Comprehensive molecular landscape of cetuximab resistance in head and neck cancer cell lines

Cetuximab is the sole anti-EGFR monoclonal antibody that is FDA approved to treat head and neck squamous cell carcinoma (HNSCC). However, no predictive biomarkers of cetuximab response are known for HNSCC. Herein, we address the molecular mechanisms underlying cetuximab resistance in an in vitro model. We established a cetuximab resistant model (FaDu), using increased cetuximab concentrations for more than eight months. The resistance and parental cells were evaluated for cell viability and functional assays. Protein expression was analyzed by Western blot and human cell surface panel by lyoplate. The mutational profile and copy number alterations (CNA) were analyzed using whole-exome sequencing (WES) and the NanoString platform. FaDu resistant clones exhibited at least two-fold higher IC50 compared to the parental cell line. WES showed relevant mutations in several cancer-related genes, and the comparative mRNA expression analysis showed 36 differentially expressed genes associated with EGFR tyrosine kinase inhibitors resistance, RAS, MAPK, and mTOR signaling. Importantly, we observed that overexpression of KRAS, RhoA, and CD44 was associated with cetuximab resistance. Protein analysis revealed EGFR phosphorylation inhibition and mTOR increase in resistant cells. Moreover, the resistant cell line demonstrated an aggressive phenotype with a significant increase in adhesion, the number of colonies, and migration rates. Overall, we identified several molecular alterations in the cetuximab resistant cell line that may constitute novel biomarkers of cetuximab response such as mTOR and RhoA overexpression. These findings indicate new strategies to overcome anti-EGFR resistance in HNSCC.This work was supported by Barretos Cancer Hospital and the Public Ministry of Labor Campinas (Research, Prevention, and Education of Occupational Cancer) in Campinas, Brazil, CAPESDFATD (88887.137283/2017-00). INFG is the recipient of a FAPESP Ph.D. fellowship (2017/22305-9)

A MEDIAÇÃO EM MUSEUS: desafios observados em duas modalidades de visitas ao MZFS

O Museu de Zoologia da Universidade Estadual de Feira de Santana/MZFS realiza diversas atividades públicas como visitas guiadas a exposição Linha do Tempo e o Museu Itinerante. De abril de 2018 a junho de 2019, realizamos 273 atendimentos no espaço do MZFSe em saídas extracampos

ALTERNATIVAS LÚDICAS PARA A RECEPÇÃO DO PÚBLICO INFANTIL NO MZFS

A DEADD tem como meta auxiliar no processo de alfabetização científica a partir do seu acervo didático zoológico. Tal processo é feito através das visitas guiadas à exposição Linha do Tempo

Phenology and Seasonal Ecosystem Productivity in an Amazonian Floodplain Forest

everal studies have explored the linkages between phenology and ecosystem productivity across the Amazon basin. However, few studies have focused on flooded forests, which correspond to c.a. 14% of the basin. In this study, we assessed the seasonality of ecosystem productivity (gross primary productivity, GPP) from eddy covariance measurements, environmental drivers and phenological patterns obtained from the field (leaf litter mass) and satellite measurements (enhanced vegetation index (EVI) from the Moderate Resolution Imaging Spectroradiometer/multi-angle implementation correction (MODIS/MAIAC)) in an Amazonian floodplain forest. We found that ecosystem productivity is limited by soil moisture in two different ways. During the flooded period, the excess of water limits GPP (Spearman’s correlation; rho = −0.22), while during non-flooded months, GPP is positively associated with soil moisture (rho = 0.34). However, GPP is maximized when cumulative water deficit (CWD) increases (rho = 0.81), indicating that GPP is dependent on the amount of water available. EVI was positively associated with leaf litter mass (Pearson’s correlation; r = 0.55) and with GPP (r = 0.50), suggesting a coupling between new leaf production and the phenology of photosynthetic capacity, decreasing both at the peak of the flooded period and at the end of the dry season. EVI was able to describe the inter-annual variations on forest responses to environmental drivers, which have changed during an observed El Niño-Southern Oscillation (ENSO) year (2015/2016)

Implications of climate change impacts for the Brazilian electricity mix

Hydropower generation is responsible for supplying most of the electricity in Brazil. Like other renewable sources, water is highly sensitive to meteorological variables, so that climate change may have a considerable impact on it. Therefore, this study aims at assessing climate change impacts on hydropower generation and their consequences for the Brazilian electricity system. Scenario data for specific average global warming levels of 2°C and 4°C from Eta_HadGEM2-ES and Eta_MIROC5 downscaled climate models are used. Outcomes indicate that the electricity system’s adaptive capacity to lower hydropower generation includes a growing share of other renewable and natural gas fired thermoelectric generation, increasing the system’s marginal cost to meet projected demand in 2030. Greenhouse gas emissions are projected to increase in a 2°C scenario, but to decrease in scenarios in which warming reaches 4°C.Hydropower generation is responsible for supplying most of the electricity in Brazil. Like other renewable sources, water is highly sensitive to meteorological variables, so that climate change may have a considerable impact on it. Therefore, this study aims at assessing climate change impacts on hydropower generation and their consequences for the Brazilian electricity system. Scenario data for specific average global warming levels of 2°C and 4°C from Eta_HadGEM2-ES and Eta_MIROC5 downscaled climate models are used. Outcomes indicate that the electricity system’s adaptive capacity to lower hydropower generation includes a growing share of other renewable and natural gas fired thermoelectric generation, increasing the system’s marginal cost to meet projected demand in 2030. Greenhouse gas emissions are projected to increase in a 2°C scenario, but to decrease in scenarios in which warming reaches 4°C

