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101.
Sébastien Fritz Aurelien Capitan Anis Djari Sabrina C. Rodriguez Anne Barbat Aurélia Baur Cécile Grohs Bernard Weiss Mekki Boussaha Diane Esquerré Christophe Klopp Dominique Rocha Didier Boichard 《PloS one》2013,8(6)
The regular decrease of female fertility over time is a major concern in modern dairy cattle industry. Only half of this decrease is explained by indirect response to selection on milk production, suggesting the existence of other factors such as embryonic lethal genetic defects. Genomic regions harboring recessive deleterious mutations were detected in three dairy cattle breeds by identifying frequent haplotypes (>1%) showing a deficit in homozygotes among Illumina Bovine 50k Beadchip haplotyping data from the French genomic selection database (47,878 Holstein, 16,833 Montbéliarde, and 11,466 Normande animals). Thirty-four candidate haplotypes (p<10−4) including previously reported regions associated with Brachyspina, CVM, HH1, and HH3 in Holstein breed were identified. Haplotype length varied from 1 to 4.8 Mb and frequencies from 1.7 up to 9%. A significant negative effect on calving rate, consistent in heifers and in lactating cows, was observed for 9 of these haplotypes in matings between carrier bulls and daughters of carrier sires, confirming their association with embryonic lethal mutations. Eight regions were further investigated using whole genome sequencing data from heterozygous bull carriers and control animals (45 animals in total). Six strong candidate causative mutations including polymorphisms previously reported in FANCI (Brachyspina), SLC35A3 (CVM), APAF1 (HH1) and three novel mutations with very damaging effect on the protein structure, according to SIFT and Polyphen-2, were detected in GART, SHBG and SLC37A2 genes. In conclusion, this study reveals a yet hidden consequence of the important inbreeding rate observed in intensively selected and specialized cattle breeds. Counter-selection of these mutations and management of matings will have positive consequences on female fertility in dairy cattle. 相似文献
102.
James L. Trevaskis Christine M. Mack Chengzao Sun Christopher J. Soares Lawrence J. D’Souza Odile E. Levy Diane Y. Lewis Carolyn M. Jodka Krystyna Tatarkiewicz Bronislava Gedulin Swati Gupta Carrie Wittmer Michael Hanley Bruce Forood David G. Parkes Soumitra S. Ghosh 《PloS one》2013,8(10)
Combination therapy is being increasingly used as a treatment paradigm for metabolic diseases such as diabetes and obesity. In the peptide therapeutics realm, recent work has highlighted the therapeutic potential of chimeric peptides that act on two distinct receptors, thereby harnessing parallel complementary mechanisms to induce additive or synergistic benefit compared to monotherapy. Here, we extend this hypothesis by linking a known anti-diabetic peptide with an anti-obesity peptide into a novel peptide hybrid, which we termed a phybrid. We report on the synthesis and biological activity of two such phybrids (AC164204 and AC164209), comprised of a glucagon-like peptide-1 receptor (GLP1-R) agonist, and exenatide analog, AC3082, covalently linked to a second generation amylin analog, davalintide. Both molecules acted as full agonists at their cognate receptors in vitro, albeit with reduced potency at the calcitonin receptor indicating slightly perturbed amylin agonism. In obese diabetic Lepob/Lep
ob mice sustained infusion of AC164204 and AC164209 reduced glucose and glycated haemoglobin (HbA1c) equivalently but induced greater weight loss relative to exenatide administration alone. Weight loss was similar to that induced by combined administration of exenatide and davalintide. In diet-induced obese rats, both phybrids dose-dependently reduced food intake and body weight to a greater extent than exenatide or davalintide alone, and equal to co-infusion of exenatide and davalintide. Phybrid-mediated and exenatide + davalintide-mediated weight loss was associated with reduced adiposity and preservation of lean mass. These data are the first to provide in vivo proof-of-concept for multi-pathway targeting in metabolic disease via a peptide hybrid, demonstrating that this approach is as effective as co-administration of individual peptides. 相似文献
103.
Rebecca McLain Melissa Poe Kelly Biedenweg Lee Cerveny Diane Besser Dale Blahna 《Human ecology: an interdisciplinary journal》2013,41(5):651-665
Ecosystem-based planning and management have stimulated the need to gather sociocultural values and human uses of land in formats accessible to diverse planners and researchers. Human Ecology Mapping (HEM) approaches offer promising spatial data gathering and analytical tools, while also addressing important questions about human-landscape connections. This article reviews and compares the characteristics of three HEM approaches that are increasingly used in natural resource management contexts, each focused on a particular aspect of human-environmental interactions. These aspects include tenure and resource use (TRU), local ecological knowledge (LEK), and sense of place (SOP). We discuss their origins, provide examples of their use, and identify challenges to their application. Our review serves as a guide for environmental managers, planners, and communities interested in gathering spatial data on aspects of human ecology important in ecosystem-based management and planning, and for scientists designing socioecological research. 相似文献
104.
