bluuebunny/crossref_metadata_2025 huggingface dataset:
Unique functions for protein kinase D1 and protein kinase D2 in mammalian cells
Authors: Matthews Sharon A. , Navarro Maria N. , Sinclair Linda V. , Emslie Elizabeth , Feijoo-Carnero Carmen , Cantrell Doreen A.
Published: September 2010

Mammalian PKD (protein kinase D) isoforms have been implicated in the regulation of diverse biological processes in response to diacylglycerol and PKC (protein kinase C) signalling. To compare the functions of PKD1 and PKD2 in vivo, we generated mice deficient in either PKD1 or PKD2 enzymatic activity, via homozygous expression of PKD1S744A/S748A or PKD2S707A/S711A ‘knockin’ alleles. We also examined PKD2-deficient mice generated using ‘gene-trap’ technology. We demonstrate that, unlike PKD1, PKD2 catalytic activity is dispensable for normal embryogenesis. We also show that PKD2 is the major PKD isoform expressed in lymphoid tissues, but that PKD2 catalytic activity is not essential for the development of mature peripheral T- and B-lymphocytes. PKD2 catalytic activity is, however, required for efficient antigen receptor-induced cytokine production in T-lymphocytes and for optimal T-cell-dependent antibody responses in vivo. Our results reveal a key in vivo role for PKD2 in regulating the function of mature peripheral lymphocytes during adaptive immune responses. They also confirm the functional importance of PKC-mediated serine phosphorylation of the PKD catalytic domain for PKD activation and downstream signalling and reveal that different PKD family members have unique and non-redundant roles in vivo.
Evolutionary origin of the cell nucleus and its functional architecture
Authors: Postberg Jan , Lipps Hans J. , Cremer Thomas
Published: September 2010

Understanding the evolutionary origin of the nucleus and its compartmentalized architecture provides a huge but, as expected, greatly rewarding challenge in the post-genomic era. We start this chapter with a survey of current hypotheses on the evolutionary origin of the cell nucleus. Thereafter, we provide an overview of evolutionarily conserved features of chromatin organization and arrangements, as well as topographical aspects of DNA replication and transcription, followed by a brief introduction of current models of nuclear architecture. In addition to features which may possibly apply to all eukaryotes, the evolutionary plasticity of higher-order nuclear organization is reflected by cell-type- and species-specific features, by the ability of nuclear architecture to adapt to specific environmental demands, as well as by the impact of aberrant nuclear organization on senescence and human disease. We conclude this chapter with a reflection on the necessity of interdisciplinary research strategies to map epigenomes in space and time.
Nucleosome dynamics and histone variants
Authors: Ray-Gallet Dominique , Almouzni Geneviève
Published: September 2010

In eukaryotes, DNA is organized into chromatin, a dynamic structure that enables DNA to be accessed for processes such as transcription, replication and repair. To form, maintain or alter this organization according to cellular needs, histones, the main protein component of chromatin, are deposited, replaced, exchanged and post-translationally modified. Histone variants, which exhibit specialized deposition modes in relation to the cell cycle and possibly particular chromatin regions, add an additional level of complexity in the regulation of histone flow. During their metabolism, from their synthesis to their delivery for nucleosome formation, the histones are escorted by proteins called histone chaperones. In the present chapter we summarize our current knowledge concerning histone chaperones and their interaction with particular histones based on key structural properties. From a compilation of selected histone chaperones identified to date, we discuss how they may be placed in a network to regulate histone dynamics. Finally, we provide working models to explain how H3 variants, deposited on to DNA using different histone chaperone machineries, can be transmitted or lost through cell divisions.
Chromatin plasticity in pluripotent cells
Authors: Melcer Shai , Meshorer Eran
Published: September 2010

ESCs (embryonic stem cells), derived from the blastocyst stage embryo, are characterized by an indefinite ability for self-renewal as well as pluripotency, enabling them to differentiate into all cell types of the three germ layers. In the undifferentiated state, ESCs display a global promiscuous transcriptional programme which is restricted gradually upon differentiation. Supporting transcriptional promiscuity, chromatin in pluripotent cells is more ‘plastic’ or ‘open’, with decondensed heterochromatin architecture, enrichment of active histone modifications, and a hyperdynamic association of chromatin proteins with chromatin. During ESC differentiation, nuclear architecture and chromatin undergo substantial changes. Heterochromatin foci appear smaller, more numerous and more condensed in the differentiated state, the nuclear lamina becomes more defined and chromatin protein dynamics becomes restricted. In the present chapter we discuss chromatin plasticity and epigenetics and the mechanisms that regulate the various chromatin states, which are currently a central theme in the studies of stem cell maintenance and differentiation, and which will no doubt assist in delineating the secrets of pluripotency and self-renewal.
Formation of metal nanoparticles of various sizes in plasma plumes produced by Ti:sapphire laser pulses
Authors: Chakravarty U. , Naik P. A. , Mukherjee C. , Kumbhare S. R. , Gupta P. D.
Published: September 2010

