Developing a new resetting tool for controlling rats

A resetting toxin device (the “Spitfire”) has been designed that delivers a toxic paste to a rat’s ventral surface when it passes through a tunnel. The rat grooms off the paste and ingests the toxin. The system was assessed in cage trials and one field trial. The purpose of the cage trials was to investigate whether a range of toxins can be delivered by the Spitfire to rats (Rattus rattus and R. norvegicus), namely 0.55% sodium fluoroacetate (1080), 0.2% brodifacoum, 15% cholecalciferol, and 12.5% zinc phosphide. The trials with 1080, brodifacoum, and zinc phosphide were successful with > 85% of rats ingesting lethal doses. The trials with cholecalciferol were less successful with only 58% of rats dying. A one-month pilot field trial was undertaken using 1080 in the Spitfires. There was a knockdown in rat (and stoat Mustela erminea) abundance, establishing proof of concept for the Spitfire delivery system with this toxin. The long-term, effective control of introduced rats will require a range of toxins with different modes of action. The Spitfire could be a useful additional control tool for rats and is currently being re-engineered to be made more reliable

Diphacinone and coumatetralyl persistence in deer and implications for wildlife management

Eason, C.T., Murphy, E., Ross, J.G., Hix, S., Arthur, D., MacMorran, D., Broome, K., Fairweather, A

The absorption-dominated model for the X-ray spectra of type I active galaxies: MCG-6-30-15

MCG-6-30-15 is the archetypal example of a type I active galaxy showing broad "red-wing" emission in its X-ray spectrum at energies below the 6.4 keV Fe K-alpha emission line and a continuum excess above 20 keV. Miller et al. (2008) showed that these spectral features could be caused by clumpy absorbing material, but Reynolds et al. (2009) have argued that the observed Fe K-alpha line luminosity is inconsistent with this explanation unless the global covering factor of the absorber(s) is very low. However, the Reynolds et al. calculation effectively considers the only source of opacity to be the Fe K bound-free transition and neglects the opacity at the line energy: correction to realistic opacity decreases the predicted line flux by a large factor. We also discuss the interpretation of the covering factor and the possible effect of occultation by the accretion disk. Finally, we consider a model for MCG-6-30-15 dominated by clumpy absorption, which is consistent with global covering factor 0.45, although models that include the effects of Compton scattering are required to reach a full understanding. Variations in covering fraction may dominate the observed X-ray spectral variability.Comment: Accepted for publication in MNRAS letter

Is oxidative stress MYC’s Achilles heel?

No abstract available

Outcomes After Virologic Failure of First-Line ART in South Africa

Article approval pendingTo determine initial 24-week outcomes among prospectively enrolled patients with failure of initial antiretroviral therapy (ART)

Progressive left ventricular remodeling in patients with hypertrophic cardiomyopathy and severe left ventricular hypertrophy

AbstractObjectivesThe aim of this study was to determine the natural history of patients with hypertrophic cardiomyopathy (HCM) and severe left ventricular hypertrophy (LVH) (i.e., maximal left ventricular wall thickness [MLVWT] ≥30 mm) and whether changes in cardiac morphology influence the course of the disease.BackgroundSevere LVH is common in young and rare among elderly patients with HCM. This has been explained by a high incidence of sudden death. We hypothesized that this age-related difference might be explained by left ventricular wall thinning.MethodsA total of 106 (age 33 ± 15 years; 71 males) consecutive patients with severe LVH underwent history taking, examination, electrocardiography, echocardiography, cardiopulmonary exercise testing, and Holter analysis. Survival data were collected at subsequent clinic visits or by communication with patients and their general practioners. In order to assess morphologic and functional changes, 71 (67.0%) patients (mean age 31 ± 15 years; 47 males) followed at our institution underwent serial (≥1 year) assessment.ResultsOf the 106 patients, the majority (78 [71.6%]) were <40 years of age. During follow-up (92 ± 50 months [range 1 to 169]), 18 (17.0%) patients died or underwent heart transplantation (13 sudden cardiac deaths, 2 heart failure deaths, 1 heart transplantation, 1 stroke, 1 postoperative death). Five-year survival from sudden death was 90.1% (95% confidence interval [CI] 84.0% to 96.3%), and that from heart failure death or transplantation was 97.7% (95% CI 94.5 to 100). In patients serially evaluated over 85 ± 51 months, there was an overall reduction in MLVWT of 0.6 mm/year (95% CI 0.31 to 0.81, p = 0.00004). Wall thinning ≥5 mm was observed in 41 patients (57.7%; age 35 ± 13 years; 28 males). On multivariate analysis, the follow-up duration only predicted wall thinning (0.6 mm/year, 95% CI 0.38 to 0.85, p < 0.00001).ConclusionsLeft ventricular remodeling is common in patients with severe LVH and contributes to the low prevalence of severe LVH seen in middle age and beyond

ANKRD1, the gene encoding cardiac ankyrin repeat protein, is a novel dilated cardiomyopathy gene.

