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Genome sequencing is an increasingly common component of infectious disease outbreak investigations. However, the relationship between pathogen transmission and observed genetic data is complex, and dependent on several uncertain factors. As such, simulation of pathogen dynamics is an important tool for interpreting observed genomic data in an infectious disease outbreak setting, in order to test hypotheses and to explore the range of outcomes consistent with a given set of parameters. We introduce ‘seedy’, an R package for the simulation of evolutionary and epidemiological dynamics (http://cran.r-project.org/web/packages/seedy/). Our software implements stochastic models for the accumulation of mutations within hosts, as well as individual-level disease transmission. By allowing variables such as the transmission bottleneck size, within-host effective population size and population mixing rates to be specified by the user, our package offers a flexible framework to investigate evolutionary dynamics during disease outbreaks. Furthermore, our software provides theoretical pairwise genetic distance distributions to provide a likelihood of person-to-person transmission based on genomic observations, and using this framework, implements transmission route assessment for genomic data collected during an outbreak. Our open source software provides an accessible platform for users to explore pathogen evolution and outbreak dynamics via simulation, and offers tools to assess observed genomic data in this context. 相似文献
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Cell density and airspace patterning in the leaf can be manipulated to increase leaf photosynthetic capacity 下载免费PDF全文
Andrew Mathers Jen Sloan Marion Bauch Alice Mitchell Chandra Bellasio Adam Green Daniel Bouyer Arp Schnittger Craig Sturrock Colin P. Osborne Stephen Rolfe Sacha Mooney Andrew J. Fleming 《The Plant journal : for cell and molecular biology》2017,92(6):981-994
The pattern of cell division, growth and separation during leaf development determines the pattern and volume of airspace in a leaf. The resulting balance of cellular material and airspace is expected to significantly influence the primary function of the leaf, photosynthesis, and yet the manner and degree to which cell division patterns affect airspace networks and photosynthesis remains largely unexplored. In this paper we investigate the relationship of cell size and patterning, airspace and photosynthesis by promoting and repressing the expression of cell cycle genes in the leaf mesophyll. Using microCT imaging to quantify leaf cellular architecture and fluorescence/gas exchange analysis to measure leaf function, we show that increased cell density in the mesophyll of Arabidopsis can be used to increase leaf photosynthetic capacity. Our analysis suggests that this occurs both by increasing tissue density (decreasing the relative volume of airspace) and by altering the pattern of airspace distribution within the leaf. Our results indicate that cell division patterns influence the photosynthetic performance of a leaf, and that it is possible to engineer improved photosynthesis via this approach. 相似文献
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Xiao Ding Xuedong Dai Kai Long Cheng Peng Daniele Andreotti Paul Bamborough Andrew J. Eatherton Colin Edge Karamjit S. Jandu Paula L. Nichols Oliver J. Philps Luigi Piero Stasi Zehong Wan Jia-Ning Xiang Kelly Dong Pamela Dossang Ming-Hsun Ho Yi Li Feng Ren 《Bioorganic & medicinal chemistry letters》2017,27(17):4034-4038
Leucine-rich repeat kinase 2 (LRRK2) has been suggested as a potential therapeutic target for Parkinson’s disease. Herein we report the discovery of 5-substituent-N-arylbenzamide derivatives as novel LRRK2 inhibitors. Extensive SAR study led to the discovery of compounds 8e, which demonstrated potent LRRK2 inhibition activity, high selectivity across the kinome, good brain exposure, and high oral bioavailability. 相似文献
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Social and spatial effects on genetic variation between foraging flocks in a wild bird population 下载免费PDF全文
Reinder Radersma Colin J. Garroway Anna W. Santure Isabelle de Cauwer Damien R. Farine Jon Slate Ben C. Sheldon 《Molecular ecology》2017,26(20):5807-5819
