bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV-1 Nef-induced Down-Regulation of MHC Class I Requires AP-1 and Clathrin but Not PACS-1 and Is Impeded by AP-2
Authors: Lubben Nienke B. , Sahlender Daniela A. , Motley Alison M. , Lehner Paul J. , Benaroch Philippe , Robinson Margaret S.
Published: June 2007

Major histocompatibility complex class I is down-regulated from the surface of human immunodeficiency virus (HIV)-1-infected cells by Nef, a virally encoded protein that is thought to reroute MHC-I to the trans-Golgi network (TGN) in a phosphofurin acidic cluster sorting protein (PACS) 1, adaptor protein (AP)-1, and clathrin-dependent manner. More recently, an alternative model has been proposed, in which Nef uses AP-1 to direct MHC-I to endosomes and lysosomes. Here, we show that knocking down either AP-1 or clathrin with small interfering RNA inhibits the down-regulation of HLA-A2 (an MHC-I isotype) by Nef in HeLa cells. However, knocking down PACS-1 has no effect, not only on Nef-induced down-regulation of HLA-A2 but also on the localization of other proteins containing acidic cluster motifs. Surprisingly, knocking down AP-2 actually enhances Nef activity. Immuno-electron microscopy labeling of Nef-expressing cells indicates that HLA-A2 is rerouted not to the TGN, but to endosomes. In AP-2–depleted cells, more of the HLA-A2 localizes to the inner vesicles of multivesicular bodies. We propose that depleting AP-2 potentiates Nef activity by altering the membrane composition and dynamics of endosomes and causing increased delivery of HLA-A2 to a prelysosomal compartment.
STAM and Hrs Down-Regulate Ciliary TRP Receptors
Authors: Hu Jinghua , Wittekind Samuel G. , Barr Maureen M.
Published: June 2007

Cilia are endowed with membrane receptors, channels, and signaling components whose localization and function must be tightly controlled. In primary cilia of mammalian kidney epithelia and sensory cilia of Caenorhabditis elegans neurons, polycystin-1 (PC1) and transient receptor polycystin-2 channel (TRPP2 or PC2), function together as a mechanosensory receptor-channel complex. Despite the importance of the polycystins in sensory transduction, the mechanisms that regulate polycystin activity and localization, or ciliary membrane receptors in general, remain poorly understood. We demonstrate that signal transduction adaptor molecule STAM-1A interacts with C. elegans LOV-1 (PC1), and that STAM functions with hepatocyte growth factor–regulated tyrosine kinase substrate (Hrs) on early endosomes to direct the LOV-1-PKD-2 complex for lysosomal degradation. In a stam-1 mutant, both LOV-1 and PKD-2 improperly accumulate at the ciliary base. Conversely, overexpression of STAM or Hrs promotes the removal of PKD-2 from cilia, culminating in sensory behavioral defects. These data reveal that the STAM-Hrs complex, which down-regulates ligand-activated growth factor receptors from the cell surface of yeast and mammalian cells, also regulates the localization and signaling of a ciliary PC1 receptor-TRPP2 complex.
Stochastic simulation GUI for biochemical networks
Authors: Vallabhajosyula Ravishankar Rao , Sauro Herbert M.
Published: June 2007

Motivation: This article describes the development of a useful graphical user interface for stochastic simulation of biochemical networks which allows model builders to run stochastic simulations of their models and perform statistical analysis on the results. These include the construction of correlations, power-spectral densities and transfer functions between selected inputs and outputs.

Availability: The software is licensed under the BSD open source license and is available at http://sourceforge.net/projects/jdesigner. In addition, a more detailed account of the algorithms employed in the tool can be found at the Wiki at http://www.sys-bio.org/sbwWiki.

Contact:  rrao@kgi.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
Visualization-based cancer microarray data classification analysis
Authors: Mramor Minca , Leban Gregor , Demšar Janez , Zupan Blaž
Published: June 2007

Motivation: Methods for analyzing cancer microarray data often face two distinct challenges: the models they infer need to perform well when classifying new tissue samples while at the same time providing an insight into the patterns and gene interactions hidden in the data. State-of-the-art supervised data mining methods often cover well only one of these aspects, motivating the development of methods where predictive models with a solid classification performance would be easily communicated to the domain expert.

Results: Data visualization may provide for an excellent approach to knowledge discovery and analysis of class-labeled data. We have previously developed an approach called VizRank that can score and rank point-based visualizations according to degree of separation of data instances of different class. We here extend VizRank with techniques to uncover outliers, score features (genes) and perform classification, as well as to demonstrate that the proposed approach is well suited for cancer microarray analysis. Using VizRank and radviz visualization on a set of previously published cancer microarray data sets, we were able to find simple, interpretable data projections that include only a small subset of genes yet do clearly differentiate among different cancer types. We also report that our approach to classification through visualization achieves performance that is comparable to state-of-the-art supervised data mining techniques.

Availability: VizRank and radviz are implemented as part of the Orange data mining suite (http://www.ailab.si/orange).

