bluuebunny/crossref_metadata_2025 huggingface dataset:
Aminoacyl tRNA synthetases and their connections to disease
Authors: Park Sang Gyu , Schimmel Paul , Kim Sunghoon
Published: August 2008

Aminoacylation of transfer RNAs establishes the rules of the genetic code. The reactions are catalyzed by an ancient group of 20 enzymes (one for each amino acid) known as aminoacyl tRNA synthetases (AARSs). Surprisingly, the etiology of specific diseases—including cancer, neuronal pathologies, autoimmune disorders, and disrupted metabolic conditions—is connected to specific aminoacyl tRNA synthetases. These connections include heritable mutations in the genes for tRNA synthetases that are causally linked to disease, with both dominant and recessive disease-causing mutations being annotated. Because some disease-causing mutations do not affect aminoacylation activity or apparent enzyme stability, the mutations are believed to affect functions that are distinct from aminoacylation. Examples include enzymes that are secreted as procytokines that, after activation, operate in pathways connected to the immune system or angiogenesis. In addition, within cells, synthetases form multiprotein complexes with each other or with other regulatory factors and in that way control diverse signaling pathways. Although much has been uncovered in recent years, many novel functions, disease connections, and interpathway connections of tRNA synthetases have yet to be worked out.
Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin
Authors: Brines Michael , Patel Nimesh S. A. , Villa Pia , Brines Courtenay , Mennini Tiziana , De Paola Massimiliano , Erbayraktar Zubeyde , Erbayraktar Serhat , Sepodes Bruno , Thiemermann Christoph , Ghezzi Pietro , Yamin Michael , Hand Carla C. , Xie Qiao-wen , Coleman Thomas , Cerami Anthony
Published: August 2008

Erythropoietin (EPO), a member of the type 1 cytokine superfamily, plays a critical hormonal role regulating erythrocyte production as well as a paracrine/autocrine role in which locally produced EPO protects a wide variety of tissues from diverse injuries. Significantly, these functions are mediated by distinct receptors: hematopoiesis via the EPO receptor homodimer and tissue protection via a heterocomplex composed of the EPO receptor and CD131, the β common receptor. In the present work, we have delimited tissue-protective domains within EPO to short peptide sequences. We demonstrate that helix B (amino acid residues 58–82) of EPO, which faces the aqueous medium when EPO is bound to the receptor homodimer, is both neuroprotective
in vitro
and tissue protective
in vivo
in a variety of models, including ischemic stroke, diabetes-induced retinal edema, and peripheral nerve trauma. Remarkably, an 11-aa peptide composed of adjacent amino acids forming the aqueous face of helix B is also tissue protective, as confirmed by its therapeutic benefit in models of ischemic stroke and renal ischemia–reperfusion. Further, this peptide simulating the aqueous surface of helix B also exhibits EPO's trophic effects by accelerating wound healing and augmenting cognitive function in rodents. As anticipated, neither helix B nor the 11-aa peptide is erythropoietic
in vitro
or
in vivo
. Thus, the tissue-protective activities of EPO are mimicked by small, nonerythropoietic peptides that simulate a portion of EPO's three-dimensional structure.
Perceiving one's nation: Entitativity, agency and security in the international arena
Authors: Sacchi Simona , Castano Emanuele , Brauer Markus
Published: August 2008

The perception of groups as real entities rather than mere aggregates of individuals has important consequences on intergroup relations. Social psychological research, in fact, shows that it affects stereotyping, identification process, and intergroup bias. Previous research has also shown that group entitativity is not a positive or negative group attribute per se; rather, it depends on the context and the relationship between the perceiver and the group. While enhancing entitativity leads to worse expectations about the out‐group actions, high entitativity is a valued characteristic when associated with an ally or with the in‐group. Indeed, enhancing in‐group entitativity leads to stronger in‐group identification. The specific reasons for why this is the case, however, remain to be ascertained. What is good about in‐group entitativity? In the present contribution we propose that in‐group entitativity may lead to perceive the group as a real entity provided with intentions and capacity for planned actions, notably ensuring the safety of its members by protecting them against external threats. We report two correlational studies conducted with American citizens (Study 1) and Italian citizens (Study 2), showing that in‐group entitativity is associated with a higher level of identification, attribution of intentionality, and perceived security provided by the in‐group. These findings were replicated in a third study—conducted with a role‐play method on a fictitious scenario—in which entitativity was manipulated rather than measured. Study 3 also shows that artificially increasing the perception of in‐group entitativity enhances perceived safety in an international context and reduces the perception of threat from an out‐group. Findings are discussed in terms of possible implications for intergroup and international relations.
Outbreak of Invasive Methicillin-ResistantStaphylococcus aureusInfection Associated With Acupuncture and Joint Injection
Authors: Murray R. J. , Pearson J. C. , Coombs G. W. , Flexman J. P. , Golledge C. L. , Speers D. J. , Dyer J. R. , McLellan D. G. , Reilly M. , Bell J. M. , Bowen S. F. , Christiansen K. J.
Published: August 2008

Objective.

To describe an outbreak of invasive methicillin-resistantStaphylococcus aureus(MRSA) infection after percutaneous needle procedures (acupuncture and joint injection) performed by a single medical practitioner.

