Bod1, a novel kinetochore protein required for chromosome biorientation

We have combined the proteomic analysis of Xenopus laevis in vitro–assembled chromosomes with RNA interference and live cell imaging in HeLa cells to identify novel factors required for proper chromosome segregation. The first of these is Bod1, a protein conserved throughout metazoans that associates with a large macromolecular complex and localizes with kinetochores and spindle poles during mitosis. Small interfering RNA depletion of Bod1 in HeLa cells produces elongated mitotic spindles with severe biorientation defects. Bod1-depleted cells form syntelic attachments that can oscillate and generate enough force to separate sister kinetochores, suggesting that microtubule–kinetochore interactions were intact. Releasing Bod1-depleted cells from a monastrol block increases the frequency of syntelic attachments and the number of cells displaying biorientation defects. Bod1 depletion does not affect the activity or localization of Aurora B but does cause mislocalization of the microtubule depolymerase mitotic centromere- associated kinesin and prevents its efficient phosphorylation by Aurora B. Therefore, Bod1 is a novel kinetochore protein that is required for the detection or resolution of syntelic attachments in mitotic spindles

Kinetochore alignment within the metaphase plate is regulated by centromere stiffness and microtubule depolymerases

During mitosis in most eukaryotic cells, chromosomes align and form a metaphase plate halfway between the spindle poles, about which they exhibit oscillatory movement. These movements are accompanied by changes in the distance between sister kinetochores, commonly referred to as breathing. We developed a live cell imaging assay combined with computational image analysis to quantify the properties and dynamics of sister kinetochores in three dimensions. We show that baseline oscillation and breathing speeds in late prometaphase and metaphase are set by microtubule depolymerases, whereas oscillation and breathing periods depend on the stiffness of the mechanical linkage between sisters. Metaphase plates become thinner as cells progress toward anaphase as a result of reduced oscillation speed at a relatively constant oscillation period. The progressive slowdown of oscillation speed and its coupling to plate thickness depend nonlinearly on the stiffness of the mechanical linkage between sisters. We propose that metaphase plate formation and thinning require tight control of the state of the mechanical linkage between sisters mediated by centromeric chromatin and cohesion

‘I just want to get on with my life’:A mixed methods study of active management of quality of life in living with dementia

The active management of the experience of living with dementia appears to improve quality of life despite the lack of disease modification (Alzheimer’s Association 2015). However, research to date has been largely of modest scale and explanatory factors for improvements under-conceptualised. Thus, although promulgated through national strategies, the evidence base is relatively weak. This paper reports on a nation-wide study of the influence of the National Dementia Strategy for England (Department of Health 2009) in relation to Dementia Adviser and Peer Support Network services in 40 demonstration sites. The research aimed to identify ways in which the services contribute to the wellbeing and resilience of people with dementia and care partners. A mixed methods research design collected data through: activity and outcome monitoring; organisational surveys; in-depth case studies, including qualitative interviews with people with dementia (n=47) and care partners (n=54), wellbeing and quality of life measures, and interviews with staff and other stakeholders (n=82). Three themes are explored: Addressing individual and community needs, Promoting independence, control and choice, Getting a life back. Services promoted independence, control and choice and consequently enabled people to re-narrate their lives as purposeful within their communities. Ways in which these are achieved resemble the public health model of lay health advisor and this research adds to the imperative to approach dementia as a key public health concern

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

"We’re all thrown in the same boat...":A qualitative analysis of peer support in dementia care

Peer support is well established in fields such as the disability movement and mental health and is increasingly recognised as one way of enabling support by and for people with a diagnosis of dementia and their immediate carers. It was central to the implementation of the National Dementia Strategy (NDS) for England, when 40 demonstration sites were established. This mixed-methods study included in-depth qualitative interviews with people living with dementia (n = 101) and staff/stakeholders (n = 82) at 8 of the 40 sites. Data analysis was a five-stage process: coding framework developed (using 25 transcripts); further development of the framework (using a further 70 transcripts); development of emerging themes; modelling of themes and verification of models based on the entire data set. Peer support had positive emotional and social impact that was rooted in identification with others, a commonality of experience and reciprocity of support. There was also a contrast between the quality of peer support and support from professionals. This emphasises the significance of lived experience and promoting a strength-based approach to interpersonal support that is enabling and challenges a deficit approach to understanding dementia

Effect of variable transmission rate on the dynamics of HIV in sub-Saharan Africa

