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Journal Cover PLoS ONE
  [SJR: 1.395]   [H-I: 181]   [717 followers]  Follow
  This is an Open Access Journal Open Access journal
   ISSN (Online) 1932-6203
   Published by PLoS Homepage  [13 journals]
  • Correction: Identification of a serum-induced transcriptional signature
           associated with metastatic cervical cancer

    • Authors: Anna Palatnik Shuyun Ye Christina Kendziorski Marissa Iden Jessica S. Zigman Martin J. Hessner Janet S. Rader
      Abstract: by Anna Palatnik, Shuyun Ye, Christina Kendziorski, Marissa Iden, Jessica S. Zigman, Martin J. Hessner, Janet S. Rader
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193687
  • Correction: Gadolinium-enhanced cardiac MR exams of human subjects are
           associated with significant increases in the DNA repair marker 53BP1, but
           not the damage marker γH2AX

    • Authors: Jennifer S. McDonald Robert J. McDonald Jacob B. Ekins Antony S. Tin Sylvain Costes Tamara M. Hudson Dana J. Schroeder Kevin Kallmes Scott H. Kaufmann Philip M. Young Aiming Lu Ramanathan Kadirvel David F. Kallmes
      Abstract: by Jennifer S. McDonald, Robert J. McDonald, Jacob B. Ekins, Antony S. Tin, Sylvain Costes, Tamara M. Hudson, Dana J. Schroeder, Kevin Kallmes, Scott H. Kaufmann, Philip M. Young, Aiming Lu, Ramanathan Kadirvel, David F. Kallmes
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193634
  • Correction: A Kolmogorov-Smirnov test for the molecular clock based on
           Bayesian ensembles of phylogenies

    • Authors: The PLOS ONE Staff
      Abstract: by The PLOS ONE Staff
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193633
  • Correction: Pre-service teachers' perceived value of general pedagogical
           knowledge for practice: Relations with epistemic beliefs and source

    • Authors: Samuel Merk Tom Rosman Julia Rueß Marcus Syring Jürgen Schneider
      Abstract: by Samuel Merk, Tom Rosman, Julia Rueß, Marcus Syring, Jürgen Schneider
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193632
  • Correction: Vaccination and nutritional status of children in Karawari,
           East Sepik Province, Papua New Guinea

    • Authors: The PLOS ONE Staff
      Abstract: by The PLOS ONE Staff
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193631
  • Correction: Divalent cations are dispensable for binding to DNA of a novel
           positively charged olivomycin A derivative

    • Authors: The PLOS One Staff
      Abstract: by The PLOS One Staff
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193630
  • Correction: Stage-specific IFN-induced and IFN gene expression reveal
           convergence of type I and type II IFN and highlight their role in both
           acute and chronic stage of pathogenic SIV infection

    • Authors: Nadia Echebli Nicolas Tchitchek Stéphanie Dupuy Timothée Bruel Caroline Passaes Nathalie Bosquet Roger Le Grand Christine Bourgeois Benoit Favier Rémi Cheynier Olivier Lambotte Bruno Vaslin
      Abstract: by Nadia Echebli, Nicolas Tchitchek, Stéphanie Dupuy, Timothée Bruel, Caroline Passaes, Nathalie Bosquet, Roger Le Grand, Christine Bourgeois, Benoit Favier, Rémi Cheynier, Olivier Lambotte, Bruno Vaslin
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193629
  • Correction: Identification of potential antimicrobials against Salmonella
           typhimurium and Listeria monocytogenes using Quantitative
           Structure-Activity Relation modeling

    • Authors: The PLOS ONE Staff
      Abstract: by The PLOS ONE Staff
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193628
  • Correction: Replication and Characterization of Association between ABO
           SNPs and Red Blood Cell Traits by Meta-Analysis in Europeans

    • Authors: The PLOS ONE Staff
      Abstract: by The PLOS ONE Staff
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193627
  • Correction: Pharmacoepidemiological assessment of adherence and
           influencing co-factors among primary open-angle glaucoma patients—An
           observational cohort study

    • Authors: The PLOS ONE Staff
      Abstract: by The PLOS ONE Staff
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193621
  • Correction: Quantification of Dialytic Removal and Extracellular Calcium
           Mass Balance during a Weekly Cycle of Hemodialysis

    • Authors: Jacek Waniewski Malgorzata Debowska Alicja Wojcik-Zaluska Andrzej Ksiazek Wojciech Zaluska
      Abstract: by Jacek Waniewski, Malgorzata Debowska, Alicja Wojcik-Zaluska, Andrzej Ksiazek, Wojciech Zaluska
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193604
  • Correction: A High Malaria Prevalence Identified by PCR among Patients
           with Acute Undifferentiated Fever in India

