Identifying optimal substrate classes of membrane transporters.

Membrane transporters are responsible for moving a wide variety of molecules across biological membranes, making them integral to key biological pathways in all organisms. Identifying all membrane transporters within a (meta-)proteome, along with their specific substrates, provides important information for various research fields, including biotechnology, pharmacology, and metabolomics. Protein datasets are frequently annotated with thousands of molecular functions that form complex networks, often with partial or full redundancy and hierarchical relationships.

U-73122, a phospholipase C inhibitor, impairs lymphocytic choriomeningitis virus virion infectivity.

Lassa virus (LASV) is an Old World (OW) mammarenavirus that causes Lassa fever, a life-threatening acute febrile disease endemic in West Africa. Lymphocytic choriomeningitis virus (LCMV) is a worldwide-distributed, prototypic OW mammarenavirus of clinical significance that has been largely neglected as a human pathogen. No licensed OW mammarenavirus vaccines are available, and the current therapeutic option is limited to the off-label use of ribavirin, which offers only partial efficacy.

Genome-wide Machine Learning Analysis of Anosmia and Ageusia with COVID-19.

The COVID-19 pandemic has caused substantial worldwide disruptions in health, economy, and society, manifesting symptoms such as loss of smell (anosmia) and loss of taste (ageusia), that can result in prolonged sensory impairment. Establishing the host genetic etiology of anosmia and ageusia in COVID-19 will aid in the overall understanding of the sensorineural aspect of the disease and contribute to possible treatments or cures. By using human genome sequencing data from the University of Iowa (UI) COVID-19 cohort (N=187) and the National Institute of Health All of Us (AoU) Research Program COVID-19 cohort (N=947), we investigated the genetics of anosmia and/or ageusia by employing feature selection techniques to construct a novel variant and gene prioritization pipeline, utilizing machine learning methods for the classification of patients.

MirGeneDB 3.0: improved taxonomic sampling, uniform nomenclature of novel conserved microRNA families and updated covariance models.

We present a major update of MirGeneDB (3.0), the manually curated animal microRNA gene database. Beyond moving to a new server and the creation of a computational mirror, we have expanded the database with the addition of 33 invertebrate species, including representatives of 5 previously unsampled phyla, and 6 mammal species.

Machine Learning-based Prognostic Subgrouping of Glioblastoma: A Multi-center Study.

Background: Glioblastoma is the most aggressive adult primary brain cancer, characterized by significant heterogeneity, posing challenges for patient management, treatment planning, and clinical trial stratification.

Methods: We developed a highly reproducible, personalized prognostication and clinical subgrouping system using machine learning (ML) on routine clinical data, MRI, and molecular measures from 2,838 demographically diverse patients across 22 institutions and 3 continents. Patients were stratified into favorable, intermediate, and poor prognostic subgroups (I, II, III) using Kaplan-Meier analysis (Cox proportional model and hazard ratios [HR]).

Higher expression of mir-31-5p is associated with reduced risk of head and neck keloid recurrence following surgical resection.

Objective: In this study, we aimed to evaluate mir-31-5p as a prognostic biomarker of keloid disease (KD) recurrence using a retrospective, treatment naïve, surgical cohort of head and neck KD cases from Henry Ford Health.

Methods: Using a tissue microarray, mir-31-5p expression was measured with miRNAscope, and mir-31-5p cell positivity was determined with QuPath. Logistic regression was used to test the association between mir-31-5p positive cells and KD recurrence at 1 year.

Comparative metagenomics of microbial communities and resistome in southern farming systems: implications for antimicrobial stewardship and public health.

Agricultural practices significantly influence microbial diversity and the distribution of virulence and antimicrobial resistance (AMR) genes, with implications for ecosystem health and food safety. This study used metagenomic sequencing to analyze 60 samples (30 per state) including water, soil, and manure (10 each) from Alabama (a mix of cattle and poultry sources) and Tennessee (primarily from cattle). The results highlighted a rich microbial diversity, predominantly comprising Bacteria (67%) and Viruses (33%), with a total of over 1,950 microbial species identified.

Bilirubin reductase shows host-specific associations in animal large intestines.

Animal gastrointestinal tracts contain diverse metabolites, including various host-derived compounds that gut-associated microbes interact with. Here, we explore the diversity and evolution of bilirubin reductase, a bacterial enzyme that metabolizes the host-derived tetrapyrrole bilirubin, performing a key role in the animal heme degradation pathway. Through an analysis of the bilirubin reductase phylogeny and predicted structures, we found that the enzyme family can be divided into three distinct clades with different structural features.

Recognition of Conus species using a combined approach of supervised learning and deep learning-based feature extraction.

Cone snails are venomous marine gastropods comprising more than 950 species widely distributed across different habitats. Their conical shells are remarkably similar to those of other invertebrates in terms of color, pattern, and size. For these reasons, assigning taxonomic signatures to cone snail shells is a challenging task.

Uncovering key predictive channels and clinical variables in the gamma band auditory steady-state response in early-stage psychosis: a longitudinal study.

