bluuebunny/crossref_metadata_2025 huggingface dataset:
Algorithm for backrub motions in protein design
Authors: Georgiev Ivelin , Keedy Daniel , Richardson Jane S. , Richardson David C. , Donald Bruce R.
Published: June 2008

Motivation: The Backrub is a small but kinematically efficient side-chain-coupled local backbone motion frequently observed in atomic-resolution crystal structures of proteins. A backrub shifts the Cα–Cβ orientation of a given side-chain by rigid-body dipeptide rotation plus smaller individual rotations of the two peptides, with virtually no change in the rest of the protein. Backrubs can therefore provide a biophysically realistic model of local backbone flexibility for structure-based protein design. Previously, however, backrub motions were applied via manual interactive model-building, so their incorporation into a protein design algorithm (a simultaneous search over mutation and backbone/side-chain conformation space) was infeasible.

Results: We present a combinatorial search algorithm for protein design that incorporates an automated procedure for local backbone flexibility via backrub motions. We further derive a dead-end elimination (DEE)-based criterion for pruning candidate rotamers that, in contrast to previous DEE algorithms, is provably accurate with backrub motions. Our backrub-based algorithm successfully predicts alternate side-chain conformations from ≤0.9 Å resolution structures, confirming the suitability of the automated backrub procedure. Finally, the application of our algorithm to redesign two different proteins is shown to identify a large number of lower-energy conformations and mutation sequences that would have been ignored by a rigid-backbone model.

Availability: Contact authors for source code.

Contact:  brd+ismb08@cs.duke.edu
POIMs: positional oligomer importance matrices—understanding support vector machine-based signal detectors
Authors: Sonnenburg Sören , Zien Alexander , Philips Petra , Rätsch Gunnar
Published: June 2008

Motivation: At the heart of many important bioinformatics problems, such as gene finding and function prediction, is the classification of biological sequences. Frequently the most accurate classifiers are obtained by training support vector machines (SVMs) with complex sequence kernels. However, a cumbersome shortcoming of SVMs is that their learned decision rules are very hard to understand for humans and cannot easily be related to biological facts.

Results: To make SVM-based sequence classifiers more accessible and profitable, we introduce the concept of positional oligomer importance matrices (POIMs) and propose an efficient algorithm for their computation. In contrast to the raw SVM feature weighting, POIMs take the underlying correlation structure of k-mer features induced by overlaps of related k-mers into account. POIMs can be seen as a powerful generalization of sequence logos: they allow to capture and visualize sequence patterns that are relevant for the investigated biological phenomena.

Availability: All source code, datasets, tables and figures are available at http://www.fml.tuebingen.mpg.de/raetsch/projects/POIM.

Contact:  Soeren.Sonnenburg@first.fraunhofer.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
ProSOM: core promoter prediction based on unsupervised clustering of DNA physical profiles
Authors: Abeel Thomas , Saeys Yvan , Rouzé Pierre , Van de Peer Yves
Published: June 2008

Motivation: More and more genomes are being sequenced, and to keep up with the pace of sequencing projects, automated annotation techniques are required. One of the most challenging problems in genome annotation is the identification of the core promoter. Because the identification of the transcription initiation region is such a challenging problem, it is not yet a common practice to integrate transcription start site prediction in genome annotation projects. Nevertheless, better core promoter prediction can improve genome annotation and can be used to guide experimental work.

Results: Comparing the average structural profile based on base stacking energy of transcribed, promoter and intergenic sequences demonstrates that the core promoter has unique features that cannot be found in other sequences. We show that unsupervised clustering by using self-organizing maps can clearly distinguish between the structural profiles of promoter sequences and other genomic sequences. An implementation of this promoter prediction program, called ProSOM, is available and has been compared with the state-of-the-art. We propose an objective, accurate and biologically sound validation scheme for core promoter predictors. ProSOM performs at least as well as the software currently available, but our technique is more balanced in terms of the number of predicted sites and the number of false predictions, resulting in a better all-round performance. Additional tests on the ENCODE regions of the human genome show that 98% of all predictions made by ProSOM can be associated with transcriptionally active regions, which demonstrates the high precision.

Availability: Predictions for the human genome, the validation datasets and the program (ProSOM) are available upon request.

Contact:  yves.vandepeer@psb.ugent.be
Optimal pooling for genome re-sequencing with ultra-high-throughput short-read technologies
Authors: Hajirasouliha Iman , Hormozdiari Fereydoun , Sahinalp S. Cenk , Birol Inanc
Published: June 2008

New generation sequencing technologies offer unique opportunities and challenges for re-sequencing studies. In this article, we focus on re-sequencing experiments using the Solexa technology, based on bacterial artificial chromosome (BAC) clones, and address an experimental design problem. In these specific experiments, approximate coordinates of the BACs on a reference genome are known, and fine-scale differences between the BAC sequences and the reference are of interest. The high-throughput characteristics of the sequencing technology makes it possible to multiplex BAC sequencing experiments by pooling BACs for a cost-effective operation. However, the way BACs are pooled in such re-sequencing experiments has an effect on the downstream analysis of the generated data, mostly due to subsequences common to multiple BACs. The experimental design strategy we develop in this article offers combinatorial solutions based on approximation algorithms for the well-known max n-cut problem and the related max n-section problem on hypergraphs. Our algorithms, when applied to a number of sample cases give more than a 2-fold performance improvement over random partitioning.

