361 resultados para DLR de Raf


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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Background: Hematology tests are useful to evaluate physiologic disturbances in fish and can provide important information for the diagnosis and prognosis of disease. Objectives: the primary purpose of this study was to define reference intervals for thrombocytes and leukocytes in healthy channel catfish (Ictalurus punctactus). In addition, the morphologic, cytochernical, and ultrastructural features of blood cells were assessed. Methods: Blood samples (0.5 mL were collected into EDTA from 40 clinically healthy catfish on a commercial fish farm in Jaboticabal, Brazil. Thrombocyte, total WBC, and differential WBC counts were determined and reference intervals were calculated as the 25-95th percentiles of data. Thrombocyte and leukocyte morphology was assessed in blood smears stained with May Griinwald-Giemsa-Wright and ultrastructurally by transmission electron microscopy. Cytochemical staining patterns were described using periodic acid-Schiff (PAS), peroxidase, nonspecific esterase, alkaline phosphatase, and toluidine blue. Results: Reference intervals were as follows: thrombocytes 58,802-99,569/mu L; total WBCs 27,460-41,523/mu L; lymphocytes 5380-11,581/mu L; monocytes 2949-7459/mu L; neutrophils 12,529-22,748/mu L, and basophils 736-2003/mu L. Neutrophils were positive for peroxidase and PAS; monocytes were positive for nonspecific esterase; and basophils were positive with toluidine blue. Conclusion: the morphologic and staining features of neutrophils and monocytes of channel catfish are similar to those of mammals, and the presence of basophils in this species was verified. These reference intervals and morphologic findings provide a foundation for future investigations on the functions and alterations of blood cells in channel catfish.

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Plan disease control techniques are used through the irrigation water, which reduces the labor and it improves application uniformity with smaller contact of the operator with toxic products, lower environmental impact and lower production cost. In order to control Botrytis cinerea the lisianthus culture, this work aimed to evaluate two fungicide application methods with different treatments. The fungicides were: thiophanate methyl (50 g i.a. L-1), thiophanate methyl + chlorothalonil (50 g i.a. L-1 + 35 g i.a. L-1) and iprodione (50 g i.a. L-1). Number of lesions, number of diseased floral buttons and height of the lisianthus plants were evaluated. It was possible to deduce, that in the growth stage (number of lesions in the plant) as well as in the final stage (number of floral buttons) of the lisianthus culture, the most efficient treatments were 2 (thiophanate methyl + chlorothalonil) and 3 (iprodione). Considering that treatment 2 is a mixture of two fungicides, a systemic and a contact one, independently of application methods, the mixture increased efficiency in relation to treatment 1 (thiophanate methyl). Thus, chemigation was as efficient as spreading technique.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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In „’Let ‘em have it – right on the chin.’ – Die Haltung der britischen Öffentlich-keit zum RAF-Flächenbombardement 1939-1945“ wird durch die Untersuchung der vier Tageszeitungen Times, Manchester Guardian, Daily Express und Daily Mirror sowie der wöchentlichen Berichte des britischen Informationsministeriums nachgewiesen, dass 1942 ein Konsens in der britischen Öffentlichkeit für Flächenbombardements eintrat. Diese Einigkeit entstand aufgrund der Kriegssituation, sozialpsychologischer Mechanismen und realpolitischer Erwägungen und verfestigte sich 1943 und zum Teil auch 1944 deutlich. Die öffentliche Meinung kehrte sich in den drei Jahren zwischen 1940 und 1943 vollständig um und wandelte sich 1944 erneut: Während 1940 die Mehrheit gegen die Bombardierung der deutschen Zivilbevölkerung eingestellt war, fand in den folgenden drei Jahren eine Entwicklung statt, die 1943 in den Konsens, 1944 aber in die Tabuisierung des Themas mündete. Dabei verstärkten insbesondere zwei Argumente den Prozess der Konsensbildung: Nachdem bis Anfang 1941 die Bedeutung der Begrifflichkeiten so weit vereinheitlicht worden war, dass beispielsweise die Mehrheit der Briten etwas mit dem Ausdruck „Flächenbombardement“ anfangen konnte, setzte sich im Laufe des Jahres 1940 – in Presse und Bevölkerung parallel – ein Feindbild durch, das das gesamte deutsche Volk in Haftung nahm und es insofern auch für die deutschen Luftangriffe auf Großbritannien verantwortlich machte. Erst daraus erwuchs die Rechtfertigung für die Forderung nach Vergeltung, die durch diese Begründung von bloßen Rachegelüsten losgelöst werden konnte. Seit dem deutschen Angriff auf die Sowjetunion im Juni 1941 galten Flächenbombardements – hier folgten Bevölkerung und Presse der britischen Regierung – außerdem als Vorbereitung für die Westoffensive. Eine Mehrheit sprach sich schon 1941 für Flächenbombardements aus, mit den großen Angriffen 1942 und vor allem 1943 war der Konsens dann so vollständig erreicht, dass kritische Stimmen fast gänzlich verstummten. Als mit der alliierten Landung in der Normandie 1944 ein wichtiges Argument für die Notwendigkeit von Flächenbombardements wegfiel, setzte eine Tabuisierung des Themas ein, die sich 1945 verfestigte. Insgesamt beleuchtet die Arbeit, durch welche Faktoren in einer Kontroverse eine gesellschaftliche Einigkeit im Großbritannien der frühen vierziger Jahre erzeugt wurde. Dieser Zusammenhalt war notwendig, um die Handlungsfähigkeit der Gesellschaft zu gewährleisten, so dass sich der Konsens in der Kriegssituation als wichtige Überlebensstrategie erwies. Erreicht wurde er aber auf Kosten des für eine demokratische Gesellschaft auch charakteristischen Pluralismus von Meinungen und Einstellungen.

