Polymorphic toxin systems: Comprehensive characterization of trafficking modes, processing, mechanisms of action, immunity and ecology using comparative genomics

Background: Proteinaceous toxins are observed across all levels of inter-organismal and intra-genomic conflicts. These include recently discovered prokaryotic polymorphic toxin systems implicated in intra-specific conflicts. They are characterized by a remarkable diversity of C-terminal toxin domains generated by recombination with standalone toxin-coding cassettes. Prior analysis revealed a striking diversity of nuclease and deaminase domains among the toxin modules. We systematically investigated polymorphic toxin systems using comparative genomics, sequence and structure analysis. Results: Polymorphic toxin systems are distributed across all major bacterial lineages and are delivered by at least eight distinct secretory systems. In addition to type-II, these include type-V, VI, VII (ESX), and the poorly characterized "Photorhabdus virulence cassettes (PVC)", PrsW-dependent and MuF phage-capsid-like systems. We present evidence that trafficking of these toxins is often accompanied by autoproteolytic processing catalyzed by HINT, ZU5, PrsW, caspase-like, papain-like, and a novel metallopeptidase associated with the PVC system. We identified over 150 distinct toxin domains in these systems. These span an extraordinary catalytic spectrum to include 23 distinct clades of peptidases, numerous previously unrecognized versions of nucleases and deaminases, ADP-ribosyltransferases, ADP ribosyl cyclases, RelA/SpoT-like nucleotidyltransferases, glycosyltranferases and other enzymes predicted to modify lipids and carbohydrates, and a pore-forming toxin domain. Several of these toxin domains are shared with host-directed effectors of pathogenic bacteria. Over 90 families of immunity proteins might neutralize anywhere between a single to at least 27 distinct types of toxin domains. In some organisms multiple tandem immunity genes or immunity protein domains are organized into polyimmunity loci or polyimmunity proteins. Gene-neighborhood-analysis of polymorphic toxin systems predicts the presence of novel trafficking-related components, and also the organizational logic that allows toxin diversification through recombination. Domain architecture and protein-length analysis revealed that these toxins might be deployed as secreted factors, through directed injection, or via inter-cellular contact facilitated by filamentous structures formed by RHS/YD, filamentous hemagglutinin and other repeats. Phyletic pattern and life-style analysis indicate that polymorphic toxins and polyimmunity loci participate in cooperative behavior and facultative 'cheating' in several ecosystems such as the human oral cavity and soil. Multiple domains from these systems have also been repeatedly transferred to eukaryotes and their viruses, such as the nucleo-cytoplasmic large DNA viruses. Conclusions: Along with a comprehensive inventory of toxins and immunity proteins, we present several testable predictions regarding active sites and catalytic mechanisms of toxins, their processing and trafficking and their role in intra-specific and inter-specific interactions between bacteria. These systems provide insights regarding the emergence of key systems at different points in eukaryotic evolution, such as ADP ribosylation, interaction of myosin VI with cargo proteins, mediation of apoptosis, hyphal heteroincompatibility, hedgehog signaling, arthropod toxins, cell-cell interaction molecules like teneurins and different signaling messengers.

Análise de vizinhança: uma nova abordagem para avaliar a rede proposicional de mapas conceituais*

A análise detalhada de Mapas Conceituais (MCs) pode revelar informações latentes que não são percebidas a partir da mera leitura do seu conjunto de proposições. O presente trabalho tem como objetivo propor a Análise de Vizinhança (AViz) como uma forma inovadora de avaliar os MCs obtidos em sala de aula. A seleção de um Conceito Obrigatório (CO) permite ao professor verificar como os alunos o relacionam com outros conceitos, os quais são classificados como Conceitos Vizinhos (CVs). As proposições estabelecidas entre o CO e os CVs são suficientes para indicar o nível de compreensão do aluno sobre o tema mapeado. MCs (n = 69) sobre mudanças climáticas formam o primeiro conjunto de dados empíricos que ratifica o potencial da AViz. O CO selecionado foi dispersão, a fim de avaliar se os alunos conseguem relacionar esse fenômeno físico com o caráter global desse problema ambiental. Os padrães identificados a partir da AViz sugerem que, apesar de serem submetidos a uma mesma sequência didática, nem todos os alunos conseguiram utilizar o CO de forma adequada. Isso pode ser explicado a partir da Teoria da Aprendizagem Significativa de David Ausubel, que destaca o papel fundamental dos conhecimentos prévios no processo de assimilação de novas informações.

Perceived neighborhood problems: multilevel analysis to evaluate psychometric properties in a Southern adult Brazilian population

Abstract Background Physical attributes of the places in which people live, as well as their perceptions of them, may be important health determinants. The perception of place in which people dwell may impact on individual health and may be a more telling indicator for individual health than objective neighborhood characteristics. This paper aims to evaluate psychometric and ecometric properties of a scale on the perceptions of neighborhood problems in adults from Florianopolis, Southern Brazil. Methods Individual, census tract level (per capita monthly familiar income) and neighborhood problems perception (physical and social disorders) variables were investigated. Multilevel models (items nested within persons, persons nested within neighborhoods) were run to assess ecometric properties of variables assessing neighborhood problems. Results The response rate was 85.3%, (1,720 adults). Participants were distributed in 63 census tracts. Two scales were identified using 16 items: Physical Problems and Social Disorder. The ecometric properties of the scales satisfactory: 0.24 to 0.28 for the intra-class correlation and 0.94 to 0.96 for reliability. Higher values on the scales of problems in the physical and social domains were associated with younger age, more length of time residing in the same neighborhood and lower census tract income level. Conclusions The findings support the usefulness of these scales to measure physical and social disorder problems in neighborhoods.

Spatial analysis of the social vulnerability of adolescent pregnancy

The purpose of this study was to present a spatial analysis of the social vulnerability of teenage pregnancy by geoprocessing data on births and deaths present on the Brazilian Ministry of Health databases in order to support intersectoral management actions and strategies based on spatial analysis in neighborhood areas. The thematic maps of the educational, occupational, birth and marital status of mothers, from all births and deaths in the city, presented a spatial correlation with teenage pregnancy. These maps were superimposed to produce social vulnerability map of adolescent pregnancy and women in general. This process presents itself as a powerful tool for the study of social vulnerability.