title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=1829 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Transcriptional activation of muscle atrophy promotes cardiac muscle remodeling during mammalian hibernation link: https://peerj.com/articles/2317 last-modified: 2016-08-11 description: Background. Mammalian hibernation in thirteen-lined ground squirrels (Ictidomys tridecemlineatus) is characterized by dramatic changes on a physiological and molecular level. During hibernation, mammalian hearts show a propensity to hypertrophy due to the need for increasing contractility to pump colder and more viscous blood. While cardiac hypertrophy is quite often a process characterized by decompensation, the ground squirrel studied is an excellent model of cardiac plasticity and cardioprotection under conditions of hypothermia and ischemia. The forkhead box O (Foxo) family of proteins and myogenin (MyoG) are transcription factors that control protein degradation and muscle atrophy by regulating the expression of the E3 ubiquitin ligases, MAFbx and MuRF1. These ligases are part of the ubiquitin proteasome system by transferring ubiquitin to proteins and targeting these proteins for degradation. Regulation of Foxo1 and 3a occurs through phosphorylation at different residues. The threonine-24 (Thr-24) and serine-319 (Ser-319) residues on Foxo1, and the Thr-32 residue on Foxo3a are phosphorylated by Akt, leading to cytoplasmic localization of Foxo. We propose that the described mechanism contributes to the changes taking place in cardiac muscle throughout hibernation.Methods. Total and phosphorylated protein levels of Foxo1 and Foxo3a, as well as total protein levels of MyoG, MAFbx, and MuRF1, were studied using immunoblotting.Results. Immunoblotting results demonstrated upregulations in Foxo1 and Foxo3a total protein levels (1.3- and 4.5-fold increases relative to euthermic control, for Foxo1 and 3a respectively) during late torpor, and protein levels remained elevated throughout the rest of torpor and at interbout arousal. We also observed decreases in inactive, phosphorylated Foxo1 and 3a proteins during throughout torpor, where levels of p-Foxo1 Ser319 and Thr24, as well as p-Foxo3a Thr32 decreased by at least 45% throughout torpor. MyoG was upregulated only during late torpor by 2.4-fold. Protein levels of MAFbx and MuRF1 increased in late torpor as well as during early arousal by as much as 2.8-fold, and MAFbx levels remained elevated during interbout arousal, whereas MuRF1 levels returned to control levels.Discussion. The present results indicate that upregulation and activation of Foxo1 and 3a, in addition to the increase in MyoG levels at late torpor, may be upregulating the expression of MAFbx and MuRF1. These findings suggest that there is activation of the ubiquitin proteasome system (UPS) as ground squirrels arouse from torpor. Therefore, the signalling pathway involving MyoG, and the E3 ligases MAFbx and MuRF1, plays a significant role in cardiac muscle remodelling during hibernation. These findings provide insights into the regulation of protein degradation and turnover in the cardiac muscle of a hibernator model. creator: Yichi Zhang creator: Oscar A. Aguilar creator: Kenneth B. Storey uri: https://doi.org/10.7717/peerj.2317 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2016 Zhang et al. title: Stereotactically-navigated percutaneous Irreversible Electroporation (IRE) compared to conventional IRE: a prospective trial link: https://peerj.com/articles/2277 last-modified: 2016-08-11 description: Purpose. The purpose of this study was to compare CT-navigated stereotactic IRE (SIRE) needle placement to non-navigated conventional IRE (CIRE) for percutaneous ablation of liver malignancies.Materials and Methods. A prospective trial including a total of 20 patients was conducted with 10 patients in each arm of the study. IRE procedures were guided using either CT fluoroscopy (CIRE) or a stereotactic planning and navigation system (SIRE). Primary endpoint was procedure time. Secondary endpoints were accuracy of needle placement, technical success rate, complication rate and dose-length product (DLP).Results. A total of 20 IRE procedures were performed to ablate hepatic malignancies (16 HCC, 4 liver metastases), 10 procedures in each arm. Mean time for placement of IRE electrodes in SIRE was significantly shorter with 27 ± 8 min compared to 87 ± 30 min for CIRE (p < 0.001). Accuracy of needle placement for SIRE was higher than CIRE (2.2 mm vs. 3.3 mm mean deviation, p < 0.001). The total DLP and the fluoroscopy DLP were significantly lower in SIRE compared to CIRE. Technical success rate and complication rates were equal in both arms.Conclusion. SIRE demonstrated a significant reduction of procedure length and higher accuracy compared to CIRE. Stereotactic navigation has the potential to reduce radiation dose for the patient and the radiologist without increasing the risk of complications or impaired technical success compared to CIRE. creator: Lukas P. Beyer creator: