Sucrose-preferring gut microbes prevent host obesity by producing exopolysaccharides.

Commensal bacteria affect host health by producing various metabolites from dietary carbohydrates via bacterial glycometabolism; however, the underlying mechanism of action remains unclear. Here, we identified Streptococcus salivarius as a unique anti-obesity commensal bacterium. We found that S.

Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprinting.

Autoimmune liver diseases (AILD) involve dysregulated CD4 T cell responses against liver self-antigens, but how these autoreactive T cells relate to liver tissue pathology remains unclear. Here we perform single-cell transcriptomic and T cell receptor analyses of circulating, self-antigen-specific CD4 T cells from patients with AILD and identify a subset of liver-autoreactive CD4 T cells with a distinct B-helper transcriptional profile characterized by PD-1, TIGIT and HLA-DR expression. These cells share clonal relationships with expanded intrahepatic T cells and exhibit transcriptional signatures overlapping with tissue-resident T cells in chronically inflamed environments.

Gut Microbiota and Osteoarthritis: From Pathogenesis to Novel Therapeutic Opportunities.

Osteoarthritis (OA) is the most common chronic degenerative joint disease, characterized by cartilage damage, synovial inflammation, subchondral bone sclerosis, marginal bone loss, and osteophyte development. Clinical manifestations include inflammatory joint pain, swelling, osteophytes, and limitation of motion. The pathogenesis of osteoarthritis has not yet been fully uncovered.

The Rbfox1/LASR complex controls alternative pre-mRNA splicing by recognition of multipart RNA regulatory modules.

The Rbfox proteins regulate alternative pre-mRNA splicing by binding to the RNA element GCAUG. In the nucleus, most of Rbfox is bound to the large assembly of splicing regulators (LASR), a complex of RNA-binding proteins that recognize additional RNA motifs. However, it remains unclear how the different subunits of the Rbfox/LASR complex act together to bind RNA and regulate splicing.

Frozen versus fresh embryo transfer in women with low prognosis for in vitro fertilisation treatment: pragmatic, multicentre, randomised controlled trial.

Objective: To test the hypothesis that a freeze-all strategy would increase the chance of live birth compared with fresh embryo transfer in women with low prognosis for in vitro fertilisation (IVF) treatment.

Design: Pragmatic, multicentre, randomised controlled trial.

Setting: Nine academic fertility centres in China.

Executive dysfunction in Parkinson's disease: From neurochemistry to circuits, genetics and neuroimaging.

Cognitive decline is one of the most significant non-motor symptoms of Parkinson's disease (PD), with executive dysfunction (EDF) being the most prominent characteristic of PD-associated cognitive deficits. Currently, lack of uniformity in the conceptualization and assessment scales for executive functions impedes the early and accurate diagnosis of executive dysfunction in PD. The neurobiological mechanisms of executive dysfunction in PD remain poorly understood.

Gene and phenome-based analysis of the shared genetic architecture of eye diseases.

While many eye disorders are linked through defects in vascularization and optic nerve degeneration, genetic correlation studies have yielded variable results despite shared features. For example, glaucoma and myopia both share optic neuropathy as a feature, but genetic correlation studies demonstrated minimal overlap. By leveraging electronic health record (EHR) resources that contain genetic variables such as genetically predicted gene expression (GPGE), researchers have the potential to improve the identification of shared genetic drivers of disease by incorporating knowledge of shared features to identify disease-causing mechanisms.

Sequence variants in HECTD1 result in a variable neurodevelopmental disorder.

Dysregulation of genes encoding the homologous to E6AP C-terminus (HECT) E3 ubiquitin ligases has been linked to cancer and structural birth defects. One member of this family, the HECT-domain-containing protein 1 (HECTD1), mediates developmental pathways, including cell signaling, gene expression, and embryogenesis. Through GeneMatcher, we identified 14 unrelated individuals with 15 different variants in HECTD1 (10 missense, 3 frameshift, 1 nonsense, and 1 splicing variant) with neurodevelopmental disorders (NDDs), including autism, attention-deficit/hyperactivity disorder, and epilepsy.

A cis-regulatory element controls expression of histone deacetylase 9 to fine-tune inflammasome-dependent chronic inflammation in atherosclerosis.

