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The substantiality of the Out of Africa hypothesis was addressed in the light of recent genomic analysis of extant humans (Homo sapiens sapiens, Hss) and progress in Neanderthal palaeontology. The examination lent no support to the commonly assumed Out of Africa scenario but favoured instead a Eurasian divergence between Neanderthals and Hss (the Askur/Embla hypothesis) and an Out of Asia/Eurasia
Finding new causes of monogenic diabetes helps understand glycaemic regulation in humans. To find novel genetic causes of maturity-onset diabetes of the young (MODY), we sequenced MODY cases with unknown aetiology and compared variant frequencies to large public databases. From 36 European patients, we identify two probands with novel RFX6 heterozygous nonsense variants. RFX6 protein truncating va
Purpose Autoantibodies against osteoprotegerin (OPG) have been associated with osteoporosis. The aim was to develop an immunoassay for OPG autoantibodies and test their diagnostic usefulness of identifying women general population with low bone mineral density. Methods Included were 698 women at mean age 55.1 years (range 50.4–60.6) randomly selected from the general population. Measurement of wri
BACKGROUND AND OBJECTIVES: Few birth cohorts have prospectively followed development of type 1 diabetes (T1D) and celiac disease (CD) autoimmunities to determine timing, extent of co-occurrence, and associated genetic and demographic factors.METHODS: In this prospective birth cohort study, 8676 children at high genetic risk of both diseases were enrolled and 5891 analyzed in median follow-up of 66
Total internal reflection fluorescence (TIRF) microscopy is a powerful method that allows examination of plasma membrane close events in real time. The last decade, the method has successfully been used to explore GLUT4 translocation in adipocytes. Here, we describe the procedure for studying GLUT4 trafficking using TIRF microscopy in isolated primary adipocytes.
Impaired albumin reabsorption by proximal tubular epithelial cells (PTECs) has been highlighted in diabetic nephropathy (DN), but little is known about the underlying molecular mechanisms. Here we find that ORAI1-3, are preferentially expressed in PTECs and downregulated in patients with DN. Hyperglycemia or blockade of insulin signaling reduces the expression of ORAI1-3. Inhibition of ORAI channe
We examined the association between plasma 25- hydroxyvitamin D [25(OH)D] concentration and islet autoimmunity (IA) and whether vitamin D gene polymorphisms modify the effect of 25(OH)D on IA risk. We followed 8,676 children at increased genetic risk of type 1 diabetes at six sites in the U.S. and Europe. We defined IA as positivity for at least one autoantibody (GADA, IAA, or IA-2A) on two or mor
Development of molecular markers that help to identify high-risk individuals or diagnose indeterminate pulmonary nodules could have a major impact on lung cancer clinical management. In this study, we evaluated the diagnostic potential of a newly-developed ELISA that specifically detects complement C4d. We measured this marker in five independent cohorts of plasma and bronchoalveolar lavage sample
To explore the effects of a single dose of the DPP-4 inhibitor sitagliptin on glucose-standardized insulin secretion and β-cell glucose sensitivity after meal ingestion, 12 healthy and 12 drug-naïve, well-controlled type 2 diabetes (T2D) subjects (mean HbA1c 43mmol/mol, 6.2%) received sitagliptin (100mg) or placebo before a meal (525kcal). β-cell function was measured as the insulin secretory rate
Coeliac disease and type 1 diabetes are the most common paediatric autoimmune disorders. Both conditions have increasing incidence and can often coexist in a patient. The diseases share many genetic and immunological features, but diagnostic and treatment approaches vary substantially worldwide. Because of the often subtle presentation of coeliac disease in children with type 1 diabetes, many are
OBJECTIVE To examine duration of breastfeeding and timing of complementary foods and risk of islet autoimmunity (IA). RESEARCH DESIGN AND METHODS The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively follows 8,676 childrenwith increased genetic risk of type 1 diabetes (T1D) in the U.S., Finland, Germany, and Sweden. This study included 7,563 children with at least 9 m
Advances in sequencing technologies led to rapid increase in the number and diversity of biological sequences, which facilitated development in the sequence research. In this paper, we present a new method for analyzing protein sequence similarity. We calculated the spectral radii of 20 amino acids (AAs) and put forward a novel 2-D graphical representation of protein sequences. To characterize pro
Type 1 diabetes, formerly known as juvenile diabetes or insulin-dependent diabetes, results from the specific autoimmune destruction of the pancreatic islet beta cells. The subsequent lack of insulin leads to increased blood and urine glucose. The classical symptoms are polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), and weight loss. The disease may be
Glucose-stimulated insulin secretion is biphasic, with a rapid first phase and a slowly developing sustained second phase; both are disturbed in type 2 diabetes (T2D). Biphasic secretion results from vastly different release probabilities of individual insulin granules, but the morphological and molecular basis for this is unclear. Here, we show that human insulin secretion and exocytosis critical
Biofilm has been implicated as a barrier to wound healing and it is widely accepted that the majority of wounds not following a normal healing trajectory contain biofilm. Therefore, strategies that inform and engage clinicians to reduce biofilm and optimise the wound tissue environment to enable wound progression are of interest to wound care providers. In March 2019, an advisory board was convene
Complement is a key first line innate host defense system in the blood of vertebrates. Upon activation, this powerful defense mechanism can elicit inflammatory responses, lyse non-self-cells, or mark them for opsonophagocytic removal. Blood-feeding arthropods thus require the ability to block host complement activation in the bloodmeal to prevent undesired cell or tissue damage during feeding. The
AQP7 is an important glycerol channel in human adipocytes, and its dysfunction is linked to metabolic disorders. The high-resolution X-ray structures of AQP7 unravels the molecular details of how glycerol travels through the channel and provide a structural basis for development of small-molecule drugs for targeting AQP7.
