Learning and reaction times in mouse touchscreen tests are differentially impacted by mutations in genes encoding postsynaptic interacting proteins SYNGAP1 , NLGN3 , DLGAP1 , DLGAP2 and SHANK2

The postsynaptic terminal of vertebrate excitatory synapses contains a highly conserved multiprotein complex that comprises neurotransmitter receptors, cell-adhesion molecules, scaffold proteins and enzymes, which are essential for brain signalling and plasticity underlying behaviour. Increasingly, mutations in genes that encode postsynaptic proteins belonging to the PSD-95 protein complex, continue to be identified in neurodevelopmental disorders (NDDs) such as autism spectrum disorder, intellectual disability and epilepsy. These disorders are highly heterogeneous, sharing genetic aetiology and comorbid cognitive and behavioural symptoms. Here, by using genetically engineered mice and innovative touchscreen-based cognitive testing, we sought to investigate whether loss-of-function mutations in genes encoding key interactors of the PSD-95 protein complex display shared phenotypes in associative learning, updating of learned associations and reaction times. Our genetic dissection of mice with loss-of-function mutations in Syngap1, Nlgn3, Dlgap1, Dlgap2 and Shank2 showed that distinct components of the PSD-95 protein complex differentially regulate learning, cognitive flexibility and reaction times in cognitive processing. These data provide insights for understanding how human mutations in these genes lead to the manifestation of diverse and complex phenotypes in NDDs

Three Styles in the Study of Violence

This is a postprint (accepted manuscript) version of the article published in Reviews in Anthropology 37:1-19. The final version of the article can be found at http://dx.doi.org/10.1080/00938150701829525 (login required to access content). The version made available in Digital Common was supplied by the author.Accepted Manuscripttru

Infant growth and body composition from birth to 24 months: Are infants developing the same?

Background: Given the importance of infancy for establishing growth trajectories, with later-life health consequences, we investigated longitudinal body composition among infants from six economically and ethnically diverse countries.Methods: We recruited mother-infant dyads using the WHO Multicenter Growth Reference Study criteria. We measured fat-free mass (FFM) in 1393 (49% female) infants from birth to 6 months of age (Australia, India, and South Africa; n = 468), 3-24 months of age (Brazil, Pakistan, South Africa, and Sri Lanka; n = 925), and derived fat mass (FM), fat mass index (FMI), and fat-free mass index (FFMI). Height-for-age (HAZ), weight-for-age (WAZ), and weight-for-length (WHZ) Z-scores were computed. Sex differences were assessed using a t-test, and country differences using a one-way analysis of covariance. We further compared subsamples of children with average (-0.25 \u3e HAZ \u3c +0.25), below-average (≤-0.25) and above-average (≥+0.25) HAZ.Results: HAZ performed well between 0 and 6 months, but less so between 3 and 24 months. The stunting prevalence peaked at 10.3% for boys and 7.8% for girls, at 24 months. By 24 months, girls had greater FMI (10%) than boys. There were significant differences in FFM (both sexes in all countries) and FM (Brazilian boys, Pakistani and South African girls) by 24 months of age between infants with average, above-average, and below-average HAZ.Conclusion: In a multi-country sample representing more ideal maternal conditions, body composition was heterogeneous even among infants who exhibited ideal length. Having a mean HAZ close to the median of the WHO standard for length reduced FFM between-country heterogeneity but not FM, suggesting that other factors may influence adiposity

A systematic review of the health and well-being benefits of biodiverse environments

This is an Accepted Manuscript of an article published by Taylor & Francis in the Journal of Toxicology and Environmental Health, Part B: Critical Reviews on 05 Mar 2014, available online: http://www.tandfonline.com/doi/pdf/10.1080/10937404.2013.856361Recent ecosystem service models have placed biodiversity as a central factor in the processes that link the natural environment to health. While it is recognized that disturbed ecosystems might negatively affect human well-being, it is not clear whether biodiversity is related to or can promote "good" human health and well-being. The aim of this study was to systematically identify, summarize, and synthesize research that had examined whether biodiverse environments are health promoting. The objectives were twofold: (1) to map the interdisciplinary field of enquiry and (2) to assess whether current evidence enables us to characterize the relationship. Due to the heterogeneity of available evidence a narrative synthesis approach was used, which is textual rather than statistical. Extensive searches identified 17 papers that met the inclusion criteria: 15 quantitative and 2 qualitative. The evidence was varied in disciplinary origin, with authors approaching the question using different study designs and methods, and conceptualizations of biodiversity, health, and well-being. There is some evidence to suggest that biodiverse natural environments promote better health through exposure to pleasant environments or the encouragement of health-promoting behaviors. There was also evidence of inverse relationships, particularly at a larger scale (global analyses). However, overall the evidence is inconclusive and fails to identify a specific role for biodiversity in the promotion of better health. High-quality interdisciplinary research is needed to produce a more reliable evidence base. Of particular importance is identifying the specific ecosystem services, goods, and processes through which biodiversity may generate good health and well-being.European Regional Development Fund Programme 2007 to 2013European Social Fund Convergence Programme for Cornwall and the Isles of Scilly

Data report: evaluation of shipboard magnetostratigraphy by alternating field demagnetization of discrete samples, Expedition 361, Site U1475

