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301.
Natacha Veerapen Manfred Brigl Salil Garg Vincenzo Cerundolo Liam R. Cox Michael B. Brenner Gurdyal S. Besra 《Bioorganic & medicinal chemistry letters》2009,19(15):4288-4291
We herein report a faster and less cumbersome synthesis of the biologically attractive, α-galactosyl ceramide (α-GalCer), known as KRN7000, and its analogues. More importantly, the use of a silicon tethered intramolecular glycosylation reaction gave easy access to the diglycosyl ceramide Gal(α1→2)GalCer, which has been shown to require uptake and processing to the biologically active α-GalCer derivative. 相似文献
302.
Genevieve Paulissen Natacha Rocks Maud M Gueders Celine Crahay Florence Quesada-Calvo Sandrine Bekaert Jonathan Hacha Mehdi El Hour Jean-Michel Foidart Agnes Noel Didier D Cataldo 《Respiratory research》2009,10(1):127
Lungs are exposed to the outside environment and therefore to toxic and infectious agents or allergens. This may lead to permanent activation of innate immune response elements. A Disintegrin And Metalloproteinases (ADAMs) and ADAMs with Thrombospondin motifs (ADAMTS) are proteinases closely related to Matrix Metalloproteinases (MMPs). These multifaceted molecules bear metalloproteinase and disintegrin domains endowing them with features of both proteinases and adhesion molecules. Proteinases of the ADAM family are associated to various physiological and pathological processes and display a wide spectrum of biological effects encompassing cell fusion, cell adhesion, "shedding process", cleavage of various substrates from the extracellular matrix, growth factors or cytokines... This review will focus on the putative roles of ADAM/ADAMTS proteinases in airway diseases such as asthma and COPD. 相似文献
303.
Diego P. V��zquez Nico Bl��thgen Luciano Cagnolo Natacha P. Chacoff 《Annals of botany》2009,103(9):1445-1457
Background
Ecologists and evolutionary biologists are becoming increasingly interested in networks as a framework to study plant–animal mutualisms within their ecological context. Although such focus on networks has brought about important insights into the structure of these interactions, relatively little is still known about the mechanisms behind these patterns.Scope
The aim in this paper is to offer an overview of the mechanisms influencing the structure of plant–animal mutualistic networks. A brief summary is presented of the salient network patterns, the potential mechanisms are discussed and the studies that have evaluated them are reviewed. This review shows that researchers of plant–animal mutualisms have made substantial progress in the understanding of the processes behind the patterns observed in mutualistic networks. At the same time, we are still far from a thorough, integrative mechanistic understanding. We close with specific suggestions for directions of future research, which include developing methods to evaluate the relative importance of mechanisms influencing network patterns and focusing research efforts on selected representative study systems throughout the world.Key words: Ant–plant interactions, forbidden links, mutualism, neutrality, trait matching, plant–animal interactions, pollination, seed dispersal 相似文献304.
Natacha Protopopoff Wim Van Bortel Niko Speybroeck Jean-Pierre Van Geertruyden Dismas Baza Umberto D'Alessandro Marc Coosemans 《PloS one》2009,4(11)
Introduction
Malaria is re-emerging in most of the African highlands exposing the non immune population to deadly epidemics. A better understanding of the factors impacting transmission in the highlands is crucial to improve well targeted malaria control strategies.Methods and Findings
A conceptual model of potential malaria risk factors in the highlands was built based on the available literature. Furthermore, the relative importance of these factors on malaria can be estimated through “classification and regression trees”, an unexploited statistical method in the malaria field. This CART method was used to analyse the malaria risk factors in the Burundi highlands. The results showed that Anopheles density was the best predictor for high malaria prevalence. Then lower rainfall, no vector control, higher minimum temperature and houses near breeding sites were associated by order of importance to higher Anopheles density.Conclusions
In Burundi highlands monitoring Anopheles densities when rainfall is low may be able to predict epidemics. The conceptual model combined with the CART analysis is a decision support tool that could provide an important contribution toward the prevention and control of malaria by identifying major risk factors. 相似文献305.
