Application of Protein Structure Encodings and Sequence Embeddings for Transporter Substrate Prediction.

Membrane transporters play a crucial role in any cell. Identifying the substrates they translocate across membranes is important for many fields of research, such as metabolomics, pharmacology, and biotechnology. In this study, we leverage recent advances in deep learning, such as amino acid sequence embeddings with protein language models (pLMs), highly accurate 3D structure predictions with AlphaFold 2, and structure-encoding 3Di sequences from FoldSeek, for predicting substrates of membrane transporters.

Unnatural Amino Acid Photo-Crosslinking Sheds Light on Gating of the Mechanosensitive Ion Channel OSCA1.2.

Mechanosensitive ion channels such as OSCA1.2 enable cells to sense and respond to mechanical forces by translating membrane tension into ionic flux. While lipid rearrangement in the inter-subunit cleft has been proposed as a key activation mechanism, the contributions of other domains to OSCA gating remain unresolved.

Whole Exome Sequencing Study Uncovers Novel Candidate Genes and Protein-Coding Variants for Cataract.

Purpose: To identify novel candidates for cataract and evaluate the contribution of protein-coding variants to cataract susceptibility.

Methods: We first leveraged a publicly-available browser, Genebass, to extract significant gene-based and single-variant association results for cataract in UK Biobank exomes (30,550 cataract cases and 364,291 controls). We then validated findings using genome-wide association study (GWAS) summary statistics from the Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort (28,092 cataract cases and 50,487 controls).

Reconstruction of endocrine subtype-complete human pluripotent stem cell-derived islets with capacity for hypoglycemia protection in vivo.

Transplantation of pluripotent stem cell-derived islets (PSC-islets), containing functional insulin-producing β cells, represents promising cell therapy for restoring glycemic control in diabetes. However, recapitulation of complete endocrine composition in PSC-islets remains challenging, and their ability to counteract hazardous hypoglycemia, crucial to metabolic safety in vivo, remains unexplored. Here, we report robust generation of non-β cells in vitro.

Structural insights into the binding modes of Arrestin-3 finger loop to the neuropeptide Y and Y receptors.

The interaction of the finger loop sequence of arrestin-3 with the neuropeptide Y and Y G protein-coupled receptors was studied. In cell assays, the finger loop part of arrestin was shown to be essential for YR internalization, but had no relevance for the interaction with YR. Here, we combined experimental data from nanoBRET, EPR, and NMR spectroscopy studies using a small library of NMR- and EPR-labeled finger loop peptides.

Impact of seasonal variation on the oral and nasopharyngeal microbiome in school-aged children: the school MicroBE initiative.

The "School MicroBE" initiative explores how the built environment impacts microbial communities in school-aged children by examining temporal dynamics and shifts in nasopharyngeal and oral microbiomes. This longitudinal study involved 119 children aged 4 to 13 at a public school, with nasopharyngeal and oral samples collected in autumn, winter, and spring of 2023. Using 16S rRNA gene sequencing, we assessed microbial composition through alpha and beta diversity analyses, characterized microbial assemblages, and evaluated the relative abundance of key taxa.

Segmental copy number amplifications are stable in the absence of selection.

Copy number variants (CNVs) are duplications and deletions of DNA sequences that contribute to genetic variation between individuals and underlie rapid adaptive evolution. Increases in gene copy number can confer a strong selective advantage in some circumstances, but CNVs can also incur fitness costs. Prior research has shown that experimental evolution of in nutrient-limited chemostats recurrently selects for amplifications of nutrient transporter genes, including , and in glutamine, ammonium and proline limited conditions, respectively.

Thor: a platform for cell-level investigation of spatial transcriptomics and histology.

Spatial transcriptomics links gene expression with tissue morphology, however, current tools often prioritize genomic analysis, lacking integrated image interpretation. To address this, we present Thor, a comprehensive platform for cell-level analysis of spatial transcriptomics and histological images. Thor employs an anti-shrinking Markov diffusion method to infer single-cell spatial transcriptome from spot-level data, effectively combining gene expression and cell morphology.

Metabolic cross-feeding of a dietary antioxidant enhances anaerobic energy metabolism by human gut bacteria.

