RESUMO
Splenic marginal zone lymphoma (SMZL) is a B-cell neoplasm whose molecular pathogenesis remains fundamentally unexplained, requiring more precise diagnostic markers. Previous molecular studies have revealed 7q loss and mutations of nuclear factor κB (NF-κB), B-cell receptor (BCR) and Notch signalling genes. We performed whole-exome sequencing in a series of SMZL cases. Results confirmed that SMZL is an entity distinct from other low-grade B-cell lymphomas, and identified mutations in multiple genes involved in marginal zone development, and others involved in NF-κB, BCR, chromatin remodelling and the cytoskeleton.
Assuntos
Biomarcadores Tumorais/genética , Diferenciação Celular , Exoma/genética , Sequenciamento de Nucleotídeos em Larga Escala , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma de Zona Marginal Tipo Células B/patologia , Mutação/genética , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/patologia , Montagem e Desmontagem da Cromatina , Citoesqueleto , Humanos , NF-kappa B/genética , Transdução de SinaisRESUMO
CCL20 is a chemokine that attracts immature dendritic cells. We show that monocytes, cells characteristic of the innate immune response, infected with Mycobacterium tuberculosis express the CCL20 gene at a much higher level than the same cells infected with non-tuberculous mycobacteria. Interferon (IFN)-γ, a fundamental cytokine in the immune response to tuberculosis, strongly inhibits both the transcription and the translation of CCL20. We have also confirmed that dendritic cells are a suitable host for mycobacteria proliferation, although CCL20 does not seem to influence their intracellular multiplication rate. The chemokine, however, down-regulates the characteristic production of reactive oxygen species (ROS) induced by M. tuberculosis in monocytes, which may affect the activity of the cells. Apoptosis mediated by the mycobacteria, possibly ROS-dependent, was also inhibited by CCL20.
Assuntos
Quimiocina CCL20/metabolismo , Monócitos/metabolismo , Monócitos/microbiologia , Mycobacterium tuberculosis/imunologia , Espécies Reativas de Oxigênio/metabolismo , Anticorpos/imunologia , Anticorpos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Quimiocina CCL2/imunologia , Quimiocina CCL2/metabolismo , Quimiocina CCL20/genética , Quimiocina CCL20/imunologia , Quimiocina CCL20/farmacologia , Quimiocinas CC/genética , Quimiotaxia/efeitos dos fármacos , Quimiotaxia/imunologia , Contagem de Colônia Microbiana , Meios de Cultivo Condicionados/farmacologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/microbiologia , Expressão Gênica/genética , Humanos , Interferon gama/farmacologia , Legionella pneumophila/citologia , Legionella pneumophila/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/microbiologia , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Mycobacterium avium/citologia , Mycobacterium avium/imunologia , Mycobacterium kansasii/citologia , Mycobacterium kansasii/imunologia , Mycobacterium tuberculosis/citologiaAssuntos
Proteínas de Ligação a DNA/genética , Ovinos/genética , Transativadores/genética , Animais , Sequência de Bases , Mapeamento Cromossômico/veterinária , Ligação Genética/genética , Escore Lod , Repetições de Microssatélites/genética , Proteínas Mitocondriais , Dados de Sequência Molecular , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
Spanish Churra sheep were studied in a daughter design for the presence on chromosome 6 of quantitative trait loci (QTL) influencing milk production traits. Eight half-sib families were genotyped for 11 microsatellites and marker-QTL effects analysed using yield deviations (YD) as quantitative measurements for the following traits: milk yield, protein yield, and protein percentage. QTL analysis was performed by interval mapping based on multimarker regression principles. Significance thresholds were estimated through a permutation test followed by a correction for multiple testing. The results suggest a region on ovine chromosome 6, close to the casein cluster, with an influence on milk traits and particularly on protein percentage. These results, the first ones reported for QTL affecting milk traits in sheep, are discussed in relation to data available for cattle, a closely related species.
Assuntos
Lactação/genética , Leite/metabolismo , Característica Quantitativa Herdável , Ovinos/genética , Animais , Mapeamento Cromossômico/veterinária , Feminino , Genótipo , Lactação/fisiologia , Repetições de Microssatélites , Proteínas do Leite/análise , Proteínas do Leite/genética , Análise de Regressão , Ovinos/fisiologiaRESUMO
Genetic relationships among six populations of Merino sheep were investigated using microsatellites. The history of the six populations is relatively well documented, with all being derived from the Spanish Merino breed within the last 400 years. Genetic variation was highest amongst the Spanish and Portuguese populations, although the preservation of genetic diversity within the other populations was high. By a variety of different statistical tests the French Mutton, German Mutton and New Zealand Merino populations could be differentiated from each other and the Iberian Merinos, indicating that microsatellites are able to track relatively recent changes in the population structure of sheep breeds. The dendrograms constructed on the basis of microsatellite allelic frequencies showed that populations that have shared selection criteria (meat vs. wool) tend to cluster together.
