bluuebunny/crossref_metadata_2025_split huggingface dataset:
GDNF gene is associated with tourette syndrome in a family study
Authors: Huertas‐Fernández Ismael , Gómez‐Garre Pilar , Madruga‐Garrido Marcos , Bernal‐Bernal Inmaculada , Bonilla‐Toribio Marta , Martín‐Rodríguez Juan Francisco , Cáceres‐Redondo María Teresa , Vargas‐González Laura , Carrillo Fátima , Pascual Alberto , Tischfield Jay A. , King Robert A. , Heiman Gary A. , Mir Pablo 
Published: June 2015

AbstractBackgroundTourette syndrome is a disorder characterized by persistent motor and vocal tics, and frequently accompanied by the comorbidities attention deficit hyperactivity disorder and obsessive‐compulsive disorder. Impaired synaptic neurotransmission has been implicated in its pathogenesis. Our aim was to investigate the association of 28 candidate genes, including genes related to synaptic neurotransmission and neurotrophic factors, with Tourette syndrome.MethodsWe genotyped 506 polymorphisms in a discovery cohort from the United States composed of 112 families and 47 unrelated singletons with Tourette syndrome (201 cases and 253 controls). Genes containing significant polymorphisms were imputed to fine‐map the signal(s) to potential causal variants. Allelic analyses in Tourette syndrome cases were performed to check the role in attention deficit hyperactivity disorder and obsessive‐compulsive disorder comorbidities. Target polymorphisms were further studied in a replication cohort from southern Spain composed of 37 families and three unrelated singletons (44 cases and 73 controls).ResultsThe polymorphism rs3096140 in glial cell line–derived neurotrophic factor gene (GDNF) was significant in the discovery cohort after correction (P = 1.5 × 10−4). No linkage disequilibrium was found between rs3096140 and other functional variants in the gene. We selected rs3096140 as target polymorphism, and the association was confirmed in the replication cohort (P = 0.01). No association with any comorbidity was found.ConclusionsAs a conclusion, a common genetic variant in GDNF is associated with Tourette syndrome. A defect in the production of GDNF could compromise the survival of parvalbumin interneurons, thus altering the excitatory/inhibitory balance in the corticostriatal circuitry. Validation of this variant in other family cohorts is necessary. © 2015 International Parkinson and Movement Disorder Society
Modifications of resting state networks in spinocerebellar ataxia type 2
Authors: Cocozza Sirio , Saccà Francesco , Cervo Amedeo , Marsili Angela , Russo Cinzia Valeria , Giorgio Sara Maria delle Acque , De Michele Giuseppe , Filla Alessandro , Brunetti Arturo , Quarantelli Mario 
Published: June 2015

AbstractPurposeWe aimed to investigate the integrity of the Resting State Networks in spinocerebellar ataxia type 2 (SCA2) and the correlations between the modification of these networks and clinical variables.MethodsResting‐state functional magnetic resonance imaging (RS‐fMRI) data from 19 SCA2 patients and 29 healthy controls were analyzed using an independent component analysis and dual regression, controlling at voxel level for the effect of atrophy by co‐varying for gray matter volume. Correlations between the resting state networks alterations and disease duration, age at onset, number of triplets, and clinical score were assessed by Spearman's coefficient, for each cluster which was significantly different in SCA2 patients compared with healthy controls.ResultsIn SCA2 patients, disruption of the cerebellar components of all major resting state networks was present, with supratentorial involvement only for the default mode network. When controlling at voxel level for gray matter volume, the reduction in functional connectivity in supratentorial regions of the default mode network, and in cerebellar regions within the default mode, executive and right fronto‐parietal networks, was still significant. No correlations with clinical variables were found for any of the investigated resting state networks.ConclusionsThe SCA2 patients show significant alterations of the resting state networks, only partly explained by the atrophy. The default mode network is the only resting state network that shows also supratentorial changes, which appear unrelated to the cortical gray matter volume. Further studies are needed to assess the clinical significance of these changes. © 2015 International Parkinson and Movement Disorder Society
Zonisamide improves wearing‐off in Parkinson's disease: A randomized, double‐blind study
Authors: Murata Miho , Hasegawa Kazuko , Kanazawa Ichiro , Fukasaka Junichi , Kochi Kenji , Shimazu Rieko ,   The Japan Zonisamide on PD Study Group
Published: June 2015

