MahmoudHamdanPier GiorgioRighettiProteomics TodayProtein Assessment and Biomarkers Using Mass Spectrometry, 2D Electrophoresis, and Microarray TechnologyWiley-Interscience Series on Mass Spectrometry2005John Wiley and Sons, IncHoboken, NJ, 07030 USAISBN 0-471-64817-5, Hardcover, $89.95, 426 pp.

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developing fragility and consequence models for buildings in the groningen field

AbstractThis paper describes the ongoing experimental and analytical activities that are being carried out to develop fatality and consequence models for the estimation of 'Inside Local Personal Risk' (ILPR) of buildings within the Groningen field. ILPR is defined as the annual probability of fatality for a hypothetical person who is continuously present without protection inside a building. In order to be able to estimate this risk metric, a robust estimate of the probability of collapse of structural and non-structural elements within a building is needed, as these have been found to be the greatest drivers of fatality risk.To estimate the collapse potential of buildings in Groningen, structural numerical models of a number of representative case studies have been developed and calibrated throughin situand laboratory testing on materials, connections, structural components and even full-scale buildings. These numerical models are then subjected to increased levels of ground shaking to estimate the probability of collapse, and the associated consequences are estimated from the observed collapse mechanisms

Deconvoluting heme biosynthesis to target blood-stage malaria parasites

Heme metabolism is central to blood-stage infection by the malaria parasite Plasmodium falciparum. Parasites retain a heme biosynthesis pathway but do not require its activity during infection of heme-rich erythrocytes, where they can scavenge host heme to meet metabolic needs. Nevertheless, heme biosynthesis in parasite-infected erythrocytes can be potently stimulated by exogenous 5-aminolevulinic acid (ALA), resulting in accumulation of the phototoxic intermediate protoporphyrin IX (PPIX). Here we use photodynamic imaging, mass spectrometry, parasite gene disruption, and chemical probes to reveal that vestigial host enzymes in the cytoplasm of Plasmodium-infected erythrocytes contribute to ALA-stimulated heme biosynthesis and that ALA uptake depends on parasite-established permeability pathways. We show that PPIX accumulation in infected erythrocytes can be harnessed for antimalarial chemotherapy using luminol-based chemiluminescence and combinatorial stimulation by low-dose artemisinin to photoactivate PPIX to produce cytotoxic reactive oxygen. This photodynamic strategy has the advantage of exploiting host enzymes refractory to resistance-conferring mutations. DOI: http://dx.doi.org/10.7554/eLife.09143.00

A database of damaging small-to-medium magnitude earthquakes

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Malaria parasites produce volatile mosquito attractants

UnlabelledThe malaria parasite Plasmodium falciparum contains a nonphotosynthetic plastid organelle that possesses plant-like metabolic pathways. Plants use the plastidial isoprenoid biosynthesis pathway to produce volatile odorants, known as terpenes. In this work, we describe the volatile chemical profile of cultured malaria parasites. Among the identified compounds are several plant-like terpenes and terpene derivatives, including known mosquito attractants. We establish the molecular identity of the odorant receptors of the malaria mosquito vector Anopheles gambiae, which responds to these compounds. The malaria parasite produces volatile signals that are recognized by mosquitoes and may thereby mediate host attraction and facilitate transmission.ImportanceMalaria is a key global health concern. Mosquitoes that transmit malaria are more attracted to malaria parasite-infected mammalian hosts. These studies aimed to understand the chemical signals produced by malaria parasites; such an understanding may lead to new transmission-blocking strategies or noninvasive malaria diagnostics

A two-channel, Thermal Dissociation Cavity-Ringdown Spectrometer for the detection of ambient NO2, RO2NO2 and RONO2

Creative Commons Attribution License 3.0We describe a thermal dissociation cavity ring-down spectrometer (TD-CRDS) for measurement of ambient NO2, total peroxy nitrates (ΣPNs) and total alkyl nitrates (ΣANs). The spectrometer has two separate cavities operating at  ∼  405.2 and 408.5 nm. One cavity (reference) samples NO2 continuously from an inlet at ambient temperature, the other samples sequentially from an inlet at 473 K in which PNs are converted to NO2 or from an inlet at 723 K in which both PNs and ANs are converted to NO2, difference signals being used to derive mixing ratios of ΣPNs and ΣANs. We describe an extensive set of laboratory experiments and numerical simulations to characterise the fate of organic radicals in the hot inlets and cavity and derive correction factors to account for the bias resulting from the interaction of peroxy radicals with ambient NO and NO2. Finally, we present the first measurements and comparison with other instruments during a field campaign, outline the limitations of the present instrument and provide an outlook for future improvements.Publication funded by the Max Planck Societ

Exploiting macrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis

Macrophages specialize in removing lipids and debris present in the atherosclerotic plaque. However, plaque progression renders macrophages unable to degrade exogenous atherogenic material and endogenous cargo including dysfunctional proteins and organelles. Here we show that a decline in the autophagy-lysosome system contributes to this as evidenced by a derangement in key autophagy markers in both mouse and human atherosclerotic plaques. By augmenting macrophage TFEB, the master transcriptional regulator of autophagy-lysosomal biogenesis, we can reverse the autophagy dysfunction of plaques, enhance aggrephagy of p62-enriched protein aggregates and blunt macrophage apoptosis and pro-inflammatory IL-1β levels, leading to reduced atherosclerosis. In order to harness this degradative response therapeutically, we also describe a natural sugar called trehalose as an inducer of macrophage autophagy-lysosomal biogenesis and show trehalose's ability to recapitulate the atheroprotective properties of macrophage TFEB overexpression. Our data support this practical method of enhancing the degradative capacity of macrophages as a therapy for atherosclerotic vascular disease

Escherichia coli biofilms have an organized and complex extracellular matrix structure

Bacterial biofilms are ubiquitous in nature, and their resilience is derived in part from a complex extracellular matrix that can be tailored to meet environmental demands. Although common developmental stages leading to biofilm formation have been described, how the extracellular components are organized to allow three-dimensional biofilm development is not well understood. Here we show that uropathogenic Escherichia coli (UPEC) strains produce a biofilm with a highly ordered and complex extracellular matrix (ECM). We used electron microscopy (EM) techniques to image floating biofilms (pellicles) formed by UPEC. EM revealed intricately constructed substructures within the ECM that encase individual, spatially segregated bacteria with a distinctive morphology. Mutational and biochemical analyses of these biofilms confirmed curli as a major matrix component and revealed important roles for cellulose, flagella, and type 1 pili in pellicle integrity and ECM infrastructure. Collectively, the findings of this study elucidated that UPEC pellicles have a highly organized ultrastructure that varies spatially across the multicellular community