Publications by authors named "Stephen White"

Local haemodynamics control arterial homeostasis and dysfunction by generating wall shear stress (WSS) which regulates endothelial cell (EC) physiology. Here we use a zebrafish model to identify genes that regulate EC proliferation in response to flow. Suppression of blood flow in zebrafish embryos (by targeting cardiac troponin) reduced EC proliferation in the intersegmental vessels (ISVs) compared to controls exposed to flow.

View Article and Find Full Text PDF
Article Synopsis
  • Bacteriophage T4's gp32 protein is crucial for DNA processing, as it binds to single-stranded DNA (ssDNA) to protect it and help initiate DNA replication and repair.
  • Researchers purified and crystallized the gp32-Dda-ssDNA complex, revealing how gp32's C-terminus interacts with the Dda helicase, shedding light on the structural details of this interaction.
  • The study confirmed through various analyses, including DNA unwinding assays, that gp32 effectively sequesters ssDNA produced by Dda, outlining important functions of the gp32-Dda interaction in DNA processing.
View Article and Find Full Text PDF

Anxiety disorders represent one of the most common and debilitating illnesses worldwide. However, the development of novel therapeutics for anxiety disorders has lagged compared to other mental illnesses. A growing body of research suggests the gut microbiota plays a role in the etiopathology of anxiety disorders and may, therefore, serve as a novel target for their treatment through the use of probiotics.

View Article and Find Full Text PDF

Serum biochemical indicators serve as vital proxies that reflect the physiological state and functions of different organs. The genetic parameters and molecular mechanisms underlying serum biochemical indicators of sheep () have not been well understood. Therefore, the aim of the present study was to identify the genetic architecture and genomic loci underlying ten serum biochemical indicators in sheep, including alanine transaminase, aspartate transferase, lactate dehydrogenase, cholesterol, glucose, phosphorus, calcium, creatinine, urea and total protein levels.

View Article and Find Full Text PDF

Observations at (sub-)millimeter wavelengths offer a complementary perspective on our Sun and other stars, offering significant insights into both the thermal and magnetic composition of their chromospheres. Despite the fundamental progress in (sub-)millimeter observations of the Sun, some important aspects require diagnostic capabilities that are not offered by existing observatories. In particular, simultaneously observations of the radiation continuum across an extended frequency range would facilitate the mapping of different layers and thus ultimately the 3D structure of the solar atmosphere.

View Article and Find Full Text PDF

Conversion of pantothenate to phosphopantothenate in humans is the first dedicated step in the coenzyme A (CoA) biosynthesis pathway and is mediated by four isoforms of pantothenate kinase. These enzymes are allosterically regulated by acyl-CoA levels, which control the rate of CoA biosynthesis. Small molecule activators of the PANK enzymes that overcome feedback suppression increase CoA levels in cultured cells and animals and have shown great potential for the treatment of pantothenate kinase-associated neurodegeneration and propionic acidemias.

View Article and Find Full Text PDF
Article Synopsis
  • Proteolytic activation of the haemagglutinin glycoprotein is crucial for the infectivity of influenza A virus (IAV), with different proteases targeting different HA motifs.
  • The study utilized CRISPR/Cas 9 technology to create gene-edited knockout (KO) pigs lacking the TMPRSS2 protease to investigate its effects on IAV replication.
  • Results showed that IAV replication was delayed in KO pigs, leading to reduced virus shedding and lower viral loads in the respiratory system, indicating the potential of GE pigs to help control IAV infections and prevent zoonotic transmissions.
View Article and Find Full Text PDF

Prenatal maternal feeding plays an important role in fetal development and has the potential to induce long-lasting epigenetic modifications. MicroRNAs (miRNAs) are non-coding, single-stranded RNAs that serve as one epigenetic mechanism. Though miRNAs have crucial roles in fetal programming, growth, and development, there is limited data regarding the maternal diet and miRNA expression in sheep.

