Glutamine Synthetase: Diverse Regulation and Functions of an Ancient Enzyme.

Glutamine synthetase (GS) is a ubiquitous enzyme central to nitrogen metabolism, catalyzing the ATP-dependent formation of glutamine from glutamate and ammonia. Positioned at the intersection of nitrogen metabolism with carbon metabolism, the activity of GS is subject to sophisticated regulation. While the intricate regulatory pathways that govern GS were established long ago, recent work has demonstrated that homologues are controlled by multiple distinct regulatory patterns, such as the metabolite induced oligomeric state formation in archaeal GS by 2-oxoglutarate.

Seagrass wasting disease prevalence and lesion area increase with invertebrate grazing across the northeastern Pacific.

Disease is a key driver of community and ecosystem structure, especially when it strikes foundation species. In the widespread marine foundation species eelgrass (Zostera marina), outbreaks of wasting disease have caused large-scale meadow collapse in the past, and the causative pathogen, Labyrinthula zosterae, is commonly found in meadows globally. Research to date has mainly focused on abiotic environmental drivers of seagrass wasting disease, but there is strong evidence from other systems that biotic interactions such as herbivory can facilitate plant diseases.

Single-particle tracking reveals heterogeneous PIEZO1 diffusion.

The mechanically-activated ion channel PIEZO1 is critical to numerous physiological processes, and is activated by diverse mechanical cues. The channel is gated by membrane tension and has been found to be mobile in the plasma membrane. We employed single particle tracking (SPT) of endogenous, tdTomato-tagged PIEZO1 using Total Internal Reflection Fluorescence Microscopy in live cells.

A single-site randomized controlled trial of partner navigation to HCV treatment for people who inject drugs: a study protocol for the You're Empowered for Treatment Initiation (YETI) partner trial.

Background: Disparities persist in testing and treatment for hepatitis C virus (HCV), leaving socially marginalized populations, including people who inject drugs (PWID), less likely to benefit from curative treatment. Linkage services are often insufficient to overcome barriers to navigating the medical system and contextual factors.

Methods: The You're Empowered for Treatment Initiation (YETI) Partner trial is a single-site randomized controlled trial evaluating the efficacy of a two-session behavioral intervention that engages injecting partners as peer navigators for HCV treatment.

DNA methylation profiling at base-pair resolution reveals unique epigenetic features of early-onset colorectal cancer in underrepresented populations.

Background: The incidence of early-onset colorectal cancer (EOCRC) has been rising at an alarming rate in the USA, and EOCRC disproportionately affects racial/ethnic minorities. Here, we construct comprehensive profiles of EOCRC DNA methylomes at base-pair resolution for a cohort of Hispanic and African American patients.

Results: We show the epigenetic landscape of these EOCRC patients differs from that of late-onset colorectal cancer patients, and methylation canyons in EOCRC tumor tissue preferentially overlapped genes in cancer-related pathways.

APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology.

Background: Apolipoprotein E ε4 (APOE4) is the strongest genetic risk factor for late-onset Alzheimer's disease (LOAD). A recent case report identified a rare variant in APOE, APOE3-R136S (Christchurch), proposed to confer resistance to autosomal dominant Alzheimer's Disease (AD). However, it remains unclear whether and how this variant exerts its protective effects.

Atherogenic index of plasma and coronary artery disease: a systematic review and meta-analysis of observational studies.

Background: Atherogenic index of plasma (AIP), a novel logarithmic index that combines fasting triglyceride and high-density lipoprotein cholesterol concentrations, is associated with the burden of atherosclerosis. This study aimed to evaluate the relationship between AIP and coronary artery disease (CAD) risk, severity, and prognosis in populations with and without established CAD.

Methods: PubMed, Embase, and Web of Science were systematically searched from the inception of each database to August 13, 2024.

Within-session propulsion asymmetry changes have a limited effect on gait asymmetry post-stroke.

Background: Biomechanical gait impairments, such as reduced paretic propulsion, are common post-stroke. Studies have used biofeedback to increase paretic propulsion and reduce propulsion asymmetry, but it is unclear if these changes impact overall gait asymmetry. There is an implicit assumption that reducing propulsion asymmetry will improve overall gait symmetry, as paretic propulsion has been related to numerous biomechanical impairments.

Demographic disparities in access to COVID-19 clinical trial sites across the United States: a geospatial analysis.

Throughout the COVID-19 pandemic, underserved populations, such as racial and ethnic minority communities, were disproportionately impacted by illness and death. Ensuring people from diverse backgrounds have the ability to participate in clinical trials is key to advancing health equity. We sought to analyze the spatial variability in locations of COVID-19 trials sites and to test associations with demographic correlates.

Association of estimated glucose disposal rate with metabolic syndrome prevalence and mortality risks: a population-based study.

Background: Insulin resistance (IR) is a central pathophysiological factor in metabolic syndrome (MetS) and an essential driver of cardiovascular disease (CVD) and mortality. The estimated glucose disposal rate (eGDR) is a reliable marker of IR and has been associated with CVD prognosis. This study aims to examine the relationship between eGDR, MetS, and their predictive roles in clinical outcomes.

