90 research outputs found

    Aplicação Da Ferramenta GUT Na Cadeia Produtiva Da Ovinocultura De Corte Da RIDE-DF / GUT Tool Application In The Productive Chain Of Sheep Meat Industry OF RIDE-DF

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    The objective of this article is to present the prioritization of objectives to solve the problems of sheep raising for meat in the RIDE-DF, by means of the SWOT analysis applied by RIBEIRO in 2006. The quadrant “Vulnerability”, consisting of the variables “Weaknesses” and “Threats” was utilized and the GUT Matrix was applied thereon, in 2013. The result revealed that the lack of confidence in and commitment to the business demonstrates that the sector needs to pursue a much more efficient collective action relationship than that which exists today, and, concomitantly, technical assistance must be guaranteed by the Government.   RESUMO O objetivo deste artigo é apresentar uma ferramenta de priorização de objetivos para sanar os principais problemas da ovinocultura de corte na Região Integrada de Desenvolvimento Econômico do Distrito Federal (RIDE-DF)1. A partir da análise das fortalezas, fraquezas, oportunidades e ameaças identificadas anteriormente em matriz SWOT, o quadrante “Vulnerabilidade”, formado pelas variáveis “Fraquezas” e “Ameaças” foi aplicado à Matriz GUT para sinalização de gravidades, urgências e tendências na cadeia em questão. O resultado revelou que a falta de confiança e comprometimento com a atividade mostram que o setor precisa perseguir uma ação coletiva muito mais eficiente da que existe atualmente, ao mesmo tempo em que deve manter a assistência técnica garantida pelo Governo.  O objetivo deste artigo é apresentar uma ferramenta de priorização de objetivos para sanar os principais problemas da ovinocultura de corte na Região Integrada de Desenvolvimento Econômico do Distrito Federal (RIDE-DF)1. A partir da análise das fortalezas, fraquezas, oportunidades e ameaças identificadas anteriormente em matriz SWOT, o quadrante “Vulnerabilidade”, formado pelas variáveis “Fraquezas” e “Ameaças” foi aplicado à Matriz GUT para sinalização de gravidades, urgências e tendências na cadeia em questão. O resultado revelou que a falta de confiança e comprometimento com a atividade mostram que o setor precisa perseguir uma ação coletiva muito mais eficiente da que existe atualmente, ao mesmo tempo em que deve manter a assistência técnica garantida pelo Governo.   ABSTRACT The objective of this article is to present the prioritization of objectives to solve the problems of sheep raising for meat in the RIDE-DF, by means of the SWOT analysis applied by RIBEIRO in 2006. The quadrant “Vulnerability”, consisting of the variables “Weaknesses” and “Threats” was utilized and the GUT Matrix was applied thereon, in 2013. The result revealed that the lack of confidence in and commitment to the business demonstrates that the sector needs to pursue a much more efficient collective action relationship than that which exists today, and, concomitantly, technical assistance must be guaranteed by the Government

