Marigold: a machine learning-based web app for zebrafish pose tracking.

Background: High-throughput behavioral analysis is important for drug discovery, toxicological studies, and the modeling of neurological disorders such as autism and epilepsy. Zebrafish embryos and larvae are ideal for such applications because they are spawned in large clutches, develop rapidly, feature a relatively simple nervous system, and have orthologs to many human disease genes. However, existing software for video-based behavioral analysis can be incompatible with recordings that contain dynamic backgrounds or foreign objects, lack support for multiwell formats, require expensive hardware, and/or demand considerable programming expertise.

NPT100-18A rescues mitochondrial oxidative stress and neuronal degeneration in human iPSC-based Parkinson's model.

Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by protein aggregates mostly consisting of misfolded alpha-synuclein (αSyn). Progressive degeneration of midbrain dopaminergic neurons (mDANs) and nigrostriatal projections results in severe motor symptoms. While the preferential loss of mDANs has not been fully understood yet, the cell type-specific vulnerability has been linked to a unique intracellular milieu, influenced by dopamine metabolism, high demand for mitochondrial activity, and increased level of oxidative stress (OS).

Metabolic profiles and potential antioxidant mechanisms of hawk tea.

Hawk tea has received increasing attention for its unique flavor and potential health benefits, with antioxidant function being one of its significant bioactivities. However, the metabolic profiles, potential antioxidant components, and action mechanisms of different types of hawk tea are still unclear. In this study, the chemical components of five hawk teas were determined using untargeted metabolomics.

Seroprevalence and risk factors of Bluetongue virus in camels in Northern Oman: a cross-sectional study.

Bluetongue virus (BTV) has emerged as a significant concern in Oman, affecting various animal species, including camels. This cross-sectional study aimed to assess the seroprevalence of BTV in camels and explore the associated risk factors within the northern region of Oman. Between October 2016 and March 2017, 439 serum samples and 100 blood samples were collected from camels in five governorates.

Sex-specific transcriptomic profiling reveals key players in bone loss associated with Alzheimer's disease.

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is frequently associated with musculoskeletal complications, including sarcopenia and osteoporosis, which substantially impair patient quality of life. Despite these clinical observations, the molecular mechanisms linking AD to bone loss remain insufficiently explored. In this study, we examined the femoral bone microarchitecture and transcriptomic profiles of APP/PS1 transgenic mouse models of AD to elucidate the disease's impact on bone pathology and identify potential gene candidates associated with bone deterioration.

Structural basis for human NKCC1 inhibition by loop diuretic drugs.

Na-K-Cl cotransporters functions as an anion importers, regulating trans-epithelial chloride secretion, cell volume, and renal salt reabsorption. Loop diuretics, including furosemide, bumetanide, and torsemide, antagonize both NKCC1 and NKCC2, and are first-line medicines for the treatment of edema and hypertension. NKCC1 activation by the molecular crowding sensing WNK kinases is critical if cells are to combat shrinkage during hypertonic stress; however, how phosphorylation accelerates NKCC1 ion transport remains unclear.

Different essential oils can inhibit Candida albicans biofilm formation on acrylic resin by suppressing aspartic proteinase: In vitro and in silico approaches.

Introduction: Cymbopogon martini, Syzygium aromaticum, and Cupressus sempervirens are used for antimicrobial purposes in the worldwide. Both their extracts and essential oil contents are rich in active ingredients.

Objective: The aim of this study was to investigate the inhibitory effect of Cymbopogon martini essential oil (CMEO), Syzygium aromaticum essential oil (SAEO) and Cupressus sempervirens essential oil (CSEO) on Candida albicans biofilm formation on heat-polymerized polymethyl methacrylate (PMMA) samples in vitro and in silico.

A human metabolic map of pharmacological perturbations reveals drug modes of action.

Understanding a small molecule's mode of action (MoA) is essential to guide the selection, optimization and clinical development of lead compounds. In this study, we used high-throughput non-targeted metabolomics to profile changes in 2,269 putative metabolites induced by 1,520 drugs in A549 lung cancer cells. Although only 26% of the drugs inhibited cell growth, 86% caused intracellular metabolic changes, which were largely conserved in two additional cancer cell lines.