Benedikt Pregler creator: Christoph Nießen creator: Andreas Schicho creator: Michael Haimerl creator: Ernst Michael Jung creator: Christian Stroszczynski creator: Philipp Wiggermann uri: https://doi.org/10.7717/peerj.2277 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2016 Beyer et al. title: Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease link: https://peerj.com/articles/2174 last-modified: 2016-08-11 description: Background. Cystic fibrosis (CF) is a genetic disease that results in chronic infections of the lungs. CF patients experience intermittent pulmonary exacerbations (CFPE) that are associated with poor clinical outcomes. CFPE involves an increase in disease symptoms requiring more aggressive therapy.Methods. Longitudinal sputum samples were collected from 11 patients (n = 44 samples) to assess the effect of exacerbations on the sputum metabolome using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The data was analyzed with MS/MS molecular networking and multivariate statistics.Results. The individual patient source had a larger influence on the metabolome of sputum than the clinical state (exacerbation, treatment, post-treatment, or stable). Of the 4,369 metabolites detected, 12% were unique to CFPE samples; however, the only known metabolites significantly elevated at exacerbation across the dataset were platelet activating factor (PAF) and a related monacylglycerophosphocholine lipid. Due to the personalized nature of the sputum metabolome, a single patient was followed for 4.2 years (capturing four separate exacerbation events) as a case study for the detection of personalized biomarkers with metabolomics. PAF and related lipids were significantly elevated during CFPEs of this patient and ceramide was elevated during CFPE treatment. Correlating the abundance of bacterial 16S rRNA gene amplicons to metabolomics data from the same samples during a CFPE demonstrated that antibiotics were positively correlated to Stenotrophomonas and Pseudomonas, while ceramides and other lipids were correlated with Streptococcus, Rothia, and anaerobes.Conclusions. This study identified PAF and other inflammatory lipids as potential biomarkers of CFPE, but overall, the metabolome of CF sputum was patient specific, supporting a personalized approach to molecular detection of CFPE onset. creator: Robert A. Quinn creator: Yan Wei Lim creator: Tytus D. Mak creator: Katrine Whiteson creator: Mike Furlan creator: Douglas Conrad creator: Forest Rohwer creator: Pieter Dorrestein uri: https://doi.org/10.7717/peerj.2174 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2016 Quinn et al. title: Changes in segmentation and setation along the anterior/posterior axis of the homonomous trunk limbs of a remipede (Crustacea, Arthropoda) link: https://peerj.com/articles/2305 last-modified: 2016-08-10 description: This study describes the segmentation and setation at different developmental stages of the homonomous trunk limbs of the remipede Speleonectes tulumensisYager, 1987 collected in anchialine caves of the Yucatan Peninsula. Most homonomous trunk limbs originate ventrolaterally and are composed of two protopodal segments, three exopodal segments and four endopodal segments; contralateral limb pairs are united by a sternal bar. However, the last few posterior limbs originate ventrally, are smaller sized, and have regressively fewer segments, suggesting that limb development passes through several intermediate steps beginning with a limb bud. A terminal stage of development is proposed for specimens on which the posterior somite bears a simple bilobate limb bud, and the adjacent somite bears a limb with a protopod comprised of a coxapod and basipod, and with three exopodal and four endopodal segments. On each trunk limb there are 20 serially homologous groups of setae, and the numbers of setae on different limbs usually varies. These groups of setae are arranged linearly and are identified based on the morphology of the setae and their position on the segments. The number of setae in these groups increases gradually from the anterior homonomous limb to a maximum between limbs 8–12; the number then decreases sharply on the more posterior limbs. Changes in the number of setae, which reach a maximum between trunk limbs 8–12, differ from changes in segmentation which vary only over the last few posterior trunk limbs. Following a vector analysis that identified a spatial pattern for these 20 groups of setae among the different homonomous limbs, the hypothesis was confirmed that the number of setae in any given group and any given limb is correlated with the group, with the position of the somite along the body axis, and with the number of somites present on the specimens. This is the first vector analysis used to analyze a pattern of developmental changes in serially homologs of an arthropod. Development of remipede limbs are compared and contrasted with similar copepod limbs. Architecture, particularly the sternal bar uniting contralateral limb pairs, proposed as homologous, and