Methylation status of oestrogen receptor-α gene promoter sequences in human ovarian epithelial cell lines

We have determined the methylation status of the CpG island of the oestrogen receptor α gene in seven human ovarian cell lines. Cell lines expressing oestrogen receptor α showed no evidence of hypermethylation. In three of four cell lines that produced no detectable oestrogen receptor α protein, hypermethylation was observed at the NotI site of the CpG island. These results indicate that aberrant hypermethylation may be responsible for a significant proportion of epithelial ovarian tumours in which oestrogen receptor α expression is lost

Is primary care a neglected piece of the jigsaw in ensuring optimal stroke care? Results of a national study

<p>Abstract</p> <p>Background</p> <p>Stroke is a major cause of mortality and morbidity with potential for improved care and prevention through general practice. A national survey was undertaken to determine current resources and needs for optimal stroke prevention and care.</p> <p>Methods</p> <p>Postal survey of random sample of general practitioners undertaken (N = 204; 46% response). Topics included practice organisation, primary prevention, acute management, secondary prevention, long-term care and rehabilitation.</p> <p>Results</p> <p>Service organisation for both primary and secondary prevention was poor. Home management of acute stroke patients was used at some stage by 50% of responders, accounting for 7.3% of all stroke patients. Being in a structured cardiovascular management scheme, a training practice, a larger practice, or a practice employing a practice nurse were associated with structures and processes likely to support stroke prevention and care.</p> <p>Conclusion</p> <p>General practices were not fulfilling their potential to provide stroke prevention and long-term management. Systems of structured stroke management in general practice are essential to comprehensive national programmes of stroke care.</p

Phylogenetic Detection of Recombination with a Bayesian Prior on the Distance between Trees

Genomic regions participating in recombination events may support distinct topologies, and phylogenetic analyses should incorporate this heterogeneity. Existing phylogenetic methods for recombination detection are challenged by the enormous number of possible topologies, even for a moderate number of taxa. If, however, the detection analysis is conducted independently between each putative recombinant sequence and a set of reference parentals, potential recombinations between the recombinants are neglected. In this context, a recombination hotspot can be inferred in phylogenetic analyses if we observe several consecutive breakpoints. We developed a distance measure between unrooted topologies that closely resembles the number of recombinations. By introducing a prior distribution on these recombination distances, a Bayesian hierarchical model was devised to detect phylogenetic inconsistencies occurring due to recombinations. This model relaxes the assumption of known parental sequences, still common in HIV analysis, allowing the entire dataset to be analyzed at once. On simulated datasets with up to 16 taxa, our method correctly detected recombination breakpoints and the number of recombination events for each breakpoint. The procedure is robust to rate and transition∶transversion heterogeneities for simulations with and without recombination. This recombination distance is related to recombination hotspots. Applying this procedure to a genomic HIV-1 dataset, we found evidence for hotspots and de novo recombination

Mild hypothermia delays the development of stone heart from untreated sustained ventricular fibrillation - a cardiovascular magnetic resonance study

<p>Abstract</p> <p>Background</p> <p>'Stone heart' resulting from ischemic contracture of the myocardium, precludes successful resuscitation from ventricular fibrillation (VF). We hypothesized that mild hypothermia might slow the progression to stone heart.</p> <p>Methods</p> <p>Fourteen swine (27 ± 1 kg) were randomized to normothermia (group I; n = 6) or hypothermia groups (group II; n = 8). Mild hypothermia (34 ± 2°C) was induced with ice packs prior to VF induction. The LV and right ventricular (RV) cross-sectional areas were followed by cardiovascular magnetic resonance until the development of stone heart. A commercial 1.5T GE Signa NV-CV/i scanner was used. Complete anatomic coverage of the heart was acquired using a steady-state free precession (SSFP) pulse sequence gated at baseline prior to VF onset. Un-gated SSFP images were obtained serially after VF induction. The ventricular endocardium was manually traced and LV and RV volumes were calculated at each time point.</p> <p>Results</p> <p>In group I, the LV was dilated compared to baseline at 5 minutes after VF and this remained for 20 minutes. Stone heart, arbitrarily defined as LV volume <1/3 of baseline at the onset of VF, occurred at 29 ± 3 minutes. In group II, there was less early dilation of the LV (p < 0.05) and the development of stone heart was delayed to 52 ± 4 minutes after onset of VF (P < 0.001).</p> <p>Conclusions</p> <p>In this closed-chest swine model of prolonged untreated VF, hypothermia reduced the early LV dilatation and importantly, delayed the onset of stone heart thereby extending a known, morphologic limit of resuscitability.</p