In this paper, an experimental study on generation of nanoparticle various sizes using Ti:sapphire laser pulses, is reported. Nanoparticle formation in plasma plumes of metals like silver and copper, expanding in vacuum, has been studied using stretched pulses of 300 ps duration [subnanoseconds (sub-ns)] from a Ti:sapphire laser. It has been compared with the nanoparticle formation (of the same materials) when compressed pulses of 45 fs duration were used under similar focusing conditions. Nanoparticle formation is observed at intensities as high as 2×1016 W/cm2. The structural analysis of the nanoparticle deposition on a silicon substrate showed that, using 45 fs pulses, smaller nanoparticles of average size ∼20 nm were generated, whereas on using the sub-ns pulses, larger particles were produced. Also, the visible light transmission and reflection from the nanoparticle film of Ag on glass substrate showed surface plasmon resonance (SPR). The SPR curves of the films of nanoparticles deposited by femtosecond pulses were always broader and reflection/transmission was always smaller when compared with the films formed using the sub-ns pulses, indicating smaller size particle formation by ultrashort pulses. Thus, it has been demonstrated that variation in the laser pulse duration of laser offers a simple tool for varying the size of the nanoparticles generated in plasma plumes.
Puckering free energy of pyranoses: A NMR and metadynamics-umbrella sampling investigation
Authors: Autieri E. , Sega M. , Pederiva F. , Guella G.
Published: September 2010

We present the results of a combined metadynamics-umbrella sampling investigation of the puckered conformers of pyranoses described using the GROMOS 45a4 force field. The free energy landscape of Cremer–Pople puckering coordinates has been calculated for the whole series of α and β aldohexoses, showing that the current force field parameters fail in reproducing proper puckering free energy differences between chair conformers. We suggest a modification to the GROMOS 45a4 parameter set which improves considerably the agreement of simulation results with theoretical and experimental estimates of puckering free energies. We also report on the experimental measurement of altrose conformer populations by means of NMR spectroscopy, which show good agreement with the predictions of current theoretical models.
Communication: Photodissociation of N2O—Frustrated NN bond breaking causes diffuse vibrational structures
Authors: Schinke R. , Suarez J. , Farantos S. C.
Published: September 2010

The photodissociation of N2O is studied by wave packet calculations using a global three-dimensional potential energy surface for the first excited A1′ state. It is shown that the weak vibrational structures of the absorption cross section are caused by large-amplitude NN stretch motion, combined with strong excitation of the bend as well as the O–NN stretch. Weakening of the NN bond toward the N+NO channel is the necessary prerequisite.
Multiscale modeling of binary polymer mixtures: Scale bridging in the athermal and thermal regime
Authors: McCarty J. , Guenza M. G.
Published: September 2010

Obtaining a rigorous and reliable method for linking computer simulations of polymer blends and composites at different length scales of interest is a highly desirable goal in soft matter physics. In this paper a multiscale modeling procedure is presented for the efficient calculation of the static structural properties of binary homopolymer blends. The procedure combines computer simulations of polymer chains on two different length scales, using a united atom representation for the finer structure and a highly coarse-grained approach on the mesoscale, where chains are represented as soft colloidal particles interacting through an effective potential. A method for combining the structural information by inverse mapping is discussed, allowing for the efficient calculation of partial correlation functions, which are compared with results from full united atom simulations. The structure of several polymer mixtures is obtained in an efficient manner for several mixtures in the homogeneous region of the phase diagram. The method is then extended to incorporate thermal fluctuations through an effective χ parameter. Since the approach is analytical, it is fully transferable to numerous systems.
Fundamental limits of energy dissipation in charge-based computing
Authors: Boechler Graham P. , Whitney Jean M. , Lent Craig S. , Orlov Alexei O. , Snider Gregory L.
Published: September 2010

According to Landauer’s principle, dissipation of energy is only necessary when information is erased, suggesting that vastly more efficient logical switches than transistors are possible. However, an influential analysis of binary switching suggests that representing information with electric charge is the root of the problem, that Landauer’s principle is fundamentally flawed, and that any movement of charge, such as charging a capacitor, must dissipate at least kBT ln(2). Here, using a RC circuit, an energy loss of much less than kBT ln(2) is demonstrated while delivering energy of 100 kBT ln(2) to the capacitor. This shows that there is no fundamental lower limit to energy dissipation in moving charge.
Visible iridescence from self-assembled periodic rippling in vertically aligned carbon nanotube forests
Authors: Vinten Phillip , Lefebvre Jacques , Finnie Paul
Published: September 2010

We observe iridescence in the form of spectrally dispersed white light reflected from the structured sidewalls of vertically aligned carbon nanotube forests. The iridescence is a result of diffraction from a self-assembled periodic rippling pattern on the forest sidewalls that acts as a reflection grating. We measure the grating spacing via white light and laser diffraction experiments and see good agreement with the spacing of the rippling pattern as measured via scanning electron microscopy. The periodic rippling pattern self-assembles during chemical vapor deposition growth of the forests.
Biologically inspired humidity sensor based on three-dimensional photonic crystals
Authors: Kim Jae Hyun , Moon Jun Hyuk , Lee Seung-Yop , Park Jungyul
Published: September 2010

