Comparing Migratory Patterns and Survival Between Wild and Wild Fish Surrogate Juvenile Spring Chinook Salmon (Oncorhynchus tshawytscha)

Anadromous salmonid populations in the Pacific Northwest have declined over the past 150 years. In 1999, wild spring Chinook salmon (Oncorhynchus tshawytscha) were federally listed as threatened within the Willamette Basin, OR. Currently, practices to restore wild populations in the upper Willamette Basin involve trapping wild adults at the base of high-head dams and hauling them upstream to historic spawning locations. Their resulting progeny must migrate downstream past the dams, highlighting the necessity of effective juvenile passage. Ideally, studies evaluating downstream juvenile passage structures would use wild fish, but this is often not feasible because of the large number of fish required for reliable estimates. The Wild Fish Surrogate Project at Oregon State University rears juvenile spring Chinook salmon as substitutes for wild-origin fish that are intended to behave similarly to wild ones and emulate wild juvenile migratory phenotypes in the Willamette Basin. We compared survival and movement of wild and wild fish surrogate juvenile Chinook salmon using a combination of PIT-tag detections at interrogation stations and seining recaptures in the McKenzie River Basin. We estimated survival with multi-state Cormack-Jolly-Seber models and compared survival between the two groups through time. Overall, detections and movements of wild and surrogate juveniles were similar, although wild fish surrogates tended to move earlier than their wild juvenile counterparts. Surrogate juveniles had a greater probability of movement within the upper Willamette River Basin compared to wild juveniles. This was likely due to the wild fish surrogates experiencing a novel environment and searching for suitable resources within the river system. Movement both within the upper Willamette River Basin and past Willamette Falls increased as the mean 7-day maximum temperature decreased, reflecting seasonal changes. Apparent survival differed between the two groups, and varied with maximum temperature. Surrogate fish had greater apparent survival at warmer temperatures compared to wild juveniles. This difference may have been a result of surrogate juveniles rearing at warmer temperatures prior to release and also being more likely to move downstream soon after being introduced into the McKenzie River

Global Extinction Risk for Seahorses, Pipefishes and Their Near Relatives (Syngnathiformes)

Few marine taxa have been comprehensively assessed for their conservation status, despite heavy pressures from fishing, habitat degradation and climate change. Here we report on the first global assessment of extinction risk for 300 species of syngnathiform fishes known as of 2017, using the IUCN Red List criteria. This order of bony teleosts is dominated by seahorses, pipefishes and seadragons (family Syngnathidae). It also includes trumpetfishes (Aulostomidae), shrimpfishes (Centriscidae), cornetfishes (Fistulariidae) and ghost pipefishes (Solenostomidae). At least 6% are threatened, but data suggest a mid-point estimate of 7.9% and an upper bound of 38%. Most of the threatened species are seahorses (Hippocampus spp.: 14/42 species, with an additional 17 that are Data Deficient) or freshwater pipefishes of the genus Microphis (2/18 species, with seven additional that are Data Deficient). Two species are Near Threatened. Nearly one-third of syngnathiformes (97 species) are Data Deficient and could potentially be threatened, requiring further field research and evaluation. Most species (61%) were, however, evaluated as Least Concern. Primary threats to syngnathids are (1) overexploitation, primarily by non-selective fisheries, for which most assessments were determined by criterion A (Hippocampus) and/or (2) habitat loss and degradation, for which assessments were determined by criterion B (Microphis and some Hippocampus). Threatened species occurred in most regions but more are found in East and South-east Asia and in South African estuaries. Vital conservation action for syngnathids, including constraining fisheries, particularly non-selective extraction, and habitat protection and rehabilitation, will benefit many other aquatic species

Predatory journals and their practices present a conundrum for systematic reviewers and evidence synthesisers of health research: A qualitative descriptive study

Predatory journals are a blemish on scholarly publishing and academia and the studies published within them are more likely to contain data that is false. The inclusion of studies from predatory journals in evidence syntheses is potentially problematic due to this propensity for false data to be included. To date, there has been little exploration of the opinions and experiences of evidence synthesisers when dealing with predatory journals in the conduct of their evidence synthesis. In this paper, the thoughts, opinions, and attitudes of evidence synthesisers towards predatory journals and the inclusion of studies published within these journals in evidence syntheses were sought. Focus groups were held with participants who were experienced evidence synthesisers from JBI (previously the Joanna Briggs Institute) collaboration. Utilising qualitative content analysis, two generic categories were identified: predatory journals within evidence synthesis, and predatory journals within academia. Our findings suggest that evidence synthesisers believe predatory journals are hard to identify and that there is no current consensus on the management of these studies if they have been included in an evidence synthesis. There is a critical need for further research, education, guidance, and development of clear processes to assist evidence synthesisers in the management of studies from predatory journals.</p

A Common Variant at the 14q32 Endometrial Cancer Risk Locus Activates AKT1 through YY1 Binding.

