Basking sharks (Cetorhinus maximus) seasonally aggregate in coastal surface waters of the North Atlantic, providing opportunities for visual observation. While putative courtship displays have been observed, actual copulation has not been documented. Here we examine video collected by an unmanned aerial vehicle ("drone") of novel behavioral interactions between basking sharks in Cape Cod Bay, Massachusetts in May 2021.
View Article and Find Full Text PDFSingle-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics datasets into a resource comprising >2.
View Article and Find Full Text PDFNeuropsychiatric genome-wide association studies (GWASs), including those for autism spectrum disorder and schizophrenia, show strong enrichment for regulatory elements in the developing brain. However, prioritizing risk genes and mechanisms is challenging without a unified regulatory atlas. Across 672 diverse developing human brains, we identified 15,752 genes harboring gene, isoform, and/or splicing quantitative trait loci, mapping 3739 to cellular contexts.
View Article and Find Full Text PDFMost genetic variants associated with psychiatric disorders are located in noncoding regions of the genome. To investigate their functional implications, we integrate epigenetic data from the PsychENCODE Consortium and other published sources to construct a comprehensive atlas of candidate brain cis-regulatory elements. Using deep learning, we model these elements' sequence syntax and predict how binding sites for lineage-specific transcription factors contribute to cell type-specific gene regulation in various types of glia and neurons.
View Article and Find Full Text PDFBackground: A better understanding of the pancreatic ductal adenocarcinoma (PDAC) immune microenvironment is critical to developing new treatments and improving outcomes. Myeloid cells are of particular importance for PDAC progression; however, the presence of heterogenous subsets with different ontogeny and impact, along with some fluidity between them, (infiltrating monocytes vs. tissue-resident macrophages; M1 vs.
View Article and Find Full Text PDFBackground: In the University setting, striving for consistency and reliability of assessment evaluation is essential to reducing the impact of marking variations. Marking processes such as consensus calibration have the potential to reduce issues which arise from the influence of markers professional knowledge and experience, as well as fixed and acquired marking habits. Furthermore, the influence of marker feedback which supports learning development is associated with the feedback literacy of both the teacher and the student.
View Article and Find Full Text PDFBackground: Neutrophil extracellular traps (NETs) occur when neutrophil chromatin is decondensed and extruded into the extracellular space in a web-like structure. Originally described as an anti-microbial function, this process has been implicated in the pathogenesis of pancreatic disease. In addition, NETs are upregulated during physiologic wound-healing and coagulation.
View Article and Find Full Text PDFAim: To examine the effects of a delirium education module on undergraduate nursing students' knowledge of and perceived confidence and competence in delirium care.
Background: Delirium is common in intensive care units (ICUs) and leads to poor clinical outcomes. The under recognition of delirium is a major problem in ICU medicine.
Recent prospective trials for esophageal cancer, gastric cancer, and gastrointestinal stromal tumor (GIST) are encouraging. This manuscript reviews selected recently published studies. Not surprisingly, immunotherapy dominates the current clinical trial landscape.
View Article and Find Full Text PDFBackground: Genome-wide association studies (GWAS) have identified 30 risk loci for primary sclerosing cholangitis (PSC). Variants within these loci are found predominantly in noncoding regions of DNA making their mechanisms of conferring risk hard to define. Epigenomic studies have shown noncoding variants broadly impact regulatory element activity.
View Article and Find Full Text PDFUnderstanding the regulatory landscape of the human genome is a long-standing objective of modern biology. Using the reference-free alignment across 241 mammalian genomes produced by the Zoonomia Consortium, we charted evolutionary trajectories for 0.92 million human candidate cis-regulatory elements (cCREs) and 15.
