Knocking Down Low Molecular Weight Protein Tyrosine Phosphatase (LMW-PTP) Reverts Chemoresistance through Inactivation of Src and Bcr-Abl Proteins

The development of multidrug resistance (MDR) limits the efficacy of continuous chemotherapeutic treatment in chronic myelogenous leukemia (CML). Low molecular weight protein tyrosine phosphatase (LMW-PTP) is up-regulated in several cancers and has been associated to poor prognosis. This prompted us to investigate the involvement of LMW-PTP in MDR. In this study, we investigated the role of LMW-PTP in a chemoresistant CML cell line, Lucena-1. Our results showed that LMW-PTP is highly expressed and 7-fold more active in Lucena-1 cells compared to K562 cells, the non-resistant cell line. Knocking down LMW-PTP in Lucena-1 cells reverted chemoresistance to vincristine and imatinib mesylate, followed by a decrease of Src and Bcr-Abl phosphorylation at the activating sites, inactivating both kinases. On the other hand, overexpression of LMW-PTP in K562 cells led to chemoresistance to vincristine. Our findings describe, for the first time, that LMW-PTP cooperates with MDR phenotype, at least in part, through maintaining Src and Bcr-Abl kinases in more active statuses. These findings suggest that inhibition of LMW-PTP may be a useful strategy for the development of therapies for multidrug resistant CML

Phenolic extraction of Moringa oleifera leaves in DES: characterization of the extracts and their application in methylcellulose films for food packaging

In this work, a qualitative study of the phenolic content of Moringa oleifera leaves (MO), extracted with deep eutectic solvents (DES) based on choline chloride (ChCl) with lactic acid (LA) or glycerol (GLY), was performed by high-resolution mass spectrometry (HPLC-DAD-ESI-MSn). The two solvents (DES-LA and DES-GLY) extract similar classes of phenolics, and ten compounds were identified. The antioxidant profile was also studied (TPC, TFC, DPPH, FRAP, ORAC, and ABTS). Both solvents show an efficient extraction of phenolic compounds and high antioxidant capacity was verified for the extracts. However, the DES-Gly have a higher capacity for polyphenolic extraction (TPC led to 38.409 ± 0.095 mg GAE.g−1 and 2.259 ± 0.023 mg QE.g−1 for TFC). Films based on methylcellulose (MC) containing different amounts of DES or MO extracts, acting as plasticizers, were developed and characterized regarding their mechanical, optical, water vapor permeability, and microstructural properties. All films are uniform, clear, and transparent with smooth, homogeneous surfaces. It was found that the presence of more than 10% of MO extract and/or DES provided more flexible films (Eb for MC 2%_DES 20% achieved 4.330 ± 0.27 %, and 8.15 ± 0.39 % for MC 2%_MO 20%) with less mechanical and barrier resistance. The ultimate objective of this study was to provide information that could assist in the development of antimicrobial active methylcellulose films for sliced wheat bread packaging.Projects UIDB/50006/2020 and UIDP/50006/2020, funded by FCT/MCTES through national funds

In vitro Antiplasmodial Activities of Alkaloids Isolated from Roots of Worsleya procera (Lem.) Traub (Amaryllidaceae)

A combined phytochemical, crystallographic and biological study of Worsleya procera roots was performed. Fifteen alkaloids were identified by gas chromatography mass spectrometry (GC-MS) and seven of them were isolated. The structures of the alkaloids were elucidated by spectroscopic methods, and a detailed crystallographic study of tazettine was carried out. The isolated alkaloids and the obtained extracts were tested in vitro against Plasmodium falciparum (3D7 and K1 strains) and human hepatocarcinoma cells (HepG2) to assess their antiplasmodial and cytotoxic effects, respectively. One of the isolated alkaloid derivatives, lycorine, exhibited antiplasmodial activity against both sensitive (3D7) and resistant (K1) parasite strains in the low micromolar range (half-maximal sample inhibitory concentration (IC50) values of 2.5 and 3.1 µM, respectively) and displayed a low cytotoxicity profile, with a selectivity index greater than 100. Our findings indicate that lycorine is a hit for antimalarial drug discovery. Keywords: isoquinolinic alkaloids; Amaryllidaceae; Plasmodium falciparum; lycorine; tazettin

The Brazilian Developments on the Regional Atmospheric Modeling System (BRAMS 5.2): An Integrated Environmental Model Tuned for Tropical Areas