The degradation of complex carbohydrates and other macromolecules by human gut bacteria generates metabolites that are used by neighboring microbes for anaerobic respiration. However, it is largely unknown whether cross-feeding of other dietary compounds can drive energy-yielding redox reactions in the gut. We show that gut bacteria from different phyla cross-feed a common dietary antioxidant to produce energy under anaerobic conditions.

Vitamin C alleviates PM-induced thyroid injury and ferroptosis by regulating the IL-17A/IL-17RA/ACT1 signaling pathway.

Fine particulate matter (PM) is a ubiquitous environmental pollutant that has been demonstrated to affect the thyroid function in women. However, its specific mechanism remains unclear, and protective drugs are deficient. In the present study, we used female rat thyroid models in vivo and rat FRTL5 cell models in vitro to investigate the thyroid toxicity mechanism of PM and the protective pathway of vitamin C in female rats.

A bottom-up approach to find lead compounds in expansive chemical spaces.

Drug discovery starts with the identification of a "hit" compound that, following a long and expensive optimization process, evolves into a drug candidate. Bigger screening collections increase the odds of finding more and better hits. For this reason, large pharmaceutical companies have invested heavily in high-throughput screening (HTS) collections that can contain several million compounds.

Synthesis, insecticidal activity against Aedes aegypti and acetylcholinesterase inhibition of new N-arylmethyl-1,2,3,4-tetrahydroquinoline derivatives containing an N-arylmethylpiperidine scaffold inspired on donepezil structure.

Reducing Aedes aegypti population using natural or synthetic insecticides remains one of the main strategies for controlling diseases such as dengue, Zika or Chikungunya, as this mosquito is their primary vector. Traditionally, some organic compounds -mainly carbamates or organophosphates derivatives- have been employed for this purpose. These insecticides act as irreversible inhibitors of the acetylcholinesterase enzyme (AChE), which results in high nonspecific toxicity.

Maximal and sub-maximal exercise tests alter PBMC microRNA expression: insights into sport- and sex-specific variations.

Introduction: Studying microRNAs in the immune cells of athletes offers a novel perspective on the molecular regulation of immune function and recovery, potentially uncovering strategies to enhance performance and resilience to physical stress. However, PBMC microRNA expression in endurance athletes, such as runners and cyclists, remains underexplored, especially with regard to sex differences.

Aims: (i) Assess sport- and sex-specific differences in PBMC microRNA expression induced by acute maximal and sub-maximal aerobic exercise in runners and cyclists and (ii) examine correlations between PBMC microRNAs and exercise performance.

Chemical reprogramming of human blood cells to pluripotent stem cells.

Chemical reprogramming offers a fundamentally innovative approach for generating human chemically induced pluripotent stem (hCiPS) cells using small molecules. Our recent studies showed that this approach was highly efficient in reprogramming human fibroblasts to hCiPS cells. However, generating hCiPS cells from human blood cells, which are the most accessible and convenient source for reprogramming, remains a challenge.

From Structure to Function: The Promise of PAMAM Dendrimers in Biomedical Applications.

PAMAM dendrimers are distinguished by their capacity for functionalization, which enhances the properties of the compounds they transport, rendering them highly versatile nanoparticles with extensive applications in the biomedical domain, including drug, vaccine, and gene delivery. These dendrimers can be internalized into cells through various endocytic mechanisms, such as passive diffusion, clathrin-mediated endocytosis, and caveolae-mediated endocytosis, allowing them to traverse the cytoplasm and reach intracellular targets, such as the mitochondria or nucleus. Despite the significant challenge posed by the cytotoxicity of these nanoparticles, which is contingent upon the dendrimer size, surface charge, and generation, numerous strategies have been documented to modify the dendrimer surface using polyethylene glycol and other chemical groups to temporarily mitigate their cytotoxic effects.

Challenges and Potential of Remote Sensing for Assessing Risk in Water Sources: Evidence from Chile.

Waterborne illnesses, including those caused by , are an increasing public health challenge, particularly in developing countries. Potential sources of salmonellosis include fruits and vegetables irrigated/treated with surface water, leading to human infections. causes millions of gastroenteritis cases annually, but early detection through routine water quality surveillance is time-consuming, requires specialized equipment, and faces limitations, such as coverage gaps, delayed data, and poor accessibility.

