bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of Antibiotic Tolerance in Sod-Deficient Mutants Is Dependent on the Energy Source and Arginine Catabolism in Enterococci
Authors: Ladjouzi Rabia , Bizzini Alain , van Schaik Willem , Zhang Xinglin , Rincé Alain , Benachour Abdellah , Hartke Axel 
Published: August 2015

ABSTRACT

Enterococci are naturally tolerant to typically bactericidal cell wall-active antibiotics, meaning that their growth is inhibited but they are not killed even when exposed to a high concentration of the drug. The molecular reasons for this extraordinary tolerance are still incompletely understood. Previous work showed that resistance to killing collapsed specifically in mutants affected in superoxide dismutase (Sod) activity, arguing that bactericidal antibiotic treatment led to induction of a superoxide burst. In the present work, we show that loss of antibiotic tolerance in Δ
sodA
mutants of pathogenic enterococci is dependent on the energy source present during antibiotic treatment. Hexoses induce greater killing than the pentose ribose, and no killing was observed with glycerol as the energy source. These results point to glycolytic reactions as crucial for antibiotic-mediated killing of Δ
sodA
mutants. A transposon mutant library was constructed in
Enterococcus faecalis ΔsodA
mutants and screened for restored tolerance of vancomycin. Partially restored tolerance was observed in mutants with transposon integrations into intergenic regions upstream of regulators implicated in arginine catabolism. In these mutants, the arginine deiminase operon was highly upregulated. A model for the action of cell wall-active antibiotics in tolerant and nontolerant bacteria is proposed.

IMPORTANCE
Antibiotic tolerance is a serious clinical concern, since tolerant bacteria have considerably increased abilities to resist killing by bactericidal drugs. Using enterococci as models for highly antibiotic-tolerant pathogens, we showed that tolerance of these bacteria is linked to their superoxide dismutase (Sod), arguing that bactericidal antibiotics induce generation of reactive oxygen species inside cells. Wild-type strains are tolerant because they detoxify these deleterious molecules by the activity of Sod, whereas Sod-deficient strains are killed. This study showed that killing depends on the energy source present during treatment and that an increase in arginine catabolism partially restored tolerance of the Sod mutants. These results are used to propose a mode-of-action model of cell wall-active antibiotics in tolerant and nontolerant bacteria.
Cross Talk Inhibition Nullified by a Receiver Domain Missense Substitution
Authors: Huynh TuAnh Ngoc , Lin Hsia-Yin , Noriega Chris E. , Lin Alice V. , Stewart Valley 
Published: August 2015

ABSTRACT

In two-component signal transduction, a sensor protein transmitter module controls cognate receiver domain phosphorylation. Most receiver domain sequences contain a small residue (Gly or Ala) at position T + 1 just distal to the essential Thr or Ser residue that forms part of the active site. However, some members of the NarL receiver subfamily have a large hydrophobic residue at position T + 1. Our laboratory previously isolated a NarL mutant in which the T + 1 residue Val-88 was replaced with an orthodox small Ala. This NarL V88A mutant confers a striking phenotype in which high-level target operon expression is both signal (nitrate) and sensor (NarX and NarQ) independent. This suggests that the NarL V88A protein is phosphorylated by cross talk from noncognate sources. Although cross talk was enhanced in
ackA
null strains that accumulate acetyl phosphate, it persisted in
pta ackA
double null strains that cannot synthesize this compound and was observed also in
narL
+
strains. This indicates that acetate metabolism has complex roles in mediating NarL cross talk. Contrariwise, cross talk was sharply diminished in an
arcB barA
double null strain, suggesting that the encoded sensors contribute substantially to NarL V88A cross talk. Separately, the V88A substitution altered the
in vitro
rates of NarL autodephosphorylation and transmitter-stimulated dephosphorylation and decreased affinity for the cognate sensor, NarX. Together, these experiments show that the residue at position T + 1 can strongly influence two distinct aspects of receiver domain function, the autodephosphorylation rate and cross talk inhibition.

