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Pepsin-like aspartic proteases (PAPs) as model systems for combining biomolecular simulation with biophysical experiments

Pepsin-like aspartic proteases (PAPs) are a class of aspartic proteases which shares tremendous structural similarity with human pepsin. One of the key structural features of PAPs is the presence of a β-hairpin motif otherwise known as flap. The biological function of the PAPs is highly dependent on the conformational dynamics of the flap region. In apo PAPs, the conformational dynamics of the fla

Statistical upscaling of ecosystem CO2 fluxes across the terrestrial tundra and boreal domain : Regional patterns and uncertainties

The regional variability in tundra and boreal carbon dioxide (CO2) fluxes can be high, complicating efforts to quantify sink-source patterns across the entire region. Statistical models are increasingly used to predict (i.e., upscale) CO2 fluxes across large spatial domains, but the reliability of different modeling techniques, each with different specifications and assumptions, has not been asses

Minimal guidewire length for central venous catheterization of the right subclavian vein : A CT-based consecutive case series

BACKGROUND: Central venous catheter (CVC) misplacement occurs frequently after right subclavian vein catheterization. It can be avoided by using ultrasound to confirm correct guidewire tip position in the lower superior vena cava prior to CVC insertion. However, retraction of the guidewire during the CVC insertion may dislocate the guidewire tip from its desired and confirmed position, thereby res

Differential expression of cerebrospinal fluid neuroinflammatory mediators depending on osteoarthritis pain phenotype

ABSTRACT: Neuroinflammation is implicated in the development and maintenance of persistent pain states, but there are limited data linking cerebrospinal fluid (CSF) inflammatory mediators with neurophysiological pain processes in humans. In a prospective observational study, CSF inflammatory mediators were compared between patients with osteoarthritis (OA) who were undergoing total hip arthroplast

Household composition and the infant fecal microbiome : The INSPIRE study

Objectives: Establishment and development of the infant gastrointestinal microbiome (GIM) varies cross-culturally and is thought to be influenced by factors such as gestational age, birth mode, diet, and antibiotic exposure. However, there is little data as to how the composition of infants' households may play a role, particularly from a cross-cultural perspective. Here, we examined relationships

Detailed phenotyping of posterior vs. anterior circulation ischemic stroke : a multi-center MRI study

Objective: Posterior circulation ischemic stroke (PCiS) constitutes 20–30% of ischemic stroke cases. Detailed information about differences between PCiS and anterior circulation ischemic stroke (ACiS) remains scarce. Such information might guide clinical decision making and prevention strategies. We studied risk factors and ischemic stroke subtypes in PCiS vs. ACiS and lesion location on magnetic

Multiple-stressor effects on stream invertebrates : DNA barcoding reveals contrasting responses of cryptic mayfly species

Most freshwater ecosystems are subject to multiple anthropogenic stressors, which commonly reduce biodiversity across all levels. Existing freshwater bioassessment programmes aim at identifying responses of aquatic biota to stressors. For practical reasons, higher-level taxonomic groups (e.g. genus or family) are often used in these programmes. This approach, however, may bias assessment results a

Climate effects on the onset of flowering in the United Kingdom

Background: A warmer climate has consequences for the timing of phenological events, as temperature is a key factor controlling plant development and flowering. In this study, we analyse the effects of the long-term climate change and an extreme weather event on the first flowering day (FFD) of five spring-flowering wild plant species in the United Kingdom. Citizen science data from the UK Woodlan

Missense mutations in the C-terminal portion of the B4GALNT2-encoded glycosyltransferase underlying the Sd(a−) phenotype

Sda is a high-frequency carbohydrate histo-blood group antigen, GalNAcβ1-4(NeuAcα2-3)Galβ, implicated in pathogen invasion, cancer, xenotransplantation and transfusion medicine. Complete lack of this glycan epitope results in the Sd(a−) phenotype observed in 4% of individuals who may produce anti-Sda. A candidate gene (B4GALNT2), encoding a Sda-synthesizing β-1,4-N-acetylgalactosaminyltransferase

Associations between autoimmune conditions and hepatobiliary cancer risk among elderly US adults

Growing evidence suggests that people with autoimmune conditions may be at increased risk of hepatobiliary tumors. In the present study, we evaluated associations between autoimmune conditions and hepatobiliary cancers among adults aged ≥66 in the United States. We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data (1992–2013) to conduct a population-based, case–control study. C

ATAC-seq reveals alterations in open chromatin in pancreatic islets from subjects with type 2 diabetes.

Impaired insulin secretion from pancreatic islets is a hallmark of type 2 diabetes (T2D). Altered chromatin structure may contribute to the disease. We therefore studied the impact of T2D on open chromatin in human pancreatic islets. We used assay for transposase-accessible chromatin using sequencing (ATAC-seq) to profile open chromatin in islets from T2D and non-diabetic donors. We identified 57,

Diabetic patients with acute coronary syndromes in contemporary European registries : Characteristics and outcomes

Aims Among patients with acute coronary syndromes (ACS), those with diabetes mellitus (DM) are at particularly high risk of recurrent cardiovascular events and premature death. We aimed to provide a descriptive overview of unadjusted analyses of patient characteristics, ACS management, and outcomes up to 1 year after hospital admission for an ACS/index-ACS event, in patients with DM in contemporar

A computational study of the hydrolysis of dGTP analogues with halomethylene-modified leaving groups in solution : implications for the mechanism of DNA polymerases

DNA polymerases make up a family of enzymes responsible for regulating DNA replication and repair, which in turn maintains the integrity of the genome. However, despite intensive kinetic, crystallographic, and computational studies, elucidation of the detailed enzymatic mechanism still presents a significant challenge. We recently developed an alternative strategy for exploring the fidelity and me

Prevalence of Mycoplasma genitalium and macrolide resistance in rectal and urine samples among men who have sex with men in Sweden

Objectives While Mycoplasma genitalium is reported as a common rectal infection among men who have sex with men (MSM), published data refer predominantly to urethral infections. Currently, most guidelines recommend M. genitalium testing from urine in men with symptomatic, non-gonococcal urethritis. Macrolide resistance-associated mutations (MRMs) among M. genitalium have increased during the last

NETest in advanced high-grade gastroenteropancreatic neuroendocrine neoplasms

Molecular blood biomarkers are lacking for high-grade (HG) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN). To histologically distinguish between neuroendocrine carcinoma (NEC), neuroendocrine tumors G3 (NET G3), adenocarcinoma and MINEN is often challenging. The mRNA-based NETest has diagnostic, prognostic and predictive value in neuroendocrine tumors G1-2 but has not been studied in

Road-traffic noise exposure and coronary atherosclerosis in the Swedish CArdioPulmonary bioImage Study (SCAPIS)

Background: Road-traffic noise may influence the development of cardiovascular events such as stroke and myocardial infarction, but etiological mechanisms remain unclear. This study aimed to assess the relationship between long-term road-traffic noise exposure and coronary atherosclerosis in Sweden. Methods: In the Swedish CArdioPulmonary bioImage Study (SCAPIS) cohort, including 30,154 subjects a