    Ovinocultura de corte na Ride-DF : cenários e perspectivas

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    Dissertação (mestrado)—Universidade de Brasília, Faculdade de Agronomia e Medicina Veterinária, Programa de Pós-Graduação em Agronegócios, 2013.O objetivo desta pesquisa é apresentar o atual cenário e seus respectivos problemas da ovinocultura de corte na RIDE-DF, diante das iniciativas tomadas para a organização da cadeia produtiva, e à luz das teorias: Microeconômica e Aspectos Contábeis da Demonstração do Resultado do Exercício - DRE; Análise Estratégica; Nova Economia Institucional/Economia dos Custos de Transação – NEI/ECT; e Teoria da Ação Coletiva - TAC, proporcionando uma perspectiva sobre o tema. O estudo foi desenvolvido em duas etapas: 1) Revisão de literatura sobre a cadeia produtiva da carne ovina no Brasil; principais contribuições da Microeconomia e DRE; contribuições acerca da NEI/ECT e também originárias da TAC; 2) Estudo de caso com pesquisa de campo – entrevistas gravadas em vídeo, conduzidas por roteiros semi-estruturados, com pessoas que integram a cadeia ovina de corte na RIDE-DF, como: governo, empresários e investidores. Os dados obtidos mostraram que, apesar de inúmeras contribuições acadêmicas e profissionais dadas ao setor, pouco se evoluiu nos últimos anos. Prova disso é que, sob à óptica da Teoria Microeconômica, existe um mercado ávido pelo fornecimento de carne ovina, porém, com produção insuficiente para atender à demanda. Por mais que se resolva o problema da regularidade de fornecimento, não há se como pensar em sucesso no setor sem que se corrijam os problemas relacionados à NEI/ECT, sobretudo, comportamento oportunista e assimetria de informações. A TAC mostrou falta de entrosamento entre os membros dos grupos que reúnem produtores, sem integração ao processo e com pensamentos distintos. Apesar de todo esse cenário obscuro, as perspectivas da ovinocultura de corte na RIDE-DF são otimistas: alguns entrevistados acreditam que a carne ovina pode ser a próxima proteína animal a ser explorada e também evidenciam que fatores genéticos podem acelerar a relação entre investimento e retorno no setor. _______________________________________________________________________________________ ABSTRACTThis study seeks to present the current state and concurrent problems of the raising of sheep for meat in the RIDE-DF, concerning the initiatives undertaken regarding the organization of the production chain, and in light of the following theories: Microeconomic and Financial Aspects of the Demonstration of Exercise Results - DER; New Institutional Economics /Transaction Costs Economics - NIE / TCE, and Collective Action Theory - CAT, providing a perspective on the subject. The research was conducted in two stages: 1) Review of literature on the production chain of mutton, hogget, and lamb in Brazil, the main contributions of Microeconomics and DER; Estrategic management; contributions regarding the NIE / TCE and also originating from the CAT, 2) case study with field research - videotaped interviews, along semi-structured itineraries, with people who take part in the sheep farming production chain in the RIDE-DF, such as government agents, businessmen and investors. The data obtained thereby showed that despite numerous academic and professional contributions to the sector, not much progress has been made in recent years. Proof of this, from the point of view of Microeconomic Theory, is that there is a keen market for mutton, but production is insufficient to meet demand. Notwithstanding the resolution of the problem of providing regular supply, success in the industry is not feasible without correcting the problems concerning the NIE / TCE, particularly opportunistic behavior and information asymmetry. The CAT showed a lack of cohesion among the members of the groups where producers meet, along with a lack of integration in the process and different schools of thought. Despite this bleak outlook, the prospects for sheep raising in the RIDE-DF are optimistic: some of those interviewed believe that mutton, hogget, and lamb may be the next animal proteins to be commercially exploited and also show that genetic factors can accelerate the relationship between investment and return in the sector

    A high-resolution mass spectrometry based proteomic dataset of human regulatory T cells

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    Regulatory T cells (Tregs) play a core role in maintaining immune tolerance, homeostasis, and host health. High-resolution analysis of the Treg proteome is required to identify enriched biological processes and pathways distinct to this important immune cell lineage. We present a comprehensive proteomic dataset of Tregs paired with conventional CD4+ (Conv CD4+) T cells in healthy individuals. Tregs and Conv CD4+ T cells were sorted to high purity using dual magnetic bead-based and flow cytometry-based methodologies. Proteins were trypsin-digested and analysed using label-free data-dependent acquisition mass spectrometry (DDA-MS) followed by label free quantitation (LFQ) proteomics analysis using MaxQuant software. Approximately 4,000 T cell proteins were identified with a 1% false discovery rate, of which approximately 2,800 proteins were consistently identified and quantified in all the samples. Finally, flow cytometry with a monoclonal antibody was used to validate the elevated abundance of the protein phosphatase CD148 in Tregs. This proteomic dataset serves as a reference point for future mechanistic and clinical T cell immunology and identifies receptors, processes, and pathways distinct to Tregs. Collectively, these data will lead to a better understanding of Treg immunophysiology and potentially reveal novel leads for therapeutics seeking Treg regulation

    TNF-α Is Involved in the Abnormal Thymocyte Migration during Experimental Trypanosoma cruzi Infection and Favors the Export of Immature Cells