    • Authors: Christel Gill Haanshuus Sara Chandy Anand Manoharan Rosario Vivek Dilip Mathai Deepika Xena Ashita Singh Nina Langeland Bjørn Blomberg George Vasanthan Usha Sitaram Jonathan Appasamy Joel Nesaraj Anil Henry Suvarna Patil Gerardo Alvarez-Uria Lois Armstrong Kristine Mørch
      Abstract: by Christel Gill Haanshuus, Sara Chandy, Anand Manoharan, Rosario Vivek, Dilip Mathai, Deepika Xena, Ashita Singh, Nina Langeland, Bjørn Blomberg, George Vasanthan, Usha Sitaram, Jonathan Appasamy, Joel Nesaraj, Anil Henry, Suvarna Patil, Gerardo Alvarez-Uria, Lois Armstrong, Kristine Mørch
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193574
  • Risk factors control for primary prevention of cardiovascular disease in
           men: Evidence from the Aragon Workers Health Study (AWHS)

    • Authors: Isabel Aguilar-Palacio Sara Malo Cristina Feja MªJesús Lallana Montserrat León-Latre José Antonio Casasnovas MªJosé Rabanaque Eliseo Guallar
      Abstract: by Isabel Aguilar-Palacio, Sara Malo, Cristina Feja, MªJesús Lallana, Montserrat León-Latre, José Antonio Casasnovas, MªJosé Rabanaque, Eliseo GuallarBenefits of cardiovascular disease (CVD) risk factors control are well known, but goals achievement remains low. The objective of this study is to evaluate the prevalence of CVD risk factors among men ina worker’s cohort with no previous CVD, to study control variations across time and the factors associated with poor control. To this end, we conducted a cohort reexamination (2010–2014) within the context of the Aragon Workers Health Study (AWHS). Data from working characteristics, analytical values and pharmacological prescription were included in the analysis. Prevalences of risk factor diagnosis and control were calculated, as well as factors associated with poor control. The prevalence of CVD risk factors was high. In 2014dyslipidaemia was the most prevalent (85.2%) followed by Hypertension (HT) (42.0%). People under treatment increased for the period analysed (p
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193541
  • Strength improvements through occlusal splints' The effects of
           different lower jaw positions on maximal isometric force production and
           performance in different jumping types

    • Authors: Christian Maurer Sebastian Heller Jil-Julia Sure Daniel Fuchs Christoph Mickel Eileen M. Wanke David A. Groneberg Daniela Ohlendorf
      Abstract: by Christian Maurer, Sebastian Heller, Jil-Julia Sure, Daniel Fuchs, Christoph Mickel, Eileen M. Wanke, David A. Groneberg, Daniela OhlendorfObjective The influence of the jaw position on postural control, body posture, walking and running pattern has been reported in the literature. All these movements have in common that a relatively small, but well controlled muscle activation is required. The induced effects on motor output through changed jaw positions have been small. Therefore, it has been questioned if it could still be observed in maximal muscle activation. Method Twenty-three healthy, mid age recreational runners (mean age = 34.0 ± 10.3 years) participated in this study. Three different jump tests (squat jump, counter movement jump, and drop jumps from four different heights) and three maximal strength tests (trunk flexion and extension, leg press of the right and left leg) were conducted. Four different dental occlusion conditions and an additional familiarization condition were tested. Subjects performed the tests on different days for which the four occlusion conditions were randomly changed. Results No familiarization effect was found. Occlusion conditions with a relaxation position and with a myocentric condylar position showed significantly higher values for several tests compared to the neutral condition and the maximal occlusion position. Significance was found in the squat jump, countermovement jump, the drop jump from 32cm and 40cm, trunk extension, leg press force and rate of force development. The effect due to the splint conditions is an improvement between 3% and 12% (min and max). No influence of the jaw position on symmetry or balance between extension and flexion muscle was found. Conclusion An influence of occlusion splints on rate of force development (RFD) and maximal strength tests could be confirmed. A small, but consistent increase in the performance parameters could be measured. The influence of the occlusion condition is most likely small compared to other influences as for example training status, age, gender and circadian rhythm.
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193540
  • Within the fortress: A specialized parasite is not discriminated against
           in a social insect society

