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151.
Stéphane Grison Gaëlle Favé Matthieu Maillot Line Manens Olivia Delissen Eric Blanchardon Nathalie Banzet Catherine Defoort Romain Bott Isabelle Dublineau Jocelyne Aigueperse Patrick Gourmelon Jean-Charles Martin Maâmar Souidi 《Metabolomics : Official journal of the Metabolomic Society》2013,9(6):1168-1180
Because uranium is a natural element present in the earth’s crust, the population may be chronically exposed to low doses of it through drinking water. Additionally, the military and civil uses of uranium can also lead to environmental dispersion that can result in high or low doses of acute or chronic exposure. Recent experimental data suggest this might lead to relatively innocuous biological reactions. The aim of this study was to assess the biological changes in rats caused by ingestion of natural uranium in drinking water with a mean daily intake of 2.7 mg/kg for 9 months and to identify potential biomarkers related to such a contamination. Subsequently, we observed no pathology and standard clinical tests were unable to distinguish between treated and untreated animals. Conversely, LC–MS metabolomics identified urine as an appropriate biofluid for discriminating the experimental groups. Of the 1,376 features detected in urine, the most discriminant were metabolites involved in tryptophan, nicotinate, and nicotinamide metabolic pathways. In particular, N-methylnicotinamide, which was found at a level seven times higher in untreated than in contaminated rats, had the greatest discriminating power. These novel results establish a proof of principle for using metabolomics to address chronic low-dose uranium contamination. They open interesting perspectives for understanding the underlying biological mechanisms and designing a diagnostic test of exposure. 相似文献
152.
Nikisha Carty Kevin R. Nash Milene Brownlow Dana Cruite Donna Wilcock Maj-Linda B. Selenica Daniel C. Lee Marcia N. Gordon Dave Morgan 《PloS one》2013,8(3)
The accumulation of β-amyloid peptides in the brain has been recognized as an essential factor in Alzheimer’s disease pathology. Several proteases, including Neprilysin (NEP), endothelin converting enzyme (ECE), and insulin degrading enzyme (IDE), have been shown to cleave β-amyloid peptides (Aβ). We have previously reported reductions in amyloid in APP+PS1 mice with increased expression of ECE. In this study we compared the vector-induced increased expression of NEP and IDE. We used recombinant adeno-associated viral vectors expressing either native forms of NEP (NEP-n) or IDE (IDE-n), or engineered secreted forms of NEP (NEP-s) or IDE (IDE-s). In a six-week study, immunohistochemistry staining for total Aβ was significantly decreased in animals receiving the NEP-n and NEP-s but not for IDE-n or IDE-s in either the hippocampus or cortex. Congo red staining followed a similar trend revealing significant decreases in the hippocampus and the cortex for NEP-n and NEP-s treatment groups. Our results indicate that while rAAV-IDE does not have the same therapeutic potential as rAAV-NEP, rAAV-NEP-s and NEP-n are effective at reducing amyloid loads, and both of these vectors continue to have significant effects nine months post-injection. As such, they may be considered reasonable candidates for gene therapy trials in AD. 相似文献
153.
Holly M. Nguyen Nazanin Ruppender Xiaotun Zhang Lisha G. Brown Ted S. Gross Colm Morrissey Roman Gulati Robert L. Vessella Frauke Schimmoller Dana T. Aftab Eva Corey 《PloS one》2013,8(10)
Cabozantinib is an inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2. In a phase II clinical trial in advanced prostate cancer (PCa), cabozantinib treatment improved bone scans in 68% of evaluable patients. Our studies aimed to determine the expression of cabozantinib targets during PCa progression and to evaluate its efficacy in hormone-sensitive and castration-resistant PCa in preclinical models while delineating its effects on tumor and bone. Using immunohistochemistry and tissue microarrays containing normal prostate, primary PCa, and soft tissue and bone metastases, our data show that levels of MET, P-MET, and VEGFR2 are increasing during PCa progression. Our data also show that the expression of cabozantinib targets are particularly pronounced in bone metastases. To evaluate cabozantinib efficacy on PCa growth in the bone environment and in soft tissues we used androgen-sensitive LuCaP 23.1 and castration-resistant C4-2B PCa tumors. In vivo, cabozantinib inhibited the growth of PCa in bone as well as growth of subcutaneous tumors. Furthermore, cabozantinib treatment attenuated the bone response to the tumor and resulted in increased normal bone volume. In summary, the expression pattern of cabozantinib targets in primary and castration-resistant metastatic PCa, and its efficacy in two different models of PCa suggest that this agent has a strong potential for the effective treatment of PCa at different stages of the disease. 相似文献
154.