AbstractBackgroundPreviously, we reported 50 mg/d zonisamide improved wearing‐off without increasing dyskinesia in patients with Parkinson's disease (PD).MethodsTo determine the efficacy of zonisamide for treatment of “off” time in PD patients, we conducted a multicenter, randomized, double‐blind, parallel‐group, placebo‐controlled study in Japan. Patients with PD and wearing‐off received placebo for 4 weeks and then were treated for 12 weeks with zonisamide 25 or 50 mg/d or placebo, in addition to their previous therapy. The primary endpoint was the change from baseline in daily “off” time as determined by patients’ diaries at the final assessment. Secondary endpoints included changes from baseline in the total scores of the Unified Parkinson's Disease Rating Scale Parts I, II, III, and IV, the dyskinesia duration, and PDQ‐39 score.ResultsOf 422 patients enrolled, 389 (131 for placebo, 130 for zonisamide 25 mg, and 128 for zonisamide 50 mg) were randomized, and 354 (120, 119, and 115, respectively) completed the study. The “off” time significantly reduced by 0.719 ± 0.179 h for zonisamide, 50 mg compared with placebo (0.011 ± 0.173 h, P = 0.005). Although the incidence of somnolence was higher for zonisamide (3.1% for zonisamide 25 mg, 6.3% for zonisamide 50 mg) than for placebo (2.3%), the incidences of the other adverse events, including dyskinesia or hallucination, for both zonisamide treatments were comparable to those for placebo.ConclusionThe study provides evidence that confirms the efficacy of zonisamide 50 mg/d for reduction in “off” time in PD patients with wearing‐off phenomena. © 2015 International Parkinson and Movement Disorder Society
Molecular Docking Study on Galantamine Derivatives as Cholinesterase Inhibitors
Authors: Atanasova Mariyana , Yordanov Nikola , Dimitrov Ivan , Berkov Strahil , Doytchinova Irini 
Published: June 2015

AbstractA training set of 22 synthetic galantamine derivatives binding to acetylcholinesterase was docked by GOLD and the protocol was optimized in terms of scoring function, rigidity/flexibility of the binding site, presence/absence of a water molecule inside and radius of the binding site. A moderate correlation was found between the affinities of compounds expressed as pIC50 values and their docking scores. The optimized docking protocol was validated by an external test set of 11 natural galantamine derivatives and the correlation coefficient between the docking scores and the pIC50 values was 0.800. The derived relationship was used to analyze the interactions between galantamine derivatives and AChE.
NMR‐Assisted Molecular Docking Methodologies
Authors: Sturlese Mattia , Bellanda Massimo , Moro Stefano 
Published: June 2015

AbstractNuclear magnetic resonance (NMR) spectroscopy and molecular docking are regularly being employed as helpful tools of drug discovery research. Molecular docking is an extremely rapid method to evaluate possible binders from a large chemical library in a fast and cheap manner. NMR techniques can directly detect a protein‐ligand interaction, can determine the corresponding association constant, and can consistently identify the ligand binding cavity. Consequently, molecular docking and NMR techniques are naturally complementary techniques where the combination of the two has the potential to improve the overall efficiency of drug discovery process. In this review, we would like to summarize the state of the art of docking methods which have been recently bridged to NMR experiments to identify novel and effective therapeutic drug candidates.
Acceleration of Binding Site Comparisons by Graph Partitioning
Authors: Krotzky Timo , Klebe Gerhard 
Published: June 2015

