Gestational exposure to PM, NO, and sex steroid hormones: Identifying critical windows of exposure in the Rochester UPSIDE Cohort.

Background: Sex steroid hormones are critical for maintaining pregnancy and optimal fetal development. Air pollutants are potential endocrine disruptors that may disturb sex steroidogenesis during pregnancy, potentially leading to adverse health outcomes.

Methods: In the Environmental influences on Child Health Outcomes Understanding Pregnancy Signals and Infant Development pregnancy cohort (Rochester, NY), sex steroid concentrations were collected at study visits in early-, mid-, and late-pregnancy in 299 participants.

Anatomical mapping of neural lineages expressing the transient receptor potential vanilloid type 1 receptor using a modified and combined PACT and CUBIC protocol for rapid tissue clearance.

Aim: Tissue clearance is a rapidly evolving technology that allows for the three-dimensional imaging of intact biological tissues. Preexisting tissue-clearing techniques, such as Passive Clarity Technique (PACT) and Clear Unobstructed Brain Imaging Cocktails and Computational Analysis (CUBIC), clear tissues adequately but have distinct disadvantages, such as taking extensive time to clear tissues and degradation of endogenous tissue fluorescence. We developed a new tissue-clearing technique combining PACT and CUBIC protocols to map the neural lineages expressing the transient receptor potential vanilloid type 1 (TRPV1) receptor.

Humanized Candida and NanoBiT Assays Expedite Discovery of Bdf1 Bromodomain Inhibitors With Antifungal Potential.

The fungal Bromodomain and Extra-Terminal (BET) protein Bdf1 is a potential antifungal target against invasive fungal infections. However, the need to selectively inhibit both Bdf1 bromodomains (BDs) over human orthologs and the lack of molecular tools to assess on-target antifungal efficacy hamper efforts to develop Bdf1 BD inhibitors as antifungal therapeutics. This study reports a phenyltriazine compound that inhibits both Bdf1 BDs from the human fungal pathogen Candida glabrata with selectivity over the orthologous BDs from the human BET protein Brd4.

Association of Alzheimer's Disease Polygenic Risk Score with Concussion Severity and Recovery Metrics.

Background: Identification of genetic alleles associated with both Alzheimer's disease (AD) and concussion severity/recovery could help explain the association between concussion and elevated dementia risk. However, there has been little investigation into whether AD risk genes associate with concussion severity/recovery, and the limited findings are mixed.

Objective: We used AD polygenic risk scores (PRS) and APOE genotypes to investigate any such associations in the NCAA-DoD Grand Alliance CARE Consortium (CARE) dataset.

Dissecting Causal Relationships Between Antihypertensive Drug, Gut Microbiota, and Type 2 Diabetes Mellitus and Its Complications: A Mendelian Randomization Study.

Limited research has investigated the impact of antihypertensive medications on type 2 diabetes mellitus (T2DM) and whether gut microbiome (GM) mediates this association. Thus, we conducted a two-sample Mendelian randomization (MR) analysis to estimate the potential impact of various antihypertensive drug target genes on T2DM and its complications. Genetic instruments for the expression of antihypertensive drug target genes were identified with expression quantitative trait loci (eQTL) in blood, which should be associated with systolic blood pressure (SBP).

The differential impacts of equivalent gating-charge mutations in voltage-gated sodium channels.

Voltage-gated sodium (Nav) channels are pivotal for cellular signaling, and mutations in Nav channels can lead to excitability disorders in cardiac, muscular, and neural tissues. A major cluster of pathological mutations localizes in the voltage-sensing domains (VSDs), resulting in either gain-of-function, loss-of-function effects, or both. However, the mechanism behind this functional diversity of mutations at equivalent positions remains elusive.

The mechanism of amyloid fibril growth from Φ-value analysis.

Amyloid fibrils are highly stable misfolded protein assemblies that play an important role in several neurodegenerative and systemic diseases. Although structural information of the amyloid state is now abundant, mechanistic details about the misfolding process remain elusive. Inspired by the Φ-value analysis of protein folding, we combined experiments and molecular simulations to resolve amino-acid contacts and determine the structure of the transition-state ensemble-the rate-limiting step-for fibril elongation of PI3K-SH3 amyloid fibrils.

