Cdk9 and H2Bub1 signal to Clr6-CII/Rpd3S to suppress aberrant antisense transcription

Mono-ubiquitylation of histone H2B (H2Bub1) and phosphorylation of elongation factor Spt5 by cyclin-dependent kinase 9 (Cdk9) occur during transcription by RNA polymerase II (RNAPII), and are mutually dependent in fission yeast. It remained unclear whether Cdk9 and H2Bub1 cooperate to regulate the expression of individual genes. Here, we show that Cdk9 inhibition or H2Bub1 loss induces intragenic antisense transcription of ∼10% of fission yeast genes, with each perturbation affecting largely distinct subsets; ablation of both pathways de-represses antisense transcription of over half the genome. H2Bub1 and phospho-Spt5 have similar genome-wide distributions; both modifications are enriched, and directly proportional to each other, in coding regions, and decrease abruptly around the cleavage and polyadenylation signal (CPS). Cdk9-dependence of antisense suppression at specific genes correlates with high H2Bub1 occupancy, and with promoter-proximal RNAPII pausing. Genetic interactions link Cdk9, H2Bub1 and the histone deacetylase Clr6-CII, while combined Cdk9 inhibition and H2Bub1 loss impair Clr6-CII recruitment to chromatin and lead to decreased occupancy and increased acetylation of histones within gene coding regions. These results uncover novel interactions between co-transcriptional histone modification pathways, which link regulation of RNAPII transcription elongation to suppression of aberrant initiation

Transient Changes in Bacterioplankton Communities Induced by the Submarine Volcanic Eruption of El Hierro (Canary Islands)

Postprint4,411

Development and Implementation of a Registry of Patients Attending Multidisciplinary Pain Treatment Clinics: The Quebec Pain Registry

The Quebec Pain Registry (QPR) is a large research database of patients suffering from various chronic pain (CP) syndromes who were referred to one of five tertiary care centres in the province of Quebec (Canada). Patients were monitored using common demographics, identical clinical descriptors, and uniform validated outcomes. This paper describes the development, implementation, and research potential of the QPR. Between 2008 and 2013, 6902 patients were enrolled in the QPR, and data were collected prior to their first visit at the pain clinic and six months later. More than 90% of them (mean age ± SD: 52.76 ± 4.60, females: 59.1%) consented that their QPR data be used for research purposes. The results suggest that, compared to patients with serious chronic medical disorders, CP patients referred to tertiary care clinics are more severely impaired in multiple domains including emotional and physical functioning. The QPR is also a powerful and comprehensive tool for conducting research in a “real-world” context with 27 observational studies and satellite research projects which have been completed or are underway. It contains data on the clinical evolution of thousands of patients and provides the opportunity of answering important research questions on various aspects of CP (or specific pain syndromes) and its management

Amyloid and tau pathology associations with personality traits, neuropsychiatric symptoms, and cognitive lifestyle in the preclinical phases of sporadic and autosomal dominant Alzheimer’s disease

Background Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression

Modulation of vascular reactivity by perivascular adipose tissue (PVAT)

Purpose of Review: In this review we discuss the role of perivascular adipose tissue (PVAT) in the modulation of vascular contractility and arterial pressure, focusing on the role of the renin-angiotensin-aldosterone system and oxidative stress/inflammation. Recent Findings: PVAT possesses an relevant endocrine-paracrine activity, which may be altered in several pathophysiological and clinical conditions. During the last two decades it has been shown PVAT may modulate vascular reactivity. It has also been previously demonstrated that inflammation in adipose tissue may be implicated in vascular dysfunction. In particular, adipocytes secrete a number of adipokines with various functions, as well as several vasoactive factors, together with components of the renin-angiotensin system which may act at local or at systemic level. It has been shown that the anticontractile effect of PVAT is lost in obesity, probably as a consequence of the development of adipocyte hypertrophy, inflammation, and oxidative stress. Summary: Adipose tissue dysfunction is interrelated with inflammation and oxidative stress, thus contributing to endothelial dysfunction observed in several pathological and clinical conditions such as obesity and hypertension. Decreased local adiponectin level, macrophage recruitment and infiltration, and activation of renin-angiotensin-aldosterone system could play an important role in this regards

Description of convective-scale numerical weather simulation use in a flight simulator within the Flysafe project

