Draft Whole-Genome Sequence of Haemophilus ducreyi Strain AUSPNG1, Isolated from a Cutaneous Ulcer of a Child from Papua New Guinea.

Haemophilus ducreyi has recently emerged as a leading cause of cutaneous ulcers in the yaws-endemic areas of Papua New Guinea and other South Pacific islands. Here, we report the draft genome sequence of the H. ducreyi strain AUSPNG1, isolated from a cutaneous ulcer of a child from Papua New Guinea

Human papillomavirus type 16 infection activates the host serine arginine protein kinase 1 (SRPK1) - splicing factor axis

The infectious life cycle of human papillomaviruses (HPVs) is tightly linked to keratinocyte differentiation. Evidence suggests a sophisticated interplay between host gene regulation and virus replication. Alternative splicing is an essential process for host and viral gene expression, and is generally upregulated by serine arginine-rich splicing factors (SRSFs). SRSF activity can be positively or negatively controlled by cycles of phosphorylation/dephosphorylation. Here we show that HPV16 infection leads to accumulation of the paradigm SRSF protein, SRSF1, in the cytoplasm in a keratinocyte differentiation-specific manner. Moreover, HPV16 infection leads to increased levels of cytoplasmic and nuclear phosphorylated SRSF1. SR protein kinase 1 (SRPK1) phosphorylates SRSF1. Similar to HPV upregulation of SRSF1, we demonstrate HPV upregulation of SRPK1 via the viral E2 protein. SRPK1 depletion or drug inhibition of SRPK1 kinase activity resulted in reduced levels of SRSF1, suggesting that phosphorylation stabilizes the protein in differentiated HPV-infected keratinocytes. Together, these data indicate HPV infection stimulates the SRPK1–SRSF axis in keratinocytes

Predictors of hospital surface contamination with Extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae: patient and organism factors

BACKGROUND: The role of the hospital environment in transmission of ESBL-Klebsiella pneumoniae (ESBL-KP) and ESBL-Escherichia coli (ESBL-EC) is poorly defined. Recent data however suggest that in the hospital setting, ESBL-KP is more transmissible than ESBL-EC. We sought therefore to measure the difference in hospital contamination rates between the two species and to identify key risk factors for contamination of the hospital environment with these organisms. METHODS: We systematically sampled 8 surfaces in the rooms and bathrooms of adult patients colonized or infected with ESBL-EC or ESBL-KP throughout their hospital stay. Data were collected on factors potentially affecting contamination rates. Environmental contamination was defined as recovery of an ESBL-producing organism matching the source patient’s isolate. Multivariate logistic regression analysis was performed at the level of the patient visit using generalized estimating equations to identify independent predictors of environmental contamination. RESULTS: 24 patients (11 with ESBL-KP, 11 ESBL-EC and 2 with both organisms) had 1104 swabs collected during 138 visits. The overall contamination rate was 3.4% (38/1104) and was significantly higher for ESBL-KP than ESBL-EC (5.4% versus 0.4%; p < 0.0001). After multivariate analysis, environmental contamination was found to be negatively associated with carbapenem exposure (OR 0.06 [95% CI 0.01-0.61]; p = 0.017) and positively associated with the presence of an indwelling urinary catheter (OR 6.12 [95% CI 1.23-30.37]; p = 0.027) and ESBL-KP in the source patient (OR 26.23 [95% CI 2.70-254.67]; p = 0.005). CONCLUSIONS: Contamination of the hospital environment with ESBL-producing Enterobacteriaceae (ESBL-E) is inversely associated with carbapenem exposure. Predictors of hospital contamination with ESBL-E include: indwelling urinary catheters and ESBL-KP. Rooms of patients with ESBL-KP have substantially higher contamination rates than those with ESBL-EC. This finding may help explain the apparently higher transmissibility of ESBL-KP in the hospital setting

'Simultaneous Immersion' : How online postgraduate study contributes to the development of reflective practice among public service practitioners

This paper examines how the process of engaging simultaneously in study and work – through online distance-based study – affects students’ capacity to apply their learning in and for the workplace. The paper takes as its starting point the importance of extending notions of “educational effectiveness” beyond course-based attainment to encompass the impact of learning within the workplace. It explores the interface between study and work, focusing on the case of online postgraduate programmes in public management at the University of York. It finds that simultaneous immersion in study and work can create the conditions for “public reflection” that underpin work-based learning and that a key factor is the student-practitioner's ability to mobilise “episodic power.” The paper suggests ways in which existing approaches to online postgraduate learning might be enhanced in order to capitalise on these conditions of simultaneous immersion

Irreducible characters of GSp(4, q) and dimensions of spaces of fixed vectors

In this paper, we compute the conjugacy classes and the list of irreducible characters of GSp(4,q), where q is odd. We also determine precisely which irreducible characters are non-cuspidal and which are generic. These characters are then used to compute dimensions of certain subspaces of fixed vectors of smooth admissible non-supercuspidal representations of GSp(4,F), where F is a non-archimedean local field of characteristic zero with residue field of order q.Comment: 48 pages, 21 tables. Corrected an error in Table 16 for type V* representations (theta_11 and theta_12 were switched

