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951.
952.
Tyler D. Rudolph Pierre Drapeau Louis Imbeau Vincent Brodeur Sonia Légaré Martin-Hugues St-Laurent 《Biodiversity and Conservation》2017,26(5):1179-1198
Conserving species-at-risk requires quantifiable knowledge of the key drivers of population change. Non-linear demographic responses to habitat loss have been documented for many species and may serve to establish quantitative habitat thresholds for management purposes. In Canada, boreal populations of woodland caribou are considered threatened; Environment Canada’s empirical model of calf recruitment–range disturbance suggests that at least 65% undisturbed habitat is required to ensure viability. We tested the relationship upon which this conservation guideline is based by pairing demographic estimates with range conditions over a 10-year period for three boreal caribou populations. Our objectives were (1) to evaluate evidence of intra-population demographic responses to fluctuations in range quality over time; (2) to evaluate inter-population differences in demographic responses to cumulative range disturbances; and (3) to evaluate the sensitivity of disturbance tolerance thresholds to variation in local population demography. We found strong evidence in support of the disturbance–recruitment relationship for within-population responses over time (R2 = 0.77). Mixed effects logistic regression modeling revealed variations in local population responses to cumulative habitat depletion. Range-specific disturbance thresholds derived from Monte Carlo simulations were highly elastic in response to observed variation in local population demography, suggesting that 65% undisturbed habitat is insufficient when adult female survival and/or sex ratio is suboptimal. Study populations were determined to be not self-sustaining (Pr(λ ≥ 0.99) = 37–47%). Adult survival was comparable to estimates reported elsewhere despite Aboriginal harvesting for subsistence purposes. Results underscored potential trade-offs between forest harvesting and wildlife habitat conservation. Protection and restoration of sufficient quantities of undisturbed habitat, particularly via road reclamation, is essential for caribou population recovery. 相似文献
953.
Andrew M. Thompson Adrian Blaser Brian D. Palmer Robert F. Anderson Sujata S. Shinde Delphine Launay Eric Chatelain Louis Maes Scott G. Franzblau Baojie Wan Yuehong Wang Zhenkun Ma William A. Denny 《Bioorganic & medicinal chemistry letters》2017,27(11):2583-2589
As part of a quest for backups to the antitubercular drug pretomanid (PA-824), we investigated the unexplored 6-nitro-2,3-dihydroimidazo[2,1-b][1,3]-thiazoles and related -oxazoles. The nitroimidazothiazoles were prepared in high yield from 2-bromo-4-nitroimidazole via heating with substituted thiiranes and diisopropylethylamine. Equivalent examples of these two structural classes provided broadly comparable MICs, with 2-methyl substitution and extended aryloxymethyl side chains preferred; albeit, S-oxidised thiazoles were ineffective for tuberculosis. Favourable microsomal stability data for a biaryl thiazole (45) led to its assessment in an acute Mycobacterium tuberculosis mouse model, alongside the corresponding oxazole (48), but the latter proved to be more efficacious. In vitro screening against kinetoplastid diseases revealed that nitroimidazothiazoles were inactive versus leishmaniasis but showed interesting activity, superior to that of the nitroimidazooxazoles, against Chagas disease. Overall, “thio-delamanid” (49) is regarded as the best lead. 相似文献
954.
NMR secondary structure and interactions of recombinant human MOZART1 protein,a component of the gamma‐tubulin complex 下载免费PDF全文
Cyprian D. Cukier Audrey Tourdes Dounia El‐Mazouni Valérie Guillet Julian Nomme Lionel Mourey Alain Milon Andreas Merdes Virginie Gervais 《Protein science : a publication of the Protein Society》2017,26(11):2240-2248
Mitotic‐spindle organizing protein associated with a ring of γ‐tubulin 1 (MOZART1) is an 8.5 kDa protein linked to regulation of γ‐tubulin ring complexes (γTuRCs), which are involved in nucleation of microtubules. Despite its small size, MOZART1 represents a challenging target for detailed characterization in vitro. We described herein a protocol for efficient production of recombinant human MOZART1 in Escherichia coli and assessed the properties of the purified protein using a combination of size exclusion chromatography coupled with multiangle light scattering (SEC‐MALS), dynamic light scattering (DLS), and nuclear magnetic resonance (NMR) experiments. MOZART1 forms heterogeneous oligomers in solution. We identified optimal detergent and buffer conditions for recording well resolved NMR experiments allowing nearly full protein assignment and identification of three distinct alpha‐helical structured regions. Finally, using NMR, we showed that MOZART1 interacts with the N‐terminus (residues 1–250) of GCP3 (γ‐tubulin complex protein 3). Our data illustrate the capacity of MOZART1 to form oligomers, promoting multiple contacts with a subset of protein partners in the context of microtubule nucleation. 相似文献
955.
