Evaluación de métodos para medir la actividad inhibitoria de extractos vegetales nativos del departamento de sucre sobre bacterias y levadura patógenas

The objective of this study was to evaluate the efficiency of two methods for measuring inhibitory activity of native ethanolic extracts plant of the Department of Sucre on bacteria and yeast human pathogenic. Sampling was conducted in the municipalities of Morroa and Sincelejo. The leaves of the plants Melia azederach, Sapium sp, Jatropha gossypilia, Psidium guajava, Origanum vulgare, Melissa officinalis, Eucalyptus sp and Cymbopogon citratus were processed using the methods of percolation and Soxhlet for the extraction of the extract. Methods were tested on agar hole method (Method 1) and the sensitive disk method (method 2) to measure the inhibitory effect on Pseudomonas aeruginosa, Klebsiella oxytoca, Enterococcus faecalis, Escherichia coli, and Bulkolderia glumaea Zygosaccharomyces microellipsoides. The results demonstrate that the method 2 allows greater efficiency and interpretation of results with regard to method 1 where there was diffusion of the extracts in the hole, which creates interference in the measurement. This is the first work in the department of Sucre where two methods are evaluated to determine inhibitory activity of a large group of native plants on pathogenic bacteria and yeast.El objetivo del presente trabajo fue evaluar la eficiencia de dos métodos para medir actividad inhibitoria de extractos vegetales etanólicos nativos del Departamento de Sucre sobre bacterias y levadura patógenas de humanos y plantas. Los muestreos se realizaron en los municipios de Morroa y Sincelejo. Las hojas de las plantas Melia Azederach, Sapium sp, Jatropha gossypilia, Psidium guajava, Origanum vulgare Melissa officinalis, Eucalyptus sp y Cymbopogon citratus fueron procesadas utilizando los métodos de percolación y de soxhlet para la extracción de los extractos. Se evaluaron los métodos de orificio sobre agar (método 1) y el método de disco sensitivos (método 2) para medir el efecto inhibitorio sobre Pseudomonas aeruginosa, Klebsiella oxytoca, Enterococcus faecalis, Escherichia coli, Bulkolderia glumaea y Zygosaccharomyces microellipsoides. Los resultados obtenidos demuestran que el método 2 permite una mayor eficacia e interpretación de los resultados con relación al método 1 donde se observó difusión de los extractos en el orificio, lo cual crea interferencia en la medición. Este es el primer trabajo en el departamento de Sucre donde se evalúan dos métodos para determinar actividad inhibitoria de un grupo amplio de plantas nativas sobre bacterias y levadura patógenas

Multigene mutation profiling and clinical characteristics of small-cell lung cancer in never-smokers vs. seavy smokers (Geno1.3-CLICaP)

Objectives: Lung cancer is a heterogeneous disease. Presentation and prognosis are known to vary according to several factors, such as genetic and demographic characteristics. Small-cell lung cancer incidence is increasing in never-smokers. However, the disease phenotype in this population is different compared with patients who have a smoking history. Material and Methods: To further investigate the clinical and genetic characteristics of this patient subgroup, a cohort of small cell lung cancer patients was divided into smokers (n = 10) and never/ever-smokers (n = 10). A somatic mutation profile was obtained using a comprehensive NGS assay. Clinical outcomes were compared using the Kaplan-Meier method and Cox proportional models. Results: Median age was 63 years (46–81), 40% were men, and 90% had extended disease. Smoker patients had significantly more cerebral metastases (p = 0.04) and were older (p = 0.03) compared to their non-smoker counterparts. For never/ever smokers, the main genetic mutations were TP53 (80%), RB1 (40%), CYLD (30%), and EGFR (30%). Smoker patients had more RB1 (80%, p = 0.04), CDKN2A (30%, p = 0.05), and CEBPA (30%, p = 0.05) mutations. Response rates to first-line therapy with etoposide plus cisplatin/carboplatin were 50% in smokers and 90% in never/ever smokers (p = 0.141). Median overall survival was significantly longer in never smokers compared with smokers (29.1 months [23.5–34.6] vs. 17.3 months [4.8–29.7]; p = 0.0054). Never/ever smoking history (HR 0.543, 95% CI 0.41–0.80), limited-stage disease (HR 0.56, 95% CI 0.40–0.91) and response to first-line platinum-based chemotherapy (HR 0.63, 95% CI 0.60–0.92) were independently associated with good prognosis. Conclusion: Our data supports that never/ever smoker patients with small-cell lung cancer have better prognosis compared to their smoker counterparts. Further, patients with never/ever smoking history who present with small-cell lung cancer have a different mutation profile compared with smokers, including a high frequency of EGFR, MET, and SMAD4 mutations. Further studies are required to assess whether the differential mutation profile is a consequence of a diverse pathological mechanism for disease onset