Contact:  blaz.zupan@fri.uni-lj.si

Supplementary information: Supplementary data are available from http://www.ailab.si/supp/bi-cancer.
PowerCore: a program applying the advanced M strategy with a heuristic search for establishing core sets
Authors: Kim Kyu-Won , Chung Hun-Ki , Cho Gyu-Taek , Ma Kyung-Ho , Chandrabalan Dorothy , Gwag Jae-Gyun , Kim Tae-San , Cho Eun-Gi , Park Yong-Jin
Published: June 2007

Motivation: Core sets are necessary to ensure that access to useful alleles or characteristics retained in genebanks is guaranteed. We have successfully developed a computational tool named ‘PowerCore’ that aims to support the development of core sets by reducing the redundancy of useful alleles and thus enhancing their richness.

Results: The program, using a new approach completely different from any other previous methodologies, selects entries of core sets by the advanced M (maximization) strategy implemented through a modified heuristic algorithm. The developed core set has been validated to retain all characteristics for qualitative traits and all classes for quantitative ones. PowerCore effectively selected the accessions with higher diversity representing the entire coverage of variables and gave a 100% reproducible list of entries whenever repeated.

Availability: PowerCore software uses the .NET Framework Version 1.1 environment which is freely available for the MS Windows platform. The files can be downloaded from http://genebank.rda.go.kr/powercore/. The distribution of the package includes executable programs, sample data and a user manual.

Contact:  yjpark@rda.go.kr
MareyMap: an R-based tool with graphical interface for estimating recombination rates
Authors: Rezvoy Clément , Charif Delphine , Guéguen Laurent , Marais Gabriel A.B.
Published: June 2007

Summary: Comparing genetic and physical maps (the so-called Marey map approach) is still the most widely used approach to estimate genome-wide recombination rates. Remarkably, there is no available bioinformatics tool specifically devoted to Marey map approach. Here, we developed such a tool called MareyMap based on GNU R and Tcl/Tk. MareyMap offers a user-friendly graphical interface and includes useful features, such as data cleaning process, sophisticated interpolation methods to estimate local rates, possibility of complex queries, various range of import–export files. Moreover, MareyMap comes with ready-to-use maps for human, Drosophila, Caenorhabditis elegans and Arabidopsis. MareyMap has been made so that it can be easily upgraded with new data and interpolation methods.

Availability:  http://pbil.univ-lyon1.fr/software/mareymap/

Contact:  marais@biomserv.univ-lyon1.fr
Evaporative cooling feature selection for genotypic data involving interactions
Authors: McKinney B.A. , Reif D.M. , White B.C. , Crowe J.E. , Moore J.H.
Published: June 2007

Motivation: The development of genome-wide capabilities for genotyping has led to the practical problem of identifying the minimum subset of genetic variants relevant to the classification of a phenotype. This challenge is especially difficult in the presence of attribute interactions, noise and small sample size.

Methods: Analogous to the physical mechanism of evaporation, we introduce an evaporative cooling (EC) feature selection algorithm that seeks to obtain a subset of attributes with the optimum information temperature (i.e. the least noise). EC uses an attribute quality measure analogous to thermodynamic free energy that combines Relief-F and mutual information to evaporate (i.e. remove) noise features, leaving behind a subset of attributes that contain DNA sequence variations associated with a given phenotype.

Results: EC is able to identify functional sequence variations that involve interactions (epistasis) between other sequence variations that influence their association with the phenotype. This ability is demonstrated on simulated genotypic data with attribute interactions and on real genotypic data from individuals who experienced adverse events following smallpox vaccination. The EC formalism allows us to combine information entropy, energy and temperature into a single information free energy attribute quality measure that balances interaction and main effects.

Availability: Open source software, written in Java, is freely available upon request.

Contact:  brett.mckinney@gmail.com
Constraint-based functional similarity of metabolic genes: going beyond network topology
Authors: Rokhlenko Oleg , Shlomi Tomer , Sharan Roded , Ruppin Eytan , Pinter Ron Y.
Published: June 2007

Motivation: Several recent studies attempted to establish measures for the similarity between genes that are based on the topological properties of metabolic networks. However, these approaches offer only a static description of the properties of interest and offer moderate (albeit significant) correlations with pertinent experimental data.

Results: Using a constraint-based large-scale metabolic model, we present two effectively computable measures of functional gene similarity, one based on the response of the metabolic network to gene knockouts and the other based on the metabolic flux activity across a variety of growth media. We applied these measures to 750 genes comprising the metabolic network of the budding yeast. Comparing the in silico computed functional similarities to Gene Ontology (GO) annotations and gene expression data, we show that our computational method captures functional similarities between metabolic genes that go beyond those obtained by the topological analysis of metabolic networks alone, thus revealing dynamic characteristics of gene function. Interestingly, the measure based on the network response to different growth environments markedly outperforms the measure based on its response to gene knockouts, though both have some added synergistic value in depicting the functional relationships between metabolic genes.