Setting.

A medical practitioner's office and 4 hospitals in Perth, Western Australia.

Patients.

Eight individuals who developed invasive MRSA infection after acupuncture or joint injection performed by the medical practitioner.

Methods.

We performed a prospective and retrospective outbreak investigation, including MRSA colonization surveillance, environmental sampling for MRSA, and detailed molecular typing of MRSA isolates. We performed an infection control auditofthe medical practitioner's premises and practices and administered MRSA decolonization therapy to the medical practitioner.

Results.

Eight cases of invasive MRSA infection were identified. Seven cases occurred as a cluster in May 2004; another case (identified retrospectively) occurred approximately 15 months earlier in February 2003. The primary sites of infection were the neck, shoulder, lower back, and hip: 5 patients had septic arthritis and bursitis, and 3 had pyomyositis; 3 patients had bacteremia, including 1 patient with possible endocarditis. The medical practitioner was found to be colonized with the same MRSA clone [ST22-MRSA-IV (EMRSA-15)] at 2 time points: shortly after the first case of infection in March 2003 and again in May 2004. After the medical practitioner's premises and practices were audited and he himself received MRSA decolonization therapy, no further cases were identified.

Conclusions.

This outbreak most likely resulted from a breakdown in sterile technique during percutaneous needle procedures, resulting in the transmission of MRSA from the medical practitioner to the patients. This report demonstrates the importance of surveillance and molecular typing in the identification and control of outbreaks of MRSA infection.
N-PARAMETRIC CANONICAL PERTURBATION METHOD BASED ON LIE TRANSFORMS
Authors: Andrade M.
Published: August 2008

In the dynamical analysis of multiple stellar systems, one usually has to deal with problems involving several perturbations: more than two bodies, mass loss, nonspherical shape, rotation, and such. In order to take into account all of them, we have derived a multiparametric theory based on Lie transforms. It allows us to solve perturbation problems involving an arbitrary number of small parameters in the Hamiltonian formulation. Based on the Lie transforms theory, a complete generalization of the Hori–Deprit method is obtained for N parameters—with N arbitrary—and general expressions are explicitly provided. This method is used to solve the classical Gyldén–Meščerskij problem—the relative motion of a binary system the components of which are losing mass over time—when the primary's oblateness, as well as relativistic effects, is taken into account. Besides this, speed and accuracy comparisons between this analytical method and a numerical one are accomplished.
Radial electric field measurement in a tokamak with magnetic field ripple
Authors: Trier E. , Eriksson L.-G. , Hennequin P. , Fenzi C. , Bourdelle C. , Falchetto G. , Garbet X. , Aniel T. , Clairet F. , Sabot R.
Published: August 2008

In the regions of the Tore Supra tokamak with significant ripple it is expected that a radial electric field (E

r
) ensures the ambipolarity of fluxes of thermal particles trapped in ripple wells. A neoclassical calculation (Connor and Hastie 1973 Nucl. Fusion
13 221, Stringer 1972 Nucl. Fusion
12 689) shows that E

r
is related to ion temperature and density gradients. The validity of this relation is investigated in a series of Tore Supra L-mode discharges without external momentum input. Doppler reflectometry measurements of fluctuations perpendicular velocity, which is dominated by the E

r
× B drift, are found to be in good agreement with the predicted neoclassical E

r
.
Optimizing amino acid groupings for GPCR classification
Authors: Davies Matthew N. , Secker Andrew , Freitas Alex A. , Clark Edward , Timmis Jon , Flower Darren R.
Published: August 2008

Motivation: There is much interest in reducing the complexity inherent in the representation of the 20 standard amino acids within bioinformatics algorithms by developing a so-called reduced alphabet. Although there is no universally applicable residue grouping, there are numerous physiochemical criteria upon which one can base groupings. Local descriptors are a form of alignment-free analysis, the efficiency of which is dependent upon the correct selection of amino acid groupings.

Results: Within the context of G-protein coupled receptor (GPCR) classification, an optimization algorithm was developed, which was able to identify the most efficient grouping when used to generate local descriptors. The algorithm was inspired by the relatively new computational intelligence paradigm of artificial immune systems. A number of amino acid groupings produced by this algorithm were evaluated with respect to their ability to generate local descriptors capable of providing an accurate classification algorithm for GPCRs.

Contact:  m.davies@mail.cryst.bbk.ac.uk
Large-scale computation of elementary flux modes with bit pattern trees
Authors: Terzer Marco , Stelling Jörg
Published: August 2008

Motivation: Elementary flux modes (EFMs)—non-decomposable minimal pathways—are commonly accepted tools for metabolic network analysis under steady state conditions. Valid states of the network are linear superpositions of elementary modes shaping a polyhedral cone (the flux cone), which is a well-studied convex set in computational geometry. Computing EFMs is thus basically equivalent to extreme ray enumeration of polyhedral cones. This is a combinatorial problem with poorly scaling algorithms, preventing the large-scale analysis of metabolic networks so far.

