bluuebunny/crossref_metadata_2025_split huggingface dataset:
Normal Temporal Discrimination in Musician's Dystonia Is Linked to Aberrant Sensorimotor Processing
Authors: Maguire Fiachra , Reilly Richard B. , Simonyan Kristina 
Published: January 2020

AbstractObjectivesAlterations in sensory discrimination are a prominent nonmotor feature of dystonia. Abnormal temporal discrimination in focal dystonia is considered to represent its mediational endophenotype, albeit unclear pathophysiological correlates. We examined the associations between the visual temporal discrimination threshold (TDT) and brain activity in patients with musician's dystonia, nonmusician's dystonia, and healthy controls.MethodsA total of 42 patients and 41 healthy controls participated in the study. Between‐group differences in TDTzscores were computed using inferential statistics. Statistical associations of TDTzscores with clinical characteristics of dystonia and resting‐state functional brain activity were examined using nonparametric rank correlations.ResultsThe TDTzscores of healthy controls were significantly different from those of patients with nonmusician's dystonia, but not of patients with musician's dystonia. Healthy controls showed a significant relationship between normal TDT levels and activity in the inferior parietal cortex. This relationship was lost in all patients. Instead, TDTzscores in musician's dystonia established additional correlations with activity in premotor, primary somatosensory, ventral extrastriate cortices, inferior occipital gyrus, precuneus, and cerebellum, whereas nonmusician's dystonia showed a trending correlation in the lingual gyrus extending to the cerebellar vermis. There were no significant relationships between TDTzscores and dystonia onset, duration, or severity.ConclusionsTDT assessment as an endophenotypic marker may only be relevant to nonmusician forms of dystonia because of the lack of apparent alterations in musician's dystonia. Compensatory adaptation of neural circuitry responsible for TDT processing likely adjusted the TDT performance to the behaviorally normal levels in patients with musician's dystonia, but not nonmusician's dystonia. © 2020 International Parkinson and Movement Disorder Society
Role of Glial Cell Line‐Derived Neurotrophic Factor in the Maintenance of Adult Mesencephalic Catecholaminergic Neurons
Authors: Enterría‐Morales Daniel , López‐López Ivette , López‐Barneo José , d'Anglemont de Tassigny Xavier 
Published: January 2020

AbstractBackgroