Gut microbial GABA imbalance emerges as a metabolic signature in mild autism spectrum disorder linked to overrepresented Escherichia.

Gut microbiota (GM) alterations have been implicated in autism spectrum disorder (ASD), yet the specific functional architecture remains elusive. Here, employing multi-omics approaches, we investigate stool samples from two distinct cohorts comprising 203 children with mild ASD or typical development. In our screening cohort, regression-based analysis for metabolomic profiling identifies an elevated γ-aminobutyric acid (GABA) to glutamate (Glu) ratio as a metabolic signature of ASD, independent of age and gender.

Emerging themes in microbial stress response and mechanistic insights: key findings from the fall 2024 ASM Theobald Smith Society meeting.

The annual fall meeting for the Theobald Smith Society was held in November 2024 on the campus of Rutgers University-New Brunswick. Eighty-six branch members from across New Jersey attended the meeting, composed of undergraduate, graduate, and postdoctoral trainees, faculty members, and government and industry professionals. This report highlights the breadth and diversity of research conducted by American Society for Microbiology members in the Theobald Smith Society and celebrates their groundbreaking discoveries.

Neonates exposed to HIV but uninfected exhibit an altered gut microbiota and inflammation associated with impaired breast milk antibody function.

Background: Infants exposed to HIV but uninfected have altered immune profiles which include heightened systemic inflammation. The mechanism(s) underlying this phenomenon is unknown. Here, we investigated differences in neonatal gut bacterial and viral microbiome and associations with inflammatory biomarkers in plasma.

Nutrient colimitation is a quantitative, dynamic property of microbial populations.

Resource availability dictates how fast and how much microbial populations grow. Quantifying the relationship between microbial growth and resource concentrations makes it possible to promote, inhibit, and predict microbial activity. Microbes require many resources, including macronutrients (e.

The mouth of America: the oral microbiome profile of the US population.

Importance: The oral microbiome is increasingly recognized to play key roles in human health and disease; yet, population-representative characterizations are lacking.

Objective: Characterize the composition, diversity, and correlates of the oral microbiome among US adults.

Design: Cross-sectional population-representative survey.

The oral microbiome and all-cause mortality in the US population.

Importance: Poor oral health, including periodontal disease, is associated with oral microbiome changes and increased mortality risk. However, no large studies have evaluated whether the oral microbiome is directly associated with mortality.

Objective: To evaluate whether measures of the oral microbiome is prospectively associated with all-cause mortality.

Impact of vascular Ehlers-Danlos Syndrome-associated Gly substitutions on structure, function, and mechanics using bacterial collagen.

Vascular Ehlers-Danlos syndrome (vEDS) arises from mutations in collagen-III, a major structural component of the extracellular matrix (ECM) in vascularized tissues, including blood vessels. Fibrillar collagens form a triple-helix that is characterized by a canonical (Gly-X-Y) sequence. The substitution of another amino acid for Gly within this conserved repeating sequence is associated with several hereditary connective tissue disorders, including vEDS.

Alternative splicing of transcript mediates the response of circadian clocks to temperature changes.

Circadian clocks respond to temperature changes over the calendar year, allowing organisms to adjust their daily biological rhythms to optimize health and fitness. In , seasonal adaptations are regulated by temperature-sensitive alternative splicing (AS) of () and () genes that encode key transcriptional repressors of clock gene expression. Although () gene encodes the critical activator of circadian gene expression, AS of its transcripts and its potential role in temperature regulation of clock function have not been explored.

Assessments of working group effectiveness in the planning of the New Jersey Kids Study: An applied mixed-methods study on the science of team science.

Introduction: The New Jersey Kids Study (NJKS) is a transdisciplinary statewide initiative to understand influences on child health, development, and disease. We conducted a mixed-methods study of project planning teams to investigate team effectiveness and relationships between team dynamics and quality of deliverables.

Methods: Ten theme-based working groups (WGs) (e.

Critical assessment of nanopore sequencing for the detection of multiple forms of DNA modifications.

While nanopore sequencing is increasingly used for mapping DNA modifications, it is important to recognize false positive calls as they can mislead biological interpretations. To assist biologists and methods developers, we describe a framework for rigorous evaluation that highlights the use of false discovery rate with rationally designed negative controls capturing both general background and confounding modifications. Our critical assessment across multiple forms of DNA modifications highlights that while nanopore sequencing performs reliably for high-abundance modifications, including 5-methylcytosine (5mC) at CpG sites in mammalian cells and 5-hydroxymethylcytosine (5hmC) in mammalian brain cells, it makes a significant proportion of false positive detections for low-abundance modifications, such as 5mC at CpH sites, 5hmC and N6-methyldeoxyadenine (6mA) in most mammal cell types.

