349 research outputs found
Finite-size scaling of the quasiespecies model
We use finite-size scaling to investigate the critical behavior of the
quasiespecies model of molecular evolution in the single-sharp-peak replication
landscape. This model exhibits a sharp threshold phenomenon at Q=Q_c=1/a, where
Q is the probability of exact replication of a molecule of length L and a is
the selective advantage of the master string.
We investigate the sharpness of the threshold and find that its
characteristic persist across a range of Q of order L^(-1) about Q_c.
Furthermore, using the data collapsing method we show that the normalized mean
Hamming distance between the master string and the entire population, as well
as the properly scaled fluctuations around this mean value, follow universal
forms in the critical region.Comment: 8 pages,tex. Submitted to Physical Review
Structure and evolutionary history of a large family of NLR proteins in the zebrafish
Multicellular eukaryotes have evolved a range of mechanisms for immune recognition. A widespread family involved in innate immunity are the NACHT-domain and leucine-rich-repeat-containing (NLR) proteins. Mammals have small numbers of NLR proteins, whereas in some species, mostly those without adaptive immune systems, NLRs have expanded into very large families. We describe a family of nearly 400 NLR proteins encoded in the zebrafish genome. The proteins share a defining overall structure, which arose in fishes after a fusion of the core NLR domains with a B30.2 domain, but can be subdivided into four groups based on their NACHT domains. Gene conversion acting differentially on the NACHT and B30.2 domains has shaped the family and created the groups. Evidence of positive selection in the B30.2 domain indicates that this domain rather than the leucine-rich repeats acts as the pathogen recognition module. In an unusual chromosomal organization, the majority of the genes are located on one chromosome arm, interspersed with other large multigene families, including a new family encoding zinc-finger proteins. The NLR-B30.2 proteins represent a new family with diversity in the specific recognition module that is present in fishes in spite of the parallel existence of an adaptive immune system
Adherence to antiretroviral therapy in a clinical cohort of HIV-infected children in East Africa
Objective To describe antiretroviral therapy (ART) adherence and associated factors for a large HIVinfected pediatric cohort followed by sites of the East Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) consortium.
Methods This study utilized prospectively collected clinical data from HIV-infected children less than 13 years of age who initiated ART within 4 clinical care programs (with 26 clinical sites) in Kenya, Uganda, and Tanzania and were followed for up to 6 years. Programs used one of 3 adherence measures, including 7-day quantitative recall, 7-day categorical recall, and clinician pill assessments. We fit a hierarchical, three-level, logistic-regression model to examine adherence, with observations nested within patient, and patients within the 26 sites providing pediatric HIV data to this analysis.
Results In East Africa, 3,304 children, 52.0% male, were enrolled in care and were subsequently observed for a median of 92 weeks (inter-quartile range [IQR] 50.3±145.0 weeks). Median age at ART initiation was 5.5 years ([IQR] 3.0±8.5 years). ÂȘGoodÂș adherence, as reported by each clinic\u27s measures, was extremely high, remaining on average above 90% throughout all years of follow-up. Longer time on ART was associated with higher adherence (adjusted Odds Ratio±aOR±per log-transformed week on ART: 1.095, 95% Confidence Interval±CI± [1.052±1.150].) Patients enrolled in higher-volume programs exhibited higher rates of clinician- assessed adherence (aOR per log-500 patients: 1.174, 95% CI [1.108±1.245]).Significant site-level variability in reported adherence was observed (0.28), with even higher variability among patients (0.71). In a sub-analysis, being an orphan at the start of ART was strongly associated with lower ART adherence rates (aOR: 0.919, 95% CI [0.864±0.976]).
