Development of a Brazilian maize core collection

The aim of this study was to evaluate methods for developing a Brazilian maize core collection. For an initial survey of the active collection, passport information, as well as characterization and evaluation of accessions, were taken into consideration, these then being divided according to geographic region and kernel-type. Multiple sampling methods were evaluated. The strategy of constant sampling generated extensive alterations in extract accession frequency. The multivariate strategy with dispersion graphs and principal components associated with the Tocher method was considered efficient for identifying the most divergent genotypes. The multivariate strategy generated greater alterations in the variance of traits. The average number of traits revealed few modifications with the various sampling strategies used. Therefore, the active collection could be considered as possessing a satisfactory amount of information for most of its accessions. Moreover, the multivariate strategy generated modifications in the variance of the traits, independent of sampling intensity

The European Portuguese version of the ASAS Health Index for Patients with Spondyloarthritis: Measurement properties

Objective: The Assessments of SpondyloArthritis international Society Health Index (ASAS HI), estimates the impact of Spondyloarthritis (SpA) on global functioning and health. This article assesses the construct validity, reliability and responsiveness of the Portuguese version of the ASAS HI. Patients And Methods: Patients fulfilling ASAS classification criteria for axial (axSpA) or peripheral SpA (pSpA) were included. Construct validity was assessed through Spearman’s correlation analysis with other health outcomes. Discriminant validity wastested comparing the ASAS HI across disease activity and functionalstates using the Kruskal–Wallistest. Internal consistency was assessed by Cronbach’s a, and test-retest reliability by intraclass correlation coefficients (ICC). Responsiveness was evaluated by the standardized response mean (SRM) in patients with active disease who required therapy escalation. Results: Among the 91 patients included, 67% were male, mean (SD) age 47.2 (12.9) years, 63 patients with axSpA and 28 patients with pSpA. The hypothesis defined a priori to test construct validity were confirmed. The ASAS HI showed ability to discriminate between patients with different disease activity and functional states (p<0.001). Internal consistency (Cronbach’s a: 0.88) and test-retest reliability [ICC=0.76 (95%CI 0.09-0.91)] were good. Responsiveness was moderate\ud (SRM=-0.53). The smallest detectable change was 3.0. Conclusions: The Portuguese version of the ASAS HI is a comprehensible questionnaire that is valid, reliable and responsive. It can be used to assess the impact of SpA and its treatment on functioning and health, in clinical practice and for research purposes

Aspectos económicos y ambientales de la producción de hidrógeno en la provincia de Córdoba, a partir de recursos eólicos

En este trabajo se presenta la Evaluación Económica y Ambiental del proyecto de instalación de un parque eólico en la provincia de Córdoba con fines de producción de hidrógeno. El potencial de hidrógeno eólico se analiza para cada departamento de la provincia, considerando los requerimientos energéticos del electrolizador y el factor de capacidad de los sitios analizados. Se analizaron cuatro aspectos del sistema: la evaluación del recurso eólico, el análisis del costo de producción de hidrógeno vía electrólisis, los requerimientos de energía eólica anual para producir hidrógeno y la evaluación de impacto ambiental del proyecto. Para ello se modela una planta que genera una potencia nominal de 60 MW. A partir del costo modelado de producción de la energía, se determina el de producción de hidrógeno. El presente análisis contribuirá a definir los desafíos y oportunidades para la producción de hidrógeno/eólico, que definirán una futura economía del hidrógeno.This paper presents the Economic and Environmental Project evaluation for installation of a wind farm in the province of Cordoba for the purpose of hydrogen production. The potential of hydrogen wind is analyzed for each department province, considering the energy requirements of the electrolyzer and the capacity factor of samples analyzed. We analyzed four aspects of system: hydrogen resource assessment, cost analysis of hydrogen production via electrolysis, wind energy requirements to produce hydrogen and annual assessment project's environmental impact. For this purpose a plant that generates a nominal power of 60 MW was modeled. From a model of cost production of energy the cost production of hydrogen was determined. This analysis should help to define the challenges and opportunities for the production of hydrogen / wind, defining a future hydrogen economy.Asociación Argentina de Energías Renovables y Medio Ambiente (ASADES

Aspectos económicos y ambientales de la producción de hidrógeno en la provincia de Córdoba, a partir de recursos eólicos

