Avaliação de híbridos de Brachiaria decumbens quanto à resistência à cigarrinha-das-pastagens Deois flavopicta.

Estudos de resistência de gramíneas forrageiras às cigarrinhas-das-pastagens têm gerado resultados decisivos para o lançamento de cultivares que se apresentem resistentes a essas pragas, o que até o momento se caracteriza como melhor método de controle das mesmas. Objetivou-se com este trabalho avaliar 38 híbridos intraespecíficos de Brachiaria decumbens (R12, R71, R81, R120, R158, R161, R165, R167, R168, R169, R176, R178, R179, R181, R183, R184, R188, R189, R193, S3, T44, T54, T66, T68, T86, T87, T89, X2, X30, X61, X72, X78, X99, X118, X121, X122, Y22, Y23) pelo método proposto pelo Centro Internacional de Agricultura Tropical (CIAT)

Resistência de híbridos intraespecíficos de Brachiaria decumbens à cigarrinha-das-pastagens Deois flavopicta.

As cigarrinhas-das-pastagens, principais pragas de pastagens, têm sido controladas essencialmente pelo uso de cultivares resistentes, método viável tanto no aspecto econômico como ambiental. No presente trabalho avaliaramse 27 híbridos intraespecíficos de Brachiaria decumbens (R4, R26, R39, R97, R126, R130, R163, R171, R175, R187, R192, S28, S47, S48, T35, T45, X6, X48, X113, X115, X116, X117, X119, X123, Y21, Z8, Z9) quanto aos parâmetros sobrevivência ninfal e dano causado pela ninfa à planta. Utilizou-se o método de avaliação proposto pelo Centro Internacional de Agricultura Tropical (CIAT)

Heterometallic Titanium-Organic Frameworks as Dual Metal Catalysts for Synergistic Non-Buffered Hydrolysis of Nerve Agent Simulants

Heterometallic metal-organic frameworks (MOFs) can offer important advantages over their homometallic counterparts to enable targeted modification of their adsorption, structural response, electronic structure, or chemical reactivity. However, controlling metal distribution in these solids still remains a challenge. The family of mesoporous titanium-organic frameworks, MUV-101(M), displays heterometallic TiM2 nodes assembled from direct reaction of Ti(IV) and M(II) salts. We use the degradation of nerve agent simulants to demonstrate that only TiFe2 nodes are capable of catalytic degradation in non-buffered conditions. By using an integrative experimental-computational approach, we rationalize how the two metals influence each other, in this case, for a synergistic mechanism reminiscent of bimetallic enzymes. Our results highlight the importance of controlling metal distribution at an atomic level to span the interest of heterometallic MOFs to a broad scope of cascade or tandem reactions. Summary Mixed-metal or heterometallic metal-organic frameworks (MOFs) are gaining importance as a route to produce materials with increasing chemical and functional complexities. We report a family of heterometallic titanium frameworks, MUV-101(M), and use them to exemplify the advantages of controlling metal distribution across the framework in heterogeneous catalysis by exploring their activity toward the degradation of a nerve agent simulant of Sarin gas. MUV-101(Fe) is the only pristine MOF capable of catalytic degradation of diisopropyl-fluorophosphate (DIFP) in non-buffered aqueous media. This activity cannot be explained only by the association of two metals, but to their synergistic cooperation, to create a whole that is more efficient than the simple sum of its parts. Our simulations suggest a dual-metal mechanism reminiscent of bimetallic enzymes, where the combination of Ti(IV) Lewis acid and Fe(III)–OH Brönsted base sites leads to a lower energy barrier for more efficient degradation of DIFP in absence of a base.Financial support for this work was provided by the Marie Skłodowska-Curie Global Fellowships (749359-EnanSET, N.M.P) within the European Union research and innovation framework programme (2014-2020

First-Line Ipatasertib, Atezolizumab, and Taxane Triplet for Metastatic Triple-Negative Breast Cancer: Clinical and Biomarker Results.