Results: Here, we introduce new algorithmic concepts that enable large-scale computation of EFMs. Distinguishing extreme rays from normal (composite) vectors is one critical aspect of the algorithm. We present a new recursive enumeration strategy with bit pattern trees for adjacent rays—the ancestors of extreme rays—that is roughly one order of magnitude faster than previous methods. Additionally, we introduce a rank updating method that is particularly well suited for parallel computation and a residue arithmetic method for matrix rank computations, which circumvents potential numerical instability problems. Multi-core architectures of modern CPUs can be exploited for further performance improvements. The methods are applied to a central metabolism network of Escherichia coli, resulting in ≈26 Mio. EFMs. Within the top 2% modes considering biomass production, most of the gain in flux variability is achieved. In addition, we compute ≈5 Mio. EFMs for the production of non-essential amino acids for a genome-scale metabolic network of Helicobacter pylori. Only large-scale EFM analysis reveals the >85% of modes that generate several amino acids simultaneously.

Availability: An implementation in Java, with integration into MATLAB and support of various input formats, including SBML, is available at http://www.csb.ethz.ch in the tools section; sources are available from the authors upon request.

Contact:  joerg.stelling@inf.ethz.ch

Supplementary information:  Supplementary data are available at Bioinformatics online.
Predicting pathway membership via domain signatures
Authors: Fröhlich Holger , Fellmann Mark , Sültmann Holger , Poustka Annemarie , Beißbarth Tim
Published: August 2008

Motivation: Functional characterization of genes is of great importance for the understanding of complex cellular processes. Valuable information for this purpose can be obtained from pathway databases, like KEGG. However, only a small fraction of genes is annotated with pathway information up to now. In contrast, information on contained protein domains can be obtained for a significantly higher number of genes, e.g. from the InterPro database.

Results: We present a classification model, which for a specific gene of interest can predict the mapping to a KEGG pathway, based on its domain signature. The classifier makes explicit use of the hierarchical organization of pathways in the KEGG database. Furthermore, we take into account that a specific gene can be mapped to different pathways at the same time. The classification method produces a scoring of all possible mapping positions of the gene in the KEGG hierarchy. Evaluations of our model, which is a combination of a SVM and ranking perceptron approach, show a high prediction performance. Moreover, for signaling pathways we reveal that it is even possible to forecast accurately the membership to individual pathway components.

Availability: The R package gene2pathway is a supplement to this article.

Contact:  h.froehlich@dkfz-heidelberg.de

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Genome-scale classification of metabolic reactions and assignment of EC numbers with self-organizing maps
Authors: Latino Diogo A. R. S. , Zhang Qing-You , Aires-de-Sousa João
Published: August 2008

Motivation: The automatic perception of chemical similarities between metabolic reactions is required for a variety of applications ranging from the computer-aided validation of classification systems, to genome-scale reconstruction (or comparison) of metabolic pathways, to the classification of enzymatic mechanisms. Comparison of metabolic reactions has been mostly based on Enzyme Commission (EC) numbers, which are extremely useful and widespread, but not always straightforward to apply, and often problematic when an enzyme catalyzes several reactions, when the same reaction is catalyzed by different enzymes, when official full EC numbers are unavailable or when reactions are not catalyzed by enzymes. Different methods should be available to compare metabolic reactions. Simultaneously, methods are required for the automatic assignment of EC numbers to reactions still not officially classified.

Results: We have proposed the MOLMAP reaction descriptors to numerically encode the structural transformations resulting from a chemical reaction. Here, such descriptors are applied to the mapping of a genome-scale database of almost 4000 metabolic reactions by Kohonen self-organizing maps (SOMs), and its screening for inconsistencies in EC numbers. This approach allowed for the SOMs to assign EC numbers at the class, subclass and sub-subclass levels for reactions of independent test sets with accuracies up to 92, 80 and 70%, respectively. Different levels of similarity between training and test sets were explored. The approach also led to the identification of a number of similar reactions bearing differences at the EC class level.

Availability: The programs to generate MOLMAP descriptors from atomic properties included in SDF files are available upon request for evaluation.

Contact:  jas@fct.unl.pt

Supplementary information:  Supplementary data are available at Bioinformatics online.
Protein-ligand interaction prediction: an improved chemogenomics approach
Authors: Jacob Laurent , Vert Jean-Philippe
Published: August 2008

Motivation: Predicting interactions between small molecules and proteins is a crucial step to decipher many biological processes, and plays a critical role in drug discovery. When no detailed 3D structure of the protein target is available, ligand-based virtual screening allows the construction of predictive models by learning to discriminate known ligands from non-ligands. However, the accuracy of ligand-based models quickly degrades when the number of known ligands decreases, and in particular the approach is not applicable for orphan receptors with no known ligand.

Results: We propose a systematic method to predict ligand–protein interactions, even for targets with no known 3D structure and few or no known ligands. Following the recent chemogenomics trend, we adopt a cross-target view and attempt to screen the chemical space against whole families of proteins simultaneously. The lack of known ligand for a given target can then be compensated by the availability of known ligands for similar targets. We test this strategy on three important classes of drug targets, namely enzymes, G-protein-coupled receptors (GPCR) and ion channels, and report dramatic improvements in prediction accuracy over classical ligand-based virtual screening, in particular for targets with few or no known ligands.