En este trabajo se presenta la Evaluación Económica y Ambiental del proyecto de instalación de un parque eólico en la provincia de Córdoba con fines de producción de hidrógeno. El potencial de hidrógeno eólico se analiza para cada departamento de la provincia, considerando los requerimientos energéticos del electrolizador y el factor de capacidad de los sitios analizados. Se analizaron cuatro aspectos del sistema: la evaluación del recurso eólico, el análisis del costo de producción de hidrógeno vía electrólisis, los requerimientos de energía eólica anual para producir hidrógeno y la evaluación de impacto ambiental del proyecto. Para ello se modela una planta que genera una potencia nominal de 60 MW. A partir del costo modelado de producción de la energía, se determina el de producción de hidrógeno. El presente análisis contribuirá a definir los desafíos y oportunidades para la producción de hidrógeno/eólico, que definirán una futura economía del hidrógeno.This paper presents the Economic and Environmental Project evaluation for installation of a wind farm in the province of Cordoba for the purpose of hydrogen production. The potential of hydrogen wind is analyzed for each department province, considering the energy requirements of the electrolyzer and the capacity factor of samples analyzed. We analyzed four aspects of system: hydrogen resource assessment, cost analysis of hydrogen production via electrolysis, wind energy requirements to produce hydrogen and annual assessment project's environmental impact. For this purpose a plant that generates a nominal power of 60 MW was modeled. From a model of cost production of energy the cost production of hydrogen was determined. This analysis should help to define the challenges and opportunities for the production of hydrogen / wind, defining a future hydrogen economy.Asociación Argentina de Energías Renovables y Medio Ambiente (ASADES

Aspectos económicos y ambientales de la producción de hidrógeno en la provincia de Córdoba, a partir de recursos eólicos

En este trabajo se presenta la Evaluación Económica y Ambiental del proyecto de instalación de un parque eólico en la provincia de Córdoba con fines de producción de hidrógeno. El potencial de hidrógeno eólico se analiza para cada departamento de la provincia, considerando los requerimientos energéticos del electrolizador y el factor de capacidad de los sitios analizados. Se analizaron cuatro aspectos del sistema: la evaluación del recurso eólico, el análisis del costo de producción de hidrógeno vía electrólisis, los requerimientos de energía eólica anual para producir hidrógeno y la evaluación de impacto ambiental del proyecto. Para ello se modela una planta que genera una potencia nominal de 60 MW. A partir del costo modelado de producción de la energía, se determina el de producción de hidrógeno. El presente análisis contribuirá a definir los desafíos y oportunidades para la producción de hidrógeno/eólico, que definirán una futura economía del hidrógeno.This paper presents the Economic and Environmental Project evaluation for installation of a wind farm in the province of Cordoba for the purpose of hydrogen production. The potential of hydrogen wind is analyzed for each department province, considering the energy requirements of the electrolyzer and the capacity factor of samples analyzed. We analyzed four aspects of system: hydrogen resource assessment, cost analysis of hydrogen production via electrolysis, wind energy requirements to produce hydrogen and annual assessment project's environmental impact. For this purpose a plant that generates a nominal power of 60 MW was modeled. From a model of cost production of energy the cost production of hydrogen was determined. This analysis should help to define the challenges and opportunities for the production of hydrogen / wind, defining a future hydrogen economy.Asociación Argentina de Energías Renovables y Medio Ambiente (ASADES

Cancer-associated fibroblasts modify lung cancer metabolism involving ROS and TGF-β signaling

Lung cancer is a major public health problem due to its high incidence and mortality rate. The altered metabolism in lung cancer is key for the diagnosis and has implications on both, the prognosis and the response to treatments. Although Cancer-associated fibroblasts (CAFs) are one of the major components of the tumor microenvironment, little is known about their role in lung cancer metabolism. We studied tumor biopsies from a cohort of 12 stage IIIA lung adenocarcinoma patients and saw a positive correlation between the grade of fibrosis and the glycolysis phenotype (Low PGC-1α and High GAPDH/MT-CO1 ratio mRNA levels). These results were confirmed and extended to other metabolism-related genes through the in silico data analysis from 73 stage IIIA lung adenocarcinoma patients available in TCGA. Interestingly, these relationships are not observed with the CAFs marker α-SMA in both cohorts. To characterize the mechanism, in vitro co-culture studies were carried out using two NSCLC cell lines (A549 and H1299 cells) and two different fibroblast cell lines. Our results confirm that a metabolic reprogramming involving ROS and TGF-β signaling occurs in lung cancer cells and fibroblasts independently of α-SMA induction. Under co-culture conditions, Cancer-Associated fibroblasts increase their glycolytic ability. On the other hand, tumor cells increase their mitochondrial function. Moreover, the differential capability among tumor cells to induce this metabolic shift and also the role of the basal fibroblasts Oxphos Phosphorylation (OXPHOS) function modifying this phenomenon could have implications on both, the diagnosis and prognosis of patients. Further knowledge in the mechanism involved may allow the development of new therapies.Work in the authors’ laboratories is supported by ‘‘Instituto de Salud Carlos III’’ PI13/01806 and PIE14/0064 to M.P. A.C-B, received a Spanish Lung Cancer Group fellowship. R.L-B, is supported by Comunidad Autónoma de Madrid “Garantía juvenil” contract

