Gene duplication in an African cichlid adaptive radiation

Background Gene duplication is a source of evolutionary innovation and can contribute to the divergence of lineages; however, the relative importance of this process remains to be determined. The explosive divergence of the African cichlid adaptive radiations provides both a model for studying the general role of gene duplication in the divergence of lineages and also an exciting foray into the identification of genomic features that underlie the dramatic phenotypic and ecological diversification in this particular lineage. We present the first genome-wide study of gene duplication in African cichlid fishes, identifying gene duplicates in three species belonging to the Lake Malawi adaptive radiation (Metriaclima estherae, Protomelas similis, Rhamphochromis “chilingali”) and one closely related species from a non-radiated riverine lineage (Astatotilapia tweddlei). Results Using Astatotilapia burtoni as reference, microarray comparative genomic hybridization analysis of 5689 genes reveals 134 duplicated genes among the four cichlid species tested. Between 51 and 55 genes were identified as duplicated in each of the three species from the Lake Malawi radiation, representing a 38%–49% increase in number of duplicated genes relative to the non-radiated lineage (37 genes). Duplicated genes include several that are involved in immune response, ATP metabolism and detoxification. Conclusions These results contribute to our understanding of the abundance and type of gene duplicates present in cichlid fish lineages. The duplicated genes identified in this study provide candidates for the analysis of functional relevance with regard to phenotype and divergence. Comparative sequence analysis of gene duplicates can address the role of positive selection and adaptive evolution by gene duplication, while further study across the phylogenetic range of cichlid radiations (and more generally in other adaptive radiations) will determine whether the patterns of gene duplication seen in this study consistently accompany rapid radiation

Gene duplication in an African cichlid adaptive radiation

BACKGROUND: Gene duplication is a source of evolutionary innovation and can contribute to the divergence of lineages; however, the relative importance of this process remains to be determined. The explosive divergence of the African cichlid adaptive radiations provides both a model for studying the general role of gene duplication in the divergence of lineages and also an exciting foray into the identification of genomic features that underlie the dramatic phenotypic and ecological diversification in this particular lineage. We present the first genome-wide study of gene duplication in African cichlid fishes, identifying gene duplicates in three species belonging to the Lake Malawi adaptive radiation (Metriaclima estherae, Protomelas similis, Rhamphochromis “chilingali”) and one closely related species from a non-radiated riverine lineage (Astatotilapia tweddlei). RESULTS: Using Astatotilapia burtoni as reference, microarray comparative genomic hybridization analysis of 5689 genes reveals 134 duplicated genes among the four cichlid species tested. Between 51 and 55 genes were identified as duplicated in each of the three species from the Lake Malawi radiation, representing a 38%–49% increase in number of duplicated genes relative to the non-radiated lineage (37 genes). Duplicated genes include several that are involved in immune response, ATP metabolism and detoxification. CONCLUSIONS: These results contribute to our understanding of the abundance and type of gene duplicates present in cichlid fish lineages. The duplicated genes identified in this study provide candidates for the analysis of functional relevance with regard to phenotype and divergence. Comparative sequence analysis of gene duplicates can address the role of positive selection and adaptive evolution by gene duplication, while further study across the phylogenetic range of cichlid radiations (and more generally in other adaptive radiations) will determine whether the patterns of gene duplication seen in this study consistently accompany rapid radiation

In vivo activity of Sapindus saponaria against azole-susceptible and -resistant human vaginal Candida species

<p>Abstract</p> <p>Background</p> <p>Study of <it>in vivo </it>antifungal activity of the hydroalcoholic extract (HE) and n-BuOH extract (BUTE) of <it>Sapindus saponaria </it>against azole-susceptible and -resistant human vaginal <it>Candida </it>spp.</p> <p>Methods</p> <p>The <it>in vitro </it>antifungal activity of HE, BUTE, fluconazole (FLU), and itraconazole (ITRA) was determined by the broth microdilution method. We obtained values of minimal inhibitory concentration (MIC) and minimum fungicide concentration (MFC) for 46 strains of <it>C. albicans </it>and 10 of <it>C. glabrata </it>isolated from patients with vulvovaginal candidiasis (VVC). VVC was induced in hyperestrogenic Wistar rats with azole-susceptible <it>C. albicans </it>(SCA), azole-resistant <it>C. albicans </it>(RCA), and azole-resistant <it>C. glabrata </it>(RCG). The rats were treated intravaginally with 0.1 mL of HE or BUTE at concentrations of 1%, 2.5% and 5%; 100 μg/mL of FLU (treatment positive control); or distilled water (negative control) at 1, 24, and 48 h after induction of the infection, and the progress of VVC was monitored by culturing and scanning electron microscopy (SEM). The toxicity was evaluated in cervical cells of the HeLa cell line.</p> <p>Results</p> <p>The extracts showed <it>in vitro </it>inhibitory and fungicidal activity against all the isolates, and the MIC and MFC values for the <it>C. glabrata </it>isolates were slightly higher. <it>In vivo</it>, the SCA, RCA, and RCG infections were eliminated by 21 days post-infection, with up to 5% HE and BUTE, comparable to the activity of FLU. No cytotoxic action was observed for either extract.</p> <p>Conclusions</p> <p>Our results demonstrated that HE and BUTE from <it>S. saponaria </it>show inhibitory and fungicidal activity <it>in vitro</it>, in addition to <it>in vivo </it>activity against azole-resistant vaginal isolates of <it>C. glabrata </it>and azole-susceptible and resistant isolates of <it>C. albicans</it>. Also considering the lack of cytotoxicity and the low concentrations of the extracts necessary to eliminate the infection <it>in vivo</it>, HE and BUTE show promise for continued studies with purified antifungal substances in VVC yeast isolates.</p

