Metabolite Profiles of Sugarcane Culm Reveal the Relationship Among Metabolism and Axillary Bud Outgrowth in Genetically Related Sugarcane Commercial Cultivars

Metabolic composition is known to exert influence on several important agronomic traits, and metabolomics, which represents the chemical composition in a cell, has long been recognized as a powerful tool for bridging phenotype–genotype interactions. In this work, sixteen truly representative sugarcane Brazilian varieties were selected to explore the metabolic networks in buds and culms, the tissues involved in the vegetative propagation of this species. Due to the fact that bud sprouting is a key trait determining crop establishment in the field, the sprouting potential among the genotypes was evaluated. The use of partial least square discriminant analysis indicated only mild differences on bud outgrowth potential under controlled environmental conditions. However, primary metabolite profiling provided information on the variability of metabolic features even under a narrow genetic background, typical for modern sugarcane cultivars. Metabolite–metabolite correlations within and between tissues revealed more complex patterns for culms in relation to buds, and enabled the recognition of key metabolites (e.g., sucrose, putrescine, glutamate, serine, and myo-inositol) affecting sprouting ability. Finally, those results were associated with the genetic background of each cultivar, showing that metabolites can be potentially used as indicators for the genetic background

O LÚDICO NO PROCESSO PEDAGÓGICO DA EDUCAÇÃO INFANTIL: IMPORTANTE, PORÉM AUSENTE

This study observed and analyzed the presence of playful teaching practice on the educational action of teachers in the kindergarten school both from the public and private sectors in the city of São José do Rio Preto. By means of a bibliographical and empirical research, schools from four different parts of the city were evaluated and systematically observed. Later, a questionnaire was applied to the teachers. The main objective was to verify whether or not there were situations in which playful activities would be part of the teacher’s daily agenda, either as a planned activity or even used randomly, as well as the understanding of the teachers concerning this matter in the infantile education.Este estudio analisó la presencia del juguete en el hacer pedagógico de las maestras en guarderías de la red pública de la ciudad de São José do Rio Preto. Por medio de encuestas bibliográficas y empíricas, fueran abordadas escuelas distribuidas en los cuatro sectores de la ciudad en los cuales se realizó una observación sistematizada, y después la aplicación de una encuesta con los maestros. El objectivo primero fue verificar si en el cotidiano de las escuelas tenía o no situaciones de utilización de actividades lúdicas, planeamento de las actividades o empleo obligatorio, como también la comprensión de las mismas acerca de los juguetes infantiles.Este estudo observou e analisou a presença do lúdico no fazer educacional das professoras das escolas infantis das redes pública e particular da cidade de São José do Rio Preto. Por meio de pesquisas bibliográfica e empírica, foram abordadas escolas distribuídas nos quatro setores da cidade, nas quais se realizou, primeiramente, uma observação sistematizada e posteriormente a aplicação de um questionário junto às professoras. O principal objetivo foi verificar se no cotidiano escolar das unidades de ensino infantil envolvidas na pesquisa havia ou não situações de utilização de atividades lúdicas, planejamento das atividades ou seu uso aleatório, assim como a compreensão das professoras acerca do brincar na educação infantil. Os dados coletados foram tratados de modo comparativo entre os dois modelos de escolas compreendidas nos setores público e privado, o que possibilitou traçar um percurso do lúdico na educação infantil e no fazer pedagógico das professoras que, na época, atuavam nos distintos segmentos com a respectiva faixa etária

The Combination of Gefitinib With ATRA and ATO Induces Myeloid Differentiation in Acute Promyelocytic Leukemia Resistant Cells

In approximately 15% of patients with acute myeloid leukemia (AML), total and phosphorylated EGFR proteins have been reported to be increased compared to healthy CD34(+) samples. However, it is unclear if this subset of patients would benefit from EGFR signaling pharmacological inhibition. Pre-clinical studies on AML cells provided evidence on the pro-differentiation benefits of EGFR inhibitors when combined with ATRA or ATO in vitro. Despite the success of ATRA and ATO in the treatment of patients with acute promyelocytic leukemia (APL), therapy-associated resistance is observed in 5-10% of the cases, pointing to a clear need for new therapeutic strategies for those patients. In this context, the functional role of EGFR tyrosine-kinase inhibitors has never been evaluated in APL. Here, we investigated the EGFR pathway in primary samples along with functional in vitro and in vivo studies using several APL models. We observed that total and phosphorylated EGFR (Tyr992) was expressed in 28% and 19% of blast cells from APL patients, respectively, but not in healthy CD34(+) samples. Interestingly, the expression of the EGF was lower in APL plasma samples than in healthy controls. The EGFR ligand AREG was detected in 29% of APL patients at diagnosis, but not in control samples. In vitro, treatment with the EGFR inhibitor gefitinib (ZD1839) reduced cell proliferation and survival of NB4 (ATRA-sensitive) and NB4-R2 (ATRA-resistant) cells. Moreover, the combination of gefitinib with ATRA and ATO promoted myeloid cell differentiation in ATRA- and ATO-resistant APL cells. In vivo, the combination of gefitinib and ATRA prolonged survival compared to gefitinib- or vehicle-treated leukemic mice in a syngeneic transplantation model, while the gain in survival did not reach statistical difference compared to treatment with ATRA alone. Our results suggest that gefitinib is a potential adjuvant agent that can mitigate ATRA and ATO resistance in APL cells. Therefore, our data indicate that repurposing FDA-approved tyrosine-kinase inhibitors could provide new perspectives into combination therapy to overcome drug resistance in APL patients

The effect of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea and uncontrolled hypertension : study design and challenges during the COVID-19 pandemic

OBJECTIVES: To describe the MORPHEOS (Morbidity in patients with uncontrolled HTN and OSA) trial, and describe the challenges imposed by the COVID-19 pandemic. METHODS: MORPHEOS is a multicenter (n=6) randomized controlled trial designed to evaluate the blood pressure (BP) lowering effects of treatment with continuous positive airway pressure (CPAP) or placebo (nasal strips) for 6 months in adult patients with uncontrolled hypertension (HTN) and moderate-to-severe obstructive sleep apnea (OSA). Patients using at least one antihypertensive medication were included. Uncontrolled HTN was confirmed by at least one abnormal parameter in the 24-hour ABPM and >= 80% medication adherence evaluated by pill counting after the run-in period. OSA was defined by an apnea-hypopnea index >= 15 events/ hours. The co-primary endpoints are brachial BP (office and ambulatory BP monitoring, ABPM) and central BP. Secondary outcomes include hypertension-mediated organ damage (HMOD) to heart, aorta, eye, and kidney. We pre-specified several sub-studies from this investigation. Visits occur once a week in the first month and once a month thereafter. The programmed sample size was 176 patients but the pandemic prevented this final target. A post-hoc power analysis will be calculated from the final sample. ClinicalTrials.gov: NCT02270658. RESULTS: The first 100 patients are predominantly males (n=69), age: 52±10 years, body mass index: 32.7±3.9 kg/m2 with frequent co-morbidities. CONCLUSIONS: The MORPHEOS trial has a unique study design including a run-in period; pill counting, and detailed analysis of hypertension-mediated organ damage in patients with uncontrolled HTN that will allow clarification of the impact of OSA treatment with CPAP