This letter presents a biomimetic humidity sensor inspired by the humidity-dependent color change observed in the cuticle of the Hercules beetle. A thin-film-type humidity sensor with nanoporous structures (three-dimensional photonic crystals) mimicking the spongy multilayer in the beetles was designed and fabricated using the colloidal templating method and a hydrophilic surface treatment. The visible color of the fabricated humidity sensor changes from blue-green to red as the environmental humidity increases. The wavelength of reflected light that is predicted by Bragg’s equation considering the effect of water absorption shows a good agreement with experimental results.
Analytical/numerical calculation of the thermal stability factor in nanostructured exchange-coupled trilayers
Authors: Lee Seul Gee , Lim S. H.
Published: September 2010

An analytical/numerical method is used to calculate the thermal stability factor in nanostructured cells of exchange-coupled (either ferromagnetically or antiferromagnetically) trilayers. The method is then critically tested by comparing the calculated results with reliable experimental results reported recently in the literature [S. Yakata, H. Kubota, T. Sugano, T. Seki, K. Yakushiji, A. Fukushima, S. Yuasa, and K. Ando, Appl. Phys. Lett. 95, 242504 (2009)]. The accuracy of the method is confirmed by the excellent agreement for an antiferromagnetically coupled trilayer. For a ferromagnetically coupled trilayer, the comparison indicates a very weak interlayer exchange coupling (0.052 erg/cm2) between the two magnetic layers where the magnetization switching occurs in the via antiparallel mode.
The electrical and switching properties of a metal-ferroelectric (Bi3.15Nd0.85Ti3O12)-insulator (Y2O3-stabilized ZrO2)-silicon diode
Authors: Zhang Y. , Zhong X. L. , Wang J. B. , Song H. J. , Ma Y. , Zhou Y. C.
Published: September 2010

Metal-ferroelectric-insulator-silicon diodes with Bi3.15Nd0.85Ti3O12 (BNT) as the ferroelectric layer and Y2O3-stabilized ZrO2 (YSZ) as the insulating buffer layer have been fabricated. Measurements revealed that the memory window of the fabricated diode reduces with increasing operating temperature, which is due to the decrease of coercive field and polarization of the BNT film. The diode demonstrates excellent retention and fatigue characteristics because of the good interface and high barrier height of YSZ/Si. In addition, the switching of the diode corresponds to an approximate constant-current process, and the complete switching time displays an obvious decrease as the gate voltage increases.
Classification of ncRNAs using position and size information in deep sequencing data
Authors: Erhard Florian , Zimmer Ralf
Published: September 2010

Motivation: Small non-coding RNAs (ncRNAs) play important roles in various cellular functions in all clades of life. With next-generation sequencing techniques, it has become possible to study ncRNAs in a high-throughput manner and by using specialized algorithms ncRNA classes such as miRNAs can be detected in deep sequencing data. Typically, such methods are targeted to a certain class of ncRNA. Many methods rely on RNA secondary structure prediction, which is not always accurate and not all ncRNA classes are characterized by a common secondary structure. Unbiased classification methods for ncRNAs could be important to improve accuracy and to detect new ncRNA classes in sequencing data.

Results: Here, we present a scoring system called ALPS (alignment of pattern matrices score) that only uses primary information from a deep sequencing experiment, i.e. the relative positions and lengths of reads, to classify ncRNAs. ALPS makes no further assumptions, e.g. about common structural properties in the ncRNA class and is nevertheless able to identify ncRNA classes with high accuracy. Since ALPS is not designed to recognize a certain class of ncRNA, it can be used to detect novel ncRNA classes, as long as these unknown ncRNAs have a characteristic pattern of deep sequencing read lengths and positions. We evaluate our scoring system on publicly available deep sequencing data and show that it is able to classify known ncRNAs with high sensitivity and specificity.

Availability: Calculated pattern matrices of the datasets hESC and EB are available at the project web site http://www.bio.ifi.lmu.de/ALPS. An implementation of the described method is available upon request from the authors.

Contact:  florian.erhard@bio.ifi.lmu.de
Vorescore—fold recognition improved by rescoring of protein structure models
Authors: Csaba Gergely , Zimmer Ralf
Published: September 2010

Summary: The identification of good protein structure models and their appropriate ranking is a crucial problem in structure prediction and fold recognition. For many alignment methods, rescoring of alignment-induced models using structural information can improve the separation of useful and less useful models as compared with the alignment score. Vorescore, a template-based protein structure model rescoring system is introduced. The method scores the model structure against the template used for the modeling using Vorolign. The method works on models from different alignment methods and incorporates both knowledge from the prediction method and the rescoring.

Results: The performance of Vorescore is evaluated in a large-scale and difficult protein structure prediction context. We use different threading methods to create models for 410 targets, in three scenarios: (i) family members are contained in the template set; (ii) superfamily members (but no family members); and (iii) only fold members (but no family or superfamily members). In all cases Vorescore improves significantly (e.g. 40% on both Gotoh and HHalign at the fold level) on the model quality, and clearly outperforms the state-of-the-art physics-based model scoring system Rosetta. Moreover, Vorescore improves on other successful rescoring approaches such as Pcons and ProQ. In an additional experiment we add high-quality models based on structural alignments to the set, which allows Vorescore to improve the fold recognition rate by another 50%.

