Browse Articles
Discover research articles across all indexed journals
Compositional data analysis enables statistical rigor in comparative glycomics
Abstract Comparative glycomics data are compositional data, where measured glycans are parts of a whole, indicated by relative abundances. Applying traditional statistical analyses to these data often results in misleading conclusions, such as spurious “decreases” of glycans when other structures increase in abundance, or high false-positive rates for differential abundance. Our work introduces a compositional data analysis framework, tailored to comparative glycomics, to account for these data dependencies. We employ center log-ratio and additive log-ratio transformations, augmented with a scale uncertainty/information model, to introduce a statistically robust and sensitive data analysis pipeline. Applied to comparative glycomics datasets, including known glycan concentrations in defined mixtures, this approach controls false-positive rates and results in reproducible biological findings. Additionally, we present specialized analysis modalities: alpha- and beta-diversity analyze glycan distributions within and between samples, while cross-class glycan correlations shed light on previously undetected interdependencies. These approaches reveal insights into glycome variations that are critical to understanding roles of glycans in health and disease.
Role of toxic and essential elements in sleep duration of patients with cardiovascular diseases
α-Synuclein fibrils enhance HIV-1 infection of human T cells, macrophages and microglia
Abstract HIV-associated neurocognitive disorders (HAND) and viral reservoirs in the brain remain a significant challenge. Despite their importance, the mechanisms allowing HIV-1 entry and replication in the central nervous system (CNS) are poorly understood. Here, we show that α-synuclein and (to a lesser extent) Aβ fibrils associated with neurological diseases enhance HIV-1 entry and replication in human T cells, macrophages, and microglia. Additionally, an HIV-1 Env-derived amyloidogenic peptide accelerated amyloid formation by α-synuclein and Aβ peptides. Mechanistic studies show that α-synuclein and Aβ fibrils interact with HIV-1 particles and promote virion attachment and fusion with target cells. Despite an overall negative surface charge, these fibrils facilitate interactions between viral and cellular membranes. The enhancing effects of human brain extracts on HIV-1 infection correlated with their binding to Thioflavin T, a dye commonly used to stain amyloids. Our results suggest a detrimental interplay between HIV-1 and brain amyloids that may contribute to the development of neurodegenerative diseases.
Presence of EGF ligand restricts the binding ability of EgB4 nanobody to EGFR extracellular domain
High-entropy assisted capacitive energy storage in relaxor ferroelectrics by chemical short-range order
Relationship between inherited genetic variation and survival from colorectal cancer stratified by tumour location
Abstract The location of a patient’s colorectal cancer (CRC) influences their outcome but inherited factors may also be involved. We studied 1899 patients with advanced CRC (514 had proximal colonic, 493 distal colonic and 892 rectal tumours) and carried out genome-wide association studies for survival. Single nucleotide polymorphisms (SNPs) suggestive of association (P < 1.0 × 10–5) were tested for replication in 5078 CRC patients from the UK Biobank. We investigated the relationship between Phosphatidylinositol 4-Kinase Type 2 Beta (PI4K2B) expression in colorectal tumours and survival in 597 patients from The Human Protein Atlas (THPA). We also analysed 3 SNPs previously associated with survival by anatomical site. We found that SNPs at 54 independent loci were suggestive of an association with survival when stratified by tumour location. rs76011559 replicated in patients with proximal tumours (COIN, COIN-B and UK Biobank combined Hazard Ratio [HR] = 1.53, 95% Confidence Intervals [CI] = 1.19–1.86, P = 7.5 × 10–7) and rs12273047 replicated in patients with rectal tumours (combined HR = 1.27, 95% CI = 1.09–1.46, P = 4.1 × 10–7). In gene analyses, PI4K2B associated with survival in patients with distal cancers (P = 2.1 × 10–6) and increased PI4K2B expression in colorectal tumours was associated with improved survival (P = 9.6 × 10–5). No previously associated SNPs were replicated. Our data identify novel loci associated with survival when stratified by tumour location.
Recombinant expression systems for production of stabilised virus-like particles as next-generation polio vaccines
Abstract Polioviruses have caused crippling disease in humans for centuries, prior to the successful development of vaccines in the mid-1900’s, which dramatically reduced disease prevalence. Continued use of these vaccines, however, threatens ultimate disease eradication and achievement of a polio-free world. Virus-like particles (VLPs) that lack a viral genome represent a safer potential vaccine, although they require particle stabilization. Using our previously established genetic techniques to stabilize the structural capsid proteins, we demonstrate production of poliovirus VLPs of all three serotypes, from four different recombinant expression systems. We compare the antigenicity, thermostability and immunogenicity of these stabilized VLPs against the current inactivated polio vaccine, demonstrating equivalent or superior immunogenicity in female Wistar rats. Structural analyses of these recombinant VLPs provide a rational understanding of the stabilizing mutations and the role of potential excipients. Collectively, we have established these poliovirus stabilized VLPs as viable next-generation vaccine candidates for the future.
