129 research outputs found
Mutation Accumulation in a Selfing Population: Consequences of Different Mutation Rates between Selfers and Outcrossers
Currently existing theories predict that because deleterious mutations accumulate at a higher rate, selfing populations suffer from more intense genetic degradation relative to outcrossing populations. This prediction may not always be true when we consider a potential difference in deleterious mutation rate between selfers and outcrossers. By analyzing the evolutionary stability of selfing and outcrossing in an infinite population, we found that the genome-wide deleterious mutation rate would be lower in selfing than in outcrossing organisms. When this difference in mutation rate was included in simulations, we found that in a small population, mutations accumulated more slowly under selfing rather than outcrossing. This result suggests that under frequent and intense bottlenecks, a selfing population may have a lower risk of genetic extinction than an outcrossing population
Within-Host Evolution of Burkholderia pseudomallei in Four Cases of Acute Melioidosis
Little is currently known about bacterial pathogen evolution and adaptation within the host during acute infection. Previous studies of Burkholderia pseudomallei, the etiologic agent of melioidosis, have shown that this opportunistic pathogen mutates rapidly both in vitro and in vivo at tandemly repeated loci, making this organism a relevant model for studying short-term evolution. In the current study, B. pseudomallei isolates cultured from multiple body sites from four Thai patients with disseminated melioidosis were subjected to fine-scale genotyping using multilocus variable-number tandem repeat analysis (MLVA). In order to understand and model the in vivo variable-number tandem repeat (VNTR) mutational process, we characterized the patterns and rates of mutations in vitro through parallel serial passage experiments of B. pseudomallei. Despite the short period of infection, substantial divergence from the putative founder genotype was observed in all four melioidosis cases. This study presents a paradigm for examining bacterial evolution over the short timescale of an acute infection. Further studies are required to determine whether the mutational process leads to phenotypic alterations that impact upon bacterial fitness in vivo. Our findings have important implications for future sampling strategies, since colonies in a single clinical sample may be genetically heterogeneous, and organisms in a culture taken late in the infective process may have undergone considerable genetic change compared with the founder inoculum
Validity of sports watches when estimating energy expenditure during running
The aim of this study was to assess the accuracy of three different sport watches in estimating energy expenditure during aerobic and anaerobic running
Oxidized LDL Receptor 1 (OLR1) as a Possible Link between Obesity, Dyslipidemia and Cancer
Recent studies have linked expression of lectin-like ox-LDL receptor 1
(OLR1) to tumorigenesis. We analyzed microarray data from
Olr1 knockout (KO) and wild type (WT) mice for genes
involved in cellular transformation and evaluated effects of
OLR1 over-expression in normal mammary epithelial cells
(MCF10A) and breast cancer cells (HCC1143) in terms of gene expression,
migration, adhesion and transendothelial migration. Twenty-six out of 238 genes
were inhibited in tissues of OLR1 KO mice; the vast majority of OLR1 sensitive
genes contained NF-ÎșB binding sites in their promoters. Further studies
revealed broad inhibition of NF-kB target genes outside of the
transformation-associated gene pool, with enrichment themes of defense response,
immune response, apoptosis, proliferation, and wound healing. Transcriptome of
Olr1 KO mice also revealed inhibition of de
novo lipogenesis, rate-limiting enzymes fatty acid synthase
(Fasn), stearoyl-CoA desaturase (Scd1) and
ELOVL family member 6 (Elovl6), as well as lipolytic
phospholipase A2 group IVB (Pla2g4b). In studies comparing
MCF10A and HCC1143, the latter displayed 60% higher OLR1
expression. Forced over-expression of OLR1 resulted in
upregulation of NF-ÎșB (p65) and its target pro-oncogenes involved in
inhibition of apoptosis (BCL2, BCL2A1,
TNFAIP3) and regulation of cell cycle
(CCND2) in both cell lines. Basal expression of
FASN, SCD1 and PLA2G4B,
as well as lipogenesis transcription factors PPARA,
SREBF2 and CREM, was higher in HCC1143
cells. Over-expression of OLR1 in HCC1143 cells also enhanced
cell migration, without affecting their adherence to TNFα-activated
endothelium or transendothelial migration. On the other hand,
OLR1 neutralizing antibody inhibited both adhesion and
transmigration of untreated HCC1143 cells. We conclude that
OLR1 may act as an oncogene by activation of NF-kB target
genes responsible for proliferation, migration and inhibition of apoptosis and
de novo lipogenesis genes
A Mighty Small Heart: The Cardiac Proteome of Adult Drosophila melanogaster
Drosophila melanogaster is emerging as a powerful model system
for the study of cardiac disease. Establishing peptide and protein maps of the
Drosophila heart is central to implementation of protein
network studies that will allow us to assess the hallmarks of
Drosophila heart pathogenesis and gauge the degree of
conservation with human disease mechanisms on a systems level. Using a
gel-LC-MS/MS approach, we identified 1228 protein clusters from 145 dissected
adult fly hearts. Contractile, cytostructural and mitochondrial proteins were
most abundant consistent with electron micrographs of the
Drosophila cardiac tube. Functional/Ontological enrichment
analysis further showed that proteins involved in glycolysis,
Ca2+-binding, redox, and G-protein signaling, among other
processes, are also over-represented. Comparison with a mouse heart proteome
revealed conservation at the level of molecular function, biological processes
and cellular components. The subsisting peptidome encompassed 5169 distinct
heart-associated peptides, of which 1293 (25%) had not been identified in
a recent Drosophila peptide compendium. PeptideClassifier
analysis was further used to map peptides to specific gene-models. 1872 peptides
provide valuable information about protein isoform groups whereas a further 3112
uniquely identify specific protein isoforms and may be used as a
