State Legislative Update

As the use of collaborative law increases, the need for uniform laws to help facilitate this process across state lines grew. In February 2007, the Uniform Law Commission (ULC) began drafting an act to address this need. At the July 2009 meeting, the Uniform Collaborative Law Act (UCLA) was unanimously approved by the Commission and was subsequently submitted to the American Bar Association (ABA) House of Delegates for approval. In March 2010, the house approved the amended act after the ULC made a few small changes per the house\u27s recommendation. Since receiving ABA approval, the UCLA has been passed in eight states, most recently Alabama, and introduced this year in five more

Understanding the “gut instinct” of expert coaches during talent identification

Coaches are an integral part of talent identification in sport and are often used as the “gold standard” against which scientific methods of talent identification are compared. However, their decision-making during this process is not well understood. In this article, we use an ecological approach to explore talent identification in combat sports. We interviewed twenty-four expert, international-level coaches from the Olympic disciplines of boxing, judo, and taekwondo (age: 48.7 + 7.5 years; experience: 20.8 + 8.3 years). Findings indicated that when coaches identify talent they rely on “gut instinct”: intuitive judgements made without conscious thought, used to direct attention to particular athletes or characteristics. Our analysis revealed four major contributors to coaches’ intuition: experiential knowledge, temporal factors, seeing athletes in context, and what can be worked with. Our findings demonstrate that i) athlete selections may be influenced by the coaches’ perceived ability to improve certain athletes (rather than solely on athlete ability); and ii) “instinctual” decisions are the result of years of experience, time spent with the athlete, and the context surrounding the decision. Based on these findings, we recommend that future research focuses on the duration and conditions that are required for coaches to confidently and reliably identify talented athletes

Bone morphogenetic protein 7 sensitizes O6-methylguanine methyltransferase expressing-glioblastoma stem cells to clinically relevant dose of temozolomide.

BackgroundTemozolomide (TMZ) is an oral DNA-alkylating agent used for treating patients with glioblastoma. However, therapeutic benefits of TMZ can be compromised by the expression of O6-methylguanine methyltransferase (MGMT) in tumor tissue. Here we used MGMT-expressing glioblastoma stem cells (GSC) lines as a model for investigating the molecular mechanism underlying TMZ resistance, while aiming to explore a new treatment strategy designed to possibly overcome resistance to the clinically relevant dose of TMZ (35 μM).MethodsMGMT-expressing GSC cultures are resistant to TMZ, and IC50 (half maximal inhibitory concentration) is estimated at around 500 μM. Clonogenic GSC surviving 500 μM TMZ (GSC-500 μM TMZ), were isolated. Molecular signatures were identified via comparative analysis of expression microarray against parental GSC (GSC-parental). The recombinant protein of top downregulated signature was used as a single agent or in combination with TMZ, for evaluating therapeutic effects of treatment of GSC.ResultsThe molecular signatures characterized an activation of protective stress responses in GSC-500 μM TMZ, mainly including biotransformation/detoxification of xenobiotics, blocked endoplasmic reticulum stress-mediated apoptosis, epithelial-to-mesenchymal transition (EMT), and inhibited growth/differentiation. Bone morphogenetic protein 7 (BMP7) was identified as the top down-regulated gene in GSC-500 μM TMZ. Although augmenting BMP7 signaling in GSC by exogenous BMP7 treatment did not effectively stop GSC growth, it markedly sensitized both GSC-500 μM TMZ and GSC-parental to 35 μM TMZ treatment, leading to loss of self-renewal and migration capacity. BMP7 treatment induced senescence of GSC cultures and suppressed mRNA expression of CD133, MGMT, and ATP-binding cassette drug efflux transporters (ABCB1, ABCG2), as well as reconfigured transcriptional profiles in GSC by downregulating genes associated with EMT/migration/invasion, stemness, inflammation/immune response, and cell proliferation/tumorigenesis. BMP7 treatment significantly prolonged survival time of animals intracranially inoculated with GSC when compared to those untreated or treated with TMZ alone (p = 0.0017), whereas combination of two agents further extended animal survival compared to BMP7 alone (p = 0.0489).ConclusionsThese data support the view that reduced endogenous BMP7 expression/signaling in GSC may contribute to maintained stemness, EMT, and chemoresistant phenotype, suggesting that BMP7 treatment may provide a novel strategy in combination with TMZ for an effective treatment of glioblastoma exhibiting unmethylated MGMT

Genetic liability to schizophrenia is associated with exposure to traumatic events in childhood