    • Authors: Emilia Solá Gracia Charissa de Bekker Ephraim M. Hanks David P. Hughes
      Abstract: by Emilia Solá Gracia, Charissa de Bekker, Ephraim M. Hanks, David P. HughesSocial insect colonies function cohesively due, in part, to altruistic behaviors performed towards related individuals. These colonies can be affected by parasites in two distinct ways, either at the level of the individual or the entire colony. As such, colonies of social insects can experience conflict with infected individuals reducing the cohesiveness that typifies them. Parasites of social insects therefore offer us a framework to study conflicts within social insect colonies in addition to the traditionally viewed conflicts afforded by groups of low genetic relatedness due to multiple mating for example. In our study, we use the behavior manipulating fungal pathogen, Ophiocordyceps kimflemingiae (= unilateralis) and its host, Camponotus castaneus, to ask if colony members are able to detect infected individuals. Such detection would be optimal for the colony since infected workers die near foraging trails where the fungus develops its external structures and releases spores that infect other colony members. To determine if C. castaneus workers can detect these future threats, we used continuous-time point observations coupled with longer continuous observations to discern any discrimination towards infected individuals. After observing 1,240 hours of video footage we found that infected individuals are not removed from the colony and continuously received food during the course of fungal infection. We also calculated the distances between workers and the nest entrance in a total of 35,691 data points to find infected workers spent more time near the entrance of the nest. Taken together, these results suggest healthy individuals do not detect the parasite inside their nestmates. The colony’s inability to detect infected individuals allows O. kimflemingiae to develop within the colony, while receiving food and protection from natural enemies, which could damage or kill its ant host before the parasite has completed its development.
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193536
  • Generation of efficient mutants of endoglycosidase from Streptococcus
           pyogenes and their application in a novel one-pot transglycosylation
           reaction for antibody modification

    • Authors: Mitsuhiro Iwamoto Yukiko Sekiguchi Kensuke Nakamura Yoshirou Kawaguchi Takeshi Honda Jun Hasegawa
      Abstract: by Mitsuhiro Iwamoto, Yukiko Sekiguchi, Kensuke Nakamura, Yoshirou Kawaguchi, Takeshi Honda, Jun HasegawaThe fine structures of Fc N-glycan modulate the biological functions and physicochemical properties of antibodies. By remodeling N-glycan to obtain a homogeneous glycoform or chemically modified glycan, antibody characteristics can be controlled or modified. Such remodeling can be achieved by transglycosylation reactions using a mutant of endoglycosidase from Streptococcus pyogenes (Endo-S) and glycan oxazoline. In this study, we generated improved mutants of Endo-S by introducing additional mutations to the D233Q mutant. Notably, Endo-S D233Q/Q303L, D233Q/E350Q, and several other mutations resulted in transglycosylation efficiencies exceeding 90%, with a single-digit donor-to-substrate ratio of five, and D233Q/Y402F/D405A and several other mutations resulted in slightly reduced transglycosylation efficiencies accompanied by no detectable hydrolysis activity for 48 h. We further demonstrated that the combined use of mutants of Endo-S with Endo-M or Endo-CC, endoglycosidases from Mucor hiemalis and Coprinopsis cinerea, enables one-pot transglycosylation from sialoglycopeptide to antibodies. This novel reaction enables glycosylation remodeling of antibodies, without the chemical synthesis of oxazoline in advance or in situ.
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193534
  • SUMO polymeric chains are involved in nuclear foci formation and chromatin
           organization in Trypanosoma brucei procyclic forms

    • Authors: Paula Ana Iribarren Lucía Ayelén Di Marzio María Agustina Berazategui Javier Gerardo De Gaudenzi Vanina Eder Alvarez
      Abstract: by Paula Ana Iribarren, Lucía Ayelén Di Marzio, María Agustina Berazategui, Javier Gerardo De Gaudenzi, Vanina Eder AlvarezSUMOylation is a post-translational modification conserved in eukaryotic organisms that involves the covalent attachment of the small ubiquitin-like protein SUMO to internal lysine residues in target proteins. This tag usually alters the interaction surface of the modified protein and can be translated into changes in its biological activity, stability or subcellular localization, among other possible outputs. SUMO can be attached as a single moiety or as SUMO polymers in case there are internal acceptor sites in SUMO itself. These chains have been shown to be important for proteasomal degradation as well as for the formation of subnuclear structures such as the synaptonemal complex in Saccharomyces cerevisiae or promyelocytic leukemia nuclear bodies in mammals. In this work, we have examined SUMO chain formation in the protozoan parasite Trypanosoma brucei. Using a recently developed bacterial strain engineered to produce SUMOylated proteins we confirmed the ability of TbSUMO to form polymers and determined the type of linkage using site-directed mutational analysis. By generating transgenic procyclic parasites unable to form chains we demonstrated that although not essential for normal growth, SUMO polymerization determines the localization of the modified proteins in the nucleus. In addition, FISH analysis of telomeres showed a differential positioning depending on the polySUMOylation abilities of the cells. Thus, our observations suggest that TbSUMO chains might play a role in establishing interaction platforms contributing to chromatin organization.
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193528
  • The longitudinal association between changes in lung function and changes
           in abdominal visceral obesity in Korean non-smokers

