657 research outputs found
Sort by
Genetic diversity in the SIR model of pathogen evolution
Get PDFWe introduce a model for assessing the levels and patterns of genetic diversity in pathogen populations, whose epidemiology follows a susceptible-infected-recovered model (SIR). We model the population of pathogens as a metapopulation composed of subpopulations (infected hosts), where pathogens replicate and mutate. Hosts transmit pathogens to uninfected hosts. We show that the level of pathogen variation is well predicted by analytical expressions, such that pathogen neutral molecular variation is bounded by the level of infection and increases with the duration of infection. We then introduce selection in the model and study the invasion probability of a new pathogenic strain whose fitness (R0(1+s)) is higher than the fitness of the resident strain (R0). We show that this invasion probability is given by the relative increment in R0 of the new pathogen (s). By analyzing the patterns of genetic diversity in this framework, we identify the molecular signatures during the replacement and compare these with those observed in sequences of influenza A
Prospects for malaria eradication in sub-Saharan Africa
Get PDFBACKGROUND: A characteristic of Plasmodium falciparum infections is the gradual acquisition of clinical immunity resulting from repeated exposures to the parasite. While the molecular basis of protection against clinical malaria remains unresolved, its effects on epidemiological patterns are well recognized. Accumulating epidemiological data constitute a valuable resource that must be intensively explored and interpreted as to effectively inform control planning. METHODOLOGY/PRINCIPAL FINDING: Here we apply a mathematical model to clinical data from eight endemic regions in sub-Saharan Africa. The model provides a quantitative framework within which differences in age distribution of clinical disease are assessed in terms of the parameters underlying transmission. The shorter infectious periods estimated for clinical infections induce a regime of bistability of endemic and malaria-free states in regions of mesoendemic transmission. The two epidemiological states are separated by a threshold that provides a convenient measure for intervention design. Scenarios of eradication and resurgence are simulated. CONCLUSIONS/SIGNIFICANCE: In regions that support mesoendemic transmission, intervention success depends critically on reducing prevalence below a threshold which separates endemic and malaria-free regime
Partial classification of heteroclinic behaviour associated with the perturbation of hexagonal planforms
No full textPhysical systems often exhibit pattern-forming instabilities. Equivariant bifurcation theory is often used to investigate the existence and stability of spatially doubly periodic solutions with respect to the hexagonal lattice. Previous studies have focused on the six- and twelve-dimensional representation of the hexagonal lattice where the symmetry of the model is perfect. Here, perturbation of group orbits of translation-free axial planforms in the six- and twelve-dimensional representations is considered. This problem is studied via the abstract action of the symmetry group of the perturbation on the group orbit of the planform. A partial classification for the behaviour of the group orbits is obtained, showing the existence of homoclinic and heteroclinic cycles between equilibri
Epigenetic reprogramming and small RNA silencing of transposable elements in pollen
Get PDFThe mutagenic activity of transposable elements (TEs) is suppressed by epigenetic silencing and small interfering RNAs (siRNAs), especially in gametes that could transmit transposed elements to the next generation. In pollen from the model plant Arabidopsis, we show that TEs are unexpectedly reactivated and transpose, but only in the pollen vegetative nucleus, which accompanies the sperm cells but does not provide DNA to the fertilized zygote. TE expression coincides with downregulation of the heterochromatin remodeler decrease in DNA methylation 1 and of many TE siRNAs. However, 21 nucleotide siRNAs from Athila retrotransposons are generated and accumulate in pollen and sperm, suggesting that siRNA from TEs activated in the vegetative nucleus can target silencing in gametes. We propose a conserved role for reprogramming in germline companion cells, such as nurse cells in insects and vegetative nuclei in plants, to reveal intact TEs in the genome and regulate their activity in gamete
Comparative transcriptomics of Arabidopsis sperm cells
Get PDFn flowering plants, the two sperm cells are embedded within the cytoplasm of the growing pollen tube and as such are passively transported to the embryo sac, wherein double fertilization occurs upon their release. Understanding the mechanisms and conditions by which male gametes mature and take part in fertilization are crucial goals in the study of plant reproduction. Studies of gene expression in male gametes of maize (Zea mays) and Plumbago and in lily (Lilium longiflorum) generative cells already showed that the previously held view of transcriptionally inert male gametes was not true, but genome-wide studies were lacking. Analyses in the model plant Arabidopsis (Arabidopsis thaliana) were hindered, because no method to isolate sperm cells was available. Here, we used fluorescence-activated cell sorting to isolate sperm cells from Arabidopsis, allowing GeneChip analysis of their transcriptome at a genome-wide level. Comparative analysis of the sperm cell transcriptome with those of representative sporophytic tissues and of pollen showed that sperm has a distinct and diverse transcriptional profile. Functional classifications of genes with enriched expression in sperm cells showed that DNA repair, ubiquitin-mediated proteolysis, and cell cycle progression are overrepresented Gene Ontology categories. Moreover, analysis of the small RNA and DNA methylation pathways suggests that distinct mechanisms might be involved in regulating the epigenetic state of the paternal genome. We identified numerous candidate genes whose involvement in sperm cell development and fertilization can now be directly tested in Arabidopsis. These results provide a roadmap to decipher the role of sperm-expressed protein
The Ypt/Rab family and the evolution of trafficking in Fungi
No full textThe evolution of the eukaryotic endomembrane system
and the transport pathways of their vesicular intermediates
are poorly understood. A common set of organelles
and pathways seems to be present in all free-living
eukaryotes, but different branches of the tree of life have
a variety of diverse, specialized organelles. Rab/Ypt
proteins are small guanosine triphosphatases with
