A New Mechanism for Recurrent Adaptive Radiations

Models of adaptive radiation through intraspecific competition have attracted mounting attention. Here we show how extending such models in a simple manner, by including a quantitative trait under weak directional selection, naturally leads to rich macroevolutionary patterns involving recurrent adaptive radiations and extinctions. Extensive tests demonstrate the robustness of this finding to a wide range of variations in model assumptions. In particular, recurrent adaptive radiations and extinctions readily unfold both for asexual and for sexual populations. Since the mechanisms driving the investigated processes of endogenous diversification result from generic geometric features of the underlying fitness landscapes - frequency-dependent disruptive selection in one trait and weak directional selection in another - the reported phenomena can be expected to occur in a wide variety of eco-evolutionary settings

Evolutionary-branching lines and areas in bivariate trait spaces

Aims: Evolutionary branching is a process of evolutionary diversification induced by frequency-dependent ecological interaction. Here we show how to predict the occurrence of evolutionary branching in bivariate traits when populations are evolving directionally. Methods: Following adaptive dynamics theory, we assume low mutation rates and small mutational step sizes. On this basis, we generalize conditions for evolutionary-branching points to conditions for evolutionary-branching lines and areas, which delineate regions of trait space in which evolutionary branching can be expected despite populations still evolving directionally along these lines and within these areas. To assess the quality of predictions provided by our new conditions for evolutionary branching lines and areas, we analyse three eco-evolutionary models with bivariate trait spaces, comparing the predicted evolutionary- branching lines and areas with actual occurrences of evolutionary branching in numerically calculated evolutionry dynamics. In the three examples, a phenotype's fitness is affected by frequency-dependent resource competition and/or predator-prey interaction. Conclusions: In the limit of infinitesimal mutational step sizes, evolutionary branching in bivariate trait spaces can occur only at evolutionary-branching points, i.e., where the evolving population experiences disruptive selection in the absence of any directional selection. In contrast, when mutational step sizes are finite, evolutionary branching can occur also along evolutioary-branching lines, i.e., where disruptive selection orthogonal to these lines is sufficiently strong relative to directional selection along them. Moreover, such evolutionary- branching lines are embedded in evolutionary-branching areas, which delineate all bivariate trait combinations for which evolutionary branching can occur when mutation rates are low, while mutational step sizes are finite. Our analyses show that evolutionary-branching lines and areas are good indicators of evolutionary branching in directionally evolving populations. We also demonstrate that not all evolutionary-branching lines and areas contain evolutionary- branching points, so evolutionary branching is possible even in trait spaces that contain no evolutionary-branching point at all

Lotka–Volterra approximations for evolutionary trait-substitution processes

A set of axioms is formulated characterizing ecologically plausible community dynamics. Using these axioms, it is proved that the transients following an invasion into a sufficiently stable equilibrium community by a mutant phenotype similar to one of the community's finitely many resident phenotypes can always be approximated by means of an appropriately chosen Lotka-Volterra model. To this end, the assumption is made that similar phenotypes in the community form clusters that are well-separated from each other, as is expected to be generally the case when evolution proceeds through small mutational steps. Each phenotypic cluster is represented by a single phenotype, which we call an approximate phenotype and assign the cluster's total population density. We present our results in three steps. First, for a set of approximate phenotypes with arbitrary equilibrium population densities before the invasion, the Lotka-Volterra approximation is proved to apply if the changes of the population densities of these phenotypes are sufficiently small during the transient following the invasion. Second, quantitative conditions for such small changes of population densities are derived as a relationship between within-cluster differences and the leading eigenvalue of the community's Jacobian matrix evaluated at the equilibrium population densities before the invasion. Third, to demonstrate the utility of our results, the 'invasion implies substitution' result for monomorphic populations is extended to arbitrarily polymorphic populations consisting of well-recognizable and -separated clusters

A quantum Monte Carlo algorithm realizing an intrinsic relaxation

We propose a new quantum Monte Carlo algorithm which realizes a relaxation intrinsic to the original quantum system. The Monte Carlo dynamics satisfies the dynamic scaling relation $\tau\sim \xi^z$ and is independent of the Trotter number. Finiteness of the Trotter number just appears as the finite-size effect. An infinite Trotter number version of the algorithm is also formulated, which enables us to observe a true relaxation of the original system. The strategy of the algorithm is a compromise between the conventional worldline local flip and the modern cluster loop flip. It is a local flip in the real-space direction and is a cluster flip in the Trotter direction. The new algorithm is tested by the transverse-field Ising model in two dimensions. An accurate phase diagram is obtained.Comment: 9 pages, 4 figure

N=2 Instanton Effective Action in Omega-background and D3/D(-1)-brane System in R-R Background

We study the relation between the ADHM construction of instantons in the Omega-background and the fractional D3/D(-1)-branes at the orbifold singularity of C \times C^2/Z_2 in Ramond-Ramond (R-R) 3-form field strength background. We calculate disk amplitudes of open strings connecting the D3/D(-1)-branes in certain R-R background to obtain the D(-1)-brane effective action deformed by the R-R background. We show that the deformed D(-1)-brane effective action agrees with the instanton effective action in the Omega-background.Comment: 35 pages, no figures, references adde

