Endothelial dysfunction markers as a therapeutic target for Sildenafil treatment and effects on metabolic control in type 2 diabetes

Endothelial dysfunction (ED) plays a role in diabetic cardiovascular complications. Hyperglycemia increases cytockines involved in vascular inflammation. Inhibition of phosphodiesterase type 5 (PDE5) exerts a relaxation on corpora cavernosa and has cardioprotective properties. The effect of chronic sildenafil treatment, on ED markers and metabolic parameters in a non-randomized study on men with type 2 diabetes (T2DM), was investigated

Grapevine DMR6-1 Is a candidate gene for susceptibility to Downy mildew

Grapevine (Vitis vinifera) is a valuable crop in Europe for both economical and cultural reasons, but highly susceptible to Downy mildew (DM). The generation of resistant vines is of critical importance for a sustainable viticulture and can be achieved either by introgression of resistance genes in susceptible varieties or by mutation of Susceptibility (S) genes, e.g., by gene editing. This second approach offers several advantages: it maintains the genetic identity of cultivars otherwise disrupted by crossing and generally results in a broad-spectrum and durable resistance, but it is hindered by the poor knowledge about S genes in grapevines. Candidate S genes are Downy mildew Resistance 6 (DMR6) and DMR6-Like Oxygenases (DLOs), whose mutations confer resistance to DM in Arabidopsis. In this work, we show that grapevine VviDMR6-1 complements the Arabidopsis dmr6-1 resistant mutant. We studied the expression of grapevine VviDMR6 and VviDLO genes in different organs and in response to the DM causative agent Plasmopara viticola. Through an automated evaluation of causal relationships among genes, we show that VviDMR6-1, VviDMR6-2, and VviDLO1 group into different co-regulatory networks, suggesting distinct functions, and that mostly VviDMR6-1 is connected with pathogenesis-responsive genes. Therefore, VviDMR6-1 represents a good candidate to produce resistant cultivars with a gene-editing approac

Transcriptomic responses of a simplified soil microcosm to a plant pathogen and its biocontrol agent reveal a complex reaction to harsh habitat

