287 research outputs found
Radiation-induced lung damage promotes breast cancer lung-metastasis through CXCR4 signaling
Radiotherapy is a mainstay in the postoperative treatment of breast cancer as it reduces the risks of local recurrence and mortality after both conservative surgery and mastectomy. Despite recent efforts to decrease irradiation volumes through accelerated partial irradiation techniques, late cardiac and pulmonary toxicity still occurs after breast irradiation. The importance of this pulmonary injury towards lung metastasis is unclear. Preirradiation of lung epithelial cells induces DNA damage, p53 activation and a secretome enriched in the chemokines SDF-1/CXCL12 and MIF. Irradiated lung epithelial cells stimulate adhesion, spreading, growth, and (transendothelial) migration of human MDA-MB-231 and murine 4T1 breast cancer cells. These metastasis-associated cellular activities were largely mimicked by recombinant CXCL12 and MIF. Moreover, an allosteric inhibitor of the CXCR4 receptor prevented the metastasis-associated cellular activities stimulated by the secretome of irradiated lung epithelial cells. Furthermore, partial (10%) irradiation of the right lung significantly stimulated breast cancer lung-specific metastasis in the syngeneic, orthotopic 4T1 breast cancer model.
Our results warrant further investigation of the potential pro-metastatic effects of radiation and indicate the need to develop efficient drugs that will be successful in combination with radiotherapy to prevent therapy-induced spread of cancer cells
Exploring conformational energy landscape of glassy disaccharides by CPMAS 13C NMR and DFT/GIAO simulations. I. Methodological aspects
The aim of this article is to assess the ability of chemical shift surfaces
to provide structural information on conformational distributions of
disaccharides in glassy solid state. The validity of the general method leading
to a simulation of inhomogeneous 13C chemical shift distributions is discussed
in detail. In particular, a proper consideration of extrema and saddle points
of the chemical shift map correctly accounts for the observed discontinuities
in the experimental CPMAS spectra. Provided that these basic requirements are
met, DFT/GIAO chemical shift maps calculated on relaxed conformations lead to a
very satisfactory description of the experimental lineshapes. On solid-state
trehalose as a model of amorphous disaccharide, this simulation approach
defines unambiguously the most populated sugar conformation in the glass, and
can help in discriminating the validity of different models of intramolecular
energy landscape. Application to other molecular systems with broad
conformational populations is foreseen to produce a larger dependence of the
calculated chemical shift distribution on the conformational map
Exploring conformational energy landscape of glassy disaccharides by CPMAS 13C NMR and DFT/GIAO simulations. II. Enhanced molecular flexibility in amorphous trehalose
This paper deals with the comparative use of the chemical shift surfaces to
simulate experimental 13C CPMAS data on amorphous solid state disaccharides,
paying particular attention to -1-1 linkage of trehalose, to
-1,4 linkage between pyranose rings (lactose) and to linkage implying a
furanose ring (sucrose). The combination of molecular mechanics with DFT/GIAO
ab-initio methods provides reliable structural information on the
conformational distribution in the glass. The results are interpreted in terms
of an enhanced flexibility that trehalose experiences in amorphous solid state
compared to the other sugars. An attempt to relate this property to the balance
between intra- and inter-molecular hydrogen bonding network in the glass is
presented
Diversity of the Insect Visitors on Calluna vulgaris (Ericaceae) in Southern France Heathlands
As part of an ongoing research project on the pollination networks in European heathlands, the objective of this study was to assess the insect visitor guild on Calluna vulgaris (L.) Hull (Ericaceae). We focused the study on a region renowned for its largely well-preserved heathlands, the Cévennes National Park, Southern France. In 2013, flower visitors were observed over 3 d per site, in four heathland sites at mont Lozère. Honeybees (Apis mellifera L.) were the main visitors (62–88% of total visitors). Besides honeybees, a high diversity of visitors was detected with 57 different species identified (42 Diptera and 15 Hymenoptera). Hoverflies (Syrphidae, Diptera) visitors were abundant and diverse, especially individuals belonging to the genera Eristalis and Episyrphus. The reported diversity of visitors was probably due to the preservation of large heathland areas at mont Lozère and to the generalist pollination system of C. vulgaris
Vulnérabilités liées à l'eau dans les Andes vénézuéliennes : influences des relations sociétés/hydrosystèmes dans le cas de Santa-Cruz-de-Mora