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    Previous studies revealed a significant production of inflammatory cytokines together with severe thymic atrophy and thymocyte migratory disturbances during experimental Chagas disease. Migratory activity of thymocytes and mature T cells seem to be finely tuned by cytokines, chemokines and extracellular matrix (ECM) components. Systemic TNF-α is enhanced during infection and appears to be crucial in the response against the parasite. However, it also seems to be involved in disease pathology, since it is implicated in the arrival of T cells to effector sites, including the myocardium. Herein, we analyzed the role of TNF-α in the migratory activity of thymocytes in Trypanosoma cruzi (T. cruzi) acutely-infected mice. We found increased expression and deposition of TNF-α in the thymus of infected animals compared to controls, accompanied by increased co-localization of fibronectin, a cell migration-related ECM molecule, whose contents in the thymus of infected mice is also augmented. In-vivo studies showed an enhanced export of thymocytes in T. cruzi-infected mice, as ascertained by intrathymic injection of FITC alone or in combination with TNF-α. The increase of immature CD4+CD8+ T cells in secondary lymphoid organs was even more clear-cut when TNF-α was co-injected with FITC. Ex-vivo transmigration assays also revealed higher number of migrating cells when TNF-α was added onto fibronectin lattices, with higher input of all thymocyte subsets, including immature CD4+CD8+. Infected animals also exhibit enhanced levels of expression of both mRNA TNF-α receptors in the CD4+CD8+ subpopulation. Our findings suggest that in T. cruzi acute infection, when TNF-α is complexed with fibronectin, it favours the altered migration of thymocytes, promoting the release of mature and immature T cells to different compartments of the immune system. Conceptually, this work reinforces the notion that thymocyte migration is a multivectorial biological event in health and disease, and that TNF-α is a further player in the process

    A primary human T-cell spectral library to facilitate large scale quantitative T-cell proteomics.

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    Data independent analysis (DIA) exemplified by sequential window acquisition of all theoretical mass spectra (SWATH-MS) provides robust quantitative proteomics data, but the lack of a public primary human T-cell spectral library is a current resource gap. Here, we report the generation of a high-quality spectral library containing data for 4,833 distinct proteins from human T-cells across genetically unrelated donors, covering ~24% proteins of the UniProt/SwissProt reviewed human proteome. SWATH-MS analysis of 18 primary T-cell samples using the new human T-cell spectral library reliably identified and quantified 2,850 proteins at 1% false discovery rate (FDR). In comparison, the larger Pan-human spectral library identified and quantified 2,794 T-cell proteins in the same dataset. As the libraries identified an overlapping set of proteins, combining the two libraries resulted in quantification of 4,078 human T-cell proteins. Collectively, this large data archive will be a useful public resource for human T-cell proteomic studies. The human T-cell library is available at SWATHAtlas and the data are available via ProteomeXchange (PXD019446 and PXD019542) and PeptideAtlas (PASS01587)

    Ageing compromises mouse thymus function and remodels epithelial cell differentiation.

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    Ageing is characterised by cellular senescence, leading to imbalanced tissue maintenance, cell death and compromised organ function. This is first observed in the thymus, the primary lymphoid organ that generates and selects T cells. However, the molecular and cellular mechanisms underpinning these ageing processes remain unclear. Here, we show that mouse ageing leads to less efficient T cell selection, decreased self-antigen representation and increased T cell receptor repertoire diversity. Using a combination of single-cell RNA-seq and lineage-tracing, we find that progenitor cells are the principal targets of ageing, whereas the function of individual mature thymic epithelial cells is compromised only modestly. Specifically, an early-life precursor cell population, retained in the mouse cortex postnatally, is virtually extinguished at puberty. Concomitantly, a medullary precursor cell quiesces, thereby impairing maintenance of the medullary epithelium. Thus, ageing disrupts thymic progenitor differentiation and impairs the core immunological functions of the thymus

    The immune checkpoint CD96 defines a distinct lymphocyte phenotype and is highly expressed on tumor-infiltrating T cells

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    CD96 has recently been shown to be a potent immune checkpoint molecule in mice, but a similar role in humans is not known. In this study, we provide a detailed map of CD96 expression across human lymphocyte lineages, the kinetics of CD96 regulation on T-cell activation and co-expression with other conventional and emerging immune checkpoint molecules. We show that CD96 is predominantly expressed by T cells and has a unique lymphocyte expression profile. CD96 high T cells exhibited distinct effector functions on activation. Of note, CD96 expression was highly correlated with T-cell markers in primary and metastatic human tumors and was elevated on antigen- experienced T cells and tumor-infiltrating lymphocytes. Collectively, these data demonstrate that CD96 may be a promising immune checkpoint to enhance T-cell function against human cancer and infectious diseas

