Cryo-EM structure of mammalian RNA polymerase II in complex with human RPAP2

Nuclear import of RNA polymerase II (Pol II) involves the conserved factor RPAP2. Here we report the cryo-electron microscopy (cryo-EM) structure of mammalian Pol II in complex with human RPAP2 at 2.8 Å resolution. The structure shows that RPAP2 binds between the jaw domains of the polymerase subunits RPB1 and RPB5. RPAP2 is incompatible with binding of downstream DNA during transcription and is displaced upon formation of a transcription pre-initiation complex

Antimicrobial and modulation effects of selected Ghanaian medicinal plants

The alarming rise in the incidences of multidrug-resistant microorganisms and the decline innew antibiotic discovery make the search for new antimicrobial agents or efforts at restoring the activity of older antibiotics to which the microbes have developed resistance very necessary. The aim of the present study is to investigate the antimicrobial and modulation effects of the 70% ethanol extracts of Lannea schimperi, Commelina nudiflora and Piliostigma reticulatum against usceptible strains of microorganisms. Using the broth microdilution method, the minimum inhibitory concentrations (MICs) of the extracts were determined. The checkerboard assay was used to determine the modulation effects when sub-inhibitory concentrations of plant extracts were combined with the standard antibiotics. All three plants extracts possessed weak antimicrobial effects. For the modulation experiments, fifteen of the twenty-seven combinatorial casesyielded biologically significant effects. The ethanol extracts of the three plants studied here are good modulators as they reduced the MIC of ciprofloxacin and ketoconazole by factors that are comparable to that of reserpine. However the exact compounds and their exact mechanism of modulation require further investigation.Keywords: Anti-infective, modulation, Lannea schimperi, Commelina nudiflora, Piliostigmareticulatum, ethnomedicin

The clinical diagnosis of pelvic inflammatory disease – reuse of electronic medical record data from 189 patients visiting a Swedish university hospital emergency department

BACKGROUND: The pelvic inflammatory disease (PID) diagnosis is mostly based on clinical findings. However, few studies have examined the clinical basis for the diagnostics of PID, which was the aim of this study. METHODS: A retrospective study was performed of 189 out-patients diagnosed as having PID at the obstetric and gynecological emergency department of a Swedish university hospital. Data on symptoms, signs, pelvic examination and laboratory tests were extracted from the electronic medical records in comparison with the diagnostic criteria of the PID Guideline of the US Center of Disease Control from 2002 (CDC 2002 Guidelines). RESULTS: Eight symptoms in varying combinations were associated with the PID diagnosis. Most of them are mentioned in the CDC 2002 Guidelines. Detected rates of C. Trachomatis (CT) and N. Gonorrhoeae (NG) were 5% and 0%, respectively, among the tested patients (CT = 52% and NG = 12%). The C-reactive protein was normal in the majority of tested patients. CONCLUSION: The clinical basis for the diagnostics of PID was largely in accordance with the criteria in the CDC 2002 Guidelines. The limited number of CT tests performed is somewhat disappointing, considering the fact that effective disease prevention includes widespread CT screening. Further studies in different settings are needed in order to analyze how the testing rate for CT can be improved in clinical praxis

Vitamin D Induction of the Human Antimicrobial Peptide Cathelicidin in the Urinary Bladder

The urinary tract is frequently being exposed to potential pathogens and rapid defence mechanisms are therefore needed. Cathelicidin, a human antimicrobial peptide is expressed and secreted by bladder epithelial cells and protects the urinary tract from infection. Here we show that vitamin D can induce cathelicidin in the urinary bladder. We analyzed bladder tissue from postmenopausal women for expression of cathelicidin, before and after a three-month period of supplementation with 25-hydroxyvitamin D3 (25D3). Cell culture experiments were performed to elucidate the mechanisms for cathelicidin induction. We observed that, vitamin D per se did not up-regulate cathelicidin in serum or in bladder tissue of the women in this study. However, when the bladder biopsies were infected with uropathogenic E. coli (UPEC), a significant increase in cathelicidin expression was observed after 25D3 supplementation. This observation was confirmed in human bladder cell lines, even though here, cathelicidin induction occurred irrespectively of infection. Vitamin D treated bladder cells exerted an increased antibacterial effect against UPEC and colocalization to cathelicidin indicated the relevance of this peptide. In the light of the rapidly growing problem of resistance to common urinary tract antibiotics, we suggest that vitamin D may be a potential complement in the prevention of UTI

Impact of Chikungunya Virus Infection on Health Status and Quality of Life: A Retrospective Cohort Study