Associations between common genetic variants and income provide insights about the socio-economic health gradient.

We conducted a genome-wide association study on income among individuals of European descent (N = 668,288) to investigate the relationship between socio-economic status and health disparities. We identified 162 genomic loci associated with a common genetic factor underlying various income measures, all with small effect sizes (the Income Factor). Our polygenic index captures 1-5% of income variance, with only one fourth due to direct genetic effects.

Biomolecular condensates in immune cell fate.

Fate decisions during immune cell development require temporally precise changes in gene expression. Evidence suggests that the dynamic modulation of these changes is associated with the formation of diverse, membrane-less nucleoprotein assemblies that are termed biomolecular condensates. These condensates are thought to orchestrate fate-determining transcriptional and post-transcriptional processes by locally and transiently concentrating DNA or RNA molecules alongside their regulatory proteins.

Extracellular vesicles in seminal plasma of Sahiwal cattle bulls carry a differential abundance of sperm fertility-associated proteins for augmenting the functional quality of low-fertile bull spermatozoa.

Poor male fertility significantly affects dairy production, primarily due to low conception rates (CR) in bulls, even when cows are inseminated with morphologically normal sperm. Seminal plasma is a key factor in evaluating the fertilizing ability of bull semen. The extracellular vesicles (EVs) in seminal plasma contain fertility-associated proteins like SPAM1, ADAM7, and SP10, which influence sperm function and fertilizing potential.

Functional innovation through new genes as a general evolutionary process.

In the past decade, our understanding of how new genes originate in diverse organisms has advanced substantially, and more than a dozen molecular mechanisms for generating initial gene structures were identified, in addition to gene duplication. These new genes have been found to integrate into and modify pre-existing gene networks primarily through mutation and selection, revealing new patterns and rules with stable origination rates across various organisms. This progress has challenged the prevailing belief that new proteins evolve from pre-existing genes, as new genes may arise de novo from noncoding DNA sequences in many organisms, with high rates observed in flowering plants.

Esketamine alleviates depressive-like behavior in neuropathic pain mice through the METTL3-GluA1 pathway.

Esketamine, a newly developed antidepressant, is the subject of this research which seeks to explore its impact on depressive symptoms in neuropathic pain mice and the potential molecular mechanisms involved. Through transcriptome sequencing and bioinformatics analysis combined with in vivo studies, it was identified that esketamine markedly boosts the levels of the m6A methyltransferase METTL3 and the AMPA receptor GluA1 subunit. Esketamine activates METTL3, allowing it to bind with GluA1 mRNA, promoting m6A modification, thereby enhancing GluA1 expression at synapses.

Identification of biomarkers associated with coronary artery disease and non-alcoholic fatty liver disease by bioinformatics analysis and machine learning.

The constantly emerging evidence indicates a close association between coronary artery disease (CAD) and non-alcoholic fatty liver disease (NAFLD). However, the exact mechanisms underlying their mutual relationship remain undefined. This study aims to explore the common signature genes, potential mechanisms, diagnostic markers, and therapeutic targets for CAD and NAFLD.

An integrated approach to predict genetic risk for Mosquito-Borne diseases in the local Population of Tehsil Haripur, Khyber Pakhtunkhwa, Pakistan.

Highly variable response shown by individuals against mosquito-borne infections suggests that host genetic factors play an important role in determining mosquito-borne disease onset. Therefore, it is necessary to determine the genetic risk of these diseases in specific populations. The current study aimed to determine the percentage of individuals in the general population carrying mosquito-borne disease susceptibility and protection-related variants.

Rapid structural analysis of bacterial ribosomes in situ.