Assessing public support for air pollution mitigation and control policies: health, socioeconomic, and ideological predictors in an overburdened and vulnerable region of the U.S.

Background: The San Joaquin Valley (SJV) in California is one of the most polluted regions in the U.S. This study examined favorability for air pollution mitigation policies, interventions, and identified predictors amongst region's residents.

Mortality risk among individuals who smoke opioids compared with those who inject: A propensity score-matched cohort analysis of United States national treatment data.

Background And Aims: Opioid smoking is becoming more common in the United States. The aim of this analysis was to estimate relative mortality risk among those who primarily smoke opioids compared with those who inject.

Design: Retrospective propensity score-matched cohort analysis.

Wealth is health: High economic status in Cameroon correlates with protective gear use in traffic injuries and improved clinical outcomes.

Introduction: Africa is the least motorized populated continent, yet it experiences the highest traffic fatality rate. Despite laws mandating helmet and seatbelt use, data on protective gear use among Cameroonian road traffic injury (RTI) patients remains sparse.

Methods: We extracted Cameroon Trauma Registry data prospectively collected from 10 hospitals during July 2022 to December 2023.

First-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase 3 trial.

Programmed cell death protein-1 (PD-1) inhibitors plus chemotherapy have been the standard of care in the first-line treatment of advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma; however, the survival benefits are modest in patients with low programmed death ligand 1 (PD-L1) expression. Here we investigated the efficacy and safety of cadonilimab (PD-1/cytotoxic T lymphocyte antigen-4 (CTLA-4) bispecific antibody) plus chemotherapy as first-line treatment in G/GEJ adenocarcinoma. The prespecified interim analysis is reported here.

Production of real signs but not pseudosigns affected by age of acquisition in American Sign Language.

Research shows that insufficient language access in early childhood significantly affects language processing. While the majority of this work focuses on syntax, phonology also appears to be affected, though it is unclear exactly how. Here we investigated phonological production across age of acquisition of American Sign Language (ASL).

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Leveraging a phased pangenome for haplotype design of hybrid potato.

The tetraploid genome and clonal propagation of the cultivated potato (Solanum tuberosum L.) dictate a slow, non-accumulative breeding mode of the most important tuber crop. Transitioning potato breeding to a seed-propagated hybrid system based on diploid inbred lines has the potential to greatly accelerate its improvement.

Tissue-resident memory CD8 T cell diversity is spatiotemporally imprinted.

Tissue-resident memory CD8 T (T) cells provide protection from infection at barrier sites. In the small intestine, T cells are found in at least two distinct subpopulations: one with higher expression of effector molecules and another with greater memory potential. However, the origins of this diversity remain unknown.

A map of the rubisco biochemical landscape.

Rubisco is the primary CO-fixing enzyme of the biosphere, yet it has slow kinetics. The roles of evolution and chemical mechanism in constraining its biochemical function remain debated. Engineering efforts aimed at adjusting the biochemical parameters of rubisco have largely failed, although recent results indicate that the functional potential of rubisco has a wider scope than previously known.

Resolving native GABA receptor structures from the human brain.

Type A GABA (γ-aminobutyric acid) receptors (GABA receptors) mediate most fast inhibitory signalling in the brain and are targets for drugs that treat epilepsy, anxiety, depression and insomnia and for anaesthetics. These receptors comprise a complex array of 19 related subunits, which form pentameric ligand-gated ion channels. The composition and structure of native GABA receptors in the human brain have been inferred from subunit localization in tissue, functional measurements and structural analysis from recombinant expression and in mice.

The maternal X chromosome affects cognition and brain ageing in female mice.

Female mammalian cells have two X chromosomes, one of maternal origin and one of paternal origin. During development, one X chromosome randomly becomes inactivated. This renders either the maternal X (X) chromosome or the paternal X (X) chromosome inactive, causing X mosaicism that varies between female individuals, with some showing considerable or complete skew of the X chromosome that remains active.

Parental Monitoring, Deviant Peer Affiliation, and Adolescents' Cyberbullying Involvement: Prospective Within-Person Associations.

Cybervictimization and cyberbullying are serious public health issues. Parental monitoring serves as a protective factor, reducing adolescents' risk of cybervictimization and cyberbullying. However, no study has systematically explored the interplay between parental monitoring, cybervictimization and cyberbullying at within-person processes, the mediating mechanisms between them, and the moderator of sex among Chinese adolescents.

Pulmonary Atresia with Intact Ventricular Septum, an Evolving Strategy in the Era of PDA Stenting: Single Center Experience.

Repair or palliation of pulmonary atresia with intact ventricular septum (PA/IVS) often falls into one of 4 categories: cardiac transplant, 2-ventricular circulation, 1.5 ventricle circulation, or single ventricle circulation. The optimal management strategy has been an area of much debate.