Lithium distribution across the membrane of motoneurons in the isolated frog spinal cord

Lithium sensitive microelectrodes were used to investigate the transmembrane distribution of lithium ions (Li+) in motoneurons of the isolated frog spinal cord. After addition of 5 mmol·l–1 LiCl to the bathing solution the extracellular diffusion of Li+ was measured. At a depth of 500 m, about 60 min elapsed before the extracellular Li+ concentration approached that of the bathing solution. Intracellular measurements revealed that Li+ started to enter the cells soon after reaching the motoneuron pool and after up to 120 min superfusion, an intra — to extracellular concentration ratio of about 0.7 was obtained. The resting membrane potential and height of antidromically evoked action potentials were not altered by 5 mmol·l–1 Li+

Vocation, Belongingness, and Balance: A Qualitative Study of Veterinary Student Well-Being

An elevated risk for suicide among veterinarians has stimulated research into the mental health of the veterinary profession, and more recently attention has turned to the veterinary student population. This qualitative study sought to explore UK veterinary students' perceptions and experiences of university life, and to consider how these may affect well-being. Semi-structured interviews were conducted with 18 students from a single UK school who were purposively selected to include perspectives from male, female, graduate-entry, standard-entry (straight from high school), and widening participation students across all 5 years of the program. Three main themes were identified: a deep-rooted vocation, navigating belongingness, and finding balance. Participants described a long-standing goal of becoming a veterinarian, with a determination reflected by often circuitous routes to veterinary school and little or no consideration of alternatives. Although some had been motivated by a love of animals, others were intrinsically interested in the scientific and problem-solving challenges of veterinary medicine. Most expressed strong feelings of empathy with animal owners. The issue of belongingness was central to participants' experiences, with accounts reflecting their efforts to negotiate a sense of belongingness both in student and professional communities. Participants also frequently expressed a degree of acceptance of poor balance between work and relaxation, with indications of a belief that this imbalance could be rectified later. This study helps highlight future avenues for research and supports initiatives aiming to nurture a sense of collegiality among veterinary students as they progress through training and into the profession

Validity of a novel computerized cognitive battery for mild cognitive impairment

BACKGROUND: The NeuroTrax Mindstreams computerized cognitive assessment system was designed for widespread clinical and research use in detecting mild cognitive impairment (MCI). However, the capability of Mindstreams tests to discriminate elderly with MCI from those who are cognitively healthy has yet to be evaluated. Moreover, the comparability between these tests and traditional neuropsychological tests in detecting MCI has not been examined. METHODS: A 2-center study was designed to assess discriminant validity of tests in the Mindstreams Mild Impairment Battery. Participants were 30 individuals diagnosed with MCI, 29 with mild Alzheimer's disease (AD), and 39 healthy elderly. Testing was with the Mindstreams battery and traditional neuropsychological tests. Receiver operating characteristic (ROC) analysis was used to examine the ability of Mindstreams and traditional measures to discriminate those with MCI from cognitively healthy elderly. Between-group comparisons were made (Mann-Whitney U test) between MCI and healthy elderly and between MCI and mild AD groups. RESULTS: Mindstreams outcome parameters across multiple cognitive domains significantly discriminated among MCI and healthy elderly with considerable effect sizes (p < 0.05). Measures of memory, executive function, visual spatial skills, and verbal fluency discriminated best, and discriminability was at least comparable to that of traditional neuropsychological tests in these domains. CONCLUSIONS: Mindstreams tests are effective in detecting MCI, providing a comprehensive profile of cognitive function. Further, the enhanced precision and ease of use of these computerized tests make the NeuroTrax system a valuable clinical tool in the identification of elderly at high risk for dementia