A recent meta-analysis of multiple genome-wide association and follow-up endometrial cancer case-control datasets identified a novel genetic risk locus for this disease at chromosome 14q32.33. To prioritize the functional SNP(s) and target gene(s) at this locus, we employed an in silico fine-mapping approach using genotyped and imputed SNP data for 6,608 endometrial cancer cases and 37,925 controls of European ancestry. Association and functional analyses provide evidence that the best candidate causal SNP is rs2494737. Multiple experimental analyses show that SNP rs2494737 maps to a silencer element located within AKT1, a member of the PI3K/AKT/MTOR intracellular signaling pathway activated in endometrial tumors. The rs2494737 risk A allele creates a YY1 transcription factor-binding site and abrogates the silencer activity in luciferase assays, an effect mimicked by transfection of YY1 siRNA. Our findings suggest YY1 is a positive regulator of AKT1, mediating the stimulatory effects of rs2494737 increasing endometrial cancer risk. Identification of an endometrial cancer risk allele within a member of the PI3K/AKT signaling pathway, more commonly activated in tumors by somatic alterations, raises the possibility that well tolerated inhibitors targeting this pathway could be candidates for evaluation as chemopreventive agents in individuals at high risk of developing endometrial cancer.The QIMR Berghofer groups were supported by a Rio Tinto Ride to Conquer Cancer (RTCC)/Weekend to End Women's Cancers (WEWC) Grant and NHMRC project grants 1058415 to SLE and 1031333 to ABS. ABS is supported by an NHMRC Senior Research Fellowship (1061779). DFE is a Principal Research Fellow of CR-UK.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Cell Press

Performance of the GeneXpert Ebola Assay for Diagnosis of Ebola Virus Disease in Sierra Leone: A Field Evaluation Study

Background: Throughout the Ebola virus disease (EVD) epidemic in West Africa, field laboratory testing for EVD has relied on complex, multi-step real-time reverse transcription PCR (RT-PCR) assays; an accurate sample-to-answer RT-PCR test would reduce time to results and potentially increase access to testing. We evaluated the performance of the Cepheid GeneXpert Ebola assay on clinical venipuncture whole blood (WB) and buccal swab (BS) specimens submitted to a field biocontainment laboratory in Sierra Leone for routine EVD testing by RT-PCR (“Trombley assay”). Methods and Findings: This study was conducted in the Public Health England EVD diagnostic laboratory in Port Loko, Sierra Leone, using residual diagnostic specimens remaining after clinical testing. EDTA-WB specimens (n = 218) were collected from suspected or confirmed EVD patients between April 1 and July 20, 2015. BS specimens (n = 71) were collected as part of a national postmortem screening program between March 7 and July 20, 2015. EDTA-WB and BS specimens were tested with Xpert (targets: glycoprotein [GP] and nucleoprotein [NP] genes) and Trombley (target: NP gene) assays in parallel. All WB specimens were fresh; 84/218 were tested in duplicate on Xpert to compare WB sampling methods (pipette versus swab); 43/71 BS specimens had been previously frozen. In all, 7/218 (3.2%) WB and 7/71 (9.9%) BS samples had Xpert results that were reported as “invalid” or “error” and were excluded, leaving 211 WB and 64 BS samples with valid Trombley and Xpert results. For WB, 22/22 Trombley-positive samples were Xpert-positive (sensitivity 100%, 95% CI 84.6%–100%), and 181/189 Trombley-negative samples were Xpert-negative (specificity 95.8%, 95% confidence interval (CI) 91.8%–98.2%). Seven of the eight Trombley-negative, Xpert-positive (Xpert cycle threshold [Ct] range 37.7–43.4) WB samples were confirmed to be follow-up submissions from previously Trombley-positive EVD patients, suggesting a revised Xpert specificity of 99.5% (95% CI 97.0%–100%). For Xpert-positive WB samples (n = 22), Xpert NP Ct values were consistently lower than GP Ct values (mean difference −4.06, 95% limits of agreement −6.09, −2.03); Trombley (NP) Ct values closely matched Xpert NP Ct values (mean difference −0.04, 95% limits of agreement −2.93, 2.84). Xpert results (positive/negative) for WB sampled by pipette versus swab were concordant for 78/79 (98.7%) WB samples, with comparable Ct values for positive results. For BS specimens, 20/20 Trombley-positive samples were Xpert-positive (sensitivity 100%, 95% CI 83.2%–100%), and 44/44 Trombley-negative samples were Xpert-negative (specificity 100%, 95% CI 92.0%–100%). This study was limited to testing residual diagnostic samples, some of which had been frozen before use; it was not possible to test the performance of the Xpert Ebola assay at point of care. Conclusions: The Xpert Ebola assay had excellent performance compared to an established RT-PCR benchmark on WB and BS samples in a field laboratory setting. Future studies should evaluate feasibility and performance outside of a biocontainment laboratory setting to facilitate expanded access to testing