A novel approach for target deconvolution from phenotype-based screening using knowledge graph
SAMHD1 shapes deoxynucleotide triphosphate homeostasis by interconnecting the depletion and biosynthesis of different dNTPs
Automated system for calving time prediction and cattle classification utilizing trajectory data and movement features
Structural basis for the interaction between the Drosophila RTK Sevenless (dROS1) and the GPCR BOSS
Abstract Sevenless, the Drosophila homologue of ROS1 (University of Rochester Sarcoma) (herein, dROS1) is a receptor tyrosine kinase (RTK) essential for the differentiation of Drosophila R7 photoreceptor cells. Activation of dROS1 is mediated by binding to the extracellular region (ECR) of the GPCR (G protein coupled receptor) BOSS (Bride Of Sevenless) on adjacent cells. Activation of dROS1 by BOSS leads to subsequent downstream signaling pathways including SOS (Son of Sevenless). However, the physical basis for how dROS1 interacts with BOSS has long remained unknown. Here we provide a cryo-EM structure of dROS1’s extracellular region, which mediates ligand binding. We show that the extracellular region of dROS1 adopts a folded-over conformation stabilized by an N-terminal domain comprised of two disulfide stapled helical hairpins. We further narrowed down the interacting binding epitopes on both dROS1 and BOSS using hydrogen-deuterium exchange mass spectrometry (HDX-MS). This includes beta-strands in dROS1’s third Fibronectin type III (FNIII) domain and a C-terminal peptide in BOSS’ ECR. Our mutagenesis studies, coupled with AlphaFold complex predictions, support a binding interaction mediated by a hydrophobic interaction and beta-strand augmentation between these regions. Our findings provide a fundamental understanding of the regulatory function of dROS1 and further provide mechanistic insight into the human ortholog and oncogene ROS1.
Identification of MORF4L1 as an endogenous substrate of CRBN and its potential role as a therapeutic target in cancer
A data-driven latent variable approach to validating the research domain criteria framework
Spatiotemporal evolution of landscape ecological risk and its driving factors of the Beijing–Tianjin–Hebei major mineral belt, 1985–2022
Incomplete human reference genomes can drive false sex biases and expose patient-identifying information in metagenomic data
Abstract As next-generation sequencing technologies produce deeper genome coverages at lower costs, there is a critical need for reliable computational host DNA removal in metagenomic data. We find that insufficient host filtration using prior human genome references can introduce false sex biases and inadvertently permit flow-through of host-specific DNA during bioinformatic analyses, which could be exploited for individual identification. To address these issues, we introduce and benchmark three host filtration methods of varying throughput, with concomitant applications across low biomass samples such as skin and high microbial biomass datasets including fecal samples. We find that these methods are important for obtaining accurate results in low biomass samples (e.g., tissue, skin). Overall, we demonstrate that rigorous host filtration is a key component of privacy-minded analyses of patient microbiomes and provide computationally efficient pipelines for accomplishing this task on large-scale datasets.
First record of microplastic contamination in adult endemic amazonian anuran species
Abstract The microplastics (MPs), due to their high dispersion and bioaccumulation rates, have been identified in various animal groups, such as anuran amphibians during both larval and adult stages. However, current studies on adult anuran amphibians focus on assessing only one exposure route, the digestive system, while other routes remain underestimated. Therefore, this present study aimed to evaluate the degree of contamination in the digestive, respiratory, and integumentary systems, in situ, of two endemic Amazonian adult anuran species (Physalaemus ephippifer and Boana multifasciata). From this, we identified and characterized microplastic particles for each exposure route, assessed the effects of morphometric measures on the total MP contamination level and in the gastrointestinal tract (GIT). Additionally, we determined different contamination indices and how they vary according to species and systems. Based on our data, the digestive and integumentary exposure routes showed the highest contamination levels for both species. Additionally, variations in MP contamination levels indicated that P. ephippifer had a higher level of MP contamination. Thus, this study provides the first evidence of microplastic exposure through respiratory and integumentary routes in adult anurans in situ, and it is the first to identify MP contamination in terrestrial biomonitors in the Amazon.