bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphatome profiling reveals PTPN2, PTPRJ and PTEN as potent negative regulators of PKB/Akt activation in Ras-mutated cancer cells
Authors: Omerovic Jasminka , Clague Michael J. , Prior Ian A. 
Published: November 2009

Oncogenic Ras mutations render the protein constitutively active and promote tumorigenesis via chronic stimulation of effector pathways. In A549 lung adenocarcinoma approx. 50% of the total Ras population is constitutively active, yet these cells display only weak activation of the effectors: ERK1/2 (extracellular-signal-regulated kinase 1/2) and Akt. In order to identify key negative regulators of oncogenic Ras signalling we performed a phosphatome RNAi (RNA interference) screen in A549 cells and ranked their effects on phosphorylation of Ser473 of Akt. As expected, the tumour suppressor PTEN (phosphatase and tensin homologue deleted on chromosome 10) emerged as a leading hit: knockdown elevated Akt activation to 70% of maximal generated by acute EGF (epidermal growth factor) stimulation. Importantly, we identified other phosphatases with similar potencies including PTPN2 (T-cell protein tyrosine phosphatase; also known as TC-PTP) and PTPRJ (protein tyrosine phosphatase receptor type J; also known as DEP-1/CD148). Potentiation of Akt phosphorylation by knockdown of PTEN or PTPRJ was contingent on the presence of oncogenic K-Ras. Our data reveal a synergy between oncogene function and the loss of a tumour suppressor within the same pathway that was necessary for full effector activation since each alone failed to elicit significant Akt phosphorylation. Taken together, these data reveal potent regulators of Akt signalling which contribute to ameliorating the consequences of oncogenic K-Ras activity.
Pathogenic mechanisms of myotonic dystrophy
Authors: Lee Johanna E. , Cooper Thomas A. 
Published: November 2009

DM (myotonic dystrophy) is a dominantly inherited genetic disorder that is the most common cause of muscular dystrophy in adults affecting 1 in 8500 individuals worldwide. Different microsatellite expansions in two loci cause different forms of the disease that share similar features: DM1 (DM type 1) is caused by a tri- (CTG) nucleotide expansion within the DMPK (dystrophia myotonica protein kinase) 3′-untranslated region and DM2 (DM type 2) is caused by a tetra- (CCTG) nucleotide expansion within intron 1 of the ZNF9 (zinc finger 9) gene. The pathogenic mechanism of this disease involves the RNA transcribed from the expanded allele containing long tracts of (CUG)n or (CCUG)n. The RNA results in a toxic effect through two RNA-binding proteins: MBNL1 (muscleblind-like 1) and CUGBP1 (CUG-binding protein 1). In DM1, MBNL1 is sequestered on CUG repeat-containing RNA resulting in its loss-of-function, while CUGBP1 is up-regulated through a signalling pathway. The downstream effects include disrupted regulation of alternative splicing, mRNA translation and mRNA stability, which contribute to the multiple features of DM1. This review will focus on the RNA gain-of-function disease mechanism, the important roles of MBNL1 and CUGBP1 in DM1, and the relevance to other RNA dominant disorders.
eEF1A2 and neuronal degeneration
Authors: Abbott Catherine M. , Newbery Helen J. , Squires Charlotte E. , Brownstein David , Griffiths Lowri A. , Soares Dinesh C. 
Published: November 2009

Translation elongation factor eEF1A (eukaryotic elongation factor 1A) exists as two individually encoded variants in mammals, which are 98% similar and 92% identical at the amino acid level. One variant, eEF1A1, is almost ubiquitously expressed, the other variant, eEF1A2, shows a very restricted pattern of expression. A spontaneous mutation was described in 1972, which gives rise to the wasted phenotype: homozygous wst/wst mice develop normally until shortly after weaning, but then lose muscle bulk, acquire tremors and gait abnormalities and die by 4 weeks. This mutation has been shown to be a deletion of 15 kb that removes the promoter and first exon of the gene encoding eEF1A2. The reciprocal pattern of expression of eEF1A1 and eEF1A2 in muscle fits well with the timing of onset of the phenotype of wasted mice: eEF1A1 declines after birth until it is undetectable by 3 weeks, whereas eEF1A2 expression increases over this time. No other gene is present in the wasted deletion, and transgenic studies have shown that the phenotype is due to loss of eEF1A2. We have shown that eEF1A2, but not eEF1A1, is also expressed at high levels in motor neurons in the spinal cord. Wasted mice develop many pathological features of motor neuron degeneration and may represent a good model for early onset of motor neuron disease. Molecular modelling of the eEF1A1 and eEF1A2 protein structures highlights differences between the two variants that may be critical for functional differences. Interactions between eEF1A2 and ZPR1 (zinc-finger protein 1), which interacts with the SMN (survival motor neuron) protein, may be important in motor neuron biology.
Use of concatamers to study GABAA receptor architecture and function: application to δ-subunit-containing receptors and possible pitfalls
Authors: Sigel Erwin , Kaur Kuldeep H. , Lüscher Benjamin P. , Baur Roland 
Published: November 2009