Contact:  cenk@cs.sfu.ca
MicroRNA prediction with a novel ranking algorithm based on random walks
Authors: Xu Yunpen , Zhou Xuefeng , Zhang Weixiong
Published: June 2008

MicroRNA (miRNAs) play essential roles in post-transcriptional gene regulation in animals and plants. Several existing computational approaches have been developed to complement experimental methods in discovery of miRNAs that express restrictively in specific environmental conditions or cell types. These computational methods require a sufficient number of characterized miRNAs as training samples, and rely on genome annotation to reduce the number of predicted putative miRNAs. However, most sequenced genomes have not been well annotated and many of them have a very few experimentally characterized miRNAs. As a result, the existing methods are not effective or even feasible for identifying miRNAs in these genomes.

Aiming at identifying miRNAs from genomes with a few known miRNA and/or little annotation, we propose and develop a novel miRNA prediction method, miRank, based on our new random walks- based ranking algorithm. We first tested our method on Homo sapiens genome; using a very few known human miRNAs as samples, our method achieved a prediction accuracy greater than 95%. We then applied our method to predict 200 miRNAs in Anopheles gambiae, which is the most important vector of malaria in Africa. Our further study showed that 78 out of the 200 putative miRNA precursors encode mature miRNAs that are conserved in at least one other animal species. These conserved putative miRNAs are good candidates for further experimental study to understand malaria infection.

Availability: MiRank is programmed in Matlab on Windows platform. The source code is available upon request.

Contact:  zhang@cse.wustl.edu
A robust framework for detecting structural variations in a genome
Authors: Lee Seunghak , Cheran Elango , Brudno Michael
Published: June 2008

Motivation: Recently, structural genomic variants have come to the forefront as a significant source of variation in the human population, but the identification of these variants in a large genome remains a challenge. The complete sequencing of a human individual is prohibitive at current costs, while current polymorphism detection technologies, such as SNP arrays, are not able to identify many of the large scale events. One of the most promising methods to detect such variants is the computational mapping of clone-end sequences to a reference genome.

Results: Here, we present a probabilistic framework for the identification of structural variants using clone-end sequencing. Unlike previous methods, our approach does not rely on an a priori determined mapping of all reads to the reference. Instead, we build a framework for finding the most probable assignment of sequenced clones to potential structural variants based on the other clones. We compare our predictions with the structural variants identified in three previous studies. While there is a statistically significant correlation between the predictions, we also find a significant number of previously uncharacterized structural variants. Furthermore, we identify a number of putative cross-chromosomal events, primarily located proximally to the centromeres of the chromosomes.

Availability: Our dataset, results and source code are available at http://compbio.cs.toronto.edu/structvar/

Contact:  seunghak@cs.toronto.edu,echeran@cs.toronto.edu,brudno@cs.toronto.edu
Annotation-based inference of transporter function
Authors: Lee Thomas J. , Paulsen Ian , Karp Peter
Published: June 2008

Motivation: We present a method for inferring and constructing transport reactions for transporter proteins based primarily on the analysis of the names of individual proteins in the genome annotation of an organism. Transport reactions are declarative descriptions of transporter activities, and thus can be manipulated computationally, unlike free-text protein names. Once transporter activities are encoded as transport reactions, a number of computational analyses are possible including database queries by transporter activity; inclusion of transporters into an automatically generated metabolic-map diagram that can be painted with omics data to aid in their interpretation; detection of anomalies in the metabolic and transport networks, such as substrates that are transported into the cell but are not inputs to any metabolic reaction or pathway; and comparative analyses of the transport capabilities of different organisms.

Results: On randomly selected organisms, the method achieves precision and recall rates of 0.93 and 0.90, respectively in identifying transporter proteins by name within the complete genome. The method obtains 67.5% accuracy in predicting complete transport reactions; if allowance is made for predictions that are overly general yet not incorrect, reaction prediction accuracy is 82.5%.

Availability: The method is implemented as part of PathoLogic, the inference component of the Pathway Tools software. Pathway Tools is freely available to researchers at non-commercial institutions, including source code; a fee applies to commercial institutions.

Contact:  tomlee@ai.sri.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
Identifying gene-disease associations using centrality on a literature mined gene-interaction network
Authors: Özgür Arzucan , Vu Thuy , Erkan Güneş , Radev Dragomir R.
Published: June 2008

Motivation: Understanding the role of genetics in diseases is one of the most important aims of the biological sciences. The completion of the Human Genome Project has led to a rapid increase in the number of publications in this area. However, the coverage of curated databases that provide information manually extracted from the literature is limited. Another challenge is that determining disease-related genes requires laborious experiments. Therefore, predicting good candidate genes before experimental analysis will save time and effort. We introduce an automatic approach based on text mining and network analysis to predict gene-disease associations. We collected an initial set of known disease-related genes and built an interaction network by automatic literature mining based on dependency parsing and support vector machines. Our hypothesis is that the central genes in this disease-specific network are likely to be related to the disease. We used the degree, eigenvector, betweenness and closeness centrality metrics to rank the genes in the network.