Availability: All models of the test set (about 2 million, 44 GB gzipped) are available upon request.

Contact:  csaba@bio.ifi.lmu.de; ralf.zimmer@ifi.lmu.de
Improved sequence-based prediction of disordered regions with multilayer fusion of multiple information sources
Authors: Mizianty Marcin J. , Stach Wojciech , Chen Ke , Kedarisetti Kanaka Durga , Disfani Fatemeh Miri , Kurgan Lukasz
Published: September 2010

Motivation: Intrinsically disordered proteins play a crucial role in numerous regulatory processes. Their abundance and ubiquity combined with a relatively low quantity of their annotations motivate research toward the development of computational models that predict disordered regions from protein sequences. Although the prediction quality of these methods continues to rise, novel and improved predictors are urgently needed.

Results: We propose a novel method, named MFDp (Multilayered Fusion-based Disorder predictor), that aims to improve over the current disorder predictors. MFDp is as an ensemble of 3 Support Vector Machines specialized for the prediction of short, long and generic disordered regions. It combines three complementary disorder predictors, sequence, sequence profiles, predicted secondary structure, solvent accessibility, backbone dihedral torsion angles, residue flexibility and B-factors. Our method utilizes a custom-designed set of features that are based on raw predictions and aggregated raw values and recognizes various types of disorder. The MFDp is compared at the residue level on two datasets against eight recent disorder predictors and top-performing methods from the most recent CASP8 experiment. In spite of using training chains with ≤25% similarity to the test sequences, our method consistently and significantly outperforms the other methods based on the MCC index. The MFDp outperforms modern disorder predictors for the binary disorder assignment and provides competitive real-valued predictions. The MFDp's outputs are also shown to outperform the other methods in the identification of proteins with long disordered regions.

Availability:  http://biomine.ece.ualberta.ca/MFDp.html

Supplementary information:  Supplementary data are available at Bioinformatics online.

Contact:  lkurgan@ece.ualberta.ca
A predictor for toxin-like proteins exposes cell modulator candidates within viral genomes
Authors: Naamati Guy , Askenazi Manor , Linial Michal
Published: September 2010

Motivation: Animal toxins operate by binding to receptors and ion channels. These proteins are short and vary in sequence, structure and function. Sporadic discoveries have also revealed endogenous toxin-like proteins in non-venomous organisms. Viral proteins are the largest group of quickly evolving proteomes. We tested the hypothesis that toxin-like proteins exist in viruses and that they act to modulate functions of their hosts.

Results: We updated and improved a classifier for compact proteins resembling short animal toxins that is based on a machine-learning method. We applied it in a large-scale setting to identify toxin-like proteins among short viral proteins. Among the ∼26 000 representatives of such short proteins, 510 sequences were positively identified. We focused on the 19 highest scoring proteins. Among them, we identified conotoxin-like proteins, growth factors receptor-like proteins and anti-bacterial peptides. Our predictor was shown to enhance annotation inference for many ‘uncharacterized’ proteins. We conclude that our protocol can expose toxin-like proteins in unexplored niches including metagenomics data and enhance the systematic discovery of novel cell modulators for drug development.

Availability: ClanTox is available at http://www.clantox.cs.huji.ac.il

Contact:  michall@cc.huji.ac.il
Discriminative and informative features for biomolecular text mining with ensemble feature selection
Authors: Van Landeghem Sofie , Abeel Thomas , Saeys Yvan , Van de Peer Yves
Published: September 2010

Motivation: In the field of biomolecular text mining, black box behavior of machine learning systems currently limits understanding of the true nature of the predictions. However, feature selection (FS) is capable of identifying the most relevant features in any supervised learning setting, providing insight into the specific properties of the classification algorithm. This allows us to build more accurate classifiers while at the same time bridging the gap between the black box behavior and the end-user who has to interpret the results.

Results: We show that our FS methodology successfully discards a large fraction of machine-generated features, improving classification performance of state-of-the-art text mining algorithms. Furthermore, we illustrate how FS can be applied to gain understanding in the predictions of a framework for biomolecular event extraction from text. We include numerous examples of highly discriminative features that model either biological reality or common linguistic constructs. Finally, we discuss a number of insights from our FS analyses that will provide the opportunity to considerably improve upon current text mining tools.

Availability: The FS algorithms and classifiers are available in Java-ML (http://java-ml.sf.net). The datasets are publicly available from the BioNLP'09 Shared Task web site (http://www-tsujii.is.s.u-tokyo.ac.jp/GENIA/SharedTask/).

Contact:  yves.vandepeer@psb.ugent.be
Utopia documents: linking scholarly literature with research data
Authors: Attwood T. K. , Kell D. B. , McDermott P. , Marsh J. , Pettifer S. R. , Thorne D.
Published: September 2010

Motivation: In recent years, the gulf between the mass of accumulating-research data and the massive literature describing and analyzing those data has widened. The need for intelligent tools to bridge this gap, to rescue the knowledge being systematically isolated in literature and data silos, is now widely acknowledged.