The DARS (Dopamine Augmented Rehabilitation in Stroke) trial: protocol for a randomised controlled trial of Co-careldopa treatment in addition to routine NHS occupational and physical therapy after stroke

Background: Stroke has a huge impact, leaving more than a third of affected people with lasting disability and rehabilitation remains a cornerstone treatment in the National Health Service (NHS). Recovery of mobility and arm function post-stroke occurs through re-learning to use the affected body parts and/or learning to compensate with the lesser affected side. Promising evidence suggests that the addition of Co-careldopa to physical therapy and occupational therapy may improve the recovery of arm and leg movement and lead to improved function. Methods/design: Dopamine Augmented Rehabilitation in Stroke (DARS) is a multi-centre double-blind, randomised, placebo, controlled clinical trial of Co-careldopa in addition to routine NHS occupational therapy and physical therapy as part of early stroke rehabilitation. Participants will be randomised on a 1:1 basis to either Co-careldopa or placebo. The primary objective of the trial is to determine whether the addition of six weeks of Co-careldopa treatment to rehabilitation therapy can improve the proportion of patients who can walk independently eight weeks post-randomisation. Discussion: The DARS trial will provide evidence as to whether Co-careldopa, in addition to routine NHS occupational and physical therapy, leads to a greater recovery of motor function, a reduction in carer dependency and advance rehabilitation treatments for people with stroke. Trial registration: ISRCTN99643613 assigned on 4 December 2009

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

Memory-guided force output is associated with self-reported ADHD symptoms in young adults

Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed mental health disorder in childhood and persists into adulthood in up to 65 % of cases. ADHD is associated with adverse outcomes such as the ability to gain and maintain employment and is associated with an increased risk for substance abuse obesity workplace injuries and traffic accidents A majority of diagnosed children have motor deficits; however, few studies have examined motor deficits in young adults. This study provides a novel examination of visuomotor control of grip force in young adults with and without ADHD. Participants were instructed to maintain force production over a 20-second trial with and without real-time visual feedback about their performance. The results demonstrated that when visual feedback was available, adults with ADHD produced slightly higher grip force than controls. However, when visual feedback was removed, adults with ADHD had a faster rate of decay of force, which was associated with ADHD symptom severity and trait impulsivity. These findings suggest that there may be important differences in the way that adults with ADHD integrate visual feedback during continuous motor tasks. These may account for some of the motor impairments reported in children with ADHD. These deficits could result from (1) dysfunctional sensory motor integration and/or (2) deficits in short-term visuomotor memory

A Two-Hybrid Assay to Study Protein Interactions within the Secretory Pathway

Interactions of transcriptional activators are difficult to study using transcription-based two-hybrid assays due to potent activation resulting in false positives. Here we report the development of the Golgi two-hybrid (G2H), a method that interrogates protein interactions within the Golgi, where transcriptional activators can be assayed with negligible background. The G2H relies on cell surface glycosylation to report extracellularly on protein-protein interactions occurring within the secretory pathway. In the G2H, protein pairs are fused to modular domains of the reporter glycosyltransferase, Och1p, and proper cell wall formation due to Och1p activity is observed only when a pair of proteins interacts. Cells containing interacting protein pairs are identified by selectable phenotypes associated with Och1p activity and proper cell wall formation: cells that have interacting proteins grow under selective conditions and display weak wheat germ agglutinin (WGA) binding by flow cytometry, whereas cells that lack interacting proteins display stunted growth and strong WGA binding. Using this assay, we detected the interaction between transcription factor MyoD and its binding partner Id2. Interfering mutations along the MyoD:Id2 interaction interface ablated signal in the G2H assay. Furthermore, we used the G2H to detect interactions of the activation domain of Gal4p with a variety of binding partners. Finally, selective conditions were used to enrich for cells encoding interacting partners. The G2H detects protein-protein interactions that cannot be identified via traditional two-hybrid methods and should be broadly useful for probing previously inaccessible subsets of the interactome, including transcriptional activators and proteins that traffic through the secretory pathway

Sequencing three crocodilian genomes to illuminate the evolution of archosaurs and amniotes

The International Crocodilian Genomes Working Group (ICGWG) will sequence and assemble the American alligator (Alligator mississippiensis), saltwater crocodile (Crocodylus porosus) and Indian gharial (Gavialis gangeticus) genomes. The status of these projects and our planned analyses are described