Results: The proposed approach can be used to extract known and to infer unknown gene-disease associations. We evaluated the approach for prostate cancer. Eigenvector and degree centrality achieved high accuracy. A total of 95% of the top 20 genes ranked by these methods are confirmed to be related to prostate cancer. On the other hand, betweenness and closeness centrality predicted more genes whose relation to the disease is currently unknown and are candidates for experimental study.

Availability: A web-based system for browsing the disease-specific gene-interaction networks is available at: http://gin.ncibi.org

Contact:  radev@umich.edu
Classification of arrayCGH data using fused SVM
Authors: Rapaport Franck , Barillot Emmanuel , Vert Jean-Philippe
Published: June 2008

Motivation: Array-based comparative genomic hybridization (arrayCGH) has recently become a popular tool to identify DNA copy number variations along the genome. These profiles are starting to be used as markers to improve prognosis or diagnosis of cancer, which implies that methods for automated supervised classification of arrayCGH data are needed. Like gene expression profiles, arrayCGH profiles are characterized by a large number of variables usually measured on a limited number of samples. However, arrayCGH profiles have a particular structure of correlations between variables, due to the spatial organization of bacterial artificial chromosomes along the genome. This suggests that classical classification methods, often based on the selection of a small number of discriminative features, may not be the most accurate methods and may not produce easily interpretable prediction rules.

Results: We propose a new method for supervised classification of arrayCGH data. The method is a variant of support vector machine that incorporates the biological specificities of DNA copy number variations along the genome as prior knowledge. The resulting classifier is a sparse linear classifier based on a limited number of regions automatically selected on the chromosomes, leading to easy interpretation and identification of discriminative regions of the genome. We test this method on three classification problems for bladder and uveal cancer, involving both diagnosis and prognosis. We demonstrate that the introduction of the new prior on the classifier leads not only to more accurate predictions, but also to the identification of known and new regions of interest in the genome.

Availability: All data and algorithms are publicly available.

Contact:  franck.rapaport@curie.fr
Modeling peptide fragmentation with dynamic Bayesian networks for peptide identification
Authors: Klammer Aaron A. , Reynolds Sheila M. , Bilmes Jeff A. , MacCoss Michael J. , Noble William Stafford
Published: June 2008

Motivation: Tandem mass spectrometry (MS/MS) is an indispensable technology for identification of proteins from complex mixtures. Proteins are digested to peptides that are then identified by their fragmentation patterns in the mass spectrometer. Thus, at its core, MS/MS protein identification relies on the relative predictability of peptide fragmentation. Unfortunately, peptide fragmentation is complex and not fully understood, and what is understood is not always exploited by peptide identification algorithms.

Results: We use a hybrid dynamic Bayesian network (DBN)/support vector machine (SVM) approach to address these two problems. We train a set of DBNs on high-confidence peptide-spectrum matches. These DBNs, known collectively as Riptide, comprise a probabilistic model of peptide fragmentation chemistry. Examination of the distributions learned by Riptide allows identification of new trends, such as prevalent a-ion fragmentation at peptide cleavage sites C-term to hydrophobic residues. In addition, Riptide can be used to produce likelihood scores that indicate whether a given peptide-spectrum match is correct. A vector of such scores is evaluated by an SVM, which produces a final score to be used in peptide identification. Using Riptide in this way yields improved discrimination when compared to other state-of-the-art MS/MS identification algorithms, increasing the number of positive identifications by as much as 12% at a 1% false discovery rate.

Availability: Python and C source code are available upon request from the authors. The curated training sets are available at http://noble.gs.washington.edu/proj/intense/. The Graphical Model Tool Kit (GMTK) is freely available at http://ssli.ee.washington.edu/bilmes/gmtk.

Contact:  noble@gs.washington.edu
Telecommunications
Authors: John Richard R.
Published: June 2008

The half-century following the Civil War witnessed an epochal transformation in American telecommunications. In the 1870s, the telegraph network became a spawning ground for a remarkable spate of inventions that included the phonograph and the telephone, and around 1900 the telephone network became the first electrical communications medium that network providers intended to be accessible to the entire population. This transformation was a centerpiece of the still unprecedented burst of inventive activity that economic historians call the Second Industrial Revolution.
Timely Resistance in the Documentary Work of Dominique Cabrera
Authors: Dobson Julia
Published: June 2008

Dominique Cabrera's œuvre attests to a consistent preoccupation with the representation and construction of a
bonheur collectif
. Through a detailed analysis of two documentary films,
Chronique d'une banlieue ordinaire
(1992) and
Demain et encore demain (journal 1995)
(1997), this article will reveal her adoption of the documentary as a therapeutic form in opposition to dominant Griersonian modes of documentary that counter the potential empowerment of representation with the conferral of victimhood on its subjects. Cabrera's films avoid such heritages through their insistence on a formal
mise en abyme
of documentary processes to perform a
réinsertion sociale
of the stigmatized communities of Val Fourré and a moving
réinsertion temporelle
of the filmmaker herself in the first-person confessional
Demain et encore demain
. This
mise en abyme
includes a meditation on the ontology of the photographic image and its pervasive relationship with mortality; both films sensitize their audience to the relationship between image, time and narrative. Such arguments are presented within the context of the dramatic increase in production of (first-person) documentary in contemporary France and the current crisis of legitimization in the conventional documentary form.
Promenades de lecteurs dans
Le Vaillant Petit Tailleur
d'Éric Chevillard
Authors: Tobiassen Elin Beate
Published: June 2008