AbstractThe comparison of protein binding sites is a prominent task in computational chemistry and has been studied in many different ways. For the automatic detection and comparison of putative binding cavities the Cavbase system has been developed which uses a coarse‐grained set of pseudocenters to represent the physicochemical properties of a binding site and employs a graph‐based procedure to calculate similarities between two binding sites. However, the comparison of two graphs is computationally quite demanding which makes large‐scale studies such as the rapid screening of entire databases hardly feasible. In a recent work, we proposed the method Local Cliques (LC) for the efficient comparison of Cavbase binding sites. It employs a clique heuristic to detect the maximum common subgraph of two binding sites and an extended graph model to additionally compare the shape of individual surface patches. In this study, we present an alternative to further accelerate the LC method by partitioning the binding‐site graphs into disjoint components prior to their comparisons. The pseudocenter sets are split with regard to their assigned phyiscochemical type, which leads to seven much smaller graphs than the original one. Applying this approach on the same test scenarios as in the former comprehensive way results in a significant speed‐up without sacrificing accuracy.
Effects of ignoring clustered data structure in confirmatory factor analysis of ordered polytomous items: a simulation study based on PANSS
Authors: Stochl Jan , Jones Peter B. , Perez Jesus , Khandaker Golam M. , Böhnke Jan R. , Croudace Tim J. 
Published: June 2015

AbstractStatistical theory indicates that hierarchical clustering by interviewers or raters needs to be considered to avoid incorrect inferences when performing any analyses including regression, factor analysis (FA) or item response theory (IRT) modelling of binary or ordinal data. We use simulated Positive and Negative Syndrome Scale (PANSS) data to show the consequences (in terms of bias, variance and mean square error) of using an analysis ignoring clustering on confirmatory factor analysis (CFA) estimates. Our investigation includes the performance of different estimators, such as maximum likelihood, weighted least squares and Markov Chain Monte Carlo (MCMC). Our simulation results suggest that ignoring clustering may lead to serious bias of the estimated factor loadings, item thresholds, and corresponding standard errors in CFAs for ordinal item response data typical of that commonly encountered in psychiatric research. In addition, fit indices tend to show a poor fit for the hypothesized structural model. MCMC estimation may be more robust against clustering than maximum likelihood and weighted least squares approaches but further investigation of these issues is warranted in future simulation studies of other datasets. Copyright © 2015 John Wiley & Sons, Ltd.
Galectin signature of the choriocarcinoma JAr cells: Galectin‐1 as a modulator of invasiveness in vitro
Authors: Kolundžić Nikola , Ćujić Danica , Abu Rabi Tamara , Bojić‐Trbojević Žanka , Kadoya Toshihiko , Vićovac Ljiljana 
Published: June 2015

SUMMARYOur previous findings showed that galectin‐1 (LGALS1) plays an important role in the in vitro invasion of normal human trophoblast cells. In the present study, choriocarcinoma JAr cells were found to express LGALS1, ‐2, ‐3, ‐8, ‐10, and ‐13 mRNA and at least LGALS1, ‐3, and ‐8 protein, as determined by reverse‐transcriptase PCR and Western blot, respectively. The galectin mRNA signature of JAr cells thus differed from that of normal first‐trimester extravillous trophoblasts. A Matrigel migration assay was also used to investigate and confirm the relevance and effect of LGALS1 on the invasive potential of JAr cells, as observed in other trophoblast models. This modulation in behavior was achieved by specific lectin‐glycan binding. Mol. Reprod. Dev. 82: 765–773, 2015. © 2015 Wiley Periodicals, Inc.
Meiotic wave adds extra asymmetry to the development of female chicken gonads
Authors: de Melo Bernardo Ana , Heeren A. Marijne , van Iperen Liesbeth , Fernandes Maria Gomes , He Nannan , Anjie Stafford , Noce Toshiaki , Ramos Ester Silveira , de Sousa Lopes Susana M. Chuva 
Published: June 2015

SUMMARYDevelopment of female gonads in the chicken is asymmetric. This asymmetry affects gene expression, morphology, and germ cell development; consequently only the left ovary develops into a functional organ, whereas the right ovary remains vestigial. In males, on the other hand, both gonads develop into functional testes. Here, we revisited the development of asymmetric traits in female (and male) chicken gonads between Hamburger Hamilton stage 16 (HH16) and hatching. At HH16, primordial germ cells migrated preferentially to the left gonad, accumulating in the left coelomic hinge between the gut mesentery and developing gonad in both males and females. Using the meiotic markers SYCP3 and phosphorylated H2AFX, we identified a previously undescribed, pronounced asymmetryc meiotic progression in the germ cells located in the central, lateral, and extreme cortical regions of the left female gonad from HH38 until hatching. Moreover, we observed that—in contrast to the current view—medullary germ cells are not apoptotic, but remain arrested in pre‐leptotene until hatching. In addition to the systematic analysis of the asymmetric distribution of germ cells in female chicken gonads, we propose an updated model suggesting that the localization of germ cells—in the left or right gonad; in the cortex or medulla of the left gonad; and in the central part or the extremities of the left cortex—has direct consequences for their development and participation in adult reproduction. Mol. Reprod. Dev. 82: 774–786, 2015. © 2015 The Authors. Molecular Reproduction and Development published by Wiley Periodicals, Inc.
A constitutive model for unsaturated soil–structure interfaces
Authors: Lashkari Ali , Kadivar Mehdi 
Published: June 2015