Contact:  olegro@cs.technion.ac.il

Supplementary information: Supplementary data are available at Bioinformatics online.
MAnGO: an interactive R-based tool for two-colour microarray analysis
Authors: Marisa Laetitia , Ichanté Jean-Laurent , Reymond Nancie , Aggerbeck Lawrence , Delacroix Hervé , Mucchielli-Giorgi Marie-Hélène
Published: June 2007

Summary: MAnGO (Microarray Analysis at the Gif/Orsay platform) is an interactive R-based tool for the analysis of two-colour microarray experiments. It is a compilation of various methods, which allows the user (1) to control data quality by detecting biases with a large number of visual representations, (2) to pre-process data (filtering and normalization) and (3) to carry out differential analyses. MAnGO is not only a ‘turn-key’ tool, oriented towards biologists but also a flexible and adaptable R script oriented towards bioinformaticians.

Availability:  http://bioinfome.cgm.cnrs-gif.fr/

Contact:  reymond@cgm.cnrs-gif.fr
Annotation-based distance measures for patient subgroup discovery in clinical microarray studies
Authors: Lottaz Claudio , Toedling Joern , Spang Rainer
Published: June 2007

Motivation: Clustering algorithms are widely used in the analysis of microarray data. In clinical studies, they are often applied to find groups of co-regulated genes. Clustering, however, can also stratify patients by similarity of their gene expression profiles, thereby defining novel disease entities based on molecular characteristics. Several distance-based cluster algorithms have been suggested, but little attention has been given to the distance measure between patients. Even with the Euclidean metric, including and excluding genes from the analysis leads to different distances between the same objects, and consequently different clustering results.

Results: We describe a new clustering algorithm, in which gene selection is used to derive biologically meaningful clusterings of samples by combining expression profiles and functional annotation data. According to gene annotations, candidate gene sets with specific functional characterizations are generated. Each set defines a different distance measure between patients, leading to different clusterings. These clusterings are filtered using a resampling-based significance measure. Significant clusterings are reported together with the underlying gene sets and their functional definition.

Conclusions: Our method reports clusterings defined by biologically focused sets of genes. In annotation-driven clusterings, we have recovered clinically relevant patient subgroups through biologically plausible sets of genes as well as new subgroupings. We conjecture that our method has the potential to reveal so far unknown, clinically relevant classes of patients in an unsupervised manner.

Availability: We provide the R package adSplit as part of Bioconductor release 1.9 and on http://compdiag.molgen.mpg.de/software

Contact:  claudio.lottaz@molgen.mpg.de
Interaction-site prediction for protein complexes: a critical assessment
Authors: Zhou Huan-Xiang , Qin Sanbo
Published: June 2007

Motivation: Proteins function through interactions with other proteins and biomolecules. Protein–protein interfaces hold key information toward molecular understanding of protein function. In the past few years, there have been intensive efforts in developing methods for predicting protein interface residues. A review that presents the current status of interface prediction and an overview of its applications and project future developments is in order.

Summary: Interface prediction methods rely on a wide range of sequence, structural and physical attributes that distinguish interface residues from non-interface surface residues. The input data are manipulated into either a numerical value or a probability representing the potential for a residue to be inside a protein interface. Predictions are now satisfactory for complex-forming proteins that are well represented in the Protein Data Bank, but less so for under-represented ones. Future developments will be directed at tackling problems such as building structural models for multi-component structural complexes.

Contact:  zhou@sb.fsu.edu
Detection of potential enzyme targets by metabolic modelling and optimization: Application to a simple enzymopathy
Authors: Vera Julio , Curto Raul , Cascante Marta , Torres Néstor V.
Published: June 2007

Motivation: A very promising approach in drug discovery involves the integration of available biomedical data through mathematical modelling and data mining. We have developed a method called optimization program for drug discovery (OPDD) that allows new enzyme targets to be identified in enzymopathies through the integration of metabolic models and biomedical data in a mathematical optimization program. The method involves four steps: (i) collection of the necessary information about the metabolic system and disease; (ii) translation of the information into mathematical terms; (iii) computation of the optimization programs prioritizing the solutions that propose the inhibition of a reduced number of enzymes and (iv) application of additional biomedical criteria to select and classify the solutions. Each solution consists of a set of predicted values for metabolites, initial substrates and enzyme activities, which describe a biologically acceptable steady state of the system that shifts the pathologic state towards a healthy state.

Results: The OPDD was used to detect target enzymes in an enzymopathy, the human hyperuricemia. An existing S-system model and bibliographic information about the disease were used. The method detected six single-target enzyme solutions involving dietary modification, one of them coinciding with the conventional clinical treatment using allopurinol. The OPDD detected a large number of possible solutions involving two enzyme targets. All except one contained one of the previously detected six enzyme targets. The purpose of this work was not to obtain solutions for direct clinical implementation but to illustrate how increasing levels of biomedical information can be integrated together with mathematical models in drug discovery.