Le roman
Le Vaillant Petit Tailleur
d'Éric Chevillard (2003), écrivain dont la production figure peut-être parmi les œuvres en prose les plus notoires de la littérature française actuelle, a été perçu par la critique comme une attaque sévère contre la forme traditionnelle du conte de fées. Explorant une nouvelle piste, cet article aborde le roman sous l'angle de la réception littéraire, argumentant que la préoccupation cruciale de son narrateur-auteur est au contraire celle qui consiste à inventer un lecteur de son propre texte. Qui est ce lecteur en jeu dans l'œuvre? Quel(s) lecteur(s) ce texte se présume-t-il? Quelles figures de lecteurs imagine-t-il au fil des pages? Et quelle place cette œuvre métatextuelle, intelligemment agencée, demandant recul, ruse, et perspicacité de la part de son lecteur, laisse-t-elle à la jouissance, à l'envoûtement? L'analyse du
Vaillant Petit Tailleur
sous cette lumière inédite permet de reconsidérer l'attitude distanciée souvent attribuée au lecteur de la métafiction moderne. S'il est un écrivain tenant d'une conception ‘intellectuelle’ du roman, refusant l'immersion mimétique à l'égard du personnage au profit d'un développement excessif du potentiel réflexif du texte, Chevillard est pourtant fort loin de vouer son lecteur à l'abstinence du plaisir.
An operational monitoring system to provide indicators of CO2-related variables in the ocean
Authors: Hardman-Mountford Nicholas J. , Moore Gerald , Bakker Dorothee C. E. , Watson Andrew J. , Schuster Ute , Barciela Rosa , Hines Adrian , Moncoiffé Gwenaelle , Brown Juan , Dye Stephen , Blackford Jerry , Somerfield Paul J. , Holt Jason , Hydes David J. , Aiken James
Published: June 2008

Hardman-Mountford, N. J., Moore, G., Bakker, D. C. E., Watson, A. J., Schuster, U., Barciela, R., Hines, A., Moncoiffé, G., Brown, J., Dye, S., Blackford, J., Somerfield, P. J., Holt, J., Hydes, D. J., and Aiken, J. 2008. An operational monitoring system to provide indicators of CO2-related variables in the ocean. – ICES Journal of Marine Science, 65: 1498–1503. Demand by governments and scientists is increasing for indicators of CO2-related variables for the ocean. We describe a recent project, CARBON-OPS, during which a “supply chain” was developed for automated measurement of pCO2 in the surface of the ocean, data processing, and its use in providing information for research and policy development. Data are gathered by new pCO2 measurement systems on five UK research ships in the Southern Ocean, Atlantic Ocean, and northwestern European shelf seas. These send data in near-real-time, via satellite communication systems, to the British Oceanographic Data Centre, where they are automatically processed, quality controlled, and archived. The data are then delivered to the UK Met Office and others for use in testing predictions from operational ocean models. These models will generate indicator products and assist government through the Marine Climate Change Impact Partnership, a partnership of scientists, government, its agencies, and NGOs, by providing information on ocean CO2 uptake, changes in ocean pH, and potential impacts on global climate and marine ecosystems.
Local effects of inbreeding on embryo number and consequences for genetic diversity in Kerguelen mouflon
Authors: Kaeuffer Renaud , Réale Denis , Pontier Dominique , Chapuis Jean-Louis , Coltman David W
Published: June 2008

A classical paradigm in population genetics is that homozygosity or inbreeding affects individual fitness through increased disease susceptibility and mortality, and diminished breeding success. Using data from an insular population of mouflon (
Ovis aries
) founded by a single pair of individuals, we compare embryo number of ewes with different levels of inbreeding. Contrary to expectations, ewes with the highest levels of homozygosity showed the largest number of embryos. Using two different statistical approaches, we showed that this relationship is probably caused by heterozygosity at specific genes. The genetics of embryo number coupled with cyclic dynamics could play a central role in promoting genetic variation in this population.
Light alters nociceptive effects of magnetic field shielding in mice: intensity and wavelength considerations
Authors: Prato Frank S , Desjardins-Holmes Dawn , Keenliside Lynn D , McKay Julia C , Robertson John A , Thomas Alex W
Published: June 2008

