Stochastic Model of Supercoiling-Dependent Transcription.

We propose a stochastic model for gene transcription coupled to DNA supercoiling, where we incorporate the experimental observation that polymerases create supercoiling as they unwind the DNA helix and that these enzymes bind more favorably to regions where the genome is unwound. Within this model, we show that when the transcriptionally induced flux of supercoiling increases, there is a sharp crossover from a regime where torsional stresses relax quickly and gene transcription is random, to one where gene expression is highly correlated and tightly regulated by supercoiling. In the latter regime, the model displays transcriptional bursts, waves of supercoiling, and up regulation of divergent or bidirectional genes.

Infant mortality at term in Canada: Impact of week of gestation.

Objectives: Infants born at term have low mortality, but risk may vary from week to week. We determined the risk of infant mortality at term by gestational week and cause.

Methods: We analyzed 4.

Improving outcomes in adults with epilepsy and intellectual disability (EpAID) using a nurse-led intervention: study protocol for a cluster randomised controlled trial.

Background: In adults with intellectual disability (ID) and epilepsy there are suggestions that improvements in management may follow introduction of epilepsy nurse-led care. However, this has not been tested in a definitive clinical trial and results cannot be generalised from general population studies as epilepsy tends to be more severe and to involve additional clinical comorbidities in adults with ID. This trial investigates whether nurses with expertise in epilepsy and ID, working proactively to a clinically defined role, can improve clinical and quality of life outcomes in the management of epilepsy within this population, compared to treatment as usual.

Histidine switch controlling pH-dependent protein folding and DNA binding in a transcription factor at the core of synthetic network devices.

Therapeutic strategies have been reported that depend on synthetic network devices in which a urate-sensing transcriptional regulator detects pathological levels of urate and triggers production or release of urate oxidase. The transcription factor involved, HucR, is a member of the multiple antibiotic resistance (MarR) protein family. We show that protonation of stacked histidine residues at the pivot point of long helices that form the scaffold of the dimer interface leads to reversible formation of a molten globule state and significantly attenuated DNA binding at physiological temperatures.

How Do Evaluators Differentiate Successful From Less-Than-Successful Experiences With Collaborative Approaches to Evaluation?

Objectives: In this exploratory study, we wanted to know how evaluators differentiate collaborative approaches to evaluation (CAE) perceived to be successful from those perceived to be less-than-successful.

Method: In an online questionnaire survey, we obtained 320 responses from evaluators who practice CAE (i.e.

Are white storks addicted to junk food? Impacts of landfill use on the movement and behaviour of resident white storks (Ciconia ciconia) from a partially migratory population.

Background: The migratory patterns of animals are changing in response to global environmental change with many species forming resident populations in areas where they were once migratory. The white stork (Ciconia ciconia) was wholly migratory in Europe but recently guaranteed, year-round food from landfill sites has facilitated the establishment of resident populations in Iberia. In this study 17 resident white storks were fitted with GPS/GSM data loggers (including accelerometer) and tracked for 9.

Estimates and determinants of HPV non-vaccination and vaccine refusal in girls 12 to 14 y of age in Canada: Results from the Childhood National Immunization Coverage Survey, 2013.

Since the introduction of HPV vaccination programs in Canada in 2007, coverage has been below public health goals in many provinces and territories. This analysis investigated the determinants of HPV non-vaccination and vaccine refusal. Data from the Childhood National Immunization Coverage Survey (CNICS) 2013 were used to estimate the prevalence of HPV non-vaccination and parental vaccine refusal in girls aged 12-14 years, for Canada and the provinces and territories.

Cellular Localization of Engineered Human LINE-1 RNA and Proteins.

The human LINE-1 retrotransposon has the ability to mobilize into a new genomic location through an intracellular replication cycle. Immunofluorescence and in situ hybridization experiments have been developed to detect subcellular localization of retrotransposition intermediates (i.e.

Seroconversion for cytomegalovirus infection in a cohort of pregnant women in Québec, 2010-2013.

Cytomegalovirus (CMV) is the leading cause of congenital infection and non-genetic sensorineural hearing loss in children. There are no recent data on the incidence of CMV infection during pregnancy in Canada. This present study was undertaken to determine the seroprevalence of CMV IgG antibodies and the rate of seroconversion in a cohort of pregnant women in the province of Québec, Canada.

A simple method to overcome the inhibitory effect of heparin on DNA amplification.

Background: Genetic material from large patient cohorts is increasingly central to translational genetic research. However, patient blood samples are a finite resource and their supply and storage are often dictated by clinical and not research protocols. Our experience supports difficulty in amplifying DNA from blood stored in herparin; a scenario that other researchers may have or will encounter.