Many membrane proteins, including the GABAA [GABA (γ-aminobutyric acid) type A] receptors, are oligomers often built from different subunits. As an example, the major adult isoform of the GABAA receptor is a pentamer built from three different subunits. Theoretically, co-expression of three subunits may result in many different receptor pentamers. Subunit concatenation allows us to pre-define the relative arrangement of the subunits. This method may thus be used to study receptor architecture, but also the nature of binding sites. Indeed, it made possible the discovery of a novel benzodiazepine site. We use here subunit concatenation to study δ-subunit-containing GABAA receptors. We provide evidence for the formation of different functional subunit arrangements in recombinant α1β3δ and α6β3δ receptors. As with all valuable techniques, subunit concatenation has also some pitfalls. Most of these can be avoided by carefully titrating and minimizing the length of the linker sequences joining the two linked subunits and avoiding inclusion of the signal sequence of all but the N-terminal subunit of a multi-subunit construct. Maybe the most common error found in the literature is that low expression can be overcome by simply overloading the expression system with genetic information. As some concatenated constructs result by themselves in a low level of expression, this erroneous assembly leading to receptor function may be promoted by overloading the expression system and leads to wrong conclusions.
Positive allosteric activation of GABAA receptors bi-directionally modulates hippocampal glutamate plasticity and behaviour
Authors: Shen Guofu , Mohamed Mahmoud S. , Das Paromita , Tietz Elizabeth I. 
Published: November 2009

Long-term BZ (benzodiazepine) anxiolytic therapy increases the risk of physical dependence manifested as withdrawal anxiety. BZ-induced potentiation of GABAAR (γ-aminobutyric acid type-A receptor) function by 1-week oral administration of FZP (flurazepam) bi-directionally modulates excitatory glutamatergic synaptic transmission in hippocampal CA1 neurons during drug withdrawal. Previous electrophysiological studies on acutely isolated and intact CA1 neurons, as well as immunofluorescence and post-embedding immunogold electron microscopy studies, suggest increased synaptic insertion of GluR (glutamate receptor) 2-lacking AMPARs (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors) in 2-day FZP-withdrawn rats. Preliminary studies indicated a similar increase in GluR1, then phospho-Ser831-GluR1, as well as CaMKIIα (Ca2+/calmodulin-dependent protein kinase IIα), but not phospho-Thr286-CaMKII levels at the same time point. In our studies, whole-cell recordings in hippocampal slices revealed that AMPAR mEPSC [miniature EPSC (excitatory postsynaptic current)] amplitude was increased in 1-day FZP-withdrawn rats followed by an increase in estimated single-channel conductance in 2-day-FZP-withdrawn rats. Enhanced conductance was no longer observed in slices pre-incubated for 2 h in the CaMKII inhibitor KN-93, but not the inactive analogue KN-92. To evaluate whether CaMKII-mediated AMPA potentiation could occlude LTP (long-term potentiation), LTP was induced by TBS (theta burst stimulation) and recorded using whole-cell and extracellular techniques. LTP was induced in both groups, but only maintained for &lt;15 min in 2-day FZP-withdrawn rats. LTP was fully restored after 7-day withdrawal. Despite the lack of LTP maintenance, impairment of object recognition, place and context was not observed in 2-day-FZP-withdrawn rats. Since L-VGCC (L-type voltage-gated calcium channel) current density was doubled on drug withdrawal and up to 2 days, Ca2+ entry through L-VGCCs and perhaps subsequently through Ca2+-permeable AMPARs are proposed to be responsible for enhanced CaMKIIα levels and AMPAR potentiation. Mechanisms associated with several different models of activity-dependent plasticity may underlie BZ physical dependence.
RNA editing and its impact on GABAA receptor function
Authors: Daniel Chammiran , Öhman Marie 
Published: November 2009