Nancy Krieger Pamela D. Waterman Anna Kosheleva Jarvis T. Chen Kevin W. Smith Dana R. Carney Gary G. Bennett David R. Williams Gisele Thornhill Elmer R. Freeman 《PloS one》2013,8(10)
Objectives
To date, limited and inconsistent evidence exists regarding racial discrimination and risk of cardiovascular disease (CVD).Methods
Cross-sectional observational study of 1005 US-born non-Hispanic black (n = 504) and white (n = 501) participants age 35–64 randomly selected from community health centers in Boston, MA (2008–2010; 82.4% response rate), using 3 racial discrimination measures: explicit self-report; implicit association test (IAT, a time reaction test for self and group as target vs. perpetrator of discrimination); and structural (Jim Crow status of state of birth, i.e. legal racial discrimination prior 1964).Results
Black and white participants both had adverse cardiovascular and socioeconomic profiles, with black participants most highly exposed to racial discrimination. Positive crude associations among black participants occurred for Jim Crow birthplace and hypertension (odds ratio (OR) 1.92, 95% confidence interval (CI) 1.28, 2.89) and for explicit self-report and the Framingham 10 year CVD risk score (beta = 0.04; 95% CI 0.01, 0.07); among white participants, only negative crude associations existed (for IAT for self, for lower systolic blood pressure (SBP; beta = −4.86; 95% CI −9.08, −0.64) and lower Framingham CVD score (beta = −0.36, 95% CI −0.63, −0.08)). All of these associations were attenuated and all but the white IAT-Framingham risk score association were rendered null in analyses that controlled for lifetime socioeconomic position and additional covariates. Controlling for racial discrimination, socioeconomic position, and other covariates did not attenuate the crude black excess risk for SBP and hypertension and left unaffected the null excess risk for the Framingham CVD score.Conclusion
Despite worse exposures among the black participants, racial discrimination and socioeconomic position were not associated, in multivariable analyses, with risk of CVD. We interpret results in relation to constrained variability of exposures and outcomes and discuss implications for valid research on social determinants of health. 相似文献155.
Plant and Soil - Global change is shown to significantly affect the C storage function of peatlands; however, a majority of previous research is focused on a single environmental stressor such as... 相似文献
156.
Berardo Cecilia Geritz Stefan Gyllenberg Mats Raoul Gaël 《Journal of mathematical biology》2020,80(7):2431-2468
Journal of Mathematical Biology - In this paper we introduce a formal method for the derivation of a predator’s functional response from a system of fast state transitions of the prey or... 相似文献
157.
Trehalose monomycolate (TMM) represents an essential element of the mycobacterial envelope. While synthesized in the cytoplasm, TMM is transported across the inner membrane by MmpL3 but, little is known regarding the MmpL3 partners involved in this process. Recently, the TMM transport factor A (TtfA) was found to form a complex with MmpL3 and to participate in TMM transport, although its biological role remains to be established. Herein, we report the crystal structure of the Mycobacterium smegmatis TtfA core domain. The phylogenetic distribution of TtfA homologues in non-mycolate containing bacteria suggests that TtfA may exert additional functions. 相似文献
158.