Unique ultrastructural organization of human rod photoreceptors.

Rod and cone photoreceptor cells are specialized neurons responsible for transforming the information reaching the eyes in the form of photons into the language of neuronal activity. Rods are the most prevalent photoreceptor type, primarily responsible for light detection under conditions of limited illumination. Here we demonstrate that human rods have a morphological organization unique among all described species, whereby the cell soma extends alongside the light-sensitive outer segment compartment to form a structure we have termed the "accessory inner segment.

B cells enhance IL-1 beta driven invasiveness in triple negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype often characterized by high lymphocyte infiltration, including tumor-infiltrating B cells (TIBs). These cells are present even in early stages of TNBC and associated with microinvasion. This study shows that co-culturing TNBC cells with B cells increases Interleukin-1β (IL-1β) expression and secretion.

Label-free nanoscopy of cell metabolism by ultrasensitive reweighted visible stimulated Raman scattering.

Super-resolution imaging of cell metabolism is hindered by the incompatibility of small metabolites with fluorescent dyes and the limited resolution of imaging mass spectrometry. We present ultrasensitive reweighted visible stimulated Raman scattering (URV-SRS), a label-free vibrational imaging technique for multiplexed nanoscopy of intracellular metabolites. We developed a visible SRS microscope with extensive pulse chirping to improve the detection limit to ~4,000 molecules and introduced a self-supervised multi-agent denoiser to suppress non-independent noise in SRS by over 7.

Gallibacterium faecale sp. nov., Isolated from Dairy Cow Feces.

A facultative anaerobic, Gram-stain-negative, non-motile, rod-shaped bacterial strain AGMB14963 was isolated from the feces of a dairy cow. A 16S rRNA gene sequence-based phylogenetic analysis revealed that strain AGMB14963 belongs to the genus Gallibacterium, with Gallibacterium salpingitidis F150 being the closest species (95.8% 16S rRNA gene sequence similarity).

Doxorubicin treatment has a biphasic effect over time on dopamine release and impulsive behavior in Wistar rats.

Doxorubicin (Dox) is a chemotherapy agent commonly used to treat multiple types of cancers and is associated with cognitive impairment. The goal of this work was to determine the effect of Dox treatment on dopamine release and uptake and behavior in rats. Rats received one dose per week of Dox (2.

Pregnancy entails a U-shaped trajectory in human brain structure linked to hormones and maternal attachment.

Growing evidence places the gestational period as a unique moment of heightened neuroplasticity in adult life. In this longitudinal study spanning pre, during, and post pregnancy, we unveil a U-shaped trajectory in gray matter (GM) volume, which dips in late pregnancy and partially recovers during postpartum. These changes are most prominent in brain regions associated with the Default Mode and Frontoparietal Network.

Artificial intelligence in cryo-EM protein particle picking: recent advances and remaining challenges.

Cryo-electron microscopy (cryo-EM) has revolutionized structural biology by enabling the determination of high-resolution 3-Dimensional (3D) structures of large biological macromolecules. Protein particle picking, the process of identifying individual protein particles in cryo-EM micrographs for building protein structures, has progressed from manual and template-based methods to sophisticated artificial intelligence (AI)-driven approaches in recent years. This review critically examines the evolution and current state of cryo-EM particle picking methods, with an emphasis on the impact of AI.

Anti-proteolytic regulation of KRAS by USP9X/NDRG3 in KRAS-driven cancer development.

Cancers with activating mutations of KRAS show a high prevalence but remain intractable, requiring innovative strategies to overcome the poor targetability of KRAS. Here, we report that KRAS expression is post-translationally up-regulated through deubiquitination when the scaffolding function of NDRG3 (N-Myc downstream-regulated gene 3) promotes specific interaction between KRAS and a deubiquitinating enzyme, USP9X. In KRAS-mutant cancer cells KRAS protein expression, downstream signaling, and cell growth are highly dependent on NDRG3.

Mendelian Randomization Analysis Reveals a Causal Relationship Between Membranous Nephropathy and the Gut Microbiome.

