SiteSeek: Post-translational modification analysis using adaptive locality-effective kernel methods and new profiles

<p>Abstract</p> <p>Background</p> <p>Post-translational modifications have a substantial influence on the structure and functions of protein. Post-translational phosphorylation is one of the most common modification that occur in intracellular proteins. Accurate prediction of protein phosphorylation sites is of great importance for the understanding of diverse cellular signalling processes in both the human body and in animals. In this study, we propose a new machine learning based protein phosphorylation site predictor, SiteSeek. SiteSeek is trained using a novel compact evolutionary and hydrophobicity profile to detect possible protein phosphorylation sites for a target sequence. The newly proposed method proves to be more accurate and exhibits a much stable predictive performance than currently existing phosphorylation site predictors.</p> <p>Results</p> <p>The performance of the proposed model was compared to nine existing different machine learning models and four widely known phosphorylation site predictors with the newly proposed PS-Benchmark_1 dataset to contrast their accuracy, sensitivity, specificity and correlation coefficient. SiteSeek showed better predictive performance with 86.6% accuracy, 83.8% sensitivity, 92.5% specificity and 0.77 correlation-coefficient on the four main kinase families (CDK, CK2, PKA, and PKC).</p> <p>Conclusion</p> <p>Our newly proposed methods used in SiteSeek were shown to be useful for the identification of protein phosphorylation sites as it performed much better than widely known predictors on the newly built PS-Benchmark_1 dataset.</p

Opposing effects of dietary n-3 and n-6 fatty acids on mammary carcinogenesis: The Singapore Chinese Health Study

10.1038/sj.bjc.6601340British Journal of Cancer8991686-1692BJCA

Subterranean, herbivore-induced plant volatile increases biological control activity of multiple beneficial nematode species in distinct habitats

While the role of herbivore-induced volatiles in plant-herbivore-natural enemy interactions is well documented aboveground, new evidence suggests that belowground volatile emissions can protect plants by attracting entomopathogenic nematodes (EPNs). However, due to methodological limitations, no study has previously detected belowground herbivore-induced volatiles in the field or quantified their impact on attraction of diverse EPN species. Here we show how a belowground herbivore-induced volatile can enhance mortality of agriculturally significant root pests. First, in real time, we identified pregeijerene (1,5-dimethylcyclodeca-1,5,7-triene) from citrus roots 9-12 hours after initiation of larval Diaprepes abbreviatus feeding. This compound was also detected in the root zone of mature citrus trees in the field. Application of collected volatiles from weevil-damaged citrus roots attracted native EPNs and increased mortality of beetle larvae (D. abbreviatus) compared to controls in a citrus orchard. In addition, field applications of isolated pregeijerene caused similar results. Quantitative real-time PCR revealed that pregeijerene increased pest mortality by attracting four species of naturally occurring EPNs in the field. Finally, we tested the generality of this root-zone signal by application of pregeijerene in blueberry fields; mortality of larvae (Galleria mellonella and Anomala orientalis) again increased by attracting naturally occurring populations of an EPN. Thus, this specific belowground signal attracts natural enemies of widespread root pests in distinct agricultural systems and may have broad potential in biological control of root pests.info:eu-repo/semantics/publishedVersio

A Granulin-Like Growth Factor Secreted by the Carcinogenic Liver Fluke, Opisthorchis viverrini, Promotes Proliferation of Host Cells

The human liver fluke, Opisthorchis viverrini, infects millions of people throughout south-east Asia and is a major cause of cholangiocarcinoma, or cancer of the bile ducts. The mechanisms by which chronic infection with O. viverrini results in cholangiocarcinogenesis are multi-factorial, but one such mechanism is the secretion of parasite proteins with mitogenic properties into the bile ducts, driving cell proliferation and creating a tumorigenic environment. Using a proteomic approach, we identified a homologue of human granulin, a potent growth factor involved in cell proliferation and wound healing, in the excretory/secretory (ES) products of the parasite. O. viverrini granulin, termed Ov-GRN-1, was expressed in most parasite tissues, particularly the gut and tegument. Furthermore, Ov-GRN-1 was detected in situ on the surface of biliary epithelial cells of hamsters experimentally infected with O. viverrini. Recombinant Ov-GRN-1 was expressed in E. coli and refolded from inclusion bodies. Refolded protein stimulated proliferation of murine fibroblasts at nanomolar concentrations, and proliferation was inhibited by the MAPK kinase inhibitor, U0126. Antibodies raised to recombinant Ov-GRN-1 inhibited the ability of O. viverrini ES products to induce proliferation of murine fibroblasts and a human cholangiocarcinoma cell line in vitro, indicating that Ov-GRN-1 is the major growth factor present in O. viverrini ES products. This is the first report of a secreted growth factor from a parasitic worm that induces proliferation of host cells, and supports a role for this fluke protein in establishment of a tumorigenic environment that may ultimately manifest as cholangiocarcinoma