Polygenic risk for alcohol use disorder affects cellular responses to ethanol exposure in a human microglial cell model.

Polygenic risk scores (PRSs) assess genetic susceptibility to alcohol use disorder (AUD), yet their molecular implications remain underexplored. Neuroimmune interactions, particularly in microglia, are recognized as notable contributors to AUD pathophysiology. We investigated the interplay between AUD PRS and ethanol in human microglia derived from iPSCs from individuals with AUD high-PRS (diagnosed with AUD) or low-PRS (unaffected).

Structure-Based Design of Covalent SARS-CoV-2 Papain-like Protease Inhibitors.

The COVID-19 pandemic is caused by SARS-CoV-2, a highly transmissible and pathogenic RNA betacoronavirus. Like other RNA viruses, SARS-CoV-2 continues to evolve with or without drug selection pressure, and many variants have emerged since the beginning of the pandemic. The papain-like protease, PL, is a cysteine protease that cleaves viral polyproteins as well as ubiquitin and ISG15 modifications from host proteins.

Beyond IQ: executive function deficits and their relation to functional, clinical, and neuroimaging outcomes in 3q29 deletion syndrome.

Background: 3q29 deletion syndrome (3q29del) is a rare (~1:30 000) genomic disorder associated with a wide array of neurodevelopmental and psychiatric phenotypes. Prior work by our team identified clinically significant executive function (EF) deficits in 47% of individuals with 3q29del; however, the nuances of EF in this population have not been described.

Methods: We used the Behavior Rating Inventory of Executive Function (BRIEF) to perform the first in-depth assessment of real-world EF in a cohort of 32 individuals with 3q29del (62.

Age and Hair Cortisol Levels as Predictors of SARS-CoV-2 Infection.

Chronic psychosocial stress is known to adversely impact immune function. During the SARS-CoV-2 pandemic, occupational stress among workers in healthcare was at an unprecedented level due to risks of infection and work demands. We performed a nested case-control study to investigate the associations between chronic stress and the risks of contracting SARS-CoV-2.

Long-term recovery of taste and smell following acute COVID-19 infection in a New Jersey cohort.

Loss of taste and smell is one of the most troubling symptoms of long COVID and may be permanent for some. Correlation between subjectively and objectively assessed olfactory and gustatory impairment is low, leading to uncertainty about how many people are affected, how many recover, and to what extent. We prospectively investigated the effects of COVID-19 on long-term chemosensory function in a university and hospital-based cohort in NJ.

The role of intestinal microbiota in physiologic and body compositional changes that accompany CLA-mediated weight loss in obese mice.

Objective: Obesity continues to be a major problem, despite known treatment strategies such as lifestyle modifications, pharmaceuticals, and surgical options, necessitating the development of novel weight loss approaches. The naturally occurring fatty acid, 10,12 conjugated linoleic acid (10,12 CLA), promotes weight loss by increasing fat oxidation and browning of white adipose tissue, leading to increased energy expenditure in obese mice. Coincident with weight loss, 10,12 CLA also alters the murine gut microbiota by enriching for microbes that produce short chain fatty acids (SCFAs), with concurrent elevations in fecal butyrate and plasma acetate.

Scaled and efficient derivation of loss-of-function alleles in risk genes for neurodevelopmental and psychiatric disorders in human iPSCs.

Translating genetic findings for neurodevelopmental and psychiatric disorders (NPDs) into actionable disease biology would benefit from large-scale and unbiased functional studies of NPD genes. Leveraging the cytosine base editing (CBE) system, we developed a pipeline for clonal loss-of-function (LoF) allele mutagenesis in human induced pluripotent stem cells (hiPSCs) by introducing premature stop codons (iSTOP) that lead to mRNA nonsense-mediated decay (NMD) or protein truncation. We tested the pipeline for 23 NPD genes on 3 hiPSC lines and achieved highly reproducible, efficient iSTOP editing in 22 genes.

Alzheimer's Disease Has Its Origins in Early Life via a Perturbed Microbiome.

Alzheimer's disease (AD) is a neurodegenerative disorder with limited therapeutic options. Accordingly, new approaches for prevention and treatment are needed. One focus is the human microbiome, the consortium of microorganisms that live in and on us, which contributes to human immune, metabolic, and cognitive development and that may have mechanistic roles in neurodegeneration.

Comprehensive network modeling approaches unravel dynamic enhancer-promoter interactions across neural differentiation.

Background: Increasing evidence suggests that a substantial proportion of disease-associated mutations occur in enhancers, regions of non-coding DNA essential to gene regulation. Understanding the structures and mechanisms of the regulatory programs this variation affects can shed light on the apparatuses of human diseases.

Results: We collect epigenetic and gene expression datasets from seven early time points during neural differentiation.