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The molecular background of the Ca2+-sensitizing effect of levosimendan relates to its specific interaction with the Ca2+-sensor troponin C molecule in the cardiac myofilaments. Over the years, significant preclinical and clinical evidence has accumulated and revealed a variety of beneficial pleiotropic effects of levosimendan and of its long-lived metabolite, OR-1896. First of all, activation of
Approximately 18% of all human genes purported to encode proteins have not been directly evidenced at the protein level, according to the validation criteria established by neXtProt, and are considered as “missing” proteins. One of the goals of the Chromosome-Centric Human Proteome Project (C-HPP) is to identify as many of these “missing” proteins as possible in human samples using mass spectromet
It is difficult to obtain fossil data from the 10% of Earth's terrestrial surface that is covered by thick glaciers and ice sheets, and hence, knowledge of the paleoenvironments of these regions has remained limited. We show that DNA and amino acids from buried organisms can be recovered from the basal sections of deep ice cores, enabling reconstructions of past flora and fauna. We show that high-
Vascular endothelial growth factor (VEGF) stimulates angiogenesis by activating VEGF receptor-2 (VEGFR-2). The role of its homolog, placental growth factor (PlGF), remains unknown. Both VEGF and PlGF bind to VEGF receptor-1 (VEGFR-1), but it is unknown whether VEGFR-1, which exists as a soluble or a membrane-bound type, is an inert decoy or a signaling receptor for PlGF during angiogenesis. Here,
The fusion-evaporation reactions Si-28(S-32,1 alpha 2p1n)Fe-53 at 125 MeV and Mg-24(S-32,2p1n)Fe-53 at a 95-MeV beam energy were used to investigate excited states in Fe-53. The combination of the Gammasphere Ge detector array and ancillary devices led to the construction of an extensive level scheme comprising some 90 transitions connecting 40 states. The lifetime of the yrast 25/2(-) state and u
High-spin states have been studied in Kr-72 and Br-72 using the Ca-40 + Ca-40 and Ar-36 + Ca-40 reactions at 164 and 145 MeV, respectively. The properties and configurations of the high-spin bands observed have been interpreted using impaired cranked Nilssou-Strutinsky (CNS), and for Kr-72, paired cranked relativistic Hartree-Bogoliubov (CRHB) calculations. In Kr-72 a new band has been identified
Background: There is an urgent need to identify subjects with Alzheimer's disease (AD) in the predementia phase, but validated diagnostic approaches are currently lacking. In this paper, we present the background, design and methods of a study, which aims to develop clinical criteria for predementia AD. We also present baseline characteristics of the subjects included. The study was part of the mu
Background The European Randomized Study of Screening for Prostate Cancer was initiated in the early 1990s to evaluate the effect of screening with prostate-specific-antigen (PSA) testing on death rates from prostate cancer. Methods We identified 182,000 men between the ages of 50 and 74 years through registries in seven European countries for inclusion in our study. The men were randomly assigned
The Bloodgen project was funded by the European Commission between 2003 and 2006, and involved academic blood centres, universities, and Progenika Biopharma S. A., a commercial supplier of genotyping platforms that incorporate glass arrays. The project has led to the development of a commercially available product, BLOODchip, that can be used to comprehensively genotype an individual for all clini
Objective: To quantify the independent associations between objectively measured physical activity (PA), cardiorespiratory fitness (CRF), and anthropometry in European men and women. Methods: 2,056 volunteers from 12 centers across Europe were fitted with a heart rate and movement sensor at 2 visits 4 months apart for a total of 8 days. CRF (ml/kg/min) was estimated from an 8 minute ramped step te
A quarter of ischaemic strokes are lacunar subtype, typically neurologically mild, usually resulting from intrinsic cerebral small vessel pathology, with risk factor profiles and outcome rates differing from other stroke subtypes. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations to assist with clinical decisions about management of lacunar ischaemic stroke
The dysregulated immune response and inflammation resulting in severe COVID-19 are still incompletely understood. Having recently determined that aberrant death-ligand-induced cell death can cause lethal inflammation, we hypothesized that this process might also cause or contribute to inflammatory disease and lung failure following SARS-CoV-2 infection. To test this hypothesis, we developed a nove
BACKGROUND: Two or more autoantibodies against either insulin (IAA), glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A) or zinc transporter 8 (ZnT8A) denote stage 1 (normoglycemia) or stage 2 (dysglycemia) type 1 diabetes prior to stage 3 type 1 diabetes. Automated multiplex Antibody Detection by Agglutination-PCR (ADAP) assays in two laboratories were compared to single plex radiobinding
Iron-centered N-heterocyclic carbene compounds have attracted much attention in recent years due to their long-lived excited states with charge transfer (CT) character. Understanding the orbital interactions between the metal and ligand orbitals is of great importance for the rational tuning of the transition metal compound properties, e.g., for future photovoltaic and photocatalytic applications.
Ferroelectricity in Hf0.5Zr0.5O2 (HZO) originates from a polymorphic landscape where the metastable orthorhombic phase competes with monoclinic and tetragonal forms, making functional properties highly sensitive to structural instability. Recent strategies have exploited ionic-vacancy mechanisms, either through redox interactions with the environment or by employing ferroionic heterostructures, to
Background: Hypertension management guidelines provide recommendations for optimal patient care. However, the limited time available of clinicians is rarely considered. The aim of this study was to evaluate the time clinicians currently spend on different components of hypertension care during an average workday and to assess physicians’ perceptions of the time required for optimal, guideline-base
Streptococcus pneumoniae resists host defenses through multiple surface factors, yet their specific contribution to protection against antimicrobial peptides remains incompletely understood. We examined the role of pneumococcal surface protein A (PspA) and the polysaccharide capsule in protection against the human defensin HNP-1. PspA conferred increased resistance to HNP-1-induced killing, show
Bladder cancer is a fast-moving and recurrent malignancy where survival hinges on early detection and precise risk stratification. The search for robust biomarkers is urgent, and CD44v6 has emerged as a compelling candidate. In this study, we explored the clinical and functional associations of CD44v6 expression in bladder cancer. Integrated analyses of patient samples and cell lines showed that h