PURPOSE: To evaluate a triplet regimen combining immune checkpoint blockade, AKT pathway inhibition, and (nab-) paclitaxel as first-line therapy for locally advanced/metastatic triple-negative breast cancer (mTNBC). PATIENTS AND METHODS: The single-arm CO40151 phase Ib study (NCT03800836), the single-arm signal-seeking cohort of IPATunity130 (NCT03337724), and the randomized phase III IPATunity170 trial (NCT04177108) enrolled patients with previously untreated mTNBC. Triplet therapy comprised intravenous atezolizumab 840 mg (days 1 and 15), oral ipatasertib 400 mg/day (days 1-21), and intravenous paclitaxel 80 mg/m2 (or nab-paclitaxel 100 mg/m2; days 1, 8, and 15) every 28 days. Exploratory translational research aimed to elucidate mechanisms and molecular markers of sensitivity and resistance. RESULTS: Among 317 patients treated with the triplet, efficacy ranged across studies as follows: median progression-free survival (PFS) 5.4 to 7.4 months, objective response rate 44% to 63%, median duration of response 5.6 to 11.1 months, and median overall survival 15.7 to 28.3 months. The safety profile was consistent with the known toxicities of each agent. Grade ≥3 adverse events were more frequent with the triplet than with doublets or single-agent paclitaxel. Patients with PFS >10 months were characterized by NF1, CCND3, and PIK3CA alterations and increased immune pathway activity. PFS <5 months was associated with CDKN2A/CDKN2B/MTAP alterations and lower predicted phosphorylated AKT-S473 levels. CONCLUSIONS: In patients with mTNBC receiving an ipatasertib/atezolizumab/taxane triplet regimen, molecular characteristics may identify those with particularly favorable or unfavorable outcomes, potentially guiding future research efforts

BRS Ipyporã ("belo começo" em guarani): híbrido de Brachiaria da Embrapa.

O híbrido BRS RB331 Ipyporã é resultado de um cruzamento entre B. ruziziensis e B. brizantha realizado em 1992, na Embrapa Gado de Corte e liberado pela Embrapa em 2017 em parceria com a UNIPASTO, após 13 anos intermitentes de avaliações. É uma planta de porte baixo, prostrado, com colmos delgados de bainhas muito pilosas e folhas pilosas em ambas as faces. As espiguetas são uniseriadas e com pouca ou nenhuma pilosidade. A BRS Ipyporã entra no mercado para suprir a demanda por uma cultivar de Brachiaria de boa produtividade e manejo relativamente fácil, como a cv. Marandu, porém com elevado grau de resistência à cigarrinha da cana do gênero Mahanarva, além de apresentar resistência às cigarrinhas típicas de pastagem dos gêneros Deois e Notozulia, principais insetos-praga de pastagens de braquiária no Brasil. A BRS Ipyporã é bastante semelhante à cv. Marandu quanto ao manejo, formando um relvado mais prostrado e denso, com alta porcentagem de folhas, portanto resultando em excelente cobertura do solo e competição com invasoras. A BRS Ipyporã foi selecionada com base na produtividade, vigor, alta qualidade, adaptação a solos de Cerrados e comportamento frente à cigarrinhas em avaliações na Embrapa Gado de Corte. Nos ensaios de VCU sob corte a BRS Ipyporã apresentou bom desempenho agronômico, com alto teor de folhas e relação folha:colmo, mas sobretudo, maior valor nutritivo que a cultivar Marandu e outras cultivares de B. brizantha. Não apresenta resistência a solos encharcados, portanto não pode ser recomendada para áreas com problemas de drenagem, ou onde haja incidência da síndrome da morte do capim-marandu. No ensaio de VCU sob pastejo no Mato Grosso do Sul, foi comprovado seu potencial para produção animal, especialmente pelo alto valor nutritivo. Os animais mantidos em pastos de capim-ipyporã apresentaram maior ganhos médios diários (GMD) em relação àqueles mantidos em capim-marandu. Apresentou ainda boa capacidade de suporte, bom desempenho na época seca e facilidade de manejo. A carência de cultivares adaptadas a solos de média fertilidade, com bom valor nutritivo e com resistência à cigarrinha Mahanarva faz dessa cultivar uma importante alternativa para diversificar áreas hoje plantadas unicamente com as cvs. Marandu, Xaraés e BRS Piatã. O excelente ganho de peso vivo por animal e por área apresentado pela BRS Ipyporã no ensaio de VCU sob pastejo associado ao alto valor nutritivo da forragem disponível, faz dessa cultivar uma forrageira recomendada para a diversificar os sistemas de produção de bovinos de corte, resultando em maior desempenho por animal, e consequentemente, reduzindo a idade de abate. Como consequência, tem-se carne de melhor qualidade e menor emissão de gases de efeito estufa, isto é, um sistema de produção mais sustentável. Pode ainda ser recomendada para as categorias de exigência nutricional mais elevada, tais como bezerros desmamados, vacas em terço final de gestação e em lactação.bitstream/item/159958/1/BRS-Ipypora-belo-comeco-em-guarani.pd

