InvS Coordinates Expression of PrgH and FimZ and Is Required for Invasion of Epithelial Cells by Salmonella enterica serovar Typhimurium

ABSTRACT Deep sequencing has revolutionized our understanding of the bacterial RNA world and has facilitated the identification of 280 small RNAs (sRNAs) in Salmonella . Despite the suspicions that sRNAs may play important roles in Salmonella pathogenesis, the functions of most sRNAs remain unknown. To advance our understanding of RNA biology in Salmonella virulence, we searched for sRNAs required for bacterial invasion into nonphagocytic cells. After screening 75 sRNAs, we discovered that the ablation of InvS caused a significant decrease of Salmonella invasion into epithelial cells. A proteomic analysis showed that InvS modulated the levels of several type III secreted Salmonella proteins. The level of PrgH, a type III secretion apparatus protein, was significantly lower in the absence of InvS, consistent with the known roles of PrgH in effector secretion and bacterial invasion. We discovered that InvS modulates fimZ expression and hence flagellar gene expression and motility. We propose that InvS coordinates the increase of PrgH and decrease in FimZ that promote efficient Salmonella invasion into nonphagocytic cells. IMPORTANCE Salmonellosis continues to be the most common foodborne infection reported by the CDC in the United States. Central to Salmonella pathogenesis is the ability to invade nonphagocytic cells and to replicate inside host cells. Invasion genes are known to be regulated by protein transcriptional networks, but little is known about the role played by small RNAs (sRNAs) in this process. We have identified a novel sRNA, InvS, that is involved in Salmonella invasion. Our result will likely provide an opportunity to better understand the fundamental question of how Salmonella regulates invasion gene expression and may inform strategies for therapeutic intervention. </jats:p

Au/n-ZnO rectifying contact fabricated with hydrogen peroxide pretreatment

Au contacts were deposited on n -type ZnO single crystals with and without hydrogen peroxide pretreatment for the ZnO substrate. The Au/ZnO contacts fabricated on substrates without H2 O2 pretreatment were Ohmic and those with H2 O2 pretreatment were rectifying. With an aim of fabricating a good quality Schottky contact, the rectifying property of the Au/ZnO contact was systemically investigated by varying the treatment temperature and duration. The best performing Schottky contact was found to have an ideality factor of 1.15 and a leakage current of ∼ 10-7 A cm-2. A multispectroscopic study, including scanning electron microscopy, positron annihilation spectroscopy, deep level transient spectroscopy, x-ray photoelectron spectroscopy, and photoluminescence, showed that the H2 O2 treatment removed the OH impurity and created Zn-vacancy related defects hence decreasing the conductivity of the ZnO surface layer, a condition favorable for forming good Schottky contact. However, the H2 O2 treatment also resulted in a deterioration of the surface morphology, leading to an increase in the Schottky contact ideality factor and leakage current in the case of nonoptimal treatment time and temperature. © 2008 American Institute of Physics.published_or_final_versio

Hydrogen peroxide treatment induced rectifying behavior of Aun-ZnO contact

Conversion of the Aun-ZnO contact from Ohmic to rectifying with H2 O2 pretreatment was studied systematically using I-V measurements, x-ray photoemission spectroscopy, positron annihilation spectroscopy, and deep level transient spectroscopy. H2 O2 treatment did not affect the carbon surface contamination or the EC -0.31 eV deep level, but it resulted in a significant decrease of the surface OH contamination and the formation of vacancy-type defects (Zn vacancy or vacancy cluster) close to the surface. The formation of a rectifying contact can be attributed to the reduced conductivity of the surface region due to the removal of OH and the formation of vacancy-type defects. © 2007 American Institute of Physics.published_or_final_versio

Beliefs about the Minds of Others Influence How We Process Sensory Information

Attending where others gaze is one of the most fundamental mechanisms of social cognition. The present study is the first to examine the impact of the attribution of mind to others on gaze-guided attentional orienting and its ERP correlates. Using a paradigm in which attention was guided to a location by the gaze of a centrally presented face, we manipulated participants' beliefs about the gazer: gaze behavior was believed to result either from operations of a mind or from a machine. In Experiment 1, beliefs were manipulated by cue identity (human or robot), while in Experiment 2, cue identity (robot) remained identical across conditions and beliefs were manipulated solely via instruction, which was irrelevant to the task. ERP results and behavior showed that participants' attention was guided by gaze only when gaze was believed to be controlled by a human. Specifically, the P1 was more enhanced for validly, relative to invalidly, cued targets only when participants believed the gaze behavior was the result of a mind, rather than of a machine. This shows that sensory gain control can be influenced by higher-order (task-irrelevant) beliefs about the observed scene. We propose a new interdisciplinary model of social attention, which integrates ideas from cognitive and social neuroscience, as well as philosophy in order to provide a framework for understanding a crucial aspect of how humans' beliefs about the observed scene influence sensory processing