A-to-I (adenosine-to-inosine) RNA editing catalysed by the ADARs (adenosine deaminases that act on RNA) is a post-transcriptional event that contributes to protein diversity in metazoans. In mammalian neuronal ion channels, editing alters functionally important amino acids and creates receptor subtypes important for the development of the nervous system. The excitatory AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) and kainate glutamate receptors, as well as the inhibitory GABAA [GABA (γ-aminobutyric acid) type A] receptor, are subject to A-to-I RNA editing. Editing affects several features of the receptors, including kinetics, subunit assembly and cell-surface expression. Here, we discuss the regulation of editing during brain maturation and the impact of RNA editing on the expression of different receptor subtypes.
GABRB2 in schizophrenia and bipolar disorder: disease association, gene expression and clinical correlations
Authors: Chen Jianhuan , Tsang Shui-Ying , Zhao Cun-You , Pun Frank W. , Yu Zhiliang , Mei Lingling , Lo Wing-Sze , Fang Shisong , Liu Hua , Stöber Gerald , Xue Hong 
Published: November 2009

The SCZ (schizophrenia)-associated GABAA receptor (γ-aminobutyric acid type A receptor) β2 subunit gene GABRB2 was recently associated with BPD (bipolar disorder). Although weaker than its association with SCZ, significant association of GABRB2 with BPD was found in both German and Chinese, especially for the haplotypes rs1816071–rs187269 and rs1816072–rs187269 for which the M–M variants showed higher frequency in disease than the control. Significant genotype-dependent reduction in GABRB2 expression was shown for BPD, but to a lesser extent than that for SCZ. Temporal effects on GABRB2 expression were observed. Moreover, for the homozygous major genotypes of rs1816071, rs1816072 and rs187269, expression increased with time in CON but decreased in SCZ and BPD. The genotypes of these three SNPs (single nucleotide polymorphisms) were further correlated with antipsychotics dosage in SCZ cohorts. The findings highlight the importance of GABRB2 in neuropsychiatric disease aetiology, with respect to haplotype association, as well as reduction of and temporal effects on gene expression in both SCZ and BPD, but to a lesser extent in the latter, supporting the suggestion that functional psychosis can be conceptualized as a continuous spectrum of clinical phenotypes rather than as distinct categories.
Nonvolatile memory with Co–SiO2 core-shell nanocrystals as charge storage nodes in floating gate
Authors: Liu Hai , Ferrer Domingo A. , Ferdousi Fahmida , Banerjee Sanjay K. 
Published: November 2009

In this letter, we reported nanocrystal floating gate memory with Co–SiO2 core-shell nanocrystal charge storage nodes. By using a water-in-oil microemulsion scheme, Co–SiO2 core-shell nanocrystals were synthesized and closely packed to achieve high density matrix in the floating gate without aggregation. The insulator shell also can help to increase the thermal stability of the nanocrystal metal core during the fabrication process to improve memory performance.
At the request of the authors, this article is being retracted effective 1 July 2010.
Exploring the Influence of the VERB™ Brand Using a Brand Equity Framework
Authors: Price Simani M. , Potter Lance D. , Das Barnali , Wang Yu-Chung L. , Huhman Marian 
Published: November 2009

The Centers for Disease Control and Prevention's Youth Media Campaign designed VERB™ as an aspirational brand to increase physical activity among children aged 9–13 years. In the current study, we explore the influence of the VERB™ brand in the campaign using a brand equity framework. Brand equity responses were collected from 1,007 children from a national cross-sectional telephone survey. Findings indicated that high VERB brand equity was associated with increased positive attitudes toward physical activity and participation in free-time physical activity. The relationship between brand equity and free-time physical activity was partially mediated through attitudes. Brand personality and leadership/popularity constructs were found to be strong predictors in determining physical activity attitudes and behaviors, respectively. As the use of a branding strategy increases in public health, brand equity offers social marketers a framework for evaluating the effectiveness of their efforts. The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Positive Deviance A New Strategy for Improving Hand Hygiene Compliance
Authors: Marra Alexandre R. , Guastelli Luciana Reis , de Araújo Carla Manuela Pereira , dos Santos Jorge L. Saraiva , Lamblet Luiz Carlos R. , Silva Moacyr , de Lima Gisele , Cal Ruy Guilherme Rodrigues , Paes Ângela Tavares , Neto Miguel Cendoroglo , Barbosa Luciana , Edmond Michael B. , dos Santos Oscar Fernando Pavão 
Published: November 2009