Profiling DNA supercoiling domains in vivo.

Transitions in DNA structure have the capacity to regulate genes, but have been poorly characterised in eukaryotes due to a lack of appropriate techniques. One important example is DNA supercoiling, which can directly regulate transcription initiation, elongation and coordinated expression of neighbouring genes. DNA supercoiling is the over- or under-winding of the DNA double helix, which occurs as a consequence of polymerase activity and is modulated by topoisomerase activity [5].

Nuclear FAK controls chemokine transcription, Tregs, and evasion of anti-tumor immunity.

Focal adhesion kinase (FAK) promotes anti-tumor immune evasion. Specifically, the kinase activity of nuclear-targeted FAK in squamous cell carcinoma (SCC) cells drives exhaustion of CD8(+) T cells and recruitment of regulatory T cells (Tregs) in the tumor microenvironment by regulating chemokine/cytokine and ligand-receptor networks, including via transcription of Ccl5, which is crucial. These changes inhibit antigen-primed cytotoxic CD8(+) T cell activity, permitting growth of FAK-expressing tumors.

[Treatment of arterial hypertension in children and adolescents--Update of therapeutic options].

Changing living conditions, which lead to physical inactivity and obesity, are probably the main reason for the establishment of risk factors for cardiovascular diseases in children and adolescents. In the past those risk factors were typically seen only in the elderly. On long-term, the elevated body-mass-index is a very important risk factor for primary arterial hypertension in children and adolescents, because it is responsible for both structural and functional changes in the cardiovascular system.

Differences in perinatal and infant mortality in high-income countries: artifacts of birth registration or evidence of true differences?

Background: Variation in birth registration criteria may compromise international comparisons of fetal and infant mortality. We examined the effect of birth registration practices on fetal and infant mortality rates to determine whether observed differences in perinatal and infant mortality rates were artifacts of birth registration or reflected true differences in health status.

Methods: A retrospective population-based cohort study was done using data from Canada, United States, Denmark, Finland, Iceland, Norway, and Sweden from 1995-2005.

Characterisation of osteoprotegerin autoantibodies in coeliac disease.

Autoantibodies neutralising the effect of the bone regulatory cytokine osteoprotegerin (OPG) have been described in a patient with severe osteoporosis and coeliac disease. This study aimed to determine the prevalence and epitope specificity of autoantibodies to OPG in patients with coeliac disease, and correlate their presence with bone mineral density. A direct enzyme-linked immunosorbent assay was developed and used to screen patients with coeliac disease for autoantibodies to OPG.

Associations of Pregnancy Outcomes and PM2.5 in a National Canadian Study.

Background: Numerous studies have examined associations between air pollution and pregnancy outcomes, but most have been restricted to urban populations living near monitors.

Objectives: We examined the association between pregnancy outcomes and fine particulate matter in a large national study including urban and rural areas.

Methods: Analyses were based on approximately 3 million singleton live births in Canada between 1999 and 2008.

Smoking cessation during pregnancy and relapse after childbirth in Canada.

Objective: This analysis was undertaken to determine the rates and determinants of smoking cessation during pregnancy and smoking relapse after childbirth in Canada.

Methods: We used data from the Maternity Experiences Survey, a cross-sectional study of mothers who gave birth to a singleton baby in Canada in 2006. A total of 1586 mothers who smoked occasionally or daily before pregnancy were included in the analysis.

U6 snRNA Pseudogenes: Markers of Retrotransposition Dynamics in Mammals.

Transposable elements comprise more than 45% of the human genome and long interspersed nuclear element 1 (LINE-1 or L1) is the only autonomous mobile element remaining active. Since its identification, it has been proposed that L1 contributes to the mobilization and amplification of other cellular RNAs and more recently, experimental demonstrations of this function has been described for many transcripts such as Alu, a nonautonomous mobile element, cellular mRNAs, or small noncoding RNAs. Detailed examination of the mobilization of various cellular RNAs revealed distinct pathways by which they could be recruited during retrotransposition; template choice or template switching.

Stillbirth and infant mortality in Aboriginal communities in Quebec.

Background: Infant mortality and stillbirth rates among Aboriginal people are higher than in the rest of Canada, but little is known on the perinatal health status of First Nations people living on reserves. This study examines stillbirth and infant mortality rates among Aboriginal people in Quebec, notably, First Nations people living on reserves, and compares these rates with those of the province's non-Aboriginal population.

Data And Methods: Data on live births and stillbirths in Quebec from 1989 to 2008 were extracted from Statistics Canada's Infant Birth-Death Linked File.