Cross-sectional validation of the Aging Perceptions Questionnaire: a multidimensional instrument for assessing self-perceptions of aging

<p>Abstract</p> <p>Background</p> <p>Self-perceptions of aging have been implicated as independent predictors of functional disability and mortality in older adults. In spite of this, research on self-perceptions of aging is limited. One reason for this is the absence of adequate measures. Specifically, there is a need to develop a measure that is theoretically-derived, has good psychometric properties, and is multidimensional in nature. The present research seeks to address this need by adopting the Self-Regulation Model as a framework and using it to develop a comprehensive, multi-dimensional instrument for assessing self-perceptions of aging. This study describes the validation of this newly-developed instrument, the Aging Perceptions Questionnaire (APQ).</p> <p>Methods</p> <p>Participants were 2,033 randomly selected community-dwelling older (+65 yrs) Irish adults who completed the APQ alongside measures of physical and psychological health. The APQ assesses self-perceptions of aging along eight distinct domains or subscales; seven of these examine views about own aging, these are: timeline chronic, timeline cyclical, consequences positive, consequences negative, control positive, control negative, and emotional representations; the eighth domain is the identity domain and this examines the experience of health-related changes.</p> <p>Results</p> <p>Mokken scale analysis showed that the majority of items within the views about aging subscales were strongly scalable. Confirmatory factor analysis also indicated that the model provided a good fit for the data. Overall, subscales had good internal reliabilities. Hierarchical linear regression was conducted to investigate the independent contribution of APQ subscales to physical and psychological health and in doing so determine the construct validity of the APQ. Results showed that self-perceptions of aging were independently related to physical and psychological health. Mediation testing also supported a role for self-perceptions of aging as partial mediators in the relationship between indices of physical functioning and physical and psychological health outcomes.</p> <p>Conclusion</p> <p>Findings support the complex and multifaceted nature of the aging experience. The good internal reliability and construct validity of the subscales suggests that the APQ is a promising instrument that can enable a theoretically informed, multidimensional assessment of self-perceptions of aging. The potential role of self-perceptions of aging in facilitating physical and psychological health in later life is also highlighted.</p

Integrated Ecosystem Assessment: Lake Ontario Water Management

BACKGROUND: Ecosystem management requires organizing, synthesizing, and projecting information at a large scale while simultaneously addressing public interests, dynamic ecological properties, and a continuum of physicochemical conditions. We compared the impacts of seven water level management plans for Lake Ontario on a set of environmental attributes of public relevance. METHODOLOGY AND FINDINGS: Our assessment method was developed with a set of established impact assessment tools (checklists, classifications, matrices, simulations, representative taxa, and performance relations) and the concept of archetypal geomorphic shoreline classes. We considered each environmental attribute and shoreline class in its typical and essential form and predicted how water level change would interact with defining properties. The analysis indicated that about half the shoreline of Lake Ontario is potentially sensitive to water level change with a small portion being highly sensitive. The current water management plan may be best for maintaining the environmental resources. In contrast, a natural water regime plan designed for greatest environmental benefits most often had adverse impacts, impacted most shoreline classes, and the largest portion of the lake coast. Plans that balanced multiple objectives and avoided hydrologic extremes were found to be similar relative to the environment, low on adverse impacts, and had many minor impacts across many shoreline classes. SIGNIFICANCE: The Lake Ontario ecosystem assessment provided information that can inform decisions about water management and the environment. No approach and set of methods will perfectly and unarguably accomplish integrated ecosystem assessment. For managing water levels in Lake Ontario, we found that there are no uniformly good and bad options for environmental conservation. The scientific challenge was selecting a set of tools and practices to present broad, relevant, unbiased, and accessible information to guide decision-making on a set of management options

