bluuebunny/crossref_metadata_2025 huggingface dataset:
A system for the targeted amplification of bacterial gene clusters multiplies antibiotic yield in
Streptomyces coelicolor
Authors: Murakami Takeshi , Burian Jan , Yanai Koji , Bibb Mervyn J. , Thompson Charles J.
Published: September 2011

Gene clusters found in bacterial species classified as
Streptomyces
encode the majority of known antibiotics as well as many pharmaceutically active compounds. A site-specific recombination system similar to those that mediate plasmid conjugation was engineered to catalyze tandem amplification of one of these gene clusters in a heterologous
Streptomyces
species. Three genetic elements were known to be required for DNA amplification in
S. kanamyceticus
: the
oriT
-like recombination sites RsA and RsB, and ZouA, a site-specific relaxase similar to TraA proteins that catalyze plasmid transfer. We inserted RsA and RsB sequences into the
S. coelicolor
genome flanking a cluster of 22 genes (
act
) responsible for biosynthesis of the polyketide antibiotic actinorhodin. Recombination between RsA and RsB generated
zouA
-dependent DNA amplification resulting in 4–12 tandem copies of the
act
gene cluster averaging nine repeats per genome. This resulted in a 20-fold increase in actinorhodin production compared with the parental strain. To determine whether the recombination event required taxon-specific genetic effectors or generalized bacterial recombination (
recA
), it was also analyzed in the heterologous host
Escherichia coli
.
zouA
was expressed under the control of an inducible promoter in wild-type and
recA
mutant strains. A plasmid was constructed with recombination sites RsA and RsB bordering a drug resistance marker. Induction of
zouA
expression generated hybrid RsB/RsA sites, evidence of site-specific recombination that occurred independently of
recA
. ZouA-mediated DNA amplification promises to be a valuable tool for increasing the activities of commercially important biosynthetic, degradative, and photosynthetic pathways in a wide variety of organisms.
Crystal structure of the hybrid state of ribosome in complex with the guanosine triphosphatase release factor 3
Authors: Jin Hong , Kelley Ann C. , Ramakrishnan V.
Published: September 2011

Protein release factor 3 (RF3), a guanosine triphosphatase, binds to ribosome after release of the nascent peptide and promotes dissociation of the class I release factors during the termination of protein synthesis. Here we present the crystal structure of the 70S ribosome with RF3 in the presence of a nonhydrolyzable GTP analogue, guanosine 5′-β,γ-methylenetriphosphate (GDPCP), refined to 3.8 Å resolution. The structure shows that the subunits of the ribosome are rotated relative to each other compared to the canonical state, resulting in a P/E hybrid state for the transfer RNA. The substantial conformational rearrangements in the complex are described and suggest how RF3, by stabilizing the hybrid state of the ribosome, facilitates the dissociation of class I release factors.
A small pool of vesicles maintains synaptic activity in vivo
Authors: Denker Annette , Bethani Ioanna , Kröhnert Katharina , Körber Christoph , Horstmann Heinz , Wilhelm Benjamin G. , Barysch Sina V. , Kuner Thomas , Neher Erwin , Rizzoli Silvio O.
Published: September 2011

Chemical synapses contain substantial numbers of neurotransmitter-filled synaptic vesicles, ranging from approximately 100 to many thousands. The vesicles fuse with the plasma membrane to release neurotransmitter and are subsequently reformed and recycled. Stimulation of synapses in vitro generally causes the majority of the synaptic vesicles to release neurotransmitter, leading to the assumption that synapses contain numerous vesicles to sustain transmission during high activity. We tested this assumption by an approach we termed cellular ethology, monitoring vesicle function in behaving animals (10 animal models, nematodes to mammals). Using FM dye photooxidation, pHluorin imaging, and HRP uptake we found that only approximately 1–5% of the vesicles recycled over several hours, in both CNS synapses and neuromuscular junctions. These vesicles recycle repeatedly, intermixing slowly (over hours) with the reserve vesicles. The latter can eventually release when recycling is inhibited in vivo but do not seem to participate under normal activity. Vesicle recycling increased only to ≈5% in animals subjected to an extreme stress situation (frog predation on locusts). Synapsin, a molecule binding both vesicles and the cytoskeleton, may be a marker for the reserve vesicles: the proportion of vesicles recycling in vivo increased to 30% in synapsin-null
Drosophila
. We conclude that synapses do not require numerous reserve vesicles to sustain neurotransmitter release and thus may use them for other purposes, examined in the accompanying paper.
The relation between the encoding of motion event information and viewpoint in English-accompanying gestures
Authors: Parrill Fey
Published: September 2011

Properties of motion events (e.g., path, manner) and point of view (e.g., character’s point of view, observer’s point of view) can both be encoded in co-speech gestures. How are these two dimensions of meaning associated? In an examination of English narrative data collected under controlled circumstances, we found that gestures encoding manner of motion were significantly more likely to appear in character viewpoint. Gestures encoding path (but not manner), on the other hand, were significantly more likely to occur in observer viewpoint. Gestures encoding both path and manner simultaneously were also significantly more likely to occur in observer viewpoint. We suggest that selection of point of view may have effects on the encoding of certain semantic features in gesture.
The length hierarchy and the graphematic syllable
Authors: Fuhrhop Nanna , Buchmann Franziska , Berg Kristian
Published: September 2011

