Effects of short-term high-fructose diets in humans: modulation by environmental factors

It is currently suspected that sugar overconsumption, and more specifically fructose, may promote the development of obesity and of several cardio-metabolic disorders. However, environmental factors, such as fish oil and dietary proteins, may prevent some deleterious effects of fructose. The aim of this thesis was to identify potential environmental factors that may modulate the metabolic effects of fructose. The first study was designed to evaluate the impact of endurance exercise in healthy young men fed a high-fructose, isocaloric diet. Fructose-induced effects on lipid profile were totally prevented by endurance exercise and may be explained by an enhanced clearance of TRL-TG and the inhibition of de novo lipogenesis. As energy intake was adjusted to energy requirement, we can conclude that exercise acts on fructose metabolism independently of energy imbalance. The second study aimed at determining whether coffee and more specifically chlorogenic acid consumption may prevent fructose-induced intrahepatic lipids accumulation, hypertriglyceridemia and hepatic insulin resistance, through a stimulation of lipid oxidation. Coffee did not prevent the fructose-induced increase in IHCL or plasma TG. Interestingly, the three coffees tested prevented the decrease in hepatic insulin sensitivity, independently of their content in caffeine or chlorogenic acid. Finally, in the third study, we evaluated the effect of essential amino acid supplementation on the increase of hepatic lipids induced by a high-fructose diet. This intervention slightly decreased IHCL concentration. The exact mechanisms remain unidentified but may involve an increased secretion of VLDL-TG. In conclusion, the environmental factors evaluated allow to prevent some of the deleterious effects of fructose and suggest that recommendations on fructose consumption should also take into account environmental factors.

Using environmental niche modeling to understand biological invasions in a changing world

L'activité humaine affecte particulièrement la biodiversité, qui décline à une vitesse préoccupante. Parmi les facteurs réduisant la biodiversité, on trouve les espèces envahissantes. Symptomatiques d'un monde globalisé où l'échange se fait à l'échelle de la planète, certaines espèces, animales ou végétales, sont introduites, volontairement ou accidentellement par l'activité humaine (par exemple lors des échanges commerciaux ou par les voyageurs). Ainsi, ces espèces atteignent des régions qu'elles n'auraient jamais pu coloniser naturellement. Une fois introduites, l'absence de compétiteur peut les rendre particulièrement nuisibles. Ces nuisances sont plus ou moins directes, allant de problèmes sanitaires (p. ex. les piqûres très aigües des fourmis de feu, originaires d'Amérique du Sud et colonisant à une vitesse fulgurante les USA, l'Australie ou la Chine) à des nuisances sur la biodiversité (p. ex. les ravages de la perche du Nil sur la diversité unique des poissons Cichlidés du Lac Victoria). Il est donc important de pouvoir prévenir de telles introductions. De plus, pour le biologiste, ces espèces représentent une rare occasion de pouvoir comprendre les mécanismes évolutifs et écologiques qui expliquent le succès des envahissantes dans un monde où les équilibres sont bouleversés. Les modèles de niche environnementale sont un outil particulièrement utile dans le cadre de cette problématique. En reliant des observations d'espèces aux conditions environnementales où elles se trouvent, ils peuvent prédire la distribution potentielle des envahissantes, permettant d'anticiper et de mieux limiter leur impact. Toutefois, ils reposent sur des hypothèses pas évidentes à démontrer. L'une d'entre elle étant que la niche d'une espèce reste constante dans le temps, et dans l'espace. Le premier objectif de mon travail est de comparer si la niche d'une espèce envahissante diffère entre sa distribution d'origine native et celle d'origine introduite. En étudiant 50 espèces de plantes et 168 espèces de Mammifères, je démontre que c'est le cas et que par corolaire, il est possible de prédire leurs distributions. La deuxième partie de mon travail consiste à comprendre quelles seront les interactions entre le changement climatiques et les envahissantes, afin d'estimer leur impact sous un climat réchauffé. En étudiant la distribution de 49 espèces de plantes envahissantes, je démontre que les montagnes, régions relativement préservée par ce problème, deviendront bien plus exposées aux risques d'invasions biologiques. J'expose aussi comment les interactions entre l'activité humaine, le réchauffement climatique et les espèces envahissantes menacent la vigne sauvage en Europe et propose des zones géographiques particulièrement adaptée pour sa conservation. Enfin, à une échelle beaucoup plus locale, je montre qu'il est possible d'utiliser ces modèles de niches le long d'une rivière à une échelle extrêmement fine (1 mètre), potentiellement utile pour rationnaliser des mesures de conservations sur le terrain. - Biodiversity is significantly negatively affected by human activity. Invasive species are one of the most important factors causing biodiversity's decline. Intimately linked to the era of global trade, some plant or animal species can be accidentally or casually introduced with human activity (e.g. trade or travel). In this way, these species reach areas they could never reach through natural dispersal. Once naturalized, the lack of competitors can make these species highly noxious. Their effect is more or less direct, from sanitary problems (e.g. the harmful sting of Fire Ants, originating from South America and now spreading throughout USA, China and Australia) or can affect biodiversity (e.g. the Nile perch, devastating the one of the richest hotspot of Cichlid fishes diversity in Lake Victoria). It is thus important to prevent such harmful introductions. Moreover, invasive species represent for biologists one of the rare occasions to understand the evolutionary and ecological mechanisms behind the success of invaders in a world where natural equilibrium is already disturbed. Environmental niche models are particularly useful to tackle this problematic. By relating species observation to the environmental conditions where they occur, they can predict the potential distribution of invasive species, allowing a better anticipation and thus limiting their impact. However, they rely on strong assumption, one of the most important being that the modeled niche remains constant through space and time. The first aim of my thesis is to quantify the difference between the native and the invaded niche. By investigating 50 plant and 168 mammal species, I show that the niche is at least partially conserved, supporting for reliable predictions of invasive' s potential distributions. The second aim of my thesis is to understand the possible interactions between climate change and invasive species, such as to assess their impact under a warmer climate. By studying 49 invasive plant species, I show that mountain areas, which were relatively preserved, will become more suitable for biological invasions. Additionally, I show how interactions between human activity, global warming and invasive species are threatening the wild grapevine in Europe and propose geographical areas particularly adapted for conservation measures. Finally, at a much finer scale where conservation plannings ultimately take place, I show that it is possible to model the niche at very high resolution (1 meter) in an alluvial area allowing better prioritizations for conservation.

