Beyond genomic weaving: molecular roles for CTCF outside cohesin loop extrusion.

CCCTC-binding factor (CTCF) is a key regulator of 3D genome organization and transcriptional activity. Beyond its well-characterized role in facilitating cohesin-mediated loop extrusion, CTCF exhibits several cohesin-independent activities relevant to chromatin structure and various nuclear processes. These functions include patterning of nucleosome arrangement and chromatin accessibility through interactions with ATP-dependent chromatin remodelers.

snRNA-seq stratifies multiple sclerosis patients into distinct white matter glial responses.

Poor understanding of the cellular and molecular basis of clinical and genetic heterogeneity in progressive multiple sclerosis (MS) has hindered the search for new effective therapies. To address this gap, we analyzed 632,000 single-nucleus RNA sequencing profiles from 156 brain tissue samples of MS and control donors to examine inter- and intra-donor heterogeneity. We found distinct cell type-specific gene expression changes between MS gray and white matter, highlighting clear pathology differences.

Targeting SARS-CoV-2 main protease: a comprehensive approach using advanced virtual screening, molecular dynamics, and in vitro validation.

The COVID-19 pandemic, driven by the SARS-CoV-2 virus, necessitates the development of effective therapeutics. The main protease of the virus, Mpro, is a key target due to its crucial role in viral replication. Our study presents a novel approach combining ligand-based pharmacophore modeling with structure-based advanced virtual screening to identify potential inhibitors of Mpro.

A structure-based mechanism for initiation of AP-3 coated vesicle formation.

Adaptor protein complex-3 (AP-3) mediates cargo sorting from endosomes to lysosomes and lysosome-related organelles. Recently, it was shown that AP-3 adopts a constitutively open conformation compared to the related AP-1 and AP-2 coat complexes, which are inactive until undergoing large conformational changes upon membrane recruitment. How AP-3 is regulated is therefore an open question.

A whole food, plant-based diet reduces amino acid levels in patients with metastatic breast cancer.

Background: Amino acids are critical to tumor survival. Tumors can acquire amino acids from the surrounding microenvironment, including the serum. Limiting dietary amino acids is suggested to influence their serum levels.

Bi-allelic variants in DAP3 result in reduced assembly of the mitoribosomal small subunit with altered apoptosis and a Perrault-syndrome-spectrum phenotype.

The mitochondrial ribosome (mitoribosome) synthesizes 13 protein subunits of the oxidative phosphorylation system encoded by the mitochondrial genome. The mitoribosome is composed of 12S rRNA, 16S rRNA, and 82 mitoribosomal proteins encoded by nuclear genes. To date, variants in 12 genes encoding mitoribosomal proteins are associated with rare monogenic disorders and frequently show combined oxidative phosphorylation deficiency.

Prolonged Immunomodulator Delivery Boosts Monocyte Exosome Secretion and Elevates Cathelicidin/LL-37 Content.

Human cathelicidin LL-37 offers significant benefits to the immune system and in treating various diseases, but its therapeutic potential is hindered by low activity and instability in physiological environments. Here, we introduce a strategy to boost LL-37 levels in exosomes derived from THP-1 monocytes by incubating cells with electrospun nanofibers containing immunomodulators (e.g.

Reduced plastid genomes of colorless facultative pathogens Prototheca (Chlorophyta) are retained for membrane transport genes.

Background: Plastids are usually involved in photosynthesis, but the secondary loss of this function is a widespread phenomenon in various lineages of algae and plants. In addition to the loss of genes associated with photosynthesis, the plastid genomes of colorless algae are frequently reduced further. To understand the pathways of reductive evolution associated with the loss of photosynthesis, it is necessary to study a number of closely related strains.

Inhibitory effects of nafcillin and diosmin on biofilm formation by Salmonella Typhimurium.

Objective: The foodborne pathogen Salmonella enterica serovar Typhimurium causes self-limiting gastroenteritis in humans and is difficult to eliminate due to its ability to adhere to surfaces and form biofilms that exhibit high resistance to antimicrobial agents. To explore alternative strategies for biofilm treatment, it is essential to investigate novel agents that inhibit Salmonella biofilms.

Method: In this study, we investigated the minimum biofilm inhibitory concentrations (MBICs) and minimum biofilm eradication concentrations (MBECs) of nafcillin and diosmin, both previously identified as Lon protease inhibitors, against biofilms formed by S.

Artificial intelligence in surgical pathology - Where do we stand, where do we go?

Surgical and neuropathologists continuously search for new and disease-specific features, such as independent predictors of tumor prognosis or determinants of tumor entities and sub-entities. This is a task where artificial intelligence (AI)/machine learning (ML) systems could significantly contribute to help with tumor outcome prediction and the search for new diagnostic or treatment stratification biomarkers. AI systems are increasingly integrated into routine pathology workflows to improve accuracy, reproducibility, productivity and to reveal difficult-to-see features in complicated histological slides, including the quantification of important markers for tumor grading and staging.

Comprehensive Multi-Omics Analysis Reveals NPC2 and ITGAV Genes as Potential Prognostic Biomarkers in Gastrointestinal Cancers.

Background: Gastrointestinal cancers (GICs) continue to dominate in terms of both incidence and mortality worldwide. Due to the absence of efficient and accurate prognostic biomarkers, the prognosis and treatment outcomes of many GICs are poor. Identifying biomarkers to predict individual clinical outcomes efficiently is a fundamental challenge in clinical oncology.