Additional file 1: Concentration of the soil microorganism in the simplified soil microcosm.Additional file 2: Primer sequences of the microcosm genes analysed by real-time RT-PCR.Additional file 3: RNA-Seq sequencing and mapping results for each replicate.Additional file 4: Distribution of read pair alignments to the genomes of the soil microorganisms. (A, B) Distribution of read pair alignments to the 13 soil microorganisms calculated with the Samtools software [30] and expressed as a percentage (%) of total alignments to the microcosm genome. (C, D) Distribution of unique read pairs mapping to genes of the 13 soil microorganisms, counted using HTSeq [32] and expressed as a percentage (%) of total unique read pairs mapping to genes in the microcosm genome. (E, F) Percentage (%) of expressed genes (more than one read pair) calculated as compared to the total predicted genes for each soil microorganism. Mean and standard error values of three replicates are reported for each condition: the simplified soil microcosm collected at the beginning of the experiment (SSM0) and 24 h after incubation either without exogenous fungi (SSM), with the biocontrol agent Trichoderma atroviride (SSM+T), with the plant pathogen Armillaria mellea (SSM+A) or with both (SSM+T+A).Additional file 5: Expression levels of genes of the simplified soil microcosm.Additional file 6: Pearson’s correlation coefficients among replicates and conditions for RNA-Seq analysis.Additional file 7: Clustering and functional annotation results of differentially expressed genes.Additional file 8: Proportion of expressed and differentially expressed genes for each soil microorganism.Additional file 9: Distribution of differentially expressed genes of each soil microorganism in 18 clusters, based on the expression profiles.Additional file 10: Metabolic pathways of the simplified soil microcosm, modulated by incubation in the soil matrix. Metabolic pathways deactivated (left panels) and activated (right panels) by 24 h incubation in the soil matrix (A) without reinforced modulation (cluster 1) and (B) with reinforced modulation (cluster 15) in the presence of Armillaria mellea and Trichoderma atroviride combined. Metabolic pathways modulated by the introduction of (C) T. atroviride (cluster 3), (D) A. mellea (cluster 5), or (E) both (cluster 7). KEGG pathways were visualised using the iPath2 tool [48], the pathways of upregulated (green) and downregulated (red) genes were highlighted, and a section of the most relevant pathways is reported for each panel.Additional file 11: Biological networks of Gene Ontology (GO) terms. GO biological process terms of the simplified soil microcosm, upregulated by incubation in the soil matrix with similar expression profiles in the presence or absence of Armillaria mellea and Trichoderma atroviride (cluster 1). Significantly enriched GO terms (P < 0.001) were identified using the BiNGO tool [42] and visualised with Cytoscape software [43]. The colour scale legend indicates the level of significance for enriched GO terms. White nodes indicate not significantly overrepresented categories.Additional file 12: Key differentially expressed genes discussed in the manuscript, based on their functional categories and expression profiles. Each sheet contains the genes in each cluster discussed.BACKGROUND : Soil microorganisms are key determinants of soil fertility and plant health. Soil phytopathogenic fungi are one of the most important causes of crop losses worldwide. Microbial biocontrol agents have been extensively studied as alternatives for controlling phytopathogenic soil microorganisms, but molecular interactions between them have mainly been characterised in dual cultures, without taking into account the soil microbial community. We used an RNA sequencing approach to elucidate the molecular interplay of a soil microbial community in response to a plant pathogen and its biocontrol agent, in order to examine the molecular patterns activated by the microorganisms. RESULTS : A simplified soil microcosm containing 11 soil microorganisms was incubated with a plant root pathogen (Armillaria mellea) and its biocontrol agent (Trichoderma atroviride) for 24 h under controlled conditions. More than 46 million paired-end reads were obtained for each replicate and 28,309 differentially expressed genes were identified in total. Pathway analysis revealed complex adaptations of soil microorganisms to the harsh conditions of the soil matrix and to reciprocal microbial competition/cooperation relationships. Both the phytopathogen and its biocontrol agent were specifically recognised by the simplified soil microcosm: defence reaction mechanisms and neutral adaptation processes were activated in response to competitive (T. atroviride) or non-competitive (A. mellea) microorganisms, respectively. Moreover, activation of resistance mechanisms dominated in the simplified soil microcosm in the presence of both A. mellea and T. atroviride. Biocontrol processes of T. atroviride were already activated during incubation in the simplified soil microcosm, possibly to occupy niches in a competitive ecosystem, and they were not further enhanced by the introduction of A. mellea. CONCLUSIONS : This work represents an additional step towards understanding molecular interactions between plant pathogens and biocontrol agents within a soil ecosystem. Global transcriptional analysis of the simplified soil microcosm revealed complex metabolic adaptation in the soil environment and specific responses to antagonistic or neutral intruders.The European Union’s Seventh Framework Programme under grant agreement: 324416 (project INNOVA, subprogramme: FP7-PEOPLE-2012-IAPP).http://www.biomedcentral.com/bmcgenomicsam2016Genetic

