Aquaporin water channels in the nervous system.

The aquaporins (AQPs) are plasma membrane water-transporting proteins. AQP4 is the principal member of this protein family in the CNS, where it is expressed in astrocytes and is involved in water movement, cell migration and neuroexcitation. AQP1 is expressed in the choroid plexus, where it facilitates cerebrospinal fluid secretion, and in dorsal root ganglion neurons, where it tunes pain perception. The AQPs are potential drug targets for several neurological conditions. Astrocytoma cells strongly express AQP4, which may facilitate their infiltration into the brain, and the neuroinflammatory disease neuromyelitis optica is caused by AQP4-specific autoantibodies that produce complement-mediated astrocytic damage

Klf15 Is Critical for the Development and Differentiation of Drosophila Nephrocytes

Insect nephrocytes are highly endocytic scavenger cells that represent the only invertebrate model for the study of human kidney podocytes. Despite their importance, nephrocyte development is largely uncharacterised. This work tested whether the insect ortholog of mammalian Kidney Krüppel-Like Factor (Klf15), a transcription factor required for mammalian podocyte differentiation, was required for insect nephrocyte development. It was found that expression of Drosophila Klf15 (dKlf15, previously known as Bteb2) was restricted to the only two nephrocyte populations in Drosophila, the garland cells and pericardial nephrocytes. Loss of dKlf15 function led to attrition of both nephrocyte populations and sensitised larvae to the xenotoxin silver nitrate. Although pericardial nephrocytes in dKlf15 loss of function mutants were specified during embryogenesis, they failed to express the slit diaphragm gene sticks and stones and did not form slit diaphragms. Conditional silencing of dKlf15 in adults led to reduced surface expression of the endocytic receptor Amnionless and loss of in vivo scavenger function. Over-expression of dKlf15 increased nephrocyte numbers and rescued age-dependent decline in nephrocyte function. The data place dKlf15 upstream of sns and Amnionless in a nephrocyte-restricted differentiation pathway and suggest dKlf15 expression is both necessary and sufficient to sustain nephrocyte differentiation. These findings explain the physiological relevance of dKlf15 in Drosophila and imply that the role of KLF15 in human podocytes is evolutionarily conserve

Limited Effects of Set Shifting Training in Healthy Older Adults

Our ability to flexibly shift between tasks or task sets declines in older age. As this decline may have adverse effects on everyday life of elderly people, it is of interest to study whether set shifting ability can be trained, and if training effects generalize to other cognitive tasks. Here, we report a randomized controlled trial where healthy older adults trained set shifting with three different set shifting tasks. The training group (n = 17) performed adaptive set shifting training for 5 weeks with three training sessions a week (45 min/session), while the active control group (n = 16) played three different computer games for the same period. Both groups underwent extensive pre-and post-testing and a 1-year follow-up. Compared to the controls, the training group showed significant improvements on the trained tasks. Evidence for near transfer in the training group was very limited, as it was seen only on overall accuracy on an untrained computerized set shifting task. No far transfer to other cognitive functions was observed. One year later, the training group was still better on the trained tasks but the single near transfer effect had vanished. The results suggest that computerized set shifting training in the elderly shows long-lasting effects on the trained tasks but very little benefit in terms of generalization

The effects of multi-domain versus single-domain cognitive training in non-demented older people: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Whether healthy older people can benefit from cognitive training (CogTr) remains controversial. This study explored the benefits of CogTr in community dwelling, healthy, older adults and compared the effects of single-domain with multi-domain CogTr interventions.</p> <p>Methods</p> <p>A randomized, controlled, 3-month trial of CogTr with double-blind assessments at baseline and immediate, 6-month and 12-month follow-up after training completion was conducted. A total of 270 healthy Chinese older people, 65 to 75 years old, were recruited from the Ganquan-area community in Shanghai. Participants were randomly assigned to three groups: multi-domain CogTr, single-domain CogTr, and a wait-list control group. Twenty-four sessions of CogTr were administrated to the intervention groups over a three-month period. Six months later, three booster training sessions were offered to 60% of the initial training participants. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS, Form A), the Color Word Stroop test (CWST), the Visual Reasoning test and the Trail Making test (TMT) were used to assess cognitive function.</p> <p>Results</p> <p>Multi-domain CogTr produced statistically significant training effects on RBANS, visual reasoning, and immediate and delayed memory, while single-domain CogTr showed training effects on RBANS, visual reasoning, word interference, and visuospatial/constructional score (all <it>P </it>< 0.05). At the 12-month posttest, the multi-domain CogTr showed training effects on RBANS, delayed memory and visual reasoning, while single-domain CogTr only showed effects on word interference. Booster training resulted in effects on RBANS, visual reasoning, time of trail making test, and visuospatial/constructional index score.</p> <p>Conclusions</p> <p>Cognitive training can improve memory, visual reasoning, visuospatial construction, attention and neuropsychological status in community-living older people and can help maintain their functioning over time. Multi-domain CogTr enhanced memory proficiency, while single-domain CogTr augmented visuospatial/constructional and attention abilities. Multi-domain CogTr had more advantages in training effect maintenance.</p> <p>Clinical Trial Registration</p> <p>Chinese Clinical Trial Registry. Registration number: ChiCTR-TRC-09000732.</p