    • Authors: Eun Kyung Choe Hae Yeon Kang Young Lee Seung Ho Choi Hee Joung Kim Joo Sung Kim
      Abstract: by Eun Kyung Choe, Hae Yeon Kang, Young Lee, Seung Ho Choi, Hee Joung Kim, Joo Sung KimObesity, particularly abdominal obesity, might be related to decreased lung function. We aimed to investigate whether obesity indices are associated with forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) in asymptomatic non-smokers through a longitudinal cohort study. The clinical records of 1,145 subjects (428 males, mean age 52.3 years) who underwent a comprehensive health evaluation, including spirometry and abdominal fat computed tomography, at least twice between 2007 and 2014 were retrospectively reviewed and analysed. The mean follow-up period was 1,105 days (over 3.0 years). The baseline total adipose tissue (TAT) and visceral adipose tissue (VAT) were inversely associated with both FEV1 and FVC (P < 0.05). The longitudinal study found that increasing TAT and VAT were significantly related to decreasing FEV1 and FVC, whereas decreasing TAT and VAT were related to increasing FEV1 and FVC in both males and females (P < 0.05). The strength and consistency of these associations were clearer in males than in females. However, no significant relationship was found between changes in subcutaneous adipose tissue and changes in lung function. In Korean non-smokers, longitudinal changes in abdominal visceral fat were found to be inversely related to changes in lung function over a mean period of three years. These results suggest that decreasing abdominal visceral obesity could increase lung function despite ageing.
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193516
  • In silico and in vitro studies of the reduction of unsaturated α,β bonds
           of trans-2-hexenedioic acid and 6-amino-trans-2-hexenoic acid –
           Important steps towards biobased production of adipic acid

    • Authors: Emma Karlsson Jae Ho Shin Gunnar Westman Leif A. Eriksson Lisbeth Olsson Valeria Mapelli
      Abstract: by Emma Karlsson, Jae Ho Shin, Gunnar Westman, Leif A. Eriksson, Lisbeth Olsson, Valeria MapelliThe biobased production of adipic acid, a precursor in the production of nylon, is of great interest in order to replace the current petrochemical production route. Glucose-rich lignocellulosic raw materials have high potential to replace the petrochemical raw material. A number of metabolic pathways have been proposed for the microbial conversion of glucose to adipic acid, but achieved yields and titers remain to be improved before industrial applications are feasible. One proposed pathway starts with lysine, an essential metabolite industrially produced from glucose by microorganisms. However, the drawback of this pathway is that several reactions are involved where there is no known efficient enzyme. By changing the order of the enzymatic reactions, we were able to identify an alternative pathway with one unknown enzyme less compared to the original pathway. One of the reactions lacking known enzymes is the reduction of the unsaturated α,β bond of 6-amino-trans-2-hexenoic acid and trans-2-hexenedioic acid. To identify the necessary enzymes, we selected N-ethylmaleimide reductase from Escherichia coli and Old Yellow Enzyme 1 from Saccharomyces pastorianus. Despite successful in silico docking studies, where both target substrates could fit in the enzyme pockets, and hydrogen bonds with catalytic residues of both enzymes were predicted, no in vitro activity was observed. We hypothesize that the lack of activity is due to a difference in electron withdrawing potential between the naturally reduced aldehyde and the carboxylate groups of our target substrates. Suggestions for protein engineering to induce the reactions are discussed, as well as the advantages and disadvantages of the two metabolic pathways from lysine. We have highlighted bottlenecks associated with the lysine pathways, and proposed ways of addressing them.
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193503
  • A new high-performance liquid chromatography-tandem mass spectrometry
           method for the determination of paclitaxel and 6α-hydroxy-paclitaxel in
           human plasma: Development, validation and application in a clinical
           pharmacokinetic study

    • Authors: Bianca Posocco Mauro Buzzo Andrea Follegot Luciana Giodini Roberto Sorio Elena Marangon Giuseppe Toffoli
      Abstract: by Bianca Posocco, Mauro Buzzo, Andrea Follegot, Luciana Giodini, Roberto Sorio, Elena Marangon, Giuseppe ToffoliPaclitaxel belongs to the taxanes family and it is used, alone or in multidrug regimens, for the therapy of several solid tumours, such as breast-, lung-, head and neck-, and ovarian cancer. Standard dosing of chemotherapy does not take into account the many inter-patient differences that make drug exposure highly variable, thus leading to the insurgence of severe toxicity. This is particularly true for paclitaxel considering that a relationship between haematological toxicity and plasma exposure was found. Therefore, in order to treat patients with the correct dose of paclitaxel, improving the overall benefit–risk ratio, Therapeutic Drug Monitoring is necessary. In order to quantify paclitaxel and its main metabolite, 6α-hydroxy-paclitaxel, in patients’ plasma, we developed a new, sensitive and specific HPLC–MS/MS method applicable to all paclitaxel dosages used in clinical routine. The developed method used a small volume of plasma sample and is based on quick protein precipitation. The chromatographic separation of the analytes was achieved with a SunFire™ C18 column (3.5 μM, 92 Å, 2,1 x 150 mm); the mobile phases were 0.1% formic acid/bidistilled water and 0.1% formic acid/acetonitrile. The electrospray ionization source worked in positive ion mode and the mass spectrometer operated in selected reaction monitoring mode. Our bioanalytical method was successfully validated according to the FDA-EMA guidelines on bioanalytical method validation. The calibration curves resulted linear (R2 ≥0.9948) over the concentration ranges (1–10000 ng/mL for paclitaxel and 1–1000 ng/mL for 6α-hydroxy-paclitaxel) and were characterized by a good accuracy and precision. The intra- and inter-day precision and accuracy were determined on three quality control concentrations for paclitaxel and 6α-hydroxy-paclitaxel and resulted respectively
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193500
  • Role of Su(Hw) zinc finger 10 and interaction with CP190 and Mod(mdg4)
           proteins in recruiting the Su(Hw) complex to chromatin sites in Drosophila

