Searching for "monogenic diabetes" in dogs using a candidate gene approach

BACKGROUND: Canine diabetes is a common endocrine disorder with an estimated breed-related prevalence ranging from 0.005% to 1.5% in pet dogs. Increased prevalence in some breeds suggests that diabetes in dogs is influenced by genetic factors and similarities between canine and human diabetes phenotypes suggest that the same genes might be associated with disease susceptibility in both species. Between 1-5% of human diabetes cases result from mutations in a single gene, including maturity onset diabetes of the adult (MODY) and neonatal diabetes mellitus (NDM). It is not clear whether monogenic forms of diabetes exist within some dog breeds. Identification of forms of canine monogenic diabetes could help to resolve the heterogeneity of the condition and lead to development of breed-specific genetic tests for diabetes susceptibility. RESULTS: Seventeen dog breeds were screened for single nucleotide polymorphisms (SNPs) in eighteen genes that have been associated with human MODY/NDM. Six SNP associations were found from five genes, with one gene (ZFP57) being associated in two different breeds. CONCLUSIONS: Some of the genes that have been associated with susceptibility to MODY and NDM in humans appear to also be associated with canine diabetes, although the limited number of associations identified in this study indicates canine diabetes is a heterogeneous condition and is most likely to be a polygenic trait in most dog breeds. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2052-6687-1-8) contains supplementary material, which is available to authorized users

Peer-review in a world with rational scientists: Toward selection of the average

One of the virtues of peer review is that it provides a self-regulating selection mechanism for scientific work, papers and projects. Peer review as a selection mechanism is hard to evaluate in terms of its efficiency. Serious efforts to understand its strengths and weaknesses have not yet lead to clear answers. In theory peer review works if the involved parties (editors and referees) conform to a set of requirements, such as love for high quality science, objectiveness, and absence of biases, nepotism, friend and clique networks, selfishness, etc. If these requirements are violated, what is the effect on the selection of high quality work? We study this question with a simple agent based model. In particular we are interested in the effects of rational referees, who might not have any incentive to see high quality work other than their own published or promoted. We find that a small fraction of incorrect (selfish or rational) referees can drastically reduce the quality of the published (accepted) scientific standard. We quantify the fraction for which peer review will no longer select better than pure chance. Decline of quality of accepted scientific work is shown as a function of the fraction of rational and unqualified referees. We show how a simple quality-increasing policy of e.g. a journal can lead to a loss in overall scientific quality, and how mutual support-networks of authors and referees deteriorate the system.Comment: 5 pages 4 figure

A simple all-microwave entangling gate for fixed-frequency superconducting qubits

We demonstrate an all-microwave two-qubit gate on superconducting qubits which are fixed in frequency at optimal bias points. The gate requires no additional subcircuitry and is tunable via the amplitude of microwave irradiation on one qubit at the transition frequency of the other. We use the gate to generate entangled states with a maximal extracted concurrence of 0.88 and quantum process tomography reveals a gate fidelity of 81%

Metabolic targets of watercress and PEITC in MCF-7 and MCF-10A cells explain differential sensitisation responses to ionising radiation

Watercress is a rich source of phytochemicals with anticancer potential, including phenethyl isothiocyanate (PEITC). We examined the potential for watercress extracts and PEITC to increase the DNA damage caused by ionising radiation (IR) in breast cancer cells and to be protective against radiation-induced collateral damage in healthy breast cells. The metabolic events that mediate such responses were explored using metabolic profiling. H nuclear magnetic resonance spectroscopy-based metabolic profiling was coupled with DNA damage-related assays (cell cycle, Comet assay, viability assays) to profile the comparative effects of watercress and PEITC in MCF-7 breast cancer cells and MCF-10A non-tumorigenic breast cells with and without exposure to IR. Both the watercress extract and PEITC-modulated biosynthetic pathways of lipid and protein synthesis and resulted in changes in cellular bioenergetics. Disruptions to the redox balance occurred with both treatments in the two cell lines, characterised by shifts in the abundance of glutathione. PEITC enhanced the sensitivity of the breast cancer cells to IR increasing the effectiveness of the cancer-killing process. In contrast, watercress-protected non-tumorigenic breast cells from radiation-induced damage. These effects were driven by changes in the cellular content of the antioxidant glutathione following exposure to PEITC and other phytochemicals in watercress. These findings support the potential prophylactic impact of watercress during radiotherapy. Extracted compounds from watercress and PEITC differentially modulate cellular metabolism collectively enhancing the therapeutic outcomes of radiotherapy

Fluvial organic carbon flux from an eroding peatland catchment, southern Pennines, UK

International audienceThis study investigates for the first time the relative importance of dissolved organic carbon (DOC) and particulate organic carbon (POC) in the fluvial carbon flux from an actively eroding peatland catchment in the southern Pennines, UK. Event scale variability in DOC and POC was examined and the annual flux of fluvial organic carbon was estimated for the catchment. At the event scale, both DOC and POC were found to increase with discharge, with event based POC export accounting for 95% of flux in only 8% of the time. On an annual cycle, 40.8 t organic carbon (OC) is exported from the catchment, which represents an areal value of 107 gC m?2 a?1. POC was the most significant form of organic carbon export, accounting for ~82% of the estimated flux. This suggests that more research is required on both the fate of POC and the rates of POC export in eroding peatland catchments

Exploratory randomized double-blind placebo controlled trial of botulinum therapy on grasp release after Stroke (PrOMBiS)

Background. OnabotulinumtoxinA injections improve upper-limb spasticity after stroke, but their effect on arm function remains uncertain. Objective. To determine whether a single treatment with onabotulinumtoxinA injections combined with upper-limb physiotherapy improves grasp release compared with physiotherapy alone after stroke. Methods. A total of 28 patients, at least 1 month poststroke, were randomized to receive either onabotulinumtoxinA or placebo injections to the affected upper limb followed by standardized upper-limb physiotherapy (10 sessions over 4 weeks). The primary outcome was time to release grasp during a functionally relevant standardized task. Secondary outcomes included measures of wrist and finger spasticity and strength using a customized servomotor, clinical assessments of stiffness (modified Ashworth Scale), arm function (Action Research Arm Test [ARAT], Nine Hole Peg Test), arm use (Arm Measure of Activity), Goal Attainment Scale, and quality of life (EQ5D). Results. There was no significant difference between treatment groups in grasp release time 5 weeks post injection (placebo median = 3.0 s, treatment median = 2.0 s; t(24) = 1.20; P = .24; treatment effect = −0.44, 95% CI = −1.19 to 0.31). None of the secondary measures passed significance after correcting for multiple comparisons. Both groups achieved their treatment goals (placebo = 65%; treatment = 71%), and made improvements on the ARAT (placebo +3, treatment +5) and in active wrist extension (placebo +9°, treatment +11°). Conclusions. In this group of stroke patients with mild to moderate spastic hemiparesis, a single treatment with onabotulinumtoxinA did not augment the improvements seen in grasp release time after a standardized upper-limb physiotherapy program