Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions

During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastroph

The Hide-and-Seek of Grain Boundaries from Moire Pattern Fringe of Two-Dimensional Graphene

Grain boundaries (GBs) commonly exist in crystalline materials and affect various properties of materials. The facile identification of GBs is one of the significant requirements for systematical study of polycrystalline materials including recently emerging two-dimensional materials. Previous observations of GBs have been performed by various tools including high resolution transmission electron microscopy. However, a method to easily identify GBs, especially in the case of low-angle GBs, has not yet been well established. In this paper, we choose graphene bilayers with a GB as a model system and investigate the effects of interlayer rotations to the identification of GBs. We provide a critical condition between adjacent moire fringe spacings, which determines the possibility of GB recognition. In addition, for monolayer graphene with a grain boundary, we demonstrate that low-angle GBs can be distinguished easily by inducing moire patterns deliberately with an artificial reference overlayopen0

Health service use in indigenous Sami and non-indigenous youth in North Norway: A population based survey

<p>Abstract</p> <p>Background</p> <p>This is the first population based study exploring health service use and ethno-cultural factors in indigenous Sami and non-Sami youth in North Norway. The first aim of the present study was to compare the frequency of health service use between Sami adolescents and their non-indigenous peers. The second aim was to explore the relationships between health service use and ethno-cultural factors, such as ethnic context, Sami self-identification, perceived discrimination and Sami language competence. Finally, we wanted to explore the relationship between use of health services and emotional and behavioural problems.</p> <p>Method</p> <p>The Norwegian Arctic Adolescent Health Study was conducted among 10th graders (15-16 years old) in junior high schools in North Norway. The sample consisted of 4,449 adolescents, of whom 450 (10.1%) were indigenous Sami and 3,999 (89.9%) were non-Sami.</p> <p>Results</p> <p>Sami and non-Sami youth used all health services with equal frequency. However, several ethno-cultural factors were found to influence health service use. Sami youth in more assimilated ethnic contexts used general practitioners more than non-Sami youth. Youth with Sami self-identification had a higher probability of using the school health service compared with other youth. Ethnic barriers to health service use were also identified. Sami speaking youth with a high degree of perceived discrimination had lower probability of using school health services than non-Sami speaking youth. Sami youth with conduct problems were less likely than non-Sami to use psychologist/psychiatrist. The present study demonstrated a relationship between health need and actual health service use.</p> <p>Conclusion</p> <p>Culture-specific factors influenced the help-seeking process in indigenous youth; some factors acted as barriers against health service use and other factors increased the probability of health service use.</p

Study protocol: EXERcise and Cognition In Sedentary adults with Early-ONset dementia (EXERCISE-ON)

<p>Abstract</p> <p>Background</p> <p>Although the development of early-onset dementia is a radical and invalidating experience for both patient and family there are hardly any non-pharmacological studies that focus on this group of patients. One type of a non-pharmacological intervention that appears to have a beneficial effect on cognition in older persons without dementia and older persons at risk for dementia is exercise. In view of their younger age early-onset dementia patients may be well able to participate in an exercise program. The main aim of the EXERCISE-ON study is to assess whether exercise slows down the progressive course of the symptoms of dementia.</p> <p>Methods/Design</p> <p>One hundred and fifty patients with early-onset dementia are recruited. After completion of the baseline measurements, participants living within a 50 kilometre radius to one of the rehabilitation centres are randomly assigned to either an <it>aerobic exercise program in a rehabilitation centre</it> or a <it>flexibility and relaxation program in a rehabilitation centre</it>. Both programs are applied three times a week during 3 months. Participants living outside the 50 kilometre radius are included in a feasibility study where participants join in a <it>daily physical activity program set at home making use of pedometers</it>. Measurements take place at baseline (entry of the study), after three months (end of the exercise program) and after six months (follow-up). Primary outcomes are cognitive functioning; psychomotor speed and executive functioning; (instrumental) activities of daily living, and quality of life. Secondary outcomes include physical, neuropsychological, and rest-activity rhythm measures.</p> <p>Discussion</p> <p>The EXERCISE-ON study is the first study to offer exercise programs to patients with early-onset dementia. We expect this study to supply evidence regarding the effects of exercise on the symptoms of early-onset dementia, influencing quality of life.</p> <p>Trial registration</p> <p>The present study is registered within The Netherlands National Trial Register (ref: NTR2124)</p