Availability: All data and algorithms are available as Supplementary Material.

Contact:  laurent.jacob@ensmp.fr

Supplementary information:  Supplementary data are available at Bioinformatics online.
Geffen Faculty Highlight Concerns Linking CAIM and Conventional Researchers at UCLA Symposium
Authors: Logue Elizabeth H.
Published: August 2008

David Geffen School of Medicine faculty, representing a wide range of disciplines, engaged speakers nationally known for their expertise on complementary, alternative and integrative medicine (CAIM) and its investigation at a January, 2008 symposium on the campus of the University of California, Los Angeles. The forum was created to educate the UCLA Institutional Review Board (IRB), and lively participation by School of Medicine faculty helped bring IRB members up to speed on controversies surrounding CAIM research. The symposium demonstrated that academics who are neither proponents nor detractors of CAIM can facilitate cross talk between opposing camps, elucidating questions important to its evaluation by those charged with protecting research subjects. It also brought attention to the universality of quandaries facing CAIM investigators and to the ingenuity with which they have addressed many of them.
Looking Toward the Future: Expanding Connections for Business Historians
Authors: Laird Pamela Walker
Published: August 2008

Last year, Will Hausman gave us a splendid overview of business history's development for his presidential address. Despite his modesty, he treated us to a review of the parallels between his career and the field's progress, which owes much to his dedication to the Business History Conference (BHC) and its various constituencies. What we have within the BHC now, thanks to Will and many others, are multiple opportunities for exciting interactions based on ideas. As we share, exchange, and rearrange our ideas, they grow, as do our pleasure in and appreciation for them. The BHC offers us a wonderful arena for advancing the life of our minds—while advancing our ideas.
Applicability of the trophic index TRIX in two transitional ecosystems: the Mar Menor lagoon (Spain) and the Mondego estuary (Portugal)
Authors: Salas Fuensanta , Teixeira Heliana , Marcos Concepción , Marques João Carlos , Pérez-Ruzafa Angel
Published: August 2008

Salas, F., Teixeira, H., Marcos, C., Marques, J. C., and Pérez-Ruzafa, A. 2008. Applicability of the trophic index TRIX in two transitional ecosystems: the Mar Menor lagoon (Spain) and the Mondego estuary (Portugal). – ICES Journal of Marine Science, 65: 1442–1448. Ecological indicators are commonly used to provide synoptic information about the state of ecosystems. Their main attribute is that they combine a range of environmental factors in a single value, which is thought useful for management and for making ecological-quality concepts easily understandable by the general public. In some European countries, the trophic state of marine and coastal waters is characterized using the trophic index TRIX. We used TRIX in the studies of the Mar Menor coastal lagoon (southeast Spain) and the Mondego estuary (northwest Portugal). These areas are under environmental stress, and eutrophication processes have been monitored in recent years. The results demonstrate the inefficacy of TRIX as a trustworthy tool to classify eutrophication status in estuarine waters. The causes of the malfunction of the index are discussed, and we suggest that, if the index is to be applied over wide areas, the classification criteria will have to be adapted to specific environments.
Patient Safety in General Practice
Authors: Baker Maureen
Published: August 2008

‘First do no harm’ is a basic principle of the medical profession, believed to be handed down to us by Hippocrates. Yet, every doctor has personal experience of patients who have come to harm while receiving care. We are all familiar with stories of hospital-acquired infection, such as MRSA or Clostridium difficile and with horror stories like those about patients who have had the wrong kidney removed. But do we, as doctors, really have any idea of the extent to which things go wrong in health care and the numbers of patients who come to harm?
Tigecycline for the treatment of multidrug-resistant Enterobacteriaceae: a systematic review of the evidence from microbiological and clinical studies
Authors: Kelesidis Theodoros , Karageorgopoulos Drosos E. , Kelesidis Iosif , Falagas Matthew E.
Published: August 2008

Objectives

Antimicrobial drug resistance is spreading among Enterobacteriaceae, limiting the utility of traditionally used agents. We sought to systematically review the microbiological activity and clinical effectiveness of tigecycline for multidrug-resistant (MDR) Enterobacteriaceae, including those resistant to broad-spectrum β-lactams due to the expression of extended-spectrum β-lactamases (ESBLs), AmpC enzymes and carbapenemases (including metallo-β-lactamases).

Methods

PubMed was searched for articles including relevant data.

Results

Twenty-six microbiological and 10 clinical studies were identified. Tigecycline was active against more than 99% of 1936 Escherichia coli isolates characterized by any of the above resistance patterns (including 1636 ESBL-producing isolates) using the US Food and Drug Administration (FDA) breakpoint of susceptibility (MIC ≤ 2 mg/L). Findings were not different using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint (≤1 mg/L). Susceptibility rates for Klebsiella spp. with any of the above resistance patterns were 91.2% for 2627 isolates by the FDA criteria and 72.3% for 1504 isolates by the EUCAST criteria (92.3% for 2030 and 72.3% for 1284 ESBL-producing isolates, by the FDA and EUCAST criteria, respectively). The degree of microbiological activity of tigecycline against 576 MDR Enterobacter spp. isolates was moderate. In clinical studies, 69.7% of the 33 reported patients treated with tigecycline achieved resolution of an infection caused by a carbapenem-resistant or ESBL-producing or MDR Enterobacteriaceae.