Sarah M. Batt Talat Jabeen Arun K. Mishra Natacha Veerapen Karin Krumbach Lothar Eggeling Gurdyal S. Besra Klaus F��tterer 《The Journal of biological chemistry》2010,285(48):37741-37752
Long term survival of the pathogen Mycobacterium tuberculosis in humans is linked to the immunomodulatory potential of its complex cell wall glycolipids, which include the phosphatidylinositol mannoside (PIM) series as well as the related lipomannan and lipoarabinomannan glycoconjugates. PIM biosynthesis is initiated by a set of cytosolic α-mannosyltransferases, catalyzing glycosyl transfer from the activated saccharide donor GDP-α-d-mannopyranose to the acceptor phosphatidyl-myo-inositol (PI) in an ordered and regio-specific fashion. Herein, we report the crystal structure of mannosyltransferase Corynebacterium glutamicum PimB′ in complex with nucleotide to a resolution of 2.0 Å. PimB′ attaches mannosyl selectively to the 6-OH of the inositol moiety of PI. Two crystal forms and GDP- versus GDP-α-d-mannopyranose-bound complexes reveal flexibility of the nucleotide conformation as well as of the structural framework of the active site. Structural comparison, docking of the saccharide acceptor, and site-directed mutagenesis pin regio-selectivity to a conserved Asp residue in the N-terminal domain that forces presentation of the correct inositol hydroxyl to the saccharide donor. 相似文献
306.
Jean-Edouard Ombetta Natacha Thelier Chang Zhi Dong Stéphanie Plocki Lydia Tsagris Fran?ois Rannou France Massicot Atimé Djimdé Elissar El-Hayek Yiming Shi Fran?oise Heymans Nohad Gresh Caroline Chauvet 《PloS one》2010,5(6)
Group IIA secreted/synovial phospholipase A2 (GIIAPLA2) is an enzyme involved in the synthesis of eicosanoids such as prostaglandin E2 (PGE2), the main eicosanoid contributing to pain and inflammation in rheumatic diseases. We designed, by molecular modeling, 7 novel analogs of 3-{4-[5(indol-1-yl)pentoxy]benzyl}-4H-1,2,4-oxadiazol-5-one, denoted C1, an inhibitor of the GIIAPLA2 enzyme. We report the results of molecular dynamics studies of the complexes between these derivatives and GIIAPLA2, along with their chemical synthesis and results from PLA2 inhibition tests. Modeling predicted some derivatives to display greater GIIAPLA2 affinities than did C1, and such predictions were confirmed by in vitro PLA2 enzymatic tests. Compound C8, endowed with the most favorable energy balance, was shown experimentally to be the strongest GIIAPLA2 inhibitor. Moreover, it displayed an anti-inflammatory activity on rabbit articular chondrocytes, as shown by its capacity to inhibit IL-1β-stimulated PGE2 secretion in these cells. Interestingly, it did not modify the COX-1 to COX-2 ratio. C8 is therefore a potential candidate for anti-inflammatory therapy in joints. 相似文献
307.
Rahelinirina S Léon A Harstskeerl RA Sertour N Ahmed A Raharimanana C Ferquel E Garnier M Chartier L Duplantier JM Rahalison L Cornet M 《PloS one》2010,5(11):e14111
Background
Leptospirosis has long been a major public health concern in the southwestern Indian Ocean. However, in Madagascar, only a few, old studies have provided indirect serological evidence of the disease in humans or animals.Methodology/Principal Findings
We conducted a large animal study focusing on small-mammal populations. Five field trapping surveys were carried out at five sites, from April 2008 to August 2009. Captures consisted of Rattus norvegicus (35.8%), R. rattus (35.1%), Mus musculus (20.5%) and Suncus murinus (8.6%). We used microbiological culture, serodiagnosis tests (MAT) and real-time PCR to assess Leptospira infection. Leptospira carriage was detected by PCR in 91 (33.9%) of the 268 small mammals, by MAT in 17 of the 151 (11.3%) animals for which serum samples were available and by culture in 9 of the 268 animals (3.3%). Rates of infection based on positive PCR results were significantly higher in Moramanga (54%), Toliara (48%) and Mahajanga (47.4%) than in Antsiranana (8.5%) and Toamasina (14%) (p = 0.001). The prevalence of Leptospira carriage was significantly higher in R. norvegicus (48.9%), S. murinus (43.5%) and R. rattus (30.8%) than in M. musculus (9.1%) (p<0.001). The MAT detected antibodies against the serogroups Canicola and Icterohaemorrhagiae. Isolates were characterized by serology, secY sequence-based phylogeny, partial sequencing of rrs, multi-locus VNTR analysis and pulsed field gel electrophoresis. The 10 isolates obtained from nine rats were all identified as species L. interrogans serogroup Canicola serovar Kuwait and all had identical partial rrs and secY sequences.Conclusions/Significance
We present here the first direct evidence of widespread leptospiral carriage in small mammals in Madagascar. Our results strongly suggest a high level of environmental contamination, consistent with probable transmission of the infection to humans. This first isolation of pathogenic Leptospira strains in this country may significantly improve the detection of specific antibodies in human cases. 相似文献308.