Genotyping squamous cell lung carcinoma in Colombia (Geno1.1-CLICaP)

Background: Lung cancer is a public health problem, and squamous cell carcinoma (SCC) is the second most prevalent subtype of this neoplasm. Compared to other subtypes, including adenocarcinoma, SCC is less well understood in terms of molecular pathogenesis, limiting therapeutic options among targeted agents approved for other disease subgroups. In this study, we sought to characterize the SCC genomic profile using a validated Next Generation Sequencing (NGS) platform. Methods: The comprehensive NGS assay (TruSight Tumor 170) was used in order to target the full coding regions of 170 cancer-related genes on SCC samples. PD-L1 expression in tumor cells (TCs) was assessed using clone 22C3 (Dako). Clinical outcomes were correlated with molecular profile, including progression free survival (PFS), overall response rate (ORR), and overall survival (OS). Results: A total of 26 samples were included, median age was 67 years (r, 33–83) and 53.8% were men. Tobacco consumption was identified in all subjects (mean 34-year package). For first-line treatment 80.8% of patients received cisplatin or carboplatin plus gemcitabine. In terms of molecular profile, we identified a high prevalence of inactivating mutations in TP53 (61.5%), PIK3CA (34.6%), MLL2 (34.6%), KEAP1 (38.4%), and NOTCH1 (26.9%). PD-L1 expression ranged from negative, 1, 2–49, and ≥50% in 23.1, 38.5, 26.9, and 11.5%, respectively. Interestingly, the genetic alterations did not have an effect in PFS, OS or ORR in this study. However, PDL1 expression was higher among those who had mutations in TP53 (p = 0.037) and greater expression of PDL1 was related to PIK3CA alterations (p = 0.05). Conclusions: The genomic profile of SCC encompasses important genes including TP53, PIK3CA and KEAP1. TP53 mutations could be associated with PDL1 expression, generating hypothesis regarding specific treatment options

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Multigene Mutation Profiling and Clinical Characteristics of Small-Cell Lung Cancer in Never-Smokers vs. Heavy Smokers (Geno1.3-CLICaP)

Objectives: Lung cancer is a heterogeneous disease. Presentation and prognosis are known to vary according to several factors, such as genetic and demographic characteristics. Small-cell lung cancer incidence is increasing in never-smokers. However, the disease phenotype in this population is different compared with patients who have a smoking history.Material and Methods: To further investigate the clinical and genetic characteristics of this patient subgroup, a cohort of small cell lung cancer patients was divided into smokers (n = 10) and never/ever-smokers (n = 10). A somatic mutation profile was obtained using a comprehensive NGS assay. Clinical outcomes were compared using the Kaplan-Meier method and Cox proportional models.Results: Median age was 63 years (46–81), 40% were men, and 90% had extended disease. Smoker patients had significantly more cerebral metastases (p = 0.04) and were older (p = 0.03) compared to their non-smoker counterparts. For never/ever smokers, the main genetic mutations were TP53 (80%), RB1 (40%), CYLD (30%), and EGFR (30%). Smoker patients had more RB1 (80%, p = 0.04), CDKN2A (30%, p = 0.05), and CEBPA (30%, p = 0.05) mutations. Response rates to first-line therapy with etoposide plus cisplatin/carboplatin were 50% in smokers and 90% in never/ever smokers (p = 0.141). Median overall survival was significantly longer in never smokers compared with smokers (29.1 months [23.5–34.6] vs. 17.3 months [4.8–29.7]; p = 0.0054). Never/ever smoking history (HR 0.543, 95% CI 0.41–0.80), limited-stage disease (HR 0.56, 95% CI 0.40–0.91) and response to first-line platinum-based chemotherapy (HR 0.63, 95% CI 0.60–0.92) were independently associated with good prognosis.Conclusion: Our data supports that never/ever smoker patients with small-cell lung cancer have better prognosis compared to their smoker counterparts. Further, patients with never/ever smoking history who present with small-cell lung cancer have a different mutation profile compared with smokers, including a high frequency of EGFR, MET, and SMAD4 mutations. Further studies are required to assess whether the differential mutation profile is a consequence of a diverse pathological mechanism for disease onset

Fragmentos: leer, traducir, dialogar.