Homemade thermometry instruments in the field.

OBJECTIVE: Esophageal temperature is the gold standard for in-the-field temperature monitoring in hypothermic victims with cardiac arrest. For practical reasons, some mountain rescue teams use homemade esophageal thermometers to measure esophageal temperature; these consist of nonmedical inside/outside temperature monitoring instruments that have been modified to allow for esophageal insertion. We planned a study to determine the accuracy of such thermometers. METHODS: Two of the same model of digital cabled indoor/outdoor thermometer were modified and tested in comparison with a reference thermometer. The thermometers were tested in a water bath at different temperatures between 10°C and 35.2°C. Three hundred measurements were taken with each thermometer. RESULTS: Our experimental study showed that both homemade thermometers provided a good correlation and a clinically acceptable agreement in comparison with the reference thermometer. Measurements were within 0.5°C in comparison with the reference thermometer 97.5% of the time. CONCLUSIONS: The homemade thermometers performed well in vitro, in comparison with a reference thermometer. However, because these devices in their original form are not designed for clinical use, their use should be restricted to situations when the use of a conventional esophageal thermometer is impossible.

Pooling of dentin microtensile bond strength data improves clinical correlation.

Purpose: To evaluate whether the correlation between in vitro bond strength data and estimated clinical retention rates of cervical restorations after two years depends on pooled data obtained from multicenter studies or single-test data. Materials and Methods: Pooled mean data for six dentin adhesive systems (Adper Prompt L-Pop, Clearfil SE, OptiBond FL, Prime & Bond NT, Single Bond, and Scotchbond Multipurpose) and four laboratory methods (macroshear, microshear, macrotensile and microtensile bond strength test) (Scherrer et al, 2010) were correlated to estimated pooled two-year retention rates of Class V restorations using the same adhesive systems. For bond strength data from a single test institute, the literature search in SCOPUS revealed one study that tested all six adhesive systems (microtensile) and two that tested five of the six systems (microtensile, macroshear). The correlation was determined with a database designed to perform a meta-analysis on the clinical performance of cervical restorations (Heintze et al, 2010). The clinical data were pooled and adjusted in a linear mixed model, taking the study effect, dentin preparation, type of isolation and bevelling of enamel into account. A regression analysis was carried out to evaluate the correlation between clinical and laboratory findings. Results: The results of the regression analysis for the pooled data revealed that only the macrotensile (adjusted R2 = 0.86) and microtensile tests (adjusted R2 = 0.64), but not the shear and the microshear tests, correlated well with the clinical findings. As regards the data from a single-test institute, the correlation was not statistically significant. Conclusion: Macrotensile and microtensile bond strength tests showed an adequate correlation with the retention rate of cervical restorations after two years. Bond strength tests should be carried out by different operators and/or research institutes to determine the reliability and technique sensitivity of the material under investigation.

