Phenotypic Screens, Chemical Genomics, and Antimalarial Lead Discovery

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Two highly divergent alcohol dehydrogenases of melon exhibit fruit ripening-specific expression and distinct biochemical characteristics

Alcohol dehydrogenases (ADH) participate in the biosynthetic pathway of aroma volatiles in fruit by interconverting aldehydes to alcohols and providing substrates for the formation of esters. Two highly divergent ADH genes (15% identity at the amino acid level) of Cantaloupe Charentais melon (Cucumis melo var. Cantalupensis) have been isolated. Cm-ADH1 belongs to the medium-chain zinc-binding type of ADHs and is highly similar to all ADH genes expressed in fruit isolated so far. Cm-ADH2 belongs to the short-chain type of ADHs. The two encoded proteins are enzymatically active upon expression in yeast. Cm-ADH1 has strong preference for NAPDH as a co-factor, whereas Cm-ADH2 preferentially uses NADH. Both Cm-ADH proteins are much more active as reductases with Kms 10–20 times lower for the conversion of aldehydes to alcohols than for the dehydrogenation of alcohols to aldehydes. They both show strong preference for aliphatic aldehydes but Cm-ADH1 is capable of reducing branched aldehydes such as 3-methylbutyraldehyde, whereas Cm-ADH2 cannot. Both Cm-ADH genes are expressed specifically in fruit and up-regulated during ripening. Gene expression as well as total ADH activity are strongly inhibited in antisense ACC oxidase melons and in melon fruit treated with the ethylene antagonist 1-methylcyclopropene (1-MCP), indicating a positive regulation by ethylene. These data suggest that each of the Cm-ADH protein plays a specific role in the regulation of aroma biosynthesis in melon fruit

Transcriptome analysis of the oil-rich seed of the bioenergy crop Jatropha curcas L

<p>Abstract</p> <p>Background</p> <p>To date, oil-rich plants are the main source of biodiesel products. Because concerns have been voiced about the impact of oil-crop cultivation on the price of food commodities, the interest in oil plants not used for food production and amenable to cultivation on non-agricultural land has soared. As a non-food, drought-resistant and oil-rich crop, <it>Jatropha curcas </it>L. fulfils many of the requirements for biofuel production.</p> <p>Results</p> <p>We have generated 13,249 expressed sequence tags (ESTs) from developing and germinating <it>Jatropha </it>seeds. This strategy allowed us to detect most known genes related to lipid synthesis and degradation. We have also identified ESTs coding for proteins that may be involved in the toxicity of <it>Jatropha </it>seeds. Another unexpected finding is the high number of ESTs containing transposable element-related sequences in the developing seed library (800) when contrasted with those found in the germinating seed library (80).</p> <p>Conclusions</p> <p>The sequences generated in this work represent a considerable increase in the number of sequences deposited in public databases. These results can be used to produce genetically improved varieties of <it>Jatropha </it>with increased oil yields, different oil compositions and better agronomic characteristics.</p

Substrate finishing and niobium content effects on the high temperature corrosion resistance in steam atmosphere of CrN/NbN superlattice coatings deposited by PVD-HIPIMS

The main objective of this work was to evaluate the oxidation resistance of three PVD-HIPIMS CrN/NbN coatings, studying the effect of the surface finishing of the substrate and the role of niobium content into the coating composition. CrN/NbN nano-multilayered films on P92 steel were tested at 650°C in pure steam atmosphere. The mass gain was measured at fixed intervals to study their oxidation kinetics. The morphology and thickness of nanoscales were measured by transmission electron microscopy (TEM). Characterization of coatings before and after the thermal treatment was performed by scanning electron microscopy-energy with facilities of dispersive X-ray spectroscopy (SEM–EDX) and X-ray diffraction (XRD). All coatings improved the oxidation resistance of the substrate material, but the best behaviour was exhibited by the CrN/NbN with the high niobium (Nb) content and deposited on the substrate with the finest surface finishing

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Metagenomic Comparison of Two Thiomicrospira Lineages Inhabiting Contrasting Deep-Sea Hydrothermal Environments

Background: The most widespread bacteria in oxic zones of carbonate chimneys at the serpentinite-hosted Lost City hydrothermal field, Mid-Atlantic Ridge, belong to the Thiomicrospira group of sulfur-oxidizing chemolithoautotrophs. It is unclear why Thiomicrospira-like organisms thrive in these chimneys considering that Lost City hydrothermal fluids are notably lacking in hydrogen sulfide and carbon dioxide. Methodology/Principal Findings: Here we describe metagenomic sequences obtained from a Lost City carbonate chimney that are highly similar to the genome of Thiomicrospira crunogena XCL-2, an isolate from a basalt-hosted hydrothermal vent in the Pacific Ocean. Even though T. crunogena and Lost City Thiomicrospira inhabit different types of hydrothermal systems in different oceans, their genomic contents are highly similar. For example, sequences encoding the sulfur oxidation and carbon fixation pathways (including a carbon concentration mechanism) of T. crunogena are also present in the Lost City metagenome. Comparative genomic analyses also revealed substantial genomic changes that must have occurred since the divergence of the two lineages, including large genomic rearrangements, gene fusion events, a prophage insertion, and transposase activity. Conclusions/Significance: Our results show significant genomic similarity between Thiomicrospira organisms inhabiting different kinds of hydrothermal systems in different oceans, suggesting that these organisms are widespread and highl

