Fine and ultrafine particle number and size measurements from industrial combustion processes : primary emissions field data

This study is to our knowledge the first to present the results of on-line measurements of residual nanoparticle numbers downstream of the flue gas treatment systems of a wide variety of medium- and large-scale industrial installations. Where available, a semi-quantitative elemental composition of the sampled particles is carried out using a Scanning Electron Microscope coupled with an Energy Dispersive Spectrometer (SEM-EDS). The semi-quantitative elemental composition as a function of the particle size is presented. EU's Best Available Technology documents (BAT) show removal efficiencies of Electrostatic Precipitator (ESP) and bag filter dedusting systems exceeding 99% when expressed in terms of weight. Their efficiency decreases slightly for particles smaller than 1 mu m but when expressed in terms of weight, still exceeds 99% for bag filters and 96% for ESP. This study reveals that in terms of particle numbers, residual nanoparticles (NP) leaving the dedusting systems dominate by several orders of magnitude. In terms of weight, all installations respect their emission limit values and the contribution of NP to weight concentrations is negligible, despite their dominance in terms of numbers. Current World Health Organisation regulations are expressed in terms of PM2.5 wt concentrations and therefore do not reflect the presence or absence of a high number of NP. This study suggests that research is needed on possible additional guidelines related to NP given their possible toxicity and high potential to easily enter the blood stream when inhaled by humans

Trim17, novel E3 ubiquitin-ligase, initiates neuronal apoptosis

Accumulating data indicate that the ubiquitin-proteasome system controls apoptosis by regulating the level and the function of key regulatory proteins. In this study, we identified Trim17, a member of the TRIM/RBCC protein family, as one of the critical E3 ubiquitin ligases involved in the control of neuronal apoptosis upstream of mitochondria. We show that expression of Trim17 is increased both at the mRNA and protein level in several in vitro models of transcription-dependent neuronal apoptosis. Expression of Trim17 is controlled by the PI3K/Akt/GSK3 pathway in cerebellar granule neurons (CGN). Moreover, the Trim17 protein is expressed in vivo, in apoptotic neurons that naturally die during post-natal cerebellar development. Overexpression of active Trim17 in primary CGN was sufficient to induce the intrinsic pathway of apoptosis in survival conditions. This pro-apoptotic effect was abolished in Bax(-/-) neurons and depended on the E3 activity of Trim17 conferred by its RING domain. Furthermore, knock-down of endogenous Trim17 and overexpression of dominant-negative mutants of Trim17 blocked trophic factor withdrawal-induced apoptosis both in CGN and in sympathetic neurons. Collectively, our data are the first to assign a cellular function to Trim17 by showing that its E3 activity is both necessary and sufficient for the initiation of neuronal apoptosis. Cell Death and Differentiation (2010) 17, 1928-1941; doi: 10.1038/cdd.2010.73; published online 18 June 201

Bacterial porin disrupts mitochondrial membrane potential and sensitizes host cells to apoptosis

The bacterial PorB porin, an ATP-binding beta-barrel protein of pathogenic Neisseria gonorrhoeae, triggers host cell apoptosis by an unknown mechanism. PorB is targeted to and imported by host cell mitochondria, causing the breakdown of the mitochondrial membrane potential (delta psi m). Here, we show that PorB induces the condensation of the mitochondrial matrix and the loss of cristae structures, sensitizing cells to the induction of apoptosis via signaling pathways activated by BH3-only proteins. PorB is imported into mitochondria through the general translocase TOM but, unexpectedly, is not recognized by the SAM sorting machinery, usually required for the assembly of beta-barrel proteins in the mitochondrial outer membrane. PorB integrates into the mitochondrial inner membrane, leading to the breakdown of delta psi m. The PorB channel is regulated by nucleotides and an isogenic PorB mutant defective in ATP-binding failed to induce delta psi m loss and apoptosis, demonstrating that dissipation of delta psi m is a requirement for cell death caused by neisserial infection