Results: To this end, we have developed Utopia Documents, a novel PDF reader that semantically integrates visualization and data-analysis tools with published research articles. In a successful pilot with editors of the Biochemical Journal (BJ), the system has been used to transform static document features into objects that can be linked, annotated, visualized and analyzed interactively (http://www.biochemj.org/bj/424/3/). Utopia Documents is now used routinely by BJ editors to mark up article content prior to publication. Recent additions include integration of various text-mining and biodatabase plugins, demonstrating the system's ability to seamlessly integrate on-line content with PDF articles.

Availability:  http://getutopia.com

Contact:  teresa.k.attwood@manchester.ac.uk
BioXSD: the common data-exchange format for everyday bioinformatics web services
Authors: Kalaš Matúš , Puntervoll Pål , Joseph Alexandre , Bartaševičiūtė Edita , Töpfer Armin , Venkataraman Prabakar , Pettifer Steve , Bryne Jan Christian , Ison Jon , Blanchet Christophe , Rapacki Kristoffer , Jonassen Inge
Published: September 2010

Motivation: The world-wide community of life scientists has access to a large number of public bioinformatics databases and tools, which are developed and deployed using diverse technologies and designs. More and more of the resources offer programmatic web-service interface. However, efficient use of the resources is hampered by the lack of widely used, standard data-exchange formats for the basic, everyday bioinformatics data types.

Results: BioXSD has been developed as a candidate for standard, canonical exchange format for basic bioinformatics data. BioXSD is represented by a dedicated XML Schema and defines syntax for biological sequences, sequence annotations, alignments and references to resources. We have adapted a set of web services to use BioXSD as the input and output format, and implemented a test-case workflow. This demonstrates that the approach is feasible and provides smooth interoperability. Semantics for BioXSD is provided by annotation with the EDAM ontology. We discuss in a separate section how BioXSD relates to other initiatives and approaches, including existing standards and the Semantic Web.

Availability: The BioXSD 1.0 XML Schema is freely available at http://www.bioxsd.org/BioXSD-1.0.xsd under the Creative Commons BY-ND 3.0 license. The http://bioxsd.org web page offers documentation, examples of data in BioXSD format, example workflows with source codes in common programming languages, an updated list of compatible web services and tools and a repository of feature requests from the community.

Contact:  matus.kalas@bccs.uib.no; developers@bioxsd.org; support@bioxsd.org
Modeling associations between genetic markers using Bayesian networks
Authors: Villanueva Edwin , Maciel Carlos Dias
Published: September 2010

Motivation: Understanding the patterns of association between polymorphisms at different loci in a population (linkage disequilibrium, LD) is of fundamental importance in various genetic studies. Many coefficients were proposed for measuring the degree of LD, but they provide only a static view of the current LD structure. Generative models (GMs) were proposed to go beyond these measures, giving not only a description of the actual LD structure but also a tool to help understanding the process that generated such structure. GMs based in coalescent theory have been the most appealing because they link LD to evolutionary factors. Nevertheless, the inference and parameter estimation of such models is still computationally challenging.

Results: We present a more practical method to build GM that describe LD. The method is based on learning weighted Bayesian network structures from haplotype data, extracting equivalence structure classes and using them to model LD. The results obtained in public data from the HapMap database showed that the method is a promising tool for modeling LD. The associations represented by the learned models are correlated with the traditional measure of LD D′. The method was able to represent LD blocks found by standard tools. The granularity of the association blocks and the readability of the models can be controlled in the method. The results suggest that the causality information gained by our method can be useful to tell about the conservability of the genetic markers and to guide the selection of subset of representative markers.

Availability: The implementation of the method is available upon request by email.

Contact:  maciel@sc.usp.br
Semi-supervised multi-task learning for predicting interactions between HIV-1 and human proteins
Authors: Qi Yanjun , Tastan Oznur , Carbonell Jaime G. , Klein-Seetharaman Judith , Weston Jason
Published: September 2010

Motivation: Protein–protein interactions (PPIs) are critical for virtually every biological function. Recently, researchers suggested to use supervised learning for the task of classifying pairs of proteins as interacting or not. However, its performance is largely restricted by the availability of truly interacting proteins (labeled). Meanwhile, there exists a considerable amount of protein pairs where an association appears between two partners, but not enough experimental evidence to support it as a direct interaction (partially labeled).

Results: We propose a semi-supervised multi-task framework for predicting PPIs from not only labeled, but also partially labeled reference sets. The basic idea is to perform multi-task learning on a supervised classification task and a semi-supervised auxiliary task. The supervised classifier trains a multi-layer perceptron network for PPI predictions from labeled examples. The semi-supervised auxiliary task shares network layers of the supervised classifier and trains with partially labeled examples. Semi-supervision could be utilized in multiple ways. We tried three approaches in this article, (i) classification (to distinguish partial positives with negatives); (ii) ranking (to rate partial positive more likely than negatives); (iii) embedding (to make data clusters get similar labels). We applied this framework to improve the identification of interacting pairs between HIV-1 and human proteins. Our method improved upon the state-of-the-art method for this task indicating the benefits of semi-supervised multi-task learning using auxiliary information.