    • Authors: Larisa Melnikova Margarita Kostyuchenko Alexander Parshikov Pavel Georgiev Anton Golovnin
      Abstract: by Larisa Melnikova, Margarita Kostyuchenko, Alexander Parshikov, Pavel Georgiev, Anton GolovninSu(Hw) belongs to the class of proteins that organize chromosome architecture and boundaries/insulators between regulatory domains. This protein contains a cluster of 12 zinc finger domains most of which are responsible for binding to three different modules in the consensus site. Su(Hw) forms a complex with CP190 and Mod(mdg4)-67.2 proteins that binds to well-known Drosophila insulators. To understand how Su(Hw) performs its activities and binds to specific sites in chromatin, we have examined the previously described su(Hw)f mutation that disrupts the 10th zinc finger (ZF10) responsible for Su(Hw) binding to the upstream module. The results have shown that Su(Hw)f loses the ability to interact with CP190 in the absence of DNA. In contrast, complete deletion of ZF10 does not prevent the interaction between Su(Hw)Δ10 and CP190. Having studied insulator complex formation in different mutant backgrounds, we conclude that both association with CP190 and Mod(mdg4)-67.2 partners and proper organization of DNA binding site are essential for the efficient recruitment of the Su(Hw) complex to chromatin insulators.
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193497
  • Cerebrospinal fluid sCD27 levels indicate active T cell-mediated
           inflammation in premanifest Huntington's disease

    • Authors: Valter Niemelä Joachim Burman Kaj Blennow Henrik Zetterberg Anders Larsson Jimmy Sundblom
      Abstract: by Valter Niemelä, Joachim Burman, Kaj Blennow, Henrik Zetterberg, Anders Larsson, Jimmy SundblomIntroduction Huntington’s disease (HD) is a neurodegenerative disorder, but evidence also suggests neuroinflammation in the pathogenesis. The immune mechanisms involved and the timing of their activation need further clarification. Methods A clinically well-characterized HD cohort and gene negative controls were enrolled. YKL-40 reflecting innate immunity and sCD27, a marker of adaptive immunity, were measured across disease stages. Comparisons were made with markers of neurodegeneration: neurofilament light (NFL), total-tau (T-tau), and phospho-tau (P-tau). Results 52 cross-sectional cerebrospinal fluid samples and 23 follow-up samples were analyzed. sCD27 was elevated in manifest HD and premanifest gene expansion carriers, whereas controls mostly had undetectable levels. YKL-40 showed a trend toward increase in manifest HD. sCD27 correlated with YKL-40 which in turn was closely associated to all included markers of neurodegeneration. YKL-40, NFL, and both forms of tau could all independently predict HD symptoms, but only NFL levels differed between groups after age-adjustment. Conclusion Increased sCD27 in premanifest HD is a sign of T cell-mediated neuroinflammation. This finding is novel since other reports almost exclusively have found early involvement of innate immunity. Validation of sCD27 in a larger HD cohort is needed. The role of adaptive immunity in HD needs further clarification, as it may hasten disease progression.
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193492
  • Contribution of S4 segments and S4-S5 linkers to the low-voltage
           activation properties of T-type CaV3.3 channels