Minuscules of the Roman alphabet can be subcategorized into graphemes with length (for example 〈b〉) and graphemes without length (for example 〈o〉). While plosives, which correspond to graphemes with length, occur at the syllable edge, vowels, corresponding to graphemes without length, constitute the syllable core. Based on these observations, a length hierarchy is established in which the feature ‘length’ becomes scalar. This hierarchy operates on graphematic grounds exclusively, thus being independent of phonological properties. Still a length sequencing principle as the ordering principle of the graphematic syllable can be formulated analogous to the phonological sonority sequencing principle. The length sequencing principle may be considered a typological feature to serve further descriptions of different graphematic systems based on the Roman alphabet. Data from German and English will be discussed.
Keywords:graphematic syllable; graphotactics; length sequencing principle; length hierarchy; letter shape; sonority
What linguistic units do Chinese characters represent?
Authors: Unger J. Marshall
Published: September 2011

Using the Internet and spreadsheet software, it is now easy to compare word and character counts for modern and literary Chinese based on very large corpora. It turns out that word counts comply with Zipf’s Law whereas character counts do not. This constitutes novel statistical evidence against the persistent claim that Chinese characters are logograms. It thus casts doubt on the practice of categorizing the elements of various writing systems as ‘phonograms’ or ‘logograms’ without regard to context, and a fortiori characterizing entire writing systems as ‘phonographic’ or ‘logographic’. Keywords: Chinese; word; character; morpheme; syllable; phonogram; logogram; Zipf’s Law; corpus
Training
Authors: Mann John
Published: September 2011

This is a new section for people to report on courses they have attended or for trainers/colleges etc., to describe their courses/syllabuses at some depth.
Training
Authors: Evans John
Published: September 2011

This section is for people to report on courses they have attended or for trainers/colleges etc. to describe their courses/syllabuses at some depth.
The Development of Social Identity through Dramatherapy
Authors: Jennings Sue
Published: September 2011

This paper is concerned with the process of structured application of dramatherapy as a means of discovering, developing and re-learning of social identity which as such can be integrated into a clinical programme of therapy, re-habilitation or re-education.

In order for this to be effective we need to understand the nature of rôle and its relationship to the psyche, especially the ego.

Only through the realisation that man both thinks and feels in dramatic form can we appreciate the implications of dramatherapy application within the clinical framework.
The Way up is the Way Down: And Other Paradoxes
Authors: Rowan John
Published: September 2011

Part one of a three part transcript of the keynote speech from the National Dramatherapy Conference (1991), ‘Chaos: The Hidden Order’.
A Challenging Safety: Further Thoughts about Catharsis
Authors: Grainger Roger
Published: September 2011

“The feeling that death is inevitable comes to us from ordinary experience; the feeling that life is inevitable comes to us from myth and fable. The latter is therefore both more true and more important.”
Thoughts on the Future of Dramatherapy Research
Authors: Grainger Roger
Published: September 2011

‘Part of the importance of art lies in its refusal to become pure thought.’
The Loneliness of the Long Distance Therapist
Authors: Jennings Sue
Published: September 2011

“Walking in the midst of others, one returns alone.”
The Dramatic World View Revisited: Reflections on the Roles Taken and Played by Young Children and Adolescents
Authors: Landy Robert J.
Published: September 2011

In this article, the author revisits an earlier paper published in 1995, “The Dramatic World View: Reflections on the Roles Taken and Played by Young Children,” which surveyed the ways and means that children acquire and play out roles in their early development. The paper was based on Landy's role theory in dramatherapy and on the observation of his two young children from eight months to four years old. The author adds his reflections upon his children twelve years later based on his observation of their projective drawings and stories. These observations lead to a discussion of role-taking and role-playing processes in the continuing development of individuals from childhood through adolescence. Throughout the article, the author examines the continuity and change of roles as manifested in the developing child's expressive activities.
A New Beginning – A Dramatherapy Group for Participants with Co-Occurring Mental Illness and Substance Abuse in a Mental Health Setting
Authors: Jaaniste Joanna
Published: September 2011

Rehabilitation for people with dual diagnosis (co-existing mental illness and substance dependence) has existed in many forms over the past thirty years and has become more urgently needed over time. Treatment for this population inevitably requires a team effort (Schwartz & Lehman, 1998). These people are difficult to engage in treatment and it takes time to unravel the interacting effects of substance abuse and their mental illness. Social relationships may also be problematic, particularly once the person has decided to discontinue drug or alcohol abuse. Often such clients find it easier to communicate socially with people who have similar problems (Hatfield, 1993).

Improvements in self-esteem and reduced intake of drugs and alcohol are rarely monitored in the one community psychiatric facility, as in this study. The method of treatment in this case was to run a small group for participants over an extended period with support from multidisciplinary teams, using a Dutch model for drug and alcohol rehabilitation. By targeting psychiatric relapse prevention and people's life stories, using a biographical developmental framework and dramatherapy interventions, the intention was to achieve outcomes of higher self esteem and reduced intake of recreational drugs. In fact the pre and post measures chosen did not show significant variance. For all participants, including those who were already abstinent, changes in lifestyle and achievement of life goals were sought. As a result, there was reported enjoyment of mutual support, sharing and understanding of individual life stories, together with strategies to increase resilience. Further research is needed to identify how best to measure outcomes.

