Ramp sequence may explain synonymous variant association with Alzheimer's disease in the Paired Immunoglobulin-like Type 2 Receptor Alpha ().

Background: Synonymous variant () in the Paired Immunoglobulin-like Type 2 Receptor Alpha () gene was previously associated with decreased risk for Alzheimer's disease (AD) in genome-wide association studies, but its biological impact is largely unknown.

Objective: We hypothesized that decreases mRNA and protein levels by destroying a ramp of slowly translated codons at the 5' end of .

Methods: We assessed predicted effects on through quantitative polymerase chain reactions (qPCR) and enzyme-linked immunosorbent assays (ELISA) using Chinese hamster ovary (CHO) cells.

A Draft Pacific Ancestry Pangenome Reference.

Individuals of Pacific ancestry suffer some of the highest rates of health disparities yet remain vastly underrepresented in genomic research, including currently available linear and pangenome references. To begin addressing this, we developed the first Pacific ancestry pangenome reference using 23 individuals with diverse Pacific ancestry. We assembled 46 haploid genomes from these 23 individuals, resulting in highly accurate and contiguous genome assemblies with an average quality value of 55.

A pleural based mass in a post-partum woman.

https://bit.ly/3S3ejVK.

Evaluating a large language model's ability to solve programming exercises from an introductory bioinformatics course.

Computer programming is a fundamental tool for life scientists, allowing them to carry out essential research tasks. However, despite various educational efforts, learning to write code can be a challenging endeavor for students and researchers in life-sciences disciplines. Recent advances in artificial intelligence have made it possible to translate human-language prompts to functional code, raising questions about whether these technologies can aid (or replace) life scientists' efforts to write code.

Short Sequence Aligner Benchmarking for Chromatin Research.

Much of today's molecular science revolves around next-generation sequencing. Frequently, the first step in analyzing such data is aligning sequencing reads to a reference genome. This step is often taken for granted, but any analysis downstream of the alignment will be affected by the aligner's ability to correctly map sequences.

The genome of a giant (trevally): .

, commonly known as giant kingfish or giant trevally, is a large, reef-associated apex predator. It is a prized sportfish, targeted throughout its tropical and subtropical range in the Indian and Pacific Oceans. It also gained significant interest in aquaculture due to its unusual freshwater tolerance.

Expanded central role of the respiratory physiotherapists in the community setting.

The development of community hubs through the Slaintecare initiative will rely on respiratory physiotherapists and clinical nurse specialists for the management of chronic respiratory diseases. The role of the respiratory physiotherapist has evolved dramatically over the last decade. We review the increasing scope of practice of the physiotherapist and the evidence base for same.

The Ramp Atlas: facilitating tissue and cell-specific ramp sequence analyses through an intuitive web interface.

Ramp sequences occur when the average translational efficiency of codons near the 5' end of highly expressed genes is significantly lower than the rest of the gene sequence, which counterintuitively increases translational efficiency by decreasing downstream ribosomal collisions. Here, we show that the relative codon adaptiveness within different tissues changes the existence of a ramp sequence without altering the underlying genetic code. We present the first comprehensive analysis of tissue and cell type-specific ramp sequences and report 3108 genes with ramp sequences that change between tissues and cell types, which corresponds with increased gene expression within those tissues and cells.

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis.

GenoRisk: A polygenic risk score for Alzheimer's disease.

Introduction: Recent clinical trials are considering inclusion of more than just apolipoprotein E () ε4 genotype as a way of reducing variability in analysis of outcomes.

Methods: Case-control data were used to compare the capacity of age, sex, and 58 Alzheimer's disease (AD)-associated single nucleotide polymorphisms (SNPs) to predict AD status using several statistical models. Model performance was assessed with Brier scores and tenfold cross-validation.

De novo genome assembly of the marine teleost, bluefin trevally (Caranx melampygus).

The bluefin trevally, Caranx melampygus, also known as the bluefin kingfish or bluefin jack, is known for its remarkable, bright-blue fins. This marine teleost is a widely prized sportfish, but few resources have been devoted to the genomics and conservation of this species because it is not targeted by large-scale commercial fisheries. Population declines from recreational and artisanal overfishing have been observed in Hawai'i, USA, resulting in both an interest in aquaculture and concerns about the long-term conservation of this species.

A comprehensive analysis of the phylogenetic signal in ramp sequences in 211 vertebrates.

Ramp sequences increase translational speed and accuracy when rare, slowly-translated codons are found at the beginnings of genes. Here, the results of the first analysis of ramp sequences in a phylogenetic construct are presented. Ramp sequences were compared from 247 vertebrates (114 Mammalian and 133 non-mammalian), where the presence and absence of ramp sequences was analyzed as a binary character in a parsimony and maximum likelihood framework.

Atypical chemokine receptor ACKR2-V41A has decreased CCL2 binding, scavenging, and activation, supporting sustained inflammation and increased Alzheimer's disease risk.

A recent genome-wide association study (GWAS) of 59 cerebrospinal fluid (CSF) proteins with a connection to Alzheimer's disease (AD) demonstrated an association between increased levels of chemokine ligand 2 (CCL2) with an atypical chemokine receptor chemokine-binding protein 2 variant V41A (ACKR2-V41A; rs2228467). High levels of CCL2 are associated with increased risk of AD development as well as other inflammatory diseases. In this study we characterized the biological function of the ACKR2-V41A receptor compared to the wild type allele by measuring its ligand binding affinity, CCL2 scavenging efficiency, and cell activation sensitivity.

Codon Pairs are Phylogenetically Conserved: A comprehensive analysis of codon pairing conservation across the Tree of Life.

Identical codon pairing and co-tRNA codon pairing increase translational efficiency within genes when two codons that encode the same amino acid are translated by the same tRNA before it diffuses from the ribosome. We examine the phylogenetic signal in both identical and co-tRNA codon pairing across 23 428 species using alignment-free and parsimony methods. We determined that conserved codon pairing typically has a smaller window size than the length of a ribosome, and codon pairing tracks phylogenies across various taxonomic groups.

Codon use and aversion is largely phylogenetically conserved across the tree of life.

Using parsimony, we analyzed codon usages across 12,337 species and 25,727 orthologous genes to rank specific genes and codons according to their phylogenetic signal. We examined each codon within each ortholog to determine the codon usage for each species. In total, 890,814 codons were parsimony informative.

Molecular epidemiology of carbapenem-resistance plasmids using publicly available sequences.

Carbapenem-resistant bacteria have quickly become a worldwide concern in nosocomial infections. Of the seven known carbapenemases, four have been shown to be particularly problematic: KPC, NDM, IMP, and VIM. To date, many local and species- or carbapenemase-specific epidemiological studies have been performed, which often focus on the organism itself.

CAM: an alignment-free method to recover phylogenies using codon aversion motifs.

Background: Common phylogenomic approaches for recovering phylogenies are often time-consuming and require annotations for orthologous gene relationships that are not always available. In contrast, alignment-free phylogenomic approaches typically use structure and oligomer frequencies to calculate pairwise distances between species. We have developed an approach to quickly calculate distances between species based on codon aversion.

Arabidopsis thaliana organelles mimic the T7 phage DNA replisome with specific interactions between Twinkle protein and DNA polymerases Pol1A and Pol1B.

Background: Plant chloroplasts and mitochondria utilize nuclear encoded proteins to replicate their DNA. These proteins are purposely built for replication in the organelle environment and are distinct from those involved in replication of the nuclear genome. These organelle-localized proteins have ancestral roots in bacterial and bacteriophage genes, supporting the endosymbiotic theory of their origin.