    • Authors: Ana Laura Sanchez-Sandoval Zazil Herrera Carrillo Clara Estela Díaz Velásquez Dulce María Delgadillo Heriberto Manuel Rivera Juan Carlos Gomora
      Abstract: by Ana Laura Sanchez-Sandoval, Zazil Herrera Carrillo, Clara Estela Díaz Velásquez, Dulce María Delgadillo, Heriberto Manuel Rivera, Juan Carlos GomoraVoltage-gated calcium channels contain four highly conserved transmembrane helices known as S4 segments that exhibit a positively charged residue every third position, and play the role of voltage sensing. Nonetheless, the activation range between high-voltage (HVA) and low-voltage (LVA) activated calcium channels is around 30–40 mV apart, despite the high level of amino acid similarity within their S4 segments. To investigate the contribution of S4 voltage sensors for the low-voltage activation characteristics of CaV3.3 channels we constructed chimeras by swapping S4 segments between this LVA channel and the HVA CaV1.2 channel. The substitution of S4 segment of Domain II in CaV3.3 by that of CaV1.2 (chimera IIS4C) induced a ~35 mV shift in the voltage-dependence of activation towards positive potentials, showing an I-V curve that almost overlaps with that of CaV1.2 channel. This HVA behavior induced by IIS4C chimera was accompanied by a 2-fold decrease in the voltage-dependence of channel gating. The IVS4 segment had also a strong effect in the voltage sensing of activation, while substitution of segments IS4 and IIIS4 moved the activation curve of CaV3.3 to more negative potentials. Swapping of IIS4 voltage sensor influenced additional properties of this channel such as steady-state inactivation, current decay, and deactivation. Notably, Domain I voltage sensor played a major role in preventing CaV3.3 channels to inactivate from closed states at extreme hyperpolarized potentials. Finally, site-directed mutagenesis in the CaV3.3 channel revealed a partial contribution of the S4-S5 linker of Domain II to LVA behavior, with synergic effects observed in double and triple mutations. These findings indicate that IIS4 and, to a lesser degree IVS4, voltage sensors are crucial in determining the LVA properties of CaV3.3 channels, although the accomplishment of this function involves the participation of other structural elements like S4-S5 linkers.
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193490
  • Gait symmetry and hip strength in women with developmental dysplasia
           following hip arthroplasty compared to healthy subjects: A cross-sectional

    • Authors: Ruud A. Leijendekkers Marco A. Marra Sjoerd Kolk Geert van Bon B. Wim Schreurs Vivian Weerdesteyn Nico Verdonschot
      Abstract: by Ruud A. Leijendekkers, Marco A. Marra, Sjoerd Kolk, Geert van Bon, B. Wim Schreurs, Vivian Weerdesteyn, Nico VerdonschotIntroduction Untreated unilateral developmental dysplasia of the hip (DDH) results in asymmetry of gait and hip strength and may lead to early osteoarthritis, which is commonly treated with a total hip arthroplasty (THA). There is limited knowledge about the obtained symmetry of gait and hip strength after the THA. The objectives of this cross-sectional study were to: a) identify asymmetries between the operated and non-operated side in kinematics, kinetics and hip strength, b) analyze if increased walking speed changed the level of asymmetry in patients c) compare these results with those of healthy subjects. Methods Women (18–70 year) with unilateral DDH who had undergone unilateral THA were eligible for inclusion. Vicon gait analysis system was used to collect frontal and sagittal plane kinematic and kinetic parameters of the hip joint, pelvis and trunk during walking at comfortable walking speed and increased walking speed. Furthermore, hip abductor and extensor muscle strength was measured. Results Six patients and eight healthy subjects were included. In the patients, modest asymmetries in lower limb kinematics and kinetics were present during gait, but trunk lateral flexion asymmetry was evident. Patients’ trunk lateral flexion also differed compared to healthy subjects. Walking speed did not significantly influence the level of asymmetry. The hip abduction strength asymmetry of 23% was not statistically significant, but the muscle strength of both sides were significantly weaker than those of healthy subjects. Conclusions In patients with a DDH treated with an IBG THA modest asymmetries in gait kinematics and kinetics were present, with the exception of a substantial asymmetry of the trunk lateral flexion. Increased walking speed did not result in increased asymmetries in gait kinematics and kinetics. Hip muscle strength was symmetrical in patients, but significantly weaker than in healthy subjects. Trunk kinematics should be included as an outcome measure to assess the biomechanical benefits of the THA surgery after DDH.
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193487
  • Validation of a SNP-based non-invasive prenatal test to detect the fetal
           22q11.2 deletion in maternal plasma samples

    • Authors: Harini Ravi Gabriel McNeill Shruti Goel Steven D. Meltzer Nathan Hunkapiller Allison Ryan Brynn Levy Zachary P. Demko
      Abstract: by Harini Ravi, Gabriel McNeill, Shruti Goel, Steven D. Meltzer, Nathan Hunkapiller, Allison Ryan, Brynn Levy, Zachary P. DemkoIntroduction Non-invasive prenatal testing (NIPT) for aneuploidy using cell-free DNA in maternal plasma has been widely adopted. Recently, NIPT coverage has expanded to detect subchromosomal abnormalities including the 22q11.2 deletion. Validation of a SNP-based NIPT for detection of 22q11.2 deletions demonstrating a high sensitivity (97.8%) and specificity (99.75%) has been reported. We sought to further demonstrate the performance of a revised version of the test in a larger set of pregnancy plasma samples. Methods Blood samples from pregnant women (10 with 22q11.2-deletion‒affected fetuses and 390 negative controls) were successfully analyzed using a revised SNP-based NIPT for the 22q11.2 deletion. The sensitivity and specificity of the assay were measured. Results Sensitivity of the assay was 90% (9/10), and specificity of the assay was 99.74% (389/390), with a corresponding false positive-rate of 0.26%. Discussion The data presented in this study add to the growing body of evidence demonstrating the ability of the SNP-based NIPT to detect 22q11.2 deletions with high sensitivity and specificity.
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193476
  • The existence of parenting styles in the owner-dog relationship