The Extinction of Dengue through Natural Vulnerability of Its Vectors

Dengue transmission has not always been confined to tropical areas. In some cases, this has been due to a reduced geographic range of the mosquitoes that are able to carry dengue viruses. In Australia, Aedes aegypti mosquitoes once occurred throughout temperate, drier parts of the country but are now restricted to the wet tropics. We used a computer modelling approach to determine whether these mosquitoes could inhabit their former range. This was done by simulating dengue mosquito populations in virtual environments that experienced 10 years of actual daily weather conditions (1998–2007) obtained for 13 locations inside and outside the current tropical range. We discovered that in areas outside the Australian wet tropics, Ae. aegypti often becomes extinct, particularly when conditions are too cool for year-round egg-laying activity, and/or too dry for eggs to hatch. Thus, despite being a global pest and disease vector, Ae. aegypti mosquitoes are naturally vulnerable to extinction in certain conditions. Such vulnerability should be exploited in vector control programs

Process evaluation of appreciative inquiry to translate pain management evidence into pediatric nursing practice

Background Appreciative inquiry (AI) is an innovative knowledge translation (KT) intervention that is compatible with the Promoting Action on Research in Health Services (PARiHS) framework. This study explored the innovative use of AI as a theoretically based KT intervention applied to a clinical issue in an inpatient pediatric care setting. The implementation of AI was explored in terms of its acceptability, fidelity, and feasibility as a KT intervention in pain management. Methods A mixed-methods case study design was used. The case was a surgical unit in a pediatric academic-affiliated hospital. The sample consisted of nurses in leadership positions and staff nurses interested in the study. Data on the AI intervention implementation were collected by digitally recording the AI sessions, maintaining logs, and conducting individual semistructured interviews. Data were analysed using qualitative and quantitative content analyses and descriptive statistics. Findings were triangulated in the discussion. Results Three nurse leaders and nine staff members participated in the study. Participants were generally satisfied with the intervention, which consisted of four 3-hour, interactive AI sessions delivered over two weeks to promote change based on positive examples of pain management in the unit and staff implementation of an action plan. The AI sessions were delivered with high fidelity and 11 of 12 participants attended all four sessions, where they developed an action plan to enhance evidence-based pain assessment documentation. Participants labeled AI a 'refreshing approach to change' because it was positive, democratic, and built on existing practices. Several barriers affected their implementation of the action plan, including a context of change overload, logistics, busyness, and a lack of organised follow-up. Conclusions Results of this case study supported the acceptability, fidelity, and feasibility of AI as a KT intervention in pain management. The AI intervention requires minor refinements (e.g., incorporating continued follow-up meetings) to enhance its clinical utility and sustainability. The implementation process and effectiveness of the modified AI intervention require evaluation in a larger multisite study

Responses of marine benthic microalgae to elevated CO<inf>2</inf>

Increasing anthropogenic CO2 emissions to the atmosphere are causing a rise in pCO2 concentrations in the ocean surface and lowering pH. To predict the effects of these changes, we need to improve our understanding of the responses of marine primary producers since these drive biogeochemical cycles and profoundly affect the structure and function of benthic habitats. The effects of increasing CO2 levels on the colonisation of artificial substrata by microalgal assemblages (periphyton) were examined across a CO2 gradient off the volcanic island of Vulcano (NE Sicily). We show that periphyton communities altered significantly as CO2 concentrations increased. CO2 enrichment caused significant increases in chlorophyll a concentrations and in diatom abundance although we did not detect any changes in cyanobacteria. SEM analysis revealed major shifts in diatom assemblage composition as CO2 levels increased. The responses of benthic microalgae to rising anthropogenic CO2 emissions are likely to have significant ecological ramifications for coastal systems. © 2011 Springer-Verlag

A Candidate Subspecies Discrimination System Involving a Vomeronasal Receptor Gene with Different Alleles Fixed in M. m. domesticus and M. m. musculus

