Anti-melanocortin-4 receptor autoantibodies in obesity

Background: The melanocortin-4 receptor (MC4R) is part of an important pathway regulating energy balance. Here we report the existence of autoantibodies (autoAbs) against the MC4R in sera of obese patients. Methods: The autoAbs were detected after screening of 216 patients' sera by using direct and inhibition ELISA with an N-terminal sequence of the MC4R. Binding to the native MC4R was evaluated by flow cytometry and pharmacological effects by measuring adenylyl cyclase activity. Results: Positive results in all tests were obtained in patients with overweight or obesity (prevalence: 3.6%) but not in normal weight patients. The selective binding properties of anti-MC4R autoAbs were confirmed by surface plasmon resonance and by immunoprecipitation with the native MC4R. Finally it was demonstrated that these autoAbs increased food intake in rats after passive transfer via intracerebroventricular injection. Conclusion: These observations suggest that inhibitory anti-MC4R autoAbs might contribute to the development of obesity in a small subpopulation of patients

Networking Effects on Cooperation in Evolutionary Snowdrift Game

The effects of networking on the extent of cooperation emerging in a competitive setting are studied. The evolutionary snowdrift game, which represents a realistic alternative to the well-known Prisoner's Dilemma, is studied in the Watts-Strogatz network that spans the regular, small-world, and random networks through random re-wiring. Over a wide range of payoffs, a re-wired network is found to suppress cooperation when compared with a well-mixed or fully connected system. Two extinction payoffs, that characterize the emergence of a homogeneous steady state, are identified. It is found that, unlike in the Prisoner's Dilemma, the standard deviation of the degree distribution is the dominant network property that governs the extinction payoffs.Comment: Changed conten

Robustness and epistasis in mutation-selection models

We investigate the fitness advantage associated with the robustness of a phenotype against deleterious mutations using deterministic mutation-selection models of quasispecies type equipped with a mesa shaped fitness landscape. We obtain analytic results for the robustness effect which become exact in the limit of infinite sequence length. Thereby, we are able to clarify a seeming contradiction between recent rigorous work and an earlier heuristic treatment based on a mapping to a Schr\"odinger equation. We exploit the quantum mechanical analogy to calculate a correction term for finite sequence lengths and verify our analytic results by numerical studies. In addition, we investigate the occurrence of an error threshold for a general class of epistatic landscape and show that diminishing epistasis is a necessary but not sufficient condition for error threshold behavior.Comment: 20 pages, 14 figure

Not all intravenous immunoglobulin preparations are equally well tolerated

Intravenous immunoglobulin (IVIG) is used for many indications beyond the original substitution in primary antibody deficiency. Whereas many reports mention adverse reactions, no comparative data exist concerning the incidence of side-effects among the different brands of IVIG. We describe here our experience with the use of different IVIG formulations and their tolerability in a select cohort of 40 patients. The IVIG dose ranged from 0.4 to 3 g/kg/day and was given for 1–2742 days. Fourteen patients (35%) experienced mild to severe adverse reactions during or within 48 h of administration of standard IVIG preparation, which did not recur after switching to an alternative preparation. Adverse reactions included headache, fever, chills, nausea, emesis, hypotension and muscle cramps. One patient experienced a severe adverse reaction; he had a 3-day headache following IVIG infusion. Among the 16 patients who received alternative preparation initially, none experienced adverse reactions. In conclusion, this study shows that IVIG preparations are not all equally well tolerated in patients. The data suggest that, perhaps to a comparable extent to the preparation itself, the infusion rate has a major effect. If a reduction in the infusion rate does not minimize side-effects, one should consider switching the IVIG formulation

Social Network Reciprocity as a Phase Transition in Evolutionary Cooperation

In Evolutionary Dynamics the understanding of cooperative phenomena in natural and social systems has been the subject of intense research during decades. We focus attention here on the so-called "Lattice Reciprocity" mechanisms that enhance evolutionary survival of the cooperative phenotype in the Prisoner's Dilemma game when the population of darwinian replicators interact through a fixed network of social contacts. Exact results on a "Dipole Model" are presented, along with a mean-field analysis as well as results from extensive numerical Monte Carlo simulations. The theoretical framework used is that of standard Statistical Mechanics of macroscopic systems, but with no energy considerations. We illustrate the power of this perspective on social modeling, by consistently interpreting the onset of lattice reciprocity as a thermodynamical phase transition that, moreover, cannot be captured by a purely mean-field approach.Comment: 10 pages. APS styl

Statistical mechanics and stability of a model eco-system

We study a model ecosystem by means of dynamical techniques from disordered systems theory. The model describes a set of species subject to competitive interactions through a background of resources, which they feed upon. Additionally direct competitive or co-operative interaction between species may occur through a random coupling matrix. We compute the order parameters of the system in a fixed point regime, and identify the onset of instability and compute the phase diagram. We focus on the effects of variability of resources, direct interaction between species, co-operation pressure and dilution on the stability and the diversity of the ecosystem. It is shown that resources can be exploited optimally only in absence of co-operation pressure or direct interaction between species.Comment: 23 pages, 13 figures; text of paper modified, discussion extended, references adde

Coexistence and Survival in Conservative Lotka-Volterra Networks

Analyzing coexistence and survival scenarios of Lotka-Volterra (LV) networks in which the total biomass is conserved is of vital importance for the characterization of long-term dynamics of ecological communities. Here, we introduce a classification scheme for coexistence scenarios in these conservative LV models and quantify the extinction process by employing the Pfaffian of the network's interaction matrix. We illustrate our findings on global stability properties for general systems of four and five species and find a generalized scaling law for the extinction time

Chains of infinite order, chains with memory of variable length, and maps of the interval

We show how to construct a topological Markov map of the interval whose invariant probability measure is the stationary law of a given stochastic chain of infinite order. In particular we caracterize the maps corresponding to stochastic chains with memory of variable length. The problem treated here is the converse of the classical construction of the Gibbs formalism for Markov expanding maps of the interval

Bose-Einstein distribution, condensation transition and multiple stationary states in multiloci evolution of diploid population

The mapping between genotype and phenotype is encoded in the complex web of epistatic interaction between genetic loci. In this rugged fitness landscape, recombination processes, which tend to increase variation in the population, compete with selection processes that tend to reduce genetic variation. Here we show that the Bose-Einstein distribution describe the multiple stationary states of a diploid population under this multi-loci evolutionary dynamics. Moreover, the evolutionary process might undergo an interesting condensation phase transition in the universality class of a Bose-Einstein condensation when a finite fraction of pairs of linked loci, is fixed into given allelic states. Below this phase transition the genetic variation within a species is significantly reduced and only maintained by the remaining polymorphic loci.Comment: (12 pages, 7 figures

Fixation times in evolutionary games under weak selection

In evolutionary game dynamics, reproductive success increases with the performance in an evolutionary game. If strategy $A$ performs better than strategy $B$, strategy $A$ will spread in the population. Under stochastic dynamics, a single mutant will sooner or later take over the entire population or go extinct. We analyze the mean exit times (or average fixation times) associated with this process. We show analytically that these times depend on the payoff matrix of the game in an amazingly simple way under weak selection, ie strong stochasticity: The payoff difference $\Delta \pi$ is a linear function of the number of $A$ individuals $i$, $\Delta \pi = u i + v$. The unconditional mean exit time depends only on the constant term $v$. Given that a single $A$ mutant takes over the population, the corresponding conditional mean exit time depends only on the density dependent term $u$. We demonstrate this finding for two commonly applied microscopic evolutionary processes.Comment: Forthcoming in New Journal of Physic