    • Authors: Ineke R. van Herwijnen Joanne A. M. van der Borg Marc Naguib Bonne Beerda
      Abstract: by Ineke R. van Herwijnen, Joanne A. M. van der Borg, Marc Naguib, Bonne BeerdaParents interact with children following specific styles, known to influence child development. These styles represent variations in the dimensions of demandingness and responsiveness, resulting in authoritarian, authoritative, permissive or uninvolved parenting. Given the similarities in the parent to child and owner to dog relationships, we determined the extent to which parenting styles exist in the owner to dog relationship using the existing Parenting Styles and Dimensions Questionnaire for the parent-child relationship and an adapted version for dog owners. Items on the parenting of children/dogs were rated for applicability on a five-point Likert scale by 518 Dutch dog owning parents. Principal Component Analyses grouped parenting propensities into styles, with some marked differences between the findings for children and dogs. Dog-directed items grouped into an authoritarian-correction orientated style, incorporating variation in demandingness and focussing on correcting a dog for behaviour verbally/physically, and in two styles based on authoritative items. An authoritative-intrinsic value orientated style reflected variation in mainly responsiveness and oriented on the assumed needs and emotions of the animal. A second authoritative-item based style, captured variations in demandingness and responsiveness. We labelled this style authoritative-training orientated, as it orientated on manners in teaching a dog how to behave in social situations. Thus, we defined dog-directed parenting styles and constructed a Dog-Directed Parenting Styles and Dimensions Questionnaire along the lines of the existing theoretical framework on parenting styles. We did not find a dog-directed parenting style of being permissive or uninvolved, which we attribute to a study population of devoted dog owners and our findings should be interpreted with this specific study population in mind. We found evidence of dog-directed parenting styles and provide a fundament for determining their possible impact on the different aspects of a dog’s life.
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193471
  • Fat max as an index of aerobic exercise performance in mice during uphill

    • Authors: Kengo Ishihara Hirokazu Taniguchi
      Abstract: by Kengo Ishihara, Hirokazu TaniguchiEndurance exercise performance has been used as a representative index in experimental animal models in the field of health sciences, exercise physiology, comparative physiology, food function or nutritional physiology. The objective of the present study was to evaluate the effectiveness of Fatmax (the exercise intensity that elicits maximal fat oxidation) as an additional index of endurance exercise performance that can be measured during running at submaximal exercise intensity in mice. We measured both Fatmax and Vo2 peak of trained ICR mice that voluntary exercised for 8 weeks and compared them with a sedentary group of mice at multiple inclinations of 20, 30, 40, and 50° on a treadmill. The Vo2 at Fatmax of the training group was significantly higher than that of the sedentary group at inclinations of 30 and 40° (P < 0.001). The running speed at Fatmax of the training group was significantly higher than that of the sedentary group at inclinations of 20, 30, and 40° (P < 0.05). Blood lactate levels sharply increased in the sedentary group (7.33 ± 2.58 mM) compared to the training group (3.13 ± 1.00 mM, P < 0.01) when running speeds exceeded the Fatmax of sedentary mice. Vo2 at Fatmax significantly correlated to Vo2 peak, running time to fatigue, and lactic acid level during running (P < 0.05) although the reproducibility of Vo2 peak was higher than that of Vo2 at Fatmax. In conclusion, Fatmax can be used as a functional assessment of the endurance exercise performance of mice during submaximal exercise intensity.
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193470
  • Transgenerational effects of prenatal restricted diet on gene expression
           and histone modifications in the rat