IMPORTANCE
Many bacterial species contain a dozen or more discrete sensor-response regulator two-component systems that convert a specific input into a distinct output pattern. Cross talk, the unwanted transfer of signals between circuits, occurs when a response regulator is phosphorylated inappropriately from a noncognate source. Cross talk is inhibited in part by the high interaction specificity between cognate sensor-response regulator pairs. This study shows that a relatively subtle missense change from Val to Ala nullifies cross talk inhibition, enabling at least two noncognate sensors to enforce an inappropriate output independently of the relevant input.
Behavioural physical activity interventions in participants with lower-limb osteoarthritis: a systematic review with meta-analysis
Authors: Williamson Wilby , Kluzek Stefan , Roberts Nia , Richards Justin , Arden Nigel , Leeson Paul , Newton Julia , Foster Charlie 
Published: August 2015

ObjectiveTo assess effectiveness of osteoarthritis interventions to promote long-term physical activity behaviour change.DesignA systematic review and meta-analysis. Protocol registration PROSPERO CRD4201300444 5 (http://www.crd.york.ac.uk/prospero/).Study selectionRandomised controlled trials (RCTs) comparing physical activity interventions with placebo, no/or minimal intervention in community-dwelling adults with symptomatic knee or hip osteoarthritis. Primary outcomes were change in physical activity or cardiopulmonary fitness after a minimum follow-up of 6 months.Data extractionOutcomes were measures of physical activity (self-reported and objectively measured) and cardiovascular fitness. Standard mean differences between postintervention values were used to describe the effect sizes.Results27 984 titles were screened and 180 papers reviewed in full. Eleven RCTs satisfied inclusion criteria, total study population of 2741 participants, mean age 62.2. The commonest reasons for study exclusion were follow-up less than 6 months and no physical activity measures. The majority of included interventions implement an arthritis self-management programme targeting coping skills and self-efficacy. Seven studies used self-report measures, the pooled effect of these studies was small with significant heterogeneity between studies (SMD 0.22 with 95% CI −0.11 to 0.56, z=1.30 (p=0.19) I2statistic of 85%). Subgroup analysis of 6–12 month outcome reduced heterogeneity and increased intervention effect compared to control (SMD 0.53, 95% CI 0.41 to 0.65, z=8.84 (p<0.00001) I2of 66%).ConclusionsArthritis self-management programmes achieve a small but significant improvement in physical activity in the short term. Effectiveness of intervention declines with extended follow-up beyond 12 months with no significant benefit compared to control. The small number of studies (11 RCTs) limited ability to define effective delivery methods. Investigation of behavioural lifestyle interventions for lower limb osteoarthritis populations would benefit from consensus on methodology and outcome reporting. This includes use of validated physical activity reporting tools and planning for long-term follow-up.
A police education programme to integrate occupational safety and HIV prevention: protocol for a modified stepped-wedge study design with parallel prospective cohorts to assess behavioural outcomes
Authors: Strathdee Steffanie A , Arredondo Jaime , Rocha Teresita , Abramovitz Daniela , Rolon Maria Luisa , Patiño Mandujano Efrain , Rangel Maria Gudelia , Olivarria Horcasitas Omar , Gaines Tommi , Patterson Thomas L , Beletsky Leo 
Published: August 2015

IntroductionPolicing practices are key drivers of HIV among people who inject drugs (PWID). This paper describes the protocol for the first study to prospectively examine the impact of a police education programme (PEP) to align law enforcement and HIV prevention. PEPs incorporating HIV prevention (including harm reduction programmes like syringe exchange) have been successfully piloted in several countries but were limited to brief pre–post assessments; the impact of PEPs on policingbehavioursand occupational safety is unknown.ObjectivesProyecto ESCUDO (SHIELD) aims to evaluate the efficacy of the PEP on uptake of occupational safety procedures, as assessed through the incidence of needle stick injuries (NSIs) (primary outcome) and changes in knowledge of transmission, prevention and treatment of HIV and viral hepatitis; attitudes towards PWID, adverse behaviours that interfere with HIV prevention and protective behaviours (secondary outcomes).Methods/analysisESCUDO is a hybrid type I design that simultaneously tests an intervention and an implementation strategy. Using a modified stepped-wedge design involving all active duty street-level police officers in Tijuana (N=∼1200), we will administer one 3 h PEP course to groups of 20–50 officers until the entire force is trained. NSI incidence and geocoded arrest data will be assessed from department-wide de-identified data. Of the consenting police officers, a subcohort (N=500) will be randomly sampled from each class to undergo pre-PEP and post-PEP surveys with a semiannual follow-up for 2 years to assess self-reported NSIs, attitudes and behaviour changes. The impact on PWIDs will be externally validated through a parallel cohort of Tijuana PWIDs.Ethics/disseminationResearch ethics approval was obtained from the USA and Mexico. Findings will be disseminated through open access to protocol materials through the Law Enforcement and HIV Network.Trial registration numberNCT02444403.
Stock market network’s topological stability: Evidence from planar maximally filtered graph and minimal spanning tree
Authors: Yan Xin-Guo , Xie Chi , Wang Gang-Jin 
Published: August 2015