development of trunk limb segmentation of the remipede is generally similar to that of copepods, but the remipede limb differs in several ways including an additional endopodal segment, the proximal, that appears simultaneously with the protopod during development. creator: Viacheslav N. Ivanenko creator: Ekaterina A. Antonenko creator: Mikhail S. Gelfand creator: Jill Yager creator: Frank D. Ferrari uri: https://doi.org/10.7717/peerj.2305 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2016 Ivanenko et al. title: Vegemite Beer: yeast extract spreads as nutrient supplements to promote fermentation link: https://peerj.com/articles/2271 last-modified: 2016-08-10 description: Vegemite is an iconic Australian food spread made from spent brewers’ yeast extract, which has been reported to be used as an ingredient in illegal home brewing. In this study, we tested the utility of Vegemite and the similar spread Marmite in promoting fermentation. We could not culture microorganisms from either Vegemite or Marmite, consistent with these food-grade spreads being essentially sterile. To test if the addition of Vegemite or Marmite could assist in fermentation when additional viable yeast was also present, solutions containing glucose and a range of concentrations of either Vegemite or Marmite were inoculated with brewers’ yeast. No fermentation occurred in any condition without addition of extra brewer’s yeast. Fermentation did not occur when yeast was inoculated into solutions containing only glucose, but progressed efficiently with when Vegemite or Marmite was also added. Gas Chromatography confirmed that ethanol was present at ∼3% v/v post-fermentation in all samples which contained glucose, Vegemite or Marmite, and brewers’ yeast. Trace amounts of methanol were also detected. Mass spectrometry proteomics identified abundant intracellular yeast proteins and barley proteins in Vegemite and Marmite, and abundant secreted yeast proteins from actively growing yeast in those samples to which extra brewers’ yeast had been added. We estimate that the real-world cost of home brewed “Vegemite Beer” would be very low. Our results show that Vegemite or other yeast extract spreads could provide cheap and readily available sources of nutrient supplementation to increase the efficiency of fermentation in home brewing or other settings. creator: Edward D. Kerr creator: Benjamin L. Schulz uri: https://doi.org/10.7717/peerj.2271 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2016 Kerr and Schulz title: Is it safe to nest near conspicuous neighbours? Spatial patterns in predation risk associated with the density of American Golden-Plover nests link: https://peerj.com/articles/2193 last-modified: 2016-08-10 description: Predation is one of the main factors explaining nesting mortality in most bird species. Birds can avoid nest predation or reduce predation pressure by breeding at higher latitude, showing anti-predator behaviour, selecting nest sites protected from predators, and nesting in association with protective species. American Golden-Plovers (Pluvialis dominica) defend their territory by using various warning and distraction behaviours displayed at varying levels of intensity (hereafter “conspicuous behaviour”), as well as more aggressive behaviours such as aerial attacks, but only in some populations. Such antipredator behaviour has the potential to repel predators and thus benefit the neighbouring nests by decreasing their predation risk. Yet, conspicuous behaviour could also attract predators by signalling the presence of a nest. To test for the existence of a protective effect associated with the conspicuous antipredator behaviour of American Golden-Plovers, we studied the influence of proximity to plover nests on predation risk of artificial nests on Igloolik Island (Nunavut, Canada) in July 2014. We predicted that the predation risk of artificial nests would decrease with proximity to and density of plover nests. We monitored 18 plover nests and set 35 artificial nests at 30, 50, 100, 200, and 500 m from seven of those plover nests. We found that the predation risk of artificial nests increases with the density of active plover nests. We also found a significant negative effect of the distance to the nearest active protector nest on predation risk of artificial nests. Understanding how the composition and structure of shorebird communities generate spatial patterns in predation risks represents a key step to better understand the importance of these species of conservation concern in tundra food webs. creator: Marie-Andrée Giroux creator: Myriam Trottier-Paquet creator: Joël Bêty creator: Vincent Lamarre creator: Nicolas Lecomte uri: https://doi.org/10.7717/peerj.2193 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2016 Giroux et al. title: A horizon scan of future threats and opportunities for pollinators and pollination link: https://peerj.com/articles/2249 last-modified: 2016-08-09 description: Background. Pollinators, which provide the agriculturally and ecologically essential