Conservation implications of midden selection and use in an endangered gazelle (Gazella gazella)

This study examines midden selection and use by mountain gazelles Gazella gazella in central Saudia Arabia and the implications of middens (dung piles) for the conservation of this species. Specifically, we tested poachers' claims that mountain gazelles are easy to kill because midden use was predictable and conspicuous. We found that midden selection in mountain gazelles is non-random, with middens typically located at the base of the most conspicuous and largest trees, although the choice of midden sites is also influenced by tree species. Middens clearly have olfactory importance; the majority of mountain gazelles that visited middens were observed sniffing the ground. Mountain gazelles visit middens at night, which corroborates poachers' claims that the animals are easily hunted at night through spotlighting. Although the use of open habitats that are accessible to automobiles makes gazelles vulnerable to hunting and being run down, our data suggest that midden use is also an attribute that makes gazelles susceptible to hunting. Poachers can locate gazelles because of middens' predictable locations, as they are placed at prominent landmarks, are visually conspicuous as large dung piles, and are visited at night, which allows the animals to be found through spotlighting. Other taxa that use predictable and prominent landmarks, or communicate through visually conspicuous methods could also be susceptible to poaching.     

Endoplasmic reticulum stress and the unfolded protein response regulate genomic cystic fibrosis transmembrane conductance regulator expression

The unfolded protein response (UPR) is a cellular recovery mechanism activated by endoplasmic reticulum (ER) stress. The UPR is coordinated with the ER-associated degradation (ERAD) to regulate the protein load at the ER. In the present study, we tested how membrane protein biogenesis is regulated through the UPR in epithelia, using the cystic fibrosis transmembrane conductance regulator (CFTR) as a model. Pharmacological methods such as proteasome inhibition and treatment with brefeldin A and tunicamycin were used to induce ER stress and activate the UPR as monitored by increased levels of spliced XBP1 and BiP mRNA. The results indicate that activation of the UPR is followed by a significant decrease in genomic CFTR mRNA levels without significant changes in the mRNA levels of another membrane protein, the transferrin receptor. We also tested whether overexpression of a wild-type CFTR transgene in epithelia expressing endogenous wild-type CFTR activated the UPR. Although CFTR maturation is inefficient in this setting, the UPR was not activated. However, pharmacological induction of ER stress in these cells also led to decreased endogenous CFTR mRNA levels without affecting recombinant CFTR message levels. These results demonstrate that under ER stress conditions, endogenous CFTR biogenesis is regulated by the UPR through alterations in mRNA levels and posttranslationally by ERAD, whereas recombinant CFTR expression is regulated only by ERAD. endoplasmic reticulum-associated degradation; messenger ribonucleic acid     

A Bayesian measure of the probability of false discovery in genetic epidemiology studies

In light of the vast amounts of genomic data that are now being generated, we propose a new measure, the Bayesian false-discovery probability (BFDP), for assessing the noteworthiness of an observed association. BFDP shares the ease of calculation of the recently proposed false-positive report probability (FPRP) but uses more information, has a noteworthy threshold defined naturally in terms of the costs of false discovery and nondiscovery, and has a sound methodological foundation. In addition, in a multiple-testing situation, it is straightforward to estimate the expected numbers of false discoveries and false nondiscoveries. We provide an in-depth discussion of FPRP, including a comparison with the q value, and examine the empirical behavior of these measures, along with BFDP, via simulation. Finally, we use BFDP to assess the association between 131 single-nucleotide polymorphisms and lung cancer in a case-control study.     

Preparation of novel anthranilic acids as antibacterial agents: extensive evaluation of structural and physical properties on antibacterial activity and human serum albumin affinity

In the past few years a significant effort has been devoted by Pharmacia toward the discovery of novel antibiotics. We have recently described the identification of an anthranilic acid lead 1 and the optimization resulting in the advanced lead 2. In this report, we describe the preparation of several selected analogs to probe the dependency of this template for antibacterial activity and the affinity these compounds have for human serum albumin (HSA). These analogs illustrate that decreased affinity for HSA can be achieved while retaining relevant antibacterial activity. The most important factor for reduced HSA affinity is decrease in logP rather than a structural change.     

