Dependence of NO rotational photoionization propensity rules on electron kinetic energy

In order to study the effect of photoelectron kinetic energy on rotational photoionization propensity rules, rotationally resolved laser photoelectron spectra were measured for excitation of specific rovibronic levels in the D 2Sigma+ (3psigma) Rydberg state of NO and their subsequent ionization by radiation at several wavelengths. The measured and calculated ion rotational branching ratios both show a significant dependence on photoelectron energy. Comparison between experimental data and theoretical calculations suggests that a strong DeltaN=0 peak in the spectra is caused by an interaction between particular vibronic levels of the A 2Sigma+ (v=4) and D 2Sigma+ (v=0) Rydberg states

A CRISPR/Cas9 Vector System for Tissue-Specific Gene Disruption in Zebrafish

SummaryCRISPR/Cas9 technology of genome editing has greatly facilitated the targeted inactivation of genes in vitro and in vivo in a wide range of organisms. In zebrafish, it allows the rapid generation of knockout lines by simply injecting a guide RNA (gRNA) and Cas9 mRNA into one-cell stage embryos. Here, we report a simple and scalable CRISPR-based vector system for tissue-specific gene inactivation in zebrafish. As proof of principle, we used our vector with the gata1 promoter driving Cas9 expression to silence the urod gene, implicated in heme biosynthesis, specifically in the erythrocytic lineage. Urod targeting yielded red fluorescent erythrocytes in zebrafish embryos, recapitulating the phenotype observed in the yquem mutant. While F0 embryos displayed mosaic gene disruption, the phenotype appeared very penetrant in stable F1 fish. This vector system constitutes a unique tool to spatially control gene knockout and greatly broadens the scope of loss-of-function studies in zebrafish

Genomic differences between nasal Staphylococcus aureus from hog slaughterhouse workers and their communities.

New human pathogens can emerge from the livestock-human interface and spread into human populations through many pathways including livestock products. Occupational contact with livestock is a risk factor for exposure to those pathogens and may cause further spreading of those pathogens in the community. The current study used whole genome sequencing to explore nasal Staphylococcus aureus obtained from hog slaughterhouse workers and their community members, all of whom resided in a livestock-dense region in rural North Carolina. Sequence data were analyzed for lineage distribution, pathogenicity-related genomic features, and mobile genetic elements. We observed evidence of nasal S. aureus differences between hog workers and non-workers. Nasal S. aureus from hog workers showed a greater lineage diversity than nasal S. aureus from community residents. Hog worker isolates were less likely to carry the φSa3 prophage and human-specific immune evasion cluster genes than community resident isolates (φSa3 prophage: 54.5% vs. 91.7%, Benjamini-Hochberg (BH) corrected p = 0.035; immune evasion cluster genes: 66.7% vs. 100%, BH p = 0.021). Hog worker isolates had a lower prevalence and diversity of enterotoxins than community resident isolates, particularly lacking the enterotoxin gene cluster (39.4% vs. 70.8%, BH p = 0.125). Moreover, hog worker isolates harbored more diverse antibiotic resistance genes, with a higher prevalence of carriage of multiple resistance genes, than community resident isolates (75.8% vs. 29.2%, BH p = 0.021). Phylogenetic analysis of all ST5 isolates, the most abundant lineage in the collection, further supported separation of isolates from hog workers and non-workers. Together, our observations suggest impact of occupational contact with livestock on nasal S. aureus colonization and highlight the need for further research on the complex epidemiology of S. aureus at the livestock-human interface

An Ileal Crohn's Disease Gene Signature Based on Whole Human Genome Expression Profiles of Disease Unaffected Ileal Mucosal Biopsies

Previous genome-wide expression studies have highlighted distinct gene expression patterns in inflammatory bowel disease (IBD) compared to control samples, but the interpretation of these studies has been limited by sample heterogeneity with respect to disease phenotype, disease activity, and anatomic sites. To further improve molecular classification of inflammatory bowel disease phenotypes we focused on a single anatomic site, the disease unaffected proximal ileal margin of resected ileum, and three phenotypes that were unlikely to overlap: ileal Crohn's disease (ileal CD), ulcerative colitis (UC), and control patients without IBD. Whole human genome (Agilent) expression profiling was conducted on two independent sets of disease-unaffected ileal samples collected from the proximal margin of resected ileum. Set 1 (47 ileal CD, 27 UC, and 25 Control non-IBD patients) was used as the training set and Set 2 was subsequently collected as an independent test set (10 ileal CD, 10 UC, and 10 control non-IBD patients). We compared the 17 gene signatures selected by four different feature-selection methods to distinguish ileal CD phenotype with non-CD phenotype. The four methods yielded different but overlapping solutions that were highly discriminating. All four of these methods selected FOLH1 as a common feature. This gene is an established biomarker for prostate cancer, but has not previously been associated with Crohn's disease. Immunohistochemical staining confirmed increased expression of FOLH1 in the ileal epithelium. These results provide evidence for convergent molecular abnormalities in the macroscopically disease unaffected proximal margin of resected ileum from ileal CD subjects