Availability:  http://www.cs.cmu.edu/∼qyj/HIVsemi

Contact:  qyj@cs.cmu.edu
Candidate gene prioritization based on spatially mapped gene expression: an application to XLMR
Authors: Piro Rosario M. , Molineris Ivan , Ala Ugo , Provero Paolo , Di Cunto Ferdinando
Published: September 2010

Motivation: The identification of genes involved in specific phenotypes, such as human hereditary diseases, often requires the time-consuming and expensive examination of a large number of positional candidates selected by genome-wide techniques such as linkage analysis and association studies. Even considering the positive impact of next-generation sequencing technologies, the prioritization of these positional candidates may be an important step for disease-gene identification.

Results: Here, we report a large-scale analysis of spatial, i.e. 3D, gene-expression data from an entire organ (the mouse brain) for the purpose of evaluating and ranking positional candidate genes, showing that the spatial gene-expression patterns can be successfully exploited for the prediction of gene–phenotype associations not only for mouse phenotypes, but also for human central nervous system-related Mendelian disorders. We apply our method to the case of X-linked mental retardation, compare the predictions to the results obtained from a previous large-scale resequencing study of chromosome X and discuss some promising novel candidates.

Contact:  rosario.piro@unito.it

Supplementary information:  Supplementary data are available at Bioinformatics online.
Detecting host factors involved in virus infection by observing the clustering of infected cells in siRNA screening images
Authors: Suratanee Apichat , Rebhan Ilka , Matula Petr , Kumar Anil , Kaderali Lars , Rohr Karl , Bartenschlager Ralf , Eils Roland , König Rainer
Published: September 2010

Motivation: Detecting human proteins that are involved in virus entry and replication is facilitated by modern high-throughput RNAi screening technology. However, hit lists from different laboratories have shown only little consistency. This may be caused by not only experimental discrepancies, but also not fully explored possibilities of the data analysis. We wanted to improve reliability of such screens by combining a population analysis of infected cells with an established dye intensity readout.

Results: Viral infection is mainly spread by cell–cell contacts and clustering of infected cells can be observed during spreading of the infection in situ and in vivo. We employed this clustering feature to define knockdowns which harm viral infection efficiency of human Hepatitis C Virus. Images of knocked down cells for 719 human kinase genes were analyzed with an established point pattern analysis method (Ripley's K-function) to detect knockdowns in which virally infected cells did not show any clustering and therefore were hindered to spread their infection to their neighboring cells. The results were compared with a statistical analysis using a common intensity readout of the GFP-expressing viruses and a luciferase-based secondary screen yielding five promising host factors which may suit as potential targets for drug therapy.

Conclusion: We report of an alternative method for high-throughput imaging methods to detect host factors being relevant for the infection efficiency of viruses. The method is generic and has the potential to be used for a large variety of different viruses and treatments being screened by imaging techniques.

Contact:  r.eils@dkfz.de; r.koenig@dkfz.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Biological Activity of the Agrobacterium rhizogenes–Derived trolC Gene of Nicotiana tabacum and Its Functional Relation to Other plast Genes
Authors: Mohajjel-Shoja Hanieh , Clément Bernadette , Perot Jonathan , Alioua Malek , Otten Léon
Published: September 2010

Agrobacterium rhizogenes induces hairy roots through the activity of three essential T-DNA genes, rolA, rolB, and rolC, whereas the orf13 gene acts as an accessory root-inducing gene. rolB, rolC, and orf13 belong to the highly diverged plast gene family with remotely related representatives in the endomycorrhizal basidiomycete Laccaria bicolor. Nicotiana glauca and N. tabacum contain A. rhizogenes–derived T-DNAs with active plast genes. Here, we report on the properties of a rolC homolog in N. tabacum, trolC. Dexamethasone-inducible trolC and A4-rolC genes from A. rhizogenes A4 induce comparable, strong growth effects affecting all parts of the plants. Several have not been described earlier and were found to be very similar to the effects of the distantly related plast gene 6b. They include leaf chlorosis and starch accumulation, enations, increase of sucrose-dependent leaf disk expansion, growth of isolated roots on low-sucrose media, and stimulation of sucrose uptake by small root fragments. Collectively, our findings indicate that enhancement of sucrose uptake plays an important role in generating the complex 6b and rolC phenotypes and might be an ancestral property of the plast genes.
Etiology and Management of a Mandarin Rind Disorder in California
Authors: Adaskaveg J. E. , Förster H. , Connell J. H.
Published: September 2010

Recent reports of a preharvest rind disorder of Satsuma mandarin fruit resulted in severe crop losses in some growing areas of California (Butte, Fresno, Tulare, and Kern Counties). Symptoms were more frequently observed on fruit on the outer perimeter of the tree and on the exposed side of the fruit. Fungal isolations from affected fruit were inconsistent among orchard sites and growing seasons. Isolations resulted in species of Alternaria, Fusarium, Macrophomina, Ulocladium, and Cladosporium. In laboratory studies, mandarin fruit that were soaked in water for 6 h at 15 to 35°C, air dried, and incubated at 20°C for 3 days developed lesions similar to those observed in the field. When fruit were treated with an agricultural summer spray oil or the antitranspirant di-1-p-menthene prior to water soaking, the incidence and severity of the disorder were significantly reduced. Similar results were obtained in 2 years of field trials at two sites using one to three preharvest applications with the agricultural antitranspirant or summer oil starting after fruit color break. In most trials, a single application of these treatments at 1 or 2 weeks after color break was highly effective. Fungicides were inconsistent in their efficacy, whereas trees that were physically protected from rain did not develop the disorder. These data suggest that this mandarin rind disorder is a physiological, abiotic disorder rather than a pathological problem caused by fungi and can be economically managed with water-repellant treatments.
Assessment of the Process of Movement ofXylella fastidiosaWithin Susceptible and Resistant Grape Cultivars
Authors: Baccari C. , Lindow S. E.
Published: September 2010

