85 research outputs found
The relationship between the error catastrophe, survival of the flattest, and natural selection
<p>Abstract</p> <p>Background</p> <p>The quasispecies model is a general model of evolution that is generally applicable to replication up to high mutation rates. It predicts that at a sufficiently high mutation rate, quasispecies with higher mutational robustness can displace quasispecies with higher replicative capacity, a phenomenon called "survival of the flattest". In some fitness landscapes it also predicts the existence of a maximum mutation rate, called the error threshold, beyond which the quasispecies enters into error catastrophe, losing its genetic information. The aim of this paper is to study the relationship between survival of the flattest and the transition to error catastrophe, as well as the connection between these concepts and natural selection.</p> <p>Results</p> <p>By means of a very simplified model, we show that the transition to an error catastrophe corresponds to a value of zero for the selective coefficient of the mutant phenotype with respect to the master phenotype, indicating that transition to the error catastrophe is in this case similar to the selection of a more robust species. This correspondence has been confirmed by considering a single-peak landscape in which sequences are grouped with respect to their Hamming distant from the master sequence. When the robustness of a classe is changed by modification of its quality factor, the distribution of the population changes in accordance with the new value of the robustness, although an error catastrophe can be detected at the same values as in the general case. When two quasispecies of different robustness competes with one another, the entry of one of them into error catastrophe causes displacement of the other, because of the greater robustness of the former. Previous works are explicitly reinterpreted in the light of the results obtained in this paper.</p> <p>Conclusions</p> <p>The main conclusion of this paper is that the entry into error catastrophe is a specific case of survival of the flattest acting on phenotypes that differ in the trade-off between replicative ability and mutational robustness. In fact, entry into error catastrophe occurs when the mutant phenotype acquires a selective advantage over the master phenotype. As both entry into error catastrophe and survival of the flattest are caused by natural selection when mutation rate is increased, we propose differentiating between them by the level of selection at which natural selection acts. So we propose to consider the transition to error catastrophe as a phenomenon of intra-quasispecies selection, and survival of the flattest as a phenomenon of inter-quasispecies selection.</p
Immune response of healthy horses to DNA constructs formulated with a cationic lipid transfection reagent
Background Deoxyribonucleic acid (DNA) vaccines are used for experimental
immunotherapy of equine melanoma. The injection of complexed linear DNA
encoding interleukin (IL)-12/IL-18 induced partial tumour remission in a
clinical study including 27 grey horses. To date, the detailed mechanism of
the anti-tumour effect of this treatment is unknown. Results In the present
study, the clinical and cellular responses of 24 healthy horses were monitored
over 72 h after simultaneous intradermal and intramuscular application of
equine IL-12/IL-18 DNA (complexed with a transfection reagent) or comparative
substances (transfection reagent only, nonsense DNA, nonsense DNA depleted of
CG). Although the strongest effect was observed in horses treated with
expressing DNA, horses in all groups treated with DNA showed systemic
responses. In these horses treated with DNA, rectal temperatures were elevated
after treatment and serum amyloid A increased. Total leukocyte and neutrophil
counts increased, while lymphocyte numbers decreased. The secretion of tumour
necrosis factor alpha (TNFα) and interferon gamma (IFNγ) from peripheral
mononuclear blood cells ex vivo increased after treatments with DNA, while
IL-10 secretion decreased. Horses treated with DNA had significantly higher
myeloid cell numbers and chemokine (C-X-C motif) ligand (CXCL)-10 expression
in skin samples at the intradermal injection sites compared to horses treated
with transfection reagent only, suggesting an inflammatory response to DNA
treatment. In horses treated with expressing DNA, however, local CXCL-10
expression was highest and immunohistochemistry revealed more intradermal
IL-12-positive cells when compared to the other treatment groups. In contrast
to non-grey horses, grey horses showed fewer effects of DNA treatments on
blood lymphocyte counts, TNFα secretion and myeloid cell infiltration in the
dermis. Conclusion Treatment with complexed linear DNA constructs induced an
inflammatory response independent of the coding sequence and of CG motif
content. Expressing IL-12/IL-18 DNA locally induces expression of the
downstream mediator CXCL-10. The grey horses included appeared to display an
attenuated immune response to DNA treatment, although grey horses bearing
melanoma responded to this treatment with moderate tumour remission in a
preceding study. Whether the different immunological reactivity compared to
other horses may contributes to the melanoma susceptibility of grey horses
remains to be elucidated
Immune response of healthy horses to DNA constructs formulated with a cationic lipid transfection reagent
Measurement of the Ratio of b Quark Production Cross Sections in Antiproton-Proton Collisions at 630 GeV and 1800 GeV
We report a measurement of the ratio of the bottom quark production cross
section in antiproton-proton collisions at 630 GeV to 1800 GeV using bottom
quarks with transverse momenta greater than 10.75 GeV identified through their
semileptonic decays and long lifetimes. The measured ratio
sigma(630)/sigma(1800) = 0.171 +/- .024 +/- .012 is in good agreement with
next-to-leading order (NLO) quantum chromodynamics (QCD)
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Effects of lorazepam on saccadic eye movements: the role of sex, task characteristics and baseline traits
Medical Research Council; National Institute for Health Research; Mental Health Biomedical Research Centre at South London; Maudsley NHS Foundation Trust; Institute of Psychiatry, Psychology; Neuroscience, King’s College London
Risk and resilience in gifted young people from low socio-economic backgrounds
Gifted and talented young people from low socio-economic backgrounds are consistently under-represented in gifted programmes in New Zealand schools. This chapter reports on a qualitative study that explored the lived experiences of 101 gifted New Zealand young people from low socio-economic back-grounds. An overarching question for this study was ‘What is it about gifted young people from low socio-economic backgrounds who have achieved to exceptional levels, that has enabled them to do so?’ The risk and resilience construct was used as a lens through which to explore their experiences across a range of contexts. These young people reflected on their perceptions of their giftedness and socio-economic circumstances, their childhoods and school ex-periences, and their home lives. The stories of the participants in this study in-dicated that there are particular risks associated with both giftedness and low socio-economic status, and contribute to ideas about how these young people might be more effectively supported to develop their potential
Managing Therapeutic Competition in Patients with Heart Failure, Lower Urinary Tract Symptoms and Incontinence
Growth Hormone-Releasing Hormone and Growth Hormone-Releasing Peptide as Potential Therapeutic Modalities
A guide to polarized airway epithelial models for studies of host-pathogen interactions.
Mammalian lungs are organs exhibiting the cellular and spatial complexity required for gas exchange to support life. The respiratory epithelium internally lining the airways is susceptible to infections due to constant exposure to inhaled microbes. Biomedical research into respiratory bacterial infections in humans has been mostly carried out using small mammalian animal models or two-dimensional, submerged cultures of undifferentiated epithelial cells. These experimental model systems have considerable limitations due to host specificity of bacterial pathogens and lack of cellular and morphological complexity. This review describes the in vitro differentiated and polarized airway epithelial cells of human origin that are used as a model to study respiratory bacterial infections. Overall, these models recapitulate key aspects of the complexity observed in vivo and can help in elucidating the molecular details of disease processes observed during respiratory bacterial infections
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