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991.
Kevin Kurt Jean-Philippe Rasigade Frederic Laurent Richard V. Goering Helena ?emli?ková Ivana Machova Marc J. Struelens Andreas E. Zautner Silva Holtfreter Barbara Br?ker Stephen Ritchie Sin Reaksmey Direk Limmathurotsakul Sharon J. Peacock Christiane Cuny Franziska Layer Wolfgang Witte Ulrich Nübel 《PloS one》2013,8(3)
We investigated the population structure of Staphylococcus aureus clonal complex CC121 by mutation discovery at 115 genetic housekeeping loci from each of 154 isolates, sampled on five continents between 1953 and 2009. In addition, we pyro-sequenced the genomes from ten representative isolates. The genome-wide SNPs that were ascertained revealed the evolutionary history of CC121, indicating at least six major clades (A to F) within the clonal complex and dating its most recent common ancestor to the pre-antibiotic era. The toxin gene complement of CC121 isolates was correlated with their SNP-based phylogeny. Moreover, we found a highly significant association of clinical phenotypes with phylogenetic affiliations, which is unusual for S. aureus. All isolates evidently sampled from superficial infections (including staphylococcal scalded skin syndrome, bullous impetigo, exfoliative dermatitis, conjunctivitis) clustered in clade F, which included the European epidemic fusidic-acid resistant impetigo clone (EEFIC). In comparison, isolates from deep-seated infections (abscess, furuncle, pyomyositis, necrotizing pneumonia) were disseminated in several clades, but not in clade F. Our results demonstrate that phylogenetic lineages with distinct clinical properties exist within an S. aureus clonal complex, and that SNPs serve as powerful discriminatory markers, able to identify these lineages. All CC121 genomes harboured a 41-kilobase prophage that was dissimilar to S. aureus phages sequenced previously. Community-associated MRSA and MSSA from Cambodia were extremely closely related, suggesting this MRSA arose in the region. 相似文献
992.
Barbara Messner Johann Kern Dominik Wiedemann Stefan Schwaiger Adrian Türkcan Christian Ploner Alexander Trockenbacher Klaus Aumayr Nikolaos Bonaros Günther Laufer Hermann Stuppner Gerold Untergasser David Bernhard 《PloS one》2013,8(3)
Background
Insufficient angiogenesis and arteriogenesis in cardiac tissue after myocardial infarction (MI) is a significant factor hampering the functional recovery of the heart. To overcome this problem we screened for compounds capable of stimulating angiogenesis, and herein investigate the most active molecule, 5-Methoxyleoligin (5ML), in detail.Methods and Results
5ML potently stimulated endothelial tube formation, angiogenic sprouting, and angiogenesis in a chicken chorioallantoic membrane assay. Further, microarray- and knock down- based analyses revealed that 5ML induces angiogenesis by upregulation of CYP26B1. In an in vivo rat MI model 5ML potently increased the number of arterioles in the peri-infarction and infarction area, reduced myocardial muscle loss, and led to a significant increase in LV function (plus 21% 28 days after MI).Conclusion
The present study shows that 5ML induces CYP26B1-dependent angiogenesis in vitro, and arteriogenesis in vivo. Whether or not CYP26B1 is relevant for in vivo arteriogenesis is not clear at the moment. Importantly, 5ML-induced arteriogenesis in vivo makes the compound even more interesting for a post MI therapy. 5ML may constitute the first low molecular weight compound leading to an improvement of myocardial function after MI. 相似文献993.
994.
