PLoS ONE (PLOS ONE)

Publications in this journal

• Article: Reducing the decline in physical activity during pregnancy: a systematic review of behaviour change interventions

  Currie S, Sinclair M, Murphy MH, Madden E, Dunwoody L, Liddle SD
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  ABSTRACT: Physical activity (PA) typically declines throughout pregnancy. Low levels of PA are associated with excessive weight gain and subsequently increase risk of pre- eclampsia, gestational diabetes mellitus, hypertension disorders, delivery by caesarean section and stillbirth. Systematic reviews on PA during pregnancy have not explored the efficacy of behaviour change techniques or related theory in altering PA behaviour. This systematic review evaluated the content of PA interventions to reduce the decline of PA in pregnant women with a specific emphasis on the behaviour change techniques employed to elicit this change. Search and Review methodology Literature searches were conducted in eight databases. Strict inclusion and exclusion criteria were employed. Two reviewers independently evaluated each intervention using the behaviour change techniques (BCT) taxonomy to identify the specific behaviour change techniques employed. Two reviewers independently assessed the risk of bias using the guidelines from the Cochrane Collaboration. Overall quality was determined using the GRADE approach. Findings A total of 1140 potentially eligible papers were identified from which 14 studies were selected for inclusion. Interventions included counselling (n=6), structured exercise (n=6) and education (n=2). Common behaviour change techniques employed in these studies were goal setting and planning, feedback, repetition and substitution, shaping knowledge and comparison of behaviours. Regular face-to-face meetings were also commonly employed. PA change over time in intervention groups ranged from increases of 28% to decreases of 25%. In 8 out of 10 studies, which provided adequate data, participants in the intervention group were more physically active post intervention than controls. Conclusions and implications Physical activity interventions incorporating behaviour change techniques help reduce the decline in PA throughout pregnancy. Range of behaviour change techniques can be implemented to reduce this decline including goals and planning, shaping knowledge and comparison of outcomes. A lack of high quality interventions hampers conclusions of intervention effectiveness.
  PLoS ONE 06/2013; In press.
• Article: Rapid countermeasure discovery against Francisella tularensis based on a metabolic network reconstruction

  Sidhartha Chaudhury, Mohamed Diwan M. AbdulHameed, Narender Singh, Gregory J. Tawa, Patrik M. D'haeseleer, Adam T. Zemla, Ali Navid, Carol E. Zhou, Matthew C. Franklin, Jonah Cheung, Michael J. Rudolph, James Love, John F. Graf, David A. Rozak, Jennifer L. Dankmeyer, Kei Amemiya, Simon Daefler, Anders Wallqvist
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  ABSTRACT: In the future, we may be faced with the need to provide treatment for an emergent biological threat against which existing vaccines and drugs have limited efficacy or availability. To prepare for this eventuality, our objective was to employ a metabolic network-based approach to rapidly identify potential drug targets and prospectively screen and validate novel small-molecule antimicrobials. Our target organism was the fully virulent Francisella tularensis subspecies tularensis Schu S4 strain, a highly infectious intracellular pathogen that is the causative agent of tularemia and is classified as a Category A biological agent by the Centers for Disease Control and Prevention. We proceeded with a staggered computational and experimental workflow that utilized a strain-specific metabolic network model, homology modeling and x-ray crystallography of protein targets, and ligand- and structure-based drug design. Selected compounds were subsequently filtered based on physiological-based pharmacokinetic modeling and we selected a final set of 40 compounds for experimental validation of antimicrobial activity. We began screening of these compounds in cell-based assays in Biosafety Level 3 facilities in the 20th week of the study and completed the screens within 12 weeks. Six compounds showed significant growth inhibition of F. tularensis and we determined their respective minimum inhibitory concentrations and mammalian cell cytotoxicities. The most promising compound had a low molecular weight, was non-toxic, and abolished bacterial growth at 13 µM, with putative activity against coaD, an enzyme involved in the biosynthesis of coenzyme A. The novel antimicrobial compounds identified in this study serve as starting points for lead optimization, animal testing, and drug development against tularemia. Our integrated in silico/in vitro approach had an overall 15% success rate in terms of active versus tested compounds over an elapsed time period of 32 weeks, from pathogen strain identification to selection and validation of novel antimicrobial compounds.
  PLoS ONE 05/2013;
• Article: Acylpeptide hydrolase inhibition as targeted strategy to induce proteasomal down-regulation

  G. Palmieri, P. Bergamo, A. Luini, M. Ruvo, M. Gogliettino, E. Langella, M. Saviano, R. N. Hegde, A. Sandomenico, M. Rossi
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  ABSTRACT: Acylpeptide hydrolase (APEH), one of the four members of the prolyl oligopeptidase class, catalyses the removal of N-acylated amino acids from acetylated peptides and it has been postulated to play a key role in protein degradation machinery. Disruption of protein turnover has been established as an effective strategy to down-regulate the ubiquitin-proteasome system (UPS) and as a promising approach in anticancer therapy.Here, we illustrate a new pathway modulating UPS and proteasome activity through inhibition of APEH. To find novel molecules able to down-regulate APEH activity, we screened a set of synthetic peptides, reproducing the reactive-site loop of a known archaeal inhibitor of APEH (SsCEI), and the conjugated linoleic acid (CLA) isomers. A 12-mer SsCEI peptide and the trans10-cis12 isomer of CLA, were identified as specific APEH inhibitors and their effects on cell-based assays were paralleled by a dose-dependent reduction of proteasome activity and the activation of the pro-apoptotic caspase cascade. Moreover, cell treatment with the individual compounds increased the cytoplasm levels of several classic hallmarks of proteasome inhibition, such as NFkappaB, p21, and misfolded or polyubiquitinylated proteins, and additive effects were observed in cells exposed to a combination of both inhibitors without any cytotoxicity. Remarkably, transfection of human bronchial epithelial cells with APEH siRNA, promoted a marked accumulation of a mutant of the cystic fibrosis transmembrane conductance regulator (CFTR), herein used as a model of misfolded protein typically degraded by UPS. Finally, molecular modeling studies, to gain insights into the APEH inhibition by the trans10-cis12 CLA isomer, were performed.Our study supports a previously unrecognized role of APEH as a negative effector of proteasome activity by an unknown mechanism and opens new perspectives for the development of strategies aimed at modulation of cancer progression.
  PLoS ONE 05/2013; 6:e25888.
• Article: Corena-McLeod M, Walss-Bass C, Oliveros A, Gordillo Villegas A, Ceballos C, et al. (2013) New Model of Action for Mood Stabilizers: Phosphoproteome from Rat Pre-Frontal Cortex Synaptoneurosomal Preparations. PLoS ONE 8(5): e52147. doi:10.1371/journal.pone.0052147

  Maria Corena-McLeod, Consuelo Walss-Bass, Alfredo Oliveros, Andres Gordillo Villegas, Carolina Ceballos, Paul J Linser, Leslie Van Ekeris, Cristine Charlesworth, Benjamin Madden, Kristin Smith, Elliott Richelson
  PLoS ONE 05/2013; 8(5):52147.
• Article: Peroxisome Proliferator-Activated Receptor (PPAR) γ and PPARα Agonists Modulate Mitochondrial Fusion-Fission Dynamics: Relevance to Reactive Oxygen Species (ROS)-Related Neurodegenerative Disorders?

  Zolezzi JM, Silva-Alvarez C, Ordenes D, Godoy JA, Carvajal FJ, Santos MJ, Inestrosa NC
  PLoS ONE 05/2013;