OBJECTIVES: We evaluated ankyrin repeat domain 1 (ANKRD1), the gene encoding cardiac ankyrin repeat protein (CARP), as a novel candidate gene for dilated cardiomyopathy (DCM) through mutation analysis of a cohort of familial or idiopathic DCM patients, based on the hypothesis that inherited dysfunction of mechanical stretch-based signaling is present in a subset of DCM patients. BACKGROUND: CARP, a transcription coinhibitor, is a member of the titin-N2A mechanosensory complex and translocates to the nucleus in response to stretch. It is up-regulated in cardiac failure and hypertrophy and represses expression of sarcomeric proteins. Its overexpression results in contractile dysfunction. METHODS: In all, 208 DCM patients were screened for mutations/variants in the coding region of ANKRD1 using polymerase chain reaction, denaturing high-performance liquid chromatography, and direct deoxyribonucleic acid sequencing. In vitro functional analyses of the mutation were performed using yeast 2-hybrid assays and investigating the effect on stretch-mediated gene expression in myoblastoid cell lines using quantitative real-time reverse transcription-polymerase chain reaction. RESULTS: Three missense heterozygous ANKRD1 mutations (P105S, V107L, and M184I) were identified in 4 DCM patients. The M184I mutation results in loss of CARP binding with Talin 1 and FHL2, and the P105S mutation in loss of Talin 1 binding. Intracellular localization of mutant CARP proteins is not altered. The mutations result in differential stretch-induced gene expression compared with wild-type CARP. CONCLUSIONS: ANKRD1 is a novel DCM gene, with mutations present in 1.9% of DCM patients. The ANKRD1 mutations may cause DCM as a result of disruption of the normal cardiac stretch-based signaling

Early Gut Microbiota Perturbations Following Intrapartum Antibiotic Prophylaxis to Prevent Group B Streptococcal Disease

peer-reviewedThe faecal microbiota composition of infants born to mothers receiving intrapartum antibiotic prophylaxis with ampicillin against group B Streptococcus was compared with that of control infants, at day 7 and 30 of life. Recruited newborns were both exclusive breastfed and mixed fed, in order to also study the effect of dietary factors on the microbiota composition. Massive parallel sequencing of the V3-V4 region of the 16S rRNA gene and qPCR analysis were performed. Antibiotic prophylaxis caused the most marked changes on the microbiota in breastfed infants, mainly resulting in a higher relative abundance of Enterobacteriaceae, compared with control infants (52% vs. 14%, p = 0.044) and mixed-fed infants (52% vs. 16%, p = 0.13 NS) at day 7 and in a lower bacterial diversity compared to mixed-fed infants and controls. Bifidobacteria were also particularly vulnerable and abundances were reduced in breastfed (p = 0.001) and mixed-fed antibiotic treated groups compared to non-treated groups. Reductions in bifidobacteria in antibiotic treated infants were also confirmed by qPCR. By day 30, the bifidobacterial population recovered and abundances significantly increased in both breastfed (p = 0.025) and mixed-fed (p = 0.013) antibiotic treated groups, whereas Enterobacteriaceae abundances remained highest in the breastfed antibiotic treated group (44%), compared with control infants (16%) and mixed-fed antibiotic treated group (28%). This study has therefore demonstrated the short term consequences of maternal intrapartum antibiotic prophylaxis on the infant faecal microbial population, particularly in that of breastfed infants.This work was part funded by the Irish Department of Agriculture Food and Marine INFANTMET Project (RefNo 10FDairy), Science Foundation of Ireland–funded Centre for Science, Engineering and Technology, the Alimentary Pharmabiotic Centre and by EU FP7 MyNewGut project (No.:613979; www.mynewgut.eu). The research activity of GM and KM were supported by the Global Grant Spinner project 2013 and a Teagasc Walsh Fellowship, respectively

A pilot study demonstrating the altered gut microbiota functionality in stable adults with Cystic Fibrosis

peer-reviewedCystic Fibrosis (CF) and its treatment result in an altered gut microbiota composition compared to non-CF controls. However, the impact of this on gut microbiota functionality has not been extensively characterised. Our aim was to conduct a proof-of-principle study to investigate if measurable changes in gut microbiota functionality occur in adult CF patients compared to controls. Metagenomic DNA was extracted from faecal samples from six CF patients and six non-CF controls and shotgun metagenomic sequencing was performed on the MiSeq platform. Metabolomic analysis using gas chromatography-mass spectrometry was conducted on faecal water. The gut microbiota of the CF group was significantly different compared to the non-CF controls, with significantly increased Firmicutes and decreased Bacteroidetes. Functionality was altered, with higher pathway abundances and gene families involved in lipid (e.g. PWY 6284 unsaturated fatty acid biosynthesis (p = 0.016)) and xenobiotic metabolism (e.g. PWY-5430 meta-cleavage pathway of aromatic compounds (p = 0.004)) in CF patients compared to the controls. Significant differences in metabolites occurred between the two groups. This proof-of-principle study demonstrates that measurable changes in gut microbiota functionality occur in CF patients compared to controls. Larger studies are thus needed to interrogate this further