Increased uptake and improved outcomes of bowel cancer screening with a faecal immunochemical test: results from a pilot study within the national screening programme in England

The funding for the evaluation of the pilot was provided by the National Office of the NHS Cancer Screening Programmes (now part of Public Health England)

Altered hippocampal function in major depression despite intact structure and resting perfusion

Background: Hippocampal volume reductions in major depression have been frequently reported. However, evidence for functional abnormalities in the same region in depression has been less clear. We investigated hippocampal function in depression using functional magnetic resonance imaging (fMRI) and neuropsychological tasks tapping spatial memory function, with complementing measures of hippocampal volume and resting blood flow to aid interpretation. Method: A total of 20 patients with major depressive disorder (MDD) and a matched group of 20 healthy individuals participated. Participants underwent multimodal magnetic resonance imaging (MRI): fMRI during a spatial memory task, and structural MRI and resting blood flow measurements of the hippocampal region using arterial spin labelling. An offline battery of neuropsychological tests, including several measures of spatial memory, was also completed. Results: The fMRI analysis showed significant group differences in bilateral anterior regions of the hippocampus. While control participants showed task-dependent differences in blood oxygen level-dependent (BOLD) signal, depressed patients did not. No group differences were detected with regard to hippocampal volume or resting blood flow. Patients showed reduced performance in several offline neuropsychological measures. All group differences were independent of differences in hippocampal volume and hippocampal blood flow. Conclusions: Functional abnormalities of the hippocampus can be observed in patients with MDD even when the volume and resting perfusion in the same region appear normal. This suggests that changes in hippocampal function can be observed independently of structural abnormalities of the hippocampus in depression

Somatostatin receptor 5 and cannabinoid receptor 1 activation inhibit secretion of glucose-dependent insulinotropic polypeptide from intestinal K cells in rodents.

AIMS/HYPOTHESIS: Glucose-dependent insulinotropic polypeptide (GIP) is an enteroendocrine hormone that promotes storage of glucose and fat. Its secretion from intestinal K cells is triggered by nutrient ingestion and is modulated by intracellular cAMP. In view of the proadipogenic actions of GIP, this study aimed to identify pathways in K cells that lower cAMP levels and GIP secretion. METHODS: Murine K cells purified by flow cytometry were analysed for expression of G(αi)-coupled receptors by transcriptomic microarrays. Somatostatin and cannabinoid receptor expression was confirmed by quantitative RT-PCR. Hormone secretion in vitro was measured in GLUTag and primary murine intestinal cultures. cAMP was monitored in GLUTag cells using the genetically encoded sensor Epac2-camps. In vivo tolerance tests were performed in cannulated rats. RESULTS: Purified murine K cells expressed high mRNA levels for somatostatin receptors (Sstrs) Sstr2, Sstr3 and Sstr5, and cannabinoid receptor type 1 (Cnr1, CB1). Somatostatin inhibited GIP and glucagon-like peptide-1 (GLP-1) secretion from primary small intestinal cultures, in part through SSTR5, and reduced cAMP generation in GLUTag cells. Although the CB1 agonist methanandamide (mAEA) inhibited GIP secretion, no significant effect was observed on GLP-1 secretion from primary cultures. In cannulated rats, treatment with mAEA prior to an oral glucose tolerance test suppressed plasma GIP but not GLP-1 levels, whereas the CB1 antagonist AM251 elevated basal GIP concentrations. CONCLUSIONS/INTERPRETATION: GIP release is inhibited by somatostatin and CB1 agonists. The differential effects of CB1 ligands on GIP and GLP-1 release may provide a new tool to dissociate secretion of these incretin hormones and lower GIP but not GLP-1 levels in vivo

An Iterative Module in the Azalomycin F Polyketide Synthase Contains a Switchable Enoylreductase Domain.

Detailed analysis of the modular Type I polyketide synthase (PKS) involved in the biosynthesis of the marginolactone azalomycin F in mangrove Streptomyces sp. 211726 has shown that only nineteen extension modules are required to accomplish twenty cycles of polyketide chain elongation. Analysis of the products of a PKS mutant specifically inactivated in the dehydratase domain of extension-module 1 showed that this module catalyzes two successive elongations with different outcomes. Strikingly, the enoylreductase domain of this module can apparently be "toggled" off and on : it functions in only the second of these two cycles. This novel mechanism expands our understanding of PKS assembly-line catalysis and may explain examples of apparent non-colinearity in other modular PKS systems

The first SSR-based genetic linkage map for cultivated groundnut (Arachis hypogaea L.)