Photosensitizing effects of m-tetrahydroxyphenylchlorin on human tumor xenografts: correlation with sensitizer uptake, tumor doubling time and tumor histology.

The photodynamic effects of m-tetrahydroxyphenylchlorin (mTHPC) were assessed on human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma xenografts grown in nude mice and were correlated with mTHPC uptake, histology and doubling time of the tumors. Non-thermal laser light was delivered to the tumor as surface radiation 4 days after intraperitoneal administration of 0.1 and 0.3 mg mTHPC/kg body weight, respectively. The extent of tumor necrosis was measured by histomorphometry. The mTHPC concentration in non-irradiated tumors was assessed by high-performance liquid chromatography (HPLC). The tumors were graded according to their doubling time and their vascular architecture as assessed by histology. The 0.1 mg/kg dose of mTHPC resulted in an equal uptake for all 3 tumor types but revealed a larger extent of photosensitized necrosis for adenocarcinoma, which displayed a delicate tumor stroma with numerous small capillary vessels, than for mesothelioma and squamous cell carcinoma, which were both poor in stroma and vessels. The 0.3 mg/kg dose of mTHPC resulted in a 2-fold higher tumor uptake for all 3 tumor types and in a larger extent of necrosis for mesothelioma and squamous cell carcinoma, but not for adenocarcinoma xenografts, compared with the lower drug dose. Our results demonstrate that different tumor xenografts respond differently to mTHPC-PDT for a given drug-light condition. In this setting, the photosensitizing effect was more closely related to the vascular architecture of the tumors than to the sensitizer uptake and doubling time of the different tumors

Correlation between vasoconstrictor roles and mRNA expression of alpha1-adrenoceptor subtypes in blood vessels of genetically engineered mice.

We examined the contribution of each alpha(1)-adrenoceptor (AR) subtype in noradrenaline (NAd)-evoked contraction in the thoracic aortas and mesenteric arteries of mice. Compared with the concentration-response curves (CRCs) for NAd in the thoracic aortas of wild-type (WT) mice, the CRCs of mutant mice showed a significantly lower sensitivity. The pD(2) value in rank order is as follows: WT mice (8.21) > alpha(1B)-adrenoceptor knockout (alpha(1B)-KO) (7.77) > alpha(1D)-AR knockout (alpha(1D)-KO) (6.44) > alpha(1B)- and alpha(1D)-AR double knockout (alpha(1BD)-KO) (5.15). In the mesenteric artery, CRCs for NAd did not differ significantly between either WT (6.52) and alpha(1B)-KO mice (7.12) or alpha(1D)-KO (6.19) and alpha(1BD)-KO (6.29) mice. However, the CRC maximum responses to NAd in alpha(1D)- and alpha(1BD)-KO mice were significantly lower than those in WT and alpha(1B)-KO mice. Except in the thoracic aortas of alpha(1BD)-KO mice, the competitive antagonist prazosin inhibited the contraction response to NAd with high affinity. However, prazosin produced shallow Schild slopes in the vessels of mice lacking the alpha(1D)-AR gene. In the thoracic aorta, pA(2) values in WT mice for KMD-3213 and BMY7378 were 8.25 and 8.46, respectively, and in alpha(1B)-KO mice they were 8.49 and 9.13, respectively. In the mesenteric artery, pA(2) values in WT mice for KMD-3213 and BMY7378 were 8.34 and 7.47, respectively, and in alpha(1B)-KO mice they were 8.11 and 7.82, respectively. These pharmacological findings were in fairly good agreement with findings from comparison of CRCs, with the exception of the mesenteric arteries of WT and alpha(1B)-KO mice, which showed low affinities to BMY7378. We performed a quantitative analysis of the mRNA expression of each alpha(1)-AR subtype in these vessels in order to examine the correlation between mRNA expression level and the predominance of each alpha(1)-AR subtype in mediating vascular contraction. The rank order of each alpha(1)-AR subtype in terms of its vasoconstrictor role was in fairly good agreement with the level of expression of mRNA of each subtype, that is, alpha(1D)-AR > alpha(1B)-AR > alpha(1A)-AR in the thoracic aorta and alpha(1D)-AR > alpha(1A)-AR > alpha(1B)-AR in the mesenteric artery. No dramatic compensatory change of alpha(1)-AR subtype in mutant mice was observed in pharmacological or quantitative mRNA expression analysis.

