Large-scale structure of brown rat (Rattus norvegicus) populations in England: effects on rodenticide resistance

The brown rat (Rattus norvegicus) is a relatively recent (<300 years) addition to the British fauna, but by association with negative impacts on public health, animal health and agriculture, it is regarded as one of the most important vertebrate pest species. Anticoagulant rodenticides were introduced for brown rat control in the 1950s and are widely used for rat control in the UK, but long-standing resistance has been linked to control failures in some regions. One thus far ignored aspect of resistance biology is the population structure of the brown rat. This paper investigates the role population structure has on the development of anticoagulant resistance. Using mitochondrial and microsatellite DNA, we examined 186 individuals (from 15 counties in England and one location in Wales near the Wales–England border) to investigate the population structure of rural brown rat populations. We also examined individual rats for variations of the VKORC1 gene previously associated with resistance to anticoagulant rodenticides. We show that the populations were structured to some degree, but that this was only apparent in the microsatellite data and not the mtDNA data. We discuss various reasons why this is the case. We show that the population as a whole appears not to be at equilibrium. The relative lack of diversity in the mtDNA sequences examined can be explained by founder effects and a subsequent spatial expansion of a species introduced to the UK relatively recently. We found there was a geographical distribution of resistance mutations, and relatively low rate of gene flow between populations, which has implications for the development and management of anticoagulant resistance

Colonization, mouse-style

Several recent papers, including one in BMC Evolutionary Biology, examine the colonization history of house mice. As well as background for the analysis of mouse adaptation, such studies offer a perspective on the history of movements of the humans that accidentally transported the mice

An in vitro investigation into the effects of 10Hz cyclic loading on tenocyte metabolism

Tendinopathy is a prevalent, highly debilitating condition, with poorly defined aetiology. A wide range of clinical treatments have been proposed, with systematic reviews largely supporting shock wave therapy or eccentric exercise. Characterising these treatments has demonstrated both generate perturbations within tendon at a frequency of approximately 812Hz. Consequently, it is hypothesised that loading in this frequency range initiates increased anabolic tenocyte behaviour, promoting tendon repair. The primary aim of this study is to investigate the effects of 10Hz perturbations on tenocyte metabolism, comparing gene expression in response to a 10Hz and 1Hz loading profile. Tenocytes from healthy and tendinopathic human tendons were seeded into 3D collagen gels and subjected to 15 mins cyclic strain at 10Hz or 1Hz. Tenocytes from healthy tendon showed increased expression of all analysed genes in response to loading, with significantly increased expression of inflammatory and degradative genes with 10Hz, relative to 1Hz loading. By contrast, whilst the response of tenocytes from tendinopathy tendon also increased with 10Hz loading, the overall response profile was more varied and less intense, possibly indicative of an altered healing response. Through inhibition of the pathway, IL1 was shown to be involved in the degradative and catabolic response of cells to high frequency loading, abrogating the loading response. This study has demonstrated for the first time that loading at a frequency of 10Hz may enhance the metabolic response of tenocytes by initiating an immediate degradatory and inflammatory cell response through the IL1 pathway, perhaps as an initial stage of tendon healing

Transcriptome sequencing of black grouse (Tetrao tetrix) for immune gene discovery and microsatellite development

The black grouse (Tetrao tetrix) is a galliform bird species that is important for both ecological studies and conservation genetics. Here, we report the sequencing of the spleen transcriptome of black grouse using 454 GS FLX Titanium sequencing. We performed a large-scale gene discovery analysis with a focus on genes that might be related to fitness in this species and also identified a large set of microsatellites. In total, we obtained 182 179 quality-filtered sequencing reads that we assembled into 9035 contigs. Using these contigs and 15 794 length-filtered (greater than 200 bp) singletons, we identified 7762 transcripts that appear to be homologues of chicken genes. A specific BLAST search with an emphasis on immune genes found 308 homologous chicken genes that have immune function, including ten major histocompatibility complex-related genes located on chicken chromosome 16. We also identified 1300 expressed sequence tag microsatellites and were able to design suitable flanking primers for 526 of these. A preliminary test of the polymorphism of the microsatellites found 10 polymorphic microsatellites of the 102 tested. Genomic resources generated in this study should greatly benefit future ecological, evolutionary and conservation genetic studies on this species