SummaryA constitutive model for simulation of the behavior of unsaturated interfaces is presented here. The model is an extension of an existing critical state compatible interface model for dry and saturated interfaces that was already proposed by one of the authors [Lashkari, A. 2013. Int. J. Numer. Anal. Meth. Geomech.37(8): 904–931]. For a proper simulation of the behavior of partially saturated interfaces, the extended model is formulated in terms of two pairs of work conjugate stress–strain‐like variables. The modified model simulations are compared with the existing data of dry, unsaturated, and saturated interfaces. For each interface type, it is shown that the proposed model can capture the essential elements of the behavior using a unique set of parameters. Copyright © 2015 John Wiley & Sons, Ltd.
Gated Silica Mesoporous Materials in Sensing Applications
Authors: Sancenón Félix , Pascual Lluís , Oroval Mar , Aznar Elena , Martínez‐Máñez Ramón 
Published: June 2015

AbstractSilica mesoporous supports (SMSs) have a large specific surface area and volume and are particularly exciting vehicles for delivery applications. Such container‐like structures can be loaded with numerous different chemical substances, such as drugs and reporters. Gated systems also contain addressable functions at openings of voids, and cargo delivery can be controlled on‐command using chemical, biochemical or physical stimuli. Many of these gated SMSs have been applied for drug delivery. However, fewer examples of their use in sensing protocols have been reported. The approach of applying SMSs in sensing uses another concept—that of loading pores with a reporter and designing a capping mechanism that is selectively opened in the presence of a target analyte, which results in the delivery of the reporter. According to this concept, we provide herein a complete compilation of published examples of probes based on the use of capped SMSs for sensing. Examples for the detection of anions, cations, small molecules and biomolecules are provided. The diverse range of gated silica mesoporous materials presented here highlights their usefulness in recognition protocols.
Voltammetric Study of the Influence of Various Phosphate Anions on Silver Nanoparticle Oxidation
Authors: Navolotskaya Daria V. , Toh Her Shuang , Batchelor–McAuley Christopher , Compton Richard G. 
Published: June 2015

AbstractThe antibacterial properties of silver are strongly controlled by the redox couple of silver/silver(I). This work reports the influence of phosphate anions on silver nanoparticle oxidation, which is important given the abundance of phosphate species in biological systems. The three different species of anions were found to have a varying degree of influence on silver oxidation with the order PO43−>HPO42−>H2PO4−. It was found that in the presence of phosphate anions, the silver oxidation potential shifts to a less positive value, which indicated the increasing ease of the oxidation reaction of silver. Given that the interplay between silver and its cation is crucial to its antibacterial properties and significant concentrations of the HPO42− anion are present at biological pH (near neutral), it is essential that the influence of the dibasic anion (HPO42−) on silver oxidation dynamics be considered for biological systems.
Activation of the FGFR1 signalling pathway by the Epstein–Barr virus‐encoded LMP1 promotes aerobic glycolysis and transformation of human nasopharyngeal epithelial cells
Authors: Lo Angela Kwok‐Fung , Dawson Christopher W , Young Lawrence S , Ko Chuen‐Wai , Hau Pok‐Man , Lo Kwok‐Wai 
Published: June 2015