Contact:  julio.vera@informartik.uni-rostock.de or julio_vera_g@yahoo.es

Supplementary information: Supplementary data are available at Bioinformatics online.
Multivariate correlation estimator for inferring functional relationships from replicated genome-wide data
Authors: Zhu Dongxiao , Li Youjuan , Li Hua
Published: June 2007

Summary: Estimating pairwise correlation from replicated genome-scale (a.k.a. OMICS) data is fundamental to cluster functionally relevant biomolecules to a cellular pathway. The popular Pearson correlation coefficient estimates bivariate correlation by averaging over replicates. It is not completely satisfactory since it introduces strong bias while reducing variance. We propose a new multivariate correlation estimator that models all replicates as independent and identically distributed (i.i.d.) samples from the multivariate normal distribution. We derive the estimator by maximizing the likelihood function. For small sample data, we provide a resampling-based statistical inference procedure, and for moderate to large sample data, we provide an asymptotic statistical inference procedure based on the Likelihood Ratio Test (LRT). We demonstrate advantages of the new multivariate correlation estimator over Pearson bivariate correlation estimator using simulations and real-world data analysis examples.

Availability: The estimator and statistical inference procedures have been implemented in an R package ‘CORREP’ that is available from CRAN [http://cran.r-project.org] and Bioconductor [http://www.bioconductor.org/].

Contact:  doz@stowers-institute.org or dongxiaozhu@yahoo.com

Supplementary information: Supplementary data are available at Bioinformatics online.
ViroBLAST: a stand-alone BLAST web server for flexible queries of multiple databases and user's datasets
Authors: Deng Wenjie , Nickle David C. , Learn Gerald H. , Maust Brandon , Mullins James I.
Published: June 2007

Summary: ViroBLAST is a stand-alone BLAST web interface for nucleotide and amino acid sequence similarity searches. It extends the utility of BLAST to query against multiple sequence databases and user sequence datasets, and provides a friendly output to easily parse and navigate BLAST results. ViroBLAST is readily useful for all research areas that require BLAST functions and is available online and as a downloadable archive for independent installation.

Availability:  http://indra.mullins.microbiol.washington.edu/blast/viroblast.php

Contact:  jmullins@u.washington.edu
The Publishing of John Tillotson's Collected Works, 1695–1757
Authors: Dixon Rosemary
Published: June 2007

This article investigates the publishing history of John Tillotson’s collected sermons in the early and mid-eighteenth century. Evidence from imprints and other printed and manuscript sources is used to establish how much the Tillotson copyright was worth, who owned it, and what kinds of editions of the sermons were produced. Publishing Tillotson’s works was a significant and profitable part of the business of many leading London booksellers. The publishing history of the sermons thus sheds light on important features of the trade in this period, such as the activities of wholesaling and copyright-owning congers, the booksellers’ sales of copyright, and the relationship between the London and Scottish trades. Detailed consideration of the editions produced by Brabazon Aylmer and Richard Chiswell also reveals the impact individual booksellers could have on the books they published.
Long‐term Outcome of the Hong Kong Vascularized, Pedicled Temporalis Fascia Flap in Reconstruction of Mastoid Cavity
Authors: Hung Terry , Leung Natalie , van Hasselt C Andrew , Liu Kwok Chung , Tong Michael
Published: June 2007

Objectives: The vascularized, pedicled temporalis fascia flap (Hong Kong flap) is an established procedure in the reconstruction of the mastoid cavity. The long‐term outcome and complications have not been studied. We set out to appraise this procedure in our study.

Study Design: The clinical records of 302 ears that had the Hong Kong flap procedure from 1987 to 2006 were retrospectively studied. The study reviewed the otologic complaints leading to Hong Kong flap, the number and findings of the second or more looks, analysis of procedures year by year, time to achieve a dry ear, and the complications.

Results: The main otologic complaint leading to use of the Hong Kong flap is otorrhoea. The number of Hong Kong flap procedures has decreased in recent years. Twenty‐one percent had second or more looks after the procedure. Forty percent of the mastoid cavities at the second look were found to have residual or recurrent cholesteatoma. It takes a median of 2 months to achieve a dry ear after the procedure.

Conclusions: We conclude that the Hong Kong flap procedure is simple and desirable for mastoid reconstruction to achieve a safe and dry cavity with few complications.
A host-race of the cuckooCuculus canoruswith nestlings attuned to the parental alarm calls of the host species
Authors: Davies N.B , Madden J.R , Butchart S.H.M , Rutila J
Published: June 2007

The common cuckoo has several host-specific races, each with a distinctive egg that tends to match its host's eggs. Here, we show that the host-race specializing on reed warblers also has a host-specific nestling adaptation. In playback experiments, the nestling cuckoos responded specifically to the reed warbler's distinctive ‘churr’ alarm (given when a predator is near the nest), by reducing begging calls (likely to betray their location) and by displaying their orange-red gape (a preparation for defence). When reed warbler-cuckoos were cross-fostered and raised by two other regular cuckoo hosts (robins or dunnocks), they did not respond to the different alarms of these new foster-parents. Instead, they retained a specific response to reed warbler alarms but, remarkably, increased both calling and gaping. This suggests innate pre-tuning to reed warbler alarms, but with exposure necessary for development of the normal silent gaping response. By contrast, cuckoo chicks of another host-race specializing on redstarts showed no response to either redstart or reed warbler alarms. If host-races are restricted to female cuckoo lineages, then chick-tuning in reed warbler-cuckoos must be under maternal control. Alternatively, some host-races might be cryptic species, not revealed by the neutral genetic markers studied so far.
Mating system and brain size in bats
Authors: Pitnick Scott , Jones Kate E , Wilkinson Gerald S
Published: June 2007