Rapid improvement in verbal fluency and aphasia following perispinal etanercept in Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>Recent clinical studies point to rapid and sustained clinical, cognitive, and behavioral improvement in both Alzheimer's disease and primary progressive aphasia following weekly perispinal administration of etanercept, a TNF-alpha inhibitor that acts by blocking the binding of this cytokine to its receptors. This outcome is concordant with recent basic science studies suggesting that TNF-alpha functions <it>in vivo </it>as a gliotransmitter that regulates synaptic function in the brain. We hypothesized that perispinal etanercept had the potential to improve verbal function in Alzheimer's disease, so we included several standarized measures of verbal ability to evaluate language skills in a clinical trial of perispinal etanercept for Alzheimer's disease.</p> <p>Methods</p> <p>This was a prospective, single-center, open-label, pilot study, in which 12 patients with mild-to-severe Alzheimer's disease were administered etanercept, 25–50 mg, weekly by perispinal administration for six months. Two additional case studies are presented.</p> <p>Results</p> <p>Two-tailed, paired t-tests were conducted comparing baseline performance to 6-month performance on all neuropsychological measures. Test batteries included the California Verbal Learning Test-Second Edition, Adult Version; Logical Memory I and II(WMS-LM-II) from the Wechsler Memory Scale-Abbreviated; the Comprehensive Trail Making Test (TMT); Boston Naming Test; and letter(FAS) and category verbal fluency. All measures revealed a significant effect except for the Boston Naming Test and the TMT-4, with WMS-LM-II being marginally significant at p = .05. The FAS test for letter fluency was most highly significant with a p < 0.0007. In addition, rapid improvement in verbal fluency and aphasia in two patients with dementia, beginning minutes after perispinal etanercept administration, is documented.</p> <p>Conclusion</p> <p>In combination with the previously reported results of perispinal etanercept in Alzheimer's disease and primary progressive aphasia, these results further argue that larger scale studies of this therapeutic intervention, including Phase 3 trials, are warranted in dementias. In addition, these results may provide insight into the basic pathophysiologic mechanisms underlying Alzheimer's disease and related forms of dementia, and suggest the existence of novel, rapidly reversible, TNF-mediated pathophysiologic mechanisms in Alzheimer's disease which are worthy of further investigation.</p

The reference frame for encoding and retention of motion depends on stimulus set size

YesThe goal of this study was to investigate the reference frames used in perceptual encoding and storage of visual motion information. In our experiments, observers viewed multiple moving objects and reported the direction of motion of a randomly selected item. Using a vector-decomposition technique, we computed performance during smooth pursuit with respect to a spatiotopic (nonretinotopic) and to a retinotopic component and compared them with performance during fixation, which served as the baseline. For the stimulus encoding stage, which precedes memory, we found that the reference frame depends on the stimulus set size. For a single moving target, the spatiotopic reference frame had the most significant contribution with some additional contribution from the retinotopic reference frame. When the number of items increased (Set Sizes 3 to 7), the spatiotopic reference frame was able to account for the performance. Finally, when the number of items became larger than 7, the distinction between reference frames vanished. We interpret this finding as a switch to a more abstract nonmetric encoding of motion direction. We found that the retinotopic reference frame was not used in memory. Taken together with other studies, our results suggest that, whereas a retinotopic reference frame may be employed for controlling eye movements, perception and memory use primarily nonretinotopic reference frames. Furthermore, the use of nonretinotopic reference frames appears to be capacity limited. In the case of complex stimuli, the visual system may use perceptual grouping in order to simplify the complexity of stimuli or resort to a nonmetric abstract coding of motion information

Barriers to participation in mental health research: are there specific gender, ethnicity and age related barriers?

<p>Abstract</p> <p>Background</p> <p>It is well established that the incidence, prevalence and presentation of mental disorders differ by gender, ethnicity and age, and there is evidence that there is also differential representation in mental health research by these characteristics. The aim of this paper is to a) review the current literature on the nature of barriers to participation in mental health research, with particular reference to gender, age and ethnicity; b) review the evidence on the effectiveness of strategies used to overcome these barriers.</p> <p>Method</p> <p>Studies published up to December 2008 were identified using MEDLINE, PsycINFO and EMBASE using relevant mesh headings and keywords.</p> <p>Results</p> <p>Forty-nine papers were identified. There was evidence of a wide range of barriers including transportation difficulties, distrust and suspicion of researchers, and the stigma attached to mental illness. Strategies to overcome these barriers included the use of bilingual staff, assistance with travel, avoiding the use of stigmatising language in marketing material and a focus on education about the disorder under investigation. There were very few evaluations of such strategies, but there was evidence that ethnically matching recruiters to potential participants did not improve recruitment rates. Educational strategies were helpful and increased recruitment.</p> <p>Conclusion</p> <p>Mental health researchers should consider including caregivers in recruitment procedures where possible, provide clear descriptions of study aims and describe the representativeness of their sample when reporting study results. Studies that systematically investigate strategies to overcome barriers to recruitment are needed.</p