Antiangiogenic therapy for breast cancer

Angiogenesis is an important component of cancer growth, invasion and metastasis. Therefore, inhibition of angiogenesis is an attractive strategy for treatment of cancer. We describe existing clinical trials of antiangiogenic agents and the challenges facing the clinical development and optimal use of these agents for the treatment of breast cancer. Currently, the most promising approach has been the use of bevacizumab, a humanized monoclonal antibody directed against the most potent pro-angiogenic factor, vascular endothelial growth factor (VEGF). Small molecular inhibitors of VEGF tyrosine kinase activity, such as sorafenib, appear promising. While, the role of sunitinib and inhibitors of mammalian target of rapamycin (mTOR) in breast cancer has to be defined. Several unanswered questions remain, such as choice of drug(s), optimal duration of therapy and patient selection criteria

Synthetic Nanoparticles for Vaccines and Immunotherapy

The immune system plays a critical role in our health. No other component of human physiology plays a decisive role in as diverse an array of maladies, from deadly diseases with which we are all familiar to equally terrible esoteric conditions: HIV, malaria, pneumococcal and influenza infections; cancer; atherosclerosis; autoimmune diseases such as lupus, diabetes, and multiple sclerosis. The importance of understanding the function of the immune system and learning how to modulate immunity to protect against or treat disease thus cannot be overstated. Fortunately, we are entering an exciting era where the science of immunology is defining pathways for the rational manipulation of the immune system at the cellular and molecular level, and this understanding is leading to dramatic advances in the clinic that are transforming the future of medicine.1,2 These initial advances are being made primarily through biologic drugs– recombinant proteins (especially antibodies) or patient-derived cell therapies– but exciting data from preclinical studies suggest that a marriage of approaches based in biotechnology with the materials science and chemistry of nanomaterials, especially nanoparticles, could enable more effective and safer immune engineering strategies. This review will examine these nanoparticle-based strategies to immune modulation in detail, and discuss the promise and outstanding challenges facing the field of immune engineering from a chemical biology/materials engineering perspectiveNational Institutes of Health (U.S.) (Grants AI111860, CA174795, CA172164, AI091693, and AI095109)United States. Department of Defense (W911NF-13-D-0001 and Awards W911NF-07-D-0004

Genome-Wide Mutagenesis of Xanthomonas axonopodis pv. citri Reveals Novel Genetic Determinants and Regulation Mechanisms of Biofilm Formation

Xanthomonas axonopodis pv. citri (Xac) causes citrus canker disease, a major threat to citrus production worldwide. Accumulating evidence suggests that the formation of biofilms on citrus leaves plays an important role in the epiphytic survival of this pathogen prior to the development of canker disease. However, the process of Xac biofilm formation is poorly understood. Here, we report a genome-scale study of Xac biofilm formation in which we identified 92 genes, including 33 novel genes involved in biofilm formation and 7 previously characterized genes, colR, fhaB, fliC, galU, gumD, wxacO, and rbfC, known to be important for Xac biofilm formation. In addition, 52 other genes with defined or putative functions in biofilm formation were identified, even though they had not previously reported been to be associated with biofilm formation. The 92 genes were isolated from 292 biofilm-defective mutants following a screen of a transposon insertion library containing 22,000 Xac strain 306 mutants. Further analyses indicated that 16 of the novel genes are involved in the production of extracellular polysaccharide (EPS) and/or lipopolysaccharide (LPS), 7 genes are involved in signaling and regulatory pathways, and 5 genes have unknown roles in biofilm formation. Furthermore, two novel genes, XAC0482, encoding a haloacid dehalogenase-like phosphatase, and XAC0494 (designated as rbfS), encoding a two-component sensor protein, were confirmed to be biofilm-related genes through complementation assays. Our data demonstrate that the formation of mature biofilm requires EPS, LPS, both flagellum-dependent and flagellum-independent cell motility, secreted proteins and extracellular DNA. Additionally, multiple signaling pathways are involved in Xac biofilm formation. This work is the first report on a genome-wide scale of the genetic processes of biofilm formation in plant pathogenic bacteria. The report provides significant new information about the genetic determinants and regulatory mechanism of biofilm formation