International audienceDes mutations agricoles sont survenues au cours des dernières décennies dans les Andes vénézuéliennes. Cette région autrefois grande productrice de café a vu sa production baisser au profit du maraîchage irrigué et du pastoralisme. Nous avons mené 2 démarches parallèles : la caractérisation des changements d'occupation du sol afin de mettre en perspective le discours des habitants ; et l'analyse des représentations sociales des risques liés à l'eau, restitués plus largement dans les représentations des hydrosystèmes
Mutarotational Kinetics and Glass Transition of Lactose
We report for the first time real time in situ and quantitative measurements
of the mutarotation reaction of lactose in the solid state. The experiments
have been performed by 13C NMR. We show that mutarotation is initiated on
heating the amorphous state, and reaches chemical equilibrium close above the
glass transition temperature Tg. We do not observe this transformation when
starting from stable crystalline states. The final ratio of and
anomers is 1:1, which suggests that the energy profile of the mutarotation
reaction pathway in the solid state is actually different from the mechanism
proposed for aqueous solution. This chemical equipartition is reached before
the crystallization into the corresponding 1:1 molecular compound. These new
data clearly illustrate the interrelation between the chemical molecular
properties, the physical state of the material, and the relaxational dynamics
of the glass
Prevalence of HIV-1 drug resistance in treated patients with viral load >50 copies/mL in 2009: a French nationwide study
Background Surveillance of HIV-1 drug resistance in treated patients with plasma viral load (VL) >50 copies/mL. Methods The protease and reverse transcriptase (RT) genes were systematically sequenced in samples from 756 patients with VL >50 copies/mL in 2009. The genotyping results were interpreted for each antiretroviral drug (ARV) by using the ANRS algorithm v21. Weighted analyses were used to derive representative estimates of percentages of patients. Prevalence rates were compared with those obtained in 2004 among patients with VL >1000 copies/mL. Results Sequences were obtained for 506 patients. Sequencing was successful in 45%, 80% and 96% of samples with VL of 51-500, 501-1000 and >1000 copies/mL, respectively. Resistance or possible resistance to at least one ARV was observed in 59% of samples. Overall, 0.9% of samples contained viruses resistant to all drugs belonging to at least three drug classes. All resistance prevalence rates were significantly lower in 2009 than in 2004. Conclusion In France, where 86% of patients were receiving combination antiretroviral therapy in 2009, only 15.0% of patients had a VL >50 copies/mL, suggesting that only 8.9% of treated patients could potentially transmit resistant viruses. Only 0.08% of patients harboured viruses fully resistant to at least three antiretroviral drug classes. Further studies are needed to determine whether resistance continues to decline over tim
Isolation and Culture of a Marine Bacterium Degrading the Sulfated Fucans from Marine Brown Algae
Future directions in conservation research on petrels and shearwaters
Shearwaters and petrels (hereafter petrels) are highly adapted seabirds that occur across all the world's oceans. Petrels are a threatened seabird group comprising 124 species. They have bet-hedging life histories typified by extended chick rearing periods, low fecundity, high adult survival, strong philopatry, monogamy and long-term mate fidelity and are thus vulnerable to change. Anthropogenic alterations on land and at sea have led to a poor conservation status of many petrels with 52 (42%) threatened species based on IUCN criteria and 65 (52%) suffering population declines. Some species are well-studied, even being used as bioindicators of ocean health, yet for others there are major knowledge gaps regarding their breeding grounds, migratory areas or other key aspects of their biology and ecology. We assembled 38 petrel conservation researchers to summarize information regarding the most important threats according to the IUCN Red List of threatened species to identify knowledge gaps that must be filled to improve conservation and management of petrels. We highlight research advances on the main threats for petrels (invasive species at breeding grounds, bycatch, overfishing, light pollution, climate change, and pollution). We propose an ambitious goal to reverse at least some of these six main threats, through active efforts such as restoring island habitats (e.g., invasive species removal, control and prevention), improving policies and regulations at global and regional levels, and engaging local communities in conservation efforts
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