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Cutaneous T-cell lymphomas (CTCLs) are malignancies of skin-homing lymphoid cells, which have so far not been investigated thoroughly for common oncogenic mutations. We screened 90 biopsy specimens from CTCL patients (41 mycosis fungoides, 36 Sézary syndrome, and 13 non-mycosis fungoides/Sézary syndrome CTCL) for somatic mutations using OncoMap technology. We detected oncogenic mutations for the RAS pathway in 4 of 90 samples. One mycosis fungoides and one pleomorphic CTCL harbored a KRAS(G13D) mutation; one Sézary syndrome and one CD30(+) CTCL harbored a NRAS(Q61K) amino acid change. All mutations were found in stage IV patients (4 of 42) who showed significantly decreased overall survival compared with stage IV patients without mutations (P = .04). In addition, we detected a NRAS(Q61K) mutation in the CTCL cell line Hut78. Knockdown of NRAS by siRNA induced apoptosis in mutant Hut78 cells but not in CTCL cell lines lacking RAS mutations. The NRAS(Q61K) mutation sensitized Hut78 cells toward growth inhibition by the MEK inhibitors U0126, AZD6244, and PD0325901. Furthermore, we found that MEK inhibitors exclusively induce apoptosis in Hut78 cells. Taken together, we conclude that RAS mutations are rare events at a late stage of CTCL, and our preclinical results suggest that such late-stage patients profit from MEK inhibitors.

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BACKGROUND Raf-1 kinase inhibitor protein (RKIP) has emerged as a significant metastatic suppressor in a variety of human cancers and is known to inhibit Ras/Raf/MEK/ERK signaling. By suppressing the activation of the NFkB/SNAIL circuit, RKIP can regulate the induction of epithelial-mesenchymal transition (EMT). The aim of this study was to evaluate RKIP expression and to determine its association with clinicopathological features, including EMT in form of tumor budding in pancreatic ductal adenocarcinoma (PDAC). METHODS Staining for RKIP was performed on a multipunch Tissue Microarray (TMA) of 114 well-characterized PDACs with clinico-pathological, follow-up and adjuvant therapy information. RKIP-expression was assessed separately in the main tumor body and in the tumor buds. Another 3 TMAs containing normal pancreatic tissue, precursor lesions (Pancreatic Intraepithelial Neoplasia, PanINs) and matched lymph node metastases were stained in parallel. Cut-off values were calculated by receiver operating characteristic (ROC) curve analysis. RESULTS We found a significant progressive loss of RKIP expression between normal pancreatic ductal epithelia (average: 74%), precursor lesions (PanINs; average: 37%), PDAC (average 20%) and lymph node metastases (average 8%, p<0.0001). RKIP expression was significantly lower in tumor buds (average: 6%) compared to the main tumor body (average 20%; p<0.005). RKIP loss in the tumor body was marginally associated with advanced T-stage (p=0.0599) as well as high-grade peritumoral (p=0.0048) and intratumoral budding (p=0.0373). RKIP loss in the buds showed a clear association with advanced T stage (p=0.0089). CONCLUSIONS The progressive loss of RKIP seems to play a major role in the neoplastic transformation of pancreas, correlates with aggressive features in PDAC and is associated with the presence of EMT in form of tumor budding.

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F. Dosṭojewski. Iberzetzṭ Z. Reizen

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Raf Kinase Inhibitor Protein (RKIP) has been identified as a phosphatidylethanolamine-binding protein capable of inhibiting Raf-1 kinase, an enzyme significant in cell proliferation and cancer development. When properly functioning, RKIP can mediate the expression of Raf-1 kinase and help prevent uncontrolled cell division. RKIP also has suggested, but unclear, roles in spindle fiber formation during mitosis, regulation of apoptosis, and cell motility. The Fenteany laboratory in the Chemistry Department identified a new small molecule, named Locostatin, as a cell migration inhibitor in mammalian cells, with RKIP as its primary molecular target. Dictyostelium discoideum possess two RKIP proteins, RKIP-A and RKIP-B. In order to begin to study the function of RKIP in D. discoideum and its role in cell motility, I created a mutant cell line which lacks a functional RKIP-A gene. In this paper, we show that removal of RKIP-A does not affect vegetative motility, but impairs chemotaxis and development in the presence of drug. Interestingly, RKIP-A knockout mutants appear more resistant to drug effects on vegetative motility than wild-type cells. More research is needed to reconcile these seemingly contrasting results, and to better develop a model for RKIP-A’s role in cell motility.