Activation of NF-κB Signaling by Optogenetic Clustering of IKKα and β.

Molecular optogenetics allows the control of molecular signaling pathways in response to light. This enables the analysis of the kinetics of signal activation and propagation in a spatially and temporally resolved manner. A key strategy for such control is the light-inducible clustering of signaling molecules, which leads to their activation and subsequent downstream signaling.

Advance in the assembly of the plant mitochondrial genomes using high-throughput DNA sequencing data of total cellular DNAs.

The assembly of plant mitochondrial genomes presents unique challenges due to difficulties in isolating mitochondrial DNA (mtDNA) and plant mitochondrial genome characteristics, such as low interspecific conservation; sequence sharing among mitochondrial, nuclear and plastid DNAs; and complex structural variations. Our laboratory has sequenced and assembled a dozen plant mitochondrial genomes, testing various strategies and identifying numerous assembly issues. This review compared the advanced methods and tools for plant mitochondrial genome assembly, categorizing assembly algorithms into three groups: (1) reference-based, (2) de novo and (3) iterative mapping and extension.

Cell-of-origin-specific behavioral deficits in oligodendrocyte-derived glioblastoma.

Glioblastoma (GBM) remains the most lethal primary brain tumor, persisting despite multimodal standard-of-care therapy. One of the major challenges for effective treatment of these tumors is their high heterogeneity, which stems, in part, from differences in the cell of origin. Using a CNP-Cre transgenic mouse model, this study investigates the role of differentiated oligodendrocytes as a candidate cell of origin for GBM.

Primary and metastatic cellular landscapes in human pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a complex tumor microenvironment (TME). We utilized single cell RNA sequencing to compare the TMEs of metastatic sites and primary tumors. We detected increased prevalence of exhausted CD8 T cells in metastases, as well as the enrichment of complement pathway encoding genes in immunosuppressive tumor-associated macrophages, consistent with profound immunosuppression in metastatic disease.

Human fetal kidney organoids model early human nephrogenesis and Notch-driven cell fate.

Pluripotent stem cell (PSC)-derived kidney organoids are used to model human renal development and disease; however, accessible models of human fetal development to benchmark PSC-derived organoids remain underdeveloped. Here, we establish a chemically defined, serum-free protocol for prolonged culture of human fetal kidney-derived organoids (hFKOs) in vitro. hFKOs self-organize into polarized renal epithelium, reinitiate from NCAM1 progenitors, and recapitulate nephrogenic and ureteric bud lineages.

Molecular Insights into Phosphonium-Based Ionic Liquid Extraction of Phenolic Pollutants from Aqueous Solutions.

Ionic liquids (ILs) are effective extractants for removing hazardous pollutants from aqueous solutions using liquid-liquid extraction (LLE). However, optimizing this process requires molecular-level insight into contaminant-IL interactions. Here, we investigated the extraction mechanisms of phenolic pollutants (PPs) utilizing phosphonium-based ionic liquids (PhILs) through molecular dynamics (MD) simulations and quantum mechanics (QM) calculations.

Analysis of metagenomic data.

Metagenomics has revolutionized our understanding of microbial communities, offering unprecedented insights into their genetic and functional diversity across Earth's diverse ecosystems. Beyond their roles as environmental constituents, microbiomes act as symbionts, profoundly influencing the health and function of their host organisms. Given the inherent complexity of these communities and the diverse environments where they reside, the components of a metagenomics study must be carefully tailored to yield accurate results that are representative of the populations of interest.

Automatic temporal analysis of speech: A quick and objective pipeline for the assessment of overt stuttering.

Fluency disorders, such as developmental stuttering, have been characterized by behavior such as blocks, repetitions, and prolongations in speech. Accurate measurement of overt stuttering behavior can aid in diagnostic evaluation and the determination of optimal treatment for this disorder. This study proposes a method - Automatic Temporal Analysis of Speech (ATAS) - for the assessment of speech fluency based on the detection and quantification of discrete pauses and vocal events.