RIP and FADD: two "death domain"-containing proteins can induce apoptosis by convergent, but dissociable, pathways.

With use of the yeast two-hybrid system, the proteins RIP and FADD/MORT1 have been shown to interact with the "death domain" of the Fas receptor. Both of these proteins induce apoptosis in mammalian cells. Using receptor fusion constructs, we provide evidence that the self-association of the death domain of RIP by itself is sufficient to elicit apoptosis. However, both the death domain and the adjacent alpha-helical region of RIP are required for the optimal cell killing induced by the overexpression of this gene. By contrast, FADD's ability to induce cell death does not depend on crosslinking. Furthermore, RIP and FADD appear to activate different apoptotic pathways since RIP is able to induce cell death in a cell line that is resistant to the apoptotic effects of Fas, tumor necrosis factor, and FADD. Consistent with this, a dominant negative mutant of FADD, lacking its N-terminal domain, blocks apoptosis induced by RIP but not by FADD. Since both pathways are blocked by CrmA, the interleukin 1 beta converting enzyme family protease inhibitor, these results suggest that FADD and RIP can act along separable pathways that nonetheless converge on a member of the interleukin 1 beta converting enzyme family of cysteine proteases.

The proteolytic fragments generated by vertebrate proteasomes: structural relationships to major histocompatibility complex class I binding peptides.

Proteasomes are involved in the proteolytic generation of major histocompatibility complex (MHC) class I epitopes but their exact role has not been elucidated. We used highly purified murine 20S proteasomes for digestion of synthetic 22-mer and 41/44-mer ovalbumin partial sequences encompassing either an immunodominant or a marginally immunogenic epitope. At various times, digests were analyzed by pool sequencing and by semiquantitative electrospray ionization mass spectrometry. Most dual cleavage fragments derived from 22-mer peptides were 7-10 amino acids long, with octa- and nonamers predominating. Digestion of 41/44-mer peptides initially revealed major cleavage sites spaced by two size ranges, 8 or 9 amino acids and 14 or 15 amino acids, followed by further degradation of the latter as well as of larger single cleavage fragments. The final size distribution was slightly broader than that of fragments derived from 22-mer peptides. The majority of peptide bonds were cleaved, albeit with vastly different efficiencies. This resulted in multiple overlapping proteolytic fragments including a limited number of abundant peptides. The immunodominant epitope was generated abundantly whereas only small amounts of the marginally immunogenic epitope were detected. The frequency distributions of amino acids flanking proteasomal cleavage sites are correlated to that reported for corresponding positions of MHC class I binding peptides. The results suggest that proteasomal degradation products may include fragments with structural properties similar to MHC class I binding peptides. Proteasomes may thus be involved in the final stages of proteolytic epitope generation, often without the need for downstream proteolytic events.

Potencialidades e alcances do monitoramento como ferramenta de gestão da saúde

No Brasil, a construção bem como as mudanças nos mais de vinte anos do Sistema Único de Saúde (SUS) tem demandado um crescente interesse em estratégias que valorizem o uso da informação em saúde. Cada vez mais as incertezas entre a complexidade deste sistema e as intervenções necessárias para atender os seus preceitos e as necessidades da população precisam de respostas ágeis e efetivas. A efetividade dos serviços e a equidade em sua prestação são cruciais na atenção à saúde e mostram-se como desafio frente à dificuldade de avaliação dos resultados das ações pela demora no impacto nos indicadores epidemiológicos clássicos. O monitoramento é uma prática que pode ser destacada pela agilidade nas respostas, porém é nítido o quanto a discussão sobre o assunto é pouco estabelecida na literatura disponível. Se apresenta como uma prática interativa e proativa que utiliza informações disponíveis com o potencial de organizar e divulgar rapidamente as descobertas feitas, gerar um aprendizado organizacional e apoiar o processo decisório. A proposta deste estudo considerou o Painel de Monitoramento da Secretaria Municipal da Saúde de São Paulo como ponto de partida para pesquisar sobre as potencialidades do monitoramento na gestão. Uma pesquisa de métodos mistos foi a opção metodológica para este trabalho que buscou aprofundar o marco referencial teórico sobre monitoramento, descrever e analisar criticamente as referências técnicas utilizadas para a construção da proposta e realizar um estudo de caso único em território descentralizado do município de São Paulo sobre a rotina local na sua utilização e com isso analisar as potencialidades e os alcances desta experiência na gestão municipal. Concluiu-se que o monitoramento por meio de indicadores selecionados a partir de dados secundários é uma estratégia oportuna de acompanhar a tendência de determinadas ações possibilitando assim a emissão de juízo de valor e tomada de decisão com rapidez. O aplicativo propicia aos gestores e técnicos informações relevantes que apoiam o processo decisório, além de possibilitar a sua utilização em diferentes contextos da gestão e portes territoriais. Por outro lado, a prática cotidiana é pautada por prioridades normativas, onde a precisão do registro, a coerência das fontes e a quantidade apontada sobrepõem-se à informação em si, o seu significado e as ações necessárias para o enfrentamento dos problemas. O uso da informação é cultura em construção e o Painel de Monitoramento traz a possibilidade de organizar, qualificar e difundir dados secundários dos diferentes sistemas de informação do Sistema Único de Saúde (SUS). Além disso, tem contribuído também no papel de fomentar as discussões sobre os diferentes temas que envolvem as prioridades de uma gestão em todos os níveis do sistema de saúde do município de São Paulo.