<p>Abstract</p> <p>Background</p> <p>The cause of the high HIV prevalence in sub-Saharan Africa is incompletely understood, with heterosexual penile-vaginal transmission proposed as the main mechanism. Heterosexual HIV transmission has been estimated to have a very low probability; but effects of cofactors that vary in space and time may substantially alter this pattern.</p> <p>Methods</p> <p>To test the effect of individual variation in the HIV infectiousness generated by co-infection, we developed and analyzed a mathematical sexual network model that simulates the behavioral components of a population from Malawi, as well as the dynamics of HIV and the co-infection effect caused by other infectious diseases, including herpes simplex virus type-2, gonorrhea, syphilis and malaria.</p> <p>Results</p> <p>The analysis shows that without the amplification effect caused by co-infection, no epidemic is generated, and HIV prevalence decreases to extinction. But the model indicates that an epidemic can be generated by the amplification effect on HIV transmission caused by co-infection.</p> <p>Conclusion</p> <p>The simulated sexual network demonstrated that a single value for HIV infectivity fails to describe the dynamics of the epidemic. Regardless of the low probability of heterosexual transmission per sexual contact, the inclusion of individual variation generated by transient but repeated increases in HIV viral load associated with co-infections may provide a biological basis for the accelerated spread of HIV in sub-Saharan Africa. Moreover, our work raises the possibility that the natural history of HIV in sub-Saharan Africa cannot be fully understood if individual variation in infectiousness is neglected.</p

Stable carbon and nitrogen isotope enrichment in primate tissues

Isotopic studies of wild primates have used a wide range of tissues to infer diet and model the foraging ecologies of extinct species. The use of mismatched tissues for such comparisons can be problematic because differences in amino acid compositions can lead to small isotopic differences between tissues. Additionally, physiological and dietary differences among primate species could lead to variable offsets between apatite carbonate and collagen. To improve our understanding of the isotopic chemistry of primates, we explored the apparent enrichment (ε*) between bone collagen and muscle, collagen and fur or hair keratin, muscle and keratin, and collagen and bone carbonate across the primate order. We found that the mean ε* values of proteinaceous tissues were small (≤1‰), and uncorrelated with body size or phylogenetic relatedness. Additionally, ε* values did not vary by habitat, sex, age, or manner of death. The mean ε* value between bone carbonate and collagen (5.6 ± 1.2‰) was consistent with values reported for omnivorous mammals consuming monoisotopic diets. These primate-specific apparent enrichment values will be a valuable tool for cross-species comparisons. Additionally, they will facilitate dietary comparisons between living and fossil primates

Trophic Ecology of Atlantic Bluefin Tuna (Thunnus thynnus) Larvae from the Gulf of Mexico and NW Mediterranean Spawning Grounds: A Comparative Stable Isotope Study

The present study uses stable isotopes of nitrogen and carbon (δ15Nandδ13C) as trophic indicators for Atlantic bluefin tuna larvae (BFT) (6–10mm standard length) in the highly contrasting environmental conditions of the Gulf of Mexico (GOM) and the Balearic Sea (MED). These regions are differentiated by their temperature regime and relative productivity, with the GOM being significantly warmer and more productive. MED BFT larvae showed the highest δ15N signatures, implying an elevated trophic position above the underlyingmicrozooplankton baseline. Ontogenetic dietary shifts were observed in the BFT larvae from the GOM and MED which indicates early life trophodynamics differences between these spawning habitats. Significant trophic differences between the GOM and MED larvae were observed in relation to δ15N signatures in favour of the MED larvae, which may have important implications in their growth during their early life stages. These low δ15N levels in the zooplankton from the GOM may be an indication of a shifting isotopic baseline in pelagic food webs due to diatrophic inputs by cyanobacteria. Lack of enrichment for δ15N in BFT larvae compared to zooplankton implies an alternative grazing pathway from the traditional food chain of phytoplankton— zooplankton—larval fish. Results provide insight for a comparative characterization of the trophic pathways variability of the two main spawning grounds for BFT larvaeVersión del editor4,411

Second Language Processing Shows Increased Native-Like Neural Responses after Months of No Exposure

Although learning a second language (L2) as an adult is notoriously difficult, research has shown that adults can indeed attain native language-like brain processing and high proficiency levels. However, it is important to then retain what has been attained, even in the absence of continued exposure to the L2—particularly since periods of minimal or no L2 exposure are common. This event-related potential (ERP) study of an artificial language tested performance and neural processing following a substantial period of no exposure. Adults learned to speak and comprehend the artificial language to high proficiency with either explicit, classroom-like, or implicit, immersion-like training, and then underwent several months of no exposure to the language. Surprisingly, proficiency did not decrease during this delay. Instead, it remained unchanged, and there was an increase in native-like neural processing of syntax, as evidenced by several ERP changes—including earlier, more reliable, and more left-lateralized anterior negativities, and more robust P600s, in response to word-order violations. Moreover, both the explicitly and implicitly trained groups showed increased native-like ERP patterns over the delay, indicating that such changes can hold independently of L2 training type. The results demonstrate that substantial periods with no L2 exposure are not necessarily detrimental. Rather, benefits may ensue from such periods of time even when there is no L2 exposure. Interestingly, both before and after the delay the implicitly trained group showed more native-like processing than the explicitly trained group, indicating that type of training also affects the attainment of native-like processing in the brain. Overall, the findings may be largely explained by a combination of forgetting and consolidation in declarative and procedural memory, on which L2 grammar learning appears to depend. The study has a range of implications, and suggests a research program with potentially important consequences for second language acquisition and related fields