Matrix metalloproteinases at key junctions in the pathomechanism of stroke

Matrix metalloproteinases play a crucial role in the remodelling of the extracellular matrix through direct degradation of its structural proteins and control of extracellular signaling. The most common cause of ischemic brain damage is an atherothrombotic lesion in the supplying arteries. The progress of the atherosclerotic plaque development and the related thrombotic complications are mediated in part by matrix metalloproteinases. In addition to their role in the underlying disease, various members of this protease family are upregulated in the acute phase of ischemic brain damage as well as in the post-ischemic brain recovery following stroke. This review summarizes the current understanding of the matrix metalloproteinase-related molecular events at three stages of the ischemic cerebrovascular disease (in the atherosclerotic plaque, in the neurovascular unit of the brain and in the regenerating brain tissue)

Development and Quality of Barley Husk Adhesion Correlates With Changes in Caryopsis Cuticle Biosynthesis and Composition

The caryopses of barley become firmly adhered to the husk during grain development through a cuticular cementing layer on the caryopsis surface. The degree of this attachment varies among cultivars, with poor quality adhesion causing “skinning”, an economically significant grain quality defect for the malting industry. Malting cultivars encompassing a range of husk adhesion qualities were grown under a misting treatment known to induce skinning. Development of the cementing layer was examined by electron microscopy and compositional changes of the cementing layer were investigated with gas-chromatography followed by mass spectroscopy. Changes in gene expression during adhesion development were examined with a custom barley microarray. The abundance of transcripts involved early in cuticular lipid biosynthesis, including those encoding acetyl-CoA carboxylase, and all four members of the fatty acid elongase complex of enzymes, was significantly higher earlier in caryopsis development than later. Genes associated with subsequent cuticular lipid biosynthetic pathways were also expressed higher early in development, including the decarbonylation and reductive pathways, and sterol biosynthesis. Changes in cuticular composition indicate that lowered proportions of alkanes and higher proportions of fatty acids are associated with development of good quality husk adhesion, in addition to higher proportions of sterols

Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity

Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR.This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations

Oligonucleotide Based Magnetic Bead Capture of Onchocerca volvulus DNA for PCR Pool Screening of Vector Black Flies

The absence of infective larvae of Onchocerca volvulus in the black fly vector of this parasite is a major criterion used to certify that transmission has been eliminated in a focus. This process requires screening large numbers of flies. Currently, this is accomplished by screening pools of flies using a PCR-based assay. The number of flies that may be included in each pool is currently limited by the DNA purification process to 50 flies for Latin American vectors and 100 flies for African vectors. Here, we describe a new method for DNA purification that relies upon a specific oligonucleotide to capture and immobilize the parasite DNA on a magnetic bead. This method permits the reliable detection of a single infective larva of O. volvulus in pools containing up to 200 individual flies. The method described here will dramatically improve the efficiency of pool screening of vector black flies, making the process of elimination certification easier and less expensive to implement

UK consumers’ perceived risk of buying products from emerging economies : a moderated mediation model

While considerable research has been conducted on consumer attitude towards foreign products, most of these studies focuses on the attitude of products from Western developed countries. Our study intends to investigate the effects of consumers’ national identification and culture sensitivity on their perceived risk of buying products from Eastern developing countries. Especially, this study advances the literature by identifying the mediation effect of consumer ethnocentrism and the moderating effect of consumer value consciousness. Taking China and India as focal emerging economies, the consumer survey (n=308) in the UK produced the following results. First, UK consumers’ national identification is positively related to their perceived risk of buying eastern products through consumer ethnocentrism, whilst their cultural sensitivity has a negative relationship. Second, the effect of consumer ethnocentrism on the perceived risk of buying eastern products is moderated by consumer value consciousness. Third, value consciousness also attenuates the indirect relationships between national identification / cultural sensitivity and perceived risk via consumer ethnocentrism

Efficacies of the new Paclitaxel-eluting Coroflex Please™ Stent in percutaneous coronary intervention; comparison of efficacy between Coroflex Please™ and Taxus™ (ECO-PLEASANT) trial: study rationale and design

<p>Abstract</p> <p>Background</p> <p>Previous randomized trials have showed the superiority of Paclitaxel-eluting stent over bare metal stent in angiographic and clinical outcomes. Coroflex Please™ stent is a newly developed drug eluting stent using the Coroflex™ stent platform combined with the drug paclitaxel contained in a polymer coating. PECOPS I trial, one-arm observational study, showed that the clinical and angiographic outcomes of Coroflex Please™ stent were within the range of those of Taxus, the 1^stgeneration paclitaxel-eluting stent (PES). However, there have been no studies directly comparing the Coroflex Please™ stent with the Taxus Liberte™ stent that is the newest version of Taxus. Therefore, prospective, randomized trial is required to demonstrate the non-inferiority of Coroflex Please™ stent compared with Taxus Liberte™ stent in a head-to-head manner.</p> <p>Methods</p> <p>In the comparison of Efficacy between COroflex PLEASe™ ANd Taxus™ stent(ECO-PLEASANT) trial, approximately 900 patients are being prospectively and randomly assigned to the either type of Coroflex Please™ stent and Taxus Liberte™ stent via web-based randomization. The primary endpoint is clinically driven target vessel revascularization at 9 months. The secondary endpoints include major cardiac adverse events, target vessel failure, stent thrombosis and angiographic efficacy endpoints.</p> <p>Discussion</p> <p>The ECO-PLEASANT trial is the study not yet performed to directly compare the efficacy and safety of the Coroflex Please™ versus Taxus Liberte™ stent. On the basis of this trial, we will be able to find out whether the Coroflex Please™ stent is non-inferior to Taxus Liberte™ stent or not.</p> <p>Trial registration</p> <p>ClinicalTrials.gov number, NCT00699543.</p

Depressive Symptoms in Children with Chronic Kidney Disease

To assess depression in children with chronic kidney disease (CKD) and to determine associations with patient characteristics, intellectual and educational levels, and health related quality of life (HRQoL)