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Biomedical subjects

Pascal Martin

Publications and source records attributed to Pascal Martin.

13 recordsLinked to original sources
PubMed2006

Chronic high-fat diet affects intestinal fat absorption and postprandial triglyceride levels in the mouse.

The effects of chronic fat overconsumption on intestinal physiology and lipid metabolism remain elusive. It is unknown whether a fat-mediated adaptation to lipid absorption takes place. To address this issue, mice fed a high-fat diet (40%, w/w) were refed or not a control diet (3%, w/w) for 3 additive weeks. Despite daily lipid intake 7.7-fold higher than in controls, fecal lipid output remained unchanged in mice fed the triglyceride (TG)-rich diet. In situ isolated jejunal loops revealed greater [1-(14)C]linoleic acid uptake without TG accumulation in mucosa, suggesting an increase in lipid absorption capacity. Induction both in intestinal mitotic index and in the expression of genes involved in fatty acid uptake, trafficking, and lipoprotein synthesis was found in high-fat diet mice. These changes were lipid-mediated, in that they were fully abolished in mice refed the control diet. A lipid load test performed in the presence or absence of the LPL inhibitor tyloxapol showed a sustained blood TG clearance in fat-fed mice likely attributable to intestinal modulation of LPL regulators (apolipoproteins C-II and C-III). These data demonstrate that a chronic high-fat diet greatly affects intestinal physiology and body lipid use in the mouse.

Animals↗
PubMed2006

Nonparametric statistical snake based on the minimum stochastic complexity.

We propose a nonparametric statistical snake technique that is based on the minimization of the stochastic complexity (minimum description length principle). The probability distributions of the gray levels in the different regions of the image are described with step functions with parameters that are estimated. The segmentation is thus obtained by minimizing a criterion that does not include any parameter to be tuned by the user. We illustrate the robustness of this technique on various types of images with level set and polygonal contour models. The efficiency of this approach is also analyzed in comparison with parametric statistical techniques.

Algorithms↗
PubMed2005

Displacement of an herbaceous plant species community by mycorrhizal and non-mycorrhizal Gmelina arborea, an exotic tree, grown in a microcosm experiment.

Gmelina arborea Roxb. (Gmelina, Yemane) is a fast growing tree, native from India and considered as a potentially invasive woody plant in West Africa. Mycorrhizal inoculation of seedlings with Glomus intraradices was performed to study (1) the effect on the growth of G. arborea, (2) the impact on the catabolic diversity of soil microbial communities and (3) the influence on the structure of herbaceous plant species communities in microcosms. Treatments consisted of control plants, pre-planting fertilizer application and arbuscular mycorrhizal (AM) inoculation. After 4 months' culture in autoclaved soil, G. arborea seedlings were either harvested for growth measurement or transferred into containers filled with the same soil but not sterilized. Other containers were kept without G. arborea seedlings. After 12 months' further culture, effects of fertilizer amendment and AM inoculation on the growth of G. arborea seedlings were recorded. AM colonization was significantly and positively correlated with plant diversity. The substrate-induced respiration response to carboxylic acids was significantly higher in the absence of G. arborea and in the presence of G. intraradices as compared to the other treatments. The influence of AM symbiosis on plant coexistence and on allelopathic processes of invasive plants are discussed.

Lamiaceae↗
PubMed2005

Liquid mechanical behavior of mixed monolayers of amino and alkyl silanes by atomic force microscopy.

The adsorption of mixed terminally aminated organosilyl compounds with long-chain n-alkyltrichlorosilanes on silica substrates has been studied by FTIR and AFM to deposit and study DNA. By optimization of deposition conditions, the mixed monolayers were found to be well organized and homogeneous. The amino group was protected to obtain a reproducible grafting and then deprotected after the film formation. In addition, atomic force microscopy (AFM) studies in both dynamical modes, amplitude modulation and frequency modulation, reveal that the layer behaves as a fluid as measured by the tip-cantilever and has a smaller characteristic time than the tip-cantilever. For three amplitudes, the experimental frequency shifts have been modeled for a fluidlike layer crossed by the tip. Finally, we show that this new fluidlike monolayer is suitable for DNA deposition and AFM studies.

Microscopy, Atomic Force↗
PubMed2005

Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia.

