Swiss EMBnet node web server

EMBnet is a consortium of collaborating bioinformatics groups located mainly within Europe (http://www.embnet.org). Each member country is represented by a ‘node', a group responsible for the maintenance of local services for their users (e.g. education, training, software, database distribution, technical support, helpdesk). Among these services a web portal with links and access to locally developed and maintained software is essential and different for each node. Our web portal targets biomedical scientists in Switzerland and elsewhere, offering them access to a collection of important sequence analysis tools mirrored from other sites or developed locally. We describe here the Swiss EMBnet node web site (http://www.ch.embnet.org), which presents a number of original services not available anywhere els

Changes in mental health, wellbeing and personality following ayahuasca consumption : results of a naturalistic longitudinal study

Background: Naturalistic and placebo-controlled studies suggest ayahuasca, a potent psychedelic beverage originating from Indigenous Amazonian tradition, may improve mental health, alter personality structure, and reduce alcohol and drug intake. To better understand ayahuasca’s therapeutic potential and to identify factors that influence therapeutic efficacy, we conducted a naturalistic, longitudinal study of facilitated ayahuasca consumption in naïve participants using a comprehensive battery of self-report questionnaires. Materials and Methods: Ayahuasca naive individuals registering for ayahuasca ceremonies were asked to complete a range of validated questionnaires assessing mental health, alcohol/cannabis use, relationships, personality, and connection to self and spirituality, prior to and 1 month after attending an ayahuasca ceremony. Data for two mental health measures (the DASS-21 and PANAS) and acute subjective effects via the MEQ-30 were also assessed 7 days post-ceremony. Repeated measures ANOVA were used to examine pre-to-post changes, and Pearson correlations explored predictors of improvement in outcomes. Results: Fifty-three attendees (32 women, 21 men) completed pre and post ayahuasca assessments with 55.6% of the sample reporting a complete mystical experience based on the MEQ-30. One-month post-ayahuasca, significant reductions were identified in depression, anxiety, stress, alcohol and cannabis use, body dissociation, accepting external influence, self-alienation, impulsivity, and negative affect/emotionality. Significant increases were identified in positive mood, self-efficacy, authentic living, extraversion, agreeableness, open-mindedness, spirituality, and satisfaction with relationships. While facets of the mystical experience held little predictive validity on outcome measures, baseline traits, particularly high negative emotionality and body dissociation, and low sense of self-efficacy, robustly predicted improvements in mental health and alcohol/cannabis use, and alterations in personality structure which are linked to better mental health. Discussion: This study suggests facilitated ayahuasca consumption in naïve participants may precipitate wide-ranging improvements in mental health, relationships, personality structure, and alcohol use. Associations between baseline traits and therapeutic improvements mark an important first step toward personalized, precision-based medicine and warrant randomized controlled trials to confirm and elaborate on these findings. Contribution Statement: Longitudinal, observational studies and randomized clinical control trials suggest ayahuasca may exert therapeutic effects on mental health and alcohol/cannabis use, and alter personality structure. However, it is unclear if improvements are diagnosis-specific and factors that predict therapeutic gains have yet to be extensively elucidated. This longitudinal, observational study examined the effects of facilitated ayahuasca consumption in naive participants on mental health, alcohol and substance use/abuse, personality traits, relationships, and connection to self and spirituality. We found wide-ranging improvements 1-month post-treatment across these domains, and identified baseline traits which predict pre-to-post changes on primary outcome measures. Improvements were not diagnostic-specific, suggesting ayahuasca may be generally efficacious. Personality traits, body dissociation, and self-efficacy were strong predictors of therapeutic improvements, marking an important first step toward personalized, precision-based medicine. Randomized controlled trials are warranted to confirm and elaborate on these findings

The Microbe browser for comparative genomics

The Microbe browser is a web server providing comparative microbial genomics data. It offers comprehensive, integrated data from GenBank, RefSeq, UniProt, InterPro, Gene Ontology and the Orthologs Matrix Project (OMA) database, displayed along with gene predictions from five software packages. The Microbe browser is daily updated from the source databases and includes all completely sequenced bacterial and archaeal genomes. The data are displayed in an easy-to-use, interactive website based on Ensembl software. The Microbe browser is available at http://microbe.vital-it.ch/. Programmatic access is available through the OMA application programming interface (API) at http://microbe.vital-it.ch/api

Dual Effect of Methylprednsolone Pulses on Apoptosis of Peripheral Leukocytes in Patients with Renal Diseases