Spontaneous vortices in the formation of Bose-Einstein condensates

Phase transitions are ubiquitous in nature, ranging from protein folding and denaturisation, to the superconductor-insulator quantum phase transition, to the decoupling of forces in the early universe. Remarkably, phase transitions can be arranged into universality classes, where systems having unrelated microscopic physics exhibit identical scaling behaviour near the critical point. Here we present an experimental and theoretical study of the Bose-Einstein condensation phase transition of an atomic gas, focusing on one prominent universal element of phase transition dynamics: the spontaneous formation of topological defects during a quench through the transition. While the microscopic dynamics of defect formation in phase transitions are generally difficult to investigate, particularly for superfluid phase transitions, Bose-Einstein condensates (BECs) offer unique experimental and theoretical opportunities for probing such details. Although spontaneously formed vortices in the condensation transition have been previously predicted to occur, our results encompass the first experimental observations and statistical characterisation of spontaneous vortex formation in the condensation transition. Using microscopic theories that incorporate atomic interactions and quantum and thermal fluctuations of a finite-temperature Bose gas, we simulate condensation and observe vortex formation in close quantitative agreement with our experimental results. Our studies provide further understanding of the development of coherence in superfluids, and may allow for direct investigation of universal phase-transition dynamics.Comment: 14 pages, 6 figures. Accepted for publication in Nature. Supplementary movie files are available at http://www.physics.uq.edu.au/people/mdavis/spontaneous_vortice

Attitudes toward and experiences of gender issues among physician teachers: A survey study conducted at a university teaching hospital in Sweden

<p>Abstract</p> <p>Background</p> <p>Gender issues are important to address during medical education, however research about the implementation of gender in medical curricula reports that there are obstacles. The aim of this study was to explore physician teachers' attitudes to gender issues.</p> <p>Methods</p> <p>As part of a questionnaire, physician teachers at Umeå University in Sweden were given open-ended questions about explanations for and asked to write examples why they found gender important or not. The 1 469 comments from the 243 respondents (78 women, 165 men) were analyzed by way of content analysis. The proportion of comments made by men and women in each category was compared.</p> <p>Results</p> <p>We found three themes in our analysis: Understandings of gender, problems connected with gender and approaches to gender. Gender was associated with differences between women and men regarding behaviour and disease, as well as with inequality of life conditions. Problems connected with gender included: delicate situations involving investigations of intimate body parts or sexual attraction, different expectations on male and female physicians and students, and difficulty fully understanding the experience of people of the opposite sex. The three approaches to gender that appeared in the comments were: 1) avoidance, implying that the importance of gender in professional relationships was recognized but minimized by comparing gender with aspects, such as personality and neutrality; 2) simplification, implying that gender related problems were easy to address, or already solved; and 3) awareness, implying that the respondent was interested in gender issues or had some insights in research about gender. Only a few individuals described gender as an area of competence and knowledge. There were comments from men and women in all categories, but there were differences in the relative weight for some categories. For example, recognizing gender inequities was more pronounced in the comments from women and avoidance more common in comments from men.</p> <p>Conclusion</p> <p>The surveyed physician teachers gave many examples of gender-related problems in medical work and education, but comments describing gender as an area of competence and knowledge were few. Approaches to gender characterized by avoidance and simplification suggest that faculty development programs on gender need to address and reflect on attitudes as well as knowledge.</p

Phosphorylation-Independent Regulation of Atf1-Promoted Meiotic Recombination by Stress-Activated, p38 Kinase Spc1 of Fission Yeast