View Article and Find Full Text PDF

Background: CALCRL (calcitonin receptor-like) protein is an important mediator of the endothelial fluid shear stress response, which is associated with the genetic risk of coronary artery disease. In this study, we functionally characterized the noncoding regulatory elements carrying coronary artery disease that risks single-nucleotide polymorphisms and studied their role in the regulation of expression in endothelial cells.

Methods: To functionally characterize the coronary artery disease single-nucleotide polymorphisms harbored around the gene , we applied an integrative approach encompassing statistical, transcriptional (RNA-seq), and epigenetic (ATAC-seq [transposase-accessible chromatin with sequencing], chromatin immunoprecipitation assay-quantitative polymerase chain reaction, and electromobility shift assay) analyses, alongside luciferase reporter assays, and targeted gene and enhancer perturbations (siRNA and clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) in human aortic endothelial cells.

View Article and Find Full Text PDF
Article Synopsis
  • Proteolytic activation of hemagglutinin (HA) in influenza A virus is crucial for its infectivity, with different proteases targeting different HA motifs.
  • * Highly pathogenic avian influenza has a multibasic cleavage site activated by common proteases, while pandemic strains, like H1N1 and H3N2, are activated by trypsin-like proteases like TMPRSS2.
  • * Gene-edited knockout pigs showed delayed virus replication, reduced virus shedding, and less severe pathology compared to wild-type pigs, highlighting the potential of using gene-edited pigs to reduce economic losses and prevent new IAV variants.*
View Article and Find Full Text PDF

Ovine footrot is an infectious disease with important contributions from and . Footrot is characterized by separation of the hoof from underlying tissue, and this causes severe lameness that negatively impacts animal wellbeing, growth, and profitability. Large economic losses result from lost production as well as treatment costs, and improved genetic tools to address footrot are a valuable long-term goal.

View Article and Find Full Text PDF

Motivation: In metagenomics, the study of environmentally associated microbial communities from their sampled DNA, one of the most fundamental computational tasks is that of determining which genomes from a reference database are present or absent in a given sample metagenome. Existing tools generally return point estimates, with no associated confidence or uncertainty associated with it. This has led to practitioners experiencing difficulty when interpreting the results from these tools, particularly for low-abundance organisms as these often reside in the "noisy tail" of incorrect predictions.

View Article and Find Full Text PDF
Article Synopsis
  • * The study found that while proteoglycans facilitate platelet adhesion, they don't activate platelets as effectively as collagen, and they actually reduce thrombus formation compared to collagen alone.
  • * Notably, the thrombus formation in eroded plaques is sensitive to aspirin, unlike that from ruptured plaques, suggesting that proteoglycans could provide a new strategy for targeted treatment of arterial thrombosis.
View Article and Find Full Text PDF

Objectives: To enhance the Business Process Management (BPM)+ Healthcare language portfolio by incorporating knowledge types not previously covered and to improve the overall effectiveness and expressiveness of the suite to improve Clinical Knowledge Interoperability.

Methods: We used the BPM+ Health and Object Management Group (OMG) standards development methodology to develop new languages, following a gap analysis between existing BPM+ Health languages and clinical practice guideline knowledge types. Proposal requests were developed based on these requirements, and submission teams were formed to respond to them.

View Article and Find Full Text PDF

The murine helminth parasite expresses a family of proteins structurally related to TGF-β Mimic 1 (TGM1), a secreted five domain protein that activates the TGF-β pathway and converts naïve T lymphocytes to immunosuppressive Tregs. TGM1 signals through the TGF-β type I and type II receptors, TβRI and TβRII, with domains 1-2 and 3 binding TβRI and TβRII, respectively, and domains 4-5 binding CD44, a co-receptor abundant on T cells. TGM6 is a homologue of TGM1 that is co-expressed with TGM1, but lacks domains 1 and 2.