The contribution of sexual selection to brain evolution has been little investigated. Through comparative analyses of bats, we show that multiple mating by males, in the absence of multiple mating by females, has no evolutionary impact on relative brain dimension. In contrast, bat species with promiscuous females have relatively smaller brains than do species with females exhibiting mate fidelity. This pattern may be a consequence of the demonstrated negative evolutionary relationship between investment in testes and investment in brains, both metabolically expensive tissues. These results have implications for understanding the correlated evolution of brains, behaviour and extravagant sexually selected traits.
Propulsive jets and their acoustics
Authors: Secundov Alexander N , Birch Stanley F , Tucker Paul G
Published: June 2007

The complex flow physics challenges and asks questions regarding these challenges a wide range of jet flows found in aerospace engineering. Hence, the daunting task facing Reynolds-averaged Navier–Stokes (RANS) technology, for which the time average of the turbulent flow field is solved, is set out. Despite the clear potential of large eddy simulation (LES)-related methods and hybrid forms involving some RANS modelling, numerous current deficiencies, mostly related to the limitations of computational resources, are identified. It is concluded that currently, these limitations make LES and hybrids most useful for understanding flow physics and refining RANS technology. The use of LES in conjunction with a ray-tracing model to elucidate the physics of acoustic wave transmission in jets and thus improved RANS technology is described. It is argued that, as a stopgap measure, pure RANS simulations can be a valuable part of the design process and can now predict acoustics spectra and directivity diagrams with useful accuracy. Ultimately, hybrid RANS–LES-type methods, and then pure LES, will dominate, but the time-scales for this transition suggests that improvements to RANS technology should not be ignored.
Unstructured mesh methods for the solution of the unsteady compressible flow equations with moving boundary components
Authors: Hassan Oubay , Morgan Kenneth , Weatherill Nigel
Published: June 2007

A review of a procedure for the simulation of time-dependent, inviscid and turbulent viscous, compressible flows involving geometries that change in time is presented. The adopted discretization technique employs unstructured meshes and both explicit and implicit time-stepping schemes. A dual time-stepping procedure and an ALE formulation enable flows involving moving boundary components to be included. Techniques that have been developed to maintain the validity of the unstructured mesh and to allow for the capture of moving flow features are also reviewed. Using the in-house developed techniques, some examples are included to demonstrate the use of the approach for the simulation of a number of flows of practical industrial interest.
The heart-forming fields: one or multiple?
Authors: Moorman Antoon F.M , Christoffels Vincent M , Anderson Robert H , van den Hoff Maurice J.B
Published: June 2007

The recent identification of a second mesodermal region as a source of cardiomyocytes has challenged the views on the formation of the heart. This second source of cardiomyocytes is localized centrally on the embryonic disc relative to the remainder of the classic cardiac crescent, a region also called the pharyngeal mesoderm. In this review, we discuss the concept of the primary and secondary cardiogenic fields in the context of folding of the embryo, and the subsequent temporal events involved in formation of the heart. We suggest that, during evolution, the heart developed initially only with the components required for a systemic circulation, namely a sinus venosus, a common atrium, a ‘left’ ventricle and an arterial cone, the latter being the myocardial outflow tract as seen in the heart of primitive fishes. These components developed in their entirety from the classic cardiac crescent. Only later in the course of evolution did the appearance of novel signalling pathways permit the central part of the cardiac crescent, and possibly the contiguous pharyngeal mesoderm, to develop into the cardiac components required for the pulmonary circulation. These latter components comprise the right ventricle, and that part of the left atrium that derives from the mediastinal myocardium, namely the dorsal atrial wall and the atrial septum. It is these elements which are now recognized as developing from the second field of pharyngeal mesoderm. We suggest that, rather than representing development from separate fields, the cardiac components required for both the systemic and pulmonary circulations are derived by patterning from a single cardiac field, albeit with temporal delay in the process of formation.
Designed triple-helical peptides as tools for collagen biochemistry and matrix engineering
Authors: Koide Takaki
Published: June 2007

Collagens, characterized by a unique triple-helical structure, are the predominant component of extracellular matrices (ECMs) existing in all multicellular animals. Collagens not only maintain structural integrity of tissues and organs, but also regulate a number of biological events, including cell attachment, migration and differentiation, tissue regeneration and animal development. The specific functions of collagens are generally triggered by specific interactions of collagen-binding molecules (membrane receptors, soluble factors and other ECM components) with certain structures displayed on the collagen triple helices. Thus, synthetic triple-helical peptides that mimic the structure of native collagens have been used to investigate the individual collagen–protein interactions, as well as collagen structure and stability. The first part of this article illustrates the design of various collagen-mimetic peptides and their recent applications in matrix biology. Collagen is also acknowledged as one of the most promising biomaterials in regenerative medicine and tissue engineering. However, the use of animal-derived collagens in human could put the recipients at risks of pathogen transmission or allergic reactions. Hence, the production of safe artificial collagen surrogates is currently of considerable interest. The latter part of this article reviews recent attempts to develop artificial collagens as novel biomaterials.
Fluid–structure interaction models of the mitral valve: function in normal and pathological states
Authors: Kunzelman K.S , Einstein D.R , Cochran R.P
Published: June 2007