Vitamin D controls calcium homeostasis and the development and maintenance of bones through vitamin D receptor activation. Prolonged therapy with rifampicin or phenobarbital has been shown to cause vitamin D deficiency or osteomalacia, particularly in patients with marginal vitamin D stores. However, the molecular mechanism of this process is unknown. Here we show that these drugs lead to the upregulation of 25-hydroxyvitamin D(3)-24-hydroxylase (CYP24) gene expression through the activation of the nuclear receptor pregnane X receptor (PXR; NR1I2). CYP24 is a mitochondrial enzyme responsible for inactivating vitamin D metabolites. CYP24 mRNA is upregulated in vivo in mice by pregnenolone 16alpha-carbonitrile and dexamethasone, 2 murine PXR agonists, and in vitro in human hepatocytes by rifampicin and hyperforin, 2 human PXR agonists. Moreover, rifampicin increased 24-hydroxylase activity in these cells, while, in vivo in mice, pregnenolone 16alpha-carbonitrile increased the plasma concentration of 24,25-dihydroxyvitamin D(3). Transfection of PXR in human embryonic kidney cells resulted in rifampicin-mediated induction of CYP24 mRNA. Analysis of the human CYP24 promoter showed that PXR transactivates the sequence between -326 and -142. We demonstrated that PXR binds to and transactivates the 2 proximal vitamin D-responsive elements of the human CYP24 promoter. These data suggest that xenobiotics and drugs can modulate CYP24 gene expression and alter vitamin D(3) hormonal activity and calcium homeostasis through the activation of PXR.

Animals↗
PubMed2004

Active hair-bundle motility harnesses noise to operate near an optimum of mechanosensitivity.

The ear relies on nonlinear amplification to enhance its sensitivity and frequency selectivity to oscillatory mechanical stimuli. It has been suggested that this active process results from the operation of dynamical systems that operate in the vicinity of an oscillatory instability, a Hopf bifurcation. In the bullfrog's sacculus, a hair cell can display spontaneous oscillations of its mechanosensory hair bundle. The behavior of an oscillatory hair bundle resembles that of a critical oscillator. We present here a theoretical description of the effects of intrinsic noise on active hair-bundle motility. An oscillatory instability can result from the interplay between a region of negative stiffness in the bundle's force-displacement relation and the Ca(2+)-regulated activity of molecular motors. We calculate a state diagram that describes the possible dynamical states of the hair bundle in the absence of fluctuations. Taking into account thermal fluctuations, the stochastic nature of transduction channels' gating, and of the forces generated by molecular motors, we discuss conditions that yield a response function and spontaneous noisy movements of the hair bundle in quantitative agreement with previously published experiments. We find that the magnitude of the fluctuations resulting from the active processes that mediate mechanical amplification remains just below that of thermal fluctuations. Fluctuations destroy the phase coherence of spontaneous oscillations and restrict the bundle's sensitivity as well as frequency selectivity to small oscillatory stimuli. We show, however, that a hair bundle studied experimentally operates near an optimum of mechanosensitivity in our state diagram.

Acoustic Stimulation↗
PubMed2004

Effects of peroxisome proliferator-activated receptor alpha activation on pathways contributing to cholesterol homeostasis in rat hepatocytes.

Peroxisome proliferator-activated receptor alpha (PPARalpha) activation by fibrates controls expression of several genes involved in hepatic cholesterol metabolism. Other genes could be indirectly controlled in response to changes in cellular cholesterol availability. To further understand how fibrates may affect cholesterol synthesis, we investigated in parallel the changes in the metabolic pathways contributing to cholesterol homeostasis in liver. Ciprofibrate increased HMG-CoA reductase and FPP synthase mRNA levels in rat hepatocytes, together with cholesterogenesis from [(14)C] acetate and [(3)H] mevalonate. The up-regulation observed in fenofibrate- and WY-14,643-treated mice was abolished in PPARalpha-null mice, showing an essential role of PPARalpha. Among the three sterol regulatory element-binding protein (SREBP) mRNA species, only SREBP-1c level was significantly increased. In ciprofibrate-treated hepatocytes, cholesterol efflux was decreased, in parallel with cholesteryl ester storage and bile acids synthesis. As expected, AOX expression was strongly induced, supporting evidence of the peroxisome proliferation. Taken together, these results show that fibrates can cause cholesterol depletion in hepatocytes, possibly in part as a consequence of an important requirement of cholesterol for peroxisome proliferation, and increase cholesterogenesis by a compensatory phenomenon afterwards. Such cholesterogenesis regulation could occur in vivo, in species responsive to the peroxisome proliferative effect of PPARalpha ligands.

Acetates↗
PubMed2004

Molecular cloning, gene structure and expression profile of two mouse peroxisomal 3-ketoacyl-CoA thiolase genes.