Assortative mating, a potentially efficient prezygotic reproductive barrier, may prevent loss of genetic potential by avoiding the production of unfit hybrids (i.e., because of hybrid infertility or hybrid breakdown) that occur at regions of secondary contact between incipient species. In the case of the mouse hybrid zone, where two subspecies of Mus musculus (M. m. domesticus and M. m. musculus) meet and exchange genes to a limited extent, assortative mating requires a means of subspecies recognition. We based the work reported here on the hypothesis that, if there is a pheromone sufficiently diverged between M. m. domesticus and M. m. musculus to mediate subspecies recognition, then that process must also require a specific receptor(s), also sufficiently diverged between the subspecies, to receive the signal and elicit an assortative mating response. We studied the mouse V1R genes, which encode a large family of receptors in the vomeronasal organ (VNO), by screening Perlegen SNP data and identified one, Vmn1r67, with 24 fixed SNP differences most of which (15/24) are nonsynonymous nucleotide substitutions between M. m. domesticus and M. m. musculus. We observed substantial linkage disequilibrium (LD) between Vmn1r67 and Abpa27, a mouse salivary androgen-binding protein gene that encodes a proteinaceous pheromone (ABP) capable of mediating assortative mating, perhaps in conjunction with its bound small lipophilic ligand. The LD we observed is likely a case of association rather than residual physical linkage from a very recent selective sweep, because an intervening gene, Vmn1r71, shows significant intra(sub)specific polymorphism but no inter(sub)specific divergence in its nucleotide sequence. We discuss alternative explanations of these observations, for example that Abpa27 and Vmn1r67 are coevolving as signal and receptor to reinforce subspecies hybridization barriers or that the unusually divergent Vmn1r67 allele was not a product of fast positive selection, but was derived from an introgressed allele, possibly from Mus spretus

Mapping Dynamic Histone Acetylation Patterns to Gene Expression in Nanog-depleted Murine Embryonic Stem Cells

Embryonic stem cells (ESC) have the potential to self-renew indefinitely and to differentiate into any of the three germ layers. The molecular mechanisms for self-renewal, maintenance of pluripotency and lineage specification are poorly understood, but recent results point to a key role for epigenetic mechanisms. In this study, we focus on quantifying the impact of histone 3 acetylation (H3K9,14ac) on gene expression in murine embryonic stem cells. We analyze genome-wide histone acetylation patterns and gene expression profiles measured over the first five days of cell differentiation triggered by silencing Nanog, a key transcription factor in ESC regulation. We explore the temporal and spatial dynamics of histone acetylation data and its correlation with gene expression using supervised and unsupervised statistical models. On a genome-wide scale, changes in acetylation are significantly correlated to changes in mRNA expression and, surprisingly, this coherence increases over time. We quantify the predictive power of histone acetylation for gene expression changes in a balanced cross-validation procedure. In an in-depth study we focus on genes central to the regulatory network of Mouse ESC, including those identified in a recent genome-wide RNAi screen and in the PluriNet, a computationally derived stem cell signature. We find that compared to the rest of the genome, ESC-specific genes show significantly more acetylation signal and a much stronger decrease in acetylation over time, which is often not reflected in an concordant expression change. These results shed light on the complexity of the relationship between histone acetylation and gene expression and are a step forward to dissect the multilayer regulatory mechanisms that determine stem cell fate.Comment: accepted at PLoS Computational Biolog

Large-scale associations between the leukocyte transcriptome and BOLD responses to speech differ in autism early language outcome subtypes.

Heterogeneity in early language development in autism spectrum disorder (ASD) is clinically important and may reflect neurobiologically distinct subtypes. Here, we identified a large-scale association between multiple coordinated blood leukocyte gene coexpression modules and the multivariate functional neuroimaging (fMRI) response to speech. Gene coexpression modules associated with the multivariate fMRI response to speech were different for all pairwise comparisons between typically developing toddlers and toddlers with ASD and poor versus good early language outcome. Associated coexpression modules were enriched in genes that are broadly expressed in the brain and many other tissues. These coexpression modules were also enriched in ASD-associated, prenatal, human-specific, and language-relevant genes. This work highlights distinctive neurobiology in ASD subtypes with different early language outcomes that is present well before such outcomes are known. Associations between neuroimaging measures and gene expression levels in blood leukocytes may offer a unique in vivo window into identifying brain-relevant molecular mechanisms in ASD