Diet composition and foraging ecology of U.S. Pacific Coast groundfishes with applications for fisheries management

Determining the prey composition and foraging habitats of U.S. Pacific Coast groundfishes are specified management directives that have not received much scientific attention. To address this knowledge gap, we conducted a meta-analysis of the feeding ecology of 18 commercially important species and their life stages during a recent review of Pacific Coast groundfish essential fish habitat. A Major Prey Index was developed to evaluate relative importance among 47 prey taxa. Based on this metric, unidentified teleosts, euphausiids, and brachyuran crabs were the most important prey groups. When 14 generalized prey categories were used, fishes represented the dominant taxon (mean % weight or volume = 32.3) followed by shrimps (11.5), crabs (10.0), and euphausiids (9.5). PERMANOVA results indicated that species-specific differences were the primary source of dietary variability among tested variables (life stage, functional group, taxonomic group). Pacific Coast groundfishes mainly were characterized as mesopredators with estimated trophic levels ranging from 3.4 to 4.2. Foraging habitats differed significantly among functional (benthic, demersal, pelagic) and taxonomic (elasmobranch, roundfish, rockfish, flatfish) groups. Using hierarchical agglomerative cluster analysis, we identified a significantly distinct trophic guild that consumes mainly polychaetes and hard-shelled molluscs (juvenile, juvenile–adult Dover Sole; juvenile–adult English Sole) and another that specializes on euphausiids (juvenile Pacific Hake; juvenile–adult Darkblotched Rockfish). Our findings filled substantial data gaps in the trophic ecology and habitat-based management of commercially important species and can be used to inform future reviews of Pacific Coast groundfish essential fish habitat.     

A microtubule interactome: complexes with roles in cell cycle and mitosis

The microtubule (MT) cytoskeleton is required for many aspects of cell function, including the transport of intracellular materials, the maintenance of cell polarity, and the regulation of mitosis. These functions are coordinated by MT-associated proteins (MAPs), which work in concert with each other, binding MTs and altering their properties. We have used a MT cosedimentation assay, combined with 1D and 2D PAGE and mass spectrometry, to identify over 250 MAPs from early Drosophila embryos. We have taken two complementary approaches to analyse the cellular function of novel MAPs isolated using this approach. First, we have carried out an RNA interference (RNAi) screen, identifying 21 previously uncharacterised genes involved in MT organisation. Second, we have undertaken a bioinformatics analysis based on binary protein interaction data to produce putative interaction networks of MAPs. By combining both approaches, we have identified and validated MAP complexes with potentially important roles in cell cycle regulation and mitosis. This study therefore demonstrates that biologically relevant data can be harvested using such a multidisciplinary approach, and identifies new MAPs, many of which appear to be important in cell division.     

Purification of galectin-3 from ovine placenta: developmentally regulated expression and immunological relevance

Galectins, beta-galactoside-binding lectins, are extensively distributed in the animal kingdom and share some basic molecular properties. Galectin-3, a member of this family, is generally associated with differentiation, morphogenesis, and metastasis. In this study, galectin-3 was isolated from ovine placental cotyledons round the middle of the gestation period by lactose extraction followed by affinity chromatography on lactosyl-agarose, and separated from galectin-1 by size exclusion chromatography on a Superose 12 column. Under native conditions this lectin behaved as a monomer with an apparent molecular weight of approximately 29,000 and an isoelectric point of 9.0. The partial amino acid sequence of the peptides obtained by tryptic digestion of this protein followed by HPLC separation showed striking homology with other members of the galectin-3 subfamily. Furthermore, ovine placental galectin-3 exhibited specific mitogenic activity toward rat spleen mononuclear cells. Besides, this protein strongly reacted with a rabbit antiserum raised against a chicken galectin. Results obtained by Western blot analysis showed that its expression was greatly decreased in term placenta with respect to the middle of the gestation period, suggesting a regulated expression throughout development.      

PyEvolve: a toolkit for statistical modelling of molecular evolution

Background  

Examining the distribution of variation has proven an extremely profitable technique in the effort to identify sequences of biological significance. Most approaches in the field, however, evaluate only the conserved portions of sequences – ignoring the biological significance of sequence differences. A suite of sophisticated likelihood based statistical models from the field of molecular evolution provides the basis for extracting the information from the full distribution of sequence variation. The number of different problems to which phylogeny-based maximum likelihood calculations can be applied is extensive. Available software packages that can perform likelihood calculations suffer from a lack of flexibility and scalability, or employ error-prone approaches to model parameterisation.