Novel antiproliferative chimeric compounds with marked histone deacetylase inhibitory activity

Given our interest in finding potential antitumor agents and in view of the multifactorial mechanistic nature of cancer, in the present work, taking advantage of the multifunctional ligands approach, new chimeric molecules were designed and synthesized by combining in single chemical entities structural features of SAHA, targeting histone deacetylases (HDACs), with substituted stilbene or terphenyl derivatives previously obtained by us and endowed with antiproliferative and pro-apoptotic activity. The new chimeric derivatives were characterized with respect to their cytotoxic activity and their effects on cell cycle progression on different tumor cell lines, as well as their HDACs inhibition. Among the other, trans -6 showed the most interesting biological profile, as it exhibited a strong pro-apoptotic activity in tumor cell lines in comparison with both of its parent compounds and a marked HDAC inhibition

Clinical compass: Navigating the relationship between clinical and didactic learning

A consistent framework is necessary to guide students, classroom faculty, and clinical instructors. The purpose of this quality improvement project is to create a new tool which would provide consistency for students, guidance to clinical faculty, improve clinical decision making, and integrate classroom and clinical

Two different acid oxidation syntheses to open C60 fullerene for heavy metal detection

Graphene oxide quantum dots (GOQDs) can be synthesized through a large variety of synthesis methods starting from different carbon allotropes such as nanotubes, graphite, C60 and exploiting various synthesis and reactions. These different approaches have great influence on the properties of the obtained materials, and, consequently, on the potential applications. In this work, Buckminster C60 fullerene has been used to prepare unfolded fullerene nanoparticles (UFNPs) via two distinct synthesis methods namely: Hummer and H2 SO4 + HNO3 solution. The different characteristics of the final materials and the different response in the presence of heavy metal ions have been investigated in view of sensing applications of water contamination

Calagem, adubação e nutrição na macieira.

A produção de maçã destaca-se nas regiões de altitude do Sul do Brasil como importante cultura geradora de mão-de-obra e renda. A produtividade, aliada à qualidade dos frutos produzidos, são aspectos de relevância e dependem do adequado manejo do pomar, principalmente em termos de fertilidade do solo e nutrição das plantas. Assim, as correções da acidez e da fertilidade do solo permitem a adequada absorção de nutrientes pela macieira, o que se reflete no bom estado nutricional da macieira e rendimento de frutos. Esse capítulo tem por objetivo sistematizar e disponibilizar conhecimentos, visando auxiliar na tomada de decisão quanto à necessidade do uso, doses e época para o uso de corretivos e adubos na macieira. O manejo inicia antes da implantação do pomar, quando por meio da análise do solo, faz-se o diagnóstico da necessidade de correção da acidez e necessidade de adubação com macro e micronutrientes. Uma vez realizada a implantação do pomar, as fases de crescimento e produção necessitam acompanhamento e manejo específico, onde a fertilidade do solo será adequada conforme a análise. Nestas fases, uma ferramenta importante é o diagnóstico nutricional da planta que é feita pela análise mineral de folhas, complementada pela análise mineral de frutos, entre outros aspectos, tais como, vigor da planta e potencial produtivo. As indicações e sugestões apresentadas neste capítulo representam importantes subsídios aos técnicos e produtores de macieira, visando a obtenção de altos rendimentos de frutos com qualidade, a partir de plantas equilibradas nutricionalmente

Discriminating between different heavy metal ions with fullerene-derived nanoparticles

A novel type of graphene-like nanoparticle, synthesized by oxidation and unfolding of C-60 buckminsterfullerene fullerene, showed multiple and reproducible sensitivity to Cu2+, Pb2+, Cd2+, and As(III) through different degrees of fluorescence quenching or, in the case of Cd2+, through a remarkable fluorescence enhancement. Most importantly, only for Cu2+ and Pb2+, the fluorescence intensity variations came with distinct modifications of the optical absorption spectrum. Time-resolved fluorescence study confirmed that the common origin of these diverse behaviors lies in complexation of the metal ions by fullerene-derived carbon layers, even though further studies are required for a complete explanation of the involved processes. Nonetheless, the different response of fluorescence and optical absorbance towards distinct cationic species makes it possible to discriminate between the presence of Cu2+, Pb2+, Cd2+, and As(III), through two simple optical measurements. To this end, the use of a three-dimensional calibration plot is discussed. This property makes fullerene-derived nanoparticles a promising material in view of the implementation of a selective, colorimetric/fluorescent detection system

Yield and critical levels of P in ‘Cabernet Sauvignon’ vineyards grown in subtropical soils.