Conclusions

Tigecycline is microbiologically active against almost all of the ESBL or MDR E. coli isolates and the great majority of ESBL or MDR Klebsiella spp. isolates. Further evaluation of its clinical utility against such resistant Enterobacteriaceae, particularly regarding non-labelled indications, is warranted.
European collectors and Japanese merchants of lacquer in ‘Old Japan’
Authors: Bincsik Monika
Published: August 2008

During the Meiji period, following the opening of Japan's borders to foreign trade, not only did the Japanese lacquer trading system and the market undergo a marked change but so too did almost all the factors affecting collecting activities: the European reception of the aesthetics and history of Japanese lacquer art, the taste of the collectors, the structure of private collections, the systematization of museum collections, along with changes in the art canon in the second half of the nineteenth century. The patterns of collecting Japanese lacquer art in the second half of the nineteenth century cannot be understood in depth without discussing shortly its preliminaries in the seventeenth and eighteenth centuries, focusing also on the art historical reception of Japanese lacquer in Europe. Supplementary material relating to this article in the form of a list of dealers and distributors of lacquer in Japan during the Meiji period (1868–1912) is available online.
Molecular interactions of ASPP1 and ASPP2 with the p53 protein family and the apoptotic promoters PUMA and Bax
Authors: Patel Seema , George Roger , Autore Flavia , Fraternali Franca , Ladbury John E. , Nikolova Penka V.
Published: August 2008

The apoptosis stimulating p53 proteins, ASPP1 and ASPP2, are the first two common activators of the p53 protein family that selectively enable the latter to regulate specific apoptotic target genes, which facilitates yes yet unknown mechanisms for discrimination between cell cycle arrest and apoptosis. To better understand the interplay between ASPP- and p53-family of proteins we investigated the molecular interactions between them using biochemical methods and structure-based homology modelling. The data demonstrate that: (i) the binding of ASPP1 and ASPP2 to p53, p63 and p73 is direct; (ii) the C-termini of ASPP1 and ASPP2 interact with the DNA-binding domains of p53 protein family with dissociation constants, Kd, in the lower micro-molar range; (iii) the stoichiometry of binding is 1:1; (iv) the DNA-binding domains of p53 family members are sufficient for these protein-protein interactions; (v) EMSA titrations revealed that while tri-complex formation between ASPPs, p53 family of proteins and PUMA/Bax is mutually exclusive, ASPP2 (but not ASPP1) formed a complex with PUMA (but not Bax) and displaced p53 and p73. The structure-based homology modelling revealed subtle differences between ASPP2 and ASPP1 and together with the experimental data provide novel mechanistic insights.
A member of the Whirly family is a multifunctional RNA- and DNA-binding protein that is essential for chloroplast biogenesis
Authors: Prikryl Jana , Watkins Kenneth P. , Friso Giulia , van Wijk Klaas J. , Barkan Alice
Published: August 2008

‘Whirly’ proteins comprise a plant-specific protein family whose members have been described as DNA-binding proteins that influence nuclear transcription and telomere maintenance, and that associate with nucleoids in chloroplasts and mitochondria. We identified the maize WHY1 ortholog among proteins that coimmunoprecipitate with CRS1, which promotes the splicing of the chloroplast atpF group II intron. ZmWHY1 localizes to the chloroplast stroma and to the thylakoid membrane, to which it is tethered by DNA. Genome-wide coimmunoprecipitation assays showed that ZmWHY1 in chloroplast extract is associated with DNA from throughout the plastid genome and with a subset of plastid RNAs that includes atpF transcripts. Furthermore, ZmWHY1 binds both RNA and DNA in vitro. A severe ZmWhy1 mutant allele conditions albino seedlings lacking plastid ribosomes; these exhibit the altered plastid RNA profile characteristic of ribosome-less plastids. Hypomorphic ZmWhy1 mutants exhibit reduced atpF intron splicing and a reduced content of plastid ribosomes; aberrant 23S rRNA metabolism in these mutants suggests that a defect in the biogenesis of the large ribosomal subunit underlies the ribosome deficiency. However, these mutants contain near normal levels of chloroplast DNA and RNAs, suggesting that ZmWHY1 is not directly required for either DNA replication or for global plastid transcription.
The triple helix: 50 years later, the outcome
Authors: Duca Maria , Vekhoff Pierre , Oussedik Kahina , Halby Ludovic , Arimondo Paola B.
Published: August 2008

Triplex-forming oligonucleotides constitute an interesting DNA sequence-specific tool that can be used to target cleaving or cross-linking agents, transcription factors or nucleases to a chosen site on the DNA. They are not only used as biotechnological tools but also to induce modifications on DNA with the aim to control gene expression, such as by site-directed mutagenesis or DNA recombination. Here, we report the state of art of the triplex-based antigene strategy 50 years after the discovery of such a structure, and we show the importance of the actual applications and the main challenges that we still have ahead of us.
Formation of an RNA polymerase II preinitiation complex on an RNA promoter derived from the hepatitis delta virus RNA genome
Authors: Abrahem Abrahem , Pelchat Martin
Published: August 2008