Structural Analysis of the UBA Domain of X-linked Inhibitor of Apoptosis Protein Reveals Different Surfaces for Ubiquitin-Binding and Self-Association

BACKGROUND: Inhibitor of apoptosis proteins (IAPs) belong to a pivotal antiapoptotic protein family that plays a crucial role in tumorigenesis, cancer progression, chemoresistance and poor patient-survival. X-linked inhibitor of apoptosis protein (XIAP) is a prominent member of IAPs attracting intense research because it has been demonstrated to be a physiological inhibitor of caspases and apoptosis. Recently, an evolutionarily conserved ubiquitin-associated (UBA) domain was identified in XIAP and a number of RING domain-bearing IAPs. This has placed the IAPs in the group of ubiquitin binding proteins. Here, we explore the three-dimensional structure of the XIAP UBA domain (XIAP-UBA) and how it interacts with mono-ubiquitin and diubiquitin conjugates. PRINCIPAL FINDINGS: The solution structure of the XIAP-UBA domain was determined by NMR spectroscopy. XIAP-UBA adopts a typical UBA domain fold of three tightly packed alpha-helices but with an additional N-terminal 3(10) helix. The XIAP-UBA binds mono-ubiquitin as well as Lys48-linked and linear-linked diubiquitins at low-micromolar affinities. NMR analysis of the XIAP-UBA-ubiquitin interaction reveals that it involves the classical hydrophobic patches surrounding Ile44 of ubiquitin and the conserved MGF/LV motif surfaces on XIAP-UBA. Furthermore, dimerization of XIAP-UBA was observed. Mapping of the self-association surface of XIAP-UBA reveals that the dimerization interface is formed by residues in the N-terminal 3(10) helix, helix alpha1 and helix alpha2, separate from the ubiquitin-binding surface. CONCLUSION: Our results provide the first structural information of XIAP-UBA and map its interaction with mono-ubiquitin, Lys48-linked and linear-linked diubiquitins. The notion that XIAP-UBA uses different surfaces for ubiquitin-binding and self-association provides a plausible model to explain the reported selectivity of XIAP in binding polyubiquitin chains with different linkages.published_or_final_versio

An ERP Assessment of Hemispheric Projections in Foveal and Extrafoveal Word Recognition

The existence and function of unilateral hemispheric projections within foveal vision may substantially affect foveal word recognition. The purpose of this research was to reveal these projections and determine their functionality.Single words (and pseudowords) were presented to the left or right of fixation, entirely within either foveal or extrafoveal vision. To maximize the likelihood of unilateral projections for foveal displays, stimuli in foveal vision were presented away from the midline. The processing of stimuli in each location was assessed by combining behavioural measures (reaction times, accuracy) with on-line monitoring of hemispheric activity using event-related potentials recorded over each hemisphere, and carefully-controlled presentation procedures using an eye-tracker linked to a fixation-contingent display.Event-related potentials 100–150 ms and 150–200 ms after stimulus onset indicated that stimuli in extrafoveal and foveal locations were projected unilaterally to the hemisphere contralateral to the presentation hemifield with no concurrent projection to the ipsilateral hemisphere. These effects were similar for words and pseudowords, suggesting this early division occurred before word recognition. Indeed, event-related potentials revealed differences between words and pseudowords 300–350 ms after stimulus onset, for foveal and extrafoveal locations, indicating that word recognition had now occurred. However, these later event-related potentials also revealed that the hemispheric division observed previously was no longer present for foveal locations but remained for extrafoveal locations. These findings closely matched the behavioural finding that foveal locations produced similar performance each side of fixation but extrafoveal locations produced left-right asymmetries.These findings indicate that an initial division in unilateral hemispheric projections occurs in foveal vision away from the midline but is not apparent, or functional, when foveal word recognition actually occurs. In contrast, the division in unilateral hemispheric projections that occurs in extrafoveal locations is still apparent, and is functional, when extrafoveal word recognition takes place

HelmCoP: An Online Resource for Helminth Functional Genomics and Drug and Vaccine Targets Prioritization