Conclusions Self-reported adherence remained high over a median of 1.8 years in HIV care, but varied according to patient-level and site-level factors. Consistent adherence monitoring with validated measures and attention to vulnerable groups is recommended
Investigating Alkylated Prodigiosenes and Their Cu(II)-Dependent Biological Activity: Interactions with DNA, Antimicrobial and Photoinduced Anticancer Activity
Prodigiosenes are a family of red pigments with versatile biological activity. Their tripyrrolic core structure has been modified many times in order to manipulate the spectrum of activity. We have been looking systematically at prodigiosenes substituted at the C ring with alkyl chains of different lengths, in order to assess the relevance of this substituent in a context that has not been investigated before for these derivatives: Cu(II) complexation, DNA binding, self-activated DNA cleavage, photoinduced cytotoxicity and antimicrobial activity. Our results indicate that the hydrophobic substituent has a clear influence on the different aspects of their biological activity. The cytotoxicity study of the Cu(II) complexes of these prodigiosenes shows that they exhibit a strong cytotoxic effect towards the tested tumor cell lines. The Cu(II) complex of a prodigiosene lacking any alkyl chain excelled in its photoinduced anticancer activity, thus demonstrating the potential of prodigiosenes and their metal complexes for an application in photodynamic therapy (PDT). Two derivatives along with their Cu(II) complexes showed also antimicrobial activity against Staphylococcus aureus strains
Statistics of selectively neutral genetic variation
Random models of evolution are instrumental in extracting rates of
microscopic evolutionary mechanisms from empirical observations on genetic
variation in genome sequences. In this context it is necessary to know the
statistical properties of empirical observables (such as the local homozygosity
for instance). Previous work relies on numerical results or assumes Gaussian
approximations for the corresponding distributions. In this paper we give an
analytical derivation of the statistical properties of the local homozygosity
and other empirical observables assuming selective neutrality. We find that
such distributions can be very non-Gaussian.Comment: 4 pages, 4 figure
Nonlinear deterministic equations in biological evolution
We review models of biological evolution in which the population frequency
changes deterministically with time. If the population is self-replicating,
although the equations for simple prototypes can be linearised, nonlinear
equations arise in many complex situations. For sexual populations, even in the
simplest setting, the equations are necessarily nonlinear due to the mixing of
the parental genetic material. The solutions of such nonlinear equations
display interesting features such as multiple equilibria and phase transitions.
We mainly discuss those models for which an analytical understanding of such
nonlinear equations is available.Comment: Invited review for J. Nonlin. Math. Phy
Error threshold in finite populations
A simple analytical framework to study the molecular quasispecies evolution
of finite populations is proposed, in which the population is assumed to be a
random combination of the constiyuent molecules in each generation,i.e.,
linkage disequilibrium at the population level is neglected. In particular, for
the single-sharp-peak replication landscape we investigate the dependence of
the error threshold on the population size and find that the replication
accuracy at threshold increases linearly with the reciprocal of the population
size for sufficiently large populations. Furthermore, in the deterministic
limit our formulation yields the exact steady-state of the quasispecies model,
indicating then the population composition is a random combination of the
molecules.Comment: 14 pages and 4 figure
Probing empirical contact networks by simulation of spreading dynamics
Disease, opinions, ideas, gossip, etc. all spread on social networks. How
these networks are connected (the network structure) influences the dynamics of
the spreading processes. By investigating these relationships one gains
understanding both of the spreading itself and the structure and function of
the contact network. In this chapter, we will summarize the recent literature
using simulation of spreading processes on top of empirical contact data. We
will mostly focus on disease simulations on temporal proximity networks --
networks recording who is close to whom, at what time -- but also cover other
types of networks and spreading processes. We analyze 29 empirical networks to
illustrate the methods
Small world effects in evolution
For asexual organisms point mutations correspond to local displacements in
the genotypic space, while other genotypic rearrangements represent long-range
jumps. We investigate the spreading properties of an initially homogeneous
population in a flat fitness landscape, and the equilibrium properties on a
smooth fitness landscape. We show that a small-world effect is present: even a
small fraction of quenched long-range jumps makes the results indistinguishable
from those obtained by assuming all mutations equiprobable. Moreover, we find
that the equilibrium distribution is a Boltzmann one, in which the fitness
plays the role of an energy, and mutations that of a temperature.Comment: 13 pages and 5 figures. New revised versio
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