Well-being at work, productivity, and coping with stress during the COVID-19 pandemic

This study aims to analyze the mechanisms through which the coronavirus disease (COVID-19) pandemic impacts on well-being at work and on productivity. The secondary objective is to identify stress management strategies for the work environment during the pandemic. This is an integrative review. Phase 1 consisted of searches of open access electronic databases (MEDLINE, SciELO, Bireme, and LILACS) for papers published in 2020 addressing mental health, work, and pandemics. Phase 2 consisted of selecting literature recommended by specialists in occupational psychiatry and positive psychology. These materials were read and critically analyzed. Forty references were included in the literature review. The articles reviewed were classified into the following categories: articles concerning work relationships in Brazil; articles describing the impact of pandemics on mental health and work; articles focusing on the work of health professionals during pandemics; articles about well-being at work; and papers proposing strategies to improve well-being and productivity and to promote mental health. The COVID-19 pandemic can have a significant impact on workers’ mental health and productivity. Most professionals face a need to adapt to changes, which can decrease their feeling of well-being. Consequently, strategies to promote well-being and mental health in the work environment should be a priority. Work routines were modified after the COVID-19 pandemic set in and assessing these changes is essential to maintain workers’ mental health. By so doing, it is possible to promote general well-being and post-traumatic recovery and reduce stress levels

Coprodução de hormônio do crescimento e prolactina em paciente com sela túrcica parcialmente vazia primária: relato de caso

Introduction: The empty sella syndrome is a neuroradiological diagnosis that shows pituitary gland reduction or flattening, with a prevalence of around 8% to 35% in general population. Objective: We report a case in which there is an association between partial primary empty sella syndrome and high levels of growth hormone and prolactin. Methods: A 67-year-old man, from Coronel Mota Hospital, Boa Vista / RR, with no specific complaints, was referred to the Endocrinology ambulatory to investigate a modification in sella area. After anamnesis and physical examination, acromegaly research began. Pituitary hormones and magnetic resonance imaging of the sella turcica with contrast were requested. Results: General physical examination revealed acromegalic face, nasal enlargement, macroglossia and frontal cutis verticis gyrata. Radiological examination showed partial empty sella. Laboratory evaluation confirmed the clinical suspicion of acromegaly and revealed hyperprolactinemia presence. It was decided to treat the patient with cabergoline 1.5 mg / week and to refer him to a center specialized in neuroendocrinology. Conclusion: This report shows a case of partial primary empty sella and co-production of growth hormone and prolactin, making this association interesting, since somatotropinomas are mostly (80%) macroadenomas. In addition, the underdiagnosis of acromegaly is highlighted, since the symptoms are nonspecific and insidious, leading to high morbidity and mortality and reduction of the affected patients life expectancy.Introdução: A síndrome da sela túrcica vazia é um diagnóstico neurorradiológico que evidencia a redução ou o achatamento da glândula pituitária, com prevalência em torno de 8 a 35% na população geral. Objetivo: Este estudo de caso relata a associação entre sela túrcica parcialmente vazia primária e elevados níveis de hormônio do crescimento e prolactina. Métodos: Homem de 67 anos, proveniente do hospital Coronel Mota, Boa Vista/RR, sem queixas específicas, encaminhado ao ambulatório de Endocrinologia para investigação de alteração em região selar. Após realização de anamnese e exame físico, iniciou-se investigação de acromegalia. Foram solicitados basais hipofisários e ressonância magnética de sela túrcica com contraste. Resultados: O exame físico geral evidenciou fácies acromegálica, alargamento nasal, macroglossia e cutis verticis gyrata frontal. O exame radiológico demonstrou sela túrcica parcialmente vazia. A avaliação laboratorial confirmou a suspeita clínica de acromegalia e revelou a presença de hiperprolactinemia. Optou-se por tratar o paciente com cabergolina 1.5mg/semana e encaminhá-lo para centro especializado em neuroendocrinologia. Conclusão: Este relato mostra um caso de sela parcialmente vazia primária e coprodução de hormônio do crescimento e prolactina, tornando esta associação interessante, uma vez que somatotropinomas são em sua maioria (80%) macroadenomas. Além disso, ressalta-se para o subdiagnóstico da acromegalia, uma vez que os sintomas são inespecíficos e insidiosos, acarretando elevada morbimortalidade e redução da expectativa de vida dos pacientes acometidos