Cholesterol is a key sterol whose homeostasis is primarily maintained through bile acid metabolism. Proper bile acid formation is vital for nutrient and fat-soluble vitamin absorption and emulsification of lipids. Synthesis of bile acids occurs through two main pathways, both of which rely on 3β-hydroxy-Δ-C-steroid oxidoreductase (HSD3B7) to begin epimerization of the 3β hydroxyl of cholesterol into its active 3α conformation.
View Article and Find Full Text PDFAntibiotic resistance is an urgent public health threat. Actions to reduce this threat include requiring prescriptions for antibiotic use, antibiotic stewardship programs, educational programs targeting patients and healthcare providers, and limiting antibiotic use in agriculture, aquaculture, and animal husbandry. Wastewater surveillance might complement clinical surveillance by tracking time/space variation essential for detecting outbreaks and evaluating efficacy of evidence-based interventions; identifying high-risk populations for targeted monitoring; providing early warning of the emergence and spread of antibiotic resistant bacteria and identifying novel antibiotic resistant threats.
View Article and Find Full Text PDFAm J Physiol Gastrointest Liver Physiol
December 2024
Physiologists may play critical roles in the development of clinician-scientists who aspire to an academic career. The complexity of contemporary biomedical science and economic matters regarding postgraduate education pose real conundrums. We report a more than 22-year follow-up of surgical trainees pursuing bench laboratory science experience through a collaboration between a physiology postgraduate program and a surgical researcher program within a single public medical school.
View Article and Find Full Text PDFOver the past forty years there has been a drastic increase in fructose-related diseases, including obesity, heart disease and diabetes. Ketohexokinase (KHK), the first enzyme in the liver fructolysis pathway, catalyzes the ATP-dependent phosphorylation of fructose to fructose 1-phosphate. Understanding the role of KHK in disease-related processes is crucial for the management and prevention of this growing epidemic.
View Article and Find Full Text PDFUnlabelled: Clear cell renal cell carcinoma (ccRCC) incidence has risen steadily over the last decade. Elevated lipid uptake and storage is required for ccRCC cell viability. As stored cholesterol is the most abundant component in ccRCC intracellular lipid droplets, it may also play an important role in ccRCC cellular homeostasis.
View Article and Find Full Text PDFInhibition of overexpressed enzymes is among the most promising approaches for targeted cancer treatment. However, many cancer-expressed enzymes are "nonlethal," in that the inhibition of the enzymes' activity is insufficient to kill cancer cells. Conventional antibody-based therapeutics can mediate efficient treatment by targeting extracellular nonlethal targets but can hardly target intracellular enzymes.
View Article and Find Full Text PDFN-terminal acetylation is a chemical modification carried out by N-terminal acetyltransferases. A major member of this enzyme family, NatB, acts on much of the human proteome, including α-synuclein (αS), a synaptic protein that mediates vesicle trafficking. NatB acetylation of αS modulates its lipid vesicle binding properties and amyloid fibril formation, which underlies its role in the pathogenesis of Parkinson's disease.
View Article and Find Full Text PDFIntroduction: The use of artificial intelligence (AI) for national defense is a matter of high societal significance and ongoing public discourse, but very little is known about public acceptance of AI in defense contexts. Currently, there is no reliable and valid measure of attitudes towards AI in defense, and more general attitudinal measures on AI use are unlikely to capture relevant perceptions and opinions. A measure was therefore developed for the assessment of Attitudes towards AI in Defense (AAID), and this work presents the initial validation of this scale.
View Article and Find Full Text PDFRelapse after cancer treatment is often attributed to the persistence of a subpopulation of tumor cells known as cancer stem cells (CSCs), which are characterized by their remarkable tumor-initiating and self-renewal capacity. Depending on the origin of the tumor (e.g.
View Article and Find Full Text PDFN-terminal acetylation is a chemical modification carried out by N-terminal acetyltransferases (NATs). A major member of this enzyme family, NatB, acts on much of the human proteome, including α-synuclein (αS), a synaptic protein that mediates vesicle trafficking. NatB acetylation of αS modulates its lipid vesicle binding properties and amyloid fibril formation, which underlies its role in the pathogenesis of Parkinson's disease.
