Quiescence and aging of melanocyte stem cells and a novel association with programmed death-ligand 1.

Cellular quiescence is a reversible and tightly regulated stem cell function essential for healthy aging. However, the elements that control quiescence during aging remain poorly defined. Using melanocyte stem cells (McSCs), we find that stem cell quiescence is neither passive nor static.

Transport of herbicides by PIN-FORMED auxin transporters.

Auxins are a group of phytohormones that control plant growth and development . Their crucial role in plant physiology has inspired development of potent synthetic auxins that can be used as herbicides . Phenoxyacetic acid derivatives are a widely used group of auxin herbicides in agriculture and research.

Assessing the role of evolutionary information for enhancing protein language model embeddings.

Embeddings from protein Language Models (pLMs) are replacing evolutionary information from multiple sequence alignments (MSAs) as the most successful input for protein prediction. Is this because embeddings capture evolutionary information? We tested various approaches to explicitly incorporate evolutionary information into embeddings on various protein prediction tasks. While older pLMs (SeqVec, ProtBert) significantly improved through MSAs, the more recent pLM ProtT5 did not benefit.

Activation of the TRPML1 Ion Channel Induces Proton Secretion in the Human Gastric Parietal Cell Line HGT-1.

The lysosomal Ca channel TRPML1 was found to be responsible for gastric acid secretion in murine gastric parietal cells by inducing the trafficking of H/K-ATPase containing tubulovesicles to the apical membrane. Therefore, we hypothesized a similar role of TRPML1 in regulating proton secretion in the immortalized human parietal cell line HGT-1. The primary focus was to investigate the involvement of TRPML1 in proton secretion using the known synthetic agonists ML-SA1 and ML-SA5 and the antagonist ML-SI3 and, furthermore, to identify food-derived compounds that target the channel.

Fine-tuning protein language models boosts predictions across diverse tasks.

Prediction methods inputting embeddings from protein language models have reached or even surpassed state-of-the-art performance on many protein prediction tasks. In natural language processing fine-tuning large language models has become the de facto standard. In contrast, most protein language model-based protein predictions do not back-propagate to the language model.

Small data methods in omics: the power of one.

Over the last decade, biology has begun utilizing 'big data' approaches, resulting in large, comprehensive atlases in modalities ranging from transcriptomics to neural connectomics. However, these approaches must be complemented and integrated with 'small data' approaches to efficiently utilize data from individual labs. Integration of smaller datasets with major reference atlases is critical to provide context to individual experiments, and approaches toward integration of large and small data have been a major focus in many fields in recent years.

Genomic and functional divergence of strains from atopic dermatitis patients and healthy individuals: insights from global and local scales.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease worldwide and is characterized by a complex interplay with skin microbiota, with often abnormally more abundant in AD patients than in healthy individuals (HE). harbors diverse strains with varied genetic compositions and functionalities, which exhibit differential connections with the severity of AD. However, the differences in strains between AD and HE remain unclear, with most variations seen at a specific geographic level, implying spontaneous adaptations rather than systematic distinctions.

Predicting T cell receptor functionality against mutant epitopes.

Cancer cells and pathogens can evade T cell receptors (TCRs) via mutations in immunogenic epitopes. TCR cross-reactivity (i.e.

An Optimized High-Resolution Mapping Method for Glucocorticoid Receptor-DNA Binding in Mouse Primary Macrophages.

ChIP-exo is a powerful tool for achieving enhanced sensitivity and single-base-pair resolution of transcription factor (TF) binding, which utilizes a combination of chromatin immunoprecipitation (ChIP) and lambda exonuclease digestion (exo) followed by high-throughput sequencing. ChIP-nexus (chromatin immunoprecipitation experiments with nucleotide resolution through exonuclease, unique barcode, and single ligation) is an updated and simplified version of the original ChIP-exo method, which has reported an efficient adapter ligation through the DNA circularization step. Building upon an established method, we present a protocol for generating NGS (next-generation sequencing) ready and high-quality ChIP-nexus library for glucocorticoid receptor (GR).

Chromatin Immunoprecipitation in Adipose Tissue and Adipocytes: How to Proceed and Optimize the Protocol for Transcription Factor DNA Binding.

Chromatin immunoprecipitation (ChIP) coupled to qPCR or sequencing is a crucial experiment to determine direct transcriptional regulation under the control of specific transcriptional factors or co-regulators at loci-specific or pan-genomic levels.Here we provide a reliable method for processing ChIP from adipocytes or frozen adipose tissue collection, isolation of nuclei, cross-linking of protein-DNA complexes, chromatin shearing, immunoprecipitation, and DNA purification. We also discuss critical steps for optimizing the experiment to perform a successful ChIP in lipid-rich cells/tissues.

Transformers in single-cell omics: a review and new perspectives.

Recent efforts to construct reference maps of cellular phenotypes have expanded the volume and diversity of single-cell omics data, providing an unprecedented resource for studying cell properties. Despite the availability of rich datasets and their continued growth, current single-cell models are unable to fully capitalize on the information they contain. Transformers have become the architecture of choice for foundation models in other domains owing to their ability to generalize to heterogeneous, large-scale datasets.

scTab: Scaling cross-tissue single-cell annotation models.

