Proteomic approach in the search of new cardiovascular biomarkers

Proteomic approach in the search of new cardiovascular biomarkers With the increasing incidence of cardiovascular diseases worldwide, specifically atherosclerosis and heart failure, the search for novel biomarkers remains a priority. As opposed to complex diagnostic techniques that may not be suitable to be applied to the wider population, biomarkers are useful for population screening. The search for novel biomarkers is based on knowledge of the molecular and cellular processes that take place in the development of a specific disease. Atherosclerosis and heart failure are characterized by a long period of silent disease progression, allowing early diagnosis and the potential of early therapeutic intervention. The use of the so-called proteomic techniques allows not only protein identification but partial characterization, which includes expression and also post-translational modification of these proteins. This allows for the discovery of previously unknown proteins involved in cardiovascular diseases, including some that may be suitable to be used as biomarkers. However, to approach this issue, we have to overcome difficulties such as tissue heterogeneity (vessel wall or myocardium) and the lack of fresh human samples. We discuss the proteomic study of human plaques, secreted proteins by pathologic and normal vessel wall, and left ventricular hypertrophy as potential sources of new biologic markers of cardiovascular disease

Quantifying the potential exposure hazard due to energetic releases of CO2 from a failed sequestration well

AbstractWells are designed to bring fluids from depth to the earth’s surface quickly. As such they are the most likely pathway for CO2 to return to the surface in large quantities and present a hazard without adequate management. We surveyed oil industry experience of CO2 well failures, and separately, calculated the maximal CO2 flow rate from a 5000 ft depth supercritical CO2 reservoir. The calculated maximum of 20,000 tonne/day was set by the sound speed and the seven-inch well casing diameter, and was greater than any observed event. We used this flux to simulate atmospheric releases and the associated hazard utilizing the National Atmospheric Release Advisory Center (NARAC) tools and real meteorology at a representative location in the High Plains of the United States. Three cases representing a maximum hazard day (quiet winds <1 m s−1 near the wellhead) and medium and minimal hazard days (average winds 3 m s−1 and 7 m s−1) were assessed. As expected for such large releases, there is a near-well hazard when there is little or no wind. In all three cases the hazardous Temporary Emergency Exposure Levels (TEEL) 2 or 3 only occurred within the first few hundreds of meters. Because the preliminary 3-D model runs may not have been run at high enough resolution to accurately simulate very small distances, we also used a simple Gaussian plume model to provide an upper bound on the distance at which hazardous conditions might exist. This extremely conservative model, which ignores inhomogeneity in the mean wind and turbulence fields, also predicts possible hazardous concentrations up to several hundred meters downwind from a maximal release

The Gothenburg Protocol: Projections, Expectations and Realities: Lessons from a National Review

The Gothenburg Protocol entered into force on the 17th of May 2005, with 24 Parties ratifying the proposed emission ceilings for a range of transboundary pollutants. These ceilings were themselves formulated in 1999 using the RAINS integrated assessment model and a broad base of relevant forecasts and calibration data. In the intervening nine years, with the 2010 ceiling deadline approaching and a potential review for a new round of future emission ceilings, there is an opportunity to review the earlier work and consider the lessons for future processes. This paper considers the original projections and expectations associated with the Gothenburg Protocol emission ceilings for six countries and contrasts these against the current realities and contemporary short-term forecasts out to 2010. In this process, the paper derives a number of considerations and lessons to be considered for future agreements of this nature

New compound sets identified from high throughput phenotypic screening against three kinetoplastid parasites:an open resource

Using whole-cell phenotypic assays, the GlaxoSmithKline high-throughput screening (HTS) diversity set of 1.8 million compounds was screened against the three kinetoplastids most relevant to human disease, i.e. Leishmania donovani, Trypanosoma cruzi and Trypanosoma brucei. Secondary confirmatory and orthogonal intracellular anti-parasiticidal assays were conducted, and the potential for non-specific cytotoxicity determined. Hit compounds were chemically clustered and triaged for desirable physicochemical properties. The hypothetical biological target space covered by these diversity sets was investigated through bioinformatics methodologies. Consequently, three anti-kinetoplastid chemical boxes of ~200 compounds each were assembled. Functional analyses of these compounds suggest a wide array of potential modes of action against kinetoplastid kinases, proteases and cytochromes as well as potential host–pathogen targets. This is the first published parallel high throughput screening of a pharma compound collection against kinetoplastids. The compound sets are provided as an open resource for future lead discovery programs, and to address important research questions.The support and funding of Tres Cantos Open Lab Foundation is gratefully acknowledgedPeer reviewe

The ISLANDS project I: Andromeda XVI, An Extremely Low Mass Galaxy not Quenched by Reionization

Based on data aquired in 13 orbits of HST time, we present a detailed evolutionary history of the M31 dSph satellite Andromeda XVI, including its life-time star formation history, the spatial distribution of its stellar populations, and the properties of its variable stars. And XVI is characterized by prolonged star formation activity from the oldest epochs until star formation was quenched ~6 Gyr ago, and, notably, only half of the mass in stars of And XVI was in place 10 Gyr ago. And XVI appears to be a low mass galaxy for which the early quenching by either reionization or starburst feedback seems highly unlikely, and thus, is most likely due to an environmental effect (e.g., an interaction), possibly connected to a late infall in the densest regions of the Local Group. Studying the star formation history as a function of galactocentric radius, we detect a mild gradient in the star formation history: the star formation activity between 6 and 8 Gyr ago is significantly stronger in the central regions than in the external regions, although the quenching age appears to be the same, within 1 Gyr. We also report the discovery of 9 RR Lyrae stars, 8 of which belong to And XVI. The RR Lyrae stars allow a new estimate of the distance, (m-M)0= 23.72+/-0.09 mag, which is marginally larger than previous estimates based on the tip of the red giant branch.Comment: Accepted for publication on Ap

