Robust study design is as important on the social as it is on the ecological side of applied ecological research

1. The effective management of natural systems often requires resource users to change their behaviour. This has led to many applied ecologists using research tools developed by social scientists. This comes with challenges as ecologists often lack relevant disciplinary training. 2. Using an example from the current issue of Journal of Applied Ecology that investigated how conservation interventions influenced conservation outcomes, we discuss the challenges of conducting interdisciplinary science. We illustrate our points using examples from research investigating the role of law enforcement and outreach activities in limiting illegal poaching and the application of the theory of planned behaviour to conservation. 3. Synthesis and applications. Interdisciplinary research requires equal rigour to be applied to ecological and social aspects. Researchers with a natural science background need to access expertise and training in the principles of social science research design and methodology, in order to permit a more balanced interdisciplinary understanding of social–ecological system

Cysteine Residues Contribute to the Dimerization and Enzymatic Activity of Human Nuclear dUTP Nucleotidohydrolase (nDut).

dUTPase is an enzyme found in all organisms that have thymine as a constituent of DNA. Through evolution, humans have two major isoforms of dUTPase: a mitochondrial (mDut) and a nuclear (nDut) isoform. The nuclear isoform of dUTPase is a 164-amino-acids-long protein containing three cysteine residues. nDut\u27s starting methionine is post-translationally cleaved, leaving four unique amino acids on its amino-terminus including one cysteine residue (C3). These are not present in the mitochondrial isoform (mDut). Using mass spectrometry analyses of recombinant dUTPase constructs, we have discovered an intermolecular disulfide bridge between cysteine-3 of each nDut monomer. We have found that these two residues stabilize a dimer configuration that is unique to the nDut isoform. We have also uncovered an intramolecular disulfide linkage between cysteine residues C78 and C134, stabilizing the monomeric state of the protein. Of note, both disulfide linkages are essential for nDut\u27s enzymatic activity and dimeric formation can be augmented by the addition of the oxidizing agent, hydrogen peroxide to cells. Analyses of endogenous cellular dUTPase proteins confirm these differences between the two isoforms. We observed that mDut appears to be a mixture of monomer, dimer, and trimer conformations, as well as higher-order subunit interactions. In contrast, nDut appeared to exist only in monomeric and dimeric forms. Cysteine-based redox switches have recently emerged as a distinct class of post-translational modification. In light of this and our results, we propose that nDut possesses a redox switch whereby cysteine interactions regulate nDut\u27s dUTP-hydrolyzing activity

The effectiveness of Payments for Ecosystem Services at delivering improvements in water quality: lessons for experiments at the landscape scale

Background Randomised Control Trials (RCTs) are used in impact evaluation in a range of fields. However, despite calls for their greater use in environmental management, their use to evaluate landscape scale interventions remains rare. Payments for Ecosystem Services (PES) incentivise land users to manage land to provide environmental benefits. We present the first RCT evaluation of a PES program aiming to improve water quality. Watershared is a program which incentivises landowners to avoid deforestation and exclude cattle from riparian forests. Using this unusual landscape-scale experiment we explore the efficacy of Watershared at improving water quality, and draw lessons for future RCT evaluations of landscape-scale environmental management interventions. Methods One hundred and twenty-nine communities in the Bolivian Andes were randomly allocated to treatment (offered Watershared agreements) or control (not offered agreements) following baseline data collection (including Escherichia coli contamination in most communities) in 2010. We collected end-line data in 2015. Using our end-line data, we explored the extent to which variables associated with the intervention (e.g. cattle exclusion, absence of faeces) predict water quality locally. We then investigated the efficacy of the intervention at improving water quality at the landscape scale using the RCT. This analysis was done in two ways; for the subset of communities for which we have both baseline and end-line data from identical locations we used difference-in-differences (matching on baseline water quality), for all sites we compared control and treatment at end-line controlling for selected predictors of water quality. Results The presence of cattle faeces in water adversely affected water quality suggesting excluding cattle has a positive impact on water quality locally. However, both the matched difference-in-differences analysis and the comparison between treatment and control communities at end-line suggested Watershared was not effective at reducing E. coli contamination at the landscape scale. Uptake of Watershared agreements was very low and the most important land from a water quality perspective (land around water intakes) was seldom enrolled. Discussion Although excluding cattle may have a positive local impact on water quality, higher uptake and better targeting would be required to achieve a significant impact on the quality of water consumed in the communities. Although RCTs potentially have an important role to play in building the evidence base for approaches such as PES, they are far from straightforward to implement. In this case, the randomised trial was not central to concluding that Watershared had not produced a landscape scale impact. We suggest that this RCT provides valuable lessons for future use of randomised experiments to evaluate landscape-scale environmental management interventions

The Small Magellanic Cloud Investigation of Dust and Gas Evolution (SMIDGE): The Dust Extinction Curve from Red Clump Stars