Although RNA polymerases (RNAPs) are able to use RNA as template, it is unknown how they recognize RNA promoters. In this study, we used an RNA fragment derived from the hepatitis delta virus (HDV) genome as a model to investigate the recognition of RNA promoters by RNAP II. Inhibition of the transcription reaction using an antibody specific to the largest subunit of RNAP II and the direct binding of purified RNAP II to the RNA promoter confirmed the involvement of RNAP II in the reaction. RNA affinity chromatography established that an active RNAP II preinitiation complex forms on the RNA promoter and indicated that this complex contains the core RNAP II subunit and the general transcription factors TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH and TFIIS. Binding assays demonstrated the direct binding of the TATA-binding protein and suggested that this protein is required to nucleate the RNAP II complex on the RNA promoter. Our findings provide a better understanding of the events leading to RNA promoter recognition by RNAP II.
Climate and the range dynamics of species with imperfect detection
Authors: Altwegg Res , Wheeler Marius , Erni Birgit
Published: August 2008

Reliable predictions for species range changes require a mechanistic understanding of range dynamics in relation to environmental variation. One obstacle is that most current models are static and confound occurrence with the probability of detecting a species if it occurs at a site. Here we draw attention to recently developed occupancy models, which can be used to examine colonization and local extinction or changes in occupancy over time. These models further account for detection probabilities, which are likely to vary spatially and temporally in many datasets. Occupancy models require repeated presence/absence surveys, for example checklists used in bird atlas projects. As an example, we examine the recent range expansion of hadeda ibises (
Bostrychia hagedash
) in South African protected areas. Colonization exceeded local extinction in most biomes, and the probability of occurrence was related to local climate. Extensions of the basic occupancy models can estimate abundance or species richness. Occupancy models are an appealing additional tool for studying species' responses to global change.
Ecophysiological constraints shape autumn migratory response to climate change in the North American field sparrow
Authors: Monahan William B , Hijmans Robert J
Published: August 2008

Our ability to accurately forecast species' geographical responses to climate change requires knowledge of the proximate and ultimate drivers of their distribution. Here, we consider the ecophysiological and demographic determinants of the distribution of a partial migrant, the North American field sparrow,Spizella pusilla. From 1940 to 1963, the field sparrow extended its winter northern range margin 222 km polewards. Such expansion was coincident with not only a geographical expansion into suitable breeding habitats, but also a decrease in mean abundance across sites occupied during the winter surveys. Combined, these trends suggest that declining populations along the expansion front either stopped migrating or altered their autumn migration. The poleward expansion was not coincident with climatically induced decreases in peak metabolic energy demand, but it did track increases in ecosystem net primary productivity. After 1963, the species' lower lethal temperature prevented further poleward movement. These findings show how different ecophysiological constraints can interact to change migration and distribution in a demographically declining species.
Three-dimensional current flow in a large-scale model of the cochlea and the mechanism of amplification of sound
Authors: Mistrík Pavel , Mullaley Chris , Mammano Fabio , Ashmore Jonathan
Published: August 2008

The mammalian inner ear uses its sensory hair cells to detect and amplify incoming sound. It is unclear whether cochlear amplification arises uniquely from a voltage-dependent mechanism (electromotility) associated with outer hair cells (OHCs) or whether other mechanisms are necessary, for the voltage response of OHCs is apparently attenuated excessively by the membrane electrical filter. The cochlea contains many thousands of hair cells organized in extensive arrays, embedded in an electrically coupled system of supporting cells. We have therefore constructed a multi-element, large-scale computational model of cochlear sound transduction to study the underlying potassium (K
+
) recirculation. We have included experimentally determined parameters of cochlear macromechanics, which govern sound transduction, and data on hair cells' electrical parameters including tonotopical variation in the membrane conductance of OHCs. In agreement with the experiment, the model predicts an exponential decay of extracellular longitudinal K
+
current spread. In contrast to the predictions from isolated cells, it also predicts low attenuation of the OHC transmembrane receptor potential (−5 dB per decade) in the 0.2–30 kHz range. This suggests that OHC electromotility could be driven by the transmembrane potential. Furthermore, the OHC electromotility could serve as a single amplification mechanism over the entire hearing range.
Roots, shoots and reproduction: sexual dimorphism in size and costs of reproductive allocation in an annual herb
Authors: Harris Mark S , Pannell John R
Published: August 2008

