The atrioventricular canal (AVC) physically separates the atrial and ventricular chambers of the heart and plays a crucial role in the development of the valves and septa. Defects in AVC development ...result in aberrant heart morphogenesis and are a significant cause of congenital heart malformations. We have used a forward genetic screen in zebrafish to identify novel regulators of cardiac morphogenesis. We isolated a mutant, named wickham (wkm), that was indistinguishable from siblings at the linear heart tube stage but exhibited a specific loss of cardiac looping at later developmental stages. Positional cloning revealed that the wkm locus encodes transmembrane protein 2 (Tmem2), a single-pass transmembrane protein of previously unknown function. Expression analysis demonstrated myocardial and endocardial expression of tmem2 in zebrafish and conserved expression in the endocardium of mouse embryos. Detailed phenotypic analysis of the wkm mutant identified an expansion of expression of known myocardial and endocardial AVC markers, including bmp4 and has2. By contrast, a reduction in the expression of spp1, a marker of the maturing valvular primordia, was observed, suggesting that an expansion of immature AVC is detrimental to later valve maturation. Finally, we show that immature AVC expansion in wkm mutants is rescued by depleting Bmp4, indicating that Tmem2 restricts bmp4 expression to delimit the AVC primordium during cardiac development.
Investigations of mood and workload in health care settings have focussed primarily on nurses and junior doctors. Given the critical shortfall in the Australian midwifery workforce, and the ...specialised nature of midwifery as an occupation, it is important to understand how mood and workload are experienced by midwives. Twenty midwives (18F, 2M) in an Australian metropolitan hospital completed logbooks assessing daily fluctuations in subjective mood and workload. Participants also provided information about history of psychopathology and sleep quality. Results revealed that midwives were relatively stable in terms of mood but did experience increased fear and decreased happiness when at work. Further, workload factors significantly predicted mood at work. Specifically, when participants felt that their work was more demanding and frustrating and required more effort, or when they felt that they could not accomplish all that was expected, mood was negatively influenced. This supports the connection between workload and negative mood change in healthcare. Given the potential for mood to influence a multitude of functions relevant to safety, performance and psychosocial wellbeing it is important to understand the factors which influence mood, particularly in light of the current shortfall in the Australian healthcare workforce.
For the past 9 years, we experimentally flooded a wetland complex (peatland surrounding an open water pond) at the Experimental Lakes Area (ELA), northwestern Ontario, Canada, to examine the ...biogeochemical cycling of methyl mercury (MeHg) in reservoirs. Using input−output budgets, we found that prior to flooding, the wetland complex was a net source of approximately 1.7 mg MeHg ha-1 yr-1 to downstream ecosystems. In the first year of flooding, net yields of MeHg from the reservoir increased 40-fold to approximately 70 mg MeHg ha-1 yr-1. Subsequently, annual net yields of MeHg from the reservoir declined (10−50 mg MeHg ha-1 yr-1) but have remained well above natural levels. The magnitude and timing of Hg methylation in the flooded peat portion of the wetland reservoir were very different than in the open water region of the reservoir. In terms of magnitude, net Hg methylation rates in the peat in the first 2 years of flooding were 2700 mg ha-1 yr-1, constituting over 97% of the MeHg produced at the whole-ecosystem level. But in the following 3 years, there was a large decrease in the mass of MeHg in the flooded peat due to microbial demethylation. In contrast, concentrations of MeHg in the open water region and in zooplankton, and body burdens of Hg in cyprinid fish, remained high for the full 9 years of this study. Microbial activity in the open water region also remained high, as evidenced by continued high concentrations of dissolved CO2 and CH4. Thus, the large short-term accumulation of MeHg mass in the peat appeared to have only a small influence on concentrations of MeHg in the biota; rather MeHg accumulation in biota was sustained by the comparatively small ongoing net methylation of Hg in the flooded pond where microbial activity remained high. In large reservoirs, where the effects of wind and fetch are greater than in the small experimental reservoir we constructed, differences can occur in the timing and extent of peat and soil erosion, effecting either transport of MeHg to the food chain or the fueling of microbial activity in open water sediments, both of which could have important long-term implications for MeHg concentrations in predatory fish.
Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden ...coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 corrected families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Using a novel trait-based measure, we examined genetic variants associated with obsessive-compulsive (OC) traits and tested whether OC traits and obsessive-compulsive disorder (OCD) shared genetic ...risk. We conducted a genome-wide association analysis (GWAS) of OC traits using the Toronto Obsessive-Compulsive Scale (TOCS) in 5018 unrelated Caucasian children and adolescents from the community (Spit for Science sample). We tested the hypothesis that genetic variants associated with OC traits from the community would be associated with clinical OCD using a meta-analysis of all currently available OCD cases. Shared genetic risk was examined between OC traits and OCD in the respective samples using polygenic risk score and genetic correlation analyses. A locus tagged by rs7856850 in an intron of PTPRD (protein tyrosine phosphatase δ) was significantly associated with OC traits at the genome-wide significance level (p = 2.48 × 10
). rs7856850 was also associated with OCD in a meta-analysis of OCD case/control genome-wide datasets (p = 0.0069). The direction of effect was the same as in the community sample. Polygenic risk scores from OC traits were significantly associated with OCD in case/control datasets and vice versa (p's < 0.01). OC traits were highly, but not significantly, genetically correlated with OCD (r
= 0.71, p = 0.062). We report the first validated genome-wide significant variant for OC traits in PTPRD, downstream of the most significant locus in a previous OCD GWAS. OC traits measured in the community sample shared genetic risk with OCD case/control status. Our results demonstrate the feasibility and power of using trait-based approaches in community samples for genetic discovery.