We present a new version of the Brazilian developments on the Regional Atmospheric Modeling System where different previous versions for weather, chemistry and carbon cycle were unified in a single integrated software system. The new version also has a new set of state-of-the-art physical parameterizations and greater computational parallel and memory usage efficiency. Together with the description of the main features are examples of the quality of the transport scheme for scalars, radiative fluxes on surface and model simulation of rainfall systems over South America in different spatial resolutions using a scale-aware convective parameterization. Besides, the simulation of the diurnal cycle of the convection and carbon dioxide concentration over the Amazon Basin, as well as carbon dioxide fluxes from biogenic processes over a large portion of South America are shown. Atmospheric chemistry examples present model performance in simulating near-surface carbon monoxide and ozone in Amazon Basin and Rio de Janeiro megacity. For tracer transport and dispersion, it is demonstrated the model capabilities to simulate the volcanic ash 3-d redistribution associated with the eruption of a Chilean volcano. Then, the gain of computational efficiency is described with some details. BRAMS has been applied for research and operational forecasting mainly in South America. Model results from the operational weather forecast of BRAMS on 5 km grid spacing in the Center for Weather Forecasting and Climate Studies, INPE/Brazil, since 2013 are used to quantify the model skill of near surface variables and rainfall. The scores show the reliability of BRAMS for the tropical and subtropical areas of South America. Requirements for keeping this modeling system competitive regarding on its functionalities and skills are discussed. At last, we highlight the relevant contribution of this work on the building up of a South American community of model developers

Vale a pena pagar para desarmar? Uma avaliação do impacto da campanha de entrega voluntária de armas sobre as mortes com armas de fogo

ResumoO objetivo deste trabalho é avaliar o impacto de curto prazo da campanha de entrega de armas (política de buy-back) sobre a incidência de óbitos com armas de fogo no Estado do Paraná. Como neste estado a campanha teve início seis meses antes da campanha nacional (Janeiro/2004), foi possível utilizar o estimador de diferenças em diferenças, em que os municípios paranaenses constituíram o grupo de tratamento e o grupo de controle (formado por alguns municípios das regiões Centro-oeste, Sudeste e Sul do país) foi delimitado com a utilização de técnicas de propensity score matching. Da mesma forma que em outros países que adotaram este tipo de política, não se verificou impacto sobre a taxa de óbitos com armas de fogo durante os seis primeiros meses de campanha no Estado do Paraná, indicando que políticas de buy-back não contribuí ram, pelo menos a curto prazo, para a redução dos crimes envolvendo armas de fogo

Genera Euastrum Ehrenberg ex Ralfs and Micrasterias C.Agardh (Conjugatophyceae-Desmidiaceae) from two Amazon black water environments (Manaus,Amazonas-Brazil)

An investigation of genera Euastrum Ehrenberg ex Ralfs and Micrasterias C.Agardh from an Amazon floodplain lake of the Negro river Basin was undertaken. The samples were collected using a plankton net in four stations on the Tupe Lake and one station near a lake on the Negro river. The species were identified and described on the basis of morphological and morphometrical characteristics. A total of 12 species were identified, five species of Euastrum genus (E. evolutum var. perornatum; E. gemmatum var. monocyclum; E. ornans; E. sinuosum; E. spinulosum), and seven of Micrasterias genus (M. borgei; M. radiata var. brasiliensis; M. torreyi; M. laticeps var. acuminata; M. mahabuleshwarensis var. amazonensis; M. rotata var. rotata; M. siolii). All species, except M. radiata Hassal var. brasiliensis Grönblad, were found in the Negro river; on the other hand, only seven species were found in the Tupé lake, three of Euastrum and four of Micrasterias.Foi realizado um inventário das espécies dos gêneros Euastrum Ehrenberg ex Ralfs e Micrasterias C.Agardh de dois ambientes de águas pretas do município de Manaus, um lago de inundação (lago Tupé), e o rio Negro. As coletas foram realizadas com rede de plâncton em quatro estações no lago e uma no rio Negro, situada próxima ao lago. Um total de 93 amostras foi analisado, coletadas em escala mensal no período de março de 2002 a outubro de 2003. As espécies foram descritas e ilustradas com base na sua morfologia e morfometria. Um total de 12 espécies foi identificado, sendo cinco do gênero Euastrum (E. evolutum var. perornatum; E. gemmatum var. monocyclum; E. ornans; E. sinuosum e E. spinulosum), e sete do gênero Micrasterias (M. borgei; M. radiata var. brasiliensis; M. torreyi; M. laticeps var. acuminata; M. mahabuleshwarensis var. amazonensis; M. rotata var. rotata; M. siolii). Todas as espécies, exceto M. radiata Hassal var. brasiliensis Grönblad, foram registradas no rio Negro, enquanto no lago Tupé foi registrado, no geral, apenas sete espécies, três de Euastrum e quatro de Micrasterias

