Preimplantation development regulatory pathway construction through a text-mining approach

BACKGROUND: The integration of sequencing and gene interaction data and subsequent generation of pathways and networks contained in databases such as KEGG Pathway is essential for the comprehension of complex biological processes. We noticed the absence of a chart or pathway describing the well-studied preimplantation development stages; furthermore, not all genes involved in the process have entries in KEGG Orthology, important information for knowledge application with relation to other organisms. RESULTS: In this work we sought to develop the regulatory pathway for the preimplantation development stage using text-mining tools such as Medline Ranker and PESCADOR to reveal biointeractions among the genes involved in this process. The genes present in the resulting pathway were also used as seeds for software developed by our group called SeedServer to create clusters of homologous genes. These homologues allowed the determination of the last common ancestor for each gene and revealed that the preimplantation development pathway consists of a conserved ancient core of genes with the addition of modern elements. CONCLUSIONS: The generation of regulatory pathways through text-mining tools allows the integration of data generated by several studies for a more complete visualization of complex biological processes. Using the genes in this pathway as "seeds" for the generation of clusters of homologues, the pathway can be visualized for other organisms. The clustering of homologous genes together with determination of the ancestry leads to a better understanding of the evolution of such process

Translocation t(1;6)(p35;p25) in B-cell lymphoproliferative disorder with evolution to Diffuse Large B-cell Lymphoma

Case report of a translocation : Translocation t(1;6)(p35;p25) in B-cell lymphoproliferative disorder with evolution to Diffuse Large B-cell Lymphoma

Trajetória profissional de egressos de cursos de doutorado nas áreas da saúde e biociências

OBJETIVO: Analisar a trajetória e satisfação profissional de egressos de cursos de doutorado na área da saúde. MÉTODOS: Estudo exploratório com 827 egressos dos cursos de doutorado da Fundação Oswaldo Cruz nas áreas da saúde coletiva, biociências e atenção à saúde, entre 1984 e 2007. Os sujeitos foram agrupados em três coortes temporais. Foi analisado o perfil dos egressos; mapeadas suas trajetórias profissionais, suas percepções sobre a formação recebida; suas motivações para escolha da instituição para realizar o doutorado; e as avaliações efetuadas sobre os cursos. Utilizou-se questionário em formato eletrônico para preenchimento on-line para coleta de dados. RESULTADOS: Existiram diferenças entre as coortes de egressos, relacionadas ao período em que cursaram o doutorado, a distintas trajetórias de formação e processos de trabalho entre egressos das áreas de biociências e saúde e as peculiaridades das diferentes áreas em que a instituição oferece cursos de doutorado: saúde coletiva, biociências e atenção à saúde. CONCLUSÕES: Os resultados possibilitam ampliar o conhecimento das instâncias de gestão acadêmica sobre os processos de formação, estabelecendo uma “linha de base” para o acompanhamento da trajetória dos egressos e contribuir com subsídios para o aprimoramento dos processos de acompanhamento de egressos dos programas de pós-graduaçãoOBJECTIVE: To analyze the career path and professional satisfaction of alumni from the doctorate degree programs in health sector. METHODS: Exploratory study with 827 alumni of doctoral programs in public health, biological and health sciences at the Fundação Oswaldo Cruz, RJ, Southeastern Brazil, from 1984 to 2007. The subjects were grouped in three cross-temporal cohorts according to year. The profiles of the alumni were analyzed, their career paths mapped and information on the perceptions of the education they received and the reasons that led them to choose the institute for their doctoral courses gathered, as well as their evaluations of the courses. The data were collected by means of an online questionnaire. RESULTS: There are differences between cohorts of alumni related to the periods they followed the courses, their distinct educational backgrounds and labor processes between those from the biological and health sciences areas, and to the specificities of the different areas where the institution offers doctoral courses: public health, biological and health sciences. CONCLUSIONS: The results allow the academic management of the educational processes to expend its knowledge, thus establishing a baseline for tracking the trajectory of alumni, and may contribute to upgrading the follow up process of Brazilian graduate program

Metabolic phenotype of skeletal muscle in early critical illness

No commercial use is permitted unless otherwise expressly granted.ZAP was funded by the National Institute of Health Research (UK). Additional funding has been received from the European Society of Intensive Care Medicine, Guy’s & St Thomas’ and King’s College London NIHR Comprehensive Biomedical Research Centre (BRC) and the Whittington Hospital NHS Trust. SDH received support from the Research Councils UK. NH received funding from the NIHR Clinical Research Facility and BRC at Guy’s and St Thomas’ NHS Foundation Trust (GSTT) and King’s College London. HEM was funded by University College London and UCLH BRC. The Clinical Phenotyping Centre is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London. MJWM is grateful to the Wellcome Trust for support in the form of a Postdoctoral Training Fellowship for part of this work. YP is grateful to Merz Pharmaceuticals for support in the form of a training fellowship award

Efeitos do treinamento muscular inspiratório em universitários tabagistas e não tabagistas