Filipe Pereira Cláudia Moreira Luís Fonseca Barbara van Asch Manuel Mota Isabel Abrantes António Amorim 《PloS one》2013,8(2)
The pinewood nematode, Bursaphelenchus xylophilus, is one of the greatest threats to coniferous forests worldwide, causing severe ecological damage and economic loss. The biology of B. xylophilus is similar to that of its closest relative, B. mucronatus, as both species share food resources and insect vectors, and have very similar morphological characteristics, although little pathogenicity to conifers has been associated with B. mucronatus. Using both nuclear and mitochondrial DNA markers, we show that B. xylophilus and B. mucronatus form distinct phylogenetic groups with contrasting phylogeographic patterns. B. xylophilus presents lower levels of intraspecific diversity than B. mucronatus, as expected for a species that evolved relatively recently through geographical or reproductive isolation. Genetic diversity was particularly low in recently colonised areas, such as in southwestern Europe. By contrast, B. mucronatus displays high levels of genetic diversity and two well-differentiated clades in both mitochondrial and nuclear DNA phylogenies. The lack of correlation between genetic and geographic distances in B. mucronatus suggests intense gene flow among distant regions, a phenomenon that may have remained unnoticed due to the reduced pathogenicity of the species. Overall, our findings suggest that B. xylophilus and B. mucronatus have different demographic histories despite their morphological resemblance and ecological overlap. These results suggest that Bursaphelenchus species are a valuable model for understanding the dispersion of invasive species and the risks posed to native biodiversity and ecosystems. 相似文献
995.
A.L. Kuipers L.H. Kuller Y. Sheu C.H. Bunker A.L. Patrick V.W. Wheeler R.W. Evans J.M. Zmuda 《Obesity (Silver Spring, Md.)》2013,21(9):1900-1907
Objective: When compared with other ethnic groups, African ancestry individuals have lower triglycerides and higher High‐density lipoprotein cholesterol (HDL‐C) levels, although the mechanisms for these differences remain unclear. A comprehensive array of factors potentially related to fasting serum lipid and lipoprotein levels in African ancestry men was evaluated. Design and Methods: Men (1,821) underwent dual‐energy X‐ray absorptiometry measures of total body fat and quantitative computed tomography assessments of calf skeletal muscle adiposity [subcutaneous and intermuscular adipose tissue (AT), and muscle density as a measure of intra‐muscular AT]. Results: Multivariable linear regression analysis identified age (?), total body fat (+), subcutaneous AT (?), fasting glucose (+), fasting insulin (+), diastolic blood pressure (+), and non‐African ancestry (+) as independent correlates of triglycerides (all P < 0.05). Total body fat (+), intra‐muscular AT (?), and diastolic blood pressure (+) were independent correlates of Low‐density lipoprotein cholesterol (LDL‐C) (all P < 0.001). Age (+), waist circumference (?), fasting insulin (?), physical activity (+), and alcohol intake (+) were independent correlates of HDL‐C (all P < 0.05). Conclusions: A novel relationship between skeletal muscle adiposity and serum lipid and lipoprotein levels in African ancestry men, independent of total and central adiposity was illuminated. In African ancestry populations, genetic factors are likely a significant determinant of triglycerides levels. 相似文献
996.
Florence Schaffner Naho Yokota Tatiana Carneiro-Lobo Maki Kitano Michael Schaffer G. Mark Anderson Barbara M. Mueller Charles T. Esmon Wolfram Ruf 《PloS one》2013,8(4)
Several markers identify cancer stem cell-like populations, but little is known about the functional roles of stem cell surface receptors in tumor progression. Here, we show that the endothelial protein C receptor (EPCR), a stem cell marker in hematopoietic, neuronal and epithelial cells, is crucial for breast cancer growth in the orthotopic microenvironment of the mammary gland. Mice with a hypomorphic allele of EPCR show reduced tumor growth in the PyMT-model of spontaneous breast cancer development and deletion of EPCR in established PyMT tumor cells significantly attenuates transplanted tumor take and growth. We find expansion of EPCR+ cancer stem cell-like populations in aggressive, mammary fat pad-enhanced human triple negative breast cancer cells. In this model, EPCR-expressing cells have markedly increased mammosphere- and tumor-cell initiating activity compared to another stable progenitor-like subpopulation present at comparable frequency. We show that receptor blocking antibodies to EPCR specifically attenuate in vivo tumor growth initiated by either EPCR+ cells or the heterogenous mixture of EPCR+ and EPCR- cells. Furthermore, we have identified tumor associated macrophages as a major source for recognized ligands of EPCR, suggesting a novel mechanism by which cancer stem cell-like populations are regulated by innate immune cells in the tumor microenvironment. 相似文献
997.