View Article and Find Full Text PDF

Small ruminants, especially sheep, are essential for sustainable agricultural production systems, future food/nutrition security, and poverty reduction in developing countries. Within developed countries, the ability of sheep to survive on low-quality forage intake could act as buffer against climate change. Besides sheep's importance in sustainable agricultural production, there has been less ongoing work in terms of sheep genetics in Near East, Middle East and in Africa.

View Article and Find Full Text PDF

In a context of backlash against diversity in many countries, we know little about how ethnic minorities respond politically when they personally experience discrimination. Moving beyond the study of electoral participation, this research investigates whether experiences of discrimination push ethnic minorities toward an alternate political pathway for those who feel sidelined by the political community: protest activity. The study also examines whether the context of discrimination (i.

View Article and Find Full Text PDF

Pantothenate kinase-associated neurodegeneration (PKAN) is characterized by a motor disorder with combinations of dystonia, parkinsonism, and spasticity, leading to premature death. PKAN is caused by mutations in the gene that result in loss or reduction of PANK2 protein function. PANK2 is one of three kinases that initiate and regulate coenzyme A biosynthesis from vitamin B5, and the ability of BBP-671, an allosteric activator of pantothenate kinases, to enter the brain and elevate coenzyme A was investigated.

View Article and Find Full Text PDF

Ambient PM (particles less than 2.5 μm in diameter) is monitored in many countries including Australia. Occasionally PM instruments may report negative measurements, although in realty the ambient air can never contain negative amounts of particles.

View Article and Find Full Text PDF

The NCI-60 human tumor cell line panel has proved to be a useful tool for the global cancer research community in the search for novel chemotherapeutics. The publicly available cell line characterization and compound screening data from the NCI-60 assay have significantly contributed to the understanding of cellular mechanisms targeted by new oncology agents. Signature sensitivity/resistance patterns generated for a given chemotherapeutic agent against the NCI-60 panel have long served as fingerprint presentations that encompass target information and the mechanism of action associated with the tested agent.

View Article and Find Full Text PDF
Article Synopsis
  • The vascular extracellular matrix (ECM), made by endothelial and smooth muscle cells, is crucial for maintaining the structure and function of blood vessels, with its composition linked to endothelial dysfunction and atherosclerosis progression.
  • Atherosclerotic plaques vary in ECM composition based on their type and vulnerability, impacting their risk of rupture and how they interact with blood clots (thrombi).
  • This review focuses on how different proteoglycans in plaques affect thrombosis and platelet function, advocating for tailored antithrombotic therapies to enhance treatment outcomes for cardiovascular diseases.
View Article and Find Full Text PDF

Modulation of glutamate receptors has demonstrated anxiolytic and/or antidepressant effects in rodent stress models. The chick social-separation stress paradigm exposes socially raised aves to an isolation stressor which elicits distress vocalizations (DVocs) in an attempt to re-establish contact. The model presents a state of panic during the first 5 min followed by a state of behavioral despair during the last 60 to 90 min.

View Article and Find Full Text PDF

Objective: To describe a case of bifid intratemporal facial nerves without associated middle or inner ear abnormalities encountered on computed tomography (CT) imaging during preoperative preparation for unilateral cochlear implant placement in an adult male with profound sensorineural hearing loss (SNHL).

Methods: A rare case of bilateral bifid intratemporal facial nerves in an adult male is presented. The finding's impact on approach to safe cochlear implantation is discussed.

View Article and Find Full Text PDF

In metagenomics, the study of environmentally associated microbial communities from their sampled DNA, one of the most fundamental computational tasks is that of determining which genomes from a reference database are present or absent in a given sample metagenome. While tools exist to answer this question, all existing approaches to date return point estimates, with no associated confidence or uncertainty associated with it. This has led to practitioners experiencing difficulty when interpreting the results from these tools, particularly for low abundance organisms as these often reside in the "noisy tail" of incorrect predictions.

View Article and Find Full Text PDF