Exosomes derived from mesenchymal stem cells enhance radiotherapy-induced cell death in tumor and metastatic tumor foci

We have recently shown that radiotherapy may not only be a successful local and regional treatment but, when combined with MSCs, may also be a novel systemic cancer therapy. This study aimed to investigate the role of exosomes derived from irradiated MSCs in the delay of tumor growth and metastasis after treatment with MSC + radiotherapy (RT). The tumor cell loss rates found after treatment with the combination of MSC and RT and for exclusive RT, were: 44.4% % and 12,1%, respectively. Concomitant and adjuvant use of RT and MSC, increased the mice surviving time 22,5% in this group, with regard to the group of mice treated with exclusive RT and in a 45,3% respect control group. Moreover, the number of metastatic foci found in the internal organs of the mice treated with MSC + RT was 60% less than the mice group treated with RT alone. We reasoned that the exosome secreted by the MSC, could be implicated in tumor growth delay and metastasis control after treatment. Our results show that exosomes derived form MSCs, combined with radiotherapy, are determinant in the enhancement of radiation effects observed in the control of metastatic spread of melanoma cells and suggest that exosome-derived factors could be involved in the bystander, and abscopal effects found after treatment of the tumors with RT plus MSC. Radiotherapy itself may not be systemic, although it might contribute to a systemic effect when used in combination with mesenchymal stem cells owing the ability of irradiated MSCs-derived exosomes to increase the control of tumor growth and metastasis.This work was supported by CNPq, Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brasil, Junta de Andalucía, project of Excellence from Junta de Andalucía P12-CTS-383 to FJO, Spanish Ministry of Economy and Competitiveness SAF2015-70520-R to FJO and JMRdA, RTICC RD12/0036/0026 and CIBER Cáncer ISCIII CB16/12/00421 to FJO

Influence of GB virus C on IFN-γ and IL-2 production and CD38 expression in T lymphocytes from chronically HIV-infected and HIV-HCV-co-infected patients

This study was designed to assess the effect of GB virus (GBV)-C on the immune response to human immunodeficiency virus (HIV) in chronically HIV-infected and HIV- hepatitis C virus (HCV)-co-infected patients undergoing antiretroviral therapy. A cohort of 159 HIV-seropositive patients, of whom 52 were HCV-co-infected, was included. Epidemiological data were collected and virological and immunological markers, including the production of interferon gamma (IFN-γ) and interleukin (IL)-2 by CD4, CD8 and Tγδ cells and the expression of the activation marker, CD38, were assessed. A total of 65 patients (40.8%) presented markers of GBV-C infection. The presence of GBV-C did not influence HIV and HCV replication or TCD4 and TCD8 cell counts. Immune responses, defined by IFN-γ and IL-2 production and CD38 expression did not differ among the groups. Our results suggest that neither GBV-C viremia nor the presence of E2 antibodies influence HIV and HCV viral replication or CD4 T cell counts in chronically infected patients. Furthermore, GBV-C did not influence cytokine production or CD38-driven immune activation among these patients. Although our results do not exclude a protective effect of GBV-C in early HIV disease, they demonstrate that this effect may not be present in chronically infected patients, who represent the majority of patients in outpatient clinics.Universidade Federal de São Paulo (UNIFESP) Laboratório de Virologia e Imunologia Disciplina de InfectologiaFleury Medicina DiagnósticaUNIFESP, Laboratório de Virologia e Imunologia Disciplina de InfectologiaSciEL

Effectiveness of PRECEDE model for health education on changes and level of control of HbA1c, blood pressure, lipids, and body mass index in patients with type 2 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Individual health education is considered to be essential in the overall care of patients with type 2 diabetes (DM2), although there is some uncertainty regarding its metabolic control benefits. There have been very few randomized studies on the effects of individual education on normal care in DM2 patients with a control group, and none of these have assessed the long-term results. Therefore, this study aims to use this design to assess the effectiveness of the PRECEDE (Predisposing, Reinforcing, Enabling, Causes in Educational Diagnosis, and Evaluation) education model in the metabolic control and the reduction of cardiovascular risk factors, in patients with type 2 diabetes.</p> <p>Methods</p> <p>An open community effectiveness study was carried out in 8 urban community health centers in the North-East Madrid Urban Area (Spain). Six hundred patients with DM2 were randomized in two groups: PRECEDE or conventional model for health promotion education. The main outcome measures were glycated hemoglobin A1c, body mass index (BMI), blood pressure, lipids and control criteria during the 2-year follow-up period.</p> <p>Results</p> <p>Glycated hemoglobin A1c and systolic blood pressure (SBP) levels decreased significantly in the PRECEDE group (multivariate analysis of covariance, with baseline glycated hemoglobin A1c, SBP, and variables showing statistically significant differences between groups at baseline visits). The decrease levels in diastolic blood pressure (DBP), triglycerides and LDL cholesterol were nonsignificant. PRECEDE increased compliance in all control criteria, except for LDL cholesterol. BMI did not change during the study in either of the two models analyzed.</p> <p>Conclusions</p> <p>PRECEDE health education model is a useful method in the overall treatment in patients with type 2 diabetes, which contributes to decrease glycated hemoglobin A1c and SBP levels and increase the compliance in all the control criteria, except for LDL cholesterol.</p> <p>Trial registration number</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01316367">NCT01316367</a></p