Background There is a wealth of literature on the observed association between childhood trauma and psychotic illness. However, the relationship between childhood trauma and psychosis is complex and could be explained, in part, by gene–environment correlation. Methods The association between schizophrenia polygenic scores (PGS) and experiencing childhood trauma was investigated using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Norwegian Mother, Father and Child Cohort Study (MoBa). Schizophrenia PGS were derived in each cohort for children, mothers, and fathers where genetic data were available. Measures of trauma exposure were derived based on data collected throughout childhood and adolescence (0–17 years; ALSPAC) and at age 8 years (MoBa). Results Within ALSPAC, we found a positive association between schizophrenia PGS and exposure to trauma across childhood and adolescence; effect sizes were consistent for both child or maternal PGS. We found evidence of an association between the schizophrenia PGS and the majority of trauma subtypes investigated, with the exception of bullying. These results were comparable with those of MoBa. Within ALSPAC, genetic liability to a range of additional psychiatric traits was also associated with a greater trauma exposure. Conclusions Results from two international birth cohorts indicate that genetic liability for a range of psychiatric traits is associated with experiencing childhood trauma. Genome-wide association study of psychiatric phenotypes may also reflect risk factors for these phenotypes. Our findings also suggest that youth at higher genetic risk might require greater resources/support to ensure they grow-up in a healthy environment

A coupled terrestrial and aquatic biogeophysical model of the Upper Merrimack River watershed, New Hampshire, to inform ecosystem services evaluation and management under climate and land-cover change

Accurate quantification of ecosystem services (ES) at regional scales is increasingly important for making informed decisions in the face of environmental change. We linked terrestrial and aquatic ecosystem process models to simulate the spatial and temporal distribution of hydrological and water quality characteristics related to ecosystem services. The linked model integrates two existing models (a forest ecosystem model and a river network model) to establish consistent responses to changing drivers across climate, terrestrial, and aquatic domains. The linked model is spatially distributed, accounts for terrestrial–aquatic and upstream–downstream linkages, and operates on a daily time-step, all characteristics needed to understand regional responses. The model was applied to the diverse landscapes of the Upper Merrimack River watershed, New Hampshire, USA. Potential changes in future environmental functions were evaluated using statistically downscaled global climate model simulations (both a high and low emission scenario) coupled with scenarios of changing land cover (centralized vs. dispersed land development) for the time period of 1980–2099. Projections of climate, land cover, and water quality were translated into a suite of environmental indicators that represent conditions relevant to important ecosystem services and were designed to be readily understood by the public. Model projections show that climate will have a greater influence on future aquatic ecosystem services (flooding, drinking water, fish habitat, and nitrogen export) than plausible changes in land cover. Minimal changes in aquatic environmental indicators are predicted through 2050, after which the high emissions scenarios show intensifying impacts. The spatially distributed modeling approach indicates that heavily populated portions of the watershed will show the strongest responses. Management of land cover could attenuate some of the changes associated with climate change and should be considered in future planning for the region

The Ess/Type VII secretion system of Staphylococcus aureus shows unexpected genetic diversity

We thank the core sequencing and informatics teams at the Sanger Institute for their assistance and The Wellcome Trust for its support of the Sanger Institute Pathogen Genomics and Biology groups. SRH, JP and MTGH were supported by Wellcome Trust grant 098051. Bioinformatics and Computational Biology analyses were supported by the University of St Andrews Bioinformatics Unit that is funded by a Wellcome Trust ISSF award (grant 105621/Z/14/Z). SP is funded by the UKCRC Translational Infection Research Initiative, and the NIHR Cambridge Biomedical Research Centre. CPH is supported by the Wellcome Trust (grant number 104241/z/14/z) TP is a Royal Society/Wolfson Merit Award Holder.BACKGROUND: Type VII protein secretion (T7SS) is a specialised system for excreting extracellular proteins across bacterial cell membranes and has been associated with virulence in Staphylococcus aureus. The genetic diversity of the ess locus, which encodes the T7SS, and the functions of proteins encoded within it are poorly understood. RESULTS: We used whole genome sequence data from 153 isolates representative of the diversity of the species to investigate the genetic variability of T7SS across S. aureus. The ess loci were found to comprise of four distinct modules based on gene content and relative conservation. Modules 1 and 4, comprising of the 5' and 3' modules of the ess locus, contained the most conserved clusters of genes across the species. Module 1 contained genes encoding the secreted protein EsxA, and the EsaAB and EssAB components of the T7SS machinery, and Module 4 contained two functionally uncharacterized conserved membrane proteins. Across the species four variants of Module 2 were identified containing the essC gene, each of which was associated with a specific group of downstream genes. The most diverse module of the ess locus was Module 3 comprising a highly variable arrangement of hypothetical proteins. RNA-Seq was performed on representatives of the four Module 2 variants and demonstrated strain-specific differences in the levels of transcription in the conserved Module 1 components and transcriptional linkage Module 2, and provided evidence of the expression of genes the variable regions of the ess loci. CONCLUSIONS: The ess locus of S. aureus exhibits modularity and organisational variation across the species and transcriptional variation. In silico analysis of ess loci encoded hypothetical proteins identified potential novel secreted substrates for the T7SS. The considerable variety in operon arrangement between otherwise closely related isolates provides strong evidence for recombination at this locus. Comparison of these recombination regions with each other, and with the genomes of other Staphylococcal species, failed to identify evidence of intra- and inter-species recombination, however the analysis identified a novel T7SS in another pathogenic staphylococci, Staphylococcus lugdunensis.Publisher PDFPeer reviewe