Previous experiments with mice have shown that repeated 1 hour daily exposure to an ambient magnetic field-shielded environment induces analgesia (antinociception). The exposures were carried out in the dark (less than 2.0×1016photons s−1 m−2) during the mid-light phase of the diurnal cycle. However, if the mice were exposed in the presence of visible light (2.0×1018photons s−1 m−2, 400–750 nm), then the analgesic effects of shielding were eliminated. Here, we show that this effect of light is intensity and wavelength dependent. Introduction of red light (peak at 635 nm) had little or no effect, presumably because mice do not have photoreceptors sensitive to red light above 600 nm in their eyes. By contrast, introduction of ultraviolet light (peak at 405 nm) abolished the effect, presumably because mice do have ultraviolet A receptors. Blue light exposures (peak at 465 nm) of different intensities demonstrate that the effect has an intensity threshold of approximately 12% of the blue light in the housing facility, corresponding to 5×1016photons s−1 m−2(integral). This intensity is similar to that associated with photoreceptor-based magnetoreception in birds and in mice stimulates photopic/cone vision. Could the detection mechanism that senses ambient magnetic fields in mice be similar to that in bird navigation?
Characterization and use of laser-based lysis for cell analysis on-chip
Authors: Lai Hsuan-Hong , Quinto-Su Pedro A , Sims Christopher E , Bachman Mark , Li G.P , Venugopalan Vasan , Allbritton Nancy L
Published: June 2008

We demonstrate the use of a pulsed laser microbeam for cell lysis followed by electrophoretic separation of cellular analytes in a microfluidic device. The influence of pulse energy and laser focal point within the microchannel on the threshold for plasma formation was measured. The thickness of the poly(dimethylsiloxane) (PDMS) layer through which the beam travelled was a critical determinant of the threshold energy. An effective optical path length,
L
eff
, for the laser beam can be used to predict the threshold for optical breakdown at different microchannel locations. A key benefit of laser-based cell lysis is the very limited zone (less than 5 μm) of lysis. A second asset is the rapid cell lysis times (approx. microseconds). These features enable two analytes, fluorescein and Oregon Green, from a cell to be electrophoretically separated in the channel in which cell lysis occurred. The resolution and efficiency of the separation of the cellular analytes are similar to those of standards demonstrating the feasibility of using a pulsed laser microbeam in single-cell analysis.
Introduction. Speciation in plants and animals: pattern and process
Authors: Abbott Richard J , Ritchie Michael G , Hollingsworth Peter M
Published: June 2008

Although approximately 150 years have passed since the publication ofOn the origin of species by means of natural selection, the definition of what species are and the ways in which species originate remain contentious issues in evolutionary biology. The biological species concept, which defines species as groups of interbreeding natural populations that are reproductively isolated from other such groups, continues to draw support. However, there is a growing realization that many animal and plant species can hybridize with their close relatives and exchange genes without losing their identity. On occasion, such hybridization can lead to the origin of new species. A key to understanding what species are and the ways in which they originate rests to a large extent on a detailed knowledge of the nature and genetics of factors that limit gene flow between species and the conditions under which such isolation originates. The collection of papers in this issue addresses these topics and deals as well with some specific issues of hybrid speciation and the causes of species radiations. The papers included arise from a 1-day symposium on speciation held during the Sixth Biennial Meeting of the Systematics Association at Edinburgh in August 2007. In this introduction, we provide some background to these papers and highlight some key points made. The papers make clear that highly significant advances to our understanding of animal and plant speciation are currently being made across the range of this topic.
Accelerated sequence divergence of conserved genomic elements inDrosophila melanogaster
Authors: Holloway Alisha K. , Begun David J. , Siepel Adam , Pollard Katherine S.
Published: June 2008

Recent genomic sequencing of 10 additionalDrosophilagenomes provides a rich resource for comparative genomics analyses aimed at understanding the similarities and differences between species and betweenDrosophilaand mammals. Using a phylogenetic approach, we identified 64 genomic elements that have been highly conserved over most of theDrosophilatree, but that have experienced a recent burst of evolution along theDrosophila melanogasterlineage. Compared to similarly defined elements in humans, these regions of rapid lineage-specific evolution inDrosophiladiffer dramatically in location, mechanism of evolution, and functional properties of associated genes. Notably, the majority reside in protein-coding regions and primarily result from rapid adaptive synonymous site evolution. In fact, adaptive evolution appears to be driving substitutions to unpreferred codons. Our analysis also highlights interesting noncoding genomic regions, such as regulatory regions in the genegooseberry-neuroand a putative novel miRNA.
Beyond transcription factors: The role of chromatin modifying enzymes in regulating transcription required for memory
Authors: Barrett Ruth M. , Wood Marcelo A.
Published: June 2008

One of the alluring aspects of examining chromatin modifications in the role of modulating transcription required for long-term memory processes is that these modifications may provide transient and potentially stable epigenetic marks in the service of activating and/or maintaining transcriptional processes. These, in turn, may ultimately participate in the molecular mechanisms required for neuronal changes subserving long-lasting changes in behavior. As an epigenetic mechanism of transcriptional control, chromatin modification has been shown to participate in maintaining cellular memory (e.g., cell fate) and may underlie the strengthening and maintenance of synaptic connections required for long-term changes in behavior. Epigenetics has become central to several fields of neurobiology, where researchers have found that regulation of chromatin modification has a significant role in epilepsy, drug addiction, depression, neurodegenerative diseases, and memory. In this review, we will discuss the role of chromatin modifying enzymes in memory processes, as well as how recent studies in yeast genetics and cancer biology may impact the way we think about how chromatin modification and chromatin remodeling regulate neuronal function.
Synthetic Lipid (DOPG) Vesicles Accumulate in the Cell Plate Region But Do Not Fuse
Authors: Esseling-Ozdoba Agnieszka , Vos Jan W. , van Lammeren André A.M. , Emons Anne Mie C.
Published: June 2008