Cervico-vaginal immunoglobulin g levels increase post-ovulation independently of neutrophils

The prevalence of sexually transmitted infections (STIs) is often higher in females than in males. Although the reproductive cycle profoundly modulates local immunity in the female reproductive tract (FRT) system, significant gaps in our knowledge of the immunobiology of the FRT still exist. An intriguing and frequently observed characteristic of the FRT is the predominant presence of immunoglobulin (Ig) G in cervico-vaginal secretions. We show here that in the mouse, IgG accumulation was enhanced approximately 5-fold post-ovulation, and was accompanied by an influx of neutrophils into the FRT. To determine whether these two events were causally related, we performed short-term neutrophil depletion experiments at individual stages throughout the estrous cycle. Our results demonstrate that neutrophils were not necessary for cycle-dependent tissue remodeling and cycle progression and that cycle-dependent IgG accumulation occurred independent of neutrophils. We thus conclude that neutrophil influx and IgG accumulation are independent events that occur in the FRT during the reproductive cycle

Lipid metabolic perturbation is an early-onset phenotype in adult spinster mutants: a Drosophila model for lysosomal storage disorders

Intracellular accumulation of lipids and swollen dysfunctional lysosomes are linked to several neurodegenerative diseases, including lysosomal storage disorders (LSD). Detailed characterization of lipid metabolic changes in relation to the onset and progression of neurodegeneration is currently missing. We systematically analyzed lipid perturbations in spinster (spin) mutants, a Drosophila model of LSD-like neurodegeneration. Our results highlight an imbalance in brain ceramide and sphingosine in the early stages of neurodegeneration, preceding the accumulation of endomembranous structures, manifestation of altered behavior, and buildup of lipofuscin. Manipulating levels of ceramidase and altering these lipids in spin mutants allowed us to conclude that ceramide homeostasis is the driving force in disease progression and is integral to spin function in the adult nervous system. We identified 29 novel physical interaction partners of Spin and focused on the lipid carrier protein, Lipophorin (Lpp). A subset of Lpp and Spin colocalize in the brain and within organs specialized for lipid metabolism (fat bodies and oenocytes). Reduced Lpp protein was observed in spin mutant tissues. Finally, increased levels of lipid metabolites produced by oenocytes in spin mutants allude to a functional interaction between Spin and Lpp, underscoring the systemic nature of lipid perturbation in LSD

Onset and Progression of Behavioral and Molecular Phenotypes in a Novel Congenic R6/2 Line Exhibiting Intergenerational CAG Repeat Stability

In the present study we report on the use of speed congenics to generate a C57BL/6J congenic line of HD-model R6/2 mice carrying 110 CAG repeats, which uniquely exhibits minimal intergenerational instability. We also report the first identification of the R6/2 transgene insertion site. The relatively stable line of 110 CAG R6/2 mice was characterized for the onset of behavioral impairments in motor, cognitive and psychiatric-related phenotypes as well as the progression of disease-related impairments from 4 to 10 weeks of age. 110Q mice exhibited many of the phenotypes commonly associated with the R6/2 model including reduced activity and impairments in rotarod performance. The onset of many of the phenotypes occurred around 6 weeks and was progressive across age. In addition, some phenotypes were observed in mice as early as 4 weeks of age. The present study also reports the onset and progression of changes in several molecular phenotypes in the novel R6/2 mice and the association of these changes with behavioral symptom onset and progression. Data from TR-FRET suggest an association of mutant protein state changes (soluble versus aggregated) in disease onset and progression