We study the topological stability of stock market network by investigating the topological robustness, namely the ability of the network to resist structural or topological changes. The stock market network is extracted by minimal spanning tree (MST) and planar maximally filtered graph (PMFG). We find that the specific delisting thresholds of the listed companies exist in both MST and PMFG networks. In comparison with MST, PMFG provides more information and is better for the aim of exploring stock market network’s robustness. The PMFG before the US sub-prime crisis (i.e., from June 2005 to May 2007) has a stronger robustness against the intentional topological damage than the other two sub-periods (i.e., from June 2007 to May 2009 and from June 2009 to May 2011). We also find that the nonfractal property exists in MSTs of S&P 500, i.e., the highly connected nodes link with each other directly, which indicates that the MSTs are vulnerable to the removal of such important nodes. Moreover, the financial institutions and high technology companies are important in maintaining the stability of S&P 500 network.
Genome-Wide Identification and Characterization of Novel Factors Conferring Resistance to Topoisomerase II Poisons in Cancer
Authors: Wijdeven Ruud H. , Pang Baoxu , van der Zanden Sabina Y. , Qiao Xiaohang , Blomen Vincent , Hoogstraat Marlous , Lips Esther H. , Janssen Lennert , Wessels Lodewyk , Brummelkamp Thijn R. , Neefjes Jacques 
Published: August 2015

Abstract
The topoisomerase II poisons doxorubicin and etoposide constitute longstanding cornerstones of chemotherapy. Despite their extensive clinical use, many patients do not respond to these drugs. Using a genome-wide gene knockout approach, we identified Keap1, the SWI/SNF complex, and C9orf82 (CAAP1) as independent factors capable of driving drug resistance through diverse molecular mechanisms, all converging on the DNA double-strand break (DSB) and repair pathway. Loss of Keap1 or the SWI/SNF complex inhibits generation of DSB by attenuating expression and activity of topoisomerase IIα, respectively, whereas deletion of C9orf82 augments subsequent DSB repair. Their corresponding genes, frequently mutated or deleted in human tumors, may impact drug sensitivity, as exemplified by triple-negative breast cancer patients with diminished SWI/SNF core member expression who exhibit reduced responsiveness to chemotherapy regimens containing doxorubicin. Collectively, our work identifies genes that may predict the response of cancer patients to the broadly used topoisomerase II poisons and defines alternative pathways that could be therapeutically exploited in treatment-resistant patients. Cancer Res; 75(19); 4176–87. ©2015 AACR.
Effects of Meteorological and Ancillary Data, Temporal Averaging, and Evaluation Methods on Model Performance and Uncertainty in a Land Surface Model
Authors: Ménard Cécile B. , Ikonen Jaakko , Rautiainen Kimmo , Aurela Mika , Arslan Ali Nadir , Pulliainen Jouni 
Published: August 2015

Abstract
A single-model 16-member ensemble is used to investigate how external model factors can affect model performance. Ensemble members are constructed with the land surface model (LSM) Joint UK Land Environment Simulator (JULES), with different choices of meteorological forcing [in situ, NCEP Climate Forecast System Reanalysis (CFSR)/CFSv2, or Water and Global Change (WATCH) Forcing Data ERA-Interim (WFDEI)] and ancillary datasets (in situ or remotely sensed), and with four time step modes. Effects of temporal averaging are investigated by comparing the hourly, daily, monthly, and seasonal ensemble performance against snow depth and water equivalent, soil temperature and moisture, and latent and sensible heat fluxes from one forest site and one clearing in the boreal ecozone of Finnish Lapland. Results show that meteorological data are the largest source of uncertainty; differences in ancillary data have little effect on model results. Although generally informative and representative, aggregated performance metrics fail to identify “right results for the wrong reasons”; to do so, scrutinizing of time series and of interactions between variables is necessary. Temporal averaging over longer intervals improves metrics—with the notable exception of bias, which increases—by reducing the effects of internal data and model variability on model response. Model evaluation during shoulder seasons (fall minus spring) identifies weaknesses in the reanalyses datasets that conventional seasonal performance (winter minus summer) neglects. In view of the importance of snow on the range of results obtained with the same model, let alone identical simulations using different temporal averaging, it is recommended that systematic evaluation, quantification of errors, and uncertainties in snow-covered regions be incorporated in future efforts to standardize evaluation methods of LSMs.
A case study of regulatory confusion: Paid parental leave and public servants
Authors: Williamson Sue 
Published: August 2015