A half-century of studies on a chromosomal hybrid zone of the house mouse

The first natural chromosomal variation in the house mouse was described nearly 50 years ago in Val Poschiavo on the Swiss side of the Swiss–Italian border in the Central Eastern Alps. Studies have extended into neighboring Valtellina, and the house mice of the Poschiavo-Valtellina area have been subject to detailed analysis, reviewed here. The maximum extent of this area is 70 km, yet it has 4 metacentric races and the standard 40-chromosome telocentric race distributed in a patchwork fashion. The metacentric races are characterized by highly reduced diploid numbers (2n = 22–26) resulting from Robertsonian fusions, perhaps modified by whole-arm reciprocal translocations. The races hybridize and the whole Poschiavo-Valtellina area can be considered a “hybrid zone.” The studies of this area have provided insights into origin of races within hybrid zones, gene flow within hybrid zones and the possibility of speciation in hybrid zones. This provides a case study of how chromosomal rearrangements may impact the genetic structure of populations and their diversification.Fil: Giménez, Mabel Dionisia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; Argentina. University of York; Reino UnidoFil: Förster, Daniel W.. Leibniz-institute For Zoo And Wildlife Research; Alemania. University of York; Reino UnidoFil: Jones, Eleanor P.. University of York; Reino Unido. Fera Science; Reino UnidoFil: Jóhannesdóttir, Fríđa. University of York; Reino Unido. Cornell University; Estados UnidosFil: Gabriel, Sofia I.. Universidade de Lisboa; Portugal. University of York; Reino UnidoFil: Panithanarak, Thadsin. Burapha University; Tailandia. University of York; Reino UnidoFil: Scascitelli, Moira. University of York; Reino UnidoFil: Merico, Valeria. Universita Di Pavia; ItaliaFil: Garagna, Silvia. Universita Di Pavia; ItaliaFil: Searle, Jeremy B.. University of York; Reino Unido. Cornell University; Estados UnidosFil: Hauffe, Heidi C.. Instituto Agrario San Michele All'adige Fondazione Edmund Mach. Centro Ricerca E Innovazione; Italia. University of York; Reino Unid

A molecular characterization of the charismatic Faroe house mouse

Faroe house mice are a &apos;classic&apos; system of rapid and dramatic morphological divergence highlighted by J. S. Huxley during the development of the Modern Synthesis. In the present study, we characterize these charismatic mice using modern molecular techniques, examining specimens from all Faroe islands occupied by mice. The aims were to classify the mice within the modern house mouse taxonomy (i.e. as either Mus musculus domesticus or Mus musculus musculus) using four molecular markers and a morphological feature, and to examine the genetic diversity and possible routes of colonization using mitochondrial (mt) control region DNA sequences and microsatellite data (15 loci). Mice on the most remote islands were characterized as M. m. domesticus and exhibited exceptionally low genetic diversity, whereas those on better connected islands were more genetically diverse and had both M. m. musculus and M. m. domesticus genetic elements, including one population which was morphologically M. m. musculus-like. The mtDNA data indicate that the majority of the mice had their origins in south-western Norway (or possibly southern Denmark/northern Germany), and probably arrived with the Vikings, earlier than suggested by Huxley. The M. m. musculus genetic component appears to derive from recent mouse immigration from Denmark

Efficacy and mechanism of sub-sensory sacral (optimised) neuromodulation in adults with faecal incontinence:Study protocol for a randomised controlled trial