Objective.To evaluate the effectiveness of a positive deviance strategy for the improvement of hand hygiene compliance in 2 adult step-down units.Design.A 9-month, controlled trial comparing the effect of positive deviance on compliance with hand hygiene.Setting.Two 20-bed step-down units at a tertiary care private hospital.Methods.The first phase of our study was a 3-month baseline period (from April to June 2008) in which hand hygiene episodes were counted by use of electronic handwashing counters. From July to September 2008 (ie, the second phase), a positive deviance strategy was implemented in the east unit; the west unit was the control unit. During the period from October to December 2008 (ie, the third phase), positive deviance was applied in both units.Results.During the first phase, there was no statistically significant difference between the 2 step-down units in the number of episodes of hand hygiene per 1,000 patient-days or in the incidence density of healthcare-associated infections (HAIs) per 1,000 patient-days. During the second phase, there were 62,000 hand hygiene episodes per 1,000 patient-days in the east unit and 33,570 hand hygiene episodes per 1,000 patient-days in the west unit (P < .01). The incidence density of HAIs per 1,000 patient-days was 6.5 in the east unit and 12.7 in the west unit (P = .04). During the third phase, there was no statistically significant difference in hand hygiene episodes per 1,000 patient-days (P = .16) or in incidence density of HAIs per 1,000 patient-days.Conclusion.A positive deviance strategy yielded a significant improvement in hand hygiene, which was associated with a decrease in the overall incidence of HAIs.
Fraught Relations in the Letters of Laura Cereta: Marriage, Friendship, and Humanist Epistolarity*
Authors: McCue Gill Amyrose 
Published: November 2009

AbstractLaura Cereta is unique among Quattrocento female humanists in directly addressing the position of women as wives and as friends in her substantial corpus of erudite Latin epistolary prose. Questioning the ideals that governed intellectual, social, and personal expectations of matrimony, Cereta's letters reflect her self-consciously double status as humanist and spouse. Her fierce critique of marriage as a site of female oppression and complicity implies an alternative that requires of humanists, husbands, and wives a radical rethinking of marriage in terms of friendship, as well as of the very project of humanist epistolarity.
In the Name of the Father: ConceptualizingPater Familiasin the Letters of William the Silent's Children*
Authors: Broomhall Susan , Van Gent Jacqueline 
Published: November 2009

AbstractFor much of their childhood and adult life, the twelve surviving children of William the Silent were separated linguistically and geographically. Many of the children forged important relationships with male primary carers who were not their biological parents. This paper explores the children's correspondence with their biological father William and with paternal figures to understand competing forms of familial authority among William's children. This paper places particular interest on analysis of the gendered negotiation of paternal bonds in the letters of William's sons and daughters, as they established multiple relationships with father figures during their childhood.
The Memory of Ruins: Quevedo'sSilvato “Roma antigua y moderna”
Authors: Casal Rodrigo Cacho 
Published: November 2009

AbstractThesilvato “Roma antigua y moderna” by Francisco de Quevedo is a complex rewriting of Joachim Du Bellay'sAntiquitez de Rome. The Spanish author makes an archeological study of his model, identifying the sources, and, through intertextual dialogue with the classical and humanistic descriptions of Rome, creates a symbolic space of memory where different stages of history are represented. In this manner, Quevedo produces a Baroque reading of the Renaissance.
Dusty plasma ring model
Authors: Sheridan T E 
Published: November 2009

