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.

Spin-polarized transport in II-VI diluted magnetic semiconductors superlattices

We studied the spin-polarized charge densities in II-VI-based diluted magnetic superlattices formed of p-doped ZnTe:Mg/ZnTe:TM/ZnTe:Mg non-magnetic/magnetic/non-magnetic layers, with TM standing for transition metal. The calculations were performed within a self-consistent k.p method, in which are also taken into account the exchange correlation effects in the local density approximation. Our results show a limit for the width of the non-magnetic layer for which the difference between the opposite spin charge densities is maximized, indicating the best conditions to obtain full polarization by varying the TM content. We also discuss these effects in the calculated photoluminescence spectra. Our findings point to the possibility of engineering the spin-polarized charge distribution by varying the widths of the magnetic and non-magnetic layers and/or varying the TM concentration in the magnetic layers, thus providing a guide for future experiments. (c) 2012 Elsevier B.V. All rights reserved.

FERM domain interaction with myosin negatively regulates FAK in cardiomyocyte hypertrophy

Focal adhesion kinase (FAK) regulates cellular processes that affect several aspects of development and disease. The FAK N-terminal FERM (4.1 protein-ezrin-radixin-moesin homology) domain, a compact clover-leaf structure, binds partner proteins and mediates intramolecular regulatory interactions. Combined chemical cross-linking coupled to MS, small-angle X-ray scattering, computational docking and mutational analyses showed that the FAK FERM domain has a molecular cleft (similar to 998 angstrom(2)) that interacts with sarcomeric myosin, resulting in FAK inhibition. Accordingly, mutations in a unique short amino acid sequence of the FERM myosin cleft, FP-1, impaired the interaction with myosin and enhanced FAK activity in cardiomyocytes. An FP-1 decoy peptide selectively inhibited myosin interaction and increased FAK activity, promoting cardiomyocyte hypertrophy through activation of the AKT-mammalian target of rapamycin pathway. Our findings uncover an inhibitory interaction between the FAK FERM domain and sarcomeric myosin that presents potential opportunities to modulate the cardiac hypertrophic response through changes in FAK activity.

Contribuição para o estudo dos Rhinotragini (Coleoptera, Cerambycidae). VI. Ecliptoides Tavakilian & Peñaherrera-Leiva, 2005

The genus Ecliptoides Tavakilian & Peñaherrera-Leiva, 2005, recently revised by Clarke (2009) to include three Bolivian species, is brought up-to-date by the inclusion of further South American species transferred from Eclipta Bates, 1873, and Odontocera Audinet-Serville, 1833. Three new species are described from Brazil: E. schmidi, E. tavakiliani, and E. hogani. Ommata eunomia var. rufula Melzer, 1934, and Ommata (Eclipta) plaumanni Fuchs, 1961, are revalidated and considered species of Ecliptoides. Species transferred from Eclipta to include Ecliptoides: E. bivitticollis (Fisher, 1952); E. eunomia (Newman, 1841); E. pilosipes (Peñaherrera-Leiva & Tavakilian, 2004); E. fanchonae (Tavakilian & Peñaherrera-Leiva, 2003); E. giuglarisi (Peñaherrera-Leiva & Tavakilian, 2004); E. vasconezi (Peñaherrera-Leiva & Tavakilian, 2004); E. vicina (Melzer, 1927); E. lauraceae (Peñaherrera-Leiva & Tavakilian, 2004); and E. bauhiniae (Peñaherrera-Leiva & Tavakilian, 2004). Species transferred from Odontocera to include Ecliptoides: O. quadrivittata Melzer, 1922; O. pusilla Gounelle, 1911; and O. monostigma (Bates, 1869). New synonymy: Ommata (Eclipta) collarti Fuchs, 1959 = Odontocera pusilla Gounelle, 1911 (= Ecliptoides pusillus). Lectotypes are designated for Ommata (Eclipta) vicina, and Ommata (Eclipta) collarti. New distribution records are provided for E. eunomia, E. pilosipes, E. plaumanni and E. fanchonae. A key to the species of Ecliptoides is given.

Gestão Social: notícias sobre o campo de estudos e práticas a partir das interações e debates do VI Enapegs

Este texto busca relatar a realização do evento Encontro Nacional da Rede de Pesquisadores em Gestão Social (Enapegs), que teve sua última edição em maio de 2012, em São Paulo. Para tanto, busca delimitar o que vem a ser o campo de estudos sobre Gestão Social, a constituição da Rede de Pesquisadores em Gestão Social (RGS), bem como a dinâmica de construção e realização do Enapegs e suas principais discussões e resultados, que no último encontro teve como temática: Gestão Social: mobilizações e conexões.

Tratamento de sequelas de queimadura de face com laser de CO2 fracionado em pacientes com fototipos III a VI

INTRODUÇÃO: Relatos sobre melhora em cicatrizes pós-traumáticas ou patológicas com o uso do laser de CO2 fracionado (CO2F) concluem tratar-se de tecnologia segura e efetiva, apesar de utilizado apenas em pacientes com fototipos II a III. O objetivo deste estudo foi avaliar a eficácia do CO2F em pacientes com sequela de queimadura facial com fototipos III a VI. MÉTODO: No total, 14 pacientes, com média de idade de 29 anos, portadores de sequela de queimadura facial e fototipos III a VI, foram submetidos a uma aplicação do laser de CO2F. Após dois meses, a queimadura foi avaliada por meio de escala com 6 parâmetros: cor, textura, hidratação, irregularidades de superfície, volume e distensibilidade. RESULTADOS: A duração média da dor foi de 19 horas; do edema, 1,3 dia; e da hiperemia, 6,5 dias. A queda das crostas finalizou entre 5 dias e 36 dias, com média de 13,4 dias. Dois meses após a sessão, 5 pacientes evoluíram com hipocromia puntiforme no padrão quadriculado correspondente aos pontos de ablação do laser. A satisfação subjetiva dos avaliadores (pacientes e médicos) com o tratamento foi de 84,6%. Para os pacientes, houve melhora das irregularidades de superfície, da distensibilidade e da textura da pele (57% dos casos), da hidratação (43%), do volume (28%) e da cor (14%). Para os médicos, houve melhora das irregularidades de superfície e da distensibilidade (43%). CONCLUSÕES: O tratamento com laser de CO2F com parâmetros suaves foi bem tolerado e apresentou alto índice de satisfação em pacientes com sequela de queimadura facial, com melhora de textura, distensibilidade e irregularidades de superfície. A alta incidência de hipopigmentação é um fator a ser considerado na indicação do laser de CO2F em pacientes com fototipos IV a VI.