359 research outputs found

    Population genetics of trypanosoma brucei rhodesiense: clonality and diversity within and between foci

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    African trypanosomes are unusual among pathogenic protozoa in that they can undergo their complete morphological life cycle in the tsetse fly vector with mating as a non-obligatory part of this development. Trypanosoma brucei rhodesiense, which infects humans and livestock in East and Southern Africa, has classically been described as a host-range variant of the non-human infective Trypanosoma brucei that occurs as stable clonal lineages. We have examined T. b. rhodesiense populations from East (Uganda) and Southern (Malawi) Africa using a panel of microsatellite markers, incorporating both spatial and temporal analyses. Our data demonstrate that Ugandan T. b. rhodesiense existed as clonal populations, with a small number of highly related genotypes and substantial linkage disequilibrium between pairs of loci. However, these populations were not stable as the dominant genotypes changed and the genetic diversity also reduced over time. Thus these populations do not conform to one of the criteria for strict clonality, namely stability of predominant genotypes over time, and our results show that, in a period in the mid 1990s, the previously predominant genotypes were not detected but were replaced by a novel clonal population with limited genetic relationship to the original population present between 1970 and 1990. In contrast, the Malawi T. b. rhodesiense population demonstrated significantly greater diversity and evidence for frequent genetic exchange. Therefore, the population genetics of T. b. rhodesiense is more complex than previously described. This has important implications for the spread of the single copy T. b. rhodesiense gene that allows human infectivity, and therefore the epidemiology of the human disease, as well as suggesting that these parasites represent an important organism to study the influence of optional recombination upon population genetic dynamics

    Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

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    Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro. In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research

    Catalytic living ring-opening metathesis polymerization

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    In living ring-opening metathesis polymerization (ROMP), a transition-metal–carbene complex polymerizes ring-strained olefins with very good control of the molecular weight of the resulting polymers. Because one molecule of the initiator is required for each polymer chain, however, this type of polymerization is expensive for widespread use. We have now designed a chain-transfer agent (CTA) capable of reducing the required amount of metal complex while still maintaining full control over the living polymerization process. This new method introduces a degenerative transfer process to ROMP. We demonstrate that substituted cyclohexene rings are good CTAs, and thereby preserve the β€˜living’ character of the polymerization using catalytic quantities of the metal complex. The resulting polymers show characteristics of a living polymerization, namely narrow molecular-weight distribution, controlled molecular weights and block copolymer formation. This new technique provides access to well- defined polymers for industrial, biomedical and academic use at a fraction of the current costs and significantly reduced levels of residual ruthenium catalyst

    The elevation in circulating anti-angiogenic factors is independent of markers of neutrophil activation in preeclampsia

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    Background - Severe preeclampsia is associated with increased neutrophil activation and elevated serum soluble endoglin (sEng) and soluble Flt-1 (sFlt-1) in the maternal circulation. To dissect the contribution of systemic inflammation and anti-angiogenic factors in preeclampsia, we investigated the relationships between the circulating markers of neutrophil activation and anti-angiogenic factors in severe preeclampsia or systemic inflammatory state during pregnancy. Methods and results - Serum sEng, sFlt-1, placenta growth factor, interleukin-6 (IL-6), calprotectin, and plasma a-defensins concentrations were measured by ELISA in 88 women of similar gestational age stratified as: severe preeclampsia (sPE, n = 45), maternal systemic inflammatory response (SIR, n = 16) secondary to chorioamnionitis, pyelonephritis or appendicitis; and normotensive controls (CRL, n = 27). Neutrophil activation occurred in sPE and SIR, as a-defensins and calprotectin concentrations were two-fold higher in both groups compared to CRL (P < 0.05 for each). IL-6 concentrations were highest in SIR (P < 0.001), but were higher in sPE than in CRL (P < 0.01). sFlt-1 (P < 0.001) and sEng (P < 0.001) were ˜20-fold higher in sPE compared to CRL, but were not elevated in SIR. In women with sPE, anti-angiogenic factors were not correlated with markers of neutrophil activation (a-defensins, calprotectin) or inflammation (IL-6). Conclusions - Increased systemic inflammation in sPE and SIR does not correlate with increased anti-angiogenic factors, which were specifically elevated in sPE indicating that excessive systemic inflammation is unlikely to be the main contributor to severe preeclampsia