service of pollination, are under threat at a global scale. Habitat loss and homogenisation, pesticides, parasites and pathogens, invasive species, and climate change have been identified as past and current threats to pollinators. Actions to mitigate these threats, e.g., agri-environment schemes and pesticide-use moratoriums, exist, but have largely been applied post-hoc. However, future sustainability of pollinators and the service they provide requires anticipation of potential threats and opportunities before they occur, enabling timely implementation of policy and practice to prevent, rather than mitigate, further pollinator declines.Methods.Using a horizon scanning approach we identified issues that are likely to impact pollinators, either positively or negatively, over the coming three decades.Results.Our analysis highlights six high priority, and nine secondary issues. High priorities are: (1) corporate control of global agriculture, (2) novel systemic pesticides, (3) novel RNA viruses, (4) the development of new managed pollinators, (5) more frequent heatwaves and drought under climate change, and (6) the potential positive impact of reduced chemical use on pollinators in non-agricultural settings.Discussion. While current pollinator management approaches are largely driven by mitigating past impacts, we present opportunities for pre-emptive practice, legislation, and policy to sustainably manage pollinators for future generations. creator: Mark J.F. Brown creator: Lynn V. Dicks creator: Robert J. Paxton creator: Katherine C.R. Baldock creator: Andrew B. Barron creator: Marie-Pierre Chauzat creator: Breno M. Freitas creator: Dave Goulson creator: Sarina Jepsen creator: Claire Kremen creator: Jilian Li creator: Peter Neumann creator: David E. Pattemore creator: Simon G. Potts creator: Oliver Schweiger creator: Colleen L. Seymour creator: Jane C. Stout uri: https://doi.org/10.7717/peerj.2249 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2016 Brown et al. title: A study of institutional spending on open access publication fees in Germany link: https://peerj.com/articles/2323 last-modified: 2016-08-09 description: Publication fees as a revenue source for open access publishing hold a prominent place on the agendas of researchers, policy makers, and academic publishers. This study contributes to the evolving empirical basis for funding these charges and examines how much German universities and research organisations spent on open access publication fees. Using self-reported cost data from the Open APC initiative, the analysis focused on the amount that was being spent on publication fees, and compared these expenditure with data from related Austrian (FWF) and UK (Wellcome Trust, Jisc) initiatives, in terms of both size and the proportion of articles being published in fully and hybrid open access journals. We also investigated how thoroughly self-reported articles were indexed in Crossref, a DOI minting agency for scholarly literature, and analysed how the institutional spending was distributed across publishers and journal titles. According to self-reported data from 30 German universities and research organisations between 2005 and 2015, expenditures on open access publication fees increased over the years in Germany and amounted to € 9,627,537 for 7,417 open access journal articles. The average payment was € 1,298, and the median was € 1,231. A total of 94% of the total article volume included in the study was supported in accordance with the price cap of € 2,000, a limit imposed by the Deutsche Forschungsgemeinschaft (DFG) as part of its funding activities for open access funding at German universities. Expenditures varied considerably at the institutional level. There were also differences in how much the institutions spent per journal and publisher. These differences reflect, at least in part, the varying pricing schemes in place including discounted publication fees. With an indexing coverage of 99%, Crossref thoroughly indexed the open access journals articles included in the study. A comparison with the related openly available cost data from Austria and the UK revealed that German universities and research organisations primarily funded articles in fully open access journals. By contrast, articles in hybrid journal accounted for the largest share of spending according to the Austrian and UK data. Fees paid for hybrid journals were on average more expensive than those paid for fully open access journals. creator: Najko Jahn creator: Marco Tullney uri: https://doi.org/10.7717/peerj.2323 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2016 Jahn et al. title: Probing the origins of human acetylcholinesterase inhibition via QSAR modeling and molecular docking link: https://peerj.com/articles/2322 last-modified: 2016-08-09 description: Alzheimer’s disease (AD) is a chronic neurodegenerative disease which leads to the gradual loss of neuronal cells. Several hypotheses for AD exists (e.g., cholinergic, amyloid, tau hypotheses, etc.). As per the cholinergic