Computational study of the mechanism of Bcl-2 apoptotic switch

Programmed cell death - apoptosis is one of the most studied biological phenomenon of recent years. Apoptotic regulatory network contains several significant control points, including probably the most important one - Bcl--2 apoptotic switch. There are two proposed hypotheses regarding its internal working - the indirect activation and direct activation models. Since these hypotheses form extreme poles of full continuum of intermediate models, we have constructed more general model with these two models as extreme cases. By studying relationship between model parameters and steady-state response ultrasensitivity we have found optimal interaction pattern which reproduces behavior of Bcl-2 apoptotic switch. Our results show, that stimulus-response ultrasensitivity is negatively related to spontaneous activation of Bcl-2 effectors - subgroup of Bcl-2 proteins. We found that ultrasensitivity requires effector's activation, mediated by another subgroup of Bcl-2 proteins - activators. We have shown that the auto-activation of effectors forms ultrasensitivity enhancing feedback loop, only if mediated by monomers, but not by oligomers. Robustness analysis revealed that interaction pattern proposed by direct activation hypothesis is able to conserve stimulus-response dependence and preserve ultrasensitivity despite large changes of its internal parameters. This ability is strongly reduced as for the intermediate to indirect side of the models. Computer simulation of the more general model presented here suggest, that stimulus-response ultrasensitivity is an emergent property of the direct activation model, that cannot originate within model of indirect activation. Introduction of indirect-model-specific interactions does not provide better explanation of Bcl-2 functioning compared to direct model

Reconstituer la ripisylve méditerranéenne (résumé).

En région méditerranéenne, et surtout dans les plaines où l'agriculture et la construction se disputent l'accès aux rivières, les ripisylves sont généralement très dégradées

Bcl-2 protein family: Implications in vascular apoptosis and atherosclerosis

Apoptosis has been recognized as a central component in the pathogenesis of atherosclerosis, in addition to the other human pathologies such as cancer and diabetes. The pathophysiology of atherosclerosis is complex, involving both apoptosis and proliferation at different phases of its progression. Oxidative modification of lipids and inflammation differentially regulate the apoptotic and proliferative responses of vascular cells during progression of the atherosclerotic lesion. Bcl-2 proteins act as the major regulators of extrinsic and intrinsic apoptosis signalling pathways and more recently it has become evident that they mediate the apoptotic response of vascular cells in response to oxidation and inflammation either in a provocative or an inhibitory mode of action. Here we address Bcl-2 proteins as major therapeutic targets for the treatment of atherosclerosis and underscore the need for the novel preventive and therapeutic interventions against atherosclerosis, which should be designed in the light of molecular mechanisms regulating apoptosis of vascular cells in atherosclerotic lesions

Global analysis of gene expression in NGF-deprived sympathetic neurons identifies molecular pathways associated with cell death

Developing sympathetic neurons depend on nerve growth factor (NGF) for survival and die by apoptosis after NGF withdrawal. This process requires de novo gene expression but only a small number of genes induced by NGF deprivation have been identified so far, either by a candidate gene approach or in mRNA differential display experiments. This is partly because it is difficult to obtain large numbers of sympathetic neurons for in vitro studies. Here, we describe for the first time, how advances in gene microarray technology have allowed us to investigate the expression of all known genes in sympathetic neurons cultured in the presence and absence of NGF

Nuclear translocation of cytochrome c during apoptosis

Release of cytochrome c from mitochondria is a major event during apoptosis. Released cytochrome c has been shown to activate caspase-dependent apoptotic signals. In this report, we provide evidence for a novel role of cytochrome c in caspase-independent nuclear apoptosis. We showed that cytochrome c, released from mitochondria upon apoptosis induction, gradually accumulates in the nucleus as evidenced by both immunofluorescence and subcellular fractionation. Parallel to nuclear accumulation of cytochrome c, acetylated histone H2A, but not unmodified H2A, was released from the nucleus to the cytoplasm. Addition of purified cytochrome c to isolated nuclei recapitulated the preferential release of acetylated, but not deacetylated, histone H2A. Cytochrome c was also found to induce chromatin condensation. These results suggest that the nuclear accumulation of cytochrome c may be directly involved in the remodeling of chromatin. Our results provide evidence of a novel role for cytochrome c in inducing nuclear apoptosis