Successful mitral valve repair is dependent upon a full understanding of normal and abnormal mitral valve anatomy and function. Computational analysis is one such method that can be applied to simulate mitral valve function in order to analyse the roles of individual components and evaluate proposed surgical repair. We developed the first three-dimensional finite element computer model of the mitral valve including leaflets and chordae tendineae; however, one critical aspect that has been missing until the last few years was the evaluation of fluid flow, as coupled to the function of the mitral valve structure. We present here our latest results for normal function and specific pathological changes using a fluid–structure interaction model. Normal valve function was first assessed, followed by pathological material changes in collagen fibre volume fraction, fibre stiffness, fibre splay and isotropic stiffness. Leaflet and chordal stress and strain and papillary muscle force were determined. In addition, transmitral flow, time to leaflet closure and heart valve sound were assessed. Model predictions in the normal state agreed well with a wide range of available
in vivo
and
in vitro
data. Further, pathological material changes that preserved the anisotropy of the valve leaflets were found to preserve valve function. By contrast, material changes that altered the anisotropy of the valve were found to profoundly alter valve function. The addition of blood flow and an experimentally driven microstructural description of mitral tissue represent significant advances in computational studies of the mitral valve, which allow further insight to be gained. This work is another building block in the foundation of a computational framework to aid in the refinement and development of a truly non-invasive diagnostic evaluation of the mitral valve. Ultimately, it represents the basis for simulation of surgical repair of pathological valves in a clinical and educational setting.
Electron Microscopic Radioautographic Study on Protein Synthesis in Mitochondria of Binucleate Hepatocytes of Aging Mice
Authors: Nagata Tetsuji
Published: June 2007

In order to study the aging changes of intramitochondrial protein synthesis in mouse hepatocytes, 10 groups of aging mice, each consisting of three individuals, total 30, from fetal day 19 to postnatal year 2, were injected with3H-leucine, a protein precursor, sacrificed 1 h later, and the liver tissues processed for electron microscopic radioautography. On electron microscopic radioautograms obtained from each animal, the numbers of mitochondria, the numbers of labeled mitochondria, and the mitochondrial labeling index labeled with3H-leucine that showed protein synthesis in each hepatocyte, both mononucleate and binucleate cells, were counted and the averages in respective aging groups were compared. From the results, it was demonstrated that the numbers of mitochondria, the numbers of labeled mitochondria, and the labeling indices of intramitochondrial protein syntheses in both mononucleate and binucleate hepatocytes of mice at various ages increased due to development of animals. The numbers of mitochondria, the numbers of labeled mitochondria, and the labeling indices of intramitochondrial protein synthesis in binucleate hepatocytes were more than those of mononucleate hepatocytes at the same aging stages.
Subjective Outcome Evaluation of the Project P.A.T.H.S.: Qualitative Findings Based on the Experiences of Program Implementers
Authors: Shek Daniel T. L. , Sun Rachael C. F.
Published: June 2007

A total of 52 schools participated in the experimental implementation phase of the project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes). After completion of the Tier 1 Program (Secondary 1 level), 344 teachers and social workers responded to the Subjective Outcome Evaluation Form (Form B), assessing their views of the program and their own performance. Qualitative data analyses based on the schools' evaluation reports showed that the program implementers had enhanced knowledge and skills, learned to establish instructor-student relationships and cooperate with colleagues, and fostered self-development. The workers also appreciated the program philosophy and values, program design and resources, process of implementation, interaction between instructors and students, and program effectiveness. The findings also revealed that the workers encountered difficulties in the program implementation and they also made suggestions on how the program design, program arrangement, manpower deployment, and support for the program implementation could be improved.
Medicago LYK3, an Entry Receptor in Rhizobial Nodulation Factor Signaling
Authors: Smit Patrick , Limpens Erik , Geurts Rene , Fedorova Elena , Dolgikh Elena , Gough Clare , Bisseling Ton
Published: June 2007

Rhizobia secrete nodulation (Nod) factors, which set in motion the formation of nitrogen-fixing root nodules on legume host plants. Nod factors induce several cellular responses in root hair cells within minutes, but also are essential for the formation of infection threads by which rhizobia enter the root. Based on studies using bacterial mutants, a two-receptor model was proposed, a signaling receptor that induces early responses with low requirements toward Nod factor structure and an entry receptor that controls infection with more stringent demands. Recently, putative Nod factor receptors were shown to be LysM domain receptor kinases. However, mutants in these receptors, in both Lotus japonicus (nfr1 and nfr5) and Medicago truncatula (Medicago; nfp), do not support the two-receptor model because they lack all Nod factor-induced responses. LYK3, the putative Medicago ortholog of NFR1, has only been studied by RNA interference, showing a role in infection thread formation. Medicago hair curling (hcl) mutants are unable to form curled root hairs, a step preceding infection thread formation. We identified the weak hcl-4 allele that is blocked during infection thread growth. We show that HCL encodes LYK3 and, thus, that this receptor, besides infection, also controls root hair curling. By using rhizobial mutants, we also show that HCL controls infection thread formation in a Nod factor structure-dependent manner. Therefore, LYK3 functions as the proposed entry receptor, specifically controlling infection. Finally, we show that LYK3, which regulates a subset of Nod factor-induced genes, is not required for the induction of NODULE INCEPTION.
Characterization of SSIIIa-Deficient Mutants of Rice: The Function of SSIIIa and Pleiotropic Effects by SSIIIa Deficiency in the Rice Endosperm
Authors: Fujita Naoko , Yoshida Mayumi , Kondo Tomonori , Saito Kaori , Utsumi Yoshinori , Tokunaga Takashi , Nishi Aiko , Satoh Hikaru , Park Jin-Hee , Jane Jay-Lin , Miyao Akio , Hirochika Hirohiko , Nakamura Yasunori
Published: June 2007

