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Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (pro)insulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining
Variants in the growth factor receptor-bound protein 10 (GRB10) gene were in a GWAS meta-analysis associated with reduced glucose-stimulated insulin secretion and increased risk of type 2 diabetes (T2D) if inherited from the father, but inexplicably reduced fasting glucose when inherited from the mother. GRB10 is a negative regulator of insulin signaling and imprinted in a parent-of-origin fashion
In the last decades, the focus in waste and wastewater treatment systems has shifted towards increased recovery of energy and nutrients. Separation of urban food waste and domestic wastewaters using source control systems could aid this increase; however their effect on overall sustainability is unknown. To obtain indicators for sustainability assessments, five urban systems for collection, transp
Close collaboration is considered important; but is close collaboration for all purchases necessary to create value-in-production? In construction as well as in other industries, companies purchase a variety of items that require different amounts of attention to the relationship with suppliers. Buyer-supplier relationships are investigated in relation to how they bring value-in-production in the
In order to fully understand the orientation behaviour of migrating birds, it is important to understand when birds set their travel direction. Departure directions of migratory passerines leaving stopover sites are often assumed to reflect the birds' intended travel directions, but this assumption has not been critically tested. We used data from an automated radiotelemetry system and a tracking
We prospectively evaluated fat intake as predictor of developing breast cancer (BC) subtypes defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 receptor (HER2), in a large (n = 337327) heterogeneous cohort of women, with 10062 BC case patients after 11.5 years, estimating BC hazard ratios (HRs) by Cox proportional hazard modeling. High total and satu
It is well established that atherosclerosis is caused by an inflammatory process in the arterial intima. However, it is only in recent years that it has become clear that this inflammation is modulated by immune responses against plaque antigens. These antigens are primarily believed to be modified self-antigens such as oxidized LDL. The immune system is challenged to determine whether these antig
The home environment is a primary context for daily activities, especially among older adults and persons with disabilities. Functional and age-related decline can generate problems in relation to certain environmental features, necessitating modifications or other provisions of support. The determination of appropriate home interventions is best served using a person–environment (P–E) fit approac
New research indicates that firms combining the science-based STI (Science, Technology, Innovation) and the experience-based DUI (Doing, Using, Interacting) modes of innovation are more efficient when it comes to improving innovation capacity and competitiveness. With regard to innovation policy, the STI mode calls for a supply-driven policy, typically aimed to commercialize research results. The
β cell dysfunction is central to the development and progression of type 2 diabetes (T2D). T2D develops when β cells are not able to compensate for the increasing demand for insulin caused by insulin resistance. Epigenetic modifications play an important role in establishing and maintaining β cell identity and function in physiological conditions. On the other hand, epigenetic dysregulation can ca
Genome-wide association studies have revealed numerous risk loci associated with diverse diseases. However, identification of disease-causing variants within association loci remains a major challenge. Divergence in gene expression due to cis-regulatory variants in noncoding regions is central to disease susceptibility. We show that integrative computational analysis of phylogenetic conservation w
Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants
Type 1 diabetes is a serious chronic disease in which the pancreatic islet beta cells are destroyed by autoimmunity specifically directed to intracellular autoantigens. Still undefined environmental factors are likely to initiate the disease process. One of the autoantigens is glutamic acid decarboxylase (GAD65) and attempts are made to induce immunological tolerance against this autoantigen. Alum
