Sphingosine 1-phosphate receptor 1signaling in macrophages reduces atherosclerosis in LDL receptor-deficient mice.

Sphingosine 1-phosphate (S1P) is a lysosphingolipid with antiatherogenic properties, but mechanisms underlying its effects remain unclear. We here investigated atherosclerosis development in cholesterol-rich diet-fed LDL receptor-deficient mice with high or low overexpression levels of S1P receptor 1 (S1P1) in macrophages. S1P1-overexpressing macrophages showed increased activity of transcription factors PU.

The Endothelial Glycocalyx as a Target of Excess Soluble Fms-like Tyrosine Kinase-1.

Soluble fms-like tyrosine kinase-1 (sFlt-1) is a secreted protein that binds heparan sulfate expressed on the endothelial glycocalyx (eGC). In this paper we analyze how excess sFlt-1 causes conformational changes in the eGC, leading to monocyte adhesion, a key event triggering vascular dysfunction. In vitro exposure of primary human umbilical vein endothelial cells to excess sFlt-1 decreased eGC height and increased stiffness as determined by atomic force microscopy (AFM).

The Soluble Fms-like Tyrosine Kinase-1 Contributes to Structural and Functional Changes in Endothelial Cells in Chronic Kidney Disease.

Endothelial cells are a critical target of the soluble Fms-like tyrosine kinase-1 (sFlt-1), a soluble factor increased in different diseases with varying degrees of renal impairment and endothelial dysfunction, including chronic kidney disease (CKD). Although the mechanisms underlying endothelial dysfunction are multifactorial and complex, herein, we investigated the damaging effects of sFlt-1 on structural and functional changes in endothelial cells. Our results evidenced that sera from patients with CKD stiffen the endothelial cell cortex in vitro, an effect correlated with sFlt-1 levels and prevented by sFlt-1 neutralization.

Impact of the Nuclear Envelope on Malignant Transformation, Motility, and Survival of Lung Cancer Cells.

Nuclear pore complexes (NPCs) selectively mediate all nucleocytoplasmic transport and engage in fundamental cell-physiological processes. It is hypothesized that NPCs are critical for malignant transformation and survival of lung cancer cells, and test the hypothesis in lowly and highly metastatic non-small human lung cancer cells (NSCLCs). It is shown that malignant transformation is paralleled by an increased NPCs density, and a balanced pathological weakening of the physiological stringency of the NPC barrier.

Apolipoprotein M and Sphingosine-1-Phosphate Receptor 1 Promote the Transendothelial Transport of High-Density Lipoprotein.

Objective: ApoM enriches S1P (sphingosine-1-phosphate) within HDL (high-density lipoproteins) and facilitates the activation of the S1P1 (S1P receptor type 1) by S1P, thereby preserving endothelial barrier function. Many protective functions exerted by HDL in extravascular tissues raise the question of how S1P regulates transendothelial HDL transport. Approach and Results: HDL were isolated from plasma of wild-type mice, Apom knockout mice, human apoM transgenic mice or humans and radioiodinated to trace its binding, association, and transport by bovine or human aortic endothelial cells.

Symmetric dimethylarginine in dysfunctional high-density lipoprotein mediates endothelial glycocalyx breakdown in chronic kidney disease.

Dysfunctional high-density lipoprotein (d-HDL) in chronic kidney disease is known to have a change in composition towards an endothelial-damaging phenotype, amongst others, via the accumulation of symmetric dimethylarginine. The endothelial glycocalyx, a carbohydrate-rich layer lining the endothelial luminal surface, is a first line defense against vascular diseases including atherosclerosis. Here we conducted a translational, cross-sectional study to determine the role of symmetric dimethylarginine in d-HDL as a mediator of glycocalyx damage.

[Return to Work after Temporary Disability Pension].

Background: In Germany, there are no statistics available that reveal how many temporary disability pensioners return to work. The aim of this study was to analyse how many persons to whom a temporary disability pension was granted in 2006 returned to work. Their socio-demographic, health-related and vocational characteristics were examined.

Staphylococcus epidermidis Activates Aryl Hydrocarbon Receptor Signaling in Human Keratinocytes: Implications for Cutaneous Defense.

Bacterial challenge of keratinocytes with the abundant skin commensal Staphylococcus epidermidis induces distinct innate immune responses, but the underlying molecular mechanisms are still emerging. We report that the aryl hydrocarbon receptor (AhR) was activated in human primary keratinocytes infected with S. epidermidis, leading to induction of the AhR-responsive gene cytochrome P450 1A1 (CYP1A1).

[Relationship Between The Use of Psychosomatic Rehabilitation and Regional Capacities for Medical and Psychotherapeutic Treatment of Mental Disorders in Westphalia].

Background: Regional disparities in mental health care are well known and become apparent in inadequate treatment capacities and long waiting time for psychotherapeutic treatment. Hence, the authors assume that there is a shift from curative to rehabilitative care. Accordingly, the purpose of this study was to analyze the relationship between regional treatment capacities and the use of psychosomatic rehabilitation on behalf of the German Statutory Pension Insurance Westphalia (i.

Endothelial glycocalyx breakdown is mediated by angiopoietin-2.

Aims: The endothelial glycocalyx (eGC), a carbohydrate-rich layer lining the luminal surface of the endothelium, provides a first vasoprotective barrier against vascular leakage and adhesion in sepsis and vessel inflammation. Angiopoietin-2 (Angpt-2), an antagonist of the endothelium-stabilizing receptor Tie2 secreted by endothelial cells, promotes vascular permeability through cellular contraction and junctional disintegration. We hypothesized that Angpt-2 might also mediate the breakdown of the eGC.

Biochemical diversity in the Trypanosoma congolense trans-sialidase family.

Trans-sialidases are key enzymes in the life cycle of African trypanosomes in both, mammalian host and insect vector and have been associated with the disease trypanosomiasis, namely sleeping sickness and nagana. Besides the previously reported TconTS1, we have identified three additional active trans-sialidases, TconTS2, TconTS3 and TconTS4, and three trans-sialidase like genes in Trypanosoma congolense. At least TconTS1, TconTS2 and TconTS4 are found in the bloodstream of infected animals.

Functional differentiation of the human lumbar perivertebral musculature revisited by means of muscle fibre type composition.

Human back muscles have been classified as local stabilizers, global stabilizers and global mobilizers. This concept is supported by the distribution of slow and fast muscle fibres in quadrupedal mammals, but has not been evaluated for humans because detailed information on the fibre type composition of their perivertebral musculature is rare. Moreover, such information is derived from spot samples, which are assumed to be representative for the respective muscle.

Distribution pattern of muscle fiber types in the perivertebral musculature of two different sized species of mice.

Many physiological parameters scale with body size. Regarding limb muscles, it has been shown that the demands for relatively faster muscles, less postural work, and greater heat production in small mammals are met by lower proportions of Type I and conversely higher proportions of Type II fibers. To investigate possible adaptations of the perivertebral musculature, we investigated the proportion, spatial distribution, and cross-sectional area (csa) of the different muscle fiber types in the laboratory and harvest mouse.

[Do people with mental disorders who, due to complete reduction in earning capacity, receive a temporary pension want to return into active employment?].

Unlabelled: In Germany the number of invalidity pensions due to mental disorders is increasing. More than one third of these insurants do not take part in rehabilitation measures before their early retirement. Only 6 % return into their employment relationship.