To better understand the processes contributing to symptoms and resistance to Pierce's disease of grape, we examined the movement and multiplication of a green fluorescent protein-marked strain of Xylella fastidiosa in the stems and petioles of Cabernet Sauvignon, Chenin Blanc, Roucaneuf, and Tampa grape cultivars that differ in their susceptibility to this disease. X. fastidiosa achieved much lower population sizes and colonized fewer xylem vessels in the stem of resistant cultivars compared with more susceptible cultivars. In contrast, X. fastidiosa achieved similarly high population sizes and colonized a similar proportion of the vessels in petioles of susceptible and resistant cultivars, suggesting that, compared with the stem, X. fastidiosa is relatively unrestricted in its movement and growth within the petiole. There was not a direct relationship between the population size of X. fastidiosa in the stem and the proportion of vessels colonized; a much higher population size of the pathogen was observed in susceptible cultivars than expected based on the proportion of vessels colonized. The high population sizes of X. fastidiosa in stems of susceptible genotypes were associated with both a high number of infected vessels and a much higher extent of colonization of those vessels that become infested than in more resistant cultivars. The formation of large cellular aggregates in vessels is not required for X. fastidiosa to move laterally in the stem to adjacent vessels because most vessels harbored only small assemblages, especially in resistant cultivars such as Roucaneuf, in which some intervessel movement was detected. Resistance to Pierce's disease is apparently not due to inhibitory compounds that circulate in the xylem because they might be expected to operate similarly in all tissues.
Towards therapeutic antibodies to membrane oncoproteins by a robust strategy using rats immunized with transfectants expressing target molecules fused to green fluorescent protein
Authors: Masuko Takashi , Ohno Yoshiya , Masuko Kazue , Yagi Hideki , Uejima Shinya , Takechi Masayuki , Hashimoto Yoshiyuki
Published: September 2010

Cell‐surface molecules containing growth factor receptors, adhesion molecules and transporter proteins are often over‐expressed in various cancer cells, and could be regarded as suitable targets for therapeutic monoclonal antibodies (mAb). Anti‐cancer therapeutic mAb are claimed to bind these cell‐surface molecules on viable cancer cells: therefore, it is necessary to produce mAb recognizing epitopes on the extracellular domains of native but not denatured proteins. We have experienced difficulty in obtaining mAb bound to viable cancer cells using synthetic peptides or recombinant proteins produced in bacteria as immunogens, although these immunogens are relatively easy to prepare. In this context, we have concluded that viable cancer cells or cells transfected with cDNA encoding target proteins are suitable immunogens for the production of anti‐cancer therapeutic mAb. Furthermore, we selected rats as the immunized animals, because of their excellent capacity to generate diverse antibodies. Because many target candidates are multi‐pass (type IV) membrane proteins, such as 7‐pass G protein‐coupled receptors and 12‐pass transporter proteins belonging to the solute carrier family, and their possible immunogenic extracellular regions are very small, production of specific mAb was extremely difficult. In this review, we summarize the successful preparation and characterization of rat mAb immunized against the extracellular domain of type I, type II and type IV membrane oncoproteins fused to green fluorescent protein as an approach using reverse genetics, and also introduce the discovery of cell‐death‐inducing antibodies as an approach using forward genetics and a strategy to produce reshaped antibodies using mimotope peptides as the immunogen. (Cancer Sci 2011; 102: 25–35)
Plasminogen deficiency
Authors: MEHTA R. , SHAPIRO A. D.
Published: September 2010

Summary.  Plasminogen deficiency has emerged as a well‐recognized disorder in which reduced levels of plasminogen lead to the development of pseudo membranes on mucosal surfaces, with subsequent end‐organ damage of the affected tissue. Ligneous conjunctivitis is the most recognizable, well‐documented, and common presentation of the clinical syndromes associated with plasminogen deficiency, although numerous other organs have been reported to be affected. Interestingly, while plasminogen deficiency was initially believed to be related to development of venous thromboembolic disease, more recent data suggest that decreased plasminogen levels may not, in and of themselves, increase the risk of thrombosis. Two types of plasminogen deficiency have been described in the literature. Type I represents a quantitative deficiency and type II a qualitative deficiency. It appears that hypoplasminogenaemia (type I deficiency) is the type most associated with pseudomembrane disease. A variety of genetic mutations has been identified recently and is reported to lead to these disorders. These defects have been identified in diverse populations, with no specific ethnic predilection. However, this disorder may have increased prevalence in areas and communities where consanguinity is more common. Despite the fact that the characteristic lesions are now better recognized and plasminogen levels are accurately and easily measured, adequate treatment of the clinical manifestations of this disorder is lacking. For ligneous conjunctivitis, a plasminogen concentrate formulated into an ophthalmologic preparation has been found to be an effective local therapy. Unfortunately, no plasminogen concentrate is currently available commercially for either systemic or local therapy.
A novel HLA‐C*01 variant allele, HLA‐C*01:38
Authors: Deng Z.‐H. , Zhou H.‐Y. , Wang D.‐M. , Xu Y.‐P.
Published: September 2010