Hatfield, A. (1993) ‘Dual Diagnosis and Mental Illness’, Journal of National Alliance for the Mentally Ill, (Online), retrieved 11.1.08

Schwartz, R. & Lehman, A. (1995) in ‘Overview of Treatment Principles’ in Lehman, A. & Dixon, L. (eds.) Double Jeopardy, Harwood Academic Publishers, Chur, Switzerland, p.77
A Story to Tell: Use of Story and Drama in Work with Substitute Families
Authors: Moore Joan
Published: September 2011

This paper discusses the use of a dramatic narrative approach with adoptive and foster families, involving the parents in enactment of their child's life history for the purpose of changing unhelpful patterns in working towards enhanced mutuality. Research on outcomes finds adoption to be mainly successful, however the likelihood of disruption increases with age from approx 20% at age 7 to 50% at age 11, identifying therapeutic support as of critical importance (Dance 2005). The families (mainly White English) referred for this Dramatherapeutic intervention, characteristically struggle with some form of cultural divide, the parents (often in professional employment) having different life experience and expectations to those of the children, many of whom expect their placement to be temporary, being already accustomed to many changes and associated losses experienced as rejection. For black children, being of different race and appearance adds yet another dimension. The article will evaluate the use of ‘water games’, clay and doll's house play and a candle ceremony as part metaphor/part physical life drama structures for exploration.
The Power of a New Story: The Bigger Picture
Authors: Bird Drew
Published: September 2011

This paper looks at the power of professionals and carers' beliefs systems and how these can cause ‘problem saturation’ for a teenage girl, in addressing her difficulty with managing her anger. The study illustrates how the client was able to utilise the concept of externalisation in Narrative Therapy to revise her unhelpful and problem saturated story. By using the Dramatherapy notions of embodiment, story and role, a re-authored narrative was created to help the client to separate and distance herself from the dominant story. Through the dramatisation of a fairytale, the client was able to author a new story that enabled her to have a different perception of herself and increase her range of self-expression.
Reconstructing the 3D etch rate distribution of silicon in anisotropic etchants using data from vicinal {1 0 0}, {1 1 0} and {1 1 1} surfaces
Authors: Gosálvez M A , Pal Prem , Sato K
Published: September 2011

We consider the reconstruction of the complete three-dimensional distribution of etch rates for crystalline silicon in a total of six markedly different etching conditions. The procedure is based on data points that, on the unit sphere, are located along the high-symmetry lines connecting the three main surface orientations Si{1 1 1}, Si{1 1 0} and Si{1 0 0}. Novel, compact formulas are presented in order to perform trilinear, triquadratic and higher order interpolations in h 
k 
l space. A wide variety of surface triangulations and tessellations are proposed in order to apply the trilinear and higher order formulas. A statistical analysis concludes that trilinear interpolation over three particular triangulations, and triquartic interpolation over a specific tessellation provide the best reconstructions for the six considered etching conditions. By combining the three triangulations and tessellation using a weighted average, the mean error is found to be less than 13% for reconstructions involving noisy experimental etch rates, while it decreases to 2–5% for less unruly distributions. The results strongly indicate that the complete orientation dependence of the etch rate can be derived from an alternative, more feasible experiment than the traditional hemispherical specimen.
Reconstructing transcription factor activities in hierarchical transcription network motifs
Authors: Ocone Andrea , Sanguinetti Guido
Published: September 2011

Motivation: A knowledge of the dynamics of transcription factors is fundamental to understand the transcriptional regulation mechanism. Nowadays, an experimental measure of transcription factor activities in vivo represents a challenge. Several methods have been developed to infer these activities from easily measurable quantities such as mRNA expression of target genes. A limitation of these methods is represented by the fact that they rely on very simple single-layer structures, typically consisting of one or more transcription factors regulating a number of target genes.

Results: We present a novel statistical inference methodology to reverse engineer the dynamics of transcription factors in hierarchical network motifs such as feed-forward loops. The approach we present is based on a continuous time representation of the system where the high-level master transcription factor is represented as a two state Markov jump process driving a system of differential equations. We solve the inference problem using an efficient variational approach and demonstrate our method on simulated data and two real datasets. The results on real data show that the predictions of our approach can capture biological behaviours in a more effective way than single-layer models of transcription, and can lead to novel biological insights.

Availability:  http://homepages.inf.ed.ac.uk/gsanguin/software.html

Contact:  g.sanguinetti@ed.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
Comparing bioassay response and similarity ensemble approaches to probing protein pharmacology
Authors: Chen Bin , McConnell Kevin J. , Wale Nikil , Wild David J. , Gifford Eric M.
Published: September 2011

Motivation: Networks to predict protein pharmacology can be created using ligand similarity or using known bioassay response profiles of ligands. Recent publications indicate that similarity methods can be highly accurate, but it has been unclear how similarity methods compare to methods that use bioassay response data directly.