Evgenya S. Shelobolina Diane K. Walker Albert E. Parker Dorian V. Lust Johanna M. Schultz Grace E. Dickerman 《Biofouling》2013,29(7):826-834
AbstractThe inactivation of Pseudomonas aeruginosa biofilms grown on glass under high shear stress and exposed to a range of dissolved ozone concentrations (2, 5 and 7?ppm) at 10 and 20?min was investigated. The regression equation, log reduction (biofilm)?=?0.64?+?0.59×(C – 2)?+?0.33×(T – 10), described the dependence of biofilm inactivation on the dissolved ozone concentration (C, ppm) and contact time (T, min). The predicted D-values were 11.1, 5.7 and 2.2?min at 2, 5 and 7?ppm, respectively. Inactivation of biofilms grown on various surfaces was tested at a single dissolved ozone concentration of 5?ppm and a single exposure time of 20?min. Biofilms grown on plastic materials showed inactivation results similar to that of biofilms on glass, while biofilms grown on ceramics were statistically significantly more difficult to inactivate, suggesting the importance of utilizing non-porous materials in industrial and clinical settings. 相似文献
105.
Multi-environment analysis and improved mapping of a yield-related QTL on chromosome 3B of wheat 总被引:1,自引:0,他引:1
Julien Bonneau Julian Taylor Boris Parent Dion Bennett Matthew Reynolds Catherine Feuillet Peter Langridge Diane Mather 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2013,126(3):747-761
Improved mapping, multi-environment quantitative trait loci (QTL) analysis and dissection of allelic effects were used to define a QTL associated with grain yield, thousand grain weight and early vigour on chromosome 3BL of bread wheat (Triticum aestivum L.) under abiotic stresses. The QTL had pleiotropic effects and showed QTL x environment interactions across 21 diverse environments in Australia and Mexico. The occurrence and the severity of water deficit combined with high temperatures during the growing season affected the responsiveness of this QTL, resulting in a reversal in the direction of allelic effects. The influence of this QTL can be substantial, with the allele from one parent (RAC875) increasing grain yield by up to 12.5 % (particularly in environments where both heat and drought stress occurred) and the allele from the other parent (Kukri) increasing grain yield by up to 9 % in favourable environments. With the application of additional markers and the genotyping of additional recombinant inbred lines, the genetic map in the QTL region was refined to provide a basis for future positional cloning. 相似文献
106.
Diane Frost 《Ethnic and racial studies》2013,36(13):2251-2258
Racism, Class and the Racialized Outsider offers a sympathetic yet critical and scholarly re-examination of historical working-class politics through a detailed analysis of ‘race’. It follows the historiographical and theoretical trail of previous radical scholars, like Nairn on English nationalism and the groundbreaking but ‘race-blind’ work of heavyweight socialist labour historians like Hobsbawm and Thompson. While there have been many seminal studies of the English working class, this book points to the failure of such histories to explore the significance of class as articulated through the lens of race. In revisiting and reworking these influential works, the book critically appraises the significant part played by racialized elements of the working class, including Irish Catholics and Jews who are shown to have occupied centre stage, forming the vanguard of early socialist movements and labour organizations. This was no accident and fed into subsequent multiracial and socialist internationalist movements. 相似文献
107.
Sally Thirkettle Julie Decock Hugh Arnold Caroline J. Pennington Diane M. Jaworski Dylan R. Edwards 《The Journal of biological chemistry》2013,288(23):16282-16294
Matrix metalloproteinase 8 (MMP-8) is a tumor-suppressive protease that cleaves numerous substrates, including matrix proteins and chemokines. In particular, MMP-8 proteolytically activates IL-8 and, thereby, regulates neutrophil chemotaxis in vivo. We explored the effects of expression of either a WT or catalytically inactive (E198A) mutant version of MMP-8 in human breast cancer cell lines. Analysis of serum-free conditioned media from three breast cancer cell lines (MCF-7, SK-BR-3, and MDA-MB-231) expressing WT MMP-8 revealed elevated levels of IL-6 and IL-8. This increase was mirrored at the mRNA level and was dependent on MMP-8 catalytic activity. However, sustained expression of WT MMP-8 by breast cancer cells was non-permissive for long-term growth, as shown by reduced colony formation compared with cells expressing either control vector or E198A mutant MMP-8. In long-term culture of transfected MDA-MB-231 cells, expression of WT but not E198A mutant MMP-8 was lost, with IL-6 and IL-8 levels returning to base line. Rare clonal isolates of MDA-MB-231 cells expressing WT MMP-8 were generated, and these showed constitutively high levels of IL-6 and IL-8, although production of the interleukins was no longer dependent upon MMP-8 activity. These studies support a causal connection between MMP-8 activity and the IL-6/IL-8 network, with an acute response to MMP-8 involving induction of the proinflammatory mediators, which may in part serve to compensate for the deleterious effects of MMP-8 on breast cancer cell growth. This axis may be relevant to the recognized ability of MMP-8 to orchestrate the innate immune system in inflammation in vivo. 相似文献
108.