Females tend to be smaller than males in woody dioecious plant species, but they tend to be larger in herbs. The smaller size of females in woody species has been attributed to higher reproductive costs, yet no satisfactory explanation has been provided for their larger size in herbs. Because herbs have higher nitrogen concentrations in their tissues than woody plants, and because pollen is particularly rich in nitrogen, we predicted that male growth would be more compromised by reproduction than female growth. To test this hypothesis, we conducted three experiments on the annual dioecious herb
Mercurialis annua
. First, we compared the timing of reproduction between males and females and found that males started flowering earlier than females; early flowering is expected to compromise growth more than later flowering. Second, we compared plants allowed to flower with those prevented from flowering by experimental debudding and found that males incurred a higher reproductive cost than females in terms of both biomass and, particularly, nitrogen. Third, we grew plants under varying levels of nitrogen availability and found that although sexual size dimorphism was unaffected by nitrogen, females, but not males, decreased their relative allocation to both roots and reproduction under high nitrogen availability. We propose that males deal with the high cost of pollen production in terms of nitrogen by allocating biomass to nitrogen-harvesting roots, whereas females pay for carbon-rich seeds and fruits by investing in photosynthetic organs. Sexual dimorphism would thus seem to be the outcome of allocation to above- versus below-ground sinks that supply resources (carbon versus nitrogen) limiting the female and male reproduction differentially.
Evolution of the mammalian transcription factor binding repertoire via transposable elements
Authors: Bourque Guillaume , Leong Bernard , Vega Vinsensius B. , Chen Xi , Lee Yen Ling , Srinivasan Kandhadayar G. , Chew Joon-Lin , Ruan Yijun , Wei Chia-Lin , Ng Huck Hui , Liu Edison T.
Published: August 2008

Identification of lineage-specific innovations in genomic control elements is critical for understanding transcriptional regulatory networks and phenotypic heterogeneity. We analyzed, from an evolutionary perspective, the binding regions of seven mammalian transcription factors (ESR1, TP53, MYC, RELA, POU5F1, SOX2, and CTCF) identified on a genome-wide scale by different chromatin immunoprecipitation approaches and found that only a minority of sites appear to be conserved at the sequence level. Instead, we uncovered a pervasive association with genomic repeats by showing that a large fraction of the bona fide binding sites for five of the seven transcription factors (ESR1, TP53, POU5F1, SOX2, and CTCF) are embedded in distinctive families of transposable elements. Using the age of the repeats, we established that these repeat-associated binding sites (RABS) have been associated with significant regulatory expansions throughout the mammalian phylogeny. We validated the functional significance of these RABS by showing that they are over-represented in proximity of regulated genes and that the binding motifs within these repeats have undergone evolutionary selection. Our results demonstrate that transcriptional regulatory networks are highly dynamic in eukaryotic genomes and that transposable elements play an important role in expanding the repertoire of binding sites.
AtCHX13 Is a Plasma Membrane K+ Transporter
Authors: Zhao Jian , Cheng Ning-Hui , Motes Christy M. , Blancaflor Elison B. , Moore Miranda , Gonzales Naomi , Padmanaban Senthilkumar , Sze Heven , Ward John M. , Hirschi Kendal D.
Published: August 2008

Potassium (K+) homeostasis is essential for diverse cellular processes, although how various cation transporters collaborate to maintain a suitable K+ required for growth and development is poorly understood. The Arabidopsis (Arabidopsis thaliana) genome contains numerous cation:proton antiporters (CHX), which may mediate K+ transport; however, the vast majority of these transporters remain uncharacterized. Here, we show that AtCHX13 (At2g30240) has a role in K+ acquisition. AtCHX13 suppressed the sensitivity of yeast (Saccharomyces cerevisiae) mutant cells defective in K+ uptake. Uptake experiments using 86Rb+ as a tracer for K+ demonstrated that AtCHX13 mediated high-affinity K+ uptake in yeast and in plant cells with a K  m of 136 and 196 μ  m, respectively. Functional green fluorescent protein-tagged versions localized to the plasma membrane of both yeast and plant. Seedlings of null chx13 mutants were sensitive to K+ deficiency conditions, whereas overexpression of AtCHX13 reduced the sensitivity to K+ deficiency. Collectively, these results suggest that AtCHX13 mediates relatively high-affinity K+ uptake, although the mode of transport is unclear at present. AtCHX13 expression is induced in roots during K+-deficient conditions. These results indicate that one role of AtCHX13 is to promote K+ uptake into plants when K+ is limiting in the environment.
Two New Clock Proteins, LWD1 and LWD2, Regulate Arabidopsis Photoperiodic Flowering
Authors: Wu Jing-Fen , Wang Ying , Wu Shu-Hsing
Published: August 2008

The “light” signal from the environment sets the circadian clock to regulate multiple physiological processes for optimal rhythmic growth and development. One such process is the control of flowering time by photoperiod perception in plants. In Arabidopsis (Arabidopsis thaliana), the flowering time is determined by the correct interconnection of light input and signal output by the circadian clock. The identification of additional clock proteins will help to better dissect the complex nature of the circadian clock in Arabidopsis. Here, we show LIGHT-REGULATED WD1 (LWD1)/LWD2 as new clock proteins involved in photoperiod control. The lwd1lwd2 double mutant has an early-flowering phenotype, contributed by the significant phase shift of CONSTANS (CO), and, therefore, an increased expression of FLOWERING LOCUS T (FT) before dusk. Under entrainment conditions, the expression phase of oscillator (CIRCADIAN CLOCK ASSOCIATED1 [CCA1], LATE ELONGATED HYPOCOTYL [LHY], TIMING OF CAB EXPRESSION1 [TOC1], and EARLY FLOWERING4 [ELF4]) and output (GIGANTEA, FLAVIN-BINDING, KELCH REPEAT, F-BOX1, CYCLING DOF FACTOR1, CO, and FT) genes in the photoperiod pathway shifts approximately 3 h forward in the lwd1lwd2 double mutant. Both the oscillator (CCA1, LHY, TOC1, and ELF4) and output (COLD, CIRCADIAN RHYTHM, AND RNA BINDING2 and CHLOROPHYLL A/B-BINDING PROTEIN2) genes have a short period length in the lwd1lwd2 double mutant. Our data imply that LWD1/LWD2 proteins function in close proximity to or within the circadian clock for photoperiodic flowering control.
Singlet Oxygen Is the Major Reactive Oxygen Species Involved in Photooxidative Damage to Plants
Authors: Triantaphylidès Christian , Krischke Markus , Hoeberichts Frank Alfons , Ksas Brigitte , Gresser Gabriele , Havaux Michel , Van Breusegem Frank , Mueller Martin Johannes
Published: August 2008

