Crossing the streams: Improving data quality and integration across the One Health genomics continuum with data standards and implementation strategies.

The Canadian Genomics Research and Development Initiative for Antimicrobial Resistance (GRDI-AMR) uses a genomics-based approach to understand how health care, food production and the environment contribute to the development of antimicrobial resistance. Integrating genomics contextual data streams across the One Health continuum is challenging because of the diversity in data scope, content and structure. To better enable data harmonization for analyses, a contextual data standard was developed.

Dynamic Contact Networks in Confined Spaces: Synthesizing Micro-Level Encounter Patterns through Human Mobility Models from Real-World Data.

This study advances the field of infectious disease forecasting by introducing a novel approach to micro-level contact modeling, leveraging human movement patterns to generate realistic temporal-dynamic networks. Through the incorporation of human mobility models and parameter tuning, this research presents an innovative method for simulating micro-level encounters that closely mirror infection dynamics within confined spaces. Central to our methodology is the application of Bayesian optimization for parameter selection, which refines our models to emulate both the properties of real-world infection curves and the characteristics of network properties.

High-throughput rapid amplicon sequencing for multilocus sequence typing of from archived clinical DNA samples.

Introduction: Spillover events of have devastating effects on the wild sheep populations. Multilocus sequence typing (MLST) is used to monitor spillover events and the spread of between the sheep populations. Most studies involving the typing of have used Sanger sequencing.

Discovery of the sEH Inhibitor Epoxykynin as a Potent Kynurenine Pathway Modulator.

Disease-related phenotypic assays enable unbiased discovery of novel bioactive small molecules and may provide novel insights into physiological systems and unprecedented molecular modes of action (MMOA). Herein, we report the identification and characterization of epoxykynin, a potent inhibitor of the soluble epoxide hydrolase (sEH). Epoxykynin was discovered by means of a cellular assay monitoring modulation of kynurenine (Kyn) levels in BxPC-3 cells upon stimulation with the cytokine interferon-γ (IFN-γ) and subsequent target identification employing affinity-based chemical proteomics.

FUBP1 is a general splicing factor facilitating 3' splice site recognition and splicing of long introns.

Splicing of pre-mRNAs critically contributes to gene regulation and proteome expansion in eukaryotes, but our understanding of the recognition and pairing of splice sites during spliceosome assembly lacks detail. Here, we identify the multidomain RNA-binding protein FUBP1 as a key splicing factor that binds to a hitherto unknown cis-regulatory motif. By collecting NMR, structural, and in vivo interaction data, we demonstrate that FUBP1 stabilizes U2AF2 and SF1, key components at the 3' splice site, through multivalent binding interfaces located within its disordered regions.

A global survey of plasmids and their associations with antimicrobial resistance.

Plasmids are the primary vector for horizontal transfer of antimicrobial resistance (AMR) within bacterial populations. We applied the MOB-suite, a toolset for reconstructing and typing plasmids, to 150 767 publicly available whole-genome sequencing samples covering 1204 distinct serovars to produce a large-scale population survey of plasmids based on the MOB-suite plasmid nomenclature. Reconstruction yielded 183 017 plasmids representing 1044 primary MOB-clusters and 830 potentially novel MOB-clusters.

Prophylactic Administration of Mesenchymal Stromal Cells Does Not Prevent Arrested Lung Development in Extremely Premature-Born Non-Human Primates.

Premature birth is a leading cause of childhood morbidity and mortality and often followed by an arrest of postnatal lung development called bronchopulmonary dysplasia. Therapies using exogenous mesenchymal stromal cells (MSC) have proven highly efficacious in term-born rodent models of this disease, but effects of MSC in actual premature-born lungs are largely unknown. Here, we investigated thirteen non-human primates (baboons; Papio spp.

Designing a Small Fluorescent Inhibitor to Investigate Soluble Epoxide Hydrolase Engagement in Living Cells.

Soluble epoxide hydrolase (sEH) is a promising target for a number of inflammation-related diseases. In addition, inhibition of sEH has been shown to reduce neuroinflammation, which plays a critical role in the development of central nervous system (CNS) diseases such as Alzheimer's disease. In this study, we present the rational design of a small fluorescent sEH inhibitor.

Denitrification in foraminifera has an ancient origin and is complemented by associated bacteria.

Benthic foraminifera are unicellular eukaryotes that inhabit sediments of aquatic environments. Several foraminifera of the order Rotaliida are known to store and use nitrate for denitrification, a unique energy metabolism among eukaryotes. The rotaliid spp.

Rapid and accurate SNP genotyping of clonal bacterial pathogens with BioHansel.

Hierarchical genotyping approaches can provide insights into the source, geography and temporal distribution of bacterial pathogens. Multiple hierarchical SNP genotyping schemes have previously been developed so that new isolates can rapidly be placed within pre-computed population structures, without the need to rebuild phylogenetic trees for the entire dataset. This classification approach has, however, seen limited uptake in routine public health settings due to analytical complexity and the lack of standardized tools that provide clear and easy ways to interpret results.

Complete Genome Sequences for 36 Canadian Salmonella enterica Serovar Typhimurium and I 1,4,[5],12:i:- Isolates from Clinical and Animal Sources.

Here, we report the complete genome sequences for 36 Canadian isolates of subsp. serovar Typhimurium and its monophasic variant I 1,4,[5]:12:i:- from both clinical and animal sources. These genome sequences will provide useful references for understanding the genetic variation within this prominent serotype.

Universal whole-sequence-based plasmid typing and its utility to prediction of host range and epidemiological surveillance.