Lemaire I Falzoni S Leduc N Zhang B Pellegatti P Adinolfi E Chiozzi P Di Virgilio F 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(10):7257-7265
Multinucleated giant cells (MGC), a hallmark of chronic inflammatory reactions, remain an enigma of cell biology. There is evidence implicating the purinergic P2X7 receptor in the fusion process leading to MGC. To investigate this, we used HEK 293 cells stably transfected with either 1) the full-length rat P2X7 receptor (P2X7 cells), 2) a rat P2X7 receptor lacking the C-terminal domain (P2X7TC), or 3) a mock vector, and rat alveolar macrophages (MA) expressing the native receptor. P2X7 cells cultured in serum-free medium formed increased numbers of MGC and displayed a higher fusion index compared with mock transfectants. Stimulation of P2X7 pore-forming activity in P2X7 cells by polymyxin B (PMB) further increased significantly the formation of MGC. Conversely, blockers of P2X-receptors including oxidized ATP, brilliant blue G, and pyridoxal phosphate-6-azophenyl-2'-4'-disulfonic acid inhibited significantly MGC formation in both unstimulated and PMB-stimulated P2X7-transfected cells. In contrast, cells transfected with the truncated P2X7TC were devoid of pore-forming activity, did not respond to PMB stimulation, and failed to form enhanced numbers of MGC, thus behaving as mock transfectants. As found for P2X7-transfected cells, PMB also potentiated dose-dependently the formation of multinucleated MA by rat alveolar MA. Pretreatment with oxidized ATP abrogated the PMB stimulatory effects. Together, these data demonstrate unequivocally the participation of P2X7 receptor in the process of MGC formation. Our study also provides evidence suggesting that stimulation of the P2X7 receptor pathway in MA may mediate increased formation of MGC during chronic inflammatory reactions. 相似文献
309.
Rui F. Oliveira Natacha Carvalho† Jason Miranda†‡ Emanuel J. Gonçalves Matthew Grober‡ & Ricardo Serrão Santos† 《Ethology : formerly Zeitschrift fur Tierpsychologie》2002,108(3):223-235
In the Azorean rock-pool blenny, sexually active males may adopt alternative reproductive tactics. In the present paper the relationship between the presence of satellite males and the reproductive success of nest-holders was investigated by comparing nests with and without an associated satellite male. Males with an associated satellite male suffered more conspecific intrusions but they did not display a higher frequency of attacks towards conspecifics. Nest-holder males were more aggressive towards other conspecifics than towards satellites and the tolerance of nest-holders towards satellites was inversely correlated with the time spent by the satellites in the breeding territory, which suggests control by the nest-holder male of the satellite investment in shared territorial defence. Nest-holders with an associated satellite male had higher condition factors and received more female visits and more spawnings. These results bear two possible interpretations. (1) Nest-holders benefit from the presence of a satellite male by increased attractiveness of their nests to females; satellite males are mutualists helping to defend the nest-owner's territory and to attract females, which is why they are tolerated. (2) Satellite males associate preferentially with more successful nest-holder males which have higher condition factors, and by doing so have more opportunities to achieve parasitic fertilizations. Only experiments will allow these two hypotheses to be distinguished. 相似文献
310.
Veronique L Billat Etienne Mouisel Natacha Roblot Judith Melki 《Journal of applied physiology》2005,98(4):1258-1263
With the generation of mouse models of human cardiovascular or neuromuscular disorders, the development of noninvasive methods to evaluate the physiological responses to exercise presents an important challenge. The possibility for determining critical speed (CS) in the mouse model was examined according to strain (CD1, C57BL/6J, FVB/N) and sex. Sixty mice performed four exhaustive runs on a treadmill to determine their CS. Twenty-one performed an incremental test to determine the velocity at the lactate threshold. CS was significantly different between the strains (P < 0.0001) but not between sexes. Two measures of heritability showed that CS was partially heritable. CS was not significantly different from lactate threshold velocity. We conclude that CS, which reflects the aerobic capacity, can be determined in mice, as in humans and horses. Considering the intrastrain variability, CS could represent a valuable means for designing an optimal and individualized physical training in mice. 相似文献