Epstein-Barr virus transcription factor Zta acts through distal regulatory elements to directly control cellular gene expression

Lytic replication of the human gamma herpes virus Epstein-Barr virus (EBV) is an essential prerequisite for the spread of the virus. Differential regulation of a limited number of cellular genes has been reported in B-cells during the viral lytic replication cycle. We asked whether a viral bZIP transcription factor, Zta (BZLF1, ZEBRA, EB1), drives some of these changes. Using genome-wide chromatin immunoprecipitation coupled to next-generation DNA sequencing (ChIP-seq) we established a map of Zta interactions across the human genome. Using sensitive transcriptome analyses we identified 2263 cellular genes whose expression is significantly changed during the EBV lytic replication cycle. Zta binds 278 of the regulated genes and the distribution of binding sites shows that Zta binds mostly to sites that are distal to transcription start sites. This differs from the prevailing view that Zta activates viral genes by binding exclusively at promoter elements. We show that a synthetic Zta binding element confers Zta regulation at a distance and that distal Zta binding sites from cellular genes can confer Zta-mediated regulation on a heterologous promoter. This leads us to propose that Zta directly reprograms the expression of cellular genes through distal elements

Investimento imobiliário na Bahia / Brasil condomínios residenciais : plano de negócio

A crise sentida na Europa e por outro lado a contrastante prosperidade dos países emergentes, faz com que os investimentos sejam canalizados para estes mercados, de forma a serem optimizados o retorno dos seus capitais. A proposta deste plano de negócio prende-se com a criação de uma empresa imobiliária, instalada em Salvador/Bahia, e cujo core-business será a análise e a implementação de empreendimentos imobiliários no Nordeste Brasileiro. Entre esses projectos dar-se-á especial relevo à criação de seis condomínios, denominados: Pablo Picasso, Joan Miró, Van Gogh, Michael Angelo, Leonardo da Vinci e Rembrandt inseridos no âmbito do plano Minha Casa, Minha Vida 2, criado pelo governo Brasileiro para possibilitar o acesso de casa própria a famílias de baixo rendimento. Cada um dos empreendimentos contará com 20 habitações de tipologia T2, cada habitação com 70m², uma área comum de lazer equipada com parque infantil, uma piscina e um espaço gourmet. O projecto envolve um investimento inicial em capital fixo de cerca de R$200 000, que será recuperado logo no primeiro ano de actividade do negócio.The crisis felt in Europe and the contrasting prosperity among emerging countries causes investments to be channeled to these markets, seeking for capital return optimization. The purpose of this business plan is the creation of a real estate company, located in Salvador, Bahia, and whose core business is the analysis and implementation of real estate in Northeast Brazil. Among these projects we will give special emphasis to the creation of the following six condominiums: Pablo Picasso, Joan Miró, Van Gogh, Michael Angelo, Leonardo da Vinci and Rembrandt, inserted under the plan Minha Casa, Minha Vida 2 created by the Brazilian government so that low income families can afford their own home. Each condominium will include 20 T2 houses, each room with 70m², a common recreational area equipped with a playground, a pool and a gourmet space. The project involves an initial investment in fixed assets of about R$ 200 000, which will be recovered in the first year of business activity

Mixed Th1 and Th2 Mycobacterium tuberculosis-specific CD4 T cell responses in patients with active pulmonary tuberculosis from Tanzania.

Mycobacterium tuberculosis (Mtb) and helminth infections elicit antagonistic immune effector functions and are co-endemic in several regions of the world. We therefore hypothesized that helminth infection may influence Mtb-specific T-cell immune responses. We evaluated the cytokine profile of Mtb-specific T cells in 72 individuals with pulmonary TB disease recruited from two Sub-Saharan regions with high and moderate helminth burden i.e. 55 from Tanzania (TZ) and 17 from South Africa (SA), respectively. We showed that Mtb-specific CD4 T-cell functional profile of TB patients from Tanzania are primarily composed of polyfunctional Th1 and Th2 cells, associated with increased expression of Gata-3 and reduced expression of T-bet in memory CD4 T cells. In contrast, the cytokine profile of Mtb-specific CD4 T cells of TB patients from SA was dominated by single IFN-γ and dual IFN-γ/TNF-α and associated with TB-induced systemic inflammation and elevated serum levels of type I IFNs. Of note, the proportion of patients with Mtb-specific CD8 T cells was significantly reduced in Mtb/helminth co-infected patients from TZ. It is likely that the underlying helminth infection and possibly genetic and other unknown environmental factors may have caused the induction of mixed Th1/Th2 Mtb-specific CD4 T cell responses in patients from TZ. Taken together, these results indicate that the generation of Mtb-specific CD4 and CD8 T cell responses may be substantially influenced by environmental factors in vivo. These observations may have major impact in the identification of immune biomarkers of disease status and correlates of protection