The cell plate is the new cell wall, with bordering plasma membrane, that is formed between two daughter cells in plants, and it is formed by fusion of vesicles (approximately 60 nm). To start to determine physical properties of cell plate forming vesicles for their transport through the phragmoplast, and fusion with each other, we microinjected fluorescent synthetic lipid vesicles that were made of 1,2-dioleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (DOPG) into Tradescantia virginiana stamen hair cells. During interphase, the 60-nm wide DOPG vesicles moved inside the cytoplasm comparably to organelles. During cytokinesis, they were transported through the phragmoplast and accumulated in the cell plate region together with the endogenous vesicles, even inside the central cell plate region. Because at this stage microtubules are virtually absent from that region, while actin filaments are present, actin filaments may have a role in the transport of vesicles toward the cell plate. Unlike the endogenous vesicles, the synthetic DOPG vesicles did not fuse with the developing cell plate. Instead, they redistributed into the cytoplasm of the daughter cells upon completion of cytokinesis. Because the redistribution of the vesicles occurs when actin filaments disappear from the phragmoplast, actin filaments may be involved in keeping the vesicles inside the developing cell plate region.
Genetic Evidence That Cellulose Synthase Activity Influences Microtubule Cortical Array Organization
Authors: Paredez Alexander R. , Persson Staffan , Ehrhardt David W. , Somerville Chris R.
Published: June 2008

To identify factors that influence cytoskeletal organization we screened for Arabidopsis (Arabidopsis thaliana) mutants that show hypersensitivity to the microtubule destabilizing drug oryzalin. We cloned the genes corresponding to two of the 131 mutant lines obtained. The genes encoded mutant alleles of PROCUSTE1 and KORRIGAN, which both encode proteins that have previously been implicated in cellulose synthesis. Analysis of microtubules in the mutants revealed that both mutants have altered orientation of root cortical microtubules. Similarly, isoxaben, an inhibitor of cellulose synthesis, also altered the orientation of cortical microtubules while exogenous cellulose degradation did not. Thus, our results substantiate that proteins involved in cell wall biosynthesis influence cytoskeletal organization and indicate that this influence on cortical microtubule stability and orientation is correlated with cellulose synthesis rather than the integrity of the cell wall.
ThePRA1Gene Family in Arabidopsis
Authors: Alvim Kamei Claire Lessa , Boruc Joanna , Vandepoele Klaas , Van den Daele Hilde , Maes Sara , Russinova Eugenia , Inzé Dirk , De Veylder Lieven
Published: June 2008

Prenylated Rab acceptor 1 (PRA1) domain proteins are small transmembrane proteins that regulate vesicle trafficking as receptors of Rab GTPases and the vacuolar soluble N-ethylmaleimide-sensitive factor attachment receptor protein VAMP2. However, little is known about PRA1 family members in plants. Sequence analysis revealed that higher plants, compared with animals and primitive plants, possess an expanded family of PRA1 domain-containing proteins. The Arabidopsis (Arabidopsis thaliana) PRA1 (AtPRA1) proteins were found to homodimerize and heterodimerize in a manner corresponding to their phylogenetic distribution. Different AtPRA1 family members displayed distinct expression patterns, with a preference for vascular cells and expanding or developing tissues. AtPRA1 genes were significantly coexpressed with Rab GTPases and genes encoding vesicle transport proteins, suggesting an involvement in the vesicle trafficking process similar to that of their animal counterparts. Correspondingly, AtPRA1 proteins were localized in the endoplasmic reticulum, Golgi apparatus, and endosomes/prevacuolar compartments, hinting at a function in both secretory and endocytic intracellular trafficking pathways. Taken together, our data reveal a high functional diversity of AtPRA1 proteins, probably dealing with the various demands of the complex trafficking system.
Crystal structure of rhodocytin, a ligand for the platelet‐activating receptor CLEC‐2
Authors: Watson Aleksandra A. , Eble Johannes A. , O'Callaghan Chris A.
Published: June 2008

Binding of the snake venom protein rhodocytin to CLEC‐2, a receptor on the surface of human platelets, initiates a signaling cascade leading to platelet activation and aggregation. We have previously solved the structure of CLEC‐2. The 2.4 Å resolution crystal structure of rhodocytin presented here demonstrates that it is the first snake venom or other C‐type lectin‐like protein to assemble as a non‐disulfide linked (αβ)2 tetramer. Rhodocytin is highly adapted for interaction with CLEC‐2 and displays a concave binding surface, which is highly complementary to the experimentally determined binding interface on CLEC‐2. Using computational dynamic methods, surface electrostatic charge and hydrophobicity analyses, and protein–protein docking predictions, we propose that the (αβ)2 rhodocytin tetramer induces clustering of CLEC‐2 receptors on the platelet surface, which will trigger major signaling events resulting in platelet activation and aggregation.
Properties of Gamma-Ray Burst Progenitor Stars
Authors: Kumar Pawan , Narayan Ramesh , Johnson Jarrett L.
Published: June 2008

