Synthesis and antitubercular activity of novel 4-arylalkyl substituted thio-, oxy- and sulfoxy-quinoline analogues targeting the cytochrome bc1 complex

A library of 4-substituted quinolines was synthesised based on the structural features of the privileged 4-(benzylthio)-6-methoxy-2-methylquinoline scaffold. Quinoline-based chemical probes have proven to be effective anti-tuberculosis agents with the ability of inhibiting components of Mycobacterium tuberculosis (MTB) respiratory chain including the b subunit of the cytochrome bc1 complex. Novel 4-(arylalkyl)-thio, -oxy and sulfoxy-quinoline analogues were tested for their ability to inhibit the growth of MTB H37Rv and QcrB mutant strains, and the compounds mode of action was investigated. Members of the 4-subtituted thio- and sulfoxyquinoline series exhibited significant growth inhibitory activity in the high nanomolar range against wild-type MTB and induced depletion of intracellular ATP. These probes also showed reduced potency in the QcrB T313I mutant strain, thus indicating the cytochrome bc1 oxidase complex as the molecular target. Interestingly, new 4-(quinolin-2-yl)oxy-quinoline 4i was more selective for the QcrB T313I strain compared to the wild-type strain

Tolerância de Anticarsia gemmatalis Hübner, Pseudoplusia includens (Walker) E Rachiplusia nu (Guenée) à proteína Cry1Ac.

A soja geneticamente modificada com o gene sintetico de Cry1Ac e uma alternativa ao controle quimico de lepidopteros pragas na cultura da soja. Com a introducao da soja Bt, tornam-se necessarios estudos de analise de risco para prevenir a selecao de insetos resistentes e tambem para compreender o nivel de suscetibilidade dos insetos-alvo a proteina Cry1Ac e com isso iniciar um programa de manejo de resistencia. O objetivo deste trabalho foi determinar a suscetibilidade de Anticarsia gemmatalis Hubner, Pseudoplusia includens (Walker) e Rachiplusia nu (Guenee) provenientes do Rio Grande do Sul a proteina Cry1Ac. Para determinar a suscetibilidade foi utilizada a proteina sintetica de Cry1Ac, MVPII (11,14%). Foram testadas sete concentracoes da proteina Cry1Ac, incorporadas na dieta artificial, apos geleificacao, em cada celula foi inoculada uma lagarta neonata. As lagartas foram mantidas na dieta por sete dias, apos esse periodo avaliou-se a mortalidade e o peso das lagartas sobreviventes. Observou-se que, em ordem decrescente de tolerancia, P. includens apresentou menor suscetibilidade (CL50 1,53 μg Cry1Ac.ml-1 de dieta) a proteina Cry1Ac, seguida por R. nu (CL50 0,70 μg Cry1Ac.ml-1) e por ultimo A. gemmatalis, a qual foi a especie com maior suscetibilidade (CL50 0,04 μg Cry1Ac.ml-1)

Coastal-ocean variability in primary production in the Canary Current upwelling region: comparison among in situ and satellite-derived estimates

Poster.-- Conferencia sobre los Sistemas de Afloramiento de Borde Oriental (EBUS): Pasado, Presente y Futuro & Segunda Conferencia Internacional sobre el Sistema de Corrientes de Humboldt, 19-23 de Septiembre de 2022, Lima, PerúThe Canary Current Eastern Boundary Upwelling Ecosystem (CanC-EBUE), unlike other EBUE, has been unabatedly warming, and decreasing (or at least not increasing) in wind intensity during the last 60 years. However, past trends in net primary production are uncertain, due to differences in the outputs of remote sensing models and the lack of in situ data to validate these models in the region. Here we compare four widely-used models – the Vertically Generalized Production Model (VGPM) and its variant based on Eppley’s description of the growth function (Eppley-VGPM), the Carbon-based Production Model (CbPM), and the Carbon, Absorption and Fluorescence Euphotic-resolving model (CAFE)- with in situ primary production (PP) data. Together with chlorophyll a concentration (Chl a) and phytoplankton biomass (B), we measured PP by 14C and 13C uptake, and oxygen evolution inside incubation bottles, along 11 stations across the transition zone expanding from the coastal upwelling to the open ocean waters at the Cape Verde Frontal Zone (17-23ºN; 16-26ºW). We compared in situ PP, Chl a and B with models’ outputs (NPP) and inputs (satellite derived Chl a and B), respectively. Although carbon and oxygen –based in situ PP estimates were frequently correlated, we found that only the Chl a-based VGPMs were significantly correlated with in situ estimates, yet these are among the the first-described models in the literature. Models based on B, however, did not correlate with in situ PP estimations, in spite that satellite-derived B presented better correlations than Chl a with the in situ dataN

Evaluation of the Allergenicity Potential of TcPR-10 Protein from Theobroma cacao