Results: We created protein networks based on ligand similarity (Similarity Ensemble Approach or SEA) and ligand bioassay response-data (BARD) using 155 Pfizer internal BioPrint assays. Both SEA and BARD successfully cluster together proteins with known relationships, and predict some non-obvious relationships. Although the approaches assess target relations from different perspectives, their networks overlap considerably (40% overlap of the top 2% of correlated edges). They can thus be considered as comparable methods, with a distinct advantage of the similarity methods that they only require simple computations (similarity of compound) as opposed to extensive experimental data.

Contacts:  djwild@indiana.edu; eric.gifford@pfizer.com

Supplementary Information:  Supplementary data are available at Bioinformatics online.
A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data
Authors: Li Heng
Published: September 2011

Motivation: Most existing methods for DNA sequence analysis rely on accurate sequences or genotypes. However, in applications of the next-generation sequencing (NGS), accurate genotypes may not be easily obtained (e.g. multi-sample low-coverage sequencing or somatic mutation discovery). These applications press for the development of new methods for analyzing sequence data with uncertainty.

Results: We present a statistical framework for calling SNPs, discovering somatic mutations, inferring population genetical parameters and performing association tests directly based on sequencing data without explicit genotyping or linkage-based imputation. On real data, we demonstrate that our method achieves comparable accuracy to alternative methods for estimating site allele count, for inferring allele frequency spectrum and for association mapping. We also highlight the necessity of using symmetric datasets for finding somatic mutations and confirm that for discovering rare events, mismapping is frequently the leading source of errors.

Availability:  http://samtools.sourceforge.net

Contact:  hengli@broadinstitute.org
Finding stable local optimal RNA secondary structures
Authors: Li Yuan , Zhang Shaojie
Published: September 2011

Motivation: Many RNAs, such as riboswitches, can fold into multiple alternate structures and perform different biological functions. These biologically functional structures usually have low free energies in their local energy landscapes and are very stable such that they cannot easily jump out of the current states and fold into other stable conformations. The conformational space of feasible RNA secondary structures is prohibitively large, and accurate prediction of functional structure conformations is challenging. Because the stability of an RNA secondary structure is determined predominantly by energetically favorable helical regions (stacks), we propose to use configurations of putative stacks to represent RNA secondary structures. By considering a reduced conformational space of local optimal stack configurations instead of all feasible RNA structures, we first present an algorithm for enumerating all possible local optimal stack configurations. In addition, we present a fast heuristic algorithm for approximating energy barriers encountered during folding pathways between each pair of local optimal stack configurations and finding all the stable local optimal structures.

Results: Benchmark tests have been conducted on several RNA riboswitches, whose alternate secondary structures have been experimentally verified. The benchmark results show that our method can successfully predict the native ‘on’ and ‘off’ secondary structures, and better rank them compared with other state-of-art approaches.

Availability: The software is freely available and can be downloaded at http://genome.ucf.edu/RNASLOpt.

Contact:  shzhang@eecs.ucf.edu

Supplementary Information:  Supplementary data are available at Bioinformatics online.
An empirical comparison of several recent epistatic interaction detection methods
Authors: Wang Yue , Liu Guimei , Feng Mengling , Wong Limsoon
Published: September 2011

Motivation: Many new methods have recently been proposed for detecting epistatic interactions in GWAS data. There is, however, no in-depth independent comparison of these methods yet.

Results: Five recent methods—TEAM, BOOST, SNPHarvester, SNPRuler and Screen and Clean (SC)—are evaluated here in terms of power, type-1 error rate, scalability and completeness. In terms of power, TEAM performs best on data with main effect and BOOST performs best on data without main effect. In terms of type-1 error rate, TEAM and BOOST have higher type-1 error rates than SNPRuler and SNPHarvester. SC does not control type-1 error rate well. In terms of scalability, we tested the five methods using a dataset with 100 000 SNPs on a 64 bit Ubuntu system, with Intel (R) Xeon(R) CPU 2.66 GHz, 16 GB memory. TEAM takes ~36 days to finish and SNPRuler reports heap allocation problems. BOOST scales up to 100 000 SNPs and the cost is much lower than that of TEAM. SC and SNPHarvester are the most scalable. In terms of completeness, we study how frequently the pruning techniques employed by these methods incorrectly prune away the most significant epistatic interactions. We find that, on average, 20% of datasets without main effect and 60% of datasets with main effect are pruned incorrectly by BOOST, SNPRuler and SNPHarvester.

Availability: The software for the five methods tested are available from the URLs below. TEAM: http://csbio.unc.edu/epistasis/download.php BOOST: http://ihome.ust.hk/~eeyang/papers.html. SNPHarvester: http://bioinformatics.ust.hk/SNPHarvester.html. SNPRuler: http://bioinformatics.ust.hk/SNPRuler.zip. Screen and Clean: http://wpicr.wpic.pitt.edu/WPICCompGen/.

