Does hunting affect the demography and genetic structure of the greywing francolin Francolinus africanus?

Hunted and unhunted populations of greywing francolin Francolinus africanus have been studied in the eastern Cape Province of South Africa in order to understand the effects of hunting on the demography and genetic structure of these populations. Greywing population density cycled annually for both hunted and unhunted populations. However, there was an apparent pulse of immigration of sub-dominant birds, and earlier reproduction, in the hunted populations immediately after the winter hunting season. Average levels of allozyme heterozygosity (H) for hunted and unhunted populations were both 0.076, and although the proportion of polymorphic loci per sample and the mean number of alleles per locus for each sample were lower for the hunted populations than for the unhunted populations, these differences were not significant. However, the hunted populations displayed higher levels of outbreeding (lower F _IS and F _IT values) than those for unhunted populations. Therefore, it is concluded that although greywing francolin populations contain relatively high levels of genetic heterogeneity, it is probably the increased levels of local immigration following hunting which reduces the effects of any reduction in genetic variation due to a decrease in local population size from hunting.     

Influence of indole carbinols and growth hormone on the metabolism of 4-androstenedione by rat liver microsomes

The effect of indole-3-carbinol (IC), an anticarcinogen present in cruciferous vegetables, to alter the metabolism of 4-androstenedione (AD) by female rat liver microsomes was investigated and compared to that of its main gastric conversion product, diindolylmethane (DIM) as well as other specific cytochrome P450 inducers. DIM was a more potent inducer of the hydroxylase which converts androsterone to its 6β-hydroxylated derivative 3,6β-dihydroxy-5-androstan-17-one (A) than IC after either oral or intraperitoneal administration and was also a better in vitro inhibitor. Isosafrole (ISF), which like IC and DIM, induces CYP1A2 as well as gestodene, were powerful inhibitors of the in vitro reaction. Naringenin produced only a weak inhibitory effect while 3-methylcholanthrene was inactive. SKF-525A, a prototypic hydroxylase inhibitor, or 17β-N,N-diethylcarbamoyl-4-methyl-4-aza-5-androst-1-ene-3-one which inhibits steroid 5-reductase, also decreased the formation of A from AD by liver microsomes. The infusion of human growth hormone by osmotic minipump, which feminizes hepatic steroid metabolism, increased the ability of male rat liver microsomes to convert AD to A and to respond to induction by IC. The identity of A, the main polar derivative of AD, induced by IC, DIM and ISF, was tentatively assigned by a combination of GC-MS and results from metabolic studies with intermediates in the pathway leading to its formation. It is proposed that the protective role of indole carbinols against mammary carcinoma due to decreased formation of 16-hydroxyestrone from estrone may be further enhanced by the diminished availability of AD for aromatization to estrone.     

PocketOptimizer 2.0: A modular framework for computer-aided ligand-binding design

The ability to design customized proteins to perform specific tasks is of great interest. We are particularly interested in the design of sensitive and specific small molecule ligand-binding proteins for biotechnological or biomedical applications. Computational methods can narrow down the immense combinatorial space to find the best solution and thus provide starting points for experimental procedures. However, success rates strongly depend on accurate modeling and energetic evaluation. Not only intra- but also intermolecular interactions have to be considered. To address this problem, we developed PocketOptimizer, a modular computational protein design pipeline, that predicts mutations in the binding pockets of proteins to increase affinity for a specific ligand. Its modularity enables users to compare different combinations of force fields, rotamer libraries, and scoring functions. Here, we present a much-improved version––PocketOptimizer 2.0. We implemented a cleaner user interface, an extended architecture with more supported tools, such as force fields and scoring functions, a backbone-dependent rotamer library, as well as different improvements in the underlying algorithms. Version 2.0 was tested against a benchmark of design cases and assessed in comparison to the first version. Our results show how newly implemented features such as the new rotamer library can lead to improved prediction accuracy. Therefore, we believe that PocketOptimizer 2.0, with its many new and improved functionalities, provides a robust and versatile environment for the design of small molecule-binding pockets in proteins. It is widely applicable and extendible due to its modular framework. PocketOptimizer 2.0 can be downloaded at https://github.com/Hoecker-Lab/pocketoptimizer .     

Cyclooxygenase and 5-lipoxygenase inhibitory activity of 2,6 di-t-butylphenols linked by a sulfur atom to 1,3,4-thiadiazoles and 1,3,4-oxadiazoles

The preparation of a series of 1,3,4-thiadiazoles and 1,3,4-oxadizoles linked by a thioether to 2,6-di-t-butylphenol and the inhibition of cyclooxygenase (CO) and 5-lipoxygenase (5-LO) by these compounds is dicussed.     