Pensar la enseñanza de la filosofía implica pensar tanto la noción de enseñanza como la concepción de filosofía. Más que en una natural secuencia o linea conjunción, esta conversación que llamamos libro, se nutre de la relación compleja que va desde la enseñanza a la filosofía pero, también, desde la filosofía a la enseñanza. Es la actualización de una invitación ya anticipada por Alejandro Cerletti en relación a pensar la enseñanza desde la filosofía, es decir, como un problema filosófico; e, igualmente, es la actualización de otra invitación, aquella consistente en pensar la filosofía desde la enseñanza, esto es, como un problema pedagógico, como práctica de formación, como ejercicio psicagógico. Siguiendo fines procedimentales, las discusiones que nutren los pasajes del libro han sido entretejidas desde cuatro ejes: Enseñanza de la filosofía, Aprender filosofía, Educación filosófica y Didáctica de la filosofía. Categorías de análisis que, en la arquitectura del libro. Ejercicios que han nutrido tanto a la filosofía como a la misma enseñanza. Tres maneras de problematizar, tres maneras de conversar, tres maneras de preguntar

Fragmentos: leer, traducir, dialogar.

Pensar la enseñanza de la filosofía implica pensar tanto la noción de enseñanza como la concepción de filosofía. Más que en una natural secuencia o linea conjunción, esta conversación que llamamos libro, se nutre de la relación compleja que va desde la enseñanza a la filosofía pero, también, desde la filosofía a la enseñanza. Es la actualización de una invitación ya anticipada por Alejandro Cerletti en relación a pensar la enseñanza desde la filosofía, es decir, como un problema filosófico; e, igualmente, es la actualización de otra invitación, aquella consistente en pensar la filosofía desde la enseñanza, esto es, como un problema pedagógico, como práctica de formación, como ejercicio psicagógico. Siguiendo fines procedimentales, las discusiones que nutren los pasajes del libro han sido entretejidas desde cuatro ejes: Enseñanza de la filosofía, Aprender filosofía, Educación filosófica y Didáctica de la filosofía. Categorías de análisis que, en la arquitectura del libro. Ejercicios que han nutrido tanto a la filosofía como a la misma enseñanza. Tres maneras de problematizar, tres maneras de conversar, tres maneras de preguntar

Proteomic and metabolomics of soybean: molecular mechanisms of resistance Anticarsia gemmatalis