View Article and Find Full Text PDFGenomic regulatory elements active in the developing human brain are notably enriched in genetic risk for neuropsychiatric disorders, including autism spectrum disorder (ASD), schizophrenia, and bipolar disorder. However, prioritizing the specific risk genes and candidate molecular mechanisms underlying these genetic enrichments has been hindered by the lack of a single unified large-scale gene regulatory atlas of human brain development. Here, we uniformly process and systematically characterize gene, isoform, and splicing quantitative trait loci (xQTLs) in 672 fetal brain samples from unique subjects across multiple ancestral populations.
View Article and Find Full Text PDFBackground: Smoking is the largest single cause of lifestyle-related preventable morbidity and mortality. Nurses form the largest cohort of health professionals and are strategically placed to implement smoking cessation interventions. However their capacity is underutilised, particularly in rural and remote areas in countries such as Australia where the incidence of smoking in is higher than average and access to healthcare is limited.
View Article and Find Full Text PDFClinical trials exploring bolus intravenous delivery of interleukin-12 (IL-12) for treatment of solid tumors ultimately failed due to lack of clinical response and severe dose-limiting toxicities. The present study was conducted to evaluate whether recombinant murine IL-12 (rmIL-12) could be successfully encapsulated within Poly (D, l-lactide-co-glycolide) (PLGA) nanospheres (rmIL-12ns) for safe and effective systemic delivery at pharmacologic scale. Optimal fabrication of rmIL-12ns occurs with dichloromethane as the organic solvent and emulsion formation via ultrasonication at 50% power (250 W sonicator) for 10 s (50W10s).
View Article and Find Full Text PDFUnderstanding shark mating dynamics and mating site use may be vital to species management. The Dry Tortugas courtship and mating ground (DTCMG) has been known as a mating site for nurse sharks, Ginglymostoma cirratum, since 1895. In a 30-yr (1992-2021) study we have documented long-term site fidelity to this area with data from 137 adult sharks (89 female, 48 male) tagged with PIT, fin, and acoustic tags.
View Article and Find Full Text PDFEvery cell in the human body inherits a copy of the same genetic information. The three billion base pairs of DNA in the human genome, and the roughly 50 000 coding and non-coding genes they contain, must thus encode all the complexity of human development and cell and tissue type diversity. Differences in gene regulation, or the modulation of gene expression, enable individual cells to interpret the genome differently to carry out their specific functions.
View Article and Find Full Text PDFMafB (a bZIP transcription factor), ß-catenin (the ultimate target of the Wnt signal transduction pathway that acts as a transcriptional co-activator of LEF/TCF proteins), and WDR77 (a transcriptional co-activator of multiple hormone receptors) are important for breast cellular transformation. Unexpectedly, these proteins interact directly with each other, and they have similar genomic binding profiles. Furthermore, while some of these common target sites coincide with those bound by LEF/TCF, the majority are located just downstream of transcription initiation sites at a position near paused RNA polymerase (Pol II) and the +1 nucleosome.
View Article and Find Full Text PDFGastric adenocarcinoma (GC) is a devastating disease and is the third leading cause of cancer deaths worldwide. This heterogeneous disease has several different classification systems that consider histological appearance and genomic alterations. Understanding the etiology of GC, including infection, hereditary conditions, and environmental factors, is of particular importance and is discussed in this review.
View Article and Find Full Text PDFWe report the successful encapsulation and elution of recombinant murine IL-12 (rmIL-12) from poly(lactide-co-glycolic) acid (PLGA) nanospheres (IL-12-NS) synthesized using the double emulsion/solvent evaporation (DESE) technique with microsphere depletion through ultracentrifugation. Images obtained with scanning electron microscopy (SEM) showcased a characteristic spherical shape with a mean particle diameter of 138.1 ± 10.
View Article and Find Full Text PDFDelirium is an acute confusional state due to physical illness and is a frequent cause of hospital admission. In this article, we describe the development and outcomes for a community delirium toolkit pilot across Greater Manchester during the COVID-19 pandemic. We conclude that delirium can be safely managed in the community by using a toolkit that incorporates structured assessment and management.
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