FLYSAFE is an Integrated Project of the 6th framework of the European Commission aiming at improving flight safety through the development of a Next Generation Integrated Surveillance System (NGISS). The NGISS will provide information to the pilot on a number of external hazards, with particular emphasis on weather, air traffic and terrain. One of its advantage will be the capability of displaying data about all three hazards on a single screen, facilitating rapid pilot assessment of the situation. In order to improve the accuracy of warnings provided to aircraft in flight, specialised tools for generating nowcasts of atmospheric hazards are under development: the Weather Information Management Systems (WIMSs). Four types of WIMSs feeding the NG-ISS were defined, each addressing one hazard: clear air turbulence, thunderstorms (CB), icing (ICE), and wake vortices. These products are generated by on-ground systems from observations and model forecasts. To evaluate the impact of these new kind of information during realistic in-flight conditions, as well as to test the NG-ISS abilities, severe weather high resolution simulations were performed. Meteorological synthetic outputs feed the WIMS, and a flight simulator including the NG-ISS. We focus here on synthetic ICE and CB WIMS diagnosed from two heavy precipitating events simulations in the vicinity of airports. The first one is a deep convection situation over the Paris Charles de Gaulle airport, on the 23rd of June, 2005. The second occurred on the 20th of September, 1999 during the Mesoscale Alpine Program (MAP-IOP2B) near the Innsbruck airport. These two simulated events will be discussed, as well as weather hazards provided by ICE and CB WIMSs

Sensitivity to Pain Traumatization Scale: development, validation, and preliminary findings

Joel Katz,1,2 Samantha R Fashler,1 Claire Wicks,1 M Gabrielle Pagé,3 Kaley M Roosen,1 Valery Kleiman,1 Hance Clarke2 1Department of Psychology, York University, 2Department of Anesthesia and Pain Management, Toronto General Hospital, Toronto, ON, 3Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC, Canada Background: This article reports three studies describing the development and validation of the 12-item Sensitivity to Pain Traumatization Scale (SPTS-12). SPT refers to the anxiety-related cognitive, emotional, and behavioral reactions to pain that resemble the features of a traumatic stress reaction.Methods: In Study 1, a preliminary set of 79 items was administered to 116 participants. The data were analyzed by using combined nonparametric and parametric item response theory resulting in a 12-item scale with a one-factor structure and good preliminary psychometric properties. Studies 2 and 3 assessed the factor structure and psychometric properties of the SPTS-12 in a community sample of 823 participants (268 with chronic pain and 555 pain-free) and a clinical sample of 345 patients (126 with chronic post-surgical pain, 92 with other nonsurgical chronic pain, and 127 with no chronic pain) at least 6 months after undergoing coronary artery bypass graft surgery, respectively. Results: The final SPTS-12 derived from Study 1 comprised 12 items that discriminated between individuals with different levels of SPT, with the overall scale showing good to very good reliability and validity. The results from Studies 2 and 3 revealed a one-factor structure for chronic pain and pain-free samples, excellent reliability and concurrent validity, and moderate convergent and discriminant validity. Conclusion: The results of the three studies provide preliminary evidence for the validity and reliability of the SPTS-12. Keywords: chronic pain, chronic post-surgical pain, trauma, psychology, scale development, measurement, item response theory analysis, factor analysi

FLYSAFE – Severe weather simulations to evaluate new warnings of meteorological hazards

FLYSAFE is an Integrated Project of the 6th framework of the European Commission aiming at improving flight safety through the development of a Next Generation Integrated Surveillance System (NGISS). The NGISS will provide information to the pilot on a number of external hazards, with particular emphasis on weather, air traffic and terrain. One of its advantage will be the capability of displaying data about all three hazards on a single screen, facilitating rapid pilot assessment of the situation. In order to improve the accuracy of warnings provided to aircraft in flight, specialised tools for generating nowcasts of atmospheric hazards are under development: the Weather Information Management Systems (WIMSs). Four types of WIMSs feeding the NG-ISS were defined, each addressing one hazard: clear air turbulence, thunderstorms (CB), icing (ICE), and wake vortices. These products are generated by on-ground systems from observations and model forecasts. To evaluate the impact of these new kind of information during realistic in-flight conditions, as well as to test the NG-ISS abilities, severe weather high resolution simulations were performed. Meteorological synthetic outputs feed the WIMS, and a flight simulator including the NG-ISS. We focus here on synthetic ICE and CB WIMS diagnosed from two heavy precipitating events simulations in the vicinity of airports. The first one is a deep convection situation over the Paris Charles de Gaulle airport, on the 23rd of June, 2005. The second occurred on the 20th of September, 1999 during the Mesoscale Alpine Program (MAP-IOP2B) near the Innsbruck airport. These two simulated events will be discussed, as well as weather hazards provided by ICE and CB WIMSs