Contact:  wangyue@nus.edu.sg
Estimating functions and the generalized method of moments
Authors: Jesus Joao , Chandler Richard E.
Published: September 2011

Estimating functions provide a very general framework for statistical inference, and are particularly useful when one is either unable or unwilling to specify a likelihood function. This paper aims to provide an accessible review of estimating function theory that has potential for application to the analysis and modelling of a wide range of complex systems. Assumptions are given in terms that can be checked relatively easily in practice, and some of the more technical derivations are relegated to an online supplement for clarity of exposition. The special case of the generalized method of moments is considered in some detail. The main points are illustrated by considering the problem of inference for a class of stochastic rainfall models based on point processes, with simulations used to demonstrate the performance of the methods.
Reduction of quinones and phenoxy radicals by extracellular glucose dehydrogenase from Glomerella cingulata suggests a role in plant pathogenicity
Authors: Sygmund Christoph , Klausberger Miriam , Felice Alfons K. , Ludwig Roland
Published: September 2011

The plant-pathogenic fungusGlomerella cingulata(anamorphColletotrichum gloeosporoides) secretes high levels of an FAD-dependent glucose dehydrogenase (GDH) when grown on tomato juice-supplemented media. To elucidate its molecular and catalytic properties, GDH was produced in submerged culture. The highest volumetric activity was obtained in shaking flasks after 6 days of cultivation (3400 U l−1, 4.2 % of total extracellular protein). GDH is a monomeric protein with an isoelectric point of 5.6. The molecular masses of the glycoforms ranged from 95 to 135 kDa, but after deglycosylation, a single 68 kDa band was obtained. The absorption spectrum is typical for an FAD-containing enzyme with maxima at 370 and 458 nm and the cofactor is non-covalently bound. The preferred substrates are glucose and xylose. Suitable electron acceptors are quinones, phenoxy radicals, 2,6-dichloroindophenol, ferricyanide and ferrocenium hexafluorophosphate. In contrast, oxygen turnover is very low. The GDH-encoding gene was cloned and phylogenetic analysis of the translated protein reveals its affiliation to the GMC family of oxidoreductases. The proposed function of this quinone and phenoxy radical reducing enzyme is to neutralize the action of plant laccase, phenoloxidase or peroxidase activities, which are increased in infected plants to evade fungal attack.
Identification of SagA as a novel vaccine target for the prevention of Enterococcus faecium infections
Authors: Kropec A. , Sava I. G. , Vonend C. , Sakinc T. , Grohmann E. , Huebner J.
Published: September 2011

Infections caused by multiresistant Gram-positive bacteria represent a major health burden in the community as well as in hospitalized patients. Enterococci, especially Enterococcus faecium, are well-known pathogens of hospitalized patients and are frequently linked with resistance against multiple antibiotics, which compromises effective therapy. Rabbit immune serum raised against heat-killed E. faecium E155, a HiRECC clone, was used in an opsonophagocytic assay, an inhibition assay and a mouse bacteraemia model to identify targets of opsonic and protective antibodies. Serum against whole heat-killed bacteria was opsonic and recognized a protein of about 72 kDa that was abundantly secreted. This protein, identified as SagA by LC-ES-MS/MS, was expressed in Escherichia coli and purified. Rabbit serum raised against the purified protein showed opsonic killing activity that was inhibited by almost 100 % using 100 µg purified protein ml−1. In a mouse bacteraemia model, a statistically significant reduction of the colony counts in blood was shown with immune rabbit serum compared with preimmune serum using the homologous and a heterologous vancomycin-resistant enterococci (VRE) strain. These results indicate that SagA could be used as a promising vaccine target to treat and/or prevent VRE bacteraemia.
Lipoproteins of Enterococcus faecalis: bioinformatic identification, expression analysis and relation to virulence
Authors: Reffuveille Fany , Leneveu Charlène , Chevalier Sylvie , Auffray Yanick , Rincé Alain
Published: September 2011

Enterococcus faecalisis a ubiquitous bacterium that is capable of surviving in a broad range of natural environments, including the human host, as either a natural commensal or an opportunistic pathogen involved in severe hospital-acquired infections. How such opportunistic pathogens cause fatal infections is largely unknown but it is likely that they are equipped with sophisticated systems to perceive external signals and interact with eukaryotic cells. Accordingly, being partially exposed at the cell exterior, some surface-associated proteins are involved in several steps of the infection process. Among them are lipoproteins, representing about 25 % of the surface-associated proteins, which could play a major role in bacterial virulence processes. This review focuses on the identification of 90 lipoprotein-encoding genes in the genome of theE. faecalisV583 clinical strain and their putative roles, and provides a transcriptional comparison of microarray data performed in environmental conditions including blood and urine. Taken together, these data suggest a potential involvement of lipoproteins inE. faecalisvirulence, making them serious candidates for vaccine production.
Time trends in fish populations in metropolitan France: insights from national monitoring data
Authors: Poulet N. , Beaulaton L. , Dembski S.
Published: September 2011

Using the electrofishing database of the French National Agency for Water and Aquatic Environment (Onema), the time trends of 48 freshwater fish taxa at 590 sites monitored for at least 8 years from 1990 to 2009 were investigated. The results demonstrated that species richness increased steadily from the beginning of the monitoring period. This is congruent with the finding that the number of species displaying a significant increase in spatial distribution or abundance was greater than those showing a significant decrease. Some species, however, had declined both in occurrence and abundance, e.g. tench Tinca tinca, common bream Abramis brama, brown trout Salmo trutta and European eel Anguilla anguilla. The species showing the most spectacular colonization were non‐native, e.g. topmouth gudgeon Pseudorasbora parva, wels catfish Silurus glanis and asp Aspius aspius. The time trends in population density were related to the maximal body size, habitat requirement, occurrence and abundance and the status (i.e. native or exotic) but not to the spawning temperature.
Impact of high‐risk classification by FISH: an Eastern Cooperative Oncology Group (ECOG) study E4A03
Authors: Jacobus Susanna J. , Kumar Shaji , Uno Hajime , Van Wier Scott A. , Ahmann Greg J. , Henderson Kimberly J. , Callander Natalie S. , Williams Michael E. , Siegel David S. , Greipp Philip R. , Rajkumar S. Vincent , Fonseca Rafael
Published: September 2011