It is well known that change in apoptosis may modulate the natural story of illness, and that many drugs may act through modulation of apoptosis, but the role of steroids in acting through apoptosis in different settings, including renal diseases, has still to be elucidated. We studied the in vivo effects of steroids by oral assumption (10 to 25 mg/deltacortene) or by intravenous pulses (300 to 1000 mg/dose) on apoptosis and cellular subsets of peripheral lymphocytes, by evaluating DNA-fragmentation and lymphocyte subsets in 79 subjects: 22 controls and 57 patients with various renal diseases (25 Lupus-GN, 19 membranous-GN (MGN), 6 rapidly progressive-GN (RPGN), 2 acute interstitial nephritis (AIN), 5 on chronic dialysis. Baseline apoptosis was present in 1/22 (4.5%) of controls, 3/25 (12%) SLE, 2/6 (33.3%) RPGN and 10/19 (52.6%) MGN. A significant decrease in CD3+CD8+ cell count and a significant increase of the CD3+CD4/CD3+CD8+ ratio were found in apoptosis-positive subjects. DNA fragmentation did not change after oral steroids, paralleling a 22 to 32% decrease in total lymphocytes. Following intravenous methylprednisolone pulses, a deeper drop of all lymphocyte subsets was observed, while DNA fragmentation turned from present to absent in 2 MGN, but not in 2 RPGN, and from absent to present in 1 ARF and 1 SLE, independently of the dosage. We demonstrated that the presence of apoptosis in renal diseases is associated with decreased CD3+CD8+ cell count. Furthermore, steroid intravenous pulses, besides inducing a profound decrease in lymphocyte subsets, do exert a dual effect on baseline leukocyte apoptosis, eventually leading to a reversal of baseline patterns, either turning from negative to positive or from positive to negative. Oral steroid therapy did not influence baseline apoptosis

Prevention of Breast cancer with tamoxifen:preliminary findings from the italian randomised trial among hysterectomised women

Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study. Veronesi U, Maisonneuve P, Costa A, Sacchini V, Maltoni C, Robertson C, Rotmensz N, Boyle P. SourceEuropean Institute of Oncology, Milan, Italy. Abstract BACKGROUND: Tamoxifen is a candidate chemopreventive agent in breast cancer, although the drug may be associated with the development of endometrial cancer. Therefore we did a trial in hysterectomised women of tamoxifen as a chemopreventive. METHODS: In October, 1992, we started a double-blind placebo-controlled, randomised trial of tamoxifen in women (mainly in Italy) who did not have breast cancer and who had had a hysterectomy. Women were randomised to receive tamoxifen 20 mg per day or placebo, both orally for 5 years. The original plan was to follow the intervention phase by 5 years' follow-up. In June, 1997, the trialists and the data-monitoring committee decided to end recruitment primarily because of the number of women dropping out of the study. Recruitment ended on July 11, 1997, and the study will continue as planned. The primary endpoints are the occurrence of and deaths from breast cancer. This preliminary interim analysis is based on intention-to-treat. FINDINGS: 5408 women were randomised; participating women have a median follow-up of 46 months for major endpoints. 41 cases of breast cancer occurred so far; there have been no deaths from breast cancer. There is no difference in breast-cancer frequency between the placebo (22 cases) and tamoxifen (19) arms. There is a statistically significant reduction of breast cancer among women receiving tamoxifen who also used hormone-replacement therapy during the trial: among 390 women on such therapy and allocated to placebo, we found eight cases of breast cancer compared with one case among 362 women allocated to tamoxifen. Compared with the placebo group, there was a significantly increased risk of vascular events and hypertriglyceridaemia among women on tamoxifen. INTERPRETATION: Although this preliminary analysis has low power, in this cohort of women at low-to-normal risk of breast cancer, the postulated protective effects of tamoxifen are not yet apparent. Women using hormone-replacement therapy appear to have benefited from use of tamoxifen. There were no deaths from breast cancer recorded in women in the study. It is essential to continue follow-up to quantify the long-term risks and benefits of tamoxifen therapy

Colonoscopic findings in coeliac disease on a gluten-free diet

Background: to date, there are few data on colonoscopic findings in patients with celiac disease, and most of these obtained in patients with iron deficiency anaemia. Aims: we assessed colonoscopic findings in unselected pa tients with coeliac disease, since there are no studies available also considering morphological aspects, and there is literature sugges tion of increased prevalence of colorectal tumours. Material and methods: colonoscopies with multiple biopsies were retrospectively analyzed in 42 coeliac disease patients on gluten-free diet above age 40; 16 had clinical or laboratory fea tures of iron deficiency anaemia. Mucosal biopsies were evaluated for the presence of intraepithelial lymphocytes and of mucosal eosinophils, in addition to conventional histologic assessment, and compared with those obtained in 15 controls. Results: macroscopic abnormalities (polyps, diverticula, in flammatory changes) were found in 26% of patients. Microscopic abnormalities (lymphocytic colitis, melanosis coli, rectal histiocyto sis) were found in 36% of patients. None of these findings was found in controls. Coeliac disease patients had significantly higher eosinophil score than controls in the right colon, whereas this was not significantly different between groups in the left colon. Conclusions: colonoscopic findings in coeliac disease on gluten-free diet may reveal significant findings, even in patients without iron deficiency anaemia. There is the need of further stud ies in larger cohorts of patients to establish whether colonoscopy in these patients may be clinically useful

prevalence of igm and igg antibodies to west nile virus among blood donors in an affected area of north eastern italy summer 2009