View Article and Find Full Text PDFDespite the availability of several effective SARS-CoV-2 vaccines, additional vaccines will be required for optimal global vaccination. In this study, we investigate the immunogenicity and protective efficacy of the GBP510 protein subunit vaccine adjuvanted with AS03, which has recently been authorized for marketing in South Korea under the trade name SKYCovione. The antigen in GBP510/AS03 is a two-part recombinant nanoparticle, which displays 60 receptor binding domain (RBD) proteins of SARS-CoV-2 Spike on its surface.
View Article and Find Full Text PDFN-terminal acetylation occurs on over 80% of human proteins and is catalyzed by a family of N-terminal acetyltransferases (NATs). All NATs contain a small catalytic subunit, while some also contain a large auxiliary subunit that facilitates catalysis and ribosome targeting for co-translational acetylation. NatC is one of the major NATs containing an NAA30 catalytic subunit, but uniquely contains two auxiliary subunits, large NAA35 and small NAA38.
View Article and Find Full Text PDFActivity-based sensing (ABS) probes equipped with a NIR bioluminescence readout are promising chemical tools to study cancer biomarkers owing to their high sensitivity and deep tissue compatibility. Despite the demand, there is a dearth of such probes because NIR substrates (e.g.
View Article and Find Full Text PDFNear-infrared (NIR) fluorophores absorbing maximally in the region beyond 800 nm, i.e., deep-NIR spectral region, are actively sought for biomedical applications.
View Article and Find Full Text PDFThe COVID-19 pandemic continues to expand globally, with case numbers rising in many areas of the world, including the Eastern Mediterranean Region. Lebanon experienced its largest wave of COVID-19 infections from January to April 2021. Limited genomic surveillance was undertaken, with just 26 SARS-CoV-2 genomes available for this period, nine of which were from travellers from Lebanon detected by other countries.
View Article and Find Full Text PDFBackground: Responding to the COVID-19 pandemic, Health Education England (HEE) mobilised a group of expert searchers from NHS libraries in England to develop a platform for librarians to share peer reviewed search strategies and results on the Knowledge for Healthcare website.
Objectives: (1) To document the origins of the COVID-19 search bank, (2) evaluate attitudes of NHS librarians in England towards the search bank and (3) identify lessons learned and consider whether the initiative might be developed further.
Methods: Structured interviews with the peer reviewers (n = 10) were conducted, and a questionnaire survey of the NHS library community using the search bank was undertaken.
Breakthrough infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have been reported frequently in vaccinated individuals with waning immunity. In particular, a cluster of over 1000 infections with the SARS-CoV-2 delta variant was identified in a predominantly fully vaccinated population in Provincetown, Massachusetts in July 2021. In this study, vaccinated individuals who tested positive for SARS-CoV-2 ( = 16) demonstrated substantially higher serum antibody responses than vaccinated individuals who tested negative for SARS-CoV-2 ( = 23), including 32-fold higher binding antibody titers and 31-fold higher neutralizing antibody titers against the SARS-CoV-2 delta variant.
View Article and Find Full Text PDFAd26.COV2.S has demonstrated durability and clinical efficacy against symptomatic COVID-19 in humans.
View Article and Find Full Text PDFSARS-CoV-2 Spike-specific binding and neutralizing antibodies, elicited either by natural infection or vaccination, have emerged as potential correlates of protection. An important question, however, is whether vaccine-elicited antibodies in humans provide direct, functional protection from SARS-CoV-2 infection and disease. In this study, we explored directly the protective efficacy of human antibodies elicited by Ad26.
View Article and Find Full Text PDFBackground: Management of single small hepatocellular carcinoma (HCC) is straightforward with curative outcomes achieved by locoregional therapy or resection. Liver transplantation is often considered for multiple small or single large HCC. Management of two small HCC whether presenting synchronously or sequentially is less clear.
View Article and Find Full Text PDFThis consensus document is endorsed by The Queen's Nursing Institute (QNI) and The Queen's Nursing Institute Scotland (QNIS).
View Article and Find Full Text PDFLive oral vaccines have been explored for their protective efficacy against respiratory viruses, particularly for adenovirus serotypes 4 and 7. The potential of a live oral vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however, remains unclear. In this study, we assessed the immunogenicity of live SARS-CoV-2 delivered to the gastrointestinal tract in rhesus macaques and its protective efficacy against intranasal and intratracheal SARS-CoV-2 challenge.
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