional differences emerge in the first place. A new study in Nature Neuroscience, titled “Glucose-dependent spatial and temporal modulation of oligodendrocyte progenitor cell proliferation via ACLY-regulated histone acetylation,” points to an unexpected driver: shifting glucose levels that act as a metabolic switch, telling progenitor cells when to divide and when to mature into myelin‑forming oligodendrocytes.
The work, led by researchers at the Advanced Science Research Center at the CUNY Graduate Center (CUNY ASRC), maps glucose distribution across the developing mouse brain and reveals that these spatial and temporal fluctuations are not just metabolic background noise. They are instructive signals. “Regions with high glucose levels exhibited greater OPC proliferation and histone acetylation than regions with low glucose,” the authors wrote in the paper’s abstract, suggesting glucose as a key regulator of oligodendrocyte progenitor cell (OPC) population dynamics.
Using MALDI imaging at the CUNY ASRC MALDI Imaging Core Facility, the team visualized glucose concentrations across brain regions during early development in mice. Areas rich in glucose contained actively dividing OPCs, while regions with lower glucose levels harbored cells beginning to differentiate into oligodendrocytes. This pattern suggested that glucose availability helps determine whether OPCs expand their numbers or transition toward myelin production.
“Our findings show that glucose is not just fuel for the brain, it’s also a signal for the cells to divide,” said lead author Sami Sauma, PhD, a postdoctoral researcher with the CUNY ASRC Neuroscience Initiative. “When glucose levels are high in a particular brain region, progenitors use it to drive proliferation. As glucose levels shift, the same cells switch gears and begin maturing.”
An enzyme, ATP‑citrate lyase (ACLY), which converts glucose‑derived citrate into acetyl‑CoA in the nucleus, is central to this process. This acetyl‑CoA fuels histone acetylation, activating genes required for cell proliferation. When the researchers deleted Acly in OPCs, the cells could no longer proliferate efficiently, leading to a temporary reduction in myelin due to decreased OPC numbers. Yet differentiation still occurred, thanks to a compensatory pathway: mature oligodendrocytes can generate acetyl‑CoA outside the nucleus from alternative fuels such as ketone bodies.
This metabolic flexibility proved more than a biochemical curiosity. When mice lacking ACLY in OPCs were placed on a ketogenic diet, their myelin deficits improved. “The same cell lineage interprets different metabolic signals at distinct stages of development,” said senior author Patrizia Casaccia, MD, PhD, founding director of the CUNY ASRC Neuroscience Initiative. “By understanding how glucose and alternative energy sources regulate proliferation and myelin formation, we are uncovering new metabolic strategies that could be harnessed to protect myelin in the developing brain.”
The developmental window examined in mice corresponds to roughly 32 to 40 weeks of human gestation—a period when premature infants are particularly vulnerable to white‑matter injury. The findings raise the possibility that metabolic support during this stage could help preserve the progenitor cells responsible for building myelin. They may also inform future approaches to repairing myelin in disorders such as multiple sclerosis.
The post Brain Glucose Levels Act as a Metabolic Switch for Myelin Formation appeared first on GEN – Genetic Engineering and Biotechnology News.
Remembering J. Craig Venter: a relentless scientist who changed biotech — and was all too easily misunderstood
J. Craig Venter, a scientist whose relentless ambition helped turn genetics from an artisanal trade into an industrialized information machine, died Wednesday at 79. The cause was side effects of a cancer treatment.
Along the way, he did things that can only be described as really cool. He raced against a government-funded project to sequence the first human genome, grabbing headlines around the world; traveled the ocean in his sailboat collecting genetic information about sea life; and removed a bacterium’s genome and rebooted the organism with an identical set of genes he and his team had synthesized. He drove fast cars, drank red wine, and pissed people off.
STAT+: Katherine Szarama named acting director of FDA’s vaccines and biologics center
WASHINGTON — The Food and Drug Administration has named Katherine Szarama as the acting director of the Center for Biologics Evaluation and Research, which regulates vaccines, gene therapies, and the blood supply.
A Health and Human Services official confirmed the move, which was first reported by Politico, to STAT.
She is replacing Vinay Prasad, who left the agency on Thursday after a tumultuous tenure during which he issued a series of controversial decisions on rare disease drugs and vaccines. FDA Commissioner Marty Makary said in March that Prasad would return to the University of California San Francisco.
Korean Medical Consultation With Open-Weight Large Language Models: Pilot Comparative Evaluation of Retrieval-Augmented Generation With Metadata Filtering
Background: This study develops an open-source large language model–based chatbot tailored for Korean health consultations. The chatbot was implemented using the retrieval-augmented generation (RAG) technique alongside metadata filtering to enhance its performance. Objective: This study aims to analyze and compare the performance of a RAG-based chatbot with other leading language models in the context of Korean health consultations. Methods: A 10.4 GB Korean medical document corpus (487,277 segments) was constructed from official websites of major Korean hospitals, public health sources, and medical textbooks. This study quantitatively compared 5 open-source large language models (Qwen3:4B, Mistral:7B, Llama-3.1:8B, Gpt-Oss:20B, and Gemma3:27B) in 3 configurations: baseline (model only), RAG-only, and RAG with metadata filtering. The RAG system used a specialized Korean embedding model (upskyy/bge-m3-korean) and an Elasticsearch store. Performance was assessed by an emergency medicine specialist using a validation set of 226 questions across 7 common diseases and scoring responses based on accuracy, safety, and helpfulness. Results: The application of RAG alone failed to yield statistically significant performance improvements and, in some cases (Llama 3.1: 8B and Gemma 3: 27B), resulted in decreased scores. However, the combination of RAG with metadata filtering yielded statistically significant (<.05) performance increases in most models. Notably, the average score for Mistral:7B increased from 3.79, SD 0.08, to 4.10, SD 0.10, and Gpt-Oss:20B increased from 4.43, SD 0.05, to 4.51, SD 0.04, with the latter achieving the highest safety score (4.61, SD 0.03). The Gemma3:27B model, which possessed a high baseline performance (4.42, SD 0.03), was an exception, exhibiting no significant improvement (=.14) even with filtering. Conclusions: The effectiveness of RAG for specialized domains such as Korean medical consultation is highly dependent on a metadata filtering process that controls the quality of retrieved information; simple information augmentation is insufficient. Furthermore, the benefit of RAG is limited when a model’s intrinsic knowledge (eg, Gemma3:27B) already meets or exceeds the quality of the external knowledge base. This finding indicates that performance enhancement strategies must account for both the retrieval mechanism’s quality and the model’s preexisting capabilities.