Reactive oxygen species act as signaling molecules but can also directly provoke cellular damage by rapidly oxidizing cellular components, including lipids. We developed a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry-based quantitative method that allowed us to discriminate between free radical (type I)- and singlet oxygen (1O2; type II)-mediated lipid peroxidation (LPO) signatures by using hydroxy fatty acids as specific reporters. Using this method, we observed that in nonphotosynthesizing Arabidopsis (Arabidopsis thaliana) tissues, nonenzymatic LPO was almost exclusively catalyzed by free radicals both under normal and oxidative stress conditions. However, in leaf tissues under optimal growth conditions, 1O2 was responsible for more than 80% of the nonenzymatic LPO. In Arabidopsis mutants favoring 1O2 production, photooxidative stress led to a dramatic increase of 1O2 (type II) LPO that preceded cell death. Furthermore, under all conditions and in mutants that favor the production of superoxide and hydrogen peroxide (two sources for type I LPO reactions), plant cell death was nevertheless always preceded by an increase in 1O2-dependent (type II) LPO. Thus, besides triggering a genetic cell death program, as demonstrated previously with the Arabidopsis fluorescent mutant, 1O2 plays a major destructive role during the execution of reactive oxygen species-induced cell death in leaf tissues.
Functional Diversification of CLAVATA3-Related CLE Proteins in Meristem Maintenance in Rice
Authors: Suzaki Takuya , Yoshida Akiko , Hirano Hiro-Yuki
Published: August 2008

Postembryonic development in plants depends on the activity of the shoot apical meristem (SAM) and root apical meristem (RAM). In Arabidopsis thaliana, CLAVATA signaling negatively regulates the size of the stem cell population in the SAM by repressing WUSCHEL. In other plants, however, studies of factors involved in stem cell maintenance are insufficient. Here, we report that two proteins closely related to CLAVATA3, FLORAL ORGAN NUMBER2 (FON2) and FON2-LIKE CLE PROTEIN1 (FCP1/Os CLE402), have functionally diversified to regulate the different types of meristem in rice (Oryza sativa). Unlike FON2, which regulates the maintenance of flower and inflorescence meristems, FCP1 appears to regulate the maintenance of the vegetative SAM and RAM. Constitutive expression of FCP1 results in consumption of the SAM in the vegetative phase, and application of an FCP1 CLE peptide in vitro disturbs root development by misspecification of cell fates in the RAM. FON1, a putative receptor of FON2, is likely to be unnecessary for these FCP1 functions. Furthermore, we identify a key amino acid residue that discriminates between the actions of FCP1 and FON2. Our results suggest that, although the basic framework of meristem maintenance is conserved in the angiosperms, the functions of the individual factors have diversified during evolution.
ArabidopsisProtein Disulfide Isomerase-5 Inhibits Cysteine Proteases during Trafficking to Vacuoles before Programmed Cell Death of the Endothelium in Developing Seeds
Authors: Andème Ondzighi Christine , Christopher David A. , Cho Eun Ju , Chang Shu-Choeng , Staehelin L. Andrew
Published: August 2008

Protein disulfide isomerase (PDI) oxidizes, reduces, and isomerizes disulfide bonds, modulates redox responses, and chaperones proteins. The Arabidopsis thaliana genome contains 12 PDI genes, but little is known about their subcellular locations and functions. We demonstrate that PDI5 is expressed in endothelial cells about to undergo programmed cell death (PCD) in developing seeds. PDI5 interacts with three different Cys proteases in yeast two-hybrid screens. One of these traffics together with PDI5 from the endoplasmic reticulum through the Golgi to vacuoles, and its recombinant form is functionally inhibited by recombinant PDI5 in vitro. Peak PDI5 expression in endothelial cells precedes PCD, whereas decreasing PDI5 levels coincide with the onset of PCD-related cellular changes, such as enlargement and subsequent collapse of protein storage vacuoles, lytic vacuole shrinkage and degradation, and nuclear condensation and fragmentation. Loss of PDI5 function leads to premature initiation of PCD during embryogenesis and to fewer, often nonviable, seeds. We propose that PDI5 is required for proper seed development and regulates the timing of PCD by chaperoning and inhibiting Cys proteases during their trafficking to vacuoles before PCD of the endothelial cells. During this transitional phase of endothelial cell development, the protein storage vacuoles become the de facto lytic vacuoles that mediate PCD.