Endothelial LRP1 transports amyloid-β1-42 across the blood-brain barrier

According to the neurovascular hypothesis, impairment of low-density lipoprotein receptor-related protein-1 (LRP1) in brain capillaries of the blood-brain barrier (BBB) contributes to neurotoxic amyloid-beta (A beta) brain accumulation and drives Alzheimer's disease (AD) pathology. However, due to conflicting reports on the involvement of LRP1 in A beta transport and the expression of LRP1 in brain endothelium, the role of LRP1 at the BBB is uncertain. As global Lrp1 deletion in mice is lethal, appropriate models to study the function of LRP1 are lacking. Moreover, the relevance of systemic A beta clearance to AD pathology remains unclear, as no BBB-specific knockout models have been available. Here, we developed transgenic mouse strains that allow for tamoxifen-inducible deletion of Lrp1 specifically within brain endothelial cells (Slo1c1-CreER(Tz) Lrp1(fl/fl) mice) and used these mice to accurately evaluate LRP1-mediated A beta BBB clearance in vivo. Selective deletion of Lrp1 in the brain endothelium of C57BL/6 mice strongly reduced brain efflux of injected [I-125] A beta(1-42). Additionally, in the 5xFAD mouse model of AD, brain endothelial-specific Lrp1 deletion reduced plasma A beta levels and elevated soluble brain A beta, leading to aggravated spatial learning and memory deficits, thus emphasizing the importance of systemic AD elimination via the BBB. Together, our results suggest that receptor-mediated A beta BBB clearance may be a potential target for treatment and prevention of A beta brain accumulation in AD

Histone deacetylase inhibitors induce apoptosis in human eosinophils and neutrophils

BACKGROUND: Granulocytes are important in the pathogenesis of several inflammatory diseases. Apoptosis is pivotal in the resolution of inflammation. Apoptosis in malignant cells is induced by histone deacetylase (HDAC) inhibitors, whereas HDAC inhibitors do not usually induce apoptosis in non-malignant cells. The aim of the present study was to explore the effects of HDAC inhibitors on apoptosis in human eosinophils and neutrophils. METHODS: Apoptosis was assessed by relative DNA fragmentation assay, annexin-V binding, and morphologic analysis. HDAC activity in nuclear extracts was measured with a nonisotopic assay. HDAC expression was measured by real-time PCR. RESULTS: A HDAC inhibitor Trichostatin A (TSA) induced apoptosis in the presence of survival-prolonging cytokines interleukin-5 and granulocyte-macrophage colony stimulating factor (GM-CSF) in eosinophils and neutrophils. TSA enhanced constitutive eosinophil and neutrophil apoptosis. Similar effects were seen with a structurally dissimilar HDAC inhibitor apicidin. TSA showed additive effect on the glucocorticoid-induced eosinophil apoptosis, but antagonized glucocorticoid-induced neutrophil survival. Eosinophils and neutrophils expressed all HDACs at the mRNA level except that HDAC5 and HDAC11 mRNA expression was very low in both cell types, HDAC8 mRNA was very low in neutrophils and HDAC9 mRNA low in eosinophils. TSA reduced eosinophil and neutrophil nuclear HDAC activities by ~50-60%, suggesting a non-histone target. However, TSA did not increase the acetylation of a non-histone target NF-κB p65. c-jun-N-terminal kinase and caspases 3 and 6 may be involved in the mechanism of TSA-induced apoptosis, whereas PI3-kinase and caspase 8 are not. CONCLUSIONS: HDAC inhibitors enhance apoptosis in human eosinophils and neutrophils in the absence and presence of survival-prolonging cytokines and glucocorticoids

Local electronic structure of interstitial hydrogen in MgH2_2 inferred from muon study

Magnesium hydride has great potential as a solid hydrogen (H) storage material because of its high H storage capacity of 7.6 wt%. However, its slow hydrogenation and dehydrogenation kinetics and the high temperature of 300 $^\circ$C required for decomposition are major obstacles to small-scale applications such as automobiles. The local electronic structure of interstitial H in MgH$_2$ is an important fundamental knowledge in solving this problem, which has been studied mainly based on density functional theory (DFT). However, few experimental studies have been performed to assess the results of DFT calculations. We have therefore introduced muon (Mu) as pseudo-H into MgH$_2$ and investigated the corresponding interstitial H states by analyzing their electronic and dynamical properties in detail. As a result, we observed multiple Mu states similar to those observed in wide-gap oxides, and found that their electronic states can be attributed to relaxed-excited states associated with donor/acceptor levels predicted by the recently proposed "ambipolarity model". This provides an indirect support for the DFT calculations on which the model is based via the donor/acceptor levels. An important implication of the muon results for improved hydrogen kinetics is that dehydrogenation, serving as a $reduction$ for hydrides, stabilizes the interstitial H$^-$ state.Comment: 14 pages, 9 figure