heart-associated peptide resource for quantitative proteomic approaches based on
multiple-reaction monitoring. In summary, identification of
excitation-contraction protein landmarks, orthologues of proteins associated
with cardiovascular defects, and conservation of protein ontologies, provides
testimony to the heart-like character of the Drosophila cardiac
tube and to the utility of proteomics as a complement to the power of genetics
in this growing model of human heart disease
Human plague: An old scourge that needs new answers
Yersinia pestis, the bacterial causative agent of plague, remains an important threat to human health. Plague is a rodent-borne disease that has historically shown an outstanding ability to colonize and persist across different species, habitats, and environments while provoking sporadic cases, outbreaks, and deadly global epidemics among humans. Between September and November 2017, an outbreak of urban pneumonic plague was declared in Madagascar, which refocused the attention of the scientific community on this ancient human scourge. Given recent trends and plagueâs resilience to control in the wild, its high fatality rate in humans without early treatment, and its capacity to disrupt social and healthcare systems, human plague should be considered as a neglected threat. A workshop was held in Paris in July 2018 to review current knowledge about plague and to identify the scientific research priorities to eradicate plague as a human threat. It was concluded that an urgent commitment is needed to develop and fund a strong research agenda aiming to fill the current knowledge gaps structured around 4 main axes: (i) an improved understanding of the ecological interactions among the reservoir, vector, pathogen, and environment; (ii) human and societal responses; (iii) improved diagnostic tools and case management; and (iv) vaccine development. These axes should be cross-cutting, translational, and focused on delivering context-specific strategies. Results of this research should feed a global control and prevention strategy within a âOne Healthâ approach
Connecting high-throughput biodiversity inventories: Opportunities for a site-based genomic framework for global integration and synthesis
Highâthroughput sequencing (HTS) is increasingly being used for the characterization and monitoring of biodiversity. If applied in a structured way, across broad geographical scales, it offers the potential for a much deeper understanding of global biodiversity through the integration of massive quantities of molecular inventory data generated independently at local, regional and global scales. The universality, reliability and efficiency of HTS data can potentially facilitate the seamless linking of data among species assemblages from different sites, at different hierarchical levels of diversity, for any taxonomic group and regardless of prior taxonomic knowledge. However, collective international efforts are required to optimally exploit the potential of siteâbased HTS data for global integration and synthesis, efforts that at present are limited to the microbial domain. To contribute to the development of an analogous strategy for the nonmicrobial terrestrial domain, an international symposium entitled âNext Generation Biodiversity Monitoringâ was held in November 2019 in Nicosia (Cyprus). The symposium brought together evolutionary geneticists, ecologists and biodiversity scientists involved in diverse regional and global initiatives using HTS as a core tool for biodiversity assessment. In this review, we summarize the consensus that emerged from the 3âday symposium. We converged on the opinion that an effective terrestrial Genomic Observatories network for global biodiversity integration and synthesis should be spatially led and strategically united under the umbrella of the metabarcoding approach. Subsequently, we outline an HTSâbased strategy to collectively build an integrative framework for siteâbased biodiversity data generation
Linking Self-Incompatibility, Dichogamy, and Flowering Synchrony in Two Euphorbia Species: Alternative Mechanisms for Avoiding Self-Fertilization?
Background: Plant species have several mechanisms to avoid selfing such as dichogamy or a self-incompatibility response.
Dichogamy in a single flower may reduce autogamy but, to avoid geitonogamy, plants must show flowering
synchronization among all their flowers (i.e. synchronous dichogamy). It is hypothesized that one species would not
simultaneously show synchronous dichogamy and self-incompatibility because they are redundant mechanisms to reduce
selfing; however, this has not been accurately assessed.
Methodology/Principal Findings: This expectation was tested over two years in two natural populations of the closely
related Mediterranean spurges Euphorbia boetica and E. nicaeensis, which completely avoid autogamy by protogyny at the
cyathia level. Both spurges showed a high population synchrony (Z,79), and their inflorescences flower synchronously. In E.
nicaeensis, there was no overlap among the cyathia in anthesis of successive inflorescence levels and the overlap between
sexual phases of cyathia of the same inflorescence level was uncommon (4â16%). In contrast, E. boetica showed a high
overlap among consecutive inflorescence levels (74â93%) and between sexual phases of cyathia of the same inflorescence
level (48â80%). The flowering pattern of both spurges was consistent in the two populations and over the two successive
years. A hand-pollination experiment demonstrated that E. nicaeensis was strictly self-compatible whereas E. boetica was
partially self-incompatible.
Conclusions/Significance: We propose that the complex pattern of synchronized protogyny in E. nicaeensis prevents
geitonogamous crosses and, consequently, avoids selfing and inbreeding depression. In E. boetica, a high probability of
geitonogamous crosses may occur but, alternatively, this plant escapes selfing through a self-incompatibility response. We
posit that synchronous dichogamy and physiological self-incompatibility do not co-occur in the same species because each
process is sufficiently effective in avoiding self-fertilization.España Ministerio de Ciencia y TecnologĂa PLO CGL2005-03731; CGL2008-02533-EEspaña Ministerio de Ciencia y TecnologĂa MA CGL2009-0825
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