Cisplatin resistance involves a metabolic reprogramming through ROS and PGC-1α in NSCLC which can be overcome by OXPHOS inhibition

Background: Platinum-based chemotherapy remains the standard of care for most lung cancer cases. However chemoresistance is often developed during the treatment, limiting clinical utility of this drug. Recently, the ability of tumor cells to adapt their metabolism has been associated to resistance to therapies. In this study, we first described the metabolic reprogramming of Non-Small Cell Lung Cancer (NSCLC) in response to cisplatin treatment. Methods: Cisplatin-resistant versions of the A549, H1299, and H460 cell lines were generated by continuous drug exposure. The long-term metabolic changes, as well as, the early response to cisplatin treatment were analyzed in both, parental and cisplatin-resistant cell lines. In addition, four Patient-derived xenograft models treated with cisplatin along with paired pre- and post-treatment biopsies from patients were studied. Furthermore, metabolic targeting of these changes in cell lines was performed downregulating PGC-1α expression through siRNA or using OXPHOS inhibitors (metformin and rotenone). Results: Two out of three cisplatin-resistant cell lines showed a stable increase in mitochondrial function, PGC1-α and mitochondrial mass with reduced glycolisis, that did not affect the cell cycle. This phenomenon was confirmed in vivo. Post-treatment NSCLC tumors showed an increase in mitochondrial mass, PGC-1α and a decrease in the GAPDH/MT-CO1 ratio. In addition, we demonstrated how a ROS-mediated metabolism reprogramming, involving PGC-1α and increased mitochondrial mass, is induced during short-time cisplatin exposure. Moreover, we tested how cells with increased PGC-1a induced by ZLN005 treatment, showed reduced cisplatin-driven apoptosis. Remarkably, the long-term metabolic changes, as well as the metabolic reprogramming during short-time cisplatin exposure can be exploited as an Achilles’ heel of NSCLC cells, as demonstrated by the increased sensitivity to PGC-1α interference or OXPHOS inhibition using metformin or rotenone. Conclusion: These results describe a new cisplatin resistance mechanism in NSCLC based on a metabolic reprogramming that is therapeutically exploitable through PGC-1α downregulation or OXPHOS inhibitors.Work in the authors’ laboratories is supported by ‘‘Instituto de Salud Carlos III’’ PI13/01806 and PIE14/0064 to M.P. A.C-B, received a Spanish Lung Cancer Group fellowship. R.L-B, is supported by Comunidad Autónoma de Madrid “Garantía juvenil” contrac

Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage

Acetaminophen overdose is one of the leading causes of acute liver failure and liver transplantation in the Western world. Magnesium is essential in several cellular processess. The Cyclin M family is involved in magnesium transport across cell membranes. Herein, we identify that among all magnesium transporters, only Cyclin M4 expression is upregulated in the liver of patients with acetaminophen overdose, with disturbances in magnesium serum levels. In the liver, acetaminophen interferes with the mitochondrial magnesium reservoir via Cyclin M4, affecting ATP production and reactive oxygen species generation, further boosting endoplasmic reticulum stress. Importantly, Cyclin M4 mutant T495I, which impairs magnesium flux, shows no effect. Finally, an accumulation of Cyclin M4 in endoplasmic reticulum is shown under hepatoxicity. Based on our studies in mice, silencing hepatic Cyclin M4 within the window of 6 to 24 h following acetaminophen overdose ingestion may represent a therapeutic target for acetaminophen overdose induced liver injury

A Contribution of the HAWC Observatory to the TeV era in the High Energy Gamma-Ray Astrophysics: The case of the TeV-Halos

We present a short overview of the TeV-Halos objects as a discovery and a relevant contribution of the High Altitude Water \v{C}erenkov (HAWC) observatory to TeV astrophysics. We discuss history, discovery, knowledge, and the next step through a new and more detailed analysis than the original study in 2017. TeV-Halos will contribute to resolving the problem of the local positron excess observed on the Earth. To clarify the latter, understanding the diffusion process is mandatory.Comment: Work presented in the 21st International Symposium on Very High Energy Cosmic Ray Interactions(ISVHECRI 2022) as part of the Ph. D. Thesis of Ramiro Torres-Escobedo (SJTU, Shanghai, China). Accepted for publication in SciPost Physics Proceedings (ISSN 2666-4003). 11 pages, 3 Figures. Short overview of HAWC and TeV Halos objects until 202

Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade 653 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design