Common genetic variants in a conserved cis-regulatory element (CRE) at histone deacetylase (HDAC)9 are a major risk factor for cardiovascular disease, including stroke and coronary artery disease. Given the consistency of this association and its proinflammatory properties, we examined the mechanisms whereby HDAC9 regulates vascular inflammation. HDAC9 bound and mediated deacetylation of NLRP3 in the NACHT and LRR domains leading to inflammasome activation and lytic cell death.

Significance of TYMS Polymorphism rs3819102 as a Prognostic Marker for Nonsmoking Lung Cancer Patients of the Han Ethnicity in China.

Introduction: With high incidence and mortality rates, lung cancer is now one of the most common cancers in the world. The 5-year survival rate of lung cancer patients is very low, and predicting the prognosis of lung cancer patients and using it to develop treatment strategies and interventions is important for prolonging the survival time of patients. Folate metabolism involves various aspects such as methylation of DNA, RNA, proteins, lipids, etc.

Chromosome length genome assembly of the stone marten (Martes foina, Mustelidae): a new view on one of the cornerstones in carnivore cytogenetics.

The stone marten (Martes foina) is an important species for cytogenetic studies in the order Carnivora. ZooFISH probes created from its chromosomes provided a strong and clean signal in chromosome painting experiments and were valuable for studying the evolution of carnivoran genome architecture. The research revealed that the stone marten chromosome set is similar to the presumed ancestral karyotype of the Carnivora, which added an additional value for the species.

Serine phosphorylation facilitates protein degradation by the human mitochondrial ClpXP protease.

ClpXP is a two-component mitochondrial matrix protease. The caseinolytic mitochondrial matrix peptidase chaperone subunit X (ClpX) recognizes and translocates protein substrates into the degradation chamber of the caseinolytic protease P (ClpP) for proteolysis. ClpXP degrades damaged respiratory chain proteins and is necessary for cancer cell survival.

Sphingolipid metabolism orchestrates establishment of the hair follicle stem cell compartment.

Sphingolipids serve as building blocks of membranes to ensure subcellular compartmentalization and facilitate intercellular communication. How cell type-specific lipid compositions are achieved and what is their functional significance in tissue morphogenesis and maintenance has remained unclear. Here, we identify a stem cell-specific role for ceramide synthase 4 (CerS4) in orchestrating fate decisions in skin epidermis.

The impact of specialised gastroenterology services for pelvic radiation disease (PRD): Results from the prospective multi-centre EAGLE study.

To undertake a mixed-methodology implementation study to improve the well-being of men with gastrointestinal late effects following radical radiotherapy for prostate cancer. All men completed a validated screening tool for late bowel effects (ALERT-B) and the Gastrointestinal Symptom Rating Score (GSRS); men with a positive score on ALERT-B were offered management following a peer reviewed algorithm for pelvic radiation disease (PRD). Health-related quality of life (HRQoL) at baseline, 6 and 12 months; and healthcare resource usage (HRU) and patient, support-giver, staff experience and acceptability of staff training (qualitative analysis) were assessed.

Quantitative Analysis of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Stabilization in a Neural Model of Alzheimer's Disease (AD).

A method to quantitate the stabilization of Mitochondria-Associated endoplasmic reticulum Membranes (MAMs) in a 3-dimensional (3D) neural model of Alzheimer's disease (AD) is presented here. To begin, fresh human neuro progenitor ReN cells expressing β-amyloid precursor protein (APP) containing familial Alzheimer's disease (FAD) or naïve ReN cells are grown in thin (1:100) Matrigel-coated tissue culture plates. After the cells reach confluency, these are electroporated with expression plasmids encoding red fluorescence protein (RFP)-conjugated mitochondria-binding sequence of AKAP1(34-63) (Mito-RFP) that detects mitochondria or constitutive MAM stabilizers MAM 1X or MAM 9X that stabilize tight (6 nm ± 1 nm gap width) or loose (24 nm ± 3 nm gap width) MAMs, respectively.

SHP2 promotes the epithelial-mesenchymal transition in triple negative breast cancer cells by regulating β-catenin.

Purpose: Growing evidence suggests that the tyrosine phosphatase SHP2 is pivotal for tumor progression. Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer, characterized by its high recurrence rate, aggressive metastasis, and resistance to chemotherapy. Understanding the mechanisms of tumorigenesis and the underlying molecular pathways in TNBC could aid in identifying new therapeutic targets.

Characterization of the host specificity of the SH3 cell wall binding domain of the staphylococcal phage 88 endolysin.