Lenalidomide with dexamethasone is a standard induction treatment regimen for newly diagnosed myeloma (although a Federal Drug Administration indication is still absent). In the context of the Phase 3 clinical trial E4A03 (lenalidomide plus dexamethasone in low or high doses), we queried whether a fluorescence in situ hybridization (FISH)‐based genetic classification into high risk (HR) and standard risk (SR) multiple myeloma (MM) would remain clinically significant. Of 445 E4A03 patients, 126 had FISH analysis; 21 were classified HR with t(4;14), t(14;16), or 17p13 deletions. Median survival follow‐up approached 3 years. Patients with FISH data tended to be younger and healthier compared to the rest of the study population and, consequently, had superior overall survival (OS) results. Within the FISH cohort, shorter OS in the HR versus SR group (P = 0·004) corresponded to a hazard ratio of 3·48 [95% confidence interval: (1·42–8·53)], an effect also observed in multivariate analysis. Two‐year OS rates were 91% for SR MM and 76% for HR MM. There was also evidence of interaction between risk status and treatment (P = 0·026). HR patients were less likely to attain good partial response (SR 46% and HR 30%, Odds Ratio = 2·0 [0·7–5·6]), but overall response rates were not different. FISH‐based risk classification retained prognostic significance in patients receiving lenalidomide‐based induction.
A glycoengineered anti‐CD19 antibody with potent antibody‐dependent cellular cytotoxicity activity in vitro and lymphoma growth inhibition in vivo
Authors: Ward Elizabeth , Mittereder Nanette , Kuta Ellen , Sims Gary P. , Bowen Michael A. , Dall’Acqua William , Tedder Thomas , Kiener Peter , Coyle Anthony J. , Wu Herren , Jallal Bahija , Herbst Ronald
Published: September 2011

Human cluster of differentiation (CD) antigen 19 is a B cell‐specific surface antigen and an attractive target for therapeutic monoclonal antibody (mAb) approaches to treat malignancies of B cell origin. MEDI‐551 is an affinity‐optimized and afucosylated CD19 mAb with enhanced antibody‐dependent cellular cytotoxicity (ADCC). The results from in vitro ADCC assays with Natural Killer cells as effector cells, demonstrate that MEDI‐551 is effective at lower mAb doses than rituximab with multiple cell lines as well as primary chronic lymphocytic leukaemia and acute lymphoblastic leukaemia samples. Targeting CD19 with MEDI‐551 was also effective in several severe combined immunodeficiency lymphoma models. Furthermore, the combination of MEDI‐551 with rituximab resulted in prolonged suppression of tumour growth, demonstrating that therapeutic mAbs with overlapping effector function can be combined for greater tumour growth inhibition. Together, the data demonstrate that MEDI‐551 has potent antitumour activity in preclinical models of B cell malignancies. The results also suggest that the combination of the ADCC‐enhanced CD19 mAb with an anti‐CD20 mAb could be a novel approach for the treatment of B cell lymphomas.
The role of culture in theories of the intergenerational transmission of violence
Authors: Kim Kihyun
Published: September 2011

The intergenerational transmission of violence has been one of the most rigorously researched hypotheses in violence research in recent decades. A number of previous studies have provided evidence supporting this hypothesis, and there has been a growing body of literature investigating its mechanism. However, the role of culture in the intergenerational transmission of violence has not received much research attention, and thus, it remains largely unknown. To suggest a better theoretical basis for understanding the role of culture in the transmission mechanism, the present paper examines three critical theories that address the intergenerational phenomenon: Dodge's social information processing theory, Nisbett's cultural cognitive theory and Turiel's social‐cognitive domain theory. The paper provides a review of the basic assumptions and core concepts of each theory and identifies the potential contributions and gaps of each theory. The three theories present different accounts of the ontogenetic origins of ideas about violence and convey different portraits of the intergenerational mechanism. However, these theories also show that they are highly likely to be related to one another and that they can help close one another's gaps. This paper suggests that a unified framework that can merge the personal and cultural factors of causation is necessary to better capture the dynamic interplay among culture, experiences with violence and the actual enactment of violent behaviours.
Justification of 150 mg clopidogrel in patients with high on‐clopidogrel platelet reactivity
Authors: Aradi Dániel , Rideg Orsolya , Vorobcsuk András , Magyarlaki Tamás , Magyari Balázs , Kónyi Attila , Pintér Tünde , Horváth Iván G. , Komócsi András
Published: September 2011

Eur J Clin Invest 2012; 42 (4): 384–392

Background  The GRAVITAS trial showed that 150 mg clopidogrel did not improve outcome in patients with high on‐clopidogrel platelet reactivity (HPR) screened by the VerifyNow assay. We aimed to determine the impact of 150 mg clopidogrel in stable angina patients with HPR identified with conventional aggregometry (LTA).