Molecular markers and genetic linkage maps are pre-requisites for molecular breeding in any crop species. In case of peanut or groundnut (Arachis hypogaea L.), an amphidiploid (4X) species, not a single genetic map is, however, available based on a mapping population derived from cultivated genotypes. In order to develop a genetic linkage map for tetraploid cultivated groundnut, a total of 1,145 microsatellite or simple sequence repeat (SSR) markers available in public domain as well as unpublished markers from several sources were screened on two genotypes, TAG 24 and ICGV 86031 that are parents of a recombinant inbred line mapping population. As a result, 144 (12.6%) polymorphic markers were identified and these amplified a total of 150 loci. A total of 135 SSR loci could be mapped into 22 linkage groups (LGs). While six LGs had only two SSR loci, the other LGs contained 3 (LG_AhXV) to 15 (LG_AhVIII) loci. As the mapping population used for developing the genetic map segregates for drought tolerance traits, phenotyping data obtained for transpiration, transpiration efficiency, specific leaf area and SPAD chlorophyll meter reading (SCMR) for 2 years were analyzed together with genotyping data. Although, 2–5 QTLs for each trait mentioned above were identified, the phenotypic variation explained by these QTLs was in the range of 3.5–14.1%. In addition, alignment of two linkage groups (LGs) (LG_AhIII and LG_AhVI) of the developed genetic map was shown with available genetic maps of AA diploid genome of groundnut and Lotus and Medicago. The present study reports the construction of the first genetic map for cultivated groundnut and demonstrates its utility for molecular mapping of QTLs controlling drought tolerance related traits as well as establishing relationships with diploid AA genome of groundnut and model legume genome species. Therefore, the map should be useful for the community for a variety of applications

Are Chinese consumers at risk due to exposure to metals in crayfish? A bioaccessibility-adjusted probabilistic risk assessment

Freshwater crayfish, the world's third largest crustacean species, has been reported to accumulate high levels of metals, while the current knowledge of potential risk associated with crayfish consumption lags behind that of finfish. We provide the first estimate of human health risk associated with crayfish (Procambarus clarkii) consumption in China, the world's largest producer and consumer of crayfish. We performed Monte Carlo Simulation on a standard risk model parameterized with local data on metal concentrations, bioaccessibility (phi), crayfish consumption rate, and consumer body mass. Bioaccessibility of metals in crayfish was found to be variable (68-95%) and metal-specific, suggesting a potential influence of metal bioaccessibility on effective metal intake. However, sensitivity analysis suggested risk of metals via crayfish consumption was predominantly explained by consumption rate (explaining >92% of total risk estimate variability), rather than metals concentration, bioaccessibility, or body mass. Mean metal concentrations (As, Cd, Cu, Ni, Pb, Se and Zn) in surveyed crayfish samples from 12 provinces in China conformed to national safety standards. However, risk calculation of phi-modified hazard quotient (HQ) and hazard index (HI) suggested that crayfish metals may pose a health risk for very high rate consumers, with a HI of over 24 for the highest rate consumers. Additionally, the phi-modified increased lifetime risk (ILTR) for carcinogenic effects due to the presence of As was above the acceptable level (10(-5)) for both the median (ILTR = 2.5 x 10(-5)) and 90th percentile (ILTR = 1.8 x 10(-4)), highlighting the relatively high risk of As in crayfish. Our results suggest a need to consider crayfish when assessing human dietary exposure to metals and associated health risks, especially for high crayfish-consuming populations, such as in China, USA and Sweden.HZ by the National Natural Science Foundation of China (41273087). LN was supported by European Union Marie Curie Actions, Grant FP People 2010 “IRSES Electroacross” and BG by the SAGE-IGERT Fellowship (US National Science Foundation)

SSR-based genetic linkage map for cultivated groundnut (Arachis hypogaea L.) for QTL analysis and comparative mapping

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A novel type of intermittency in a nonlinear dynamo in a compressible flow

The transition to intermittent mean--field dynamos is studied using numerical simulations of isotropic magnetohydrodynamic turbulence driven by a helical flow. The low-Prandtl number regime is investigated by keeping the kinematic viscosity fixed while the magnetic diffusivity is varied. Just below the critical parameter value for the onset of dynamo action, a transient mean--field with low magnetic energy is observed. After the transition to a sustained dynamo, the system is shown to evolve through different types of intermittency until a large--scale coherent field with small--scale turbulent fluctuations is formed. Prior to this coherent field stage, a new type of intermittency is detected, where the magnetic field randomly alternates between phases of coherent and incoherent large--scale spatial structures. The relevance of these findings to the understanding of the physics of mean--field dynamo and the physical mechanisms behind intermittent behavior observed in stellar magnetic field variability are discussed.Comment: 19 pages, 13 figure

Two rapid assays for screening of patulin biodegradation

Artículo sobre distintos ensayos para comprobar la biodegradación de la patulinaThe mycotoxin patulin is produced by the blue mould pathogen Penicillium expansum in rotting apples during postharvest storage. Patulin is toxic to a wide range of organisms, including humans, animals, fungi and bacteria. Wash water from apple packing and processing houses often harbours patulin and fungal spores, which can contaminate the environment. Ubiquitous epiphytic yeasts, such as Rhodosporidium kratochvilovae strain LS11 which is a biocontrol agent of P. expansum in apples, have the capacity to resist the toxicity of patulin and to biodegrade it. Two non-toxic products are formed. One is desoxypatulinic acid. The aim of the work was to develop rapid, high-throughput bioassays for monitoring patulin degradation in multiple samples. Escherichia coli was highly sensitive to patulin, but insensitive to desoxypatulinic acid. This was utilized to develop a detection test for patulin, replacing time-consuming thin layer chromatography or high-performance liquid chromatography. Two assays for patulin degradation were developed, one in liquid medium and the other in semi-solid medium. Both assays allow the contemporary screening of a large number of samples. The liquid medium assay utilizes 96-well microtiter plates and was optimized for using a minimum of patulin. The semisolid medium assay has the added advantage of slowing down the biodegradation, which allows the study and isolation of transient degradation products. The two assays are complementary and have several areas of utilization, from screening a bank of microorganisms for biodegradation ability to the study of biodegradation pathways