To describe sleep, stress and compensatory behaviors in nurses and midwives.
The study included 41 midwives and 21 nurses working in Australian hospitals between 2005 and 2009. Participation was ...voluntary. All participants recorded on a daily basis their work and sleep hours, levels of stress and exhaustion, caffeine intake and use of sleep aids for a month (1,736 days, 1,002 work shifts).
Participants reported moderate to high levels of stress and exhaustion on 20-40% of work days; experienced sleep disruption on more than 50% of work days; struggled to remain awake on 27% of work days; and suffered extreme drowsiness or experienced a near accident while travelling home on 9% of workdays. Age, perceived sleep duration and work hours were significant predictors of caffeine intake. About 60% of participants reported using sleep aids (about 20% reported taking prescription medications and 44% of nurses and 9% of midwives reported alcohol use as a sleep aid at least once during the study). Stress and workdays were significant predictors of sedative use. Overall, 22% reported being indifferent or mildly dissatisfied with their job.
Sleep problems, high levels of stress and exhaustion and low job satisfaction are prevalent among nurses and midwives. The use of alcohol and sleeping pills as sleep aids, and the use of caffeine to help maintain alertness is also common. Nurses and midwives may use caffeine to compensate for reduced sleep, especially on workdays, and sleeping pills to cope with their daily work-related stress.
Background: In 1982, the National Surgical Adjuvant Breast and Bowel Project initiated a randomized, double-blinded, placebo-controlled trial (B-14) to determine the effectiveness of adjuvant ...tamoxifen therapy in patients with primary operable breast cancer who had estrogen receptor-positive tumors and no axillary lymph node involvement. The findings indicated that tamoxifen therapy provided substantial benefit to patients with early stage disease. However, questions arose about how long the observed benefit would persist, about the duration of therapy necessary to maintain maximum benefit, and about the nature and severity of adverse effects from prolonged treatment Purpose: We evaluated the outcome of patients in the B-14 trial through 10 years of follow-up. In addition, the effects of 5 years versus more than 5 years of tamoxifen therapy were compared. Methods: In the trial, patients were initially assigned to receive either tamoxifen at 20 mg/day (n = 1404) or placebo (n = 1414). Tamoxifen-treated patients who remained disease free after 5 years of therapy were then reassigned to receive either another 5 years of tamoxifen (n = 322) or 5 years of placebo (n = 321). After the study began, another group of patients who met the same protocol eligibility requirements as the randomly assigned patients were registered to receive tamoxifen (n = 1211). Registered patients who were disease free after 5 years of treatment were also randomly assigned to another 5 years of tamoxifen (n = 261) or to 5 years of placebo (n = 249). To compare 5 years with more than 5 years of tamoxifen therapy, data relating to all patients reassigned to an additional 5 years of the drug were combined. Patients who were not reassigned to either tamoxifen or placebo continued to be followed in the study. Survival, disease-free survival, and distant disease-free survival (relating to failure at distant sites) were estimated by use of the Kaplan-Meier method; differences between the treatment groups were assessed by use of the logrank test. The relative risks of failure (with 95% confidence intervals CIs) were determined by use of the Cox proportional hazards model. Reported P values are two-sided. Results: Through 10 years of follow-up, a significant advantage in disease-free survival (69% versus 57%, P<.0001; relative risk = 0.66; 95% CI = 0.58–0.74), distant diseasefree survival (76% versus 67%, P<.0001; relative risk = 0.70; 95% CI = 0.61-0.81), and survival (80% versus 76%, P = .02; relative risk = 0.84; 95% CI = 0.71–0.99) was found for patients in the group first assigned to receive tamoxifen. The survival benefit extended to those 49 years of age or younger and to those 50 years of age or older. Tamoxifen therapy was associated with a 37% reduction in the incidence of contralateral (opposite) breast cancer (P =.007). Through 4 years after the reassignment of tamoxifentreated patients to either continued-therapy or placebo groups, advantages in disease-free survival (92% versus 86%, P =.003) and distant disease-free survival (96% versus 90%, P = .01) were found for those who discontinued tamoxifen treatment. Survival was 96% for those who discontinued tamoxifen compared with 94% for those who continued tamoxifen treatment (P = .08). A higher incidence of thromboembolic events was seen in tamoxifen-treated patients (through 5 years, 1.7% versus 0.4%). Except for endometrial cancer, the incidence of second cancers was not increased with tamoxifen therapy. Conclusions and Implications: The benefit from 5 years of tamoxifen therapy persists through 10 years of follow-up. No additional advantage is obtained from continuing tamoxifen therapy for more than 5 years. J Natl Cancer Inst 1996; 88:1529–42
The Journal of Physiology Annual Report 2011–12 Paterson, David J.; Huxley, Carol
The Journal of physiology,
February 2012, 2012-Feb-01, 2012-02-00, 20120201, Letnik:
590, Številka:
3
Journal Article
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