A cultura da soja (Glycine max (L.) Merrill) é umas das mais importantes para a economia do Brasil sendo o segundo maior produtor e exportador mundial. As grandes lavouras de soja, porém, encontram-se expostas a estresses bióticos como o desfolhamento ocasionado por insetos-praga como Anticarsia gemmatalis, que diminuem a produtividade. O manejo integrado de pragas no Brasil, inclui o uso de pesticidas que podem afetar o equílibro dos ecossistemas, controle biológico e melhoramento genético para produção de plantas resistentes, mas pouco se conhece sobre as características moleculares de resistência delas. O objetivo deste trabalho foi aprofundar no conhecimento sobre os mecanismos moleculares de defesa da soja em plantas susceptíveis e resistentes a insetos praga, e aplica-lo para determinar o efeito na biologia de A. gemmatalis. Neste trabalho foram aplicadas várias estratégias metodológicas, em busca de escolher a variedade com melhor resistência, como as análises de sobrevivência durante a fase larval de A. gemmatalis em plantas de soja UFV TN 105 AP e “IAC PL1” (susceptíveis) e IAC 17, “IAC 19” e IAC 24 (resistentes). Para avaliar o efeito dos compostos produzidos pelas plantas na sobrevivência dos insetos, prepararam-se extratos metanólicos, os quais foram liofilizados, se adicionaram às dietas dos insetos para fazer analises de sobrevivência, e se analisaram os flavonoides por LC-MS. As respostas fisiológicas e bioquímicas das plantas foram comparadas entre genótipos. Para isso foram feitos análises de fito-hormônios, metabôlomica e proteômica nos extratos das plantas. Os resultados mostraram que o genótipo IAC 17 teve as melhores caraterísticas de resistência. Os extratos das plantas tem efeito negativo no desenvolvimento das lagartas, afetam as enzimas intestinais e ocasionam dano neste tipo de células. As análises dos flavonoides mostraram que os genótipos têm diferenças em alguns flavonoides como a genisteína, a quercetina, o kaempferol e seus conjugados. A proteômica mostrou que houve diferenças no proteoma quando as plantas foram expostas à infestação. O proteoma no geral foi muito semelhante entre variedades. Algumas das mudanças no proteoma em 8 viesposta ao inseto entre os genótipos foram as mesmas, mas a grande maioria das proteínas que tiveram abundancia diferencial foram únicas para cada genótipo. A resposta fito- hormonal das plantas à presença da lagarta não variou muito durante os diferentes tempos avaliados, mas entre as variedades existem diferenças nas concentrações dos fito- hormônios avaliados. Fito-hormônios como o acido salicílico tiveram concentrações maiores nos genótipos resistentes e o acido jasmónico nas susceptíveis, mostrando que não todas as respostas de resistência estão relacionadas ao ácido jasmônico. As análises de metabôlomica mostraram um aumento dos metabólitos como o eriodictiol e secologanina, relacionados com defesa depois de 24h de infestação, e mudanças no metabolismo primário. A analise de PCA mostrou uma distribuição diferenciada dos dados às 24h de infestação. As plantas de soja podem ser fontes viáveis para o controle de pragas porque contêm compostos com caraterísticas de bioativos. A defesa de plantas de soja se compõe de uma rede complexa de vias, este estudo mostrou que as caraterísticas obedecem a defesa constitutiva, que pode conduzir a antibiose e tolerância da soja às pragas. O genótipo IAC 17 tem as melhores caraterísticas de resistência à herbívoria, seguido do IAC 24, mostrando ter caraterísticas de antibiose e tolerância. As plantas caracterizadas como suscetíveis e usadas neste estudo também apresentam respostas á herbívoria, mas não o suficiente para causar dano significativo à lagarta-da-soja.The soybean crop (Glycine max (L.) Merrill) is very important for the economy of Brazil being the second largest producer and exporter in the world. However, large soybean crops are exposed to biotic stresses such as defoliation caused by insect pests such as Anticarsia gemmatalis, which decrease productivity. Integrated pest management in Brazil includes the use of pesticides that can affect ecosystem balance, biological control and genetic improvement for the production of resistant plants, but the knowledge about the molecular resistance characteristics of these plants is minimal. The aim of this work was to delve into the knowledge on the molecular mechanisms of soybean defense in plants susceptible and resistant to insect pests, and applied it to determine the effect on the biology of A. gemmatalis. In this work several methodological strategies were applied in order to select the best resistant variety, such as survival analyzes during the larval phase of A. gemmatalis in soybean plants UFV TN 105 AP and “IAC PL1” (susceptible) and IAC 17, “IAC 19” and IAC 24 (resistant). To evaluate the effect of the compounds produced by plants on insect survival, methanoic extracts were prepared, lyophilized and added to the caterpillar diets and the insect survival analyzed, and flavonoids analyzed by LC-MS. The physiological and biochemical responses of the plants compared between genotypes. For this, phytohormones, metabolic and proteomic analyzes were performed on plant extracts. The results showed that the genotype IAC 17 had the best resistance characteristics. Plant extracts have a negative effect on the development of caterpillars, affect intestinal enzymes and cause damage in this cells. The flavonoid analyzes showed that the genotypes have differences in some flavonoids like genistein, quercetin, kaempferol and their conjugates. Proteomics showed that there were differences in the proteome when the plants exposed to infestation. The proteoma was very similar between varieties. Some changes in proteome response to insect between genotypes were the same, but the great majority of the proteins that had differential abundance were unique for each genotype. The phytohormonal response of the plants to the presence of the caterpillar did 10 viiinot vary much in the different times evaluated, but between the varieties, there are differences in the concentrations of phytohormones evaluated. Phytohormones like salicylic acid had higher concentrations in the resistant and the jasmonic acid in the susceptible genotypes, showing that not all resistance responses are related to jasmonic acid. Metabolomics analyzes showed an increase in defense-related metabolites like eriodyctiol and secologannin after 24 hours of infestation, and some changes in primary metabolism. PCA analysis showed a differentiated distribution of data at 24 h of infestation. Soybean plants can be viable sources of pest control because they contain compounds with bioactive characteristics. The defense of soybean plants is composed of a complex network of pathways; this study showed that the characteristics obey the constitutive defense, which can lead to antibiosis and tolerance of soybean to pests. Genotype IAC 17 has the best characteristics of resistance to herbivory, followed by IAC 24, showing to have characteristics of antibiosis and tolerance. The plants characterized like susceptible and used in this study also present responses to the herbivory, but not enough to cause significant damage to the soybean caterpillar.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superio