The paleomagnetic shipboard data of International Ocean Discovery Program Site U1475, with a record reaching back to approximately 7 Ma, allowed for the identification of major magnetic polarity chrons and subchrons back to ~3.5 Ma. However, the natural remanent magnetization (NRM) was very weak, and transitional intervals with unclear polarity were as thick as several meters. The midpoints of these transitional intervals were reported in the shipboard results without decimal places because of the poor data quality. To evaluate and possibly refine the shipboard magnetostratigraphy, subsampling was performed across the polarity transitions. Detailed alternating field (AF) demagnetization experiments were conducted on these discrete samples and were complemented by anhysteretic remanent magnetization acquisition measurements and subsequent demagnetization. AF demagnetization data of NRM were analyzed using anchored principal component analysis (PCA) to obtain the characteristic remanent magnetization. These PCA results generally confirm the smoothed signal across polarity transitions at Site U1475. However, the midpoint depths of the top of the Keana Subchron, the Gauss-Matuyama and Matuyama-Brunhes boundaries, and the base of the Olduvai Subchron were adjusted

A behavioral database for masked form priming

Reading involves a process of matching an orthographic input with stored representations in lexical memory. The masked priming paradigm has become a standard tool for investigating this process. Use of existing results from this paradigm can be limited by the precision of the data and the need for cross-experiment comparisons that lack normal experimental controls. Here, we present a single, large, high-precision, multicondition experiment to address these problems. Over 1,000 participants from 14 sites responded to 840 trials involving 28 different types of orthographically related primes (e.g., castfe–CASTLE) in a lexical decision task, as well as completing measures of spelling and vocabulary. The data were indeed highly sensitive to differences between conditions: After correction for multiple comparisons, prime type condition differences of 2.90 ms and above reached significance at the 5% level. This article presents the method of data collection and preliminary findings from these data, which included replications of the most widely agreed-upon differences between prime types, further evidence for systematic individual differences in susceptibility to priming, and new evidence regarding lexical properties associated with a target word’s susceptibility to priming. These analyses will form a basis for the use of these data in quantitative model fitting and evaluation and for future exploration of these data that will inform and motivate new experiments

The African Genome Variation Project shapes medical genetics in Africa.

Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterization of African genetic diversity is needed. The African Genome Variation Project provides a resource with which to design, implement and interpret genomic studies in sub-Saharan Africa and worldwide. The African Genome Variation Project represents dense genotypes from 1,481 individuals and whole-genome sequences from 320 individuals across sub-Saharan Africa. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across sub-Saharan Africa. We identify new loci under selection, including loci related to malaria susceptibility and hypertension. We show that modern imputation panels (sets of reference genotypes from which unobserved or missing genotypes in study sets can be inferred) can identify association signals at highly differentiated loci across populations in sub-Saharan Africa. Using whole-genome sequencing, we demonstrate further improvements in imputation accuracy, strengthening the case for large-scale sequencing efforts of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa

Biodiversity, cultural pathways, and human health: a framework.

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.Direct contact with biodiversity is culturally important in a range of contexts. Many people even join conservation organisations to protect biodiversity that they will never encounter first-hand. Despite this, we have little idea how biodiversity affects people's well-being and health through these cultural pathways. Human health is sensitive to apparently trivial psychological stimuli, negatively affected by the risk of environmental degradation, and positively affected by contact with natural spaces. This suggests that well-being and health should be affected by biodiversity change, but few studies have begun to explore these relationships. Here, we develop a framework for linking biodiversity change with human cultural values, well-being, and health. We argue that better understanding these relations might be profoundly important for biodiversity conservation and public health.Natural Environment Research CouncilEuropean Regional Development Fund Programme 2007 to 2013European Social Fund Convergence Programme for Cornwall and the Isles of Scilly

An Amphioxus Gli Gene Reveals Conservation of Midline Patterning and the Evolution of Hedgehog Signalling Diversity in Chordates

Background. Hedgehog signalling, interpreted in receiving cells by Gli transcription factors, plays a central role in the development of vertebrate and Drosphila embryos. Many aspects of the signalling pathway are conserved between these lineages, however vertebrates have diverged in at least one key aspect: they have evolved multiple Gli genes encoding functionally-distinct proteins, increasing the complexity of the hedgehog-dependent transcriptional response. Amphioxus is one of the closest living relatives of the vertebrates, having split from the vertebrate lineage prior to the widespread gene duplication prominent in early vertebrate evolution. Principal findings. We show that amphioxus has a single Gli gene, which is deployed in tissues adjacent to sources of hedgehog signalling derived from the midline and anterior endoderm. This shows the duplication and divergence of the Gli family, and hence the origin of vertebrate Gli functional diversity, was specific to the vertebrate lineage. However we also show that the single amphioxus Gli gene produces two distinct transcripts encoding different proteins. We utilise three tests of Gli function to examine the transcription regulatory capacities of these different proteins, demonstrating one has activating activity similar to Gli2, while the other acts as a weak repressor, similar to Gli3. Conclusions. These data show that the vertebrates and amphioxus have evolved functionally-similar repertoires of Gli proteins using parallel molecular routes; vertebrates via gene duplication and divergence, and amphioxus via alternate splicing of a single gene. Our results demonstrate that similar functional complexity of intercellular signalling can be achieved via different evolutionary pathways