Following reports of West Nile neuroinvasive disease in the north-eastern area of Italy in 2009, all blood donations dating from the period between 1 August and 31 October 2009 in the Rovigo province of the Veneto region were routinely checked to exclude those with a positive nucleic acid test for West Nile virus (WNV). Only one of 5,726 blood donations was positive (17.5 per 100,000 donations; 95% confidence interval (CI): 0.4-97.3). In addition, a selection of 2,507 blood donations collected during the period from 20 July to 15 November 2009 were screened by ELISA for IgG and IgM antibodies against WNV. A positive result was received for 94 of them. The positive sera were further evaluated using immunofluorescence and plaque reduction neutralisation test (PRNT), in which only 17 sera were confirmed positive. This corresponds to a prevalence of 6.8 per 1,000 sera (95% CI: 4.0-10.9). In a case-control study that matched each of the 17 PRNT-positive sera with four negative sera with the same date of donation and same donation centre, we did not find a significant association with age and sex of the donor; donors who worked mainly outdoors were significantly more at risk to have a positive PRNT for WNV

HPV sensitizes OPSCC cells to cisplatin-induced apoptosis by inhibiting autophagy through E7-mediated degradation of AMBRA1

Oropharyngeal squamous cell carcinoma (OPSCC) is an increasing world health problem with a more favorable prognosis for patients with human papillomavirus (HPV)-positive tumors compared to those with HPV-negative OPSCC. How HPV confers a less aggressive phenotype, however, remains undefined. We demonstrated that HPV-positive OPSCC cells display reduced macroautophagy/autophagy activity, mediated by the ability of HPV-E7 to interact with AMBRA1, to compete with its binding to BECN1 and to trigger its calpain-dependent degradation. Moreover, we have shown that AMBRA1 downregulation and pharmacological inhibition of autophagy sensitized HPV-negative OPSCC cells to the cytotoxic effects of cisplatin. Importantly, semi-quantitative immunohistochemical analysis in primary OPSCCs confirmed that AMBRA1 expression is reduced in HPV-positive compared to HPV-negative tumors. Collectively, these data identify AMBRA1 as a key target of HPV to impair autophagy and propose the targeting of autophagy as a viable therapeutic strategy to improve treatment response of HPV-negative OPSCC. Abbreviations: AMBRA1: autophagy and beclin 1 regulator 1; CDDP: cisplatin (CDDP); FFPE: formalin-fixed paraffin-embedded (FFPE); HNC: head and neck cancers (HNC); HPV: human papillomavirus (HPV); hrHPV: high risk human papillomavirus (hrHPV); OCSCC: oral cavity squamous carcinomas (OCSSC); OPSCC: oropharyngeal squamous cell carcinoma (OPSCC); OS: overall survival (OS); qPCR: quantitative polymerase chain reaction; RB1: RB transcriptional corepressor 1; ROC: receiver operating characteristic curve (ROC)

Homochirality and the need of energy

The mechanisms for explaining how a stable asymmetric chemical system can be formed from a symmetric chemical system, in the absence of any asymmetric influence other than statistical fluctuations, have been developed during the last decades, focusing on the non-linear kinetic aspects. Besides the absolute necessity of self-amplification processes, the importance of energetic aspects is often underestimated. Going down to the most fundamental aspects, the distinction between a single object -- that can be intrinsically asymmetric -- and a collection of objects -- whose racemic state is the more stable one -- must be emphasized. A system of strongly interacting objects can be described as one single object retaining its individuality and a single asymmetry; weakly or non-interacting objects keep their own individuality, and are prone to racemize towards the equilibrium state. In the presence of energy fluxes, systems can be maintained in an asymmetric non-equilibrium steady-state. Such dynamical systems can retain their asymmetry for times longer than their racemization time.Comment: 8 pages, 7 figures, submitted to Origins of Life and Evolution of Biosphere

Effects of antenatal betamethasone on preterm human and mouse ductus arteriosus: comparison with baboon data.

BackgroundAlthough studies involving preterm infants ≤34 weeks gestation report a decreased incidence of patent ductus arteriosus after antenatal betamethasone, studies involving younger gestation infants report conflicting results.MethodsWe used preterm baboons, mice, and humans (≤276/7 weeks gestation) to examine betamethasone's effects on ductus gene expression and constriction both in vitro and in vivo.ResultsIn mice, betamethasone increased the sensitivity of the premature ductus to the contractile effects of oxygen without altering the effects of other contractile or vasodilatory stimuli. Betamethasone's effects on oxygen sensitivity could be eliminated by inhibiting endogenous prostaglandin/nitric oxide signaling. In mice and baboons, betamethasone increased the expression of several developmentally regulated genes that mediate oxygen-induced constriction (K+ channels) and inhibit vasodilator signaling (phosphodiesterases). In human infants, betamethasone increased the rate of ductus constriction at all gestational ages. However, in infants born ≤256/7 weeks gestation, betamethasone's contractile effects were only apparent when prostaglandin signaling was inhibited, whereas at 26-27 weeks gestation, betamethasone's contractile effects were apparent even in the absence of prostaglandin inhibitors.ConclusionsWe speculate that betamethasone's contractile effects may be mediated through genes that are developmentally regulated. This could explain why betamethasone's effects vary according to the infant's developmental age at birth