Sex chromosome complement contributes to sex differences in coxsackievirus B3 but not influenza A virus pathogenesis

<p>Abstract</p> <p>Background</p> <p>Both coxsackievirus B3 (CVB3) and influenza A virus (IAV; H1N1) produce sexually dimorphic infections in C57BL/6 mice. Gonadal steroids can modulate sex differences in response to both viruses. Here, the effect of sex chromosomal complement in response to viral infection was evaluated using four core genotypes (FCG) mice, where the <it>Sry </it>gene is deleted from the Y chromosome, and in some mice is inserted into an autosomal chromosome. This results in four genotypes: XX or XY gonadal females (XXF and XYF), and XX or XY gonadal males (XXM and XYM). The FCG model permits evaluation of the impact of the sex chromosome complement independent of the gonadal phenotype.</p> <p>Methods</p> <p>Wild-type (WT) male and female C57BL/6 mice were assigned to remain intact or be gonadectomized (Gdx) and all FCG mice on a C57BL/6 background were Gdx. Mice were infected with either CVB3 or mouse-adapted IAV, A/Puerto Rico/8/1934 (PR8), and monitored for changes in immunity, virus titers, morbidity, or mortality.</p> <p>Results</p> <p>In CVB3 infection, mortality was increased in WT males compared to females and males developed more severe cardiac inflammation. Gonadectomy suppressed male, but increased female, susceptibility to CVB3. Infection with IAV resulted in greater morbidity and mortality in WT females compared with males and this sex difference was significantly reduced by gonadectomy of male and female mice. In Gdx FCG mice infected with CVB3, XY mice were less susceptible than XX mice. Protection correlated with increased CD4+ forkhead box P3 (FoxP3)+ T regulatory (Treg) cell activation in these animals. Neither CD4+ interferon (IFN)γ (T helper 1 (Th1)) nor CD4+ interleukin (IL)-4+ (Th2) responses differed among the FCG mice during CVB3 infection. Infection of Gdx FCG mice revealed no effect of sex chromosome complement on morbidity or mortality following IAV infection.</p> <p>Conclusions</p> <p>These studies indicate that sex chromosome complement can influence pathogenicity of some, but not all, viruses.</p

Association between trial registration and positive study findings: cross sectional study (Epidemiological Study of Randomized Trials—ESORT)

Objective To assess whether randomised controlled trials (RCTs) that were registered were less likely to report positive study findings compared with RCTs that were not registered and whether the association varied by funding source. Design Cross sectional study. Study sample All primary RCTs published in December 2012 and indexed in PubMed by November 2013. Trial registration was determined based on the report of a trial registration number in published RCTs or the identification of the trial in a search of trial registries. Trials were separated into prospectively and retrospectively registered studies. Main outcome measure Association between trial registration and positive study findings. Results 1122 eligible RCTs were identified, of which 593 (52.9%) were registered and 529 (47.1%) were not registered. Overall, registration was marginally associated with positive study findings (adjusted risk ratio 0.87, 95% confidence interval 0.78 to 0.98), even with stratification as prospectively and retrospectively registered trials (0.87, 0.74 to 1.03 and 0.88, 0.78 to 1.00, respectively). The interaction term between overall registration and funding source was marginally statistically significant and relative risk estimates were imprecise (0.75, 0.63 to 0.89 for non-industry funded and 1.03, 0.79 to 1.36 for industry funded, P interaction=0.046). Furthermore, a statistically significant interaction was not maintained in sensitivity analyses. Within each stratum of funding source, relative risk estimates were also imprecise for the association between positive study findings and prospective and retrospective registration. Conclusion Among published RCTs, there was little evidence of a difference in positive study findings between registered and non-registered clinical trials, even with stratification by timing of registration. Relative risk estimates were imprecise in subgroups of non-industry and industry funded trials

A cyclin-binding motif in human papillomavirus type 18 (HPV18) E1^E4 is necessary for association with CDK–cyclin complexes and G2/M cell cycle arrest of keratinocytes, but is not required for differentiation-dependent viral genome amplification or L1 capsid protein expression

Investigation into the effects the HPV E4 protein has in viral life cycleThe G2/M arrest function of human papillomavirus (HPV) E4 proteins is hypothesized to be necessary for viral genome amplification. Full-length HPV18 E1^E4 protein is essential for efficient viral genome amplification. Here we identify key determinants within a CDK-bipartite consensus recognition motif in HPV18 E1^E4 that are critical for association with active CDK–cyclin complexes and in vitro phosphorylation at the predicted CDK phosphorylation site (threonine 23). The optimal cyclin-binding sequence (43RRLL46) within this E4 motif is required for G2/M arrest of primary keratinocytes and correlates with cytoplasmic retention of cyclin B1, but not cyclin A. Disruption of this motif in the E4 ORF of HPV18 genomes, and the subsequent generation of stable cell lines in primary keratinocytes revealed that this motif was not essential for viral genome amplification or L1 capsid protein induction. We conclude that the HPV18 E4 G2/M arrest function does not play a role in early vegetative events