Schacktermansen7469

We identify the focal adhesion protein kindlin-2 as player in a novel mechanotransduction pathway that controls profibrotic cardiac fibroblast to myofibroblast activation. Kindlin-2 is co-upregulated with the myofibroblast marker α-smooth muscle actin (α-SMA) in fibrotic rat hearts and in human cardiac fibroblasts exposed to fibrosis-stiff culture substrates and pro-fibrotic TGF-β1. Stressing fibroblasts using ferromagnetic microbeads, stretchable silicone membranes, and cell contraction agonists all result in kindlin-2 translocation to the nucleus. Overexpression of full-length kindlin-2 but not of kindlin-2 missing a putative nuclear localization sequence (∆NLS kindlin-2) results in increased α-SMA promoter activity. Downregulating kindlin-2 with siRNA leads to decreased myofibroblast contraction and reduced α-SMA expression, which is dependent on CC(A/T)-rich GG(CArG) box elements in the α-SMA promoter. Lost myofibroblast features under kindlin-2 knockdown are rescued with wild-type but not ∆NLS kindlin-2, indicating that myofibroblast control by kindlin-2 requires its nuclear translocation. Because kindlin-2 can act as a mechanotransducer regulating the transcription of α-SMA, it is a potential target to interfere with myofibroblast activation in tissue fibrosis.The impact of occupational and environmental exposure to external airborne agents on cognitive function, especially in incidence of dementia, is understudied. The present study was conducted to elucidate the association between severe external airborne agents' exposure and incidence of dementia among an elderly population and to explore the effects of exposure to severe external airborne agents on preclinical dementia using the screening test of dementia. From the National Health Insurance Service-Health Screening Cohort (NHIS-HealS, 2002-2015), 514,580 participants were used for data analysis. We estimated the standardized incidence ratio (SIR) according to the exposure to external airborne agents. Of the total participants (n = 514,580), 1340 (0.3%) experienced severe external airborne agents exposure, and 26,050 (5.1%) had been diagnosed with dementia. The SIRs (95%CI) of dementia in Alzheimer's disease, vascular dementia, dementia in other diseases, and unspecific dementia were 1.24 (1.01-1.49), 0.88 (0.37-1.32), 1.16 (0.01-2.77), and 0.69 (0.36-1.02), respectively. The risk of testing positive in the dementia screening significantly increased with exposure to severe external airborne agents after adjusting for all confounding variables. This study found that exposure to severe external airborne agents is a potential risk factor for dementia, especially in Alzheimer's disease. It is essential to create international awareness regarding the effect of airborne agents' exposure on dementia.Isoflavones are phenolic compounds with a chemical structure similar to that of estradiol. They are present in several vegetables, mainly in legumes such as soy, white and red clover, alfalfa and beans. The most significant food source of isoflavones in humans is soy-derived products. Isoflavones could be used as an alternative therapy for pathologies dependent on hormonal disorders such as breast and prostate cancer, cardiovascular diseases, as well as to minimize menopausal symptoms. According to the results gathered in the present review, it can be stated that there is scientific evidence showing the beneficial effect of isoflavones on bone health and thus in the prevention and treatment of osteoporosis on postmenopausal women, although the results do not seem entirely conclusive as there are discrepancies among the studies, probably related to their experimental designs. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. Fluzoparib By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Regarding cancer, scientific evidence suggests that isoflavones could be useful in reducing the risk of suffering some types of cancer, such as breast and endometrial cancer, but further studies are needed to confirm these results. Finally, isoflavones could be useful in reducing hot flushes associated with menopause. However, a limitation in this field is that there is still a great heterogeneity among studies. Lastly, with regard to isoflavone consumption safety, it seems that they are safe and that the most common adverse effect is mild and occurs at the gastrointestinal level.Lassa virus is the etiologic agent of Lassa fever, an acute and often fatal illness endemic to West Africa. It is important to develop new reagents applicable either for the specific diagnosis or as improved therapeutics for the treatment of Lassa fever. Here, we describe the development and initial testing of llama-derived single-domain antibodies that are specific for the Lassa virus nucleoprotein. Four sequence families based on complementarity-determining region (CDR) homology were identified by phage-based enzyme-linked immunosorbent assays, however, the highest affinity clones all belonged to the same sequence family which possess a second disulfide bond between Framework 2 and CDR3. The affinity and thermal stability were evaluated for each clone. A MagPlex-based homogeneous sandwich immunoassay for Lassa virus-like particles was also demonstrated to show their potential for further development as diagnostic reagents.Delaminations within aerospace composites are of particular concern, presenting within composite laminate structures without visible surface indications. Transmission based thermography techniques using contact temperature sensors and surface mounted heat sources are able to detect reductions in thermal conductivity and in turn impact damage and large disbonds can be detected. However delaminations between Carbon Fibre Reinforced Polymer (CFRP) plies are not immediately discoverable using the technique. The use of transient thermal conduction profiles induced from zonal heating of a CFRP laminate to ascertain inter-laminate differences has been demonstrated and the paper builds on this method further by investigating the impact of inter laminate inclusions, in the form of delaminations, to the transient thermal conduction profile of multi-ply bi-axial CFRP laminates. Results demonstrate that as the distance between centre of the heat source and delamination increase, whilst maintaining the delamination within the heated area, the resultant transient thermal conduction profile is measurably different to that of a homogeneous region at the same distance.