Bacterial plasmids play a large role in allowing bacteria to adapt to changing environments and can pose a significant risk to human health if they confer virulence and antimicrobial resistance (AMR). Plasmids differ significantly in the taxonomic breadth of host bacteria in which they can successfully replicate, this is commonly referred to as 'host range' and is usually described in qualitative terms of 'narrow' or 'broad'. Understanding the host range potential of plasmids is of great interest due to their ability to disseminate traits such as AMR through bacterial populations and into human pathogens.

Challenges and opportunities for public health made possible by advances in natural language processing.

Natural language processing (NLP) is a subfield of artificial intelligence devoted to understanding and generation of language. The recent advances in NLP technologies are enabling rapid analysis of vast amounts of text, thereby creating opportunities for health research and evidence-informed decision making. The analysis and data extraction from scientific literature, technical reports, health records, social media, surveys, registries and other documents can support core public health functions including the enhancement of existing surveillance systems (e.

Synergistic targeting of FLT3 mutations in AML via combined menin-MLL and FLT3 inhibition.

The interaction of menin (MEN1) and MLL (MLL1, KMT2A) is a dependency and provides a potential opportunity for treatment of NPM1-mutant (NPM1mut) and MLL-rearranged (MLL-r) leukemias. Concomitant activating driver mutations in the gene encoding the tyrosine kinase FLT3 occur in both leukemias and are particularly common in the NPM1mut subtype. In this study, transcriptional profiling after pharmacological inhibition of the menin-MLL complex revealed specific changes in gene expression, with downregulation of the MEIS1 transcription factor and its transcriptional target gene FLT3 being the most pronounced.

Checklist, assemblage composition, and biogeographic assessment of Recent benthic foraminifera (Protista, Rhizaria) from São Vincente, Cape Verdes.

We describe for the first time subtropical intertidal foraminiferal assemblages from beach sands on São Vincente, Cape Verdes. Sixty-five benthic foraminiferal species were recognised, representing 47 genera, 31 families, and 8 superfamilies. Endemic species were not recognised.

Consistently dated Atlantic sediment cores over the last 40 thousand years.

Rapid changes in ocean circulation and climate have been observed in marine-sediment and ice cores over the last glacial period and deglaciation, highlighting the non-linear character of the climate system and underlining the possibility of rapid climate shifts in response to anthropogenic greenhouse gas forcing. To date, these rapid changes in climate and ocean circulation are still not fully explained. One obstacle hindering progress in our understanding of the interactions between past ocean circulation and climate changes is the difficulty of accurately dating marine cores.

A Novel Eukaryotic Denitrification Pathway in Foraminifera.

Benthic foraminifera are unicellular eukaryotes inhabiting sediments of aquatic environments. Several species were shown to store and use nitrate for complete denitrification, a unique energy metabolism among eukaryotes. The population of benthic foraminifera reaches high densities in oxygen-depleted marine habitats, where they play a key role in the marine nitrogen cycle.

[The environment as a reservoir for antimicrobial resistance : A growing problem for public health?].

Antimicrobial resistance (AMR) is a threat to public and animal health on the global scale. The origin of the genes associated with resistance has long been unknown. Recently, there is a growing body of evidence demonstrating that environmental bacteria are resistant to a multitude of antibiotic substances and that this environmental reservoir of AMR is still growing.

Coupling of oceanic carbon and nitrogen facilitates spatially resolved quantitative reconstruction of nitrate inventories.

Anthropogenic impacts are perturbing the global nitrogen cycle via warming effects and pollutant sources such as chemical fertilizers and burning of fossil fuels. Understanding controls on past nitrogen inventories might improve predictions for future global biogeochemical cycling. Here we show the quantitative reconstruction of deglacial bottom water nitrate concentrations from intermediate depths of the Peruvian upwelling region, using foraminiferal pore density.

Stereoselective One-Pot Synthesis of Dihydropyrimido[2,1-a]isoindole-6(2H)-ones.

A diastereoselective one-pot synthesis of highly substituted dihydropyrimido[2,1-a]isoindole-6(2H)-ones containing three continuous stereocenters is reported. The reaction sequence is based on a hetero-Diels-Alder reaction between an enimide and a N-acylimine followed by an unprecedented Brønsted acid mediated rearrangement of an intermediate 5,6-dihydro-4H-1,3-oxazine to a pyrimido[2,1-a]isoindole.

Critical dynamics in population vaccinating behavior.

Vaccine refusal can lead to renewed outbreaks of previously eliminated diseases and even delay global eradication. Vaccinating decisions exemplify a complex, coupled system where vaccinating behavior and disease dynamics influence one another. Such systems often exhibit critical phenomena-special dynamics close to a tipping point leading to a new dynamical regime.

Microgravity validation of a novel system for RNA isolation and multiplex quantitative real time PCR analysis of gene expression on the International Space Station.

The International Space Station (ISS) National Laboratory is dedicated to studying the effects of space on life and physical systems, and to developing new science and technologies for space exploration. A key aspect of achieving these goals is to operate the ISS National Lab more like an Earth-based laboratory, conducting complex end-to-end experimentation, not limited to simple microgravity exposure. Towards that end NASA developed a novel suite of molecular biology laboratory tools, reagents, and methods, named WetLab-2, uniquely designed to operate in microgravity, and to process biological samples for real-time gene expression analysis on-orbit.

Humans rather than climate the primary cause of Pleistocene megafaunal extinction in Australia.

Environmental histories that span the last full glacial cycle and are representative of regional change in Australia are scarce, hampering assessment of environmental change preceding and concurrent with human dispersal on the continent ca. 47,000 years ago. Here we present a continuous 150,000-year record offshore south-western Australia and identify the timing of two critical late Pleistocene events: wide-scale ecosystem change and regional megafaunal population collapse.