Abstract Tropical and subtropical soils in vineyards show high phospho­rus (P) adsorption ability and, consequently, low P availability to plants. However, P critical levels (CL) and sufficiency ranges (SR) in soils and leaves in subtropical regions for yield and the must variables remain unknown. This study aimed to assess the yield response of ‘Cabernet Sauvignon’ grown in acidic soils with a high organic matter content in subtropical regions and to suggest CL and SR of P in the soil and leaves using bayesian change point quantile regression models. The study was carried out in the 2013/14, 2014/15, 2015/16, 2016/17, and 2017/18 crop sea­sons in a vineyard located in southern Brazil, treated with 0, 13, 26, 40, and 52 kg Pha-1 year-1, which were assessed. The P avail­ability in the soil was determined by Mehlich-1. The P in leaves (veraison), yield parameters, and must composition were eval­uated. Phosphate fertilizer applications to ‘Cabernet Sauvignon’ increased soil P, mainly on the soil surface. However, it did not increase the P concentration in leaves or influence yield or alter must pH and composition, such as pH, total soluble solids (TSS), total titratable acidity (TTA), and total polyphenols (TP). While P treatments had no effect on yield and fruit quality it was possible to utilize natural variation and Bayesian change point quantile regression models to determine CL’s for various attrib­utes. The CL of P in the 0-20 cm soil layer was 13.2 mg dm-3. The CL of P in leaves, regarding yield, TSS, and TTA, was 0.61, 0.88, and 0.52%, respectively

Yield and critical levels of P in ‘Cabernet Sauvignon’ vineyards grown in subtropical soils

Tropical and subtropical soils in vineyards show high phospho­rus (P) adsorption ability and, consequently, low P availability to plants. However, P critical levels (CL) and sufficiency ranges (SR) in soils and leaves in subtropical regions for yield and the must variables remain unknown. This study aimed to assess the yield response of ‘Cabernet Sauvignon’ grown in acidic soils with a high organic matter content in subtropical regions and to suggest CL and SR of P in the soil and leaves using bayesian change point quantile regression models. The study was carried out in the 2013/14, 2014/15, 2015/16, 2016/17, and 2017/18 crop sea­sons in a vineyard located in southern Brazil, treated with 0, 13, 26, 40, and 52 kg Pha-1 year-1, which were assessed. The P avail­ability in the soil was determined by Mehlich-1. The P in leaves (veraison), yield parameters, and must composition were eval­uated. Phosphate fertilizer applications to ‘Cabernet Sauvignon’ increased soil P, mainly on the soil surface. However, it did not increase the P concentration in leaves or influence yield or alter must pH and composition, such as pH, total soluble solids (TSS), total titratable acidity (TTA), and total polyphenols (TP). While P treatments had no effect on yield and fruit quality it was possible to utilize natural variation and Bayesian change point quantile regression models to determine CL’s for various attrib­utes. The CL of P in the 0-20 cm soil layer was 13.2 mg dm-3. The CL of P in leaves, regarding yield, TSS, and TTA, was 0.61, 0.88, and 0.52%, respectively

Establishment of potassium reference values using Bayesian models in grapevines

Critical levels (CL) of available potassium (K) in soils and leaves and maximum technical efficiency (MTE) doses are relevant information to define the best K fertilization strategies. The aim of this study was to determine reference values of K in leaves and soil, using Bayesian analysis, in order to maximize grape yield and must quality of ‘Chardonnay’ and ‘Pinot Noir’ grown in a subtropical climate. The vines were subjected to applications of 0, 20, 40, 60 and 80 kg K2O ha−1 year−1. The CL and MTE doses of K, in leaves and soils, were determined using Bayesian hierarchical models. The range of probability of the occurrence of CL in leaves was 15.8 to 18.9 g K kg−1 in ‘Chardonnay’ and 16.8 to 19.1 g K kg−1 in ‘Pinot Noir’ at flowering. Moreover, the range was 15.3 to 18.1 g K kg−1 in ‘Chardonnay’ and 16.1 to 18.2 g K kg−1 in ‘Pinot Noir’ at veraison. In the soil, the CL of available K for ‘Chardonnay’ was 27.4 mg K kg−1 and for ‘Pinot Noir’ it was 23.2 mg K kg−1. The increase of K in leaves and soil increased the TSS, while the TTA decreased in both cultivars after sufficiency rate. The MTE was estimated in ‘Pinot Noir’. The proposition of CL and/or MTE doses of K can help increase the efficiency of K fertilization in vineyards

Effectiveness of benralizumab in severe eosinophilic asthma: Distinct sub-phenotypes of response identified by cluster analysis.

Background: Benralizumab is effective in severe eosinophilic asthma (SEA), but suboptimal responses are observed in some patients. Although several factors have been associated with benralizumab response, no cluster analysis has yet been undertaken to identify different responsiveness sub-phenotypes. Objective: To identify SEA sub-phenotypes with differential responsiveness to benralizumab. Methods: One hundred and five patients diagnosed with SEA who had completed 6 months of benralizumab treatment were included in a hierarchical cluster analysis based on a set of clinical variables that can be easily collected in routine practice (age, age at disease onset, disease length, allergen sensitization status, blood eosinophil count, IgE levels, FEV1% predicted, nasal polyposis, bronchiectasis). Results: Four clusters were identified: Clusters 2 and 3 included patients with high levels of both IgE and eosinophils (type-2 biomarkers high), whereas Clusters 1 and 4 included patients with only one type-2 biomarker at a high level: IgE in Cluster 1 and eosinophils in Cluster 4. Clusters 2 and 3 (both type-2 biomarkers high) showed the highest response rate to benralizumab in terms of elimination of exacerbations (79% and 80% respectively) compared to Clusters 1 and 4 (52% and 60% respectively). When super-response (the absence of exacerbation without oral corticosteroid use) was assessed, Cluster 2, including patients with more preserved lung function than the other clusters, but comparable exacerbation rate, oral corticosteroid use and symptom severity, was the most responsive cluster (87.5% of patients). Conclusions: Our cluster analysis identified benralizumab differential response sub-phenotypes in SEA, with the potential of improving disease treatment and precision management