Social interactions are rarely random. In some instances, animals exhibit homophily or heterophily, the tendency to interact with similar or dissimilar conspecifics, respectively. Genetic homophily and heterophily influence the evolutionary dynamics of populations, because they potentially affect sexual and social selection. Here, we investigate the link between social interactions and allele frequencies in foraging flocks of great tits (Parus major) over three consecutive years. We constructed co‐occurrence networks which explicitly described the splitting and merging of 85,602 flocks through time (fission–fusion dynamics), at 60 feeding sites. Of the 1,711 birds in those flocks, we genotyped 962 individuals at 4,701 autosomal single nucleotide polymorphisms (SNPs). By combining genomewide genotyping with repeated field observations of the same individuals, we were able to investigate links between social structure and allele frequencies at a much finer scale than was previously possible. We explicitly accounted for potential spatial effects underlying genetic structure at the population level. We modelled social structure and spatial configuration of great tit fission–fusion dynamics with eigenvector maps. Variance partitioning revealed that allele frequencies were strongly affected by group fidelity (explaining 27%–45% of variance) as individuals tended to maintain associations with the same conspecifics. These conspecifics were genetically more dissimilar than expected, shown by genomewide heterophily for pure social (i.e., space‐independent) grouping preferences. Genomewide homophily was linked to spatial configuration, indicating spatial segregation of genotypes. We did not find evidence for homophily or heterophily for putative socially relevant candidate genes or any other SNP markers. Together, these results demonstrate the importance of distinguishing social and spatial processes in determining population structure. 相似文献
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Firdissa E. Bokore Richard D. Cuthbert Ron E. Knox Harpinder S. Randhawa Colin W. Hiebert Ron M. DePauw Asheesh K. Singh Arti Singh Andrew G. Sharpe Amidou N’Diaye Curtis J. Pozniak Curt McCartney Yuefeng Ruan Samia Berraies Brad Meyer Catherine Munro Andy Hay Karim Ammar Julio Huerta-Espino Sridhar Bhavani 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2017,130(12):2617-2635
Key message
Quantitative trait loci controlling stripe rust resistance were identified in adapted Canadian spring wheat cultivars providing opportunity for breeders to stack loci using marker-assisted breeding.Abstract
Stripe rust or yellow rust, caused by Puccinia striiformis Westend. f. sp. tritici Erikss., is a devastating disease of common wheat (Triticum aestivum L.) in many regions of the world. The objectives of this research were to identify and map quantitative trait loci (QTL) associated with stripe rust resistance in adapted Canadian spring wheat cultivars that are effective globally, and investigate opportunities for stacking resistance. Doubled haploid (DH) populations from the crosses Vesper/Lillian, Vesper/Stettler, Carberry/Vesper, Stettler/Red Fife and Carberry/AC Cadillac were phenotyped for stripe rust severity and infection response in field nurseries in Canada (Lethbridge and Swift Current), New Zealand (Lincoln), Mexico (Toluca) and Kenya (Njoro), and genotyped with SNP markers. Six QTL for stripe rust resistance in the population of Vesper/Lillian, five in Vesper/Stettler, seven in Stettler/Red Fife, four in Carberry/Vesper and nine in Carberry/AC Cadillac were identified. Lillian contributed stripe rust resistance QTL on chromosomes 4B, 5A, 6B and 7D, AC Cadillac on 2A, 2B, 3B and 5B, Carberry on 1A, 1B, 4A, 4B, 7A and 7D, Stettler on 1A, 2A, 3D, 4A, 5B and 6A, Red Fife on 2D, 3B and 4B, and Vesper on 1B, 2B and 7A. QTL on 1A, 1B, 2A, 2B, 3B, 4A, 4B, 5B, 7A and 7D were observed in multiple parents. The populations are compelling sources of recombination of many stripe rust resistance QTL for stacking disease resistance. Gene pyramiding should be possible with little chance of linkage drag of detrimental genes as the source parents were mostly adapted cultivars widely grown in Canada.1000.
Omer Nevo Kim Valenta Alex G. Tevlin Patrick Omeja Sarah A. Styler Derek J. Jackson Colin A. Chapman Manfred Ayasse 《Evolutionary ecology》2017,31(6):913-923
Plants are prone to attack by a great diversity of antagonists against which they deploy various defence mechanisms, of which the two principle ones are mechanical and chemical defences. These defences are hypothesized to be negatively correlated due to either functional redundancy or a trade-off, i.e., plants which rely on increased mechanical defence should downregulate their degree of chemical defence and vice versa. A competing hypothesis is that different defences perform distinct functions and draw from different pools of resources, which should result in their independent evolution. We examine these competing hypotheses using two independent datasets of fleshy fruits we collected from Madagascar and Uganda. We sampled mechanical defences, indexed by fruit puncture resistance, and defensive defences, indexed by defensive volatile organic compounds, and examined their associations using phylogenetically-controlled models. In both systems, we found no correlation between mechanical and chemical defences, thus supporting the independent evolution hypothesis. This implies that fruit defence mechanisms reflect a more complex array of selection pressures and constraints than previously perceived. 相似文献