Rapid structural analysis of purified proteins and their complexes has become increasingly common thanks to key methodological advances in cryo-electron microscopy (cryo-EM) and associated data processing software packages. In contrast, analogous structural analysis in cells via cryo-electron tomography (cryo-ET) remains challenging due to critical technical bottlenecks, including low-throughput sample preparation and imaging, and laborious data processing methods. Here, we describe a rapid in situ cryo-ET sample preparation and data analysis workflow that results in the routine determination of sub-nm resolution ribosomal structures.

Molecular epidemiology of chicken and turkey parvovirus in Turkiye: high risk, genetic recombination signals, and first complete genome analysis.

The aim of this study was to detect chicken parvovirus (ChPV) and turkey parvovirus (TuPV) on Turkish poultry farms and examine the molecular epidemiology of these viruses. In 2023, a total of 1,060 fecal samples were collected from 76 broiler farms and 30 turkey farms across various regions of Turkiye. The overall positivity rate was 72.

Association between changes in genital immune markers and vaginal microbiome transitions in bacterial vaginosis.

Bacterial vaginosis (BV), characterized by an imbalance in the vaginal microbiota, is a prevalent condition among women of reproductive age and a risk factor for human immunodeficiency virus, sexually transmitted infections, and preterm birth. BV is generally considered to induce mucosal inflammation, but the specific pathways and cell types involved are not well characterized. This prospective study aimed to assess associations between microbial changes and mucosal immune responses in BV patients.

Evaluation of ampicillin plus ceftobiprole combination therapy in treating Enterococcus faecalis infective endocarditis and bloodstream infection.

Enterococcus faecalis is responsible for numerous serious infections, and treatment options often include ampicillin combined with an aminoglycoside or dual beta-lactam therapy with ampicillin and a third-generation cephalosporin. The mechanism of dual beta-lactam therapy relies on the saturation of penicillin-binding proteins (PBPs). Ceftobiprole exhibits high affinity binding to nearly all E.

Isolation, identification, and characterisation of the malachite green detoxifying bacterial strain Bacillus pacificus ROC1 and the azoreductase AzrC.

Malachite green (MG) is used as a dye for materials such as wood, cotton, and nylon, and is used in aquaculture to prevent fungal and protozoan diseases. However, it is highly toxic, with carcinogenic, mutagenic, and teratogenic properties, resulting in bans worldwide. Despite this, MG is still frequently used in many countries due to its efficacy and economy.

α-Copaene is a potent repellent against the Asian Citrus Psyllid Diaphorina citri.

The Asian Citrus Psyllid (ACP), Diaphorina citri, severely threatens citrus production worldwide by transmitting the greening (= Huanglongbing)-causing bacterium Candidatus Liberibacter asiaticus. There is growing evidence that the push-pull strategy is suitable to partially mitigate HLB by repelling ACP with transgenic plants engineered to produce repellents and attracting the vector to plants with a minimal disease transmission rate. Species that pull ACP away from commercial citrus plants have been identified, and transgenic plants that repel ACP have been developed.

Convergent evolution of oxidized sugar metabolism in commensal and pathogenic microbes in the inflamed gut.

Inflammation-associated perturbations of the gut microbiome are well characterized, but poorly understood. Here, we demonstrate that disparate taxa recapitulate the metabolism of the oxidized sugars glucarate and galactarate, utilizing enzymatically divergent, yet functionally equivalent, gud/gar pathways. The divergent pathway in commensals includes a putative 5-KDG aldolase (GudL) and an uncharacterized ABC transporter (GarABC) that recapitulate the function of their non-homologous counterparts in pathogens.

PARP inhibition-associated heterochromatin confers increased DNA replication stress and vulnerability to ATR inhibition in SMARCA4-deficient cells.

DNA replication stress (RS), a prevalent feature of various malignancies, arises from both genetic mutations and genotoxic exposure. Elevated RS levels increase the vulnerability of cancer cells to ataxia telangiectasia and Rad3-related kinase inhibitors (ATRis). Here, we screened for DNA damage response inhibitors that enhance ATRi-induced cytotoxicity using SWI/SNF complex-deficient cells and identified a potent synergy between ATRi and poly(ADP-ribose) polymerase inhibitor (PARPi), particularly in SMARCA4-deficient cells.