The Rueter-Hess Dam and Reservoir Project: A Question of Sustainable Water

Water in sufficient quantities throughout the Colorado Front Range is becoming increasingly limited. This paper examines the consequences for continued unsustainable use of water for communities of the Denver metropolitan area. This paper also looks at the effect that water law in the West has for otherwise optimum distributions of water. In addition, four regional and state water studies are reviewed for their contribution to sustainable water. Finally, the Final Environmental Impact Statement of the Rueter-Hess dam and reservoir project in Parker, Colorado is explored. Key findings conclude that the Rueter-Hess project may not, by itself, provide sustainable water for Parker; but the project will create incentive and opportunity for communities throughout the region to address the question of sustainable water.

Serological diagnosis of echinococcosis: the diagnostic potential of native antigens

PURPOSE: Human alveolar (AE) and cystic echinococcosis (CE) caused by the metacestode stages of Echinococcus multilocularis and E. granulosus, respectively, lack pathognomonic clinical signs. Diagnosis therefore relies on the results of imaging and serological studies. The primary goal of this study was to evaluate the efficacy of several easy-to-produce crude or partially purified E. granulosus and E. multilocularis metacestode-derived antigens as tools for the serological diagnosis and differential diagnosis of patients suspicious for AE or CE. METHODS: The sera of 51 treatment-naïve AE and 32 CE patients, 98 Swiss blood donors and 38 patients who were initially suspicious for echinococcosis but suffering from various other liver diseases (e.g., liver neoplasia, etc.) were analysed. RESULTS: According to the results of enzyme-linked immunosorbent assays (ELISA), metacestode-derived antigens of E. granulosus had sensitivities varying from 81 to 97% and >99.9% for the diagnosis of CE and AE, respectively. Antigens derived from E. multilocularis metacestodes had sensitivities ranging from 84 to 91% and >99.9% for the diagnosis of CE and AE, respectively. Specificities ranged from 92 to >99.9%. Post-test probabilities for the differential diagnosis of AE from liver neoplasias, CE from cystic liver lesions, and screening for AE in Switzerland were around 95, 86 and 2.2%, respectively. Cross-reactions with antibodies in sera of patients with other parasitic affections (fasciolosis, schistosomosis, amebosis, cysticercosis, and filarioses) did occur at variable frequencies, but could be eliminated through the use of confirmatory testing. CONCLUSIONS: Different metacestode-derived antigens of E. granulosus and E. multilocularis are valuable, widely accessible, and cost-efficient tools for the serological diagnosis of echinococcosis. However, confirmatory testing is necessary, due to the lack of species specificity and the occurrence of cross-reactions to other helminthic diseases.

Structural features in ODP Holes 128-794D and 128-799B

Numerous structural features occur in the Leg 128 cores from the Japan Sea. They include (1) gravity-induced structures such as slump folds, (2) dewatering structures comprising several sets of veins, and (3) larger faults and veins developed in the volcanic basement of the Yamato Basin as well as in the sedimentary rocks of the Oki Ridge and Kita-Yamato Trough. Gravity-induced structures, mainly slumps and associated faults, suggest the existence of paleoslopes and the dominance of gravitational tectonics during the early and middle Miocene, at the Pliocene/Pleistocene boundary, and during the Quaternary. Several types of mud-filled veins having various shapes were observed. These are especially abundant in the middle Miocene siliceous claystones and porcellanites from the Kita-Yamato Trough. They have been interpreted as dewatering conduits that formed preferentially in highly porous, water-saturated diatomaceous muds on a slope, because of episodic loss of sediment strength, collapse of the sediment framework, and consequent fluid migration. The central part of the vein serves once as a fluid conduit, whereas the transition between conduit-controlled and intergranular flow occurs at the branching extremities, with concentration of fines. The likely trigger responsible for the strength loss is seismic activity. Development of these veins, spatially and chronologically linked to small normal microfaults, implies an extensional regime having layer-parallel extension and a local bedding-parallel shear couple, probably the result of gravitational gliding. The brittle fractures found in Yamato Basin basement Hole 794D cores comprise joints, faults, and veins filled with chlorite-saponite, saponite, and calcite. They suggest a likely transpressive to transtensional regime around the early Miocene/ middle Miocene boundary, with a north-northeast-south-southwest compression alternating with a west-northwest-eastsoutheast extension. The faults from Site 799 cores on the Yamato Rise exhibit a prominent early Miocene-middle Miocene extensional environment, a late Miocene-early Pliocene phase of normal and strike-slip faulting, and a final phase that began during the latest Pliocene. Site 798, on the Oki Ridge, reveals faults that recorded a consistent extensional tectonic regime from Pliocene to the Holocene. These data support the pull-apart kinematic model for early Miocene-middle Miocene time, as regarding the stress regime deduced from the Yamato Basin basement fractures. The recent compression known in the eastern margin of the Japan Sea was not documented by compressive structures at any site. The late Miocene-early Pliocene faulting phase corresponds to a major and general reorganization of the stress distribution in the arc area. Evidence for rapid and main subsidence and synsedimentary extension of the Yamato Basin and Yamato Rise areas between 20 and 15 Ma, and the concomitant rotation of southwest Japan, raise the question of links between this opening and the Shimanto Belt collision in southwest Japan, between the arc and the Philippine Sea Plate.

Christian liberty /

Written as a devotional booklet to accompany a letter to Pope Leo X.

Birds of the Pymatuning region /

Includes index.

The Harvard classics /

Vols. 1-49 indexed in The Idexicon.

Goethes werke.

Mode of access: Internet.

Deutsche Grammatik /

Contiene: Erster Theil - Zweiter Theil - Dritter Theil (1831 - VIII, 788 p.) - Vierter Theil (1837 - VIII, 964 p.)

Joan Eckii ... De materia iuramenti accutiss[imi] decisio ad Georgium Kungspergium augustanum.

Mode of access: Internet.

Histoire naturelle des glacieres de Suisse /

Mode of access: Internet.

Deutsche Rechtsalterthümer /

Mode of access: Internet.