Identifying cellular identities is a key use case in single-cell transcriptomics. While machine learning has been leveraged to automate cell annotation predictions for some time, there has been little progress in scaling neural networks to large data sets and in constructing models that generalize well across diverse tissues. Here, we propose scTab, an automated cell type prediction model specific to tabular data, and train it using a novel data augmentation scheme across a large corpus of single-cell RNA-seq observations (22.

Multi-omics characterization of type 2 diabetes associated genetic variation.

Discerning the mechanisms driving type 2 diabetes (T2D) pathophysiology from genome-wide association studies (GWAS) remains a challenge. To this end, we integrated omics information from 16 multi-tissue and multi-ancestry expression, protein, and metabolite quantitative trait loci (QTL) studies and 46 multi-ancestry GWAS for T2D-related traits with the largest, most ancestrally diverse T2D GWAS to date. Of the 1,289 T2D GWAS index variants, 716 (56%) demonstrated strong evidence of colocalization with a molecular or T2D-related trait, implicating 657 -effector genes, 1,691 distal-effector genes, 731 metabolites, and 43 T2D-related traits.

Injection of antioxidant trace minerals/vitamins into peripartum crossbred cows improves the nutritional and immunological properties of colostrum/milk and the health of their calves under heat stress conditions.

Multimineral and vitamin injections can provide better nutrient availability at the cellular level, which is essential for mitigating transition period stress and improving the wellbeing and productivity of dairy cows. The present study was conducted to assess the colostrum quality and calf health after intramuscular injection of multi-minerals (MM) and multi-vitamins (MV) to peripartum cows during winter (THI = 58 to 66) and summer (THI = 78 to 82) months. In each season, twenty-four pregnant crossbred Karan Fries cows were grouped into four, each consisting of six cows.

T cell dysfunction and therapeutic intervention in cancer.

Recent advances in immunotherapy have affirmed the curative potential of T cell-based approaches for treating relapsed and refractory cancers. However, the therapeutic efficacy is limited in part owing to the ability of cancers to evade immunosurveillance and adapt to immunological pressure. In this Review, we provide a brief overview of cancer-mediated immunosuppressive mechanisms with a specific focus on the repression of the surveillance and effector function of T cells.

Distinct prophage gene profiles of strains from atopic dermatitis patients and healthy individuals.

Unlabelled: strains exhibit varying associations with atopic dermatitis (AD), but the genetic determinants underpinning the pathogenicity are yet to be fully characterized. To reveal the genetic differences between strains from AD patients and healthy individuals (HE), we developed and employed a random forest classifier to identify potential marker genes responsible for their phenotypic variations. The classifier was able to effectively distinguish strains from AD and HE.

A bipolar disorder-associated missense variant alters adenylyl cyclase 2 activity and promotes mania-like behavior.

The single nucleotide polymorphism rs13166360, causing a substitution of valine (Val) 147 to leucine (Leu) in the adenylyl cyclase 2 (ADCY2), has previously been associated with bipolar disorder (BD). Here we show that the disease-associated ADCY2 missense mutation diminishes the enzyme´s capacity to generate the second messenger 3',5'-cylic adenosine monophosphate (cAMP) by altering its subcellular localization. We established mice specifically carrying the Val to Leu substitution using CRISPR/Cas9-based gene editing.

Panpipes: a pipeline for multiomic single-cell and spatial transcriptomic data analysis.

Single-cell multiomic analysis of the epigenome, transcriptome, and proteome allows for comprehensive characterization of the molecular circuitry that underpins cell identity and state. However, the holistic interpretation of such datasets presents a challenge given a paucity of approaches for systematic, joint evaluation of different modalities. Here, we present Panpipes, a set of computational workflows designed to automate multimodal single-cell and spatial transcriptomic analyses by incorporating widely-used Python-based tools to perform quality control, preprocessing, integration, clustering, and reference mapping at scale.

Network analyses predict major regulators of resistance to early blight disease complex in tomato.

Background: Early blight and brown leaf spot are often cited as the most problematic pathogens of tomato in many agricultural regions. Their causal agents are Alternaria spp., a genus of Ascomycota containing numerous necrotrophic pathogens.

Leveraging Integrated RNA Sequencing to Decipher Adrenomedullin's Protective Mechanisms in Experimental Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly affecting premature infants, with limited therapeutic options and increased long-term consequences. Adrenomedullin (), a proangiogenic peptide hormone, has been found to protect rodents against experimental BPD. This study aims to elucidate the molecular and cellular mechanisms through which influences BPD pathogenesis using a lipopolysaccharide (LPS)-induced model of experimental BPD in mice.

Nanodisc Technology: Direction toward Physicochemical Characterization of Chemosensory Membrane Proteins in Food Flavor Research.

Chemosensory membrane proteins such as G-protein-coupled receptors (GPCRs) drive flavor perception of food formulations. To achieve this, a detailed understanding of the structure and function of these membrane proteins is needed, which is often limited by the extraction and purification methods involved. The proposed nanodisc methodology helps overcome some of these existing challenges such as protein stability and solubilization along with their reconstitution from a native cell-membrane environment.