BACKGROUND: In rats, two peroxisomal 3-ketoacyl-CoA thiolase genes (A and B) have been cloned, whereas only one thiolase gene is found in humans. The aim of this study was thus to clone the different mouse thiolase genes in order to study both their tissue expression and their associated enzymatic activity. RESULTS: In this study, we cloned and characterized two mouse peroxisomal 3-ketoacyl-CoA thiolase genes (termed thiolase A and B). Both thiolase A and B genes contain 12 exons and 11 introns. Using RNA extracted from mouse liver, we cloned the two corresponding cDNAs. Thiolase A and B cDNAs possess an open reading frame of 1272 nucleotides encoding a protein of 424 amino acids. In the coding sequence, the two thiolase genes exhibited approximately equal to 97% nucleotide sequence identity and approximately equal to 96% identity at the amino acid level. The tissue-specific expression of the two peroxisomal 3-ketoacyl-CoA thiolase genes was studied in mice. Thiolase A mRNA was mainly expressed in liver and intestine, while thiolase B mRNA essentially exhibited hepatic expression and weaker levels in kidney, intestine and white adipose tissue. Thiolase A and B expressions in the other tissues such as brain or muscle were very low though these tissues were chiefly involved in peroxisomal disorders. At the enzymatic level, thiolase activity was detected in liver, kidney, intestine and white adipose tissue but no significant difference was observed between these four tissues. Moreover, thiolase A and B genes were differently induced in liver of mice treated with fenofibrate. CONCLUSION: Two mouse thiolase genes and cDNAs were cloned. Their corresponding transcripts are mostly expressed in the liver of mice and are differently induced by fenofibrate.

Acetyl-CoA C-Acyltransferase↗
PubMed2003

Spontaneous oscillation by hair bundles of the bullfrog's sacculus.

One prominent manifestation of mechanical activity in hair cells is spontaneous otoacoustic emission, the unprovoked emanation of sound by an internal ear. Because active hair bundle motility probably constitutes the active process of nonmammalian hair cells, we investigated the ability of hair bundles in the bullfrog's sacculus to produce oscillations that might underlie spontaneous otoacoustic emissions. When maintained in the normal ionic milieu of the ear, many bundles oscillated spontaneously through distances as great as 80 nm at frequencies of 5-50 Hz. Whole-cell recording disclosed that the positive phase of movement was associated with the opening of transduction channels. Gentamicin, which blocks transduction channels, reversibly arrested oscillation; drugs that affect the cAMP phosphorylation pathway and might influence the activity of myosin altered the rate of oscillation. Increasing the Ca 2+ concentration rendered oscillations faster and smaller until they were suppressed; lowering the Ca 2+ concentration moderately with chelators had the opposite effect. When a bundle was offset with a stimulus fiber, oscillations were transiently suppressed but gradually resumed. Loading a bundle by partial displacement clamping, which simulated the presence of the accessory structures to which a bundle is ordinarily attached, increased the frequency and diminished the magnitude of oscillation. These observations accord with a model in which oscillations arise from the interplay of the hair bundle's negative stiffness with the activity of adaptation motors and with Ca 2+-dependent relaxation of gating springs.

Animals↗
PubMed2002

Comparative effect of fenofibrate on hepatic desaturases in wild-type and peroxisome proliferator-activated receptor alpha-deficient mice.

In this study is presented the effect of fenofibrate, a prototypical peroxisome proliferator of the fibrate class, on wild-type and peroxisome proliferator-activated receptor alpha (PPARalpha)-/- mouse liver FA profile, desaturase mRNA levels, and activities. We established that, following peroxisome proliferator exposure, the hepatic FA profile was greatly modified. These modifications in hepatic FA content required the expression of PPARalpha, as they are suppressed in transgenic mice deficient in this nuclear receptor. Following peroxisome proliferator exposure, delta6- and delta5-desaturase mRNA levels and activities were increased in wild-type but not in PPARalpha-deficient mouse liver. These results suggest the involvement of PPARalpha in the control of hepatic delta6- and delta5-desaturases in mice. Their roles in minimizing long-chain PUFA depletion in the liver during peroxisome proliferator exposure are discussed.

Animals↗
PubMedDate not supplied

Selection of biomarkers by a multivariate statistical processing of composite metabonomic data sets using multiple factor analysis.

We introduce a statistical approach for integrating data from several analytical platforms. We illustrate this approach using (1)H-(13)C Heteronuclear Multiple Bond Connectivity nuclear magnetic resonance spectroscopy ((1)H-(13)C HMBC NMR) and Pyrolysis Metastable Atom Bombardment Time-of-Flight mass spectrometry (Py-MAB-TOF-MS) to perform metabolic fingerprinting on cattle treated with anabolic steroids. Multiple factor analysis (MFA) integrates complementary aspects from NMR and MS data into a unique metabolic signature describing the biomarkers related to the dose-response. This work also indicates that, from a practical point of view, metabonomics and other "-omics" biotechnologies can benefit significantly from a generalized multi-platform integrative approach using multiple factor analysis.

Animals↗