Background: Faecal incontinence (FI) is a substantial health problem with a prevalence of approximately 8% in community-dwelling populations. Sacral neuromodulation (SNM) is considered the first-line surgical treatment option in adults with FI in whom conservative therapies have failed. The clinical efficacy of SNM has never been rigorously determined in a trial setting and the underlying mechanism of action remains unclear. Methods/design: The design encompasses a multicentre, randomised, double-blind crossover trial and cohort follow-up study. Ninety participants will be randomised to one of two groups (SNM/SHAM or SHAM/SNM) in an allocation ratio of 1:1. The main inclusion criteria will be adults aged 18-75 years meeting Rome III and ICI definitions of FI, who have failed non-surgical treatments to the UK standard, who have a minimum of eight FI episodes in a 4-week screening period, and who are clinically suitable for SNM. The primary objective is to estimate the clinical efficacy of sub-sensory SNM vs. SHAM at 32 weeks based on the primary outcome of frequency of FI episodes using a 4-week paper diary, using mixed Poisson regression analysis on the intention-to-treat principle. The study is powered (0.9) to detect a 30% reduction in frequency of FI episodes between sub-sensory SNM and SHAM stimulation over a 32-week crossover period. Secondary objectives include: measurement of established and new clinical outcomes after 1 year of therapy using new (2017 published) optimised therapy (with standardised SNM-lead placement); validation of new electronic outcome measures (events) and a device to record them, and identification of potential biological effects of SNM on underlying anorectal afferent neuronal pathophysiology (hypothesis: SNM leads to increased frequency of perceived transient anal sphincter relaxations; improved conscious sensation of defaecatory urge and cortical/subcortical changes in afferent responses to anorectal electrical stimulation (main techniques: high-resolution anorectal manometry and magnetoencephalography). Discussion: This trial will determine clinical effect size for sub-sensory chronic electrical stimulation of the sacral innervation. It will provide experimental evidence of modifiable afferent neurophysiology that may aid future patient selection as well as a basic understanding of the pathophysiology of FI

C-STICH2: emergency cervical cerclage to prevent miscarriage and preterm birth—study protocol for a randomised controlled trial

Abstract Background Cervical cerclage is a recognised treatment to prevent late miscarriage and pre-term birth (PTB). Emergency cervical cerclage (ECC) for cervical dilatation with exposed unruptured membranes is less common and the potential benefits of cerclage are less certain. A randomised control trial is needed to accurately assess the effectiveness of ECC in preventing pregnancy loss compared to an expectant approach. Methods C-STICH2 is a multicentre randomised controlled trial in which women presenting with cervical dilatation and unruptured exposed membranes at 16 + 0 to 27 + 6 weeks gestation are randomised to ECC or expectant management. Trial design includes 18 month internal pilot with embedded qualitative process evaluation, minimal data set and a within-trial health economic analysis. Inclusion criteria are ≥16 years, singleton pregnancy, exposed membranes at the external os, gestation 16 + 0–27 + 6 weeks, and informed consent. Exclusion criteria are contraindication to cerclage, cerclage in situ or previous cerclage in this pregnancy. Randomisation occurs via an online service in a 1:1 ratio, using a minimisation algorithm to reduce chance imbalances in key prognostic variables (site, gestation and dilatation). Primary outcome is pregnancy loss; a composite including miscarriage, termination of pregnancy and perinatal mortality defined as stillbirth and neonatal death in the first week of life. Secondary outcomes include all core outcomes for PTB. Two-year development outcomes will be assessed using general health and Parent Report of Children’s Abilities-Revised (PARCA-R) questionnaires. Intended sample size is 260 participants (130 each arm) based on 60% rate of pregnancy loss in the expectant management arm and 40% in the ECC arm, with 90% power and alpha 0.05. Analysis will be by intention-to-treat. Discussion To date there has been one small trial of ECC in 23 participants which included twin and singleton pregnancies. This small trial along with the largest observational study (n = 161) found ECC to prolong pregnancy duration and reduce deliveries before 34 weeks gestation. It is important to generate high quality evidence on the effectiveness of ECC in preventing pregnancy loss, and improve understanding of the prevalence of the condition and frequency of complications associated with ECC. An adequately powered RCT will provide the highest quality evidence regarding optimum care for these women and their babies. Trial registration ISRCTN Registry ISRCTN12981869 . Registered on 13th June 2018

Search for lepton-flavor violation in Z-boson decays with τ leptons with the ATLAS detector

A search for lepton-flavor-violating Z→eτ and Z→μτ decays with pp collision data recorded by the ATLAS detector at the LHC is presented. This analysis uses 139  fb−1 of Run 2 pp collisions at √s=13  TeV and is combined with the results of a similar ATLAS search in the final state in which the τ lepton decays hadronically, using the same data set as well as Run 1 data. The addition of leptonically decaying τ leptons significantly improves the sensitivity reach for Z→ℓτ decays. The Z→ℓτ branching fractions are constrained in this analysis to B(Z→eτ)<7.0×10−6 and B(Z→μτ)<7.2×10−6 at 95% confidence level. The combination with the previously published analyses sets the strongest constraints to date: B(Z→eτ)<5.0×10−6 and B(Z→μτ)<6.5×10−6 at 95% confidence level