Rates and pattern of evolution among Cretaceous radiolarians: relations with global paleoceanographic events

We present a new approach for analyzing the turnover rates of Cretaceous radiolarians recorded in pelagic sequences of western Tethys, The analysis of major extinction-radiation events and the fluctuation of diversity are compared with major paleoceanographic events and variation of diversity in dinoflagellates, calcareous nannoplankton and ammonites. There is an extraordinary correlation between biotic changes and sea level changes, temperatures, O, C and Sr isotopes, phosphorus accumulation rates and anoxic episodes. This reveals a predominantly abiotic control on the evolution of radiolarians. The rate of turnover and the diversity through time of two major orders of radiolarians (nassellarians and spumellarians) exhibits (1) the quasi-parallelism of their diversity curves, excluding a direct competition between them, (2) greater resistance of spumellarians to extinction during the early stage of extinction intervals and (3) a stronger post-extinction recovery of nassellarians. Evolutionary rates of radiolarians can be a good means of monitoring global environmental changes and allowing us to understand more clearly the relationship between plankton evolution, climate and pale oceanographic processes.

Use of new biochemical plasmatic markers, plasma free and total metanephrines, for the diagnosis and follow-up of neuroblastoma in children with clinical correlation

Background: Neuroblastoma is a paediatrictumour derived from the neural crest. Biochemical diagnosis and follow up rely on quantitation of urinary catecholamines (dopamine and noradrenaline) and their metabolites vanillylmandelic acid (VMA) and homovanillic acid (HVA) (gold-standard). When combined, these analyses have a sensitivity of 95%. However, they are clearly limited by inaccuracy of urine collection in young children and normalisation of catecholamine concentrations by creatininuria. Recent development in biochemical diagnosis of pheochromocytoma, another neural crest tumour found in adults, shows that plasmatic measurement of methoxylated catecholamines called metanephrines are more sensitive and specific than other biomarkers. Moreover, a study to determine the reference intervals for metanephrines in a pediatric population has recently been completed. The aim of this work is to describe the role of metanephrines monitoring in the follow up of neuroblastoma. Method: This retrospective study included patients with neuroblastoma in whom the following parameters were determined: plasma free and total metanephrines, plasma catecholamines, 24h urinary catecholamines and metanephrines in absolute value and corrected by creatinine, VMA and HVA at the diagnosis and during treatment at the University Hospital of Lausanne (Switzerland). Eleven patients aged between the first day of life and 7 years old were followed between 2005 and 2012. Clinical outcome and biochemical concentrations of the analytes were correlated. Results: At diagnosis, plasma free and total normetanephrines and methoxytyramine have a sensitivity of 100% compared to 85% for the actual gold standard. Metanephrine remain below the upper reference limit as expected since these tumours do not produce adrenaline. The relationship between biochemical markers and clinical outcome is illustrated graphically. Plasma or urinary normetanephrine and methoxytyramine correlate better with the history of the patient than VMA and HVA, as evaluated by ordinal logistic regression. Concentrations of analytes in urine show a better correlation with clinical events when the results are corrected by creatininuria. Conclusion: Normetanephrine and methoxytyramine reflect disease history in neuroblastoma patients and could play a significant role in the follow up of this type of tumour. Formal studies in a sufficient number of patients are needed to confirm this preliminary observation.

Fishery-induced selection on an Alpine whitefish: quantifying genetic and environmental effects on individual growth rate

Size-selective fishing, environmental changes and reproductive strategies are expected to affect life-history traits such as the individual growth rate. The relative contribution of these factors is not clear, particularly whether size-selective fishing can have a substantial impact on the genetics and hence on the evolution of individual growth rates in wild populations. We analysed a 25-year monitoring survey of an isolated population of the Alpine whitefish Coregonus palaea. We determined the selection differentials on growth rate, the actual change of growth rate over time and indicators of reproductive strategies that may potentially change over time. The selection differential can be reliably estimated in our study population because almost all the fish are harvested within their first years of life, i.e. few fish escape fishing mortality. We found a marked decline in average adult growth rate over the 25 years and a significant selection differential for adult growth, but no evidence for any linear change in reproductive strategies over time. Assuming that the heritability of growth in this whitefish corresponds to what was found in other salmonids, about a third of the observed decline in growth rate would be linked to fishery-induced evolution. Size-selective fishing seems to affect substantially the genetics of individual growth in our study population.