    Immune-neuroendocrine and metabolic disorders in human and experimental T. cruzi infection: New clues for understanding Chagas disease pathology

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    Studies in mice undergoing acute Trypanosoma cruzi infection and patients with Chagas disease, led to identify several immune-neuroendocrine disturbances and metabolic disorders. Here, we review relevant findings concerning such abnormalities and discuss their possible influence on disease physiopathology.Fil: González, Florencia Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Villar, Silvina Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Pacini, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Bottasso, Oscar Adelmo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Perez, Ana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentin

    C5b-9 membrane attack complex formation and extracellular vesicle shedding in Barrett's esophagus and esophageal adenocarcinoma

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    The early complement components have emerged as mediators of pro-oncogenic inflammation, classically inferred to cause terminal complement activation, but there are limited data on the activity of terminal complement in cancer. We previously reported elevated serum and tissue C9, the terminal complement component, in esophageal adenocarcinoma (EAC) compared to the precursor condition Barrett’s Esophagus (BE) and healthy controls. Here, we investigate the level and cellular fates of the terminal complement complex C5b-9, also known as the membrane attack complex. Punctate C5b-9 staining and diffuse C9 staining was detected in BE and EAC by multiplex immunohistofluorescence without corresponding increase of C9 mRNA transcript. Increased C9 and C5b-9 staining were observed in the sequence normal squamous epithelium, BE, low- and high-grade dysplasia, EAC. C5b-9 positive esophageal cells were morphologically intact, indicative of sublytic or complement-evasion mechanisms. To investigate this at a cellular level, we exposed non-dysplastic BE (BAR-T and CP-A), high-grade dysplastic BE (CP-B and CP-D) and EAC (FLO-1 and OE-33) cell lines to the same sublytic dose of immunopurified human C9 (3 µg/ml) in the presence of C9-depleted human serum. Cellular C5b-9 was visualized by immunofluorescence confocal microscopy. Shed C5b-9 in the form of extracellular vesicles (EV) was measured in collected conditioned medium using recently described microfluidic immunoassay with capture by a mixture of three tetraspanin antibodies (CD9/CD63/CD81) and detection by surface-enhanced Raman scattering (SERS) after EV labelling with C5b-9 or C9 antibody conjugated SERS nanotags. Following C9 exposure, all examined cell lines formed C5b-9, internalized C5b-9, and shed C5b-9+ and C9+ EVs, albeit at varying levels despite receiving the same C9 dose. In conclusion, these results confirm increased esophageal C5b-9 formation during EAC development and demonstrate capability and heterogeneity in C5b-9 formation and shedding in BE and EAC cell lines following sublytic C9 exposure. Future work may explore the molecular mechanisms and pathogenic implications of the shed C5b-9+ EV

    Papel das interações mediadas pelos receptores de prolactina e glicocorticoide na atrofia tímica que ocorre na infecção experimental pelo Trypanosoma Cruzi