A model of a dusty plasma (Yukawa) ring is presented. We consider n identical particles confined in a two-dimensional (2D) annular potential well and interacting through a Debye (i.e. Yukawa or screened Coulomb) potential. Equilibrium configurations are computed versus n, the Debye shielding parameter and the trap radius. When the particle separation exceeds a critical value the particles form a 1D chain with a ring topology. Below the critical separation the zigzag instability gives a 2D configuration. Computed critical separations are shown to agree well with a theoretical prediction for the zigzag threshold. Normal mode spectra for 1D rings are computed and found to be in excellent agreement with the longitudinal and transverse dispersion relations for unbounded straight chains. When the longitudinal and transverse dispersion relations intersect we observe a resonance due to the finite curvature of the ring.
VIBE 2.0: Visual Integration for Bayesian Evaluation
Authors: Beagley Nathaniel , Stratton Kelly G. , Webb-Robertson Bobbie-Jo M. 
Published: November 2009

Abstract
Summary: Data fusion methods are powerful tools for evaluating experiments designed to discover measurable features of directly unobservable systems. We describe an interactive software platform, Visual Integration for Bayesian Evaluation, that ingests or creates Bayesian posterior probability matrices, performs data fusion and allows the user to interactively evaluate the classification power of fusing various combinations of data sources, such as transcriptomic, proteomics, metabolomics, biochemistry and function.
Availability: http://omics.pnl.gov/software/VIBE.php
Contact: bj@pnl.gov
Supplementary information: Supplementary data are available at Bioinformatics online.
Pathway analysis using random forests with bivariate node-split for survival outcomes
Authors: Pang Herbert , Datta Debayan , Zhao Hongyu 
Published: November 2009

Abstract
Motivation: There is great interest in pathway-based methods for genomics data analysis in the research community. Although machine learning methods, such as random forests, have been developed to correlate survival outcomes with a set of genes, no study has assessed the abilities of these methods in incorporating pathway information for analyzing microarray data. In general, genes that are identified without incorporating biological knowledge are more difficult to interpret. Correlating pathway-based gene expression with survival outcomes may lead to biologically more meaningful prognosis biomarkers. Thus, a comprehensive study on how these methods perform in a pathway-based setting is warranted.
Results: In this article, we describe a pathway-based method using random forests to correlate gene expression data with survival outcomes and introduce a novel bivariate node-splitting random survival forests. The proposed method allows researchers to identify important pathways for predicting patient prognosis and time to disease progression, and discover important genes within those pathways. We compared different implementations of random forests with different split criteria and found that bivariate node-splitting random survival forests with log-rank test is among the best. We also performed simulation studies that showed random forests outperforms several other machine learning algorithms and has comparable results with a newly developed component-wise Cox boosting model. Thus, pathway-based survival analysis using machine learning tools represents a promising approach in dissecting pathways and for generating new biological hypothesis from microarray studies.
Availability: R package Pwayrfsurvival is available from URL: http://www.duke.edu/∼hp44/pwayrfsurvival.htm
Contact: pathwayrf@gmail.com
Supplementary information: Supplementary data are available at Bioinformatics online.
Annotation and merging of SBML models with semanticSBML
Authors: Krause Falko , Uhlendorf Jannis , Lubitz Timo , Schulz Marvin , Klipp Edda , Liebermeister Wolfram 
Published: November 2009

Abstract
Summary: Systems Biology Markup Language (SBML) is the leading exchange format for mathematical models in Systems Biology. Semantic annotations link model elements with external knowledge via unique database identifiers and ontology terms, enabling software to check and process models by their biochemical meaning. Such information is essential for model merging, one of the key steps towards the construction of large kinetic models. SemanticSBML is a tool that helps users to check and edit MIRIAM annotations and SBO terms in SBML models. Using a large collection of biochemical names and database identifiers, it supports modellers in finding the right annotations and in merging existing models. Initially, an element matching is derived from the MIRIAM annotations and conflicting element attributes are categorized and highlighted. Conflicts can then be resolved automatically or manually, allowing the user to control the merging process in detail.
Availability: SemanticSBML comes as a free software written in Python and released under the GPL 3. A Debian package, a source package for other Linux distributions, a Windows installer and an online version of semanticSBML with limited functionality are available at http://www.semanticsbml.org. A preinstalled version can be found on the Linux live DVD SB.OS, available at http://www.sbos.eu.
Contact: wolfram.liebermeister@biologie.hu-berlin.de
Supplementary information: Supplementary data are available at Bioinformatics online.