801 research outputs found

    RNAseq reveals hydrophobins that are involved in the adaptation of aspergillus nidulans to lignocellulose

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    Background Sugarcane is one of the world’s most profitable crops. Waste steam-exploded sugarcane bagasse (SEB) is a cheap, abundant, and renewable lignocellulosic feedstock for the next-generation biofuels. In nature, fungi seldom exist as planktonic cells, similar to those found in the nutrient-rich environment created within an industrial fermenter. Instead, fungi predominantly form biofilms that allow them to thrive in hostile environments. Results In turn, we adopted an RNA-sequencing approach to interrogate how the model fungus, Aspergillus nidulans, adapts to SEB, revealing the induction of carbon starvation responses and the lignocellulolytic machinery, in addition to morphological adaptations. Genetic analyses showed the importance of hydrophobins for growth on SEB. The major hydrophobin, RodA, was retained within the fungal biofilm on SEB fibres. The StuA transcription factor that regulates fungal morphology was up-regulated during growth on SEB and controlled hydrophobin gene induction. The absence of the RodA or DewC hydrophobins reduced biofilm formation. The loss of a RodA or a functional StuA reduced the retention of the hydrolytic enzymes within the vicinity of the fungus. Hence, hydrophobins promote biofilm formation on SEB, and may enhance lignocellulose utilisation via promoting a compact substrate-enzyme-fungus structure. Conclusion This novel study highlights the importance of hydrophobins to the formation of biofilms and the efficient deconstruction of lignocellulose

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

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    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)

    O Programa de Cidades Históricas : por uma política integrada de preservação do patrimônio cultural urbano

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    O Programa de Cidades Históricas (PCH), implementado a partir de 1973, foi o primeiro programa federal que investiu recursos para a recuperação do patrimônio cultural urbano. Implementado pelo Ministério do Planejamento, buscava o desenvolvimento econômico das cidades históricas e dialogava com outros assuntos em pauta naquele momento, como o desenvolvimento urbano e regional e o turismo cultural. Tinha em sua concepção uma mudança na maneira de abordar as cidades históricas: a partir do entendimento da cidade como produtora de capital, o patrimônio cultural geraria desenvolvimento econômico pelo seu consumo para a atividade turística. De 1973 a 1979, foram investidos 17,3 milhões de dólares, realizando-se 143 obras em monumentos (85% dos investimentos); 8 cursos de qualificação de mão de obra nos três níveis (superior, intermediário e operário); 7 planos urbanísticos; 6 obras em espaços públicos (urbanos); e 10 ações de tipos diversos. Nossa análise busca entender essa política a partir do seu processo de formulação e implementação, no período de 1972 a 1979. Pretende, nesse sentido: a) avaliar as relações de poder em jogo durante a construção e a implementação do programa; b) compreender o grau de sucesso que o programa obteve na construção de um Sistema Nacional de Patrimônio Cultural, analisando sua articulação junto aos estados e outros órgãos federais; e c) avaliar o papel do programa enquanto indutor de novas práticas institucionais no campo da preservação do patrimônio cultural, especialmente com relação ao Iphan e aos estados federativos brasileiros.The Historic Cities Program (PCH: 1973-1979) was the first federal program that has invested resources to the recovery of the urban cultural heritage. Implemented by the Ministry of Planning, sought economic development of historic towns and dialogued with other items on the agenda at the time, such as urban and regional development and cultural tourism. It brought a change in the way of approach the historic towns: from the understanding of the city as a producer of capital, heritage would generate economic development through its consume by the tourism. From 1973 to 1979 it was invested 17.3 million dollars, performing 143 works on monuments (85% of investments); 8 hand-to-work training courses in three levels (top, middle and working class); 7 urban plans; 6 works in public spaces (urban); and 10 shares of various types. Our analysis seeks to understand this policy from its formulation and implementation in the period from 1972 to 1979. The aim, in this sense, is: a) to assess the power relations at play during construction and implementation of the Program; b) to understand the degree of success that the program achieved in building a national system, analyzing its relationship with states and other federal agencies; and c) to evaluate the role of Program while inducing new institutional practices in the field of preservation of cultural heritage, especially with regard to Iphan

    Pervasive gaps in Amazonian ecological research

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    Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

    Pervasive gaps in Amazonian ecological research

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