Plasma and exhaled breath condensate nitrite-nitrate level in relation to environmental exposures in adults in the EGEA study

This study evaluated the associations between biological markers in the nitrate-nitrite-NO pathway and four environmental exposures among subjects examined in the second survey (2003-2007) of the French Epidemiological study on Genetics and Environment of Asthma (EGEA). Total nitrite and nitrate (NO(2)(-) /NO(3)(-)) levels were measured both in plasma and in exhaled breath condensate (EBC) in 949 adults. Smoking, diet and exposure to chlorine products were assessed using standardized questionnaires. Exposure to air pollutants was estimated by using geostatistical models. All estimates were obtained with generalized estimating equations for linear regression models. Median levels of NO(2)(-)/NO(3)(-) were 36.3μM (1st-3rd quartile: 25.7, 51.1) in plasma and 2.0μmol/mg proteins (1st-3rd quartile 0.9, 3.9) in EBC. After adjustment for asthma, age, sex and menopausal status, plasma NO(2)(-)/NO(3)(-) level increased with leafy vegetable consumption (above versus below median=0.04 (95%CI: 0.001, 0.07)) and decreased in smokers (versus non/ex-smokers=-0.08 (95%CI: -0.11, -0.04). EBC NO(2)(-)/NO(3)(-) level decreased in smokers (-0.08 (95%CI: -0.16, -0.001)) and with exposure to ambient O(3) concentration (above versus below median=-0.10 (95%CI: -0.17, -0.03)). Cured meat, chlorine products, PM(10) and NO(2) concentrations were not associated with NO(2)(-)/NO(3)(-) levels. Results suggest that potential modifiable environmental and behavioral risk factors may modify NO(2)(-)/NO(3)(-) levels in plasma and EBC according to the route of exposure.     

Computational Modelling of Metastasis Development in Renal Cell Carcinoma

The biology of the metastatic colonization process remains a poorly understood phenomenon. To improve our knowledge of its dynamics, we conducted a modelling study based on multi-modal data from an orthotopic murine experimental system of metastatic renal cell carcinoma. The standard theory of metastatic colonization usually assumes that secondary tumours, once established at a distant site, grow independently from each other and from the primary tumour. Using a mathematical model that translates this assumption into equations, we challenged this theory against our data that included: 1) dynamics of primary tumour cells in the kidney and metastatic cells in the lungs, retrieved by green fluorescent protein tracking, and 2) magnetic resonance images (MRI) informing on the number and size of macroscopic lesions. Critically, when calibrated on the growth of the primary tumour and total metastatic burden, the predicted theoretical size distributions were not in agreement with the MRI observations. Moreover, tumour expansion only based on proliferation was not able to explain the volume increase of the metastatic lesions. These findings strongly suggested rejection of the standard theory, demonstrating that the time development of the size distribution of metastases could not be explained by independent growth of metastatic foci. This led us to investigate the effect of spatial interactions between merging metastatic tumours on the dynamics of the global metastatic burden. We derived a mathematical model of spatial tumour growth, confronted it with experimental data of single metastatic tumour growth, and used it to provide insights on the dynamics of multiple tumours growing in close vicinity. Together, our results have implications for theories of the metastatic process and suggest that global dynamics of metastasis development is dependent on spatial interactions between metastatic lesions.     

Linear versus geometric morphometric approaches for the analysis of head shape dimorphism in lizards

Differences between the sexes may arise because of differences in reproductive strategy, with females investing more in traits related to reproductive output and males investing more in traits related to resource holding capacity and territory defence. Sexual dimorphism is widespread in lizards and in many species males and females also differ in head shape. Males typically have bigger heads than females resulting in intersexual differences in bite force. Whereas most studies documenting differences in head dimensions between sexes use linear dimensions, the use of geometric morphometrics has been advocated as more appropriate to characterize such differences. This method may allow the characterization of local shape differences that may have functional consequences, and provides unbiased indicators of shape. Here, we explore whether the two approaches provide similar results in an analyses of head shape in Tupinambis merianae. The Argentine black and white tegu differs dramatically in body size, head size, and bite force between the sexes. However, whether the intersexual differences in bite force are simply the result of differences in head size or whether more subtle modifications (e.g., in muscle insertion areas) are involved remains currently unknown. Based on the crania and mandibles of 19 lizards with known bite force, we show intersexual differences in the shape of the cranium and mandible using both linear and geometric morphometric approaches. Although both types of analyses showed generally similar results for the mandible, this was not the case for the cranium. Geometric morphometric approaches provided better insights into the underlying functional relationships between the cranium and the jaw musculature, as illustrated by shape differences in muscle insertion areas not detected using linear morphometric data. J. Morphol. 275:1016–1026, 2014. © 2014 Wiley Periodicals, Inc.     

Kinetics and mechanism of the substitution reactions of [PtCl(bpma)]<Superscript>+</Superscript>, [PtCl(gly-met-<Emphasis Type="Italic">S,N,N</Emphasis>)] and their aqua analogues with <Emphasis Type="SmallCaps">l</Emphasis>-methionine,glutathione and 5′-GMP

The substitution reactions of [PtCl(bpma)]+, [PtCl(gly-met-S,N,N)], [Pt(bpma)(H(2)O)](2+) and [Pt(gly-met-S,N,N)(H(2)O)](+) [where bpma is bis(2-pyridylmethyl)amine and gly-met-S,N,N is glycylmethionine] with L-methionine, glutathione and guanosine 5'-monophosphate (5'-GMP) were studied in aqueous solutions in 0.10 M NaClO(4) under pseudo-first-order conditions as a function of concentration and temperature using UV-vis spectrophotometry. The reactions of the chloro complexes were followed in the presence of 10 mM NaCl and at pH approximately 5, whereas the reactions of the aqua complexes were studied at pH 2.5. The [PtCl(bpma)]+ complex is more reactive towards the chosen nucleophiles than [PtCl(gly-met-S,N,N)]. Also, the aqua complexes are more reactive than the corresponding chloro complexes. The activation parameters for all the reactions studied suggest an associative substitution mechanism. The reactions of [PtCl(bpma)]+ and [PtCl(gly-met-S,N,N)] with 5'-GMP were studied by using (1)H NMR spectroscopy at 298 K. The pK (a) value of the [Pt(gly-met-S,N,N)(H(2)O)]+ complex is 5.95. Density functional theory calculations (B3LYP/LANL2DZp) show that in all cases guanine coordination to the L(3)Pt fragment (L(3) is terpyridine, bpma, diethylenetriamine, gly-met-S,N,N) is much more favorable than the thioether-coordinated form. The calculations collectively support the experimentally observed substitution of thioethers from Pt(II) complexes by N7-GMP. This study throws more light on the mechanistic behavior of platinum antitumor complexes.