We determined some basic properties of stars that produce spectacular gamma-ray bursts at the end of their lives. We assumed that accretion of the outer portion of the stellar core by a central black hole fuels the prompt emission and that fall-back and accretion of the stellar envelope later produce the plateau in the x-ray light curve seen in some bursts. Using x-ray data for three bursts, we estimated the radius of the stellar core to be ∼(1 – 3) × 10
10
cm and that of the stellar envelope to be ∼(1 – 2) × 10
11
cm. The density profile in the envelope is fairly shallow, with ρ ∼
r
–2
(where ρ is density and
r
is distance from the center of the explosion). The rotation speeds of the core and envelope are ∼0.05 and ∼0.2 of the local Keplerian speed, respectively.
Measurement of the Distribution of Site Enhancements in Surface-Enhanced Raman Scattering
Authors: Fang Ying , Seong Nak-Hyun , Dlott Dana D.
Published: June 2008

On nanotextured noble-metal surfaces, surface-enhanced Raman scattering (SERS) is observed, where Raman scattering is enhanced by a factor,
Ḡ
, that is frequently about one million, but underlying the factor
Ḡ
is a broad distribution of local enhancement factors, η. We have measured this distribution for benzenethiolate molecules on a 330-nanometer silver-coated nanosphere lattice using incident light of wavelength 532 nanometers. A series of laser pulses with increasing electric fields burned away molecules at sites with progressively decreasing electromagnetic enhancement factors. The enhancement distribution
P
(η)
d
η was found to be a power law proportional to (η)
–1.75
, with minimum and maximum values of 2.8 × 10
4
and 4.1 × 10
10
, respectively. The hottest sites (η >10
9
) account for just 63 in 1,000,000 of the total but contribute 24% to the overall SERS intensity.
Crystal Structure of the Termination Module of a Nonribosomal Peptide Synthetase
Authors: Tanovic Alan , Samel Stefan A. , Essen Lars-Oliver , Marahiel Mohamed A.
Published: June 2008

Nonribosomal peptide synthetases (NRPSs) are modular multidomain enzymes that act as an assembly line to catalyze the biosynthesis of complex natural products. The crystal structure of the 144-kilodalton
Bacillus subtilis
termination module SrfA-C was solved at 2.6 angstrom resolution. The adenylation and condensation domains of SrfA-C associate closely to form a catalytic platform, with their active sites on the same side of the platform. The peptidyl carrier protein domain is flexibly tethered to this platform and thus can move with its substrate-loaded 4′-phosphopantetheine arm between the active site of the adenylation domain and the donor side of the condensation domain. The SrfA-C crystal structure has implications for the rational redesign of NRPSs as a means of producing novel bioactive peptides.
Epigenetic dysregulation of the DAP kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in acute leukaemias
Authors: Chim C S , Chan W W L , Kwong Y L
Published: June 2008

Background:

Dysregulation of apoptosis is important in carcinogenesis.

Aim and Methods:

To analyse the potential inactivation of the DAP kinase/p14/HDM2/p53/Apaf-1 pathway by aberrant promoter methylation in acute leukaemias.

Results:

Of five leukaemic lines examined,p14was unmethylated in Raji, HL60 and U937, but completely deleted in Jurkat and NB4.DAP kinasewas totally methylated in Raji and NB4, but unmethylated in HL60, Jurkat and U937.Apaf-1was unmethylated in all the lines. At diagnosis,DAP kinasemethylation occurred in eight (25%) APL patients and none of the other AML patients (8/32 vs 0/50, p = 0.001).DAP kinasemethylation was detected in four (16%) ALL patients.p14andApaf-1methylation was not detected in any of the 32 cases of acute promyelocytic leukaemia (APL), 50 cases of other subtypes of acute myeloid leukaemia (AML), and 25 cases of acute lymphoblastic leukaemia.

Conclusion:

Among AML subtypes,DAP kinaseis preferentially hypermethylated in APL.
Mantle cell lymphoma lacking the t(11;14) translocation: a case report and brief review of the literature: Figure 1
Authors: Hunt K E , Reichard K K , Wilson C S
Published: June 2008

The diagnosis of mantle cell lymphoma (MCL) requires a multifaceted approach with integration of morphology and immunophenotype, supported by cyclin D1 positivity or identification of t(11;14)(q13;q32). Interphase fluorescence in situ hybridisation (FISH) using a dual colour, dual fusion probe strategy for t(11;14) is a rapid test with high sensitivity and specificity for MCL, and is easily performed on routine bone marrow aspirate or peripheral blood specimens. This test has become the method of choice for many pathologists to confirm a diagnosis of MCL. This report describes a case of MCL with a normal (negative) FISH signal pattern for t(11;14) that was found to be cyclin D1 positive by immunohistochemistry in tissue sections. This case illustrates the need for additional testing when the t(11;14) abnormality is not identified but the morphology and immunophenotype are otherwise suggestive of MCL.
Fibroadenoma of the anogenital region
Authors: Vella J E O , Taibjee S M , Sanders D S A , Stellakis M , Carr R A
Published: June 2008