Materials and methods  Clopidogrel‐naive stable angina patients before ad hoc percutaneous coronary intervention were recruited into a randomized, double‐blind, placebo‐controlled trial (NCT00638326). Twelve to 24 h after the 600‐mg loading dose of clopidogrel, ADP5μM‐stimulated maximal (AGGmax), late platelet aggregation (AGGlate) and vasodilator‐stimulated phosphoprotein phosphorylation (VASP‐PRI) were evaluated. Patients with HPR (AGGmax ≥ 34%) were randomly allocated to 75 or 150 mg clopidogrel after 4 weeks. After control platelet function measurements at day 28, 75 mg clopidogrel was administered to all patients until 1 year.

Results  The study was prematurely terminated at the stage of 200 enroled patients. Administration of 150 mg clopidogrel significantly reduced platelet aggregation (AGGmax: 45·0 ± 6·8 vs. 33·8 ± 15·1, P < 0·01; AGGlate: 27·1 ± 14·7 vs. 13·8 ± 18·0, P < 0·01) and VASP‐PRI (57·5 ± 15·2 vs. 37·2 ± 17·1; P < 0·01), while platelet reactivity remained unchanged in patients with HPR receiving 75 mg clopidogrel. The higher maintenance dose of clopidogrel was associated with a significant reduction in cardiovascular (CV) death and myocardial infarction (MI) (0% vs. 11·4%, P = 0·04) and in CV death, MI or target vessel revascularization (24·6% vs. 3·1%; P = 0·01) during 1 year.

Conclusions  One‐month administration of 150 mg maintenance dose of clopidogrel reduces platelet reactivity and might decrease the risk of thrombo‐ischaemic complications in stable angina patients with HPR identified by LTA.
Effect of a Bacterial Lipopolysaccharide Treatment on Rabbit Testis and Ejaculated Sperm
Authors: Collodel G , Castellini C , del Vecchio MT , Cardinali R , Geminiani M , Rossi B , Spreafico A , Moretti E
Published: September 2011

Contents

In a previous study, we reported the short‐ and long‐term effects of bacterial lipopolysaccharide (LPS)‐induced inflammation on rabbit sperm quality. This study was aimed at exploring the spermatogenesis of the rabbit model focussing on the possible damages occurring to the testis and ejaculated sperm. Twenty New Zealand White rabbit bucks were divided into two groups. One group was inoculated intra‐peritoneally with LPS, the other group, considered as control, was treated under the same conditions with saline only. Semen samples were collected before LPS injection, the 7th, 14th, 21st, 30th, 45th, 60th and 90th day after LPS treatment. Semen parameters were evaluated following international guidelines. The kinetic characteristics of ejaculated sperm were analysed using a computer‐assisted sperm analyzer and the ultrastructural characteristics were explored by transmission electron microscopy (TEM). On the 7th, 14th and 30th day, testis from treated rabbits and controls were obtained. Testis samples were analysed by light microscopy and TEM. The induced LPS lesions in the testis became evident the 7th day after treatment, with a decrease in germinal cells and with an increase in structurally altered Sertoli cells; normal spermatogenesis was restored on the 30th day. The testicular damages observed on day 7 were probably responsible for the reduction in sperm concentration and motility and the ultrastructural alterations that were detected in the ejaculated sperm on the 14th through the 30th days after treatment. In conclusion, rabbit buck treated with LPS could be a useful model for studying the effect of an induced systemic inflammation on spermatogenesis.
Challenging Ronald: McDonald versus McDonald's
Authors: McDonald David
Published: September 2011

Obesity is the most prevalent health condition affecting first world children in 2011. This article recounts a campaign that opposed the construction of a fast food outlet in close proximity to a large school complex. The epidemiologic evidence that there is a negative health impact on children that attend schools close to fast food outlets is reiterated. There is an urgent need for planning laws to be modernised to reflect that evidence.
Host preference of a temperate mistletoe: Disproportional infection on three co‐occurring host species influenced by differential success
Authors: LEMAITRE ANDREA B. , TRONCOSO ALEJANDRA J. , NIEMEYER HERMANN M.
Published: September 2011

The mistletoe Tristerix verticillatus (Loranthaceae) parasitizes within a small area of the Yerba Loca Nature Sanctuary near Santiago, Chile, three co‐occurring hosts: Schinus montanus (Anacardiaceae), Fabiana imbricata (Solanaceae) and Berberis montana (Berberidaceae). Previous studies suggest that T. verticillatus may be favoured when parasitizing S. montanus relative to the other two host species. We hypothesize that infection of S. montanus is not proportional to its local abundance or appearance, that S. montanus is more intensively parasitized than other available hosts, and that host provenance is a determinant of the fate of the infecting seed. We compare the incidence of infection of T. verticillatus in relation to local availability and appearance variables, and the intensity of infection of T. verticillatus, on the three co‐occurring host species. We then test the effects of host provenance on mistletoe seed establishment success with a seed cross inoculation experiment varying the donor and receptor hosts. Finally, we test whether there are differences in establishment success between manually processed seeds and seeds defecated by the avian disperser Mimus thenca (Passeriformes: Mimidae). Our results show that the three hosts have an aggregated spatial distribution. Schinus montanus was parasitized at a higher rate than expected by its local availability and appearance, and inoculated seeds showed differential development depending on the origin of the seeds: seeds from T. verticillatus parasitizing S. montanus inoculated to S. montanus twigs showed higher germination and lower mortality than seeds from T. verticillatus parasitizing F. imbricata inoculated to S. montanus twigs. Furthermore, seeds defecated by the avian disperser, M. thenca, had higher adherence and reduced mortality when compared to manually processed seeds. The disproportional host infection found is discussed in terms of the differential establishment of mistletoe seeds, morphological characteristics of hosts and the behaviour of dispersing birds.
Engaging reluctant adolescents in family therapy: an exploratory study of in‐session processes of change
Authors: Higham Jane E. , Friedlander Myrna L. , Escudero Valentín , Diamond Gary
Published: September 2011