We use Hubble Space Telescope (HST) observations of red clump stars taken as part of the Small Magellanic Cloud Investigation of Dust and Gas Evolution (SMIDGE) program to measure the average dust extinction curve in a ~ 200 pc x 100 pc region in the southwest bar of the Small Magellanic Cloud (SMC). The rich information provided by our 8-band ultra-violet through near-infrared photometry allows us to model the color-magnitude diagram of the red clump accounting for the extinction curve shape, a log-normal distribution of $A_{V}$, and the depth of the stellar distribution along the line of sight. We measure an extinction curve with $R_{475} = A_{475}/(A_{475}-A_{814})$ = 2.65 $\pm$ 0.11. This measurement is significantly larger than the equivalent values of published Milky Way $R_{V}$ = 3.1 ($R_{475} = 1.83$) and SMC Bar $R_{V}$ = 2.74 ($R_{475} = 1.86$) extinction curves. Similar extinction curve offsets in the Large Magellanic Cloud (LMC) have been interpreted as the effect of large dust grains. We demonstrate that the line-of-sight depth of the SMC (and LMC) introduces an apparent "gray" contribution to the extinction curve inferred from the morphology of the red clump. We show that no gray dust component is needed to explain extinction curve measurements when a full-width half-max depth of 10 $\pm$ 2 kpc in the stellar distribution of the SMC (5 $\pm$ 1 kpc for the LMC) is considered, which agrees with recent studies of Magellanic Cloud stellar structure. The results of our work demonstrate the power of broad-band HST imaging for simultaneously constraining dust and galactic structure outside the Milky Way.Comment: 16 pages, 12 figures, 5 tables. Accepted for publication in Ap

Functional plasticity of antibacterial EndoU toxins.

Bacteria use several different secretion systems to deliver toxic EndoU ribonucleases into neighboring cells. Here, we present the first structure of a prokaryotic EndoU toxin in complex with its cognate immunity protein. The contact-dependent growth inhibition toxin CdiA-CTSTECO31 from Escherichia coli STEC_O31 adopts the eukaryotic EndoU fold and shares greatest structural homology with the nuclease domain of coronavirus Nsp15. The toxin contains a canonical His-His-Lys catalytic triad in the same arrangement as eukaryotic EndoU domains, but lacks the uridylate-specific ribonuclease activity that characterizes the superfamily. Comparative sequence analysis indicates that bacterial EndoU domains segregate into at least three major clades based on structural variations in the N-terminal subdomain. Representative EndoU nucleases from clades I and II degrade tRNA molecules with little specificity. In contrast, CdiA-CTSTECO31 and other clade III toxins are specific anticodon nucleases that cleave tRNAGlu between nucleotides C37 and m2 A38. These findings suggest that the EndoU fold is a versatile scaffold for the evolution of novel substrate specificities. Such functional plasticity may account for the widespread use of EndoU effectors by diverse inter-bacterial toxin delivery systems

Inflammation and immunity in schizophrenia: implications for pathophysiology and treatment.

Complex interactions between the immune system and the brain might have important aetiological and therapeutic implications for neuropsychiatric brain disorders. A possible association between schizophrenia and the immune system was postulated over a century ago, and is supported by epidemiological and genetic studies pointing to links with infection and inflammation. Contrary to the traditional view that the brain is an immunologically privileged site shielded behind the blood-brain barrier, studies in the past 20 years have noted complex interactions between the immune system, systemic inflammation, and the brain, which can lead to changes in mood, cognition, and behaviour. In this Review, we describe some of the important areas of research regarding innate and adaptive immune response in schizophrenia and related psychotic disorders that, we think, will be of interest to psychiatric clinicians and researchers. We discuss potential mechanisms and therapeutic implications of these findings, including studies of anti-inflammatory drugs in schizophrenia, describe areas for development, and offer testable hypotheses for future investigations.The work was supported by a doctoral clinical research training fellowship grant from the Wellcome Trust to Golam Khandaker (094790/Z/10/Z; 2010-‘13), grants from the Stanley Medical Research Institute and the National Institutes of Mental Health (grant# MH-94268) to Robert Yolken, and grants from the Wellcome Trust (095844/Z/11/Z & 088869/Z/09/Z), and the NIHR (RP-PG-0606-1335) to Peter Jones.This is the accepted manuscript. The final version is available from Elsevier at http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366%2814%2900122-9/abstrac

Telomere dysfunction accurately predicts clinical outcome in chronic lymphocytic leukaemia, even in patients with early stage disease

© 2014 John Wiley & Sons Ltd. Defining the prognosis of individual cancer sufferers remains a significant clinical challenge. Here we assessed the ability of high-resolution single telomere length analysis (STELA), combined with an experimentally derived definition of telomere dysfunction, to predict the clinical outcome of patients with chronic lymphocytic leukaemia (CLL). We defined the upper telomere length threshold at which telomere fusions occur and then used the mean of the telomere 'fusogenic' range as a prognostic tool. Patients with telomeres within the fusogenic range had a significantly shorter overall survival (P  <  0·0001; Hazard ratio [HR] = 13·2, 95% confidence interval [CI]  = 11·6-106·4) and this was preserved in early-stage disease patients (P  <  0·0001, HR=19·3, 95% CI = 17·8-802·5). Indeed, our assay allowed the accurate stratification of Binet stage A patients into those with indolent disease (91% survival at 10 years) and those with poor prognosis (13% survival at 10 years). Furthermore, patients with telomeres above the fusogenic mean showed superior prognosis regardless of their IGHV mutation status or cytogenetic risk group. In keeping with this finding, telomere dysfunction was the dominant variable in multivariate analysis. Taken together, this study provides compelling evidence for the use of high-resolution telomere length analysis coupled with a definition of telomere dysfunction in the prognostic assessment of CLL

ResearchCOVID‐19 Preparedness in Michigan Nursing Homes

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155466/1/jgs16490_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155466/2/jgs16490.pd