    Heritable determinants of male fertilization success in the nematode Caenorhabditis elegans

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    <p>Abstract</p> <p>Background</p> <p>Sperm competition is a driving force in the evolution of male sperm characteristics in many species. In the nematode <it>Caenorhabditis elegans</it>, larger male sperm evolve under experimentally increased sperm competition and larger male sperm outcompete smaller hermaphrodite sperm for fertilization within the hermaphrodite reproductive tract. To further elucidate the relative importance of sperm-related traits that contribute to differential reproductive success among males, we quantified within- and among-strain variation in sperm traits (size, rate of production, number transferred, competitive ability) for seven male genetic backgrounds known previously to differ with respect to some sperm traits. We also quantified male mating ability in assays for rates of courtship and successful copulation, and then assessed the roles of these pre- and post-mating traits in first- and second-male fertilization success.</p> <p>Results</p> <p>We document significant variation in courtship ability, mating ability, sperm size and sperm production rate. Sperm size and production rate were strong indicators of early fertilization success for males that mated second, but male genetic backgrounds conferring faster sperm production make smaller sperm, despite virgin males of all genetic backgrounds transferring indistinguishable numbers of sperm to mating partners.</p> <p>Conclusions</p> <p>We have demonstrated that sperm size and the rate of sperm production represent dominant factors in determining male fertilization success and that <it>C. elegans </it>harbors substantial heritable variation for traits contributing to male reproductive success. <it>C. elegans </it>provides a powerful, tractable system for studying sexual selection and for dissecting the genetic basis and evolution of reproduction-related traits.</p

    Coordinated Translocation of Mammalian Gli Proteins and Suppressor of Fused to the Primary Cilium

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    Intracellular transduction of Hedgehog (Hh) signals in mammals requires functional primary cilia. The Hh signaling effectors, the Gli family of transcription factors, and their negative regulator, Suppressor of Fused (Sufu), accumulate at the tips of cilia; however, the molecular mechanism regulating this localization remains elusive. In the current study, we show that the ciliary localization of mammalian Gli proteins depends on both their N-terminal domains and a central region lying C-terminal to the zinc-finger DNA-binding domains. Invertebrate Gli homologs Ci and Tra1, when over-expressed in ciliated mouse fibroblasts, fail to localize to the cilia, suggesting the lack of a vertebrate-specific structural feature required for ciliary localization. We further show that activation of protein kinase A (PKA) efficiently inhibits ciliary localization of Gli2 and Gli3, but only moderately affects the ciliary localization of Gli1. Interestingly, variants of Gli2 mimicking the phosphorylated or non-phosphorylated states of Gli2 are both localized to the cilia, and their ciliary localizations are subjected to the inhibitory effect of PKA activation, suggesting a likely indirect mechanism underlying the roles of PKA in Gli ciliary localization. Finally, we show that ciliary localization of Sufu is dependent on ciliary-localized Gli proteins, and is inhibited by PKA activation, suggesting a coordinated mechanism for the ciliary translocation of Sufu and Gli proteins

    Vitamin D prevents endothelial progenitor cell dysfunction induced by sera from women with preeclampsia or conditioned media from hypoxic placenta

