Neurotoxicité des pesticides : quel impact sur les maladies neurodégénératives ?

Several epidemiological studies suggest that pesticides could lead to neurodegenerative diseases such as Parkinson\u27s and Alzheimer\u27s diseases. Among pesticides, insecticides appear more neurotoxic than others but the neurotoxic mechanisms leading to adverse health effects remain unclear. The currently used pesticides such as rotenone and paraquat could disrupt mitochondrial bioenergetic function, reactive oxygen metabolism, redox function and promote alpha-synuclein aggregation. In addition, recent studies demonstrate that genetic susceptibility to Parkinson\u27s disease could monitor pesticide susceptibility, as demonstrated for polymorphisms in pesticide metabolizing enzymes that are involved in organophosphorus sensitivity

The imprints of bars on the vertical stellar population gradients of galactic bulges

This is the second paper of a series aimed to study the stellar kinematics and population properties of bulges in highly-inclined barred galaxies. In this work, we carry out a detailed analysis of the stellar age, metallicity and [Mg/Fe] of 28 highly-inclined ($i > 65^{o}$) disc galaxies, from S0 to S(B)c, observed with the SAURON integral-field spectrograph. The sample is divided into two clean samples of barred and unbarred galaxies, on the basis of the correlation between the stellar velocity and h$_3$ profiles, as well as the level of cylindrical rotation within the bulge region. We find that while the mean stellar age, metallicity and [Mg/Fe] in the bulges of barred and unbarred galaxies are not statistically distinct, the [Mg/Fe] gradients along the minor axis (away from the disc) of barred galaxies are significantly different than those without bars. For barred galaxies, stars that are vertically further away from the midplane are in general more [Mg/Fe]--enhanced and thus the vertical gradients in [Mg/Fe] for barred galaxies are mostly positive, while for unbarred bulges the [Mg/Fe] profiles are typically negative or flat. This result, together with the old populations observed in the barred sample, indicates that bars are long-lasting structures, and therefore are not easily destroyed. The marked [Mg/Fe] differences with the bulges of unbarred galaxies indicate that different formation/evolution scenarios are required to explain their build-up, and emphasizes the role of bars in redistributing stellar material in the bulge dominated regions.Comment: 22 pages, 7 main body figures +8 appendix figures, 2 tables. Accepted by MNRA

Updated review of postmortem biochemical exploration of hypothermia with a presentation of standard strategy of sampling and analyses.

Hypothermia is defined as a core body temperature below 35°C and can be caused by environmental exposure, drug intoxication, metabolic or nervous system dysfunction. This lethal pathology with medico-legal implications is complex to diagnose because macroscopic and microscopic lesions observed at the autopsy and the histological analysis are suggestive but not pathognomonic. Postmortem biochemical explorations have been progressively developed through the study of several biomarkers to improve the diagnosis decision cluster. Here, we present an updated review with novel biomarkers (such as catecholamines O-methylated metabolites, thrombomodulin and the cardiac oxyhemoglobin ratio) as well as some propositional interpretative postmortem thresholds and, to the best of our knowledge, for the first time, we present the most adapted strategy of sampling and analyses to identify biomarkers of hypothermia. For our consideration, the most relevant identified biomarkers are urinary catecholamines and their O-methylated metabolites, urinary free cortisol, blood cortisol, as well as blood, vitreous humor and pericardial fluid for ketone bodies and blood free fatty acids. These biomarkers are increased in response either to cold-mediated stress or to bioenergetics ketogenesis crisis and significantly contribute to the diagnosis by exclusion of death by hypothermia

Approaching the Coverability Problem Continuously

The coverability problem for Petri nets plays a central role in the verification of concurrent shared-memory programs. However, its high EXPSPACE-complete complexity poses a challenge when encountered in real-world instances. In this paper, we develop a new approach to this problem which is primarily based on applying forward coverability in continuous Petri nets as a pruning criterion inside a backward coverability framework. A cornerstone of our approach is the efficient encoding of a recently developed polynomial-time algorithm for reachability in continuous Petri nets into SMT. We demonstrate the effectiveness of our approach on standard benchmarks from the literature, which shows that our approach decides significantly more instances than any existing tool and is in addition often much faster, in particular on large instances.Comment: 18 pages, 4 figure

SAURON Observations of Disks in Early-Type Galaxies

We briefly describe the SAURON project, aimed at determining the intrinsic shape and internal dynamics of spheroids. We focus here on the ability of SAURON to identify gaseous and stellar disks and to measure their morphology and kinematics. We illustrate some of our results with complete maps of NGC3377, NGC3623, and NGC4365.Comment: 4 pages, 4 figures (newpasp.sty). To appear in ASP Conf. Series "Galaxy Disks and Disk Galaxies", eds. J.G. Funes S.J. & E.M. Corsini. Version with full resolution images available at http://www.strw.leidenuniv.nl/~bureau/pub_list.htm

