124 research outputs found
The origins of postmating reproductive isolation: testing hypotheses in the grasshopper Chorthippus parallelus
Although there are several well-established hypotheses for the origins of postmating isolation during allopatric divergence, there have been very few attempts, to determine their relative importance in nature. We have developed an approach based on knowledge of the differing evolutionary histories of populations within species that allows systematic comparison of the predictions of these hypotheses. In previous work, we have applied this methodology to mating signal variation and premating reproductive isolation between populations of the meadow grasshopper Chorthippus parallelus. Here we review the principles behind our approach and report a study measuring postmating isolation in the same set of populations. The populations have known and differing evolutionary histories and relationships resulting from the colonization of northern Europe following the last glaciation. We use a maximum-likelihood analysis to compare the observed pattern of postmating isolation with the predictions of the hypotheses that isolation primarily evolves either as a result of gradual accumulation of mutations in allopatry, or through processes associated with colonization, such as founder events., We also quantify the extent to which degree of postmating isolation can be predicted by genetic distance. Our results suggest that although there is only a weak correlation between genetic distance and postmating isolation, long periods of allopatry do lead to postmating isolation. In contrast to the pattern of premating isolation described in our previous study, colonization does not seem to be associated with increased postmating isolation
Pragmatic considerations for negative control outcome studies to guide non-randomized comparative analyses: A narrative review
Purpose: This narrative review describes the application of negative control outcome (NCO) methods to assess potential bias due to unmeasured or mismeasured confounders in non-randomized comparisons of drug effectiveness and safety. An NCO is assumed to have no causal relationship with a treatment under study while subject to the same confounding structure as the treatment and outcome of interest; an association between treatment and NCO then reflects the potential for uncontrolled confounding between treatment and outcome. Methods: We focus on two recently completed NCO studies that assessed the comparability of outcome risk for patients initiating different osteoporosis medications and lipid-lowering therapies, illustrating several ways in which confounding may result. In these studies, NCO methods were implemented in claims-based data sources, with the results used to guide the decision to proceed with comparative effectiveness or safety analyses. Results: Based on this research, we provide recommendations for future NCO studies, including considerations for the identification of confounding mechanisms in the target patient population, the selection of NCOs expected to satisfy required assumptions, the interpretation of NCO effect estimates, and the mitigation of uncontrolled confounding detected in NCO analyses. We propose the use of NCO studies prior to initiating comparative effectiveness or safety research, providing information on the potential presence of uncontrolled confounding in those comparative analyses. Conclusions: Given the increasing use of non-randomized designs for regulatory decision-making, the application of NCO methods will strengthen study design, analysis, and interpretation of real-world data and the credibility of the resulting real-world evidence
Determination of Population Structure of Wheat Core Collection for Association Mapping
The microsatellites, as one of the most robust markers for identification of wheat varieties, were used for assessment of genetic diversity and population structure to promote effective use of genetic resources. In this study, the set of 284 wheat varieties were genotyped using 30 microsatellite markers. The chosen SSR markers were located among almost all linkage groups and covered all three genomes. The genotypes used originate from 24 different breeding centers worldwide and are included in an extensive core collection of the Institute of Field and Vegetable Crops in Novi Sad, Serbia. The total number of detected alleles was 349 at all analyzed loci. The average number of detected allelic variant per locus was 11.5. The mean value of polymorphic information content was 0.68. According to the probability of data obtained by program Structure, the results have shown presence of 6 subpopulations within the studied set of genotypes. The population structure positively correlated to some extent with geographic origin. The available pedigree data were included for additional explanation of population structure. The results of this study should provide valuable information for future association studies using the diverse wheat breeding material
Non-canonical Hedgehog signaling mediates profibrotic hematopoiesis-stroma crosstalk in myeloproliferative neoplasms.
The role of hematopoietic Hedgehog signaling in myeloproliferative neoplasms (MPNs) remains incompletely understood despite data suggesting that Hedgehog (Hh) pathway inhibitors have therapeutic activity in patients. We aim to systematically interrogate the role of canonical vs. non-canonical Hh signaling in MPNs. We show that Gli1 protein levels in patient peripheral blood mononuclear cells (PBMCs) mark fibrotic progression and that, in murine MPN models, absence of hematopoietic Gli1, but not Gli2 or Smo, significantly reduces MPN phenotype and fibrosis, indicating that GLI1 in the MPN clone can be activated in a non-canonical fashion. Additionally, we establish that hematopoietic Gli1 has a significant effect on stromal cells, mediated through a druggable MIF-CD74 axis. These data highlight the complex interplay between alterations in the MPN clone and activation of stromal cells and indicate that Gli1 represents a promising therapeutic target in MPNs, particularly that Hh signaling is dispensable for normal hematopoiesis
Review of magnetic gear technologies and their applications in marine energy
The marine energy industry is in its early stages but has a large potential for growth. One of the most significant challenges is the reduction of operation and maintenance costs. Magnetic gears (MGs) offer the potential for long periods between maintenance intervals due to their frictionless torque transmission which could reduce these costs. This study presents a summary of the state of the art in MG technology and then investigates its potential for marine energy applications. A brief overview is given of the state of the marine energy industry and the environment in which marine energy converters (MECs) operate. A short history of MG development over the past century is then presented followed by a discussion of the leading MG technologies and their relative advantages. In order to demonstrate the potential of MGs in marine applications, the current technologies, i.e. mechanically geared and direct drive machines, are examined in terms of sizing, reliability and economic value using previous studies on a similar technology, namely wind. MGs are applied to four types of MECs to demonstrate how the technology can be incorporated. The potential to deploy at scale and potential obstacles to this are then discussed
Sex and virulence in Escherichia coli: an evolutionary perspective
Pathogenic Escherichia coli cause over 160 million cases of dysentery and one million deaths per year, whereas non-pathogenic E. coli constitute part of the normal intestinal flora of healthy mammals and birds. The evolutionary pathways underlying this dichotomy in bacterial lifestyle were investigated by multilocus sequence typing of a global collection of isolates. Specific pathogen types [enterohaemorrhagic E. coli, enteropathogenic E. coli, enteroinvasive E. coli, K1 and Shigella] have arisen independently and repeatedly in several lineages, whereas other lineages contain only few pathogens. Rates of evolution have accelerated in pathogenic lineages, culminating in highly virulent organisms whose genomic contents are altered frequently by increased rates of homologous recombination; thus, the evolution of virulence is linked to bacterial sex. This long-term pattern of evolution was observed in genes distributed throughout the genome, and thereby is the likely result of episodic selection for strains that can escape the host immune response
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