Resolution of inflammation: a new therapeutic frontier

Dysregulated inflammation is a central pathological process in diverse disease states. Traditionally, therapeutic approaches have sought to modulate the pro- or anti-inflammatory limbs of inflammation, with mixed success. However, insight into the pathways by which inflammation is resolved has highlighted novel opportunities to pharmacologically manipulate these processes — a strategy that might represent a complementary (and perhaps even superior) therapeutic approach. This Review discusses the state of the art in the biology of resolution of inflammation, highlighting the opportunities and challenges for translational research in this field

Epistemicídio, ensino de ciências e a obra “quarto de despejo: diário de uma favelada” de Carolina Maria de Jesus

We explore didactic potentialities for an anti-racist, anti-sexist and anti-capitalist teaching of Natural Science based on the book by Carolina Maria de Jesus intitled “Quarto de Despejo: diário de uma favelada”. This is an essay that seeks to raise the possibility of developing Natural Science Teaching projects. The absence of authors and especially black woman authors mentioned in the field of Science Teaching is symptomatic of a racist, murderous and suicidal society. This pointed out absence seems to be not enough to produce the genocide of racialized peoples, especially black peoples and peoples originating from the Americas. For the colonialist interests of the imperialist countries, when it is not possible to westernize, it is necessary to systematically produce the murder of the knowledge of these peoples. Annihilating the bodies and spirits of racialized peoples is a necropower strategy of those who are sovereign in capitalist society. What we observe is that racism and sexism are not social pathologies or individual behavioral deviations. They are structuring and structured ideologies, based on modernity, in the western context, in the capitalist mode of production. Thus, the reproduction of capitalism necessarily requires the reproduction of racism and sexism. There is no way to radically overcome racism or sexism without radically overcoming capitalism.Este estudio apunta potencialidades didácticas para una Enseñanza de las Ciencias Naturales antirracista, antisexista y anticapitalista, a partir de la narrativa y de Carolina María de Jesús en “Quarto de Despejo: diario de una favelada”. Este es un ensayo que busca plantear la posibilidad de desarrollar proyectos de Enseñanza de las Ciencias Naturales. La ausencia de autores y especialmente de autores negros mencionados en el campo de la Enseñanza de las Ciencias es sintomática de una sociedad racista, asesina y suicida. Aparentemente no fue suficiente para producir y seguir produciendo el genocidio de los pueblos racializados, en especial de los pueblos negros y originarios de las Américas. Por los intereses colonialistas de los países imperialistas, cuando no es posible occidentalizarse, es necesario producir sistemáticamente el asesinato del saber de estos pueblos. Aniquilar los cuerpos y espíritus de los pueblos racializados es una estrategia de necropoder de quienes son soberanos en la sociedad capitalista. Lo que observamos es que el racismo y el sexismo no son patologías sociales ni desviaciones conductuales individuales. Son ideologías estructurantes y estructuradas, basadas en la modernidad, en el contexto occidental, en el modo de producción capitalista. Así, la reproducción del capitalismo necesariamente requiere la reproducción del racismo y el sexismo. No hay manera de superar radicalmente el racismo o el sexismo sin superar radicalmente el capitalismo.Este estudo aponta potencialidades didáticas para um Ensino de Ciências da Natureza antirracista, antissexista e anticapitalista, a partir da narrativa e Carolina Maria de Jesus em “Quarto de Despejo: diário de uma favelada”. Trata-se de um ensaio que busca suscitar a possibilidade do desenvolvimento de projetos de Ensino de Ciências Naturais. A ausência de autores e principalmente de autoras negras evocadas no campo do Ensino de Ciências é sintomático de uma sociedade racista, assassina e suicidária. Ao que parece não foi o bastante produzir e continuar produzindo o genocídio dos povos racializados, sobretudo os povos negros e os povos originários das Américas. Aos interesses colonialistas dos países imperialistas, quando não é possível ocidentalizar, é necessário produzir, sistematicamente, o assassinato dos saberes desses povos. Aniquilar os corpos e o espírito dos povos racializados é uma estratégia do necropoder daqueles que são soberanos na sociedade capitalista. O que observamos é que o racismo e o sexismo não são patologias sociais ou desvios de comportamento individuais. São ideologias estruturantes e estruturadas, a partir da modernidade, no contexto ocidental, no modo de produção capitalista. Deste modo, a reprodução do capitalismo necessita da reprodução do racismo e do sexismo. Não há como superar radicalmente o racismo ou o sexismo sem que se supere radicalmente o capitalismo.

Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols

(Poly)phenols are a large group of compounds, found in food, beverages, dietary supplements and herbal medicines. Owing to their biological activities, absorption and metabolism of the most abundant compounds in humans are well understood. Both the chemical structure of the phenolic moiety and any attached chemical groups define whether the polyphenol is absorbed in the small intestine, or reaches the colon and is subject to extensive catabolism by colonic microbiota. Untransformed substrates may be absorbed, appearing in plasma primarily as methylated, sulfated and glucuronidated derivatives, with in some cases the unchanged substrate. Many of the catabolites are well absorbed from the colon and appear in the plasma either similarly conjugated, or as glycine conjugates, or in some cases unchanged. Although many (poly)phenol catabolites have been identified in human plasma and / or urine, the pathways from substrate to final catabolite, and the species of bacteria and enzymes involved, are still scarcely reported. While it is clear that the composition of the human gut microbiota can be modulated in vivo by supplementation with some (poly)phenol-rich commodities, such modulation is definitely not an inevitable consequence of supplementation, it depends on the treatment, length of time and on the individual metabotype, and it is not clear whether the modulation is sustained when supplementation ceases. Some catabolites have been recorded in plasma of volunteers at concentrations similar to those shown to be effective in in vitro studies suggesting that some benefit may be achieved in vivo by diets yielding such catabolites

Avaliação do estado nutricional de pacientes com pênfigo foliáceo sob corticoterapia prolongada

Our objective was to compare food intake and nutritional status of Pemphigus Foliaceus patients (PG) on long term glucocorticoid therapy to a Control Group (CG). Fourteen PG female inpatients receiving prednisone (0.33 ± 0.22mg/kg) for at least 12 months and twelve CG subjects were submitted to nutritional evaluation, including anthropometry, urinary creatinine determination and serum biochemical measurements, besides 48-h-based food intake records. Groups were compared by Chi-square, Mann-Whitney and "t" tests. PG patients and CG were paired, respectively, in relation to age (24.7 ± 14.1 vs. 22.0 ± 12.0 years), body mass index (25.8 ± 6.4 vs. 24.0 ± 5.6kg/m2), daily protein intake (132.9 ± 49.8 vs. 95.2 ± 58.9g), and serum albumin (median; range) (3.8; 3.5-4.1 vs. 3.8; 3.6-5.0g/dl). However, PG patients had lower height-creatinine index (64.8 ± 17.6 vs. 90.1 ± 33.4%), and higher daily energy (3080 ± 1099 vs. 2187 ± 702kcal) and carbohydrate (376.8 ± 135.8 vs. 242.0 ± 80.7g) intakes. Despite high food, protein and energy consumption, PG patients on long term glucocorticoid therapy had lower body muscle mass than controls, while showing high body fat stores. These findings are possibly related to combined metabolic effects of long term corticotherapy and inflammatory disease plus corticosteroid-induced increased appetite.O objetivo deste trabalho foi comparar o estado nutricional e dados de ingestão alimentar de pacientes com Pênfigo Foliáceo (PF, n=14) sob corticoterapia prolongada (prednisona, 0,33 ± 0,22mg/kg/dia há mais de 12 meses) com um Grupo Controle (GC, n=12). A avaliação constou de inquérito alimentar de 48 horas, antropometria e determinação de creatinina urinária de 24h e albumina sérica. Os grupos PF e GC foram pareados, respectivamente, quanto à idade (24,7 ± 14,1 vs 22,0 ± 12,0 anos), índice de massa corporal (25,8 ± 6,4 vs 24,0 ± 5,6kg/m2), ingestão diária de proteína (132,9 ± 49,8 vs 95,2 ± 58,9g) e albumina sérica (mediana;faixa de variação) (3,8;3,5-4,1 vs 3,8;3,6-5,0g/dl). Pacientes com pênfigo apresentaram menor índice creatinina-altura (64,8 ± 17,6 vs 90,1 ± 33,4%) e maior ingestão de energia (3080 ± 1099 vs 2187 ± 702kcal/dia) e carboidratos (376,8 ± 135,8 vs 242,0 ± 80,7g/dia). Apesar do maior consumo de alimentos, os pacientes com pênfigo apresentaram menor massa muscular que os controles, achados possivelmente relacionados ao aumento do apetite e efeitos metabólicos combinados da corticoterapia e da doença inflamatória crônica

Naupliar and Metanaupliar development of Thysanoessa raschii (Malacostraca, Euphausiacea) from Godthåbsfjord, Greenland, with a reinstatement of the ancestral status of the free-living Nauplius in Malacostracan evolution