tissue-specific and organelle-specific localization that
emerged as markers for organelle diversity. Here, I characterize
the Rab/Ypt family in the kingdom Fungi, a sister
kingdom of Animals. I identify and annotate these proteins
in 26 genomes representing near one billion years of
evolution, multiple lifestyles and cellular types. Surprisingly,
the minimal set of Rab/Ypt present in fungi is
similar to, perhaps smaller than, the predicted eukaryotic
ancestral set. This suggests that the saprophytic fungal
lifestyle, multicellularity as well as the highly polarized
secretion associated with hyphal growth did not require
any major innovation in the molecular machinery that
regulates protein trafficking. The Rab/Ypt and other protein
traffic-related families are kept small, not paralleling
increases in genome size, in contrast to the expansion of
such components observed in other branches of the tree
of life, such as the animal and plant kingdoms. This
analysis suggests that multicellularity and cellular diversity
in fungi followed different routes from those followed
by plants and metazo
Rapid Experimental Evolution of Pesticide Resistance in C. elegans Entails No Costs and Affects the Mating System
Get PDFPesticide resistance is a major concern in natural populations and a model trait to study adaptation. Despite the importance of this trait, the dynamics of its evolution and of its ecological consequences remain largely unstudied. To fill this gap, we performed experimental evolution with replicated populations of Caenorhabditis elegans exposed to the pesticide Levamisole during 20 generations. Exposure to Levamisole resulted in decreased survival, fecundity and male frequency, which declined from 30% to zero. This was not due to differential susceptibility of males. Rather, the drug affected mobility, resulting in fewer encounters, probably leading to reduced outcrossing rates. Adaptation, i.e., increased survival and fecundity, occurred within 10 and 20 generations, respectively. Male frequency also increased by generation 20. Adaptation costs were undetected in the ancestral environment and in presence of Ivermectin, another widely-used pesticide with an opposite physiological effect. Our results demonstrate that pesticide resistance can evolve at an extremely rapid pace. Furthermore, we unravel the effects of behaviour on life-history traits and test the environmental dependence of adaptation costs. This study establishes experimental evolution as a powerful tool to tackle pesticide resistance, and paves the way to further investigations manipulating environmental and/or genetic factors underlying adaptation to pesticides
Sex and deleterious mutations
Get PDFFor access the publication please visit the following link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2390638/The evolutionary advantage of sexual reproduction has been considered as one of the most pressing questions in evolutionary biology. While a pluralistic view of the evolution of sex and recombination has been suggested by some, here we take a simpler view and try to quantify the conditions under which sex can evolve given a set of minimal assumptions. Since real populations are finite and also subject to recurrent deleterious mutations, this minimal model should apply generally to all populations. We show that the maximum advantage of recombination occurs for an intermediate value of the deleterious effect of mutations. Furthermore we show that the conditions under which the biggest advantage of sex is achieved are those that produce the fastest fitness decline in the corresponding asexual population and are therefore the conditions for which Muller's ratchet has the strongest effect. We also show that the selective advantage of a modifier of the recombination rate depends on its strength. The quantification of the range of selective effects that favors recombination then leads us to suggest that, if in stressful environments the effect of deleterious mutations is enhanced, a connection between sex and stress could be expected, as it is found in several specie
Overexpression of delta-like 4 induces arterialization and attenuates
Get PDFThe importance of Notch signaling pathway in the regulation of vascular development and angiogenesis is suggested by the expression of Notch receptors and ligands in vascular endothelial cells (ECs) and the observed vascular phenotypes in mutants of Notch receptors or ligands, especially Dll4. DLL4 is specifically expressed in arterial ECs during development, and haplo-insufficiency is embryonically lethal in mice. To address the role of Dll4 in vascular development, we produced mDll4 conditionally overexpressed transgenic mice that were crossed with constitutive recombinase cre lines. Double transgenic embryos displayed grossly enlarged dorsal aortae (DA) and died before embryonic day 10.5 (E10.5), showing a variable degree of premature arteriovenous fusion. Veins displayed ectopic expression of arterial markers. Other defects included reduced vascular sprouting, EC proliferation, and migration. mDll4 overexpression also inhibited VEGF signaling and increased fibronectin accumulation around the vessels. In vitro and in vivo studies of DLL4-FL (Dll4-full-length) in ECs recapitulate many of the mDll4 transgenics findings, including decreased tube formation, reduced vascular branching, fewer vessels, increased pericyte recruitment, and increased fibronectin expression. These results establish the role of Dll4 in arterial identity determination, and regulation of angiogenesis subject to dose and location
Towards an image of a memory trace
Get PDFLearning and memory lead to functional and structural changes in the brain, ultimately providing a basis for adaptive behavior. The honeybee is an elegant model for the study of learning and memory formation as it permits both the visualization of neural activity related to the events occurring in olfactory learning and the behavioral assessment of olfactory learning (Galizia and Menzel, 2000 ). The formation of odor memories in the honeybee is thought to involve the two primary processing centers of the olfactory system, the antennal lobe (AL) and the mushroom body (MB). The intrinsic neurons of the MB – the Kenyon cells (KCs), located within the lip region of the MB calyx – are the site of convergence of the neural pathways that transmit odor information from the projection neurons (PNs) of the AL and reward information from the VUMmx1 neuron (Hammer, 1997 ). In recent years, imaging studies performed in the honeybee AL and MB lip have indicated that pairing odor and reward induces changes in neural activity (Faber and Menzel, 2001 ; Faber et al., 1999 ), reinforcing the anatomical suggestion that KCs are likely to undergo associative plasticity during learning