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Neutrophil Extracellular Traps That Are Not Degraded in Systemic Lupus Erythematosus Activate Complement Exacerbating the Disease.

Ongoing inflammation including activation of the complement system is a hallmark of systemic lupus erythematosus (SLE). Antimicrobial neutrophil extracellular traps (NETs) are composed of secreted chromatin that may act as a source of autoantigens typical for SLE. In this study, we investigated how complement interacts with NETs and how NET degradation is affected by complement in SLE patients. We

Deregulation of the Wilms' tumour gene 1 protein (WT1) by BCR/ABL1 mediates resistance to imatinib in human leukaemia cells

The Wilms' tumour gene 1 (WT1) protein is highly expressed in most leukaemias. Co-expression of WT1 and the fusion protein AML1-ETO in mice rapidly induces acute myeloid leukaemia (AML). Mechanisms behind expression of WT1, as well as consequences thereof, are still unclear. Here, we report that the fusion protein BCR/ABL1 increases expression of WT1 mRNA and protein via the phosphatidylinositol-3

LRP4 association to bone properties and fracture and interaction with genes in the Wnt- and BMP signaling pathways.

Osteoporosis is a common complex disorder in postmenopausal women leading to changes in the micro-architecture of bone and increased risk of fracture. Members of the low-density lipoprotein receptor-related protein (LRP) gene family regulates the development and physiology of bone through the Wnt/β-catenin (Wnt) pathway that in turn cross-talks with the bone morphogenetic protein (BMP) pathway. In

Vascular function and sphingosine-1-phosphate regulate development of the dorsal pancreatic mesenchyme

Early growth and differentiation of the pancreatic endoderm is regulated by soluble factors from the pancreatic mesenchyme. Previously, we demonstrated that N-cadherin-deficient mice lack a dorsal pancreas, due to a critical role of N-cadherin in dorsal pancreatic mesenchymal cell survival. Here, we show that restoring cardiac and circulatory function in N-cadherin null mice by cardiac-specific ex

CNTF plus BDNF treatment and neuroprotective pathways in the rd1 mouse retina

The rd1 mouse is a relevant model for studying the mechanisms of photoreceptor degeneration in retinitis pigmentosa. Treatment with ciliary neurotrophic factor (CNTF) in combination with brain derived neurotrophic factor (BDNF) is known to rescue photoreceptors in cultured rd1 retinal explants. To shed light on the underlying mechanisms, we studied the effects of 9 days (starting at postnatal day

Can we beat the complexity of very large–scale requirements engineering?

Competitive development of complex embedded systems such as mobile phones requires management of massive amounts of complex requirements. This paper defines and discusses orders of magnitudes in RE and implications of the highest order of magnitude that we have experienced in industrial settings. Based on experiences from the mobile phone domain we propose research areas that, if ad-dressed succes

Assessment of volume of fluid and immersed boundary methods for droplet computations

The volume of fluid (VOF) and immersed boundary (IB) methods are two popular computational techniques for multi-fluid dynamics. To help shed light on the performance of both techniques, we present accuracy assessment, which includes interfacial geometry, detailed and global fluid flow characteristics, and computational robustness. The investigation includes the simulations of a droplet under stati

Fe II emission spectra in AGN: observations and theoretical interpretation

The enrichment of Fe, relative to alpha elements such as O and Mg, represents a potential means to measure the ages of quasi-stellar object (QSO) host galaxies and probe nucleosynthesis in the early universe. QSOs exhibit prominent Fe II features and Mg II 2800 angstrom resonance doublet emission in the ultraviolet. Although chemical evolutionary models predict that the Fe/Mg abundance ratio decre

Revisiting the risk of celiac disease in children born small for gestational age: A sibling design perspective.

Objective: An association between small for gestational age (SGA) and risk for celiac disease (CD) in childhood has previously been reported. However, this association may reflect residual confounding by genetic or environmental factors. For example, presence of subclinical CD in the mother might be a common cause of both SGA and CD in the offspring. We investigate whether SGA is causally associat

Acculturation and celiac disease risk in second-generation immigrants: a nationwide cohort study in Sweden.

Objectives: The burden of celiac disease (CD) is increasingly recognized as a global problem. However, whether this situation depends on genetics or environmental factors is uncertain. The authors examined these aspects in Sweden, a country in which the risk of CD is generally considered to be high. If environmental factors are relevant, CD risk in second-generation immigrant children should be re

Longitudinal assessment of femoral knee cartilage quality using contrast enhanced MRI (dGEMRIC) in patients with anterior cruciate ligament injury - comparison with asymptomatic volunteers.

OBJECTIVE: In this observational longitudinal study we estimate knee joint cartilage glycosaminoglycan (GAG) content, in patients with an acute anterior cruciate ligament (ACL) injury, with or without a concomitant meniscus injury. METHODS: 29 knees (19 men/10 women) were prospectively examined by repeat delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), approximately 3

The acute response of plasma brain-derived neurotrophic factor as a result of exercise in major depressive disorder.

Brain-derived neurotrophic factor (BDNF) and other neurotrophins are believed to play an important role in affective disorders. In this study we investigated plasma-BDNF response during an incremental exercise test in 18 patients suffering from moderate major depressive disorder (MDD) and 18 controls. The patients were not treated with antidepressants or neuroleptics. Possible associations between

Sex differences in coeliac disease risk: A Swedish sibling design study.

BACKGROUND: For unknown reasons girls are at an increased risk of coeliac disease compared to boys. However, the observed association might be confounded, since maternal coeliac disease is associated with both an increased risk of the disease in first-degree relatives as well as an increased ratio of girls to boys in offspring. AIMS: We investigate the effect of sex on the risk of coeliac dise

Genetic risk scores ascertained in early adulthood and the prediction of type 2 diabetes later in life.

It is hoped that information garnered from studies on population genetics will one day be translated into a form in which it meaningfully improves the prediction, prevention or treatment of type 2 diabetes. Type 2 diabetes genetics researchers have made extraordinary progress in identifying common genetic variants that are associated with type 2 diabetes, which has shed light on the biological pat

Socioeconomic Position, Comorbidity, and Mortality in Aortic Aneurysms: A 13-Year Prospective Cohort Study.

BACKGROUND: To evaluate factors associated with incidence and 3-year all-cause mortality in patients with aortic aneurysm (AA). The design is sex and age-stratified (60-79 and 80-90 years) prospective cohort. By using the population register, we constituted a cohort of all men and women born between 1900 and 1930 and living in Scania by 1991, and followed them for 13 years. Identification of AA wa

Common variation in PPARGC1A/B and progression to diabetes or change in metabolic traits following preventive interventions: the Diabetes Prevention Program.

AIMS/HYPOTHESIS: PPARGC1A and PPARGC1B encode transcriptional coactivators that regulate numerous type 2 diabetes-related metabolic processes. Common genetic variation across PPARGC1A/B was characterised by genotyping tagging variants. We then tested associations of these variants with diabetes incidence or change in quantifiable metabolic traits directly or via interactions (with metformin treatm