Starch synthase IIIa (SSIIIa)-deficient rice (Oryza sativa) mutants were generated using retrotransposon insertion and chemical mutagenesis. The lowest migrating SS activity bands on glycogen-containing native polyacrylamide gel, which were identified to be those for SSIIIa, were completely absent in these mutants, indicating that they are SSIIIa null mutants. The amylopectin B2 to B4 chains with degree of polymerization (DP) ≥ 30 and the M  r of amylopectin in the mutant were reduced to about 60% and 70% of the wild-type values, respectively, suggesting that SSIIIa plays an important part in the elongation of amylopectin B2 to B4 chains. Chains with DP 6 to 9 and DP 16 to 19 decreased while chains with DP 10 to 15 and DP 20 to 25 increased in the mutants amylopectin. These changes in the SSIIIa mutants are almost opposite images of those of SSI-deficient rice mutant and were caused by 1.3- to 1.7-fold increase of the amount of SSI in the mutants endosperm. Furthermore, the amylose content and the extralong chains (DP ≥ 500) of amylopectin were increased by 1.3- and 12-fold, respectively. These changes in the composition in the mutants starch were caused by 1.4- to 1.7-fold increase in amounts of granules-bound starch synthase (GBSSI). The starch granules of the mutants were smaller with round shape, and were less crystalline. Thus, deficiency in SSIIIa, the second major SS isozyme in developing rice endosperm affected the structure of amylopectin, amylase content, and physicochemical properties of starch granules in two ways: directly by the SSIIIa deficiency itself and indirectly by the enhancement of both SSI and GBSSI gene transcripts.
Transcriptionally Active Heterochromatin in Rye B Chromosomes
Authors: Carchilan Mariana , Delgado Margarida , Ribeiro Teresa , Costa-Nunes Pedro , Caperta Ana , Morais-Cecílio Leonor , Jones R. Neil , Viegas Wanda , Houben Andreas
Published: June 2007

B chromosomes (Bs) are dispensable components of the genomes of numerous species. Thus far, there is a lack of evidence for any transcripts of Bs in plants, with the exception of some rDNA sequences. Here, we show that the Giemsa banding-positive heterochromatic subterminal domain of rye (Secale cereale) Bs undergoes decondensation during interphase. Contrary to the heterochromatic regions of A chromosomes, this domain is simultaneously marked by trimethylated H3K4 and by trimethylated H3K27, an unusual combination of apparently conflicting histone modifications. Notably, both types of B-specific high copy repeat families (E3900 and D1100) of the subterminal domain are transcriptionally active, although with different tissue type–dependent activity. No small RNAs were detected specifically for the presence of Bs. The lack of any significant open reading frame and the highly heterogeneous size of mainly polyadenylated transcripts indicate that the noncoding RNA may function as structural or catalytic RNA.
Suppression of Antiviral Silencing by Cucumber Mosaic Virus 2b Protein in Arabidopsis Is Associated with Drastically Reduced Accumulation of Three Classes of Viral Small Interfering RNAs
Authors: Diaz-Pendon Juan A. , Li Feng , Li Wan-Xiang , Ding Shou-Wei
Published: June 2007

We investigated the genetic pathway in Arabidopsis thaliana targeted during infection by cucumber mosaic virus (CMV) 2b protein, known to suppress non-cell-autonomous transgene silencing and salicylic acid (SA)–mediated virus resistance. We show that 2b expressed from the CMV genome drastically reduced the accumulation of 21-, 22-, and 24-nucleotide classes of viral small interfering RNAs (siRNAs) produced by Dicer-like4 (DCL4), DCL2, and DCL3, respectively. The defect of a CMV 2b–deletion mutant (CMV-Δ2b) in plant infection was efficiently rescued in Arabidopsis mutants producing neither 21- nor 22-nucleotide viral siRNAs. Since genetic analysis further identifies a unique antiviral role for DCL3 upstream of DCL4, our data indicate that inhibition of the accumulation of distinct viral siRNAs plays a key role in 2b suppression of antiviral silencing. Strikingly, disease symptoms caused by CMV-Δ2b in Arabidopsis mutants defective in antiviral silencing were as severe as those caused by CMV, demonstrating an indirect role for the silencing suppressor activity in virus virulence. We found that production of CMV siRNAs without 2b interference depended largely on RNA-dependent RNA polymerase 1 (RDR1) inducible by SA. Given the known role of RDR6-dependent transgene siRNAs in non-cell-autonomous silencing, our results suggest a model in which 2b inhibits the production of RDR1-dependent viral siRNAs that confer SA-dependent virus resistance by directing non-cell-autonomous antiviral silencing.
ACTIN BINDING PROTEIN29 fromLiliumPollen Plays an Important Role in Dynamic Actin Remodeling
Authors: Xiang Yun , Huang Xi , Wang Ting , Zhang Yan , Liu Qinwen , Hussey Patrick J. , Ren Haiyun
Published: June 2007