The ubiquitous presence of exopolygalacturonase in maize suggests a fundamental cellular function for this enzyme

Exopolygalacturonase (exoPG) is a pectin-degrading enzyme abundant in maize pollen. Using immunochemistry and in situ hybridization it is shown that in addition to its presence in pollen, exoPG is also present in sporophytic tissues, such as the tapetum and mesophyll cells. The enzyme is located in the cytoplasm of pollen and of some mesophyll cells. In other mesophyll cells, the tapetum and the pollen tube, exoPG is located in the cell wall. The measurement of enzyme activity shows that exoPG is ubiquitous in the vegetative organs. These results suggest a general function for exoPG in cell wall edification or degradation. ExoPG is encoded by a closely related multigene family. The regulation of the expression of one of the exoPG genes was analyzed in transgenic tobacco. Reporter GUS activity was detected in anthers, seeds and stems but not in leaves or roots of transgenic plants. This strongly suggests that the ubiquitous presence of exoPG in maize is the result of the expression of different exoPG genes.     

Inhibition of the HIV-1 and HIV-2 proteases by curcumin and curcumin boron complexes

Curcumin, a relatively non-toxic natural product isolated from Curcuma longa, is a modest inhibitor of the HIV-1 (1050 = 100 μM) and HIV-2 (IC₅₀ = 250 μM) proteases. Simple modifications of the curcumin structure raise the IC₅₀ value but complexes of the central dihydroxy groups of curcumin with boron lower the IC₅₀ to a value as low as 6 μM. The boron complexes are also time-dependent inactivators of the HIV proteases. The increased affinity of the boron complexes may reflect binding of the orthogonal domains of the inhibitor in intersecting sites within the substrate-binding cavity of the enzyme, while activation of the ,β-unsaturated carbonyl group of curcumin by chelation to boron probably accounts for time-dependent inhibition of the enzyme.     

Expression in cowpea seedlings of chimeric transgenes after electroporation into seed-derived embryos

Summary Cowpea (Vigna unguiculata Walp) embryos mechanically isolated from mature seeds and incubated in the presence of plasmid DNA harboring chimeric gus genes were shown to germinate into seedlings expressing -glucuronidase activity in a variety of tissues, including the apical meristem. Embryo electroporation in the presence of DNA and protectants such as spermine and Lipofectin^TM increased both the proportion of embryo-derived seedlings expressing the chimeric gene and the level of gene expression. Microscopic observations of thin sections showed that the blue crystals representing the end product of transgene activity on X-glu were exclusively located inside the treated cells. Histological localization of the blue dye crystals varied with the promoter used to drive the transgene.     

Associating somatic mutation with clinical outcomes through kernel regression and optimal transport

Somatic mutations in cancer patients are inherently sparse and potentially high dimensional. Cancer patients may share the same set of deregulated biological processes perturbed by different sets of somatically mutated genes. Therefore, when assessing the associations between somatic mutations and clinical outcomes, gene-by-gene analysis is often under-powered because it does not capture the complex disease mechanisms shared across cancer patients. Rather than testing genes one by one, an intuitive approach is to aggregate somatic mutation data of multiple genes to assess their joint association with clinical outcomes. The challenge is how to aggregate such information. Building on the optimal transport method, we propose a principled approach to estimate the similarity of somatic mutation profiles of multiple genes between tumor samples, while accounting for gene–gene similarities defined by gene annotations or empirical mutational patterns. Using such similarities, we can assess the associations between somatic mutations and clinical outcomes by kernel regression. We have applied our method to analyze somatic mutation data of 17 cancer types and identified at least five cancer types, where somatic mutations are associated with overall survival, progression-free interval, or cytolytic activity.     

Combining parametric and nonparametric models to estimate treatment effects in observational studies

Performing causal inference in observational studies requires we assume confounding variables are correctly adjusted for. In settings with few discrete-valued confounders, standard models can be employed. However, as the number of confounders increases these models become less feasible as there are fewer observations available for each unique combination of confounding variables. In this paper, we propose a new model for estimating treatment effects in observational studies that incorporates both parametric and nonparametric outcome models. By conceptually splitting the data, we can combine these models while maintaining a conjugate framework, allowing us to avoid the use of Markov chain Monte Carlo (MCMC) methods. Approximations using the central limit theorem and random sampling allow our method to be scaled to high-dimensional confounders. Through simulation studies we show our method can be competitive with benchmark models while maintaining efficient computation, and illustrate the method on a large epidemiological health survey.     

Coexisting mangrove-coral habitat use by reef fishes in the Caribbean

We conducted visual fish surveys in coexisting mangrove-coral (CMC) habitats in Panama to analyze the effect of coral presence in mangrove habitats on the fish assemblage. Our study revealed that CMC habitats harbor distinct fish assemblages compared to mangrove habitats without coral, with greater species richness and increased herbivore abundance. Abstract in Spanish is available with online material.