Vascular endothelial growth factor B-mediated fatty acid flux in the adipose-kidney axis contributes to lipotoxicity in diabetic kidney disease.

A common observation in diabetic kidney disease is lipid accumulation, but the mechanism(s) underlying this pathology is unknown. Inhibition of Vascular endothelial growth factor B (VEGF-B) signaling was shown to prevent glomerular lipid accumulation and ameliorated diabetic kidney disease in experimental models. Here, we examined kidney biopsies from patients with Type 2 (84%) and Type 1 diabetes (16%), combined with data mining of RNA-seq dataset analyses in patients with diabetic kidney disease.

Distinct inflammatory profiles in mustard lung: A study of sulfur mustard-exposed patients with serious pulmonary complications.

Mustard Lung (ML) refers to respiratory complications caused by sulfur mustard (SM) exposure, a chemical warfare agent. This study explores the inflammatory profile of SM-exposed veterans with serious ML, aiming to distinguish it from other respiratory diseases. The aim is also to comprehend the role of inflammatory markers in disease severity.

Association of hormone profile with various respiratory disorders in sulfur mustard-chemical veterans.

Backgrounds: Chronic respiratory complications such as asthma, bronchiolitis obliterans, and chronic bronchitis are prevalent among individuals exposed to sulfur mustard (SM). This study investigates the hormonal changes associated with SM-induced respiratory disorders.

Methods: A cross-sectional analysis was conducted involving 276 male participants exposed to SM during the Iraq-Iran war and 64 healthy controls.

Biological amelioration of water stress in rapeseed (Brassica napus L.) by exopolysaccharides-producing Pseudomonas protegens ML15.

Rapeseed (Brassica napus L.) is a globally significant oilseed crop with high economic value. However, water deficit significantly limits its growth and productivity.

Impairment of Skeletal Muscle Contraction by Inhibitors of GABA Transporters.

γ-Aminobutyric acid (GABA) has a significant impact on the functioning of not only the central but also the peripheral part of the nervous system. Recently, various elements of the GABAergic signaling system have been discovered in the area of the neuromuscular junction of mammals. At the same time, the functional activity of membrane-bound GABA transporters (GATs) and their role in neuromuscular transmission have not been identified.

Investigating How Lysophosphatidylcholine and Lysophosphatidylethanolamine Enhance the Membrane Permeabilization Efficacy of Host Defense Peptide Piscidin 1.

Lysophospholipids (LPLs) and host defense peptides (HDPs) are naturally occurring membrane-active agents that disrupt key membrane properties, including the hydrocarbon thickness, intrinsic curvature, and molecular packing. Although the membrane activity of these agents has been widely examined separately, their combined effects are largely unexplored. Here, we use experimental and computational tools to investigate how lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE), an LPL of lower positive spontaneous curvature, influence the membrane activity of piscidin 1 (P1), an α-helical HDP from fish.

Biochemical and neurophysiological effects of deficiency of the mitochondrial import protein TIMM50.

TIMM50, an essential TIM23 complex subunit, is suggested to facilitate the import of ~60% of the mitochondrial proteome. In this study, we characterized a disease-causing mutation in human fibroblasts and noted significant decreases in TIM23 core protein levels (TIMM50, TIMM17A/B, and TIMM23). Strikingly, TIMM50 deficiency had no impact on the steady-state levels of most of its putative substrates, suggesting that even low levels of a functional TIM23 complex are sufficient to maintain the majority of TIM23 complex-dependent mitochondrial proteome.

HIV-1 single transcription start site mutants display complementary replication functions that are restored by reversion.

HIV-1 transcription initiates at two positions, generating RNAs with either 1G or 3G 5' ends. The replication fates of these RNAs di\er, with viral particles encapsidating almost exclusively 1G RNAs and 3G RNAs retained in cells where they are enriched on polysomes and among spliced viral RNAs. Here, we studied replication properties of virus promoter mutants that produced only one RNA 5' isoform or the other: separately, in combination, and during spreading infection.

Application of fluorescence i-motif DNA silver nanocluster sensor to visualize endogenous reactive oxygen species in plant cells.

A novel fluorescent i-motif DNA silver nanoclusters system has been developed for visualization of reactive oxygen species in plants, enabling the detection of intracellular signaling in plant cells. Reactive oxygen species (ROS) are crucial in plant growth, defense, and stress responses, making them vital for improving crop resilience. Various ROS sensing methods for plants have been developed to detect ROS in vitro and in vivo.

Participation of lipids in the tumor response to photodynamic therapy and its exploitation for therapeutic gain.

Hydroperoxides of unsaturated membrane lipids (LOOHs) are the most abundant non-radical intermediates generated by photodynamic therapy (PDT) of soft tissues such as tumors and have far longer average lifetimes than singlet oxygen or oxygen radicals formed during initial photodynamic action. LOOH-initiated post-irradiation damage to remaining membrane lipids (chain peroxidation) or to membrane-associated proteins remains largely unrecognized. Such after-light processes could occur during clinical oncological PDT, but this is not well-perceived by practitioners of this therapy.

FcRn-dependent IgG accumulation in adipose tissue unmasks obesity pathophysiology.

Immunoglobulin G (IgG) is traditionally recognized as a plasma protein that neutralizes antigens for immune defense. However, our research demonstrates that IgG predominantly accumulates in adipose tissue during obesity development, triggering insulin resistance and macrophage infiltration. This accumulation is governed by neonatal Fc receptor (FcRn)-dependent recycling, orchestrated in adipose progenitor cells and macrophages during the early and late stages of diet-induced obesity (DIO), respectively.