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    Context: Placenta-derived circulating factors contribute to the maternal endothelial dysfunction underlying preeclampsia. Endothelial colony forming cells (ECFC), a sub-population of endothelial progenitor cells (EPCs), are thought to be involved in vasculogenesis and endothelial repair. Low vitamin D concentrations are associated with an increased risk for preeclampsia. Objective: We hypothesized that the function of human fetal ECFCs in culture would be suppressed by exposure to preeclampsia-related factors-preeclampsia serum or hypoxic placental conditioned medium- in a fashion reversed by vitamin D. Design, Setting, Patients: ECFCs were isolated from cord blood of uncomplicated pregnancies and expanded in culture. Uncomplicated pregnancy villous placenta in explant culture were exposed to either 2% (hypoxic), 8% (normoxic) or 21% (hyperoxic) O2 for 48 h, after which the conditioned media (CM) was collected. Outcome Measures: ECFC tubule formation (Matrigel assay) and migration were examined in the presence of either maternal serum from preeclampsia cases or uncomplicated pregnancy controls, or pooled CM, in the presence or absence of 1,25(OH)2 vitamin D3. Results: 1,25(OH)2 vitamin D3 reversed the adverse effects of preeclampsia serum or CM from hypoxic placenta on ECFCs capillary-tube formation and migration. Silencing of VDR expression by VDR siRNA, VDR blockade, or VEGF pathway blockade reduced ECFC functional abilities. Effects of VDR or VEGF blockade were partially prevented by vitamin D. Conclusion: Vitamin D promotes the capillary-like tubule formation and migration of ECFCs in culture, minimizing the negative effects of exposure to preeclampsia-related factors. Further evaluation of the role of vitamin D in ECFC regulation and preeclampsia is warranted. Β© 2014 Brodowski et al

    Going Solo: Discovery of the First Parthenogenetic Gordiid (Nematomorpha: Gordiida)

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    Despite the severe fitness costs associated with sexual reproduction, its persistence and pervasiveness among multicellular organisms testifies to its intrinsic, short-term advantages. However, the reproductive assurance hypothesis predicts selection favoring asexual reproduction in sparse populations and when mate finding is difficult. Difficulties in finding mates is especially common in parasites, whose life cycles involve multiple hosts, or being released from the host into the external environment where the parasite can find itself trapped without a sexual partner. To solve this problem and guarantee reproduction, parasites in numerous phyla have evolved reproductive strategies, as predicted by the reproductive assurance hypothesis, such as hermaphroditism or parthenogenesis. However, this type of strategy has not been reported from species in the phylum Nematomorpha, whose populations have often been described as sparse. A new Nematomorpha species, Paragordius obamai n. sp., was discovered from Kenya, Africa, and appears to have solved the problem of being trapped without a mate by eliminating the need for males. Paragordius obamai n. sp. represents the first and only known species within this phylum to reproduce asexually. To determine the mechanism of this mating strategy, we ruled out the involvement of reproduction manipulating endosymbionts by use of next generation sequencing data, thus suggesting that parthenogenesis is determined genetically and may have evolved as a means to assure reproduction. Since this new parthenogenetic species and a closely related gonochoristic North American congener, P. varius, are easy to propagate in the laboratory, these gordiids can be used as model systems to test hypotheses on the genetic advantages and disadvantages of asexual reproduction and the genetic determinants of reproductive strategies in parasites

    Estimation of Isolation Times of the Island Species in the Drosophila simulans Complex from Multilocus DNA Sequence Data

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    Background: The Drosophila simulans species complex continues to serve as an important model system for the study of new species formation. The complex is comprised of the cosmopolitan species, D. simulans, and two island endemics, D. mauritiana and D. sechellia. A substantial amount of effort has gone into reconstructing the natural history of the complex, in part to infer the context in which functional divergence among the species has arisen. In this regard, a key parameter to be estimated is the initial isolation time (t) of each island species. Loci in regions of low recombination have lower divergence within the complex than do other loci, yet divergence from D. melanogaster is similar for both classes. This might reflect gene flow of the lowrecombination loci subsequent to initial isolation, but it might also reflect differential effects of changing population size on the two recombination classes of loci when the low-recombination loci are subject to genetic hitchhiking or pseudohitchhiking Methodology/Principal Findings: New DNA sequence variation data for 17 loci corroborate the prior observation from 13 loci that DNA sequence divergence is reduced in genes of low recombination. Two models are presented to estimate t and other relevant parameters (substitution rate correction factors in lineages leading to the island species and, in the case of the 4-parameter model, the ratio of ancestral to extant effective population size) from the multilocus DNA sequence data. Conclusions/Significance: In general, it appears that both island species were isolated at about the same time, here estimated at,250,000 years ago. It also appears that the difference in divergence patterns of genes in regions of low an
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