Lara Massai Luigi Messori Nicola Micale Tanja Schirmeister Louis Maes Dolores Fregona Maria Agostina Cinellu Chiara Gabbiani 《Biometals》2017,30(2):313-320
Gold compounds form a new class of promising metal-based drugs with a number of potential therapeutic applications, particularly in the fields of anticancer and antimicrobial treatments. Previous research revealed that a group of structurally diverse gold compounds cause conspicuous inhibition of the protease activities of the human proteasome. Given the pharmacological importance of protease inhibition, the present study further explored whether these gold compounds might inhibit a few other proteases that are accepted druggable targets for disease treatment. In particular, four distinct cysteine proteases were considered here: cathepsin B and L that play a primary role in tumor-cell invasion and metastasis; rhodesain, the major cathepsin L-like cysteine protease of Trypanosoma brucei rhodesiense and CPB2.8ΔCTE, a Leishmania mexicana mature cysteine protease. Based on the encouraging results obtained for some of the tested gold compounds on the two parasitic cysteine proteases, especially against CPB2.8ΔCTE, with IC50s in the micromolar range, we next evaluated whether those gold compounds might contrast effectively the growth of the respective protozoa and indeed important antiprotozoal properties were disclosed; on the other hand a certain lack of selectivity was highlighted. Also, no direct or clear correlation could be established between the in vitro antiprotozoal properties and the level of protease inhibition. The implications of these results are discussed in relation to possible pharmaceutical applications. 相似文献
956.
Mycobacterium tuberculosis, the etiological agent of human tuberculosis, harbours five ESAT‐6/type VII secretion (ESX/T7S) systems. The first esx gene clusters were identified during the genome‐sequencing project of M. tuberculosis H37Rv. Follow‐up studies revealed additional genes playing important roles in ESX/T7S systems. Among the latter genes, one can find those that encode Pro‐Glu (PE) and Pro‐Pro‐Glu (PPE) proteins as well as a gene cluster that is encoded >260 kb upstream of the esx‐1 locus and encodes ESX‐1 secretion‐associated proteins EspA (Rv3616c), EspC (Rv3615c) and EspD (Rv3614c). The espACD cluster has been suggested to have an important function in ESX‐1 secretion since EspA‐EspC and EsxA–EsxB are mutually co‐dependent on each other for secretion. However, the molecular mechanism of this co‐dependence and interaction between the substrates remained unknown. In this issue of Molecular Microbiology, Lou and colleagues show that EspC forms high‐molecular weight polymerization complexes that resemble selected components of type II, III and/or IV secretion systems of Gram‐negative bacteria. Indeed, EspC‐multimeric complexes form filamentous structures that could well represent a secretion needle of ESX‐1 type VII secretion systems. This exciting observation opens new avenues for research to discover and characterize ESX/T7S components and elucidates the co‐dependence of EsxA/B secretion with EspA/C. 相似文献
957.
Louis Bernatchez Maren Wellenreuther Cristián Araneda David T. Ashton Julia M.I. Barth Terry D. Beacham Gregory E. Maes Jann T. Martinsohn Kristina M. Miller Kerry A. Naish Jennifer R. Ovenden Craig R. Primmer Ho Young Suk Nina O. Therkildsen Ruth E. Withler 《Trends in ecology & evolution》2017,32(9):665-680
958.
959.
Exposure to Bordetella pertussis adenylate cyclase toxin affects integrin‐mediated adhesion and mechanics in alveolar epithelial cells 下载免费PDF全文
960.
Animal movement in the absence of predation: environmental drivers of movement strategies in a partial migration system 下载免费PDF全文
Guillaume Bastille‐Rousseau James P. Gibbs Charles B. Yackulic Jacqueline L. Frair Fredy Cabrera Louis‐Philippe Rousseau Martin Wikelski Franz Kümmeth Stephen Blake 《Oikos》2017,126(7):1004-1019
Animal movement strategies including migration, dispersal, nomadism, and residency are shaped by broad‐scale spatial‐temporal structuring of the environment, including factors such as the degrees of spatial variation, seasonality and inter‐annual predictability. Animal movement strategies, in turn, interact with the characteristics of individuals and the local distribution of resources to determine local patterns of resource selection with complex and poorly understood implications for animal fitness. Here we present a multi‐scale investigation of animal movement strategies and resource selection. We consider the degree to which spatial variation, seasonality, and inter‐annual predictability in resources drive migration patterns among different taxa and how movement strategies in turn shape local resource selection patterns. We focus on adult Galapagos giant tortoises Chelonoidis spp. as a model system since they display many movement strategies and evolved in the absence of predators of adults. Specifically, our analysis is based on 63 individuals among four taxa tracked on three islands over six years and almost 106 tortoise re‐locations. Tortoises displayed a continuum of movement strategies from migration to sedentarism that were linked to the spatio‐temporal scale and predictability of resource distributions. Movement strategies shaped patterns of resource selection. Specifically, migratory individuals displayed stronger selection toward areas where resources were more predictable among years than did non‐migratory individuals, which indicates a selective advantage for migrants in seasonally structured, more predictable environments. Our analytical framework combines large‐scale predictions for movement strategies, based on environmental structuring, with finer‐scale analysis of space‐use. Integrating different organizational levels of analysis provides a deeper understanding of the eco‐evolutionary dynamics at play in the emergence and maintenance of migration and the critical role of resource predictability. Our results highlight that assessing the potential benefits of differential behavioral responses first requires an understanding of the interactions among movement strategies, resource selection and individual characteristics. 相似文献