A vast majority of the burden from neglected tropical diseases result from helminth infections (nematodes and platyhelminthes). Parasitic helminthes infect over 2 billion, exerting a high collective burden that rivals high-mortality conditions such as AIDS or malaria, and cause devastation to crops and livestock. The challenges to improve control of parasitic helminth infections are multi-fold and no single category of approaches will meet them all. New information such as helminth genomics, functional genomics and proteomics coupled with innovative bioinformatic approaches provide fundamental molecular information about these parasites, accelerating both basic research as well as development of effective diagnostics, vaccines and new drugs. To facilitate such studies we have developed an online resource, HelmCoP (Helminth Control and Prevention), built by integrating functional, structural and comparative genomic data from plant, animal and human helminthes, to enable researchers to develop strategies for drug, vaccine and pesticide prioritization, while also providing a useful comparative genomics platform. HelmCoP encompasses genomic data from several hosts, including model organisms, along with a comprehensive suite of structural and functional annotations, to assist in comparative analyses and to study host-parasite interactions. The HelmCoP interface, with a sophisticated query engine as a backbone, allows users to search for multi-factorial combinations of properties and serves readily accessible information that will assist in the identification of various genes of interest. HelmCoP is publicly available at: http://www.nematode.net/helmcop.html

Functional Foveal Splitting: Evidence from Neuropsychological and Multimodal MRI Investigations in a Chinese Patient with a Splenium Lesion

It remains controversial and hotly debated whether foveal information is double-projected to both hemispheres or split at the midline between the two hemispheres. We investigated this issue in a unique patient with lesions in the splenium of the corpus callosum and the left medial occipitotemporal region, through a series of neuropsychological tests and multimodal MRI scans. Behavioral experiments showed that (1) the patient had difficulties in reading simple and compound Chinese characters when they were presented in the foveal but left to the fixation, (2) he failed to recognize the left component of compound characters when the compound characters were presented in the central foveal field, (3) his judgments of the gender of centrally presented chimeric faces were exclusively based on the left half-face and he was unaware that the faces were chimeric. Functional MRI data showed that Chinese characters, only when presented in the right foveal field but not in the left foveal field, activated a region in the left occipitotemporal sulcus in the mid-fusiform, which is recognized as visual word form area. Together with existing evidence in the literature, results of the current study suggest that the representation of foveal stimuli is functionally split at object processing levels

Evaluating Effects of Divided Hemispheric Processing on Word Recognition in Foveal and Extrafoveal Displays: The Evidence from Arabic

Background: Previous studies have claimed that a precise split at the vertical midline of each fovea causes all words to the left and right of fixation to project to the opposite, contralateral hemisphere, and this division in hemispheric processing has considerable consequences for foveal word recognition. However, research in this area is dominated by the use of stimuli from Latinate languages, which may induce specific effects on performance. Consequently, we report two experiments using stimuli from a fundamentally different, non-Latinate language (Arabic) that offers an alternative way of revealing effects of split-foveal processing, if they exist. Methods and Findings: Words (and pseudowords) were presented to the left or right of fixation, either close to fixation and entirely within foveal vision, or further from fixation and entirely within extrafoveal vision. Fixation location and stimulus presentations were carefully controlled using an eye-tracker linked to a fixation-contingent display. To assess word recognition, Experiment 1 used the Reicher-Wheeler task and Experiment 2 used the lexical decision task. Results: Performance in both experiments indicated a functional division in hemispheric processing for words in extrafoveal locations (in recognition accuracy in Experiment 1 and in reaction times and error rates in Experiment 2) but no such division for words in foveal locations. Conclusions: These findings from a non-Latinate language provide new evidence that although a functional division i

Stereochemical plasticity modulates cooperative binding in a CoII12L6 cuboctahedron

Biomolecular receptors are able to process information by responding differentially to combinations of chemical signals. Synthetic receptors that are likewise capable of multi-stimuli response can form the basis of programmable molecular systems, wherein specific input sequences create distinct outputs. Here we report a pseudo-cuboctahedral assembly capable of cooperatively binding anionic and neutral guest species. The binding of pairs of fullerene guests was observed to effect the all-or-nothing cooperative templation of an S6-symmetric host stereoisomer. This bis-fullerene adduct exhibits different cooperativity in binding pairs of anions from the fullerene-free parent: in one case, positive cooperativity is observed, while in another all binding affinities are enhanced by an order of magnitude, and in a third the binding events are only minimally perturbed. This intricate modulation of binding affinity, and thus cooperativity, renders our new cuboctahedral receptor attractive for incorporation into systems with complex, programmable responses to different sets of stimuli.This work was supported by the UK Engineering and Physical Sciences Research Council (EPSRC). F.J.R. acknowledges Cambridge Australia Scholarships and the Cambridge Trust for PhD funding