BACKGROUND:Persistent symptoms, mainly joint and muscular pain and depression, have been reported several months after Chikungunya virus (CHIKV) infection. Their frequency and their impact on quality of life have not been compared with those of an unexposed population. In the present study, we aimed to describe the frequency of prolonged clinical manifestations of CHIKV infection and to measure the impact on quality of life and health care consumption in comparison with that of an unexposed population, more than one year after infection. METHODOLOGY/PRINCIPAL FINDINGS:In a retrospective cohort study, 199 subjects who had serologically confirmed CHIKV infection (CHIK+) were compared with 199 sero-negative subjects (CHIK-) matched for age, gender and area of residence in La Réunion Island. Following an average time of 17 months from the acute phase of infection, participants were interviewed by telephone about current symptoms, medical consumption during the last 12 months and quality of life assessed by the 12-items Short-Form Health Survey (SF-12) scale. At the time of study, 112 (56%) CHIK+ persons reported they were fully recovered. CHIK+ complained more frequently than CHIK- of arthralgia (relative risk = 1.9; 95% confidence interval: 1.6-2.2), myalgia (1.9; 1.5-2.3), fatigue (2.3; 1.8-3), depression (2.5; 1.5-4.1) and hair loss (3.8; 1.9-7.6). There was no significant difference between CHIK+ and CHIK- subjects regarding medical consumption in the past year. The mean (SD) score of the SF-12 Physical Component Summary was 46.4 (10.8) in CHIK+ versus 49.1 (9.3) in CHIK- (p = 0.04). There was no significant difference between the two groups for the Mental Component Summary. CONCLUSIONS/SIGNIFICANCE:More than one year following the acute phase of infection, CHIK+ subjects reported more disabilities than those who were CHIK-. These persistent disabilities, however, have no significant influence on medical consumption, and the impact on quality of life is moderate

Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009

International audienceBACKGROUND: To date, there is little information that reflects the true extent of spread of the pH1N1/2009v influenza pandemic at the community level as infection often results in mild or no clinical symptoms. This study aimed at assessing through a prospective study, the attack rate of pH1N1/2009 virus in Reunion Island and risk factors of infection, during the 2009 season.METHODOLOGY/PRINCIPAL FINDINGS: A serosurvey was conducted during the 2009 austral winter, in the frame of a prospective population study. Pairs of sera were collected from 1687 individuals belonging to 772 households, during and after passage of the pandemic wave. Antibodies to pH1N1/2009v were titered using the hemagglutination inhibition assay (HIA) with titers ≥ 1/40 being considered positive. Seroprevalence during the first two weeks of detection of pH1N1/2009v in Reunion Island was 29.8% in people under 20 years of age, 35.6% in adults (20-59 years) and 73.3% in the elderly (≥ 60 years) (P<0.0001). Baseline corrected cumulative incidence rates, were 42.9%, 13.9% and 0% in these age groups respectively (P<0.0001). A significant decline in antibody titers occurred soon after the passage of the epidemic wave. Seroconversion rates to pH1N1/2009 correlated negatively with age: 63.2%, 39.4% and 16.7%, in each age group respectively (P<0.0001). Seroconversion occurred in 65.2% of individuals who were seronegative at inclusion compared to 6.8% in those who were initially seropositive.CONCLUSIONS: Seroincidence of pH1N1/2009v infection was three times that estimated from clinical surveillance, indicating that almost two thirds of infections occurring at the community level have escaped medical detection. People under 20 years of age were the most affected group. Pre-epidemic titers ≥ 1/40 prevented seroconversion and are likely protective against infection. A concern was raised about the long term stability of the antibody responses

Estimation of risk measures on electricity markets with fat-tailed distributions

This paper proposes an autoregressive-generalized autoregressive conditional heteroscedasticity (AR-GARCH)-type extreme value theory (EVT) model with various innovations based on value-at-risk (VaR) and conditional value-at-risk (CVaR) for energy price risk quantification in different emerging energy markets.We assess the best-fitting AR-exponential GARCH-EVT and AR-threshold GARCH-EVT models for Powernext and the European Energy Exchange, respectively. EVT is adopted explicitly to model the tails of the return distribution in order to capture extremal events. One of the main contributions of this paper is the estimation ofVaR and CVaR via EVT on the lower and upper tails of the return distribution in order to capture the extreme events of the distribution. This paper also contributes to the literature by analyzing both the upper and lower tails, in order to satisfy the different perspectives of regulators and investors in the energy market