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    Submitted by Anderson Silva ([email protected]) on 2012-10-11T18:05:38Z No. of bitstreams: 1 ailin_l_oliveira_ioc_bcm_0048_2011.pdf: 2784238 bytes, checksum: 109591f3b041c2482398b825d1bb7d51 (MD5)Made available in DSpace on 2012-10-11T18:05:38Z (GMT). No. of bitstreams: 1 ailin_l_oliveira_ioc_bcm_0048_2011.pdf: 2784238 bytes, checksum: 109591f3b041c2482398b825d1bb7d51 (MD5) Previous issue date: 2011Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, BrasilNo curso das doenças infecciosas, os circuitos neuroendócrinos e imunes atuam em conjunto facilitando a resposta do hospedeiro. Alterações no eixo hipotálamo-hipófise- adrenal são frequentemente associadas a infecções, como as causadas pelo Trypanosoma cruzi, o agente etiológico da doença de Chagas. Durante a fase aguda da infecção por T. cruzi, a ação pró-apoptótica de glicocorticóides (GC), sistemicamente aumentados, sobre timócitos CD4+CD8+ (DP), resulta em atrofia tímica. Recentemente, nosso grupo demonstrou expressão alterada de prolactina (PRL), um outro hormônio relacionado ao estresse, durante a infecção por T. cruzi. Com base no conhecimento das ações imunomoduladoras de PRL, como a proteção de timócitos da apoptose induzida por GC, pretendemos no presente estudo investigar uma possível função da ativação cruzada entre os receptores intratímicos de PRL e GC (PRLR e GR, respectivamente) no desencadeamento da atrofia tímica induzida por T. cruzi. Observamos um circuito intratímico específico de modulação de ambos os hormônios durante a infecção experimental por T. cruzi em camundongos adultos jovens. Enquanto os níveis plasmáticos de PRL e GC apresentaram-se aumentados no início da fase aguda da infecção, quando o processo de atrofia tímica é instaurado, os níveis intratímicos desses hormônios diminuíram, restabelecendo-se posteriormente aos níveis fisiológicos do controle não-infectado. Paralelamente, variações da expressão intratímica de PRLR e GR, ocorreram em acordo com a modulação local de seus ligantes. No início do processo de atrofia tímica, quando muitas células DP estão entrando em apoptose, observamos aumento da expressão de GR e diminuição de PRLR. Em um segundo momento, durante a fase mais tardia da infecção experimental por T. cruzi, houve restabelecimento da expressão gênica de ambos os receptores nessas células. Nessa fase, quando o processo de morte celular encontra-se estabilizado e somente algumas células aparentemente mais resistentes à ação pró-apoptótica de GC sobreviveram, observamos aumento da proteína Bcl-xl, um importante fator anti apoptótico induzido por PRL. Em acordo com esses achados, utilizando-se um modelo de indução de apoptose in vitro, verificamos maior Suscetibilidade de timócitos à morte induzida por GC nos períodos iniciais da infecção, bem como aos efeitos protetores de PRL, o que não foi observado na fase mais tardia da infecção. Tomados em conjunto, nossos dados apontam para uma função cruzada (cross-talk) entre PRLR e GR intratímicos, e que seria responsável pela manutenção da homeostasia tímica. Nesse sentido, alterações desse circuito podem contribuir para o processo de atrofia tímica característico da fase aguda da infecção pelo T. cruzi.During infectious diseases, neuroendocrine and immune networks act in concert, facilitating host response. Disorders in the hypothalamic-pituitary-adrenal axis are frequently observed associated to infections. It has been demonstrated that increased level of circulating glucocorticoids (GC) systemic levels during the acute phase of Trypanosoma cruzi infection, the etiological agent of Chaga ́s disease, results in thymus atrophy. Such steroid can trigger apoptosis on cortical thymocytes bearing the phenotype CD4+CD8+ (DP) via a specific glucocorticoid receptor (GR). Changes in thymocyte development may have an important consequence for the disease, i.e., further autoimmune reactions. Recently our group demonstrated altered expression of prolactin (PRL), another hormone related to stress, during T. cruzi infection. Based on studies showing expression of PRL receptors (PRLR) on lymphocytes, and its effects on growth, differentiation, and apoptosis in lymphoid cells, this hormone is supposed to functions as an immunomodulator. Furthermore, prolactin protects T cells from GC- induced apoptosis both in vivo and in vitro, which corroborates to this hypothesis. Based on these data, here we aim to investigate the possible role of intrathymic GR- PRLR cross-talk to the outcome of T. cruzi induced thymus atrophy. Our results demonstrate altered intrathymic PRL and corticosterone levels during the acute phase of T. cruzi infection. When the same hormones were evaluated on plasma, a different modulation was detected, suggesting an independence of intrathymic and systemic circuits that may be related to thymus atrophy. Furthermore, we detected the variation of PRLR and GR intrathymic expression, that ocurred in accordance to the modulation of their locally produced ligands. The analysis of DP cells that survived to the apoptosis process at the late phase of acute infection, demonstrated increased PRLR expression in parallel to the decrease of GR levels, This receptor expression profile courses with an increase of anti apoptotic proteins and the stabilization of the thymus atrophy process and seems an important factor for the survival of these cells. Using an in vitro model of thymocyte apoptosis induction, we observed that such alterations result in different GC-induced cell death susceptibility as well as an altered answer to prolactin anti -apoptotic effects. Taken together our results point to an relevant intrathymic PRLR-GR cross-talk involved in thymus homeostasis. In this way, changes of this circuit may contribute to the outcome of the thymus atrophy characteristic of the acute phase of T. cruzi infection
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