Informed by a trans‐theoretical model of the therapeutic alliance in conjoint family therapy, this exploratory study was the initial stage in a task analysis of critical shifts in adolescent engagement. Specifically, we compared sessions in which a resistant adolescent either did or did not shift from negative to positive engagement during the session. Two successful and two unsuccessful change events were selected from an archival data set based on SOFTA ratings of the therapeutic alliance. The results suggested that one parent element (support) and five therapist elements (structuring therapeutic conversations, fostering autonomy, building systemic awareness, rolling with resistance and understanding the adolescent's subjective experience) seemed critical for successfully facilitating adolescent engagement. The qualitative results were informed by the adolescent's self‐reported target complaints pretreatment, which suggested varying reasons for the teenagers’ active or passive disengagement. Implications for practice and recommendations for future research are offered to continue this line of inquiry.
In planta production of the highly potent resveratrol analogue pterostilbene via stilbene synthase and O‐methyltransferase co‐expression
Authors: Rimando Agnes M. , Pan Zhiqiang , Polashock James J. , Dayan Franck E. , Mizuno Cassia S. , Snook Maurice E. , Liu Chang‐Jun , Baerson Scott R.
Published: September 2011

Resveratrol and related stilbenes are thought to play important roles in defence responses in several plant species and have also generated considerable interest as nutraceuticals owing to their diverse health‐promoting properties. Pterostilbene, a 3,5‐dimethylether derivative of resveratrol, possesses properties similar to its parent compound and, additionally, exhibits significantly higher fungicidal activity in vitro and superior pharmacokinetic properties in vivo. Recombinant enzyme studies carried out using a previously characterized O‐methyltransferase sequence from Sorghum bicolor (SbOMT3) demonstrated its ability to catalyse the A ring‐specific 3,5‐bis‐O‐methylation of resveratrol, yielding pterostilbene. A binary vector was constructed for the constitutive co‐expression of SbOMT3 with a stilbene synthase sequence from peanut (AhSTS3) and used for the generation of stably transformed tobacco and Arabidopsis plants, resulting in the accumulation of pterostilbene in both species. A reduced floral pigmentation phenotype observed in multiple tobacco transformants was further investigated by reversed‐phase HPLC analysis, revealing substantial decreases in both dihydroquercetin‐derived flavonoids and phenylpropanoid‐conjugated polyamines in pterostilbene‐producing SbOMT3/AhSTS3 events. These results demonstrate the potential utility of this strategy for the generation of pterostilbene‐producing crops and also underscore the need for the development of additional approaches for minimizing concomitant reductions in key phenylpropanoid‐derived metabolites.
Money on the road to empire: Japan's adoption of gold monometallism, 1873–971
Authors: SCHILTZ MICHAEL
Published: September 2011

In the macro‐economic literature, Japan has at several times been treated as a canonical example of why countries joined the gold standard. On the one hand, the country has been linked to the argument that there exists a relationship between the gold standard and lowered borrowing costs; on the other hand, it has been discussed as motivated by a desire to expand its trade with gold standard countries. This article argues against both strands in the literature, and argues for a third interpretation. It demonstrates that the specificities of Japan's gold standard reveal a concern with ‘original sin’, or the impossibility of raising foreign loans in Japan's own currency, and explains that there were grave costs to gold standard adoption.
Fiscal policies and the institution of a tax state in Anglo‐Saxon England within a comparative context1
Authors: WAREHAM ANDREW
Published: September 2011

This article begins by noting that military revolutions and civil wars in early modern Europe provide an unduly narrow framework for understanding the transition from a domain to a tax state. Taking Anglo‐Saxon England as a case study, it is suggested that political restrictions led to the establishment of direct and indirect taxation, thereby providing rulers with revenues which surpassed those from domain resources. The main section of the article uses sources from coinage and wills to poetry and letters in order to give a general idea of the chronological development of a medieval tax state. This analysis challenges the views of the new fiscal historians, who argue that a collapse in a medieval domain state acts as the precondition for the emergence of a tax state. Instead, this article suggests that new policies arose because of the need of Anglo‐Saxon kings and their advisers to take account of the requirements of ecclesiastical authorities, as well as a heavy revenue imperative, in paying for resistance against the Vikings. The article ends with a discussion of the comparative applications of the contexts and catalysts which lead to the adoption of pioneering fiscal policies.