p21Waf1 expression is regulated by nuclear intermediate filament vimentin in neuroblastoma

<p>Abstract</p> <p>Background</p> <p>Human neuroblastoma (NB) cell lines may present with either one of the so-called S-and N-subtypes. We have previously reported a strong correlation between protein expression levels of vimentin, an S-subtype marker, and the p21^Waf1cyclin-dependent kinase inhibitor. We here investigated whether this correlation extend to the mRNA level in NB cell lines as well as in patients' tumors. We also further explored the relationship between expression of vimentin and p21, by asking whether vimentin could regulate p21 expression.</p> <p>Methods</p> <p>Vimentin and p21 mRNA levels in NB cell lines as well as in patients' tumors (<it>n </it>= 77) were quantified using Q-PCR. Q-PCR data obtained from tumors of high risk NB patients (<it>n </it>= 40) were analyzed in relation with the overall survival using the Log-rank Kaplan-Meier estimation. siRNA-mediated depletion or overexpression of vimentin in highly or low expressing vimentin cell lines, respectively, followed by protein expression and promoter activation assays were used to assess the role of vimentin in modulating p21 expression.</p> <p>Results</p> <p>We extend the significant correlation between vimentin and p21 expression to the mRNA level in NB cell lines as well as in patients' tumors. Overall survival analysis from Q-PCR data obtained from tumors of high risk patients suggests that lower levels of p21 expression could be associated with a poorer outcome. Our data additionally indicate that the correlation observed between p21 and vimentin expression levels results from p21 transcriptional activity being regulated by vimentin. Indeed, downregulating vimentin resulted in a significant decrease in p21 mRNA and protein expression as well as in p21 promoter activity. Conversely, overexpressing vimentin triggered an increase in p21 promoter activity in cells with a nuclear expression of vimentin.</p> <p>Conclusion</p> <p>Our results suggest that p21 mRNA tumor expression level could represent a refined prognostic factor for high risk NB patients. Our data also show that vimentin regulates p21 transcription; this is the first demonstration of a gene regulating function for this type III-intermediate filament.</p

European Consensus Statement on Expert Colposcopy

Peer reviewedPublisher PD

The Problematization of Sexuality among Women Living with HIV and a New Feminist Approach for Understanding and Enhancing Women’s Sexual Lives

In the context of HIV, women’s sexual rights and sexual autonomy are important but frequently overlooked and violated. Guided by community voices, feminist theories, and qualitative empirical research, we reviewed two decades of global quantitative research on sexuality among women living with HIV. In the 32 studies we found, conducted in 25 countries and composed mostly of cis-gender heterosexual women, sexuality was narrowly constructed as sexual behaviours involving risk (namely, penetration) and physiological dysfunctions relating to HIV illness, with far less attention given to the fullness of sexual lives in context, including more&nbsp;positive and rewarding experiences such as satisfaction and pleasure. Findings suggest that women experience declines in sexual activity, function, satisfaction, and pleasure following HIV diagnosis, at least for some period. The extent of such declines, however, is varied, with numerous contextual forces shaping women’s sexual well-being. Clinical markers of HIV (e.g., viral load, CD4 cell count) poorly predicted sexual outcomes, interrupting widely held assumptions about sexuality for women with HIV. Instead, the effects of HIV-related stigma intersecting with inequities related to trauma, violence, intimate relations, substance use, poverty, aging, and other social and cultural conditions primarily influenced the ways in which women experienced and enacted their sexuality. However, studies framed through a medical lens tended to pathologize outcomes as individual “problems,” whereas others driven by a public health agenda remained primarily preoccupied with protecting the public from HIV. In light of these findings, we present a new feminist approach for research, policy, and practice toward understanding and enhancing women’s sexual lives—one that affirms sexual diversity; engages deeply with society, politics, and history; and is grounded in women’s sexual rights

Sex in the shadow of HIV:A systematic review of prevalence, risk factors, and interventions to reduce sexual risk-taking among HIVpositive adolescents and youth in sub-Saharan Africa

