Increasing access to water through flexible entitlements?

This article discusses 2 ideas for reforming abstraction of water from the natural environment in order to provide a balance between environmental protection and secure, sustainable access to water also for future generations. This matters in light of an increased risk of water scarcity and drought due to growth and a changing climate. The first of these ideas – a sliding scale of legal protection for abstractions seeks to match the strength of legal protection through the abstraction licence to how much water is abstracted, as well as to how critical to business use, and environmentally beneficial the abstraction is. The second idea – ‘bubble licensing’ – involves capping the amount of water available for abstraction in a catchment and to promote exchanges of water between abstractors, not just through trading, but also through reciprocity exchanges and bartering. This collective action approach is intended to transcend an individual fixed entitlement approach to abstracting water. The article develops its argument through an analysis of literature on water rights, pollution trading, water charges, as well as a reference to ongoing reform debates about abstraction licensing in England

Improved detection of Staphylococcus intermedius group in a routine diagnostic laboratory

PublishedEvaluation StudiesJournal ArticleThis is the final version of the article. Available from ASM via the DOI in this record.The Staphylococcus intermedius group (SIG) includes zoonotic pathogens traditionally associated with dog bites. We describe a simple scheme for improved detection of SIG using routine laboratory methods, report its effect on isolation rates, and use sequencing to confirm that, apart from one atypical SIG strain, most isolates are Staphylococcus pseudintermedius

Human and Porcine Hepatitis E Virus Strains, United Kingdom

We describe a case of acquired infection of a strain of hepatitis E virus (HEV)with a 100% amino acid identity to the analogous region in strains of HEV circulating in a United Kingdom pig herd. This case further supports the theory that autochthonous HEV infection in industrialized countries is zoonotic

The transcriptional landscape of αβ T cell differentiation

αβT cell differentiation from thymic precursors is a complex process, explored here with the breadth of ImmGen expression datasets, analyzing how differentiation of thymic precursors gives rise to transcriptomes. After surprisingly gradual changes though early T commitment, transit through the CD4+CD8+ stage involves a shutdown or rare breadth, and correlating tightly with MYC. MHC-driven selection promotes a large-scale transcriptional reactivation. We identify distinct signatures that mark cells destined for positive selection versus apoptotic deletion. Differential expression of surprisingly few genes accompany CD4 or CD8 commitment, a similarity that carries through to peripheral T cells and their activation, revealed by mass cytometry phosphoproteomics. The novel transcripts identified as candidate mediators of key transitions help define the “known unknown” of thymocyte differentiation

Testing for differential abundance in mass cytometry data.

When comparing biological conditions using mass cytometry data, a key challenge is to identify cellular populations that change in abundance. Here, we present a computational strategy for detecting 'differentially abundant' populations by assigning cells to hyperspheres, testing for significant differences between conditions and controlling the spatial false discovery rate. Our method (http://bioconductor.org/packages/cydar) outperforms other approaches in simulations and finds novel patterns of differential abundance in real data.This work was supported by Cancer Research UK (core funding to J.C.M., award no. A17197), the University of Cambridge and Hutchison Whampoa Limited. J.C.M. was also supported by core funding from EMBL

A Thirty Million Year-Old Inherited Heteroplasmy

Due to essentially maternal inheritance and a bottleneck effect during early oogenesis, newly arising mitochondrial DNA (mtDNA) mutations segregate rapidly in metazoan female germlines. Consequently, heteroplasmy (i.e. the mixture of mtDNA genotypes within an organism) is generally resolved to homoplasmy within a few generations. Here, we report an exceptional transpecific heteroplasmy (predicting an alanine/valine alloacceptor tRNA change) that has been stably inherited in oniscid crustaceans for at least thirty million years. Our results suggest that this heteroplasmy is stably transmitted across generations because it occurs within mitochondria and therefore escapes the mtDNA bottleneck that usually erases heteroplasmy. Consistently, at least two oniscid species possess an atypical trimeric mitochondrial genome, which provides an adequate substrate for the emergence of a constitutive intra-mitochondrial heteroplasmy. Persistence of a mitochondrial polymorphism on such a deep evolutionary timescale suggests that balancing selection may be shaping mitochondrial sequence evolution in oniscid crustaceans

A Complex Role for FGF-2 in Self-Renewal, Survival, and Adhesion of Human Embryonic Stem Cells

The transcription program that is responsible for the pluripotency of human ESCs (hESCs) is believed to be comaintained by exogenous fibroblast growth factor-2 (FGF-2), which activates FGF receptors (FGFRs) and stimulates the mitogen-activated protein kinase (MAPK) pathway. However, the same pathway is stimulated by insulin receptors, insulin-like growth factor 1 receptors, and epidermal growth factor receptors. This mechanism is further complicated by intracrine FGF signals. Thus, the molecular mechanisms by which FGF-2 promotes the undifferentiated growth of hESCs are unclear. Here we show that, in undifferentiated hESCs, exogenous FGF-2 stimulated the expression of stem cell genes while suppressing cell death and apoptosis genes. Inhibition of autocrine FGF signaling caused upregulation of differentiation-related genes and downregulation of stem cell genes. Thus, exogenous FGF-2 reinforced the pluripotency maintenance program of intracrine FGF-2 signaling. Consistent with this hypothesis, expression of endogenous FGF-2 decreased during hESC differentiation and FGF-2 knockdown-induced hESC differentiation. In addition, FGF-2 signaling via FGFR2 activated MAPK kinase/extracellular signal-regulated kinase and AKT kinases, protected hESC from stress-induced cell death, and increased hESC adhesion and cloning efficiency. This stimulation of self-renewal, cell survival, and adhesion by exogenous and endogenous FGF-2 may synergize to maintain the undifferentiated growth of hESCs. Stem Cells 2009;27:1847–185

Clinical phenotype and outcome of hepatitis E virus - associated neuralgic amyotrophy

Objective: To determine the clinical phenotype and outcome in hepatitis E virus–associated neuralgic amyotrophy (HEV-NA). Methods: Cases of NA were identified in 11 centers from 7 European countries, with retrospective analysis of demographics, clinical/laboratory findings, and treatment and outcome. Cases of HEV-NA were compared with NA cases without evidence of HEV infection. Results: Fifty-seven cases of HEV-NA and 61 NA cases without HEV were studied. Fifty-six of 57 HEV-NA cases were anti-HEV IgM positive; 53/57 were IgG positive. In 38 cases, HEV RNA was recovered from the serum and in 1 from the CSF (all genotype 3). Fifty-one of 57 HEV-NA cases were anicteric; median alanine aminotransferase 259 IU/L (range 12–2,961 IU/L); in 6 cases, liver function tests were normal. HEV-NA cases were more likely to have bilateral involvement (80.0% vs 8.6%, p < 0.001), damage outside the brachial plexus (58.5% vs 10.5%, p < 0.01), including phrenic nerve and lumbosacral plexus injury (25.0% vs 3.5%, p = 0.01, and 26.4% vs 7.0%, p = 0.001), reduced reflexes (p = 0.03), sensory symptoms (p = 0.04) with more extensive damage to the brachial plexus. There was no difference in outcome between the 2 groups at 12 months. Conclusions: Patients with HEV-NA are usually anicteric and have a distinct clinical phenotype, with predominately bilateral asymmetrical involvement of, and more extensive damage to, the brachial plexus. Involvement outside the brachial plexus is more common in HEV-NA. The relationship between HEV and NA is likely to be causal, but is easily overlooked. Patients presenting with NA should be tested for HEV, irrespective of liver function test results. Prospective treatment/outcome studies of HEV-NA are warranted