Bacteriophages produce endolysins at the end of the lytic cycle, which are crucial for lysing the host cells and releasing virion progeny. This lytic feature allows endolysins to act as effective antimicrobial alternatives when applied exogenously. Staphylococcal endolysins typically possess a modular structure with one or two enzymatically active N-terminal domains (EADs) and a C-terminal cell wall binding domain (CBD).

Developing an Intervention to Enhance Aging in Place for Older Veterans Living in Permanent Supportive Housing.

Background And Objectives: The Housing and Urban Development-Veterans Affairs Supported Housing (HUD-VASH) program provides rental subsidies, case management, and supportive services to Veterans who are currently or formerly homeless, 77% of whom are ages ≥50. Few interventions have been developed to address the needs of older Veterans in HUD-VASH.

Research Design And Methods: We conducted a 2-stage study to inform the development of an intervention to promote aging in place in HUD-VASH.

Quantitative Profiling pH Heterogeneity of Acidic Endolysosomal Compartments using Fluorescence Lifetime Imaging Microscopy.

The endo-lysosomal system plays a crucial role in maintaining cellular homeostasis and promoting organism fitness. The pH of its acidic compartments is a crucial parameter for proper function, and it is dynamically influenced by both intracellular and environmental factors. Here, we present a method based on fluorescence lifetime imaging microscopy (FLIM) for quantitatively analyzing the pH profiles of acidic endolysosomal compartments in diverse types of primary mammalian cells and in live organism .

Fibroblast transcriptomics uncovers pathogenic genomic variants in individuals with exome-negative childhood onset epilepsy.

Objective: This study aims to improve genetic diagnosis in childhood onset epilepsy with neurodevelopmental problems by utilizing RNA sequencing of fibroblasts to identify pathogenic variants that may be missed by exome sequencing and copy number variation analysis.

Methods: We enrolled 41 individuals with childhood onset epilepsy and neurodevelopmental problems who previously had inconclusive genetic testing. Fibroblast samples were cultured and analyzed using RNA sequencing to detect aberrant expression, aberrant splicing, and monoallelic expression using the Detection of RNA Outlier Pipeline (DROP) pipeline.

Structural analysis of extracellular ATP-independent chaperones of streptococcal species and protein substrate interactions.

Unlabelled: During infection, bacterial pathogens rely on secreted virulence factors to manipulate the host cell. However, in gram-positive bacteria, the molecular mechanisms underlying the folding and activity of these virulence factors after membrane translocation are not clear. Here, we solved the protein structures of two secreted parvulin and two secreted cyclophilin-like peptidyl-prolyl isomerase (PPIase) ATP-independent chaperones found in gram-positive streptococcal species.

Multi-omics analysis reveals distinct gene regulatory mechanisms between primary and organoid-derived human hepatocytes.

Hepatic organoid cultures are a powerful model to study liver development and diseases in vitro. However, hepatocyte-like cells differentiated from these organoids remain immature compared to primary human hepatocytes (PHHs), which are the benchmark in the field. Here, we applied integrative single-cell transcriptome and chromatin accessibility analysis to reveal gene regulatory mechanisms underlying these differences.

PEBP1 amplifies mitochondrial dysfunction-induced integrated stress response.

Mitochondrial dysfunction is involved in numerous diseases and the aging process. The integrated stress response (ISR) serves as a critical adaptation mechanism to a variety of stresses, including those originating from mitochondria. By utilizing mass spectrometry-based cellular thermal shift assay (MS-CETSA), we uncovered that phosphatidylethanolamine-binding protein 1 (PEBP1), also known as Raf kinase inhibitory protein (RKIP), is thermally stabilized by stresses which induce mitochondrial ISR.

The novel p.A30G SNCA pathogenic variant in Greek patients with familial and sporadic Parkinson's disease.

Background: The p.A53T variant in the SNCA gene was considered, until recently, to be the only SNCA variant causing familial Parkinson's disease (PD) in the Greek population. We identified a novel heterozygous p.

Hereditary Transthyretin Amyloidosis in Israel: Genetic Landscape and Clinical Characteristics.

Background: Hereditary transthyretin (ATTRv) amyloidosis is a rare, adult-onset autosomal-dominant disorder caused by pathogenic variants in the transthyretin (TTR) gene. Data about relevant variants in specific populations and typical initial manifestations may facilitate early diagnosis and treatment. We here describe the genetic landscape of ATTRv amyloidosis in Israel.