hypothesis, the deficiency of choline is responsible for AD; therefore, the inhibition of AChE is a lucrative therapeutic strategy for the treatment of AD. Acetylcholinesterase (AChE) is an enzyme that catalyzes the breakdown of the neurotransmitter acetylcholine that is essential for cognition and memory. A large non-redundant data set of 2,570 compounds with reported IC50 values against AChE was obtained from ChEMBL and employed in quantitative structure-activity relationship (QSAR) study so as to gain insights on their origin of bioactivity. AChE inhibitors were described by a set of 12 fingerprint descriptors and predictive models were constructed from 100 different data splits using random forest. Generated models afforded R2, ${Q}_{\mathrm{CV }}^{2}$QCV2 and ${Q}_{\mathrm{Ext}}^{2}$QExt2 values in ranges of 0.66–0.93, 0.55–0.79 and 0.56–0.81 for the training set, 10-fold cross-validated set and external set, respectively. The best model built using the substructure count was selected according to the OECD guidelines and it afforded R2, ${Q}_{\mathrm{CV }}^{2}$QCV2 and ${Q}_{\mathrm{Ext}}^{2}$QExt2 values of 0.92 ± 0.01, 0.78 ± 0.06 and 0.78 ± 0.05, respectively. Furthermore, Y-scrambling was applied to evaluate the possibility of chance correlation of the predictive model. Subsequently, a thorough analysis of the substructure fingerprint count was conducted to provide informative insights on the inhibitory activity of AChE inhibitors. Moreover, Kennard–Stone sampling of the actives were applied to select 30 diverse compounds for further molecular docking studies in order to gain structural insights on the origin of AChE inhibition. Site-moiety mapping of compounds from the diversity set revealed three binding anchors encompassing both hydrogen bonding and van der Waals interaction. Molecular docking revealed that compounds 13, 5 and 28 exhibited the lowest binding energies of −12.2, −12.0 and −12.0 kcal/mol, respectively, against human AChE, which is modulated by hydrogen bonding, π–π stacking and hydrophobic interaction inside the binding pocket. These information may be used as guidelines for the design of novel and robust AChE inhibitors. creator: Saw Simeon creator: Nuttapat Anuwongcharoen creator: Watshara Shoombuatong creator: Aijaz Ahmad Malik creator: Virapong Prachayasittikul creator: Jarl E.S. Wikberg creator: Chanin Nantasenamat uri: https://doi.org/10.7717/peerj.2322 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2016 Simeon et al. title: Temporal dynamics of the developing lung transcriptome in three common inbred strains of laboratory mice reveals multiple stages of postnatal alveolar development link: https://peerj.com/articles/2318 last-modified: 2016-08-09 description: To characterize temporal patterns of transcriptional activity during normal lung development, we generated genome wide gene expression data for 26 pre- and post-natal time points in three common inbred strains of laboratory mice (C57BL/6J, A/J, and C3H/HeJ). Using Principal Component Analysis and least squares regression modeling, we identified both strain-independent and strain-dependent patterns of gene expression. The 4,683 genes contributing to the strain-independent expression patterns were used to define a murine Developing Lung Characteristic Subtranscriptome (mDLCS). Regression modeling of the Principal Components supported the four canonical stages of mammalian embryonic lung development (embryonic, pseudoglandular, canalicular, saccular) defined previously by morphology and histology. For postnatal alveolar development, the regression model was consistent with four stages of alveolarization characterized by episodic transcriptional activity of genes related to pulmonary vascularization. Genes expressed in a strain-dependent manner were enriched for annotations related to neurogenesis, extracellular matrix organization, and Wnt signaling. Finally, a comparison of mouse and human transcriptomics from pre-natal stages of lung development revealed conservation of pathways associated with cell cycle, axon guidance, immune function, and metabolism as well as organism-specific expression of genes associated with extracellular matrix organization and protein modification. The mouse lung development transcriptome data generated for this study serves as a unique reference set to identify genes and pathways essential for normal mammalian lung development and for investigations into the developmental origins of respiratory disease and cancer. The gene expression data are available from the Gene Expression Omnibus (GEO) archive (GSE74243). Temporal expression patterns of mouse genes can be investigated using a study specific web resource (http://lungdevelopment.jax.org). creator: Kyle J. Beauchemin creator: Julie M. Wells creator: Alvin T. Kho creator: Vivek M. Philip creator: Daniela Kamir creator: Isaac S. Kohane creator: Joel H. Graber creator: Carol J. Bult uri: https://doi.org/10.7717/peerj.2318 license: http://creativecommons.org/licenses/by/4.0/ rights: ©2016 Beauchemin et al.