BACKGROUND:Stress-activated protein kinases regulate multiple cellular responses to a wide variety of intracellular and extracellular conditions. The conserved, multifunctional, ATF/CREB protein Atf1 (Mts1, Gad7) of fission yeast binds to CRE-like (M26) DNA sites. Atf1 is phosphorylated by the conserved, p38-family kinase Spc1 (Sty1, Phh1) and is required for many Spc1-dependent stress responses, efficient sexual differentiation, and activation of Rec12 (Spo11)-dependent meiotic recombination hotspots like ade6-M26. METHODOLOGY/PRINCIPAL FINDINGS:We sought to define mechanisms by which Spc1 regulates Atf1 function at the ade6-M26 hotspot. The Spc1 kinase was essential for hotspot activity, but dispensable for basal recombination. Unexpectedly, a protein lacking all eleven MAPK phospho-acceptor sites and detectable phosphorylation (Atf1-11M) was fully proficient for hotspot recombination. Furthermore, tethering of Atf1 to ade6 in the chromosome by a heterologous DNA binding domain bypassed the requirement for Spc1 in promoting recombination. CONCLUSIONS/SIGNIFICANCE:The Spc1 protein kinase regulates the pathway of Atf1-promoted recombination at or before the point where Atf1 binds to chromosomes, and this pathway regulation is independent of the phosphorylation status of Atf1. Since basal recombination is Spc1-independent, the principal function of the Spc1 kinase in meiotic recombination is to correctly position Atf1-promoted recombination at hotspots along chromosomes. We also propose new hypotheses on regulatory mechanisms for shared (e.g., DNA binding) and distinct (e.g., osmoregulatory vs. recombinogenic) activities of multifunctional, stress-activated protein Atf1

Empowerment and Parent Gain as Mediators and Moderators of Distress in Mothers of Children with Autism Spectrum Disorders

Mothers of children with Autism Spectrum Disorders (ASD) experience considerable amounts of distress and experiences of crisis. The Family Adjustment and Adaptation Response model provides a theory for understanding the experience of distress and family crisis in families, and the purpose of the present study was to examine experiences of distress in mothers of individuals with ASD using this framework. We specifically investigated how parent empowerment and positive gain are related to their experiences of distress, whether as mediators or as moderators of child aggression. Participants included 156 mothers of children with ASD ranging in age from 4 – 21 years. Mothers completed an online survey of demographics, problem behaviors, family empowerment, positive gain, and distress. We conducted path analyses of multiple mediation and moderation. Results indicated that greater child problem behavior was related to less parent empowerment, which was related to greater maternal distress, supporting empowerment as a partial mediator. At the same time, greater child aggression was not related to maternal distress in mothers who report high rates of positive gain, suggesting that parent gain functions as a moderator. The implications for how and when clinicians intervene with families of children with ASD are discussed

An Allograft Glioma Model Reveals the Dependence of Aquaporin-4 Expression on the Brain Microenvironment

Aquaporin-4 (AQP4), the main water channel of the brain, is highly expressed in animal glioma and human glioblastoma in situ. In contrast, most cultivated glioma cell lines don’t express AQP4, and primary cell cultures of human glioblastoma lose it during the first passages. Accordingly, in C6 cells and RG2 cells, two glioma cell lines of the rat, and in SMA mouse glioma cell lines, we found no AQP4 expression. We confirmed an AQP4 loss in primary human glioblastoma cell cultures after a few passages. RG-2 glioma cells if grafted into the brain developed AQP4 expression. This led us consider the possibility of AQP4 expression depends on brain microenvironment. In previous studies, we observed that the typical morphological conformation of AQP4 as orthogonal arrays of particles (OAP) depended on the extracellular matrix component agrin. In this study, we showed for the first time implanted AQP4 negative glioma cells in animal brain or flank to express AQP4 specifically in the intracerebral gliomas but neither in the extracranial nor in the flank gliomas. AQP4 expression in intracerebral gliomas went along with an OAP loss, compared to normal brain tissue. AQP4 staining in vivo normally is polarized in the astrocytic endfoot membranes at the glia limitans superficialis and perivascularis, but in C6 and RG2 tumors the AQP4 staining is redistributed over the whole glioma cell as in human glioblastoma. In contrast, primary rat or mouse astrocytes in culture did not lose their ability to express AQP4, and they were able to form few OAPs