The novel HLA‐C*01:38 variant allele differs from the closest allele C*01:02:01 by a single nucleotide change at coding sequence (CDS) nt 430 G>A (codon 120 GGC>AGC) in exon 3, which causes an amino acid change Gly120Ser.
Metabolite profile analysis: from raw data to regression and classification
Authors: Steinfath Matthias , Groth Detlef , Lisec Jan , Selbig Joachim
Published: September 2010

Successful metabolic profile analysis will aid in the fundamental understanding of physiology. Here, we present a possible analysis workflow. Initially, the procedure to transform raw data into a data matrix containing relative metabolite levels for each sample is described. Given that, because of experimental issues in the technical equipment, the levels of some metabolites cannot be universally determined or that different experiments need to be compared, missing value estimation and normalization are presented as helpful preprocessing steps. Regression methods are presented in this review as tools to relate metabolite levels with other physiological properties like biomass and gene expression. As the number of measured metabolites often exceeds the number of samples, dimensionality reduction methods are required. Two of these methods are discussed in detail in this review. Throughout this article, practical examples illustrating the application of the aforementioned methods are given. We focus on the uncovering the relationship between metabolism and growth‐related properties.
Higher parasite resistance in Daphnia populations with recent epidemics
Authors: SCHOEBEL C. N. , WOLINSKA J. , SPAAK P.
Published: September 2010

Natural populations often show genetic variation in parasite resistance, forming the basis for evolutionary response to selection imposed by parasitism. We investigated whether previous epidemics selected for higher resistance to novel parasite isolates in a Daphnia galeata–microparasite system by comparing susceptibility of host clones from populations with varying epidemic history. We manipulated resource availability to evaluate whether diet influences Daphnia susceptibility as epidemics are common in nutrient‐rich lakes. Exposing clones from 10 lakes under two food treatments to an allopatric protozoan parasite, we found that Daphnia originating from lakes (mainly nutrient rich) with previous epidemics better resist infection. Despite this result, there was a tendency of higher susceptibility in the low food treatment, suggesting that higher resistance of clones from populations with epidemic background is not directly caused by lake nutrient level. Rather, our results imply that host populations respond to parasite‐mediated selection by evolving higher parasite resistance.
The lifetime costs of increased male reproductive effort: courtship, copulation and the Coolidge effect
Authors: JORDAN L. A. , BROOKS R. C.
Published: September 2010

The reproductive effort that a male directs to a familiar female declines over time, suggesting decreasing marginal returns. But is this diminishing returns a function of increasing reproductive costs or decreasing benefits of sustained effort? Here, we use the restoration of male reproductive effort with unfamiliar females to differentiate the role of diminishing returns and lifetime costs of increased reproductive effort of male guppies. We kept males with familiar or unfamiliar females throughout their lives and manipulated their ability to either court or mate with females. We found that increased male reproductive effort with novel mates lead to an immediate trade‐off in the form of reduced foraging effort. Further, males able to mate with a series of unfamiliar females had lower lifetime growth, indicating the primary cost of male reproductive effort in guppies arises from copulation rather than courtship. The lifetime growth trade‐offs were significant only when males mated with unfamiliar mates, suggesting that male reproductive effort with familiar females declines before it is restricted by physical exhaustion. These findings provide some of the first evidence of longitudinal costs of increased male reproductive effort in a vertebrate.
Regeneration of the gut requires retinoic acid in the budding ascidian Polyandrocarpa misakiensis
Authors: Kaneko Nagamoto , Katsuyama You , Kawamura Kazuo , Fujiwara Shigeki
Published: September 2010

The protochordate ascidian Polyandrocarpa misakiensis has a striking ability to regenerate. When the posterior half of the adult body is amputated, the anterior half completely loses the esophagus, stomach and intestine. These organs are reconstituted in a week. Histological observation revealed that the regeneration involves transdifferentiation of the atrial epithelium near the cut surface. The morphological features of the gut primordium were similar to those observed in the developing bud of this species. Inhibitors of the synthesis of retinoic acid (RA) suppressed the formation of the gut. 13‐cis RA rescued the regenerates from the inhibitor‐induced hypoplasia. These results suggest that RA is required for the regeneration of the gut. A gene encoding the RA receptor (Pm‐RAR) and its target gene, TRAMP, were expressed in and around the regenerating gut. Pm‐RAR‐specific and TRAMP‐specific double‐stranded RNA molecules inhibited the regeneration of the gut, indicating that the RA signal is mediated at least in part by Pm‐RAR and TRAMP. These results suggested that RA triggers the transdifferentiation of the atrial epithelium into the gut in regenerating animals, as it does during asexual reproduction.