Background Evidence on sexual risk-taking among HIV-positive adolescents and youth in sub-Saharan Africa is urgently needed. This systematic review synthesizes the extant research on prevalence, factors associated with, and interventions to reduce sexual risk-taking among HIV-positive adolescents and youth in sub-Saharan Africa. Methods Studies were located through electronic databases, grey literature, reference harvesting, and contact with researchers. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Quantitative studies that reported on HIV-positive participants (10-24 year olds), included data on at least one of eight outcomes (early sexual debut, inconsistent condom use, older partner, transactional sex, multiple sexual partners, sex while intoxicated, sexually transmitted infections, and pregnancy), and were conducted in sub-Saharan Africa were included. Two authors piloted all processes, screened studies, extracted data independently, and resolved any discrepancies. Due to variance in reported rates and factors associated with sexual risk-taking, meta-analyses were not conducted. Results 610 potentially relevant titles/abstracts resulted in the full text review of 251 records. Forty-two records (n=35 studies) reported one or multiple sexual practices for 13,536 HIV-positive adolescents/youth from 13 sub-Saharan African countries. Seventeen cross-sectional studies reported on individual, relationship, family, structural, and HIV-related factors associated with sexual risk-taking. However, the majority of the findings were inconsistent across studies, and most studies scored Conclusions Sexual risk-taking among HIV-positive adolescents and youth is high, with inconclusive evidence on potential determinants. Few known studies test secondary HIV-prevention interventions for HIV-positive youth. Effective and feasible low-cost interventions to reduce risk are urgently needed for this group.</p

Bilan un an après le premier couplage de Superphénix

Les auteurs tirent les conclusions des essais et des premiers mois de fonctionnement de Superphénix. Leur article est complété par un développement concernant l'incident de la cuve du barillet (fuite de sodium) survenu en mars 1987

Vaccins contre le papillomavirus humain et prévention des cancers gynécologiques: Résultats actuels et nouvelles perspectives [HPV vaccines and prevention of gynecological cancers: Current results, new perspectives]

National audienceThe HPV vaccine is the result of progress in the knowledge of HPV-induced malignancies and represents an hope for primary prevention of many epithelial cancers, mainly the cervix cancer in women. Its efficacy and safety are proven by methodologically adequate trials (randomized double-blind trials). The impact of the vaccine on large populations begins to be perceived in countries with proactive vaccination programs. Unfortunatly, vaccination brakes exist today in France explaining the relative failure of vaccination: the conviction of doctors, and the establishment of an early and wide vaccination program under the authority of government could overcome this reluctance. Progresses can be expected with the development of vaccine containing new genotypes, as in the nonavalent vaccine that compares favorably with the quadrivalent vaccine. Copyright © 2016 JLE

Sidewall and thermal boundary condition effects on the evolution of longitudinal rolls in Rayleigh-Bénard-Poiseuille convection

Experimental and numerical studies of steady longitudinal convection rolls that develop in a Poiseuille air flow in a rectangular channel heated from below and cooled from the top are conducted in the range 3500 ≤ Ra ≤ 6000 and 20 ≤ Re ≤ 200. The effect of the lateral vertical walls on the onset and development of the convection cells is investigated by changing the transverse aspect ratio of the channel from 4.7 to 18.4. The influence of the entrance temperature and of adiabatic or conductive thermal boundary conditions at the side and top walls of the channel is also investigated. The scenario of the roll formation is described in details. It results in a symmetric pattern in the form of steady longitudinal rolls with an even number of rolls that depends not only on the aspect ratio but possibly on the inlet temperature of the flow. It is shown that the fully developed pattern is determined by the two rolls nearby each vertical side wall that are triggered just at the entrance of the channel due to the presence of velocity boundary layers adjacent to the walls. It is also shown that the heat conduction in the top horizontal wall of the experimental channel must be taken into account in the numerical simulations so that the experimental wavenumber can be properly depicted. 1 I