Geochemical compositions of marine fossils as proxies for reconstructing ancient environmental conditions.

A brief summary is given here about some of the geochemical methodologies that are often used to obtain information from fossils and sediments about the past environment. Such methods are frequently applied in our project in which the formation of Paleogene phosphate sequences in North Africa is investigated. These layers were deposited in shallow marine seas during a period of extreme warm climate with a high CO(2) concentration in the atmosphere. Some of the characteristics of this greenhouse interval are similar to the modern anthropogenic situation hence it is intensively investigated from several aspects by many scientists. Here the geochemical compositions of fossils deposited during this time are discussed, focusing on how the data are obtained and how they could be evaluated in terms of palaeo-environmental conditions.

The mapping of the local contributions of Fermi and Coulomb correlation into intracule and extracule density distributions

The contributions of the correlated and uncorrelated components of the electron-pair density to atomic and molecular intracule I(r) and extracule E(R) densities and its Laplacian functions ∇2I(r) and ∇2E(R) are analyzed at the Hartree-Fock (HF) and configuration interaction (CI) levels of theory. The topologies of the uncorrelated components of these functions can be rationalized in terms of the corresponding one-electron densities. In contrast, by analyzing the correlated components of I(r) and E(R), namely, IC(r) and EC(R), the effect of electron Fermi and Coulomb correlation can be assessed at the HF and CI levels of theory. Moreover, the contribution of Coulomb correlation can be isolated by means of difference maps between IC(r) and EC(R) distributions calculated at the two levels of theory. As application examples, the He, Ne, and Ar atomic series, the C2-2, N2, O2+2 molecular series, and the C2H4 molecule have been investigated. For these atoms and molecules, it is found that Fermi correlation accounts for the main characteristics of IC(r) and EC(R), with Coulomb correlation increasing slightly the locality of these functions at the CI level of theory. Furthermore, IC(r), EC(R), and the associated Laplacian functions, reveal the short-ranged nature and high isotropy of Fermi and Coulomb correlation in atoms and molecules

Basis set and electron correlation effects on initial convergence for vibrational nonlinear optical properties of conjugated organic molecules

The level of ab initio theory which is necessary to compute reliable values for the static and dynamic (hyper)polarizabilities of three medium size π-conjugated organic nonlinear optical (NLO) molecules is investigated. With the employment of field-induced coordinates in combination with a finite field procedure, the calculations were made possible. It is stated that to obtain reasonable values for the various individual contributions to the (hyper)polarizability, it is necessary to include electron correlation. Based on the results, the convergence of the usual perturbation treatment for vibrational anharmonicity was examined

Occupational and non-occupational exposure of non-smokers to environmental tobacco smoke in Switzerland : preliminary results of an original campaig

A passive sampling device called Monitor of NICotine or "MoNIC", was constructed and evaluated by IST laboratory for determining nicotine in Environmental Tobacco Smoke (ETS). Vapour nicotine was passively collected on a potassium bisulfate treated glass fibre filter as collection medium. Analysis of amount of nicotine on the treated filter by gas chromatography equipped with Thermoionic-Specific Detector (GCTSD) after liquid-liquid extraction of 1mL of 5N NaOH : 1 mL of n-heptane saturated with NH3 using quinoline as internal standard. Based on nicotine amount of 0.2 mg/cigarette as reference, the inhaled Cigarette Equivalents (CE) by non-smokers can be calculated. Using the detected CE on the badge for nonsmokers, and comparing with amount of nicotine and cotinine level in saliva of both smokers and exposed non-smokers (N=49), we can confirm the use of the CE concept for estimating exposure to ETS. The Valais CIPRET (Center of information and prevention of the addiction to smoking), is going to organize a big campaign on the subject of the passive addiction to smoking entitled "Smoked passive, we suffer from it, we die from it ". This campaign will take place in 2007 and has for objective to inform clearly the population of Valais of the dangerousness of the passive smoke. More than 1'500 MoNIC badges were gracefully distributed to Swiss population to perform a self-monitoring of population exposure level to ETS, expressed in term of CE. Non-stimulated saliva were also collected to determine ETS biomarkers nicotine/cotinine levels of participating volunteers. Preliminary results of different levels of CE in occupational and non-occupational situations in relation with ETS were presented in this study.