Arnaud G. Barras Sophie Marti Sarah Ettlin Sergio Vignali Jaime Resano-Mayor Veronika Braunisch Raphaël Arlettaz 《Ibis》2020,162(2):505-519
Species inhabiting mountain ecosystems are expected to be particularly vulnerable to environmental change, yet information on their basic ecology is often lacking. Knowledge from field-based empirical studies remains essential to refine our understanding of the impact of current habitat alterations and for the consequential development of meaningful conservation management strategies. This study focuses on a poorly investigated and vulnerable mountain bird species in Europe, the Ring Ouzel Turdus torquatus. Our aim was to identify the species’ key ecological requirements during the crucial period of nestling provisioning in the context of environmental change. We radiotracked and observed Alpine Ring Ouzels in a high-density population, investigating their pattern of foraging habitat selection in 2015 and 2017, and evaluated the transferability of these results over a wider geographical range across the SW Swiss Alps. Foraging birds selected, consistently in space and time, short grass swards (< 10 cm) with interspersed patches of accessible and penetrable soils, at intermediate moisture levels (around 40–65% volumetric water content). In Alpine ecosystems, this microhabitat configuration is typically widespread during the spring snowmelt, but extremely seasonal, with a rapid decrease in its availability over the course of the breeding season. This underlines the high vulnerability of the Ring Ouzel to environmental change: an earlier snowmelt could generate a temporal mismatch between the peak of the breeding effort and optimal foraging conditions; however, abandoning grazing activities on semi-wooded Alpine pastures may further decrease foraging habitat suitability through taller and denser grass swards, and subsequent woody vegetation encroachment. This study provides a mechanistic appraisal of the challenges Ring Ouzels will face in the future, as well as initial guidelines for targeted habitat management within timberline ecotones. 相似文献
159.
Meir Schechter Merav Atias Suaad Abd Elhadi Dana Davidi Daniel Gitler Ronit Sharon 《The Journal of biological chemistry》2020,295(52):18076
α-Synuclein (α-Syn) is a protein implicated in the pathogenesis of Parkinson''s disease (PD). It is an intrinsically disordered protein that binds acidic phospholipids. Growing evidence supports a role for α-Syn in membrane trafficking, including, mechanisms of endocytosis and exocytosis, although the exact role of α-Syn in these mechanisms is currently unclear. Here we investigate the associations of α-Syn with the acidic phosphoinositides (PIPs), phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2). Our results show that α-Syn colocalizes with PIP2 and the phosphorylated active form of the clathrin adaptor protein 2 (AP2) at clathrin-coated pits. Using endocytosis of transferrin as an indicator for clathrin-mediated endocytosis (CME), we find that α-Syn involvement in endocytosis is specifically mediated through PI(4,5)P2 levels on the plasma membrane. In accord with their effects on PI(4,5)P2 levels, the PD associated A30P, E46K, and A53T mutations in α-Syn further enhance CME in neuronal and nonneuronal cells. However, lysine to glutamic acid substitutions at the KTKEGV repeat domain of α-Syn, which interfere with phospholipid binding, are ineffective in enhancing CME. We further show that the rate of synaptic vesicle (SV) endocytosis is differentially affected by the α-Syn mutations and associates with their effects on PI(4,5)P2 levels, however, with the exception of the A30P mutation. This study provides evidence for a critical involvement of PIPs in α-Syn–mediated membrane trafficking. 相似文献
160.
Jean-François Briand Ikram Djeridi Dominique Jamet Stéphane Coupé Christine Bressy Maëlle Molmeret 《Biofouling》2013,29(5):453-463
Marine biofilm communities that developed on artificial substrata were investigated using molecular and microscopic approaches. Polystyrene, Teflon® and four antifouling (AF) paints were immersed for 2 weeks at two contrasting sites near Toulon on the French Mediterranean coast (Toulon military harbour and the natural protected area of Porquerolles Island). Biofilms comprising bacteria and diatoms were detected on all the coatings. The population structure as well as the densities of the microorganisms differed in terms of both sites and coatings. Lower fouling densities were observed at Porquerolles Island compared to Toulon harbour. All bacterial communities (analysed by PCR-DGGE) showed related structure, controlled both by the sites and the type of substrata. Pioneer microalgal communities were dominated by the same two diatom species, viz. Licmophora gracilis and Cylindrotheca closterium, at both sites, irrespective of the substrata involved. However, the density of diatoms followed the same trend at both sites with a significant effect of all the AF coatings compared to Teflon and polystyrene. 相似文献