Dukgyu Lee Tatsujiro Oka Beth Hunter Alison Robinson Sylvia Papp Kimitoshi Nakamura Wattamon Srisakuldee Barbara E. Nickel Peter E. Light Jason R. B. Dyck Gary D. Lopaschuk Elissavet Kardami Michal Opas Marek Michalak 《PloS one》2013,8(2)
Background
Calreticulin, a Ca2+-buffering chaperone of the endoplasmic reticulum, is highly expressed in the embryonic heart and is essential for cardiac development. After birth, the calreticulin gene is sharply down regulated in the heart, and thus, adult hearts have negligible levels of calreticulin. In this study we tested the role of calreticulin in the adult heart.Methodology/Principal Findings
We generated an inducible transgenic mouse in which calreticulin is targeted to the cardiac tissue using a Cre/loxP system and can be up-regulated in adult hearts. Echocardiography analysis of hearts from transgenic mice expressing calreticulin revealed impaired left ventricular systolic and diastolic function and impaired mitral valve function. There was altered expression of Ca2+ signaling molecules and the gap junction proteins, Connexin 43 and 45. Sarcoplasmic reticulum associated Ca2+-handling proteins (including the cardiac ryanodine receptor, sarco/endoplasmic reticulum Ca2+-ATPase, and cardiac calsequestrin) were down-regulated in the transgenic hearts with increased expression of calreticulin.Conclusions/Significance
We show that in adult heart, up-regulated expression of calreticulin induces cardiomyopathy in vivo leading to heart failure. This is due to an alternation in changes in a subset of Ca2+ handling genes, gap junction components and left ventricle remodeling. 相似文献998.
Letizia Mattii Chiara Ippolito Cristina Segnani Barbara Battolla Rocchina Colucci Amelio Dolfi Gabrio Bassotti Corrado Blandizzi Nunzia Bernardini 《PloS one》2013,8(2)
Background
The pathogenesis of diverticular disease (DD) is thought to result from complex interactions among dietary habits, genetic factors and coexistence of other bowel abnormalities. These conditions lead to alterations in colonic pressure and motility, facilitating the formation of diverticula. Although electrophysiological studies on smooth muscle cells (SMCs) have investigated colonic motor dysfunctions, scarce attention has been paid to their molecular abnormalities, and data on SMCs in DD are lacking. Accordingly, the main purpose of this study was to evaluate the expression patterns of molecular factors involved in the contractile functions of SMCs in the tunica muscularis of colonic specimens from patients with DD.Methods and Findings
By means of immunohistochemistry and image analysis, we examined the expression of Cx26 and Cx43, which are prominent components of gap junctions in human colonic SMCs, as well as pS368-Cx43, PKCps, RhoA and αSMA, all known to regulate the functions of gap junctions and the contractile activity of SMCs.The immunohistochemical analysis revealed significant abnormalities in DD samples, concerning both the expression and distribution patterns of most of the investigated molecular factors.Conclusion
This study demonstrates, for the first time, that an altered pattern of factors involved in SMC contractility is present at level of the tunica muscularis of DD patients. Moreover, considering that our analysis was conducted on colonic tissues not directly affected by diverticular lesions or inflammatory reactions, it is conceivable that these molecular alterations may precede and predispose to the formation of diverticula, rather than being mere consequences of the disease. 相似文献999.
1000.
Barbara A. Rath Kaveh Pouran Yousef David K. Katzenstein Robert W. Shafer Christof Schütte Max von Kleist Thomas C. Merigan 《PloS one》2013,8(4)