Fibroadenoma of the anogenital region is a rare tumour histologically similar to fibroadenoma of the breast. Morphological and immunophenotypic features of a case with pseudoangiomatous stromal hyperplasia are presented here.
A new rapid and sensitive assay for detecting the T315IBCR-ABLkinase domain mutation in chronic myeloid leukaemia
Authors: Khorashad J S , Thelwell N , Milojkovic D , Marin D , Watson J A , Goldman J M , Apperley J F , Foroni L , Reid A G
Published: June 2008

A significant minority of chronic myeloid leukaemia patients eventually develop resistance to imatinib, often as a result of point mutations within theBCR-ABLkinase domain. Second-line tyrosine kinase inhibitors (TKIs) are effective against mutations that confer imatinib resistance; however, the T315IBCR-ABLmutant has proved resistant to all available TKIs. An assay facilitating early identification ofBCR-ABLT315Iwould therefore aid in identifying high-risk patients who may benefit from alternative therapy. This report describes the development of a sensitive T315I mutation detection methodology based on real-time PCR with self-probing fluorescent primers. The technique demonstrated complete concordance with direct sequencing, correctly identifying 34 T315I-positive samples from a total of 61 samples screened. In a limiting dilution assay, the mutated clone was detectable to a level of 1% of total cells. The data show that Scorpions PCR enables rapid screening forBCR-ABLT315Iin chronic myeloid leukaemia patients and is appropriate for use in a clinical setting.
Rb–Sr and U–Pb geochronology and setting of the Buffalo Head Hills kimberlite field, northern AlbertaThis article is one of a selection of papers published in this Special Issue on the themeGeology of northeastern British Columbia and northwestern Alberta: diamonds, shallow gas, gravel, and glaciers.
Authors: Eccles D. Roy , Creaser Robert A. , Heaman Larry M. , Ward Jeff
Published: June 2008

New Rb–Sr phlogopite and U–Pb perovskite age determinations for 12 of 38 known ultramafic bodies in the Buffalo Head Hills area of north-central Alberta show that kimberlitic magmatism occurred in at least two separate episodes during Late Cretaceous and Paleocene time. Nine kimberlites yield Coniacian to Campanian ages of between 88 ± 5 Ma (U–Pb perovskite, K5A) and 81.2 ± 2.3 Ma (Rb–Sr phlogopite, K252). A Danian U–Pb perovskite isochron age of 63.5 ± 0.7 Ma was obtained for the BM2 kimberlite, and Selandian Rb–Sr ages of 59.6 ± 2.8 and 60.3 ± 0.8 Ma were determined for the K1A and K19 bodies, respectively. These specific periods of magmatism correspond to characteristic intra-field features such as kimberlite spatial distribution, diamond content, rock classification, and mechanisms of emplacement. The ∼88–81 Ma group generally occurs in the northwestern part of the field and defines the diamond window for the Buffalo Head Hills kimberlite field. This volcanism is contemporaneous with sedimentary host rock deposition, which has important implications for the size and morphological complexity of the kimberlite bodies. The ∼64 Ma BM2 body represents the only known occurrence of hypabyssal-facies kimberlite in this field and is similar in terms of source composition to the ∼88–81 Ma kimberlites, but is not diamond bearing. The ∼60 Ma group occurs in the southwestern part of the field, is derived from a weakly diamondiferous – barren hybrid ultramafic source and features bodies that are eroded to present-day stratigraphic levels.
Landform assemblages produced by the Laurentide Ice Sheet in northeastern British Columbia and adjacent Northwest Territories — constraints on glacial lakes and patterns of ice retreatThis article is one of a selection of papers published in this Special Issue on the theme Geology of northeastern British Columbia and northwestern Alberta: diamonds, shallow gas, gravel, and glaciers.
Authors: Bednarski Jan M.
Published: June 2008

The Laurentide Ice Sheet reached the Canadian Cordillera during the last glacial maximum in northeastern British Columbia and adjacent Northwest Territories and all regional drainage to unglaciated areas in the north was dammed by the ice. Converging ice-flow patterns near the mountain front suggest that the Laurentide Ice Sheet likely coalesced with the Cordilleran Ice Sheet during the last glaciation. With deglaciation, the ice masses separated, but earlier ice retreat in the south meant that meltwater pooled between the mountain front and the Laurentide margin. The level of the flooding was controlled by persistent ice cover on the southern Franklin Mountains. Glacial Lake Liard formed when the Laurentide Ice Sheet retreated east of the southern Liard Range and, at its maximum extent, may have impounded water at least as far south as the Fort Nelson River. Deglaciation of the plains was marked by local variations in ice flow caused by a thin ice sheet becoming more affected by the topography and forming lobes in places. These lobes caused diversions in local drainage readily traced by abandoned meltwater channels. Radiocarbon ages from adjacent areas suggest the relative chronology of deglaciation presented here occurred between 13 and 11 ka BP.