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Background and aims: TCF7L2 is both an activator and an inhibitor of transcription and the most highly associated type 2 diabetes gene known to date. It influences beta cell survival and function, i.e. incretin hormonal effects, insulin processing and secretion. However, its target genes in pancreatic islets are not fully described and the molecular mechanism whereby it propagates its effects on i
Despite early reports and the contemporary consensus on microsaccades as purely binocular phenomena, recent work has proposed not only the existence of monocular microsaccades, but also that they serve functional purposes. We take a critical look at the detection of monocular microsaccades from a signal perspective, using raw data and a state-of-the-art, video-based eye tracker. In agreement with
Background: For different migrant groups living in an area with few people from the same ethnic background is associated with increased psychosis incidence (the ethnic density effect). We set out to answer the question: are there generational differences in this effect? Methods: Analysis of a population based cohort (2.2 million) comprising all those born 1st January 1965, or later, living in Denm
The strong ties known in China as guanxi can be distinguished by a high level of trust relatively independent of the surrounding social structure. Using network data from a stratified probability sample of 700 entrepreneurs citing 4664 contacts, we study guanxi relative to other relations to learn how much individual differences such as well-being, business differences, political participation and
Background. The role of Helicobacter pylori infection in the development of oesophageal malignancies was investigated through a multivariate conditional logistic regression analysis in a nested case-control study. Methods. Blood samples and a questionnaire on smoking and alcohol habits were collected from a cohort of 32,906 city residents during a health-screening programme between 1974 and 1992.
Aim: To investigate the urethral motor function in incontinent women. Materials and Methods: The intraurethral pressure was measured continuously in the high-pressure zone of the urethra at rest and during repeated short squeezes around the microtip transducer catheter in a group of 205 women with clinically manifest urinary incontinence (severe), and compared with the findings of investigations i
Bone disease is an important feature of multiple myeloma, and hypercalcaemia is a frequent complication of this disease. We examined the association between serum calcium and quality of life (QOL) scores of 686 multiple myeloma patients at the time of diagnosis. Data from two Nordic studies using the EORTC QLQ-C30 questionnaire were analysed by means of linear regression analysis and a curve fitti
Levodopa is generally regarded the first choice therapy for parkinsonism associated with multiple system atrophy (MSA-P). However, MSA-P patients often show a poor or unsustained levodopa response which inflicts high dose therapy. This is generally attributed to progressive striatal degeneration with loss of dopamine receptors. Experimental evidence suggests that dopaminergic stimulation may accel
Collagen type II (CII) is a cartilage-specific target of pathologic humoral autoimmune responses in rheumatoid arthritis as well as in the collagen-induced arthritis model. The aim of the present study is to investigate the critical amino acid residues conferring CII epitope specificity of the prototypic arthritogenic murine mAb CIIC1. A homology model of the CIIC1 single-chain antibody fragment (
Background: Previous studies support a role of oxygen-free radicals in the development of congestive heart failure (CHF). The aim of this study was to investigate whether lipid peroxidation is increased in CHF patients on modem pharmacological therapy and whether there is a positive correlation between plasma levels of markers of lipid peroxidation and severity of heart failure (HF). Plasma malond
Background: Asthmatic patients have higher microbiome diversity and an altered composition, with more Proteobacteria and less Bacteroidetes compared with healthy control subjects. Studies comparing airway inflammation and the airway microbiome are sparse, especially in subjects not receiving anti-inflammatory treatment. Objective: We sought to describe the relationship between the airway microbiom
Creatine kinases are important in maintaining cellular-energy homeostasis, and neuroprotective effects have been attributed to the administration of creatine and creatine-like compounds. Herein we examine whether ablation of the cytosolic brain-type creatine kinase (B-CK) in mice has detrimental effects on brain development, physiological integrity or task performance. Mice deficient in B-CK (B-CK
Approximately 1-5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors. Thus, assays to detect BRCA1/BRCA2-deficient tumors have been sought. Recently,
The cystic fibrosis transmembrane conductance regulator (CFTR) attenuates sphingosine- 1-phosphate (S1P) signaling in resistance arteries and has emerged as a prominent regulator of myogenic vasoconstriction. This investigation demonstrates that S1P inhibits CFTR activity via adenosine monophosphate-activated kinase (AMPK), establishing a potential feedback link. In Baby Hamster Kidney (BHK) cells
Preeclampsia (PE) has been associated with placental dysfunction, resulting in fetal hypoxia, accelerated erythropoiesis, and increased erythroblast count in the umbilical cord blood (UCB). Although the detailed effects remain unknown, placental dysfunction can also cause inflammation, nutritional, and oxidative stress in the fetus that can affect erythropoiesis. Here, we compared the expression o
Fifty-one patients with deep-seated soft tissue sarcoma of the extremities and trunk wall were examined with contrast-enhanced CT for presence of nonenhanced tumor areas (CT necrosis). After a median follow-up time of 3 years, 19 of the 41 patients with CT necrosis had developed metastases, compared to none of the 10 patients who had tumors without CT necrosis. Tumors with CT necrosis were larger
Intrinsically disordered proteins (IDPs) can form functional oligomers and in some cases, insoluble disease related aggregates. It is therefore vital to understand processes and mechanisms that control pathway distribution. Divalent cations including Zn2+ can initiate IDP oligomerisation through the interaction with histidine residues but the mechanisms of doing so are far from understood. Here we