AbstractAustralian policy on paid parental leave (PPL) has been highly controversial in recent years. While a universal PPL scheme become operative in 2011 under the Australian Labor Party, alternative policies continued to be proposed by the leader of the Liberal Party. These ranged from an expanded, comparatively generous PPL scheme, to one which would maintain the status quo, to a scheme with lesser provisions than are currently available. This article examines the PPL policy which would have provided the most generous entitlements to employees, and considers how public servants may have fared had it been introduced. The proposal would have meant that public servants would no longer have been able to access PPL provisions in their industrial instruments, but would only have been entitled to the legislated provisions. This article assesses whether public servants may have gained or lost under such a change, and then considers the broader issue of the most appropriate avenues to regulate public sector employment conditions. While a rare opportunity for enhanced PPL has been lost, this may be the best outcome in ensuring that unions can continue to bargain collectively for this important provision and ongoing improvements to it.
A systematic review and meta-analysis of plasma amyloid 1-42 and tau as biomarkers for Alzheimer’s disease
Authors: Shanthi Keerthanaa Balasubramanian , Krishnan Sreeram , Rani P 
Published: August 2015

Objective: Amyloid 1-42 (Aβ42) and tau in cerebrospinal fluid are currently used as markers for diagnosis of Alzheimer’s disease. Conflicting reports exist regarding their plasma levels in Alzheimer’s disease patients. A meta-analysis was performed to statistically validate the use of plasma Aβ42 and tau as biomarkers for Alzheimer’s disease. Methods: Different databases were searched using the search key: (amyloid OR amyloid1-42 OR Aβ42) AND (tau OR total tau) AND plasma AND (alzheimer’s OR alzheimer’s disease), and for databases not accepting boolean search, records were retrieved using the search key: plasma + amyloid + tau + alzheimer’s. A total of 1880 articles for Aβ42 and 1508 articles for tau were shortlisted. The abstracts were screened, and 69 articles reporting plasma Aβ42 levels and 6 articles reporting plasma tau were identified. After exclusion, 25 studies reporting plasma Aβ42 and 6 studies reporting total tau were analysed in Review Manager version 5.2 using weighted mean difference method, and the bias between studies was assessed using the funnel plot. Results: Plasma Aβ42 and tau did not vary significantly between Alzheimer’s disease patients and controls. The funnel plot showed that there was no bias between studies for Aβ42, while possible bias existed for tau due to availability of limited studies. Conclusion: This analysis pinpoints that plasma Aβ42 and tau could not serve as reliable markers independently for diagnosis of Alzheimer’s disease and a cohort study with age, sex and apolipoprotein E correction is warranted for their possible use as Alzheimer’s disease markers.
Contribution of Germline Mutations in the RAD51B, RAD51C, and RAD51D Genes to Ovarian Cancer in the Population
Authors: Song Honglin , Dicks Ed , Ramus Susan J. , Tyrer Jonathan P. , Intermaggio Maria P. , Hayward Jane , Edlund Christopher K. , Conti David , Harrington Patricia , Fraser Lindsay , Philpott Susan , Anderson Christopher , Rosenthal Adam , Gentry-Maharaj Aleksandra , Bowtell David D. , Alsop Kathryn , Cicek Mine S. , Cunningham Julie M. , Fridley Brooke L. , Alsop Jennifer , Jimenez-Linan Mercedes , Høgdall Estrid , Høgdall Claus K. , Jensen Allan , Kjaer Susanne Krüger , Lubiński Jan , Huzarski Tomasz , Jakubowska Anna , Gronwald Jacek , Poblete Samantha , Lele Shashi , Sucheston-Campbell Lara , Moysich Kirsten B. , Odunsi Kunle , Goode Ellen L. , Menon Usha , Jacobs Ian J. , Gayther Simon A. , Pharoah Paul D.P. 
Published: August 2015