The ISLAndS project II: The Lifetime Star Formation Histories of Six Andromeda dSphs

The Initial Star formation and Lifetimes of Andromeda Satellites (ISLAndS) project uses Hubble Space Telescope imaging to study a representative sample of six Andromeda dSph satellite companion galaxies. The main goal of the program is to determine whether the star formation histories (SFHs) of the Andromeda dSph satellites demonstrate significant statistical differences from those of the Milky Way, which may be attributable to the different properties of their local environments. Our observations reach the oldest main sequence turn-offs, allowing a time resolution at the oldest ages of ~ 1 Gyr, which is comparable to the best achievable resolution in the MW satellites. We find that the six dSphs present a variety of SFHs that are not strictly correlated with luminosity or present distance from M31. Specifically, we find a significant range in quenching times (lookback times from 9 to 6 Gyr), but with all quenching times more than ~ 6 Gyr ago. In agreement with observations of Milky Way companions of similar mass, there is no evidence of complete quenching of star formation by the cosmic UV background responsible for reionization, but the possibility of a degree of quenching at reionization cannot be ruled out. We do not find significant differences between the SFHs of the three members of the vast, thin plane of satellites and the three off-plane dSphs. The primary difference between the SFHs of the ISLAndS dSphs and Milky Way dSph companions of similar luminosities and host distances is the absence of very late quenching (< 5 Gyr ago) dSphs in the ISLAndS sample. Thus, models that can reproduce satellite populations with and without late quenching satellites will be of extreme interest.Comment: 24 pages, 11 figures, 3 tables, submitted to the Ap

The Pisces Plume and the Magellanic wake

Using RR Lyrae stars in the Gaia Data Release 2 and Pan-STARRS1 we study the properties of the Pisces overdensity, a diffuse substructure in the outer halo of the Milky Way. We show that along the line of sight, Pisces appears as a broad and long plume of stars stretching from 40 to 110 kpc with a steep distance gradient. On the sky Pisces’s elongated shape is aligned with the Magellanic Stream. Using follow-up VLT FORS2 spectroscopy, we have measured the velocity distribution of the Pisces candidate member stars and have shown it to be as broad as that of the Galactic halo but offset to negative velocities. Using a suite of numerical simulations, we demonstrate that the structure has many properties in common with the predicted behaviour of the Magellanic wake, i.e. the Galactic halo overdensity induced by the infall of the Magellanic Clouds

Towards the understanding of the cocoa transcriptome: Production and analysis of an exhaustive dataset of ESTs of Theobroma cacao L. generated from various tissues and under various conditions

Theobroma cacao L., is a tree originated from the tropical rainforest of South America. It is one of the major cash crops for many tropical countries. T. cacao is mainly produced on smallholdings, providing resources for 14 million farmers. Disease resistance and T. cacao quality improvement are two important challenges for all actors of cocoa and chocolate production. T. cacao is seriously affected by pests and fungal diseases, responsible for more than 40% yield losses and quality improvement, nutritional and organoleptic, is also important for consumers. An international collaboration was formed to develop an EST genomic resource database for cacao. Fifty-six cDNA libraries were constructed from different organs, different genotypes and different environmental conditions. A total of 149,650 valid EST sequences were generated corresponding to 48,594 unigenes, 12,692 contigs and 35,902 singletons. A total of 29,849 unigenes shared significant homology with public sequences from other species. Gene Ontology (GO) annotation was applied to distribute the ESTs among the main GO categories. A specific information system (ESTtik) was constructed to process, store and manage this EST collection allowing the user to query a database. To check the representativeness of our EST collection, we looked for the genes known to be involved in two different metabolic pathways extensively studied in other plant species and important for T. cacao qualities: the flavonoid and the terpene pathways. Most of the enzymes described in other crops for these two metabolic pathways were found in our EST collection. A large collection of new genetic markers was provided by this ESTs collection. This EST collection displays a good representation of the T. cacao transcriptome, suitable for analysis of biochemical pathways based on oligonucleotide microarrays derived from these ESTs. It will provide numerous genetic markers that will allow the construction of a high density gene map of T. cacao. This EST collection represents a unique and important molecular resource for T. cacao study and improvement, facilitating the discovery of candidate genes for important T. cacao trait variation. (Résumé d'auteur

Laboratory estimation of black carbon emissions from cookstoves

Recent estimations show that residential solid fuel combustion accounts for 25% of global black carbon (BC) emissions (Lamarque et al., 2010). Thus, the control of these emissions through the implementation of cleaner cooking technologies could be crucial for climate change mitigation (Venkataraman et al., 2005). However, BC emission factors for biofuel cooking stoves have been poorly estimated due to the wide distribution and remote location of the stoves and the relatively complex existing assessment methods. This work presents results on BC emission factors (EF) estimation from combustion of biomass cooking systems in Western Africa (in Senegal). Three stones fire (traditional stove), Noflaye Jegg (rocket stove), Jambaar bois (ceramic improved stove) and a gasifier were analysed under laboratory conditions at the Centre de Recherche sur les Energies Renouvelables (CERER) in Dakar. Two types of fuels (wood species) were tested: Casuarina Equisetifolia (Filao) and Cordyla Pinnata (Dimb). Three replicates of the standardized Water Boiling Test with two phases (cold start and simmer) were conducted at the laboratory to test each cooking system. PM2.5 emissions were collected on quartz fibre filters, and BC content was subsequently analysed using three analytical methods: i) Nexleaf system, in which a photograph of the filter is compared with a calibrated reference scale; ii) the EEL43 Smoke Stain Reflectometer; and iii) the Sunset Laboratory OCEC Analyzer. The two first were compared with the third one, considered the internal reference