Cell-phone traces reveal infection-associated behavioral change

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadEpidemic preparedness depends on our ability to predict the trajectory of an epidemic and the human behavior that drives spread in the event of an outbreak. Changes to behavior during an outbreak limit the reliability of syndromic surveillance using large-scale data sources, such as online social media or search behavior, which could otherwise supplement healthcare-based outbreak-prediction methods. Here, we measure behavior change reflected in mobile-phone call-detail records (CDRs), a source of passively collected real-time behavioral information, using an anonymously linked dataset of cell-phone users and their date of influenza-like illness diagnosis during the 2009 H1N1v pandemic. We demonstrate that mobile-phone use during illness differs measurably from routine behavior: Diagnosed individuals exhibit less movement than normal (1.1 to 1.4 fewer unique tower locations; [Formula: see text]), on average, in the 2 to 4 d around diagnosis and place fewer calls (2.3 to 3.3 fewer calls; [Formula: see text]) while spending longer on the phone (41- to 66-s average increase; [Formula: see text]) than usual on the day following diagnosis. The results suggest that anonymously linked CDRs and health data may be sufficiently granular to augment epidemic surveillance efforts and that infectious disease-modeling efforts lacking explicit behavior-change mechanisms need to be revisited. Keywords: call detail records; disease; influenza; outbreak; surveillance.Alan Turing Institute Engineering and Physical Sciences Research Council EP/N510129/1 UK Research & Innovation (UKRI) Medical Research Council UK (MRC) European Commission National Institute for Health Research (NIHR) Health Protection Research Unit in Evaluation of Interventions at the University of Brist

Impact of a disease-management program on symptom burden and health-related quality of life in patients with idiopathic pulmonary fibrosis and their care partners

Patients were recruited from the Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, located within the University of Pittsburgh Medical Center. Idiopathic pulmonary fibrosis results in scarring of the lung and respiratory failure, and has a median survival of 3 to 5 years from the time of diagnosis. The purpose of this study was to determine whether patients with idiopathic pulmonary fibrosis and their care partners could be more optimally managed by a disease-management intervention entitled “Program to Reduce Idiopathic Pulmonary Fibrosis Symptoms and Improve Management,” which nurses delivered using the format of a support group. We hypothesized that participation would improve perceptions of health-related quality of life (HRQoL) and decrease symptom burden

Association between Common Germline Genetic Variation in 94 Candidate Genes or Regions and Risks of Invasive Epithelial Ovarian Cancer

Background: Recent studies have identified several single nucleotide polymorphisms (SNPs) in the population that are associated with variations in the risks of many different diseases including cancers such as breast, prostate and colorectal. For ovarian cancer, the known highly penetrant susceptibility genes (BRCA1 and BRCA2) are probably responsible for only 40% of the excess familial ovarian cancer risks, suggesting that other susceptibility genes of lower penetrance exist.Methods: We have taken a candidate approach to identifying moderate risk susceptibility alleles for ovarian cancer. To date, we have genotyped 340 SNPs from 94 candidate genes or regions, in up to 1,491 invasive epithelial ovarian cancer cases and 3,145 unaffected controls from three different population based studies from the UK, Denmark and USA.Results: After adjusting for population stratification by genomic control, 18 SNPs (5.3%) were significant at the 5% level, and 5 SNPs (1.5%) were significant at the 1% level. The most significant association was for the SNP rs2107425, located on chromosome 11p15.5, which has previously been identified as a susceptibility allele for breast cancer from a genome wide association study (P-trend = 0.0012). When SNPs/genes were stratified into 7 different pathways or groups of validation SNPs, the breast cancer associated SNPs were the only group of SNPs that were significantly associated with ovarian cancer risk (P-heterogeneity = 0.0003; P-trend = 0.0028; adjusted (for population stratification) P-trend = 0.006). We did not find statistically significant associations when the combined data for all SNPs were analysed using an admixture maximum likelihood (AML) experiment- wise test for association (P-heterogeneity = 0.051; P-trend = 0.068).Conclusion: These data suggest that a proportion of the SNPs we evaluated were associated with ovarian cancer risk, but that the effect sizes were too small to detect associations with individual SNPs