Gene expression and microrna expression analysis in small arteries of spontaneously hypertensive rats. Evidence for er stress

Small arteries are known to develop functional and structural alterations in hypertension. However, the mechanisms of this remodeling are not fully understood.We hypothesized that altered gene expression is associated with the development of hypertension in mesenteric arteries of spontaneously hypertensive rats (SHR). Three sublines of SHR and normotensive Wistar Kyoto rats (WKY) were studied at 6 weeks and 5 months of age. MiRNA and mRNA microarray experiments were performed and analyzed with bioinformatical tools, including Ingenuity Pathway Analysis (IPA). Principal component analysis showed a clear separation in both miRNA and mRNA expression levels between both ages studied, demonstrating strong age-related changes in expression. At the miRNA level, IPA identified differences between SHR and WKY related to metabolic diseases, cellular growth, and proliferation. The mRNAs differentially expressed between SHR and WKY were related to metabolism, cellular movement and proliferation. The most strongly upregulated gene (9.2- fold) was thrombospondin 4 (Thbs4), a protein involved in the endoplasmic reticulum (ER) stress response that activates transcription factor 6α (ATF6α). ATF6α downstream targets were also differentially expressed in SHR vs. WKY. Differential expression of THBS4, the cleaved form of ATF6α, and two of its targets were further confirmed at the protein level by western blot. In summary, these data revealed a number of genes (n = 202) and miRNAs (n = 3) in mesenteric arteries of SHR that had not been related to hypertension previously. The most prominent of these, Thbs4, is related to vascular ER stress that is associated with hypertensionThis work was supported by the European Union, Marie Curie ITN number 606998 and 23571

On the Role of Faith in Sustainability Management: A Conceptual Model and Research Agenda

International audienceThe objective of this article is to develop a faith development perspective on corporate sustainability. A firm’s management of sustainability is arguably determined by the way decision-makers relate to the other and the natural environment, and this relationship is fundamentally shaped by faith. This study advances theoretical understanding of the approach managers take on sustainability issues by explaining how four distinct phases of faith development—improvidence, obedience, irreverence and providence—determine a manager’s disposition towards sustainability. Combining insights from intentional and relational faith development theories, the analysis reveals that a manager’s faith disposition can be measured according to four interrelated process criteria: (1) connectivity as a measure of a manager’s actual engagement and activities aimed at relating to sustainability; (2) inclusivity as a measure of who and what is included or excluded in a manager’s moral consideration; (3) emotional affinity as a measure of a manager’s sensitivity and affection towards the well-being of others and ecological welfare; and (4) reciprocity as a measure of the degree to which a manager is rewarded for responding to the needs and concerns of ‘Others’, mainly in the form of a positive emotional (and relational) stimulus. The conceptual model consolidates earlier scholarly works on the psychological drivers of sustainability management by illuminating our search for a process of faith development that connects with an increasingly complex understanding of the role of business in society

The effect of pelvic tilt and cam on hip range of motion in young elite skiers and nonathletes

Anna Swärd Aminoff,1 Cecilia Agnvall,2,3 Carl Todd,1 Páll Jónasson,4 Mikael Sansone,1 Olof Thoreson,1 Leif Swärd,1 Jon Karlsson,1 Adad Baranto1 1Department of Orthopaedics, Institute of Clinical Sciences at Sahlgrenska Academy, University of Gothenburg, and Sahlgrenska University Hospital, Gothenburg, Sweden; 2Sports Medicine Åre, Åre, Sweden; 3Åre Ski Academy, Åre, Sweden; 4Orkuhúsið Orthopedic Clinic, Reykjavik, Iceland Background: Current knowledge of the effect of changes in posture and the way cam morphology of the hip joint may affect hip range of motion (ROM) is limited. Purpose: To determine the effect of changes in pelvic tilt (PT) on hip ROM and with/without the presence of cam. Study design: This was a cross-sectional study. Materials and methods: The hip ROM of 87 subjects (n=61 young elite skiers, n=26 nonathletes) was examined using a goniometer, in three different seated postures (flexed, neutral, and extended). The hips of the subjects were further subgrouped into cam and no-cam morphology, based on the magnetic resonance imaging findings in the hips. Results: There was a significant correlation between the hip ROM and the seated posture in both extended and flexed postures compared with the neutral posture. There was a significant decrease in internal hip rotation when the subjects sat with an extended posture with maximum anterior PT (p<0.0001). There was a significant increase in internal hip rotation when the subjects sat with a flexed posture with maximum posterior PT (p<0.001). External rotation was significantly decreased in an extended posture with maximum anterior PT (p<0.0001), but there was no difference in flexed posture with maximum posterior PT. The hips with cam morphology had reduced internal hip rotation in all three positions, but they responded to the changes in position in a similar manner to hips without cam morphology. Conclusion: Dynamic changes in PT significantly influence hip ROM in young people, independent of cam or no-cam morphology. Keywords: hip, cross-sectional studies, rotation, hip joint, range of motion (articular), pelvis, posture, magnetic resonance imagin

The involvement of protein kinase C in myosin phosphorylation and force development in rat tail arterial smooth muscle.