AbstractNon‐keratinizing nasopharyngeal carcinoma (NPC) is closely associated with Epstein–Barr virus (EBV) infection. The EBV‐encoded latent membrane protein 1 (LMP1) is believed to play an important role in NPC pathogenesis by virtue of its ability to activate multiple cell signalling pathways which collectively promote cell proliferation, transformation, angiogenesis, and invasiveness, as well as modulation of energy metabolism. In this study, we report that LMP1 increases cellular uptake of glucose and glutamine, enhances LDHA activity and lactate production, but reduces pyruvate kinase activity and pyruvate concentrations. LMP1 also increases the phosphorylation of PKM2, LDHA, and FGFR1, as well as the expression of PDHK1, FGFR1, c‐Myc, and HIF‐1α, regardless of oxygen availability. Collectively, these findings suggest that LMP1 promotes aerobic glycolysis. With respect to FGFR1 signalling, LMP1 not only increases FGFR1 expression, but also up‐regulates FGF2, leading to constitutive activation of the FGFR1 signalling pathway. Furthermore, two inhibitors of FGFR1 (PD161570 and SU5402) attenuate LMP1‐mediated aerobic glycolysis, cellular transformation (proliferation and anchorage‐independent growth), cell migration, and invasion in nasopharyngeal epithelial cells, identifying FGFR1 signalling as a key pathway in LMP1‐mediated growth transformation. Immunohistochemical staining revealed that high levels of phosphorylated FGFR1 are common in primary NPC specimens and that this correlated with the expression of LMP1. In addition, FGFR1 inhibitors suppress cell proliferation and anchorage‐independent growth of NPC cells. Our current findings demonstrate that LMP1‐mediated FGFR1 activation contributes to aerobic glycolysis and transformation of epithelial cells, thereby implicating FGF2/FGFR1 signalling activation in the EBV‐driven pathogenesis of NPC. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The effect of molecular weight on the separation of semiconducting single‐walled carbon nanotubes using poly(2,7‐carbazole)s
Authors: Rice Nicole A. , Subrahmanyam Ayyagari V. , Laengert Scott E. , Adronov Alex 
Published: June 2015

ABSTRACTThe use of selective interactions between conjugated polymers and single‐walled carbon nanotubes has emerged as a promising method for the separation of nanotubes by electronic type. Although much attention has been devoted to investigating polyfluorenes and their ability to disperse semiconducting carbon nanotubes under specific conditions, other polymer families, such as poly(2,7‐carbazole)s, have been relatively overlooked. Poly(2,7‐carbazole)s have been shown to also preferentially interact with semiconducting carbon nanotubes, however a detailed investigation of polymer parameters, such as molecular weight, has not been performed. We have prepared seven different molecular weights of a poly(2,7‐carbazole), from short chain oligomers to high molecular weight polymers, and have investigated their effectiveness at dispersing semiconducting single‐walled carbon nanotubes. Although all polymer chain lengths were able to efficiently exfoliate carbon nanotube bundles using a mild dispersion protocol, only polymers above a certain threshold molecular weight (Mn ∼ 27 kDa) were found to exhibit complete selectivity for semiconducting nanotubes, with no observable signals from metallic species. Additionally, we found the quality of separation to be strongly dependent on the ratio of polymer to carbon nanotube. Contrary to previous reports, we have found that an excess of poly(2,7‐carbazole) leads to incomplete removal of metallic carbon nanotubes. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 2510–2516
Effect of oxidant on electronic transport in polypyrrole nanotubes synthesized in the presence of methyl orange
Authors: Varga Martin , Kopecká Jitka , Morávková Zuzana , Křivka Ivo , Trchová Miroslava , Stejskal Jaroslav , Prokeš Jan 
Published: June 2015

ABSTRACTPolypyrrole nanotubes with diameter 60–400 nm are synthesized with methyl orange as template and various oxidants, iron(III) chloride hexahydrate, iron(III) sulfate hydrate, and ammonium peroxydisulfate. The highest electrical conductivity of compressed pellets, 66 S cm−1, is found for iron(III) chloride. Regions with 3D variable range hopping in series with ordered regions near metal–insulator transition govern the charge transport. Other oxidants and globular morphology provide less conducting samples, <10 S cm−1. The transport mechanism is identified with the heterogeneous model of tunneling between (bi)polaronic clusters with parallel contribution of Arrhenius‐like activated conductivity. The results of conductivity are correlated with the protonation level reflected in the infrared spectra and with the ratio of bipolaron/polaron bands revealed by Raman spectroscopy. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015, 53, 1147–1159