Niche as a determinant of word fate in online groups

Patterns of word use both reflect and influence a myriad of human activities and interactions. Like other entities that are reproduced and evolve, words rise or decline depending upon a complex interplay between {their intrinsic properties and the environments in which they function}. Using Internet discussion communities as model systems, we define the concept of a word niche as the relationship between the word and the characteristic features of the environments in which it is used. We develop a method to quantify two important aspects of the size of the word niche: the range of individuals using the word and the range of topics it is used to discuss. Controlling for word frequency, we show that these aspects of the word niche are strong determinants of changes in word frequency. Previous studies have already indicated that word frequency itself is a correlate of word success at historical time scales. Our analysis of changes in word frequencies over time reveals that the relative sizes of word niches are far more important than word frequencies in the dynamics of the entire vocabulary at shorter time scales, as the language adapts to new concepts and social groupings. We also distinguish endogenous versus exogenous factors as additional contributors to the fates of words, and demonstrate the force of this distinction in the rise of novel words. Our results indicate that short-term nonstationarity in word statistics is strongly driven by individual proclivities, including inclinations to provide novel information and to project a distinctive social identity.Comment: Supporting Information is available here: http://www.plosone.org/article/fetchSingleRepresentation.action?uri=info:doi/10.1371/journal.pone.0019009.s00

Does publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of US national institutes of health-funded trials

Background The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for depression. Methods and Findings We identified US National Institutes of Health grants awarded to fund randomized clinical trials comparing psychological treatment to control conditions or other treatments in patients diagnosed with major depressive disorder for the period 1972–2008, and we determined whether those grants led to publications. For studies that were not published, data were requested from investigators and included in the meta-analyses. Thirteen (23.6%) of the 55 funded grants that began trials did not result in publications, and two others never started. Among comparisons to control conditions, adding unpublished studies (Hedges’ g = 0.20; CI95% -0.11~0.51; k = 6) to published studies (g = 0.52; 0.37~0.68; k = 20) reduced the psychotherapy effect size point estimate (g = 0.39; 0.08~0.70) by 25%. Moreover, these findings may overestimate the "true" effect of psychological treatment for depression as outcome reporting bias could not be examined quantitatively. Conclusion The efficacy of psychological interventions for depression has been overestimated in the published literature, just as it has been for pharmacotherapy. Both are efficacious but not to the extent that the published literature would suggest. Funding agencies and journals should archive both original protocols and raw data from treatment trials to allow the detection and correction of outcome reporting bias. Clinicians, guidelines developers, and decision makers should be aware that the published literature overestimates the effects of the predominant treatments for depression

Manganese hexacyanomanganate open framework as a high-capacity positive electrode material for sodium-ion batteries

Potential applications of sodium-ion batteries in grid-scale energy storage, portable electronics and electric vehicles have revitalized research interest in these batteries. However, the performance of sodium-ion electrode materials has not been competitive with that of lithium-ion electrode materials. Here we present sodium manganese hexacyanomanganate (Na2MnII[Mn-II(CN)(6)]), an open-framework crystal structure material, as a viable positive electrode for sodium-ion batteries. We demonstrate a high discharge capacity of 209 mAh g(-1) at C/5 (40 mA g(-1)) and excellent capacity retention at high rates in a propylene carbonate electrolyte. We provide chemical and structural evidence for the unprecedented storage of 50% more sodium cations than previously thought possible during electrochemical cycling. These results represent a step forward in the development of sodium-ion batteries.open212

Graphene Photonics and Optoelectronics

The richness of optical and electronic properties of graphene attracts enormous interest. Graphene has high mobility and optical transparency, in addition to flexibility, robustness and environmental stability. So far, the main focus has been on fundamental physics and electronic devices. However, we believe its true potential to be in photonics and optoelectronics, where the combination of its unique optical and electronic properties can be fully exploited, even in the absence of a bandgap, and the linear dispersion of the Dirac electrons enables ultra-wide-band tunability. The rise of graphene in photonics and optoelectronics is shown by several recent results, ranging from solar cells and light emitting devices, to touch screens, photodetectors and ultrafast lasers. Here we review the state of the art in this emerging field.Comment: Review Nature Photonics, in pres

Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming

Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH