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Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the
Background The activity of the human enzyme thiopurine methyltransferase (TPMT) varies greatly between individuals because of genetic polymorphism. TPMT is involved in the detoxification and activation of thiopurines such as 6-mercaptopurine, 6-thioguanine, and azathioprine. These drugs are used in the treatment of acute lymphoblastic leukemia and inflammatory bowel disease. A total of 29 sequence
Background: Free and total human kallikrein 2 (hK2) might improve the discrimination between prostate cancer and benign prostatic hyperplasia. Concentrations of hK2 are 100-fold lower than concentrations of prostate-specific antigen (PSA); therefore, an hK2 assay must have a low detection limit and good specificity. Methods: PSA- and hK2-specific monoclonal antibodies were used in solid-phase, two
This thesis has evaluated the immunological- and epidemiological aspects of human papillomavirus transmission dynamics and its effect on circumcision. Effective prophylactic vaccines are based on type-specific neutralizing antibodies. A major neutralizing epitope is defined by the monoclonal antibody H16.V5. To investigate the importance of this epitope for overall immunogenicity of HPV16, we en
Abstract in UndeterminedUzbekistan, after gaining independence from the Soviet Union in 1991, had publicly declared that it would adhere to democratic governance principles in designing and implementing its public administration policies. As a newly-independent state with democracy claims, Uzbekistan had tried to establish new democratic institutions with an effort to capture international communi
Estimates of relevant source area of pollen (RSAP) and relative pollen productivity (PPE) are critical parameters for quantitative reconstructions of past vegetation and land cover. This study provides estimates for PPE relative to Poaceae for ten taxa, characterizing the cultural landscape of south Estonia and the RSAP for 40 lakes with an average radius of approximately 100 m (22-274 m, average
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
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
225Ac-PSMA-617 targeted-therapy has demonstrated efficacy in 75-85% of patients; however, responses are not durable. We aimed to establish translatable mouse models of disseminated prostate cancer (PCa) to evaluate effectiveness of 225Ac-PSMA-617 at various disease stages. Methods: C4-2, C4-2B, or 22Rv1 cells were injected into the left ventricle of male NSG mice. Disease progression was monitored
The calcitonin gene-related peptide (CGRP) family of neuropeptides, consists of CGRP, adrenomedullin, amylin, and calcitonin. The receptors consist of either calcitonin receptor-like receptor (CLR) or calcitonin receptor (CTR) which for function needs an accessory protein, receptor activity-modifying proteins (RAMPs). CGRP has a pivotal role in primary headaches but the role of the other members o
Botulinum neurotoxins (BoNTs) are a family of bacterial toxins with seven major serotypes (BoNT/A-G). The ability of these toxins to target and bind to motor nerve terminals is a key factor determining their potency and efficacy. Among these toxins, BoNT/B is one of the two types approved for medical and cosmetic uses. Besides binding to well-established receptors, an extended loop in the C-termin
Background: ACMG/AMP and AMP/ASCO/CAP have released guidelines for variation interpretation, and ESHG for diagnostic sequencing. These guidelines contain recommendations including the use of computational prediction methods. The guidelines per se and the way they are implemented cause some problems. Methods: Logical reasoning based on domain knowledge. Results: According to the guidelines, several
Assessing status of natural resources and ecosystem components is pivotal for management, where indicators or indices often are used as proxies of ecological state. Many indicators, however, lack reference points and are associated with sampling errors and environmental noise, limiting their usefulness in management. Here we present a method for assessing state changes in ecological indicator from
A group of pauci-immune vasculitides, characterized by neutrophil-rich necrotizing inflammation of small vessels and the presence of antineutrophil cytoplasmic antibodies (ANCAs), is referred to as ANCA-associated vasculitis (AAV). ANCAs against proteinase 3 (PR3) (PR3-ANCA) or myeloperoxidase (MPO) (MPO-ANCA) are found in over 90% of patients with active disease, and these ANCAs are implicated in
For patients hospitalized with severe influenza A virus infection, morbidity and mortality remain high. MHAA4549A, a human monoclonal antibody targeting the influenza A virus hemagglutinin stalk, has demonstrated pharmacological activity in animal studies and in a human influenza A challenge study. We evaluated the safety and efficacy of MHAA4549A plus oseltamivir against influenza A virus infecti
Abstract: Progranulin is a glycoprotein marking chronic inflammation in obesity and type 2 diabetes. Previous studies suggested PSRC1 (proline and serine rich coiled-coil 1) to be a target of genetic variants associated with serum progranulin levels. We aimed to identify potentially functional variants and characterize their role in regulation of PSRC1. Phylogenetic module complexity analysis (PMC
55 m.ö.h. på Balsbergets södra sluttning finner man en av Sydsveriges största grottor, Balsbergsgrottan. Ungefär 250 meter vindlande gångar grenar sig ut från två större salar. Grottan har en rik historia, både ur ett geologiskt och ett funktionalistiskt perspektiv. De sedimentära bergarterna som bildades för 100 miljoner års sedan lade grunden till, att det efter förra istiden kunde bildas en gro55 meters above sea level on the southern slope of Balsberget you can find one of southern Sweden's largest caves, the Balsberg cave. Approximately 250 meters winding paths branch out from two large halls. The cave has a rich history, both from a geological and a functional perspective. The sedimentary rocks, formed 100 million years ago, laid the foundations for the advent of a cave here afte
Klimatförändringar har amplifierats sedan den industriella revolutionen och modeller pekar på att förändringen kommer forsätta att öka åtminstone till slutet av detta århundrande. Globala temperaturer och nederbörd förväntas öka avsevärt under detta århundrade. Dessa ökningar förväntas bli särskilt markanta i de arktiska områdena. Torvmyrar belägna på höga latituder vid 0ºC isothermen, såsom StorfThe rate of change of our climate has been amplified since the industrial revolution and is expected to change even further by the end of this century. Global temperature and precipitation are expected to increase considerably over the next century. These increases are expected to be magnified in the Arctic regions. In a high latitude peatland like Storflaket, near Abisko (Northern Sweden), at the