The presence of a characteristic crustacean larval type, the nauplius, in many crustacean taxa has often been considered one of the few uniting characters of the Crustacea. Within Malacostraca, the largest crustacean group, nauplii are only present in two taxa, Euphauciacea (krill) and Decapoda Dendrobranchiata. The presence of nauplii in these two taxa has traditionally been considered a retained primitive characteristic, but free-living nauplii have also been suggested to have reappeared a couple of times from direct developing ancestors during malacostracan evolution. Based on a re-study of Thysanoessa raschii (Euphausiacea) using preserved material collected in Greenland, we readdress this important controversy in crustacean evolution, and, in the process, redescribe the naupliar and metanaupliar development of T. raschii. In contrast to most previous studies of euphausiid development, we recognize three (not two) naupliar (= ortho-naupliar) stages (N1-N3) followed by a metanauplius (MN). While there are many morphological changes between nauplius 1 and 2 (e.g., appearance of long caudal setae), the changes between nauplius 2 and 3 are few but distinct. They involve the size of some caudal spines (largest in N3) and the setation of the antennal endopod (an extra seta in N3). A wider comparison between free-living nauplii of both Malacostraca and non-Malacostraca revealed similarities between nauplii in many taxa both at the general level (e.g., the gradual development and number of appendages) and at the more detailed level (e.g., unclear segmentation of naupliar appendages, caudal setation, presence of frontal filaments). We recognize these similarities as homologies and therefore suggest that free-living nauplii were part of the ancestral malacostracan type of development. The derived morphology (e.g., lack of feeding structures, no fully formed gut, high content of yolk) of both euphausiid and dendrobranchiate nauplii is evidently related to their non-feeding (lecithotrophic) status

Unity in defence: honeybee workers exhibit conserved molecular responses to diverse pathogens

This is the final version of the article. Available from the publisher via the DOI in this record.Background: Organisms typically face infection by diverse pathogens, and hosts are thought to have developed specific responses to each type of pathogen they encounter. The advent of transcriptomics now makes it possible to test this hypothesis and compare host gene expression responses to multiple pathogens at a genome-wide scale. Here, we performed a meta-analysis of multiple published and new transcriptomes using a newly developed bioinformatics approach that filters genes based on their expression profile across datasets. Thereby, we identified common and unique molecular responses of a model host species, the honey bee (Apis mellifera), to its major pathogens and parasites: the Microsporidia Nosema apis and Nosema ceranae, RNA viruses, and the ectoparasitic mite Varroa destructor, which transmits viruses. Results: We identified a common suite of genes and conserved molecular pathways that respond to all investigated pathogens, a result that suggests a commonality in response mechanisms to diverse pathogens. We found that genes differentially expressed after infection exhibit a higher evolutionary rate than non-differentially expressed genes. Using our new bioinformatics approach, we unveiled additional pathogen-specific responses of honey bees; we found that apoptosis appeared to be an important response following microsporidian infection, while genes from the immune signalling pathways, Toll and Imd, were differentially expressed after Varroa/virus infection. Finally, we applied our bioinformatics approach and generated a gene co-expression network to identify highly connected (hub) genes that may represent important mediators and regulators of anti-pathogen responses. Conclusions: Our meta-analysis generated a comprehensive overview of the host metabolic and other biological processes that mediate interactions between insects and their pathogens. We identified key host genes and pathways that respond to phylogenetically diverse pathogens, representing an important source for future functional studies as well as offering new routes to identify or generate pathogen resilient honey bee stocks. The statistical and bioinformatics approaches that were developed for this study are broadly applicable to synthesize information across transcriptomic datasets. These approaches will likely have utility in addressing a variety of biological questions.This article is a joint effort of the working group TRANSBEE and an outcome of two workshops kindly supported by sDiv, the Synthesis Centre for Biodiversity Sciences within the German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, funded by the German Science Foundation (FZT 118). New datasets were performed thanks to the Insect Pollinators Initiative (IPI grant BB/I000100/1 and BB/I000151/1), with participation of the UK-USA exchange funded by the BBSRC BB/I025220/1 (datasets #4, 11 and 14). The IPI is funded jointly by the Biotechnology and Biological Sciences Research Council, the Department for Environment, Food and Rural Affairs, the Natural Environment Research Council, the Scottish Government and the Wellcome Trust, under the Living with Environmental Change Partnershi

NATUREZA EM CENA: A IMPORTÂNCIA DO CINEMA PARA AS AULAS DE EDUCAÇÃO AMBIENTAL

O trabalho em questão visa introduzir o cinema enquanto ferramenta didática à educação ambiental, cientes de que é possível refletir sobre as dinâmicas da relação sociedade e natureza com o incremento de novas propostas metodológicas. Para tanto, foram realizadas revisões bibliográficas acerca de conceitos como natureza e capitalismo e também sobre o cinema como protagonista no processo de ensino/aprendizagem atrelados à educação ambiental. Desta feita, utilizar-se-á do método dialético como forma de compreensão da realidade contraditória que emerge na relação sociedade e natureza, provocando diversos desequilíbrios a esta última e por fim, com a obtenção dos resultados, foram discutidas duas obras cinematográficas através de um estudo de caso. Ambos os filmes evidenciam o capitalismo como um sistema voltado para o domínio do capital sobre o meio ambiente, sendo inseridos como proposta didática