Background: The pathogenesis related protein PR10 (TcPR-10), obtained from the Theobroma cacao-Moniliophthora perniciosa interaction library, presents antifungal activity against M. perniciosa and acts in vitro as a ribonuclease. However, despite its biotechnological potential, the TcPR-10 has the P-loop motif similar to those of some allergenic proteins such as Bet v 1 (Betula verrucosa) and Pru av 1 (Prunus avium). The insertion of mutations in this motif can produce proteins with reduced allergenic power. The objective of the present work was to evaluate the allergenic potential of the wild type and mutant recombinant TcPR-10 using bioinformatics tools and immunological assays. Methodology/Principal Findings: Mutant substitutions (T10P, I30V, H45S) were inserted in the TcPR-10 gene by sitedirected mutagenesis, cloned into pET28a and expressed in Escherichia coli BL21(DE3) cells. Changes in molecular surface caused by the mutant substitutions was evaluated by comparative protein modeling using the three-dimensional structure of the major cherry allergen, Pru av 1 as a template. The immunological assays were carried out in 8-12 week old female BALB/c mice. The mice were sensitized with the proteins (wild type and mutants) via subcutaneous and challenged intranasal for induction of allergic airway inflammation. Conclusions/Significance: We showed that the wild TcPR-10 protein has allergenic potential, whereas the insertion of mutations produced proteins with reduced capacity of IgE production and cellular infiltration in the lungs. On the other hand, in vitro assays show that the TcPR-10 mutants still present antifungal and ribonuclease activity against M. perniciosa RNA. In conclusion, the mutant proteins present less allergenic potential than the wild TcPR-10, without the loss of interesting biotechnological properties. (Résumé d'auteur

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

Measuring the Effect of Revealed Cultural Preferences on Tourism Exports

The aim of this article is to propose a novel method for measuring the effect of cultural preference on bilateral tourism receipts. The method applied is inspired from Disdier et al. (2010). Using the UNESCO classification and data on bilateral trade in cultural product, a proxy for cultural preferences is constructed. The variable is used in a gravity model for tourism export, which is estimated using a two-step procedure to avoid issues related to endogeneity. The data set used is a panel of 12 OECD countries for a period of 11 years. The variable for cultural preferences eliminates the problems with traditional methods, which by using dummy variables to account for cultural preferences, assume that the latter are time-invariant and symmetrical. The cultural variable constructed is found to be significant in explaining bilateral tourism exports with an elasticity of 0.39. © The Author(s) 2018

Gender Dimorphism in Skeletal Muscle Leptin Receptors, Serum Leptin and Insulin Sensitivity

To determine if there is a gender dimorphism in the expression of leptin receptors (OB-R170, OB-R128 and OB-R98) and the protein suppressor of cytokine signaling 3 (SOCS3) in human skeletal muscle, the protein expression of OB-R, perilipin A, SOCS3 and alpha-tubulin was assessed by Western blot in muscle biopsies obtained from the m. vastus lateralis in thirty-four men (age = 27.1±6.8 yr) and thirty-three women (age = 26.7±6.7 yr). Basal serum insulin concentration and HOMA were similar in both genders. Serum leptin concentration was 3.4 times higher in women compared to men (P<0.05) and this difference remained significant after accounting for the differences in percentage of body fat or soluble leptin receptor. OB-R protein was 41% (OB-R170, P<0.05) and 163% (OB-R128, P<0.05) greater in women than men. There was no relationship between OB-R expression and the serum concentrations of leptin or 17β-estradiol. In men, muscle OB-R128 protein was inversely related to serum free testosterone. In women, OB-R98 and OB-R128 were inversely related to total serum testosterone concentration, and OB-R128 to serum free testosterone concentration. SOCS3 protein expression was similar in men and women and was not related to OB-R. In women, there was an inverse relationship between the logarithm of free testosterone and SCOS3 protein content in skeletal muscle (r = −0.46, P<0.05). In summary, there is a gender dimorphism in skeletal muscle leptin receptors expression, which can be partly explained by the influence of testosterone. SOCS3 expression in skeletal muscle is not up-regulated in women, despite very high serum leptin concentrations compared to men. The circulating form of the leptin receptor can not be used as a surrogate measure of the amount of leptin receptors expressed in skeletal muscles

SCAview: an Intuitive Visual Approach to the Integrative Analysis of Clinical Data in Spinocerebellar Ataxias

With SCAview, we present a prompt and comprehensive tool that enables scientists to browse large datasets of the most common spinocerebellar ataxias intuitively and without technical effort. Basic concept is a visualization of data, with a graphical handling and filtering to select and define subgroups and their comparison. Several plot types to visualize all data points resulting from the selected attributes are provided. The underlying synthetic cohort is based on clinical data from five different European and US longitudinal multicenter cohorts in spinocerebellar ataxia type 1, 2, 3, and 6 (SCA1, 2, 3, and 6) comprising > 1400 patients with overall > 5500 visits. First, we developed a common data model to integrate the clinical, demographic, and characterizing data of each source cohort. Second, the available datasets from each cohort were mapped onto the data model. Third, we created a synthetic cohort based on the cleaned dataset. With SCAview, we demonstrate the feasibility of mapping cohort data from different sources onto a common data model. The resulting browser-based visualization tool with a thoroughly graphical handling of the data offers researchers the unique possibility to visualize relationships and distributions of clinical data, to define subgroups and to further investigate them without any technical effort. Access to SCAview can be requested via the Ataxia Global Initiative and is free of charge