Background: With the increasing prevalence of membranous nephropathy (MN), the gut microbiome (GM) is increasingly implicated in its cause, yet the intricate mechanisms remain unclear. Whether changes in the diversity and richness of gut microbial populations among MN patients contribute to disease prevalence is still unanswered, necessitating further exploration into the potential causative link between the GM and MN.

Methods: We conducted a comprehensive bidirectional Mendelian randomization (MR) study.

Level of elderly-supportive infrastructure, fine particulate matter and cardiovascular disease hospitalisations: a time-stratified case-crossover study in Wuhan.

Background: Amid rapid urbanisation, the health effects of the built-environment have been widely studied, while research on elderly-supportive infrastructure and its interaction with PM (PM, Particulate Matter) exposure remains limited.

Objectives: To examine the effect of PM on cardiovascular hospitalisation risk among the elderly and the moderating role of elderly-supportive infrastructure in Wuhan, a city undergoing rapid urbanisation.

Methods: A time-stratified case-crossover design was adopted in which the K-means cluster analysis was applied to categorize elderly-supportive infrastructure.

One size does not fit all: revising traditional paradigms for assessing accuracy of QSAR models used for virtual screening.

Traditional best practices for quantitative structure activity relationship (QSAR) modeling recommend dataset balancing and balanced accuracy (BA) as the key desired objective of model development. This study explores the value of the conventional norms in the context of using QSAR models for virtual screening of modern large and ultra-large chemical libraries. For this increasingly common task, we now recommend the use of models with the highest positive predictive value (PPV) built on imbalanced training sets as preferred virtual screening tools.

Satellite microglia: marker of traumatic brain injury and regulator of neuronal excitability.

Traumatic brain injury is a leading cause of chronic neurologic disability and a risk factor for development of neurodegenerative disease. However, little is known regarding the pathophysiology of human traumatic brain injury, especially in the window after acute injury and the later life development of progressive neurodegenerative disease. Given the proposed mechanisms of toxic protein production and neuroinflammation as possible initiators or contributors to progressive pathology, we examined phosphorylated tau accumulation, microgliosis and astrogliosis using immunostaining in the orbitofrontal cortex, a region often vulnerable across traumatic brain injury exposures, in an age and sex-matched cohort of community traumatic brain injury including both mild and severe cases in midlife.

CRISPR-Cas9-mediated editing of gene improves tolerance to drought stress in maize.

Maize ( L.) is a widely grown food crop around the world. Drought stress seriously affects the growth and development process of plants and causes serious damage to maize yield.

Assays to Enhance Metabolic Phenotyping in the Kidney.

The kidney is highly metabolically active, and injury induces changes in metabolism that can impact repair and fibrosis progression. Changes in expression of metabolism-related genes and proteins provide valuable data, but functional metabolic assays are critical to confirm changes in metabolic activity. Stable isotope metabolomics are the gold standard, but these involve considerable cost and specialized expertise.

Associations of Cardiorespiratory Fitness with Cerebral Cortical Thickness and Gray Matter Volume Across the Adult Lifespan.

High cardiorespiratory fitness (CRF) is associated with reduced cortical thinning and gray matter (GM) shrinkage in older adults. We investigated associations of CRF measured with peak oxygen consumption (V̇ O) with cortical thickness and GM volume across the adult lifespan. We hypothesized that higher CRF is associated with less cortical thinning and GM shrinkage across the adult lifespan, which is associated with better cognitive performance.

The multispecifier model for conduct disorder in detained boys: Relations with conduct disorder criteria and etiologically and clinically relevant correlates.

A multispecifier model for subtyping children and adolescents with conduct disorder (CD) has been proposed that, in addition to callous-unemotional (CU) traits, also considers grandiose-manipulative (GM) and daring-impulsive (DI) traits. Yet, concerns have been raised about the potential overlap of these latter two specifiers with existing CD criteria and their limited added value to the prediction of etiologically and clinically relevant correlates. The present study was designed to address these concerns while using data from 286 detained boys with a CD diagnosis (ages 16 to 17 years).