Métabolomique et spectrométrie de masse : de nouvelles perspectives en analyse biomédicale

Metabolomics is defined as an integrative approach consisting in the comprehensive analysis of all of the small molecules of a biological system (the "metabolome"). The main objective of metabolomics in medecine is to discover metabolic biomarkers for diseases. Mass spectrometry (MS) coupled to liquid or gas chromatography is amongst major analytical tools used in metabolomics. However, the holistic approach used in metabolomics requires very good performances of the analytical system (chromatographic column and MS equipment) and the use of non-conventional validation strategies. Metabolomics workflow can be divided in three main steps: sample preparation, MS data acquisition and processing, and statistical analysis. Processing of the "raw" data (obtained after MS acquisition) is mostly required to normalise chromatographic conditions and to carry out accurate quantification of MS features. Features resulting from this processing may be identified later. The statistical analyses include typically multivariate techniques such as supervised and non-supervised methods. Supervised methods make use of the response variable (e.g., case/control) for model construction while non-supervised methods do not use this piece of information. When the study is focused on a particular set of metabolites, targeted metabolomics could be an interesting alternative to the holistic approach since it may allow absolute quantitation and be associated with a reduced cost

Commentary: The proposed legislation on termination of pregnancy does not protect women or children in Malawi and is not fit for the intended purpose: Christian Medical and Dental Fellowshipi position

No Abstrac

Metabolomics and Lipidomics Profiling of a Combined Mitochondrial Plus Endoplasmic Reticulum Fraction of Human Fibroblasts: A Robust Tool for Clinical Studies

Mitochondria and endoplasmic reticulum (ER) are physically and functionally connected. This close interaction, via mitochondria-associated membranes, is increasingly explored and supports the importance of studying these two organelles as a whole. Metabolomics and lipidomics are powerful approaches for the exploration of metabolic pathways that may be useful to provide deeper information on these organelles\u27 functions, dysfunctions, and interactions. We developed a quick and simple experimental procedure for the purification of a mitochondria-ER fraction from human fibroblasts. We applied combined metabolomics and lipidomics analyses by mass spectrometry with excellent reproducibility. Seventy-two metabolites and 418 complex lipids were detected with a mean coefficient of variation around 12%, among which many were specific to the mitochondrial metabolism. Thus this strategy based on robust mitochondria-ER extraction and "omics" combination will be useful for investigating the pathophysiology of complex diseases

OPA1 functions in mitochondria and dysfunctions in optic nerve

OPA1 is the major gene responsible for Dominant Optic Atrophy (DOA), a blinding disease that affects specifically the retinal ganglion cells (RGCs), which function consists in connecting the neuro-retina to the brain. OPA1 encodes an intra-mitochondrial dynamin, involved in inner membrane structures and ubiquitously expressed, raising the critical question of the origin of the disease pathophysiology. Here, we review the fundamental knowledge on OPA1 functions and regulations, highlighting their involvements in mitochondrial respiration, membrane dynamic and apoptosis. In light of these functions, we then describe the remarkable RGC mitochondrial network physiology and analyse data collected from animal models expressing OPA1 mutations. If, to date RGC mitochondria does not present any peculiarity at the molecular level, they represent possible targets of numerous assaults, like light, pressure, oxidative stress and energetic impairment, which jeopardize their function and survival, as observed in OPA1 mouse models. Although fascinating fields of investigation are still to be addressed on OPA1 functions and on DOA pathophysiology, we have reached a conspicuous state of knowledge with pertinent cell and animal models, from which therapeutic trials can be initiated and deeply evaluated

Optical/NIR stellar absorption and emission-line indices from luminous infrared galaxies

We analyze a set of optical-to-near-infrared long-slit nuclear spectra of 16 infrared-luminous spiral galaxies. All of the studied sources present H$_2$ emission, which reflects the star-forming nature of our sample, and they clearly display H I emission lines in the optical. Their continua contain many strong stellar absorption lines, with the most common features due to Ca I, Ca II, Fe I, Na I, Mg I, in addition to prominent absorption bands of TiO, VO, ZrO, CN and CO. We report a homogeneous set of equivalent width (EW) measurements for 45 indices, from optical to NIR species for the 16 star-forming galaxies as well as for 19 early type galaxies where we collected the data from the literature. This selected set of emission and absorption-feature measurements can be used to test predictions of the forthcoming generations of stellar population models. We find correlations among the different absorption features and propose here correlations between optical and NIR indices, as well as among different NIR indices, and compare them with model predictions. While for the optical absorption features the models consistently agree with the observations,the NIR indices are much harder to interpret. For early-type spirals the measurements agree roughly with the models, while for star-forming objects they fail to predict the strengths of these indices.Comment: accepted for publication in MNRA