Villin/gelsolin/fragmin superfamily proteins have been shown to function in tip-growing plant cells. However, genes encoding gelsolin/fragmin do not exist in the Arabidopsis thaliana and rice (Oryza sativa) databases, and it is possible that these proteins are encoded by villin mRNA splicing variants. We cloned a 1006-bp full-length cDNA from Lilium longiflorum that encodes a 263–amino acid predicted protein sharing 100% identity with the N terminus of 135-ABP (Lilium villin) except for six C-terminal amino acids. The deduced 29-kD protein, Lilium ACTIN BINDING PROTEIN29 (ABP29), contains only the G1 and G2 domains and is the smallest identified member of the villin/gelsolin/fragmin superfamily. The purified recombinant ABP29 accelerates actin nucleation, blocks barbed ends, and severs actin filaments in a Ca2+- and/or phosphatidylinositol 4,5-bisphosphate–regulated manner in vitro. Microinjection of the protein into stamen hair cells disrupted transvacuolar strands whose backbone is mainly actin filament bundles. Transient expression of ABP29 by microprojectile bombardment of lily pollen resulted in actin filament fragmentation and inhibited pollen germination and tube growth. Our results suggest that ABP29 is a splicing variant of Lilium villin and a member of the villin/gelsolin/fragmin superfamily, which plays important roles in rearrangement of the actin cytoskeleton during pollen germination and tube growth.
In Vivo Visualization of Mg-ProtoporphyrinIX, a Coordinator of Photosynthetic Gene Expression in the Nucleus and the Chloroplast
Authors: Ankele Elisabeth , Kindgren Peter , Pesquet Edouard , Strand Åsa
Published: June 2007

The photosynthetic apparatus is composed of proteins encoded by genes from both the nucleus and the chloroplast. To ensure that the photosynthetic complexes are assembled stoichiometrically and to enable their rapid reorganization in response to a changing environment, the plastids emit signals that regulate nuclear gene expression to match the status of the plastids. One of the plastid signals, the chlorophyll intermediate Mg-ProtoporphyrinIX (Mg-ProtoIX) accumulates under stress conditions and acts as a negative regulator of photosynthetic gene expression. By taking advantage of the photoreactive property of tetrapyrroles, Mg-ProtoIX could be visualized in the cells using confocal laser scanning spectroscopy. Our results demonstrate that Mg-ProtoIX accumulated both in the chloroplast and in the cytosol during stress conditions. Thus, the signaling metabolite is exported from the chloroplast, transmitting the plastid signal to the cytosol. Our results from the Mg-ProtoIX over- and underaccumulating mutants copper response defect and genome uncoupled5, respectively, demonstrate that the expression of both nuclear- and plastid-encoded photosynthesis genes is regulated by the accumulation of Mg-ProtoIX. Thus, stress-induced accumulation of the signaling metabolite Mg-ProtoIX coordinates nuclear and plastidic photosynthetic gene expression.
Inactivation of Thioredoxin Reductases Reveals a Complex Interplay between Thioredoxin and Glutathione Pathways in Arabidopsis Development
Authors: Reichheld Jean-Philippe , Khafif Mehdi , Riondet Christophe , Droux Michel , Bonnard Géraldine , Meyer Yves
Published: June 2007

NADPH-dependent thioredoxin reductases (NTRs) are key regulatory enzymes determining the redox state of the thioredoxin system. The Arabidopsis thaliana genome has two genes coding for NTRs (NTRA and NTRB), both of which encode mitochondrial and cytosolic isoforms. Surprisingly, plants of the ntra ntrb knockout mutant are viable and fertile, although with a wrinkled seed phenotype, slower plant growth, and pollen with reduced fitness. Thus, in contrast with mammals, our data demonstrate that neither cytosolic nor mitochondrial NTRs are essential in plants. Nevertheless, in the double mutant, the cytosolic thioredoxin h3 is only partially oxidized, suggesting an alternative mechanism for thioredoxin reduction. Plant growth in ntra ntrb plants is hypersensitive to buthionine sulfoximine (BSO), a specific inhibitor of glutathione biosynthesis, and thioredoxin h3 is totally oxidized under this treatment. Interestingly, this BSO-mediated growth arrest is fully reversible, suggesting that BSO induces a growth arrest signal but not a toxic accumulation of activated oxygen species. Moreover, crossing ntra ntrb with rootmeristemless1, a mutant blocked in root growth due to strongly reduced glutathione synthesis, led to complete inhibition of both shoot and root growth, indicating that either the NTR or the glutathione pathway is required for postembryonic activity in the apical meristem.