    • Authors: Joanna Nowacka-Woszuk Izabela Szczerbal Anna M. Malinowska Agata Chmurzynska
      Abstract: by Joanna Nowacka-Woszuk, Izabela Szczerbal, Anna M. Malinowska, Agata ChmurzynskaDietary triggers acting on a developing fetus can affect the functioning of the body in later life; this can be observed on various levels, including epigenetic modifications and gene expression. Early-life programmed changes may be transmitted to successive generations. In this study, the impact of prenatal restricted diet was studied in four generations of rats. We hypothesized that this diet can induce changes in the expression of major genes involved in two epigenetic mechanisms: DNA methylation and histone modifications. The transcript level of six genes involved in these processes (Dnmt1, Dnmt3a, Dnmt3b, Mecp2, Hdac1, and Sin3a) was therefore determined in three tissues (liver, adipose, and muscle). This diet was found to have no effect on the F0 pregnant females. In the F1 progeny (fetuses at day 19 of pregnancy and 4-week-old rats) significant differences in the expression of the genes were observed mostly in the liver; in subsequent generations, we therefore studied only this tissue. Among the genes encoding DNA methyltransferases, significant changes were observed for Dnmt1 in the F1 animals from the restricted group, but these were no longer evident in F2 and F3. The Dnmt3a and Dnmt3b genes showed no differences in mRNA level in F1 fetuses. Concerning the transcript level of the Mecp2 gene only in F1 generation significant changes were found. For the histone modification genes, an increase in the expression of Hdac1 in fetus liver was found in F1 and F2, while its level decreased in F3. The abundance of the Sin3a transcript varied in all generations. It was also found that the mRNA levels of the studied genes correlated highly positive with each other, but only in fetuses from the F1 restricted group. The DNA methylation cell potential, defined as the ratio of SAM (S-adenosylmethionine) to SAH (S-adenosylhomocysteine), was measured in the liver, with no alterations being found in the restricted groups. Evaluation of global histone H3 acetylation showed that it underwent a significant increase in the fetal livers of F1, while during aging (four-week old animals) this difference was no longer maintained. A tendency of increased H3 acetylation in fetuses was also detected in F2 generation. In F1 fetuses from restricted group the increased H3 acetylation positively correlated with transcriptional status of the studied genes. Our results indicate that the prenatal restriction diet can affect the activity of genes involved in epigenetic mechanisms in the liver across generations. Moreover, this feeding type influenced the global histone H3 acetylation in fetal liver.
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193464
  • Development of reaching during mid-childhood from a Developmental Systems

    • Authors: Laura Golenia Marina M. Schoemaker Egbert Otten Leonora J. Mouton Raoul M. Bongers
      Abstract: by Laura Golenia, Marina M. Schoemaker, Egbert Otten, Leonora J. Mouton, Raoul M. BongersInspired by the Developmental Systems perspective, we studied the development of reaching during mid-childhood (5–10 years of age) not just at the performance level (i.e., endpoint movements), as commonly done in earlier studies, but also at the joint angle level. Because the endpoint position (i.e., the tip of the index finger) at the reaching target can be achieved with multiple joint angle combinations, we partitioned variability in joint angles over trials into variability that does not (goal-equivalent variability, GEV) and that does (non-goal-equivalent variability, NGEV) influence the endpoint position, using the Uncontrolled Manifold method. Quantifying this structure in joint angle variability allowed us to examine whether and how spatial variability of the endpoint at the reaching target is related to variability in joint angles and how this changes over development. 6-, 8- and 10-year-old children and young adults performed reaching movements to a target with the index finger. Polynomial trend analysis revealed a linear and a quadratic decreasing trend for the variable error. Linear decreasing and cubic trends were found for joint angle standard deviations at movement end. GEV and NGEV decreased gradually with age, but interestingly, the decrease of GEV was steeper than the decrease of NGEV, showing that the different parts of the joint angle variability changed differently over age. We interpreted these changes in the structure of variability as indicating changes over age in exploration for synergies (a family of task solutions), a concept that links the performance level with the joint angle level. Our results suggest changes in the search for synergies during mid-childhood development.
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193463
  • Researchers’ participation in and motivations for engaging with research
           information management systems

    • Authors: Besiki Stvilia Shuheng Wu Dong Joon Lee
      Abstract: by Besiki Stvilia, Shuheng Wu, Dong Joon LeeResearchers’ participation in online RIMSs This article examined how researchers participated in research information management systems (RIMSs), their motivations for participation, and their priorities for those motivations. Profile maintenance, question-answering, and endorsement activities were used to define three cumulatively increasing levels of participation: Readers, Record Managers, and Community Members. Junior researchers were more engaged in RIMSs than were senior researchers. Postdocs had significantly higher odds of endorsing other researchers for skills and being categorized as Community Members than did full and associate professors. Assistant professors were significantly more likely to be Record Managers than were members of any other seniority categories. Finally, researchers from the life sciences showed a significantly higher propensity for being Community Members than Readers and Record Managers when compared with researchers from engineering and the physical sciences, respectively. Researchers’ motivations to participate in RIMSs When performing activities, researchers were motivated by the desire to share scholarship, feel competent, experience a sense of enjoyment, improve their status, and build ties with other members of the community. Moreover, when researchers performed activities that directly benefited other members of a RIMS, they assigned higher priorities to intrinsic motivations, such as perceived self-efficacy, enjoyment, and building community ties. Researchers at different stages of their academic careers and disciplines ranked some of the motivations for engaging with RIMSs differently. The general model of research participation in RIMSs; the relationships among RIMS activities; the motivation scales for activities; and the activity, seniority, and discipline-specific priorities for the motivations developed by this study provide the foundation for a framework for researcher participation in RIMSs. This framework can be used by RIMSs and institutional repositories to develop tools and design mechanisms to increase researchers’ engagement in RIMSs.
      PubDate: 2018-02-23T22:00:00Z
      DOI: 10.1371/journal.pone.0193459
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