O hábito de fumar pode reduzir a capacidade aeróbica, aumentar a resistência ao fluxo aéreo e afetar a função dos músculos respiratórios. O objetivo deste estudo foi comparar os efeitos do Treinamento Muscular Inspiratório (TMI) entre dois grupos: tabagistas e não tabagistas. Participaram 44 voluntários universitários, divididos em dois grupos: tabagistas (GT), composto por 20 indivíduos (25,60±7,01 anos) e não tabagistas, constituindo o Grupo Controle (GC), composto por 24 voluntários (24,08±7,52 anos). Ambos os grupos foram submetidos ao TMI, por meio do uso do manovacuômetro aneroide, com duração de 6 semanas, sendo 3 sessões semanais, totalizando 18 sessões. Os resultados mostraram diferença estatisticamente significativa (p<0,05) pós-TMI no GC para as variáveis: Pressão Inspiratória Máxima (PImáx), Pico de Fluxo Expiratório (PFE), Pressão Arterial Média ao repouso (PAM pré-TC6) e Teste de Caminhada de Seis Minutos (TC6). No GT, houve diferença estatisticamente significativa pós-TMI para as variáveis: PImáx, PFE, TC6 e saturação periférica de oxigênio após o TC6 (SpO2 pós-imediata). A comparação das médias das variáveis entre GT e GC mostrou diferença estatisticamente significativa no pós-TMI para as variáveis PImáx e PFE. A variável TC6 não apresentou diferença estatisticamente significativa. Conclui-se que o TMI proporcionou um aumento significativo da força muscular inspiratória, melhora da função pulmonar e melhora do desempenho físico nos indivíduos estudados

Inflammation-Associated Nitrotyrosination Affects TCR Recognition through Reduced Stability and Alteration of the Molecular Surface of the MHC Complex

Nitrotyrosination of proteins, a hallmark of inflammation, may result in the production of MHC-restricted neoantigens that can be recognized by T cells and bypass the constraints of immunological self-tolerance. Here we biochemically and structurally assessed how nitrotyrosination of the lymphocytic choriomeningitis virus (LCMV)-associated immunodominant MHC class I-restricted epitopes gp33 and gp34 alters T cell recognition in the context of both H-2Db and H-2Kb. Comparative analysis of the crystal structures of H-2Kb/gp34 and H-2Kb/NY-gp34 demonstrated that nitrotyrosination of p3Y in gp34 abrogates a hydrogen bond interaction formed with the H-2Kb residue E152. As a consequence the conformation of the TCR-interacting E152 was profoundly altered in H-2Kb/NY-gp34 when compared to H-2Kb/gp34, thereby modifying the surface of the nitrotyrosinated MHC complex. Furthermore, nitrotyrosination of gp34 resulted in structural over-packing, straining the overall conformation and considerably reducing the stability of the H-2Kb/NY-gp34 MHC complex when compared to H-2Kb/gp34. Our structural analysis also indicates that nitrotyrosination of the main TCR-interacting residue p4Y in gp33 abrogates recognition of H-2Db/gp33-NY complexes by H-2Db/gp33-specific T cells through sterical hindrance. In conclusion, this study provides the first structural and biochemical evidence for how MHC class I-restricted nitrotyrosinated neoantigens may enable viral escape and break immune tolerance

Caracterização das habilidades funcionais na síndrome de Rett

O objetivo deste estudo foi identificar as áreas de maior comprometimento nas habilidades funcionais na síndrome de Rett (SR). Foram avaliadas 64 pacientes que preenchiam os critérios para a forma clássica da doença, com idade entre 2 e 26 anos. Foi aplicado o Inventário de avaliação pediátrica de incapacidade (PEDI) que contém 197 itens nas áreas de autocuidado, mobilidade e função social. Dentre as 73 atividades da área de autocuidado, 52 (71,2%) não foram realizadas por qualquer paciente; na mobilidade, dentre as 59 atividades propostas, 8 (13,5%); e na área de função social, dentre as 65 atividades, 50 (76,9%) não foram realizadas por paciente alguma. O desempenho médio ajustado em escala de 0 a 100 para a área de autocuidado foi de 8,9/100, variando de 0 a 19; na área de mobilidade, foi de 30,2/100, variando de 1 a 44; e na de função social, 5,2/100, com variação de 0 a 14. Foi possível verificar fortes correlações entre a área de autocuidado e as de mobilidade e função social; no entanto, entre as áreas de mobilidade e função social não foi detectada correlação significativa. Infelizmente, devido à gravidade da síndrome, o menor comprometimento da mobilidade, comparado ao das áreas de autocuidado e função social, não traz vantagens adaptativas ou maior independência às pacientes com SR.The purpose of this study was to determine the areas of greater impairment in functional abilities of patients with Rett syndrome. Sixty-four patients aged 2 to 26 years old, who filled out criteria for the classic form of the disease, were assessed by the Pediatric Evaluation of Disability Inventory (PEDI) of which 197 items are grouped in the areas of self-care, mobility, and social function. From the 73 activities in self-care area, 52 (71.2%) were not accomplished by any patient; in mobility area, among the 59 proposed activities, 8 (13.5%); and in social function area, from 65 activities, 50 (76.9%) could not be accomplished. Adjusted mean results in a 0-to-100 scale were: self-care, 8.9/100, varying from 0 to 19; mobility, 30.2/100, varying from 1 to 44; and social function, 5.2/100, varying from 0 to 14. Strong correlations were found between self-care area and mobility and social function areas, but no significant correlation between the latter. Unfortunately, due to the serious impairment of the disease, the fact that mobility is affected to a lesser degree, as compared to self-care and social function, does not bring Rett syndrome patients any adaptive advantage nor greater independence