Pulmonary edema in mice infected withPlasmodium berghei. Involvement of catecholamines

Summary Mice inoculated withPlasmodium berghei developed a drastic and significant pulmonary edema. Treatment of animals with phenoxybenzamine rendered mice hyporeactive to this physiopathological alteration.This work was supported by a grant aided by «Conselho Nacional de Desenvolvimento Científico e Tecnológico» (CNPq, Brasil). Presented in preliminary form at the XIX Annual Meeting of the Brazilian Society of Tropical Medicine, Rio de Janeiro, R. J., February 20, 1983.Acknowledgments. We thank Mr Antonio Fernando de P. Oliveira and Solano S. Martins for their excellent technical help.     

Transcriptome analysis of the acoelomate human parasite Schistosoma mansoni

Schistosoma mansoni is the primary causative agent of schistosomiasis, which affects 200 million individuals in 74 countries. We generated 163,000 expressed-sequence tags (ESTs) from normalized cDNA libraries from six selected developmental stages of the parasite, resulting in 31,000 assembled sequences and 92% sampling of an estimated 14,000 gene complement. By analyzing automated Gene Ontology assignments, we provide a detailed view of important S. mansoni biological systems, including characterization of metazoa-specific and eukarya-conserved genes. Phylogenetic analysis suggests an early divergence from other metazoa. The data set provides insights into the molecular mechanisms of tissue organization, development, signaling, sexual dimorphism, host interactions and immune evasion and identifies novel proteins to be investigated as vaccine candidates and potential drug targets.     

A Combinatorial Approach to Assess the Separability of Clusters

Separability of clusters is an issue that arises in many different areas, and is often used in a rather vague and subjective manner. We introduce a combinatorial notion of interiority to derive a global view on separability of a set of entities. We develop this approach further to evaluate the overall separability of a partition in the context of cluster analysis. Our approach captures combinatorial and geometrical aspects of data and provides, in addition to numerical evaluations, graphical representations particularly useful when data are not easily visualized. We illustrate the methodology on some real and simulated datasets.     

FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity

Naturally occurring variation in gene copy number is increasingly recognized as a heritable source of susceptibility to genetically complex diseases. Here we report strong association between FCGR3B copy number and risk of systemic lupus erythematosus (P = 2.7 x 10(-8)), microscopic polyangiitis (P = 2.9 x 10(-4)) and Wegener's granulomatosis in two independent cohorts from the UK (P = 3 x 10(-3)) and France (P = 1.1 x 10(-4)). We did not observe this association in the organ-specific Graves' disease or Addison's disease. Our findings suggest that low FCGR3B copy number, and in particular complete FCGR3B deficiency, has a key role in the development of systemic autoimmunity.     

A high-resolution map of human evolutionary constraint using 29 mammals

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ～4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ～60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.     

Pulmonary edema in mice infected with Plasmodium berghei. Involvement of catecholamines

Mice inoculated with Plasmodium berghei developed a drastic and significant pulmonary edema. Treatment of animals with phenoxybenzamine rendered mice hyporeactive to this physiopathological alteration.     

The Systemic Approach of SSM: The Case of a Brazilian Company

This paper aims to describe the application of Soft Systems Methodology (SSM) to the reality of a Brazilian enterprise. Systemic practices are ways of putting to use systemic thought in the real world, using the precepts of the systemic approach, which is very important for knowledge management and globalization. The systemic practice SSM is used in the resolution of ill-defined problems, which often involve behavioral variables and, thus, cannot be addressed by the so-called hard methodologies. In this paper, SSM is applied to the problematic of a middle-market business, an auto supply distributor, whose managers consulted the authors of this paper as regards proposing improvements of its performance. As a result of this work, the authors were able to propose core changes in attitudes, leading to changes in structure and process.