Purpose The aim of this study was to estimate the contribution of deleterious mutations in the RAD51B, RAD51C, and RAD51D genes to invasive epithelial ovarian cancer (EOC) in the population and in a screening trial of individuals at high risk of ovarian cancer. Patients and Methods The coding sequence and splice site boundaries of the three RAD51 genes were sequenced and analyzed in germline DNA from a case-control study of 3,429 patients with invasive EOC and 2,772 controls as well as in 2,000 unaffected women who were BRCA1/BRCA2 negative from the United Kingdom Familial Ovarian Cancer Screening Study (UK_FOCSS) after quality-control analysis. Results In the case-control study, we identified predicted deleterious mutations in 28 EOC cases (0.82%) compared with three controls (0.11%; P < .001). Mutations in EOC cases were more frequent in RAD51C (14 occurrences, 0.41%) and RAD51D (12 occurrences, 0.35%) than in RAD51B (two occurrences, 0.06%). RAD51C mutations were associated with an odds ratio of 5.2 (95% CI, 1.1 to 24; P = .035), and RAD51D mutations conferred an odds ratio of 12 (95% CI, 1.5 to 90; P = .019). We identified 13 RAD51 mutations (0.65%) in unaffected UK_FOCSS participants (RAD51C, n = 7; RAD51D, n = 5; and RAD51B, n = 1), which was a significantly greater rate than in controls (P < .001); furthermore, RAD51 mutation carriers were more likely than noncarriers to have a family history of ovarian cancer (P < .001). Conclusion These results confirm that RAD51C and RAD51D are moderate ovarian cancer susceptibility genes and suggest that they confer levels of risk of EOC that may warrant their use alongside BRCA1 and BRCA2 in routine clinical genetic testing.
Reviews Books
Authors: Frank Zoë June , Lerner Sarah E. , Lordan Tom , Ward Caleb Andrew , Warfield Lizzie , Wolfman Archie 
Published: August 2015

Abstract
Continental Strangers: German Exile Cinema, 1933–1951, Gerd Gemünden, (2014) New York: Columbia University, 296pp., ISBN: 9780231166799 (pbk), $30.00, ISBN: 9780231166782 (cloth), $90.00
Technology and Desire: The Transgressive Art of Moving Images, Rania Gaafar and Martin Schulz, (2014) Bristol, UK: Intellect, 350pp., ISBN: 9781841504612 (pbk), $43.00
The Cinema of Alexander Sokurov: Figures of Paradox, Jeremi Szaniawski, (2014) New York: Wallflower Press, 256pp., ISBN: 9780231167352 (pbk), $25.00
The Cinema of Michael Winterbottom: Borders, Intimacy, Terror, Bruce Bennett, (2013) New York: Wallflower Press, 224pp., ISBN: 9780231167376 (pbk), $25.00, ISBN: 9780231167369 (hbk), $75.00
Finding Ourselves at the Movies: Philosophy for a New Generation, Paul W. Kahn, (2013) New York: Columbia University Press, 256pp., ISBN: 9780231164382 (hbk), $35.99, ISBN: 9780231164382 (ebook), $34.99
Two Bicycles: The Work of Jean-Luc Godard and Anne-Marie Miéville, Jerry White, (2013) Ontario: Wilfred Laurier University Press, 202pp., ISBN: 9781554589357 (pbk), $39.99
Rol mediador docente en la comprensión de textos
Authors: García Sandra Milena 
Published: August 2015

<p>Este artículo resultado de investigaciónanaliza las relaciones que emergen entre el rol mediador del docente y la lectura de textos expositivos, el uso de estrategias metacognitivas se plantea como una herramienta didáctica útil para la formación de lectores autónomos desde el diseño de investigación - acción se muestran transformaciones significativas en las interacciones de aula asociadas al mejoramiento de la comprensión lectora de un grupo de estudiantes de educación media.</p><div> </div><p><br /><strong></strong></p>
Desarrollo de la competencia argumentativa a través de la toma de decisiones en el abordaje de la cuestión sociocientífica “uso y comercialización del PVC”
Authors: Achury Lady Carolina , Alvarez Hoyos Jenny 
Published: August 2015

<p>Se presenta el diseño y la puesta a punto de una estrategia de intervención didáctica con la implementación de una secuencia didáctica aplicada en estudiantes de grado undécimo de un colegio público de la ciudad de Bogotá-Colombia. Utilizamos una perspectiva de investigación cualitativa usando categorías de análisis adoptadas, contextualizadas y ampliadas a partir del trabajo de Driver y Newton citado por Moreno y Martínez (2009) y la toma de decisiones propuesta por Janis y Mann (1977); Wheeler y Janis (1980) en Maguregi, (2010). Buscamos aumentar la comprensión de la viabilidad de esta estrategia en términos de la articulación de la competencia argumentativa en la toma de decisiones; mediante el abordaje de la cuestión sociocientífica “uso y comercialización del Policloruro de Vinilo (PVC)”. En un primer momento se analizan las concepciones de los estudiantes frente a los polímeros, específicamente al PVC, con el objetivo de establecer algunos parámetros que permitan mejorar la secuencia a implementar. Posteriormente, se presentan los resultados obtenidos en la actividad llamada “La controversia” en donde se discutió una noticia que fue publicada en un periódico nacional sobre el PVC como un plástico nocivo para la salud y el medio ambiente, así como videos relacionados con el uso del PVC, analizando el nivel de argumentación en los estudiantes.</p><p><strong> </strong></p>