The Brazilian developments on the Regional Atmospheric Modeling System (BRAMS 5.2): an integrated environmental model tuned for tropical areas

We present a new version of the Brazilian developments on the Regional Atmospheric Modeling System (BRAMS), in which different previous versions for weather, chemistry, and carbon cycle were unified in a single integrated modeling system software. This new version also has a new set of state-of-the-art physical parameterizations and greater computational parallel and memory usage efficiency. The description of the main model features includes several examples illustrating the quality of the transport scheme for scalars, radiative fluxes on surface, and model simulation of rainfall systems over South America at different spatial resolutions using a scale aware convective parameterization. Additionally, the simulation of the diurnal cycle of the convection and carbon dioxide concentration over the Amazon Basin, as well as carbon dioxide fluxes from biogenic processes over a large portion of South America, are shown. Atmospheric chemistry examples show the model performance in simulating near-surface carbon monoxide and ozone in the Amazon Basin and the megacity of Rio de Janeiro. For tracer transport and dispersion, the model capabilities to simulate the volcanic ash 3-D redistribution associated with the eruption of a Chilean volcano are demonstrated. The gain of computational efficiency is described in some detail. BRAMS has been applied for research and operational forecasting mainly in South America. Model results from the operational weather forecast of BRAMS on 5 km grid spacing in the Center for Weather Forecasting and Climate Studies, INPE/Brazil, since 2013 are used to quantify the model skill of near-surface variables and rainfall. The scores show the reliability of BRAMS for the tropical and subtropical areas of South America. Requirements for keeping this modeling system competitive regarding both its functionalities and skills are discussed. Finally, we highlight the relevant contribution of this work to building a South American community of model developers.CNPqFAPESPEarth System Research Laboratory at the National Oceanic and Atmospheric Administration (ESRL/NOAA), Boulder, USAInst Nacl Pesquisas Espaciais, Ctr Previsao Tempo & Estudos Climat, Cachoeira Paulista, SP, BrazilDiv Ciência da Computação, Instituto Tecnológico de Aeronáutica, São José dos Campos, SP, BrazilUniv Estadual Paulista Unesp, Fac Ciencias, Bauru, SP, BrazilCtr Meteorol Bauru IPMet, Bauru, SP, BrazilUniv Fed Sao Paulo, Dept Ciencias Ambientais, Diadema, SP, BrazilUniv Sao Paulo, Inst Astron Geofis & Ciencias Atmosfer, Sao Paulo, SP, BrazilUniv Fed Campina Grande, Dept Ciencias Atmosfer, Campina Grande, PB, BrazilEmbrapa Informat Agr, Campinas, SP, BrazilUniv Fed Sao Paulo, Inst Ciencia & Tecnol, Sao Jose Dos Campos, SP, BrazilUniv Fed Rio Grande do Norte, Dept Ciencias Atmosfer & Climat, Programa Pos Grad Ciencias Climat, Natal, RN, BrazilInst Nacl Pesquisas Espaciais, Ctr Ciencias Sistema, Sao Jose Dos Campos, SP, BrazilUniv Fed Sao Joao Del Rei, Dept Geociencias, Sao Joao Del Rei, MG, BrazilInst Nacl Pesquisas Espaciais, Lab Associado Computacao & Matemat Aplica, Sao Jose Dos Campos, BrazilUniv Evora, Inst Ciencias Agr & Ambientais Mediterr, Evora, PortugalUniv Lusofona Humanidades & Tecnol, Ctr Interdisciplinar Desenvolvimento Ambient Gest, Lisbon, PortugalUniv Fed Pelotas, Fac Meteorol, Pelotas, RS, BrazilUnive Tecnol Fed Parana, Londrina, PR, BrazilNASA, Goddard Space Flight Ctr, Univ Space Res Assoc, Goddard Earth Sci Technol & Res Global Modeling &, Greenbelt, MD USAUniv Fed Sao Paulo, Inst Ciencia & Tecnol, Sao Jose Dos Campos, SP, BrazilUniv Fed Sao Paulo, Inst Ciencia & Tecnol, Sao Jose Dos Campos, SP, BrazilCNPq: 306340/2011-9FAPESP: 2014/01563-1FAPESP: 2015/10206-0FAPESP: 2014/01564-8Web of Scienc