Knockdown of MLO genes reduces susceptibility to powdery mildew in grapevine

10openInternationalItalian coauthor/editorErysiphe necator is the causal agent of powdery mildew (PM), one of the most destructive diseases of grapevine. PM is controlled by sulfur-based and synthetic fungicides, which every year are dispersed into the environment. This is why PM-resistant varieties should become a priority for sustainable grapevine and wine production. PM resistance can be achieved in other crops by knocking out susceptibility S-genes, such as those residing at genetic loci known as MLO (Mildew Locus O). All MLO S-genes of dicots belong to the phylogenetic clade V, including grapevine genes VvMLO7, 11 and 13, which are upregulated during PM infection, and VvMLO6, which is not upregulated. Before adopting a gene-editing approach to knockout candidate S-genes, the evidence that loss of function of MLO genes can reduce PM susceptibility is necessary. This paper reports the knockdown through RNA interference of VvMLO6, 7, 11 and 13. The knockdown of VvMLO6, 11 and 13 did not decrease PM severity, whereas the knockdown of VvMLO7 in combination with VvMLO6 and VvMLO11 reduced PM severity up to 77%. The knockdown of VvMLO7 and VvMLO6 seemed to be important for PM resistance, whereas a role for VvMLO11 does not seem likely. Cell wall appositions (papillae) were present in both resistant and susceptible lines in response to PM attack. Thirteen genes involved in defense were less upregulated in infected mlo plants, highlighting the early mlo-dependent disruption of PM invasionopenPessina, S.; Lenzi, L.; Perazzolli, M.; Campa, M.; Dalla Costa, L.; Urso, S.; Vale, G.; Salamini, F.; Velasco, R.; Malnoy, M.Pessina, S.; Lenzi, L.; Perazzolli, M.; Campa, M.; Dalla Costa, L.; Urso, S.; Vale, G.; Salamini, F.; Velasco, R.; Malnoy, M.A

Grapevine DMR6-1 Is a Candidate Gene for Susceptibility to Downy mildew

Grapevine (Vitis vinifera) is a valuable crop in Europe for both economical and cultural reasons, but highly susceptible to Downy mildew (DM). The generation of resistant vines is of critical importance for a sustainable viticulture and can be achieved either by introgression of resistance genes in susceptible varieties or by mutation of Susceptibility (S) genes, e.g., by gene editing. This second approach offers several advantages: it maintains the genetic identity of cultivars otherwise disrupted by crossing and generally results in a broad-spectrum and durable resistance, but it is hindered by the poor knowledge about S genes in grapevines. Candidate S genes are Downy mildew Resistance 6 (DMR6) and DMR6-Like Oxygenases (DLOs), whose mutations confer resistance to DM in Arabidopsis. In this work, we show that grapevine VviDMR6-1 complements the Arabidopsis dmr6-1 resistant mutant. We studied the expression of grapevine VviDMR6 and VviDLO genes in different organs and in response to the DM causative agent Plasmopara viticola. Through an automated evaluation of causal relationships among genes, we show that VviDMR6-1, VviDMR6-2, and VviDLO1 group into different co-regulatory networks, suggesting distinct functions, and that mostly VviDMR6-1 is connected with pathogenesis-responsive genes. Therefore, VviDMR6-1 represents a good candidate to produce resistant cultivars with a gene-editing approach

Hepatitis C virus infection acquired in childhood

Hepatitis C virus (HCV) infection occurs less frequently in children than in adult patients, and the natural history, prognosis, and clinical significance of HCV infection in children are poorly defined. We report here a descriptive follow-up of the clinical course, biochemical data, and viral markers observed in 37 children with anti-HCV. Ten patients included in the study tested persistently negative for serum HCV-RNA (group 1) and 27 patients tested persistently positive (group 2). In group 1, serum alanine aminotransferase (ALT) was normal in all patients, while two patients had non-organ-specific autoantibodies. In group 2, serum ALT was elevated in 13 of 27 patients, and five patients had non-organ-specific autoantibodies. HCV genotype 1a and 1b were the most prevalent among HCV-RNA-positive patients. Twenty liver biopsies were carried out on 17 patients in our series (mean evolution time, 11.2 years; range, 3–21 years). The liver specimens showed mild necroinflammatory changes in most patients, and fibrosis was absent or low grade. Two HCV-RNA-positive patients became persistently HCV-RNA negative. Of the 26 children investigated, 7 (one in group 1, six in group 2) had a co-infection with hepatitis G virus. Conclusion Most children chronically infected with HCV were asymptomatic and presented only mild biochemical evidence of hepatic injury. Autoimmunity in the form of non-organ-specific autoantibodies was common. HCV in children induced mild changes in the liver with a low level of fibrosis and at a low rate of progression

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011