Karen L. Maxwell Mostafa Fatehi Hassanabad Tom Chang Nawaz Pirani Diane Bona Aled M. Edwards Alan R. Davidson 《Journal of bacteriology》2013,195(24):5461-5468
A variety of bacterial pathogenicity determinants, including the type VI secretion system and the virulence cassettes from Photorhabdus and Serratia, share an evolutionary origin with contractile-tailed myophages. The well-characterized Escherichia coli phage P2 provides an excellent system for studies related to these systems, as its protein composition appears to represent the “minimal” myophage tail. In this study, we used nuclear magnetic resonance (NMR) spectroscopy to determine the solution structure of gpX, a 68-residue tail baseplate protein. Although the sequence and structure of gpX are similar to those of LysM domains, which are a large family associated with peptidoglycan binding, we did not detect a peptidoglycan-binding activity for gpX. However, bioinformatic analysis revealed that half of all myophages, including all that possess phage T4-like baseplates, encode a tail protein with a LysM-like domain, emphasizing a widespread role for this domain in baseplate function. While phage P2 gpX comprises only a single LysM domain, many myophages display LysM domain fusions with other tail proteins, such as the DNA circulation protein found in Mu-like phages and gp53 of T4-like phages. Electron microscopy of P2 phage particles with an incorporated gpX-maltose binding protein fusion revealed that gpX is located at the top of the baseplate, near the junction of the baseplate and tail tube. gpW, the orthologue of phage T4 gp25, was also found to localize to this region. A general colocalization of LysM-like domains and gpW homologues in diverse phages is supported by our bioinformatic analysis. 相似文献
109.
Jeff A. O'Meara Christopher T. Lemke Cédrickx Godbout George Kukolj Lisette Lagacé Beno?t Moreau Diane Thibeault Peter W. White Montse Llinàs-Brunet 《The Journal of biological chemistry》2013,288(8):5673-5681
Although optimizing the resistance profile of an inhibitor can be challenging, it is potentially important for improving the long term effectiveness of antiviral therapy. This work describes our rational approach toward the identification of a macrocyclic acylsulfonamide that is a potent inhibitor of the NS3-NS4A proteases of all hepatitis C virus genotypes and of a panel of genotype 1-resistant variants. The enhanced potency of this compound versus variants D168V and R155K facilitated x-ray determination of the inhibitor-variant complexes. In turn, these structural studies revealed a complex molecular basis of resistance and rationalized how such compounds are able to circumvent these mechanisms. 相似文献
110.
Frank Maldarelli Mary Kearney Sarah Palmer Robert Stephens JoAnn Mican Michael A. Polis Richard T. Davey Joseph Kovacs Wei Shao Diane Rock-Kress Julia A. Metcalf Catherine Rehm Sarah E. Greer Daniel L. Lucey Kristen Danley Harvey Alter John W. Mellors John M. Coffin 《Journal of virology》2013,87(18):10313-10323
HIV infection is characterized by rapid and error-prone viral replication resulting in genetically diverse virus populations. The rate of accumulation of diversity and the mechanisms involved are under intense study to provide useful information to understand immune evasion and the development of drug resistance. To characterize the development of viral diversity after infection, we carried out an in-depth analysis of single genome sequences of HIV pro-pol to assess diversity and divergence and to estimate replicating population sizes in a group of treatment-naive HIV-infected individuals sampled at single (n = 22) or multiple, longitudinal (n = 11) time points. Analysis of single genome sequences revealed nonlinear accumulation of sequence diversity during the course of infection. Diversity accumulated in recently infected individuals at rates 30-fold higher than in patients with chronic infection. Accumulation of synonymous changes accounted for most of the diversity during chronic infection. Accumulation of diversity resulted in population shifts, but the rates of change were low relative to estimated replication cycle times, consistent with relatively large population sizes. Analysis of changes in allele frequencies revealed effective population sizes that are substantially higher than previous estimates of approximately 1,000 infectious particles/infected individual. Taken together, these observations indicate that HIV populations are large, diverse, and slow to change in chronic infection and that the emergence of new mutations, including drug resistance mutations, is governed by both selection forces and drift. 相似文献