Myosin light-chain phosphorylation is the primary mechanism for activating smooth-muscle contraction and occurs principally at Ser-19 of the 20 kDa light chains of myosin (LC(20)). In some circumstances, Thr-18 phosphorylation may also occur. Protein kinase C (PKC) can regulate LC(20) phosphorylation indirectly via signalling pathways leading to inhibition of myosin light-chain phosphatase. The goal of this study was to determine the relative importance of myosin light-chain kinase (MLCK) and PKC in basal and stimulated LC(20) phosphorylation in rat tail arterial smooth-muscle strips (RTA). Two MLCK inhibitors (ML-9 and wortmannin) and two PKC inhibitors (chelerythrine and calphostin C) that have different mechanisms of action were used. Results showed the following: (i) basal LC(20) phosphorylation in intact RTA is mediated by MLCK; (ii) alpha(1)-adrenoceptor stimulation increases LC(20) phosphorylation via MLCK and PKC; (iii) Ca(2+)-induced LC(20) phosphorylation in Triton X-100-demembranated RTA is catalysed exclusively by MLCK, consistent with the quantitative loss of PKCs alpha and beta following detergent treatment; (iv) very little LC(20) diphosphorylation (i.e. Thr-18 phosphorylation) occurs in intact or demembranated RTA at rest or in response to contractile stimuli; and (v) the level of LC(20) phosphorylation correlates with contraction in intact and demembranated RTA, although the steady-state tension-LC(20) phosphorylation relationship is markedly different between the two preparations such that the basal level of LC(20) phosphorylation in intact muscles is sufficient to generate maximal force in demembranated preparations. This may be due, in part, to differences in the phosphatase/kinase activity ratio, resulting from disruption of a signalling pathway leading to myosin light-chain phosphatase inhibition following detergent treatment

Changes in synovial fluid and serum concentrations of cartilage oligomeric matrix protein over 5 years after anterior cruciate ligament rupture : an exploratory analysis in the KANON trial

Objective: To monitor longitudinal changes of cartilage oligomeric matrix protein (COMP) in synovial fluid (sf) and serum (s) over 5 years after acute anterior cruciate ligament (ACL) rupture, and to compare results from two commercial COMP immunoassays. Design: Bio-fluids were collected from 121 patients on six occasions over 5 years after acute ACL injury, and from 25 knee healthy reference subjects. Concentrations of sf- and sCOMP were measured by AnaMar (sCOMP-Ana) and by BioVendor (sf- and sCOMP-Bio) immunoassays; other biomarkers were previously assessed. We used ANCOVA for group comparisons and linear mixed models for associations between biomarkers over 5-years with P < 0.05 considered a statistically significant difference or association. Results: Compared to the reference group, sfCOMP-Bio concentrations were 2-fold elevated within 6 weeks after ACL injury and remained elevated 5 years thereafter, whereas sCOMP-Bio and sCOMP-Ana concentrations were no different from reference levels at any time point. Over the 5-year period, there was an association between sCOMP-Bio and sCOMP-Ana concentrations, although neither sCOMP-Bio nor sCOMP-Ana associated with sfCOMP-Bio. sfCOMP-Bio associated with SF ARGS-aggrecan, urine type I and II collagens (uNTX-I and uCTX-II) and SF cytokines, while sCOMP-Bio associated inversely with uCTX-II, uNTX-I and SF cytokines. Conclusion: The local process after an acute ACL injury generates increased SF COMP concentrations in the injured knee up to 5 years after injury. This response is not detected in serum. Discrepancies in associations between sCOMP measured by BioVendor and AnaMar immunoassays with other biomarkers indicate differences in detected COMP fragments

Factors influencing factor VIII activity in frozen plasma.

Backgrounds and Objectives Fresh frozen human plasma is an important raw material in the production of coagulation factor concentrates used in patients with haemorrhagic disorders. The aim of the study was to determine how the handling of plasma influences the recovery of coagulation factor VIII activity (FVIII:C), i.e. the influence of time between donation and freezing, of the freezing time and of the ice front velocity. We also studied a tentative eutectic point in human plasma. Materials and Methods Aliquots of plasma from 12 different donors were kept at room temperature for 2, 4 and 6 h before start of freezing. We achieved fast freezing with a freezer that blows cooled air at a high velocity on the plasma containers. Freezing times were 0.5, 1, 4 and 24 h. Temperature was registered continuously during freezing. Plasma and NaCl solutions were frozen slowly to investigate the eutectic point. Results Storage at room temperature for 6 h caused a small but statistically significant decrease in FVIII:C. Slow freezing with programmed freezing times of 4 and 24 h caused a more pronounced drop in FVIII:C as compared to that of 30 and 60 min. We found no eutectic point in plasma or in plasma with addition of 2 % (w/v) NaCl. Conclusion For an optimal yield of FVIII, freezing should start within 4 h after plasma donation. We propose the use of the term 'ice front velocity' instead of 'freezing speed', taking into consideration that the volume and shape of plasma containers may differ. We found only a marginal loss of FVIII:C when the ice front velocity was 26 mm/h or faster, but a significant loss when it was 9 mm/h or slower. We recommend freezing times of 60 min or shorter. We were not able to demonstrate any eutectic point in human plasma. We therefore recommend that the term eutectic point should not be used as a reference temperature in guidelines on plasma handling