Objective: Psychotic disorders are characterised by abnormalities in the synchronisation of neuronal responses. A 40 Hz gamma band deficit during auditory steady-state response (ASSR) measured by electroencephalogram (EEG) is a robust observation in psychosis and is associated with symptoms and functional deficits. However, the majority of ASSR studies focus on specific electrode sites, while whole scalp analysis using all channels, and the association with clinical symptoms, are rare.

Multispecies emergence of dual carbapenemase-producing Enterobacterales recovered from invasive infections in Chile.

Carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) represent a significant global threat. The emergence of dual CP-CRE is particularly alarming, as they can potentially compromise the efficacy of newer antibiotics, further decreasing therapeutic alternatives. Herein, we report the emergence of multiple species of CP-CRE recovered from invasive infections in Chile that simultaneously harbor and and provide an in-depth genomic characterization of these worrisome pathogens.

Combining crystallographic and binding affinity data towards a novel dataset of small molecule overlays.

Although small molecule superposition is a standard technique in drug discovery, a rigorous performance assessment of the corresponding methods is currently challenging. Datasets in this field are sparse, small, tailored to specific applications, unavailable, or outdated. The newly developed LOBSTER set described herein offers a publicly available and method-independent dataset for benchmarking and method optimization.

Artificial intelligence related safety issues associated with FDA medical device reports.

The Biden 2023 Artificial Intelligence (AI) Executive Order calls for the creation of a patient safety program. Patient safety reports are a natural starting point for identifying issues. We examined the feasibility of this approach by analyzing reports associated with AI/Machine Learning (ML)-enabled medical devices.

Kinome-wide CRISPR-Cas9 screens revealed as a positive regulator of TGF-β signaling.

The TGF-β signaling pathway is closely associated with human health and disease, and the systematic identification of factors involved in the TGF-β signaling pathway significantly contributes to the understanding and treatment of various diseases. Through kinome-wide CRISPR screen, we identified 13 candidate regulatory targets. Notably, the well-known hallmark genes and emerged as the top two candidate targets.

Discovery of Vascular Endothelial Growth Factor Receptor 2 Inhibitors Employing Junction Tree Variational Autoencoder with Bayesian Optimization and Gradient Ascent.

In the development of anticancer medications, vascular endothelial growth factor receptor 2 (VEGFR-2), which belongs to the protein tyrosine kinase family, emerges as one of the most significant targets of interest. The ongoing Food and Drug Administration (FDA) approval of novel therapeutic medicines toward VEGFR-2 emphasizes the urgent need to discover sophisticated molecular structures that are capable of reliably limiting VEGFR-2 activity. Recognizing the huge potential of deep-learning-based molecular model advancements, we focused our study on exploring the chemical space to find small molecules potentially inhibiting VEGFR-2.

Charting the shared genetic architecture of Alzheimer's disease, cognition, and educational attainment, and associations with brain development.

The observation that the risk of developing Alzheimer's disease is reduced in individuals with high premorbid cognitive functioning, higher educational attainment, and occupational status has led to the 'cognitive reserve' hypothesis. This hypothesis suggests that individuals with greater cognitive reserve can tolerate a more significant burden of neuropathological changes before the onset of cognitive decline. The underpinnings of cognitive reserve remain poorly understood, although a shared genetic basis between measures of cognitive reserve and Alzheimer's disease has been suggested.

Lethal COVID-19 associates with RAAS-induced inflammation for multiple organ damage including mediastinal lymph nodes.

Lethal COVID-19 outcomes are attributed to classic cytokine storm. We revisit this using RNA sequencing of nasopharyngeal and 40 autopsy samples from patients dying of SARS-CoV-2. Subsets of the 100 top-upregulated genes in nasal swabs are upregulated in the heart, lung, kidney, and liver, but not mediastinal lymph nodes.

Gut Microbiota Composition Positively Correlates with Sports Performance in Competitive Non-Professional Female and Male Runners.

There is still a pressing need for further investigation to bridge the gap in understanding the differences in gut microbiota composition between female runners and their male counterparts. We aimed to determine the gut microbiota composition in competitive non-professional female and male runners and to correlate the gut bacteria to performance. Our study included 40 subjects, of which 22 were runners (13 males and 9 females) and 18 control subjects (9 males and 9 females, representing the general population who perform light physical activity with a weekly running volume of ≤5 km per week).

Genetically Engineered Filamentous Bacteriophages Displaying TGF-β1 Promote Angiogenesis in 3D Microenvironments.

Combined 3D cell culture in vitro assays with microenvironment-mimicking systems are effective for cell-based screening tests of drug and chemical toxicity. Filamentous bacteriophages have diverse applications in material science, drug delivery, tissue engineering, energy, and biosensor development. Specifically, genetically modified bacteriophages have the potential to deliver therapeutic molecules or genes to targeted tumor tissues.

Bilirubin bioconversion to urobilin in the gut-liver-kidney axis: A biomarker for insulin resistance in the Cardiovascular-Kidney-Metabolic (CKM) Syndrome.

The rising rates of obesity worldwide have increased the incidence of cardiovascular disease (CVD), making it the number one cause of death. Higher plasma bilirubin levels have been shown to prevent metabolic dysfunction and CVD. However, reducing levels leads to deleterious outcomes, possibly due to reduced bilirubin half-life that escalates the production of its catabolized product, urobilinogen, produced by gut bacteria and naturally oxidized to urobilin.