Heterotic Sigma Models with N=2 Space-Time Supersymmetry

We study the non-linear sigma model realization of a heterotic vacuum with N=2 space-time supersymmetry. We examine the requirements of (0,2) + (0,4) world-sheet supersymmetry and show that a geometric vacuum must be described by a principal two-torus bundle over a K3 manifold.Comment: 20 pages, uses xy-pic; v3: typos corrected, reference added, discussion of constraints on Hermitian form modifie

Baryonic symmetries and M5 branes in the AdS_4/CFT_3 correspondence

We study U(1) symmetries dual to Betti multiplets in the AdS_4/CFT_3 correspondence for M2 branes at Calabi-Yau four-fold singularities. Analysis of the boundary conditions for vector fields in AdS_4 allows for a choice where wrapped M5 brane states carrying non-zero charge under such symmetries can be considered. We begin by focusing on isolated toric singularities without vanishing six-cycles, and study in detail the cone over Q^{111}. The boundary conditions considered are dual to a CFT where the gauge group is U(1)^2 x SU(N)^4. We find agreement between the spectrum of gauge-invariant baryonic-type operators in this theory and wrapped M5 brane states. Moreover, the physics of vacua in which these symmetries are spontaneously broken precisely matches a dual gravity analysis involving resolutions of the singularity, where we are able to match condensates of the baryonic operators, Goldstone bosons and global strings. We also argue more generally that theories where the resolutions have six-cycles are expected to receive non-perturbative corrections from M5 brane instantons. We give a general formula relating the instanton action to normalizable harmonic two-forms, and compute it explicitly for the Q^{222} example. The holographic interpretation of such instantons is currently unclear.Comment: 92 pages, 10 figure

A framework for parameter estimation and model selection from experimental data in systems biology using approximate Bayesian computation.

As modeling becomes a more widespread practice in the life sciences and biomedical sciences, researchers need reliable tools to calibrate models against ever more complex and detailed data. Here we present an approximate Bayesian computation (ABC) framework and software environment, ABC-SysBio, which is a Python package that runs on Linux and Mac OS X systems and that enables parameter estimation and model selection in the Bayesian formalism by using sequential Monte Carlo (SMC) approaches. We outline the underlying rationale, discuss the computational and practical issues and provide detailed guidance as to how the important tasks of parameter inference and model selection can be performed in practice. Unlike other available packages, ABC-SysBio is highly suited for investigating, in particular, the challenging problem of fitting stochastic models to data. In order to demonstrate the use of ABC-SysBio, in this protocol we postulate the existence of an imaginary reaction network composed of seven interrelated biological reactions (involving a specific mRNA, the protein it encodes and a post-translationally modified version of the protein), a network that is defined by two files containing 'observed' data that we provide as supplementary information. In the first part of the PROCEDURE, ABC-SysBio is used to infer the parameters of this system, whereas in the second part we use ABC-SysBio's relevant functionality to discriminate between two different reaction network models, one of them being the 'true' one. Although computationally expensive, the additional insights gained in the Bayesian formalism more than make up for this cost, especially in complex problems

Amount of Information Needed for Model Choice in Approximate Bayesian Computation

Approximate Bayesian Computation (ABC) has become a popular technique in evolutionary genetics for elucidating population structure and history due to its flexibility. The statistical inference framework has benefited from significant progress in recent years. In population genetics, however, its outcome depends heavily on the amount of information in the dataset, whether that be the level of genetic variation or the number of samples and loci. Here we look at the power to reject a simple constant population size coalescent model in favor of a bottleneck model in datasets of varying quality. Not only is this power dependent on the number of samples and loci, but it also depends strongly on the level of nucleotide diversity in the observed dataset. Whilst overall model choice in an ABC setting is fairly powerful and quite conservative with regard to false positives, detecting weaker bottlenecks is problematic in smaller or less genetically diverse datasets and limits the inferences possible in non-model organism where the amount of information regarding the two models is often limited. Our results show it is important to consider these limitations when performing an ABC analysis and that studies should perform simulations based on the size and nature of the dataset in order to fully assess the power of the study

No evidence for association between SLC11A1 and visceral leishmaniasis in India.

BACKGROUND: SLC11A1 has pleiotropic effects on macrophage function and remains a strong candidate for infectious disease susceptibility. 5' and/or 3' polymorphisms have been associated with tuberculosis, leprosy, and visceral leishmaniasis (VL). Most studies undertaken to date were under-powered, and none has been replicated within a population. Association with tuberculosis has replicated variably across populations. Here we investigate SLC11A1 and VL in India. METHODS: Nine polymorphisms (rs34448891, rs7573065, rs2276631, rs3731865, rs17221959, rs2279015, rs17235409, rs17235416, rs17229009) that tag linkage disequilibrium blocks across SLC11A1 were genotyped in primary family-based (313 cases; 176 families) and replication (941 cases; 992 controls) samples. Family- and population-based analyses were performed to look for association between SLC11A1 variants and VL. Quantitative RT/PCR was used to compare SLC11A1 expression in mRNA from paired splenic aspirates taken before and after treatment from 24 VL patients carrying different genotypes at the functional promoter GTn polymorphism (rs34448891). RESULTS: No associations were observed between VL and polymorphisms at SLC11A1 that were either robust to correction for multiple testing or replicated across primary and replication samples. No differences in expression of SLC11A1 were observed when comparing pre- and post-treatment samples, or between individuals carrying different genotypes at the GTn repeat. CONCLUSIONS: This is the first well-powered study of SLC11A1 as a candidate for VL, which we conclude does not have a major role in regulating VL susceptibility in India.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are