Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid

Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria

How water retention in porous media with cellulose ethers works

Cellulose ethers (CE) are widely used in mortars as water retaining agents; however the cause of retention remains unknown. This paper attempts to clarify the involved mechanisms using several macroscopic experiments (water retention WR standard tests, imbibition and filtration tests). We highlight that WR is not specific to cement but occurs for every porous media. Then, using model porous media and different fluids we point out a critical mechanism of WR with CE solutions: a jamming effect during water transport through the porous medium. This effect may be explained by the presence of polydisperse aggregates which result from native cellulose or hydrophobic interactions. Finally we present a statistical model for filtration which predicts all the qualitative trends observed experimentally. 2012 Elsevier Ltd. All rights reserved

Key role of receptor density in colloid/cell specific interaction: a quantitative biomimetic study on giant vesicles

This paper presents an experimental study of the adsorption of colloids on model membranes mediated by specific ligand-receptor interactions. The colloids consist of lipid multilamellar liposomes (spherulites) functionalized with the B-subunit of Shiga Toxin (STxB), while the membranes are lipid Giant Unilamellar Vesicles (GUV) containing STxB lipid receptor, Globotriaosylceramide (Gb3). Through confocal microscopy and flow cytometry, we show the specificity of the adsorption. Moreover, we show that flow cytometry can be used to efficiently quantify the kinetics of colloid adsorption on GUVs with very good statistics. By varying the bulk colloid concentration and receptor density in the membrane, we point out the existence of an optimum Gb3 density for adsorption. We propose that this optimum corresponds to a transition between reversible colloid adsorption at low Gb3 density and irreversible adsorption, and likely spherulite fusion, at high density. We compare our results both to STxB-colloids adhering on living cells and to free STxB proteins interacting with GUVs containing Gb3. This biomimetic system could be used for a quantitative evaluation of the early stage of virus infection or drug delivery

Economic Issues and Methodology in Arms Race Analysis

This article reviews the recent contributions of economic analysis to the literature concerned with the process of national arms accumulation and the potential for arms control and disarmament. The role of formal model building as an aid to understanding the armament process is discussed. The existing economic literature in this area is organized and reviewed on the basis of the different modeling approaches that have been explored to date. Finally, strands of economic thought that have not yet been introduced into the arms race literature are explored, with the purpose of suggesting further applications of the economic approach to this important area of analysis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66574/2/10.1177_0022002785029003006.pd

Transporte intra-hospitalar de pacientes sob ventilação invasiva: repercussões cardiorrespiratórias e eventos adversos Intrahospital transport of patients on invasive ventilation: cardiorespiratory repercussions and adverse events

OBJETIVO: Verificar a ocorrência de alterações cardiorrespiratórias e identificar eventos adversos durante o transporte intra-hospitalar de pacientes sob ventilação invasiva. MÉTODOS: Estudo observacional prospectivo não-randomizado, conduzido em dois hospitais terciários, entre abril de 2005 e dezembro de 2006. Foram incluídos pacientes sob ventilação invasiva que necessitaram de transporte intra-hospitalar durante o período do estudo. Os critérios de exclusão foram: estar sob suspeita de morte encefálica; ter sido submetido a períodos de ventilação mecânica e de nebulização em tubo T; e ter sido transportado para o centro cirúrgico. Antes e após o transporte, os seguintes parâmetros foram avaliados: gasometria arterial, sinais vitais, uso de medicamentos através de uma bomba de infusão contínua, parâmetros do ventilador mecânico, duração do transporte, distância percorrida e número de profissionais envolvidos. RESULTADOS: Foram incluídos 48 pacientes, num total de 58 transportes. Observou-se alteração cardiorrespiratória importante em 39 transportes, totalizando 86 episódios, assim como 16 eventos adversos relacionados à falha de equipamento e falha da equipe, dentre eles problemas com baterias e falhas de comunicação. CONCLUSÕES: Durante o transporte intra-hospitalar de pacientes submetidos à ventilação invasiva, alterações cardiorrespiratórias foram frequentes (67,2%), e eventos adversos ocorreram em 75,7% dos transportes realizados.<br>OBJECTIVE: To determine the occurrence of cardiorespiratory alterations and to identify adverse events during the intrahospital transport of patients on invasive ventilation. METHODS: A prospective observational non-randomized study was conducted at two tertiary hospitals between April of 2005 and December of 2006. We included patients on invasive ventilation who required intrahospital transport during the study period. Exclusion criteria were as follows: being under suspicion of brain death; being submitted to alternate periods of mechanical ventilation/nebulization via a T-piece; and being transported to the operating room. Prior to and after transport, we evaluated blood gas analysis results, vital signs, use of medications by means of a continuous infusion pump, parameters regarding the mechanical ventilator, duration of transport, transport distance and number of professionals involved. RESULTS: We included 48 patients in a total of 58 intrahospital transports. Relevant cardiorespiratory alterations were identified in 39 transports, totaling 86 episodes, as well as 16 adverse events related to equipment or personnel failure, such as problems related to batteries and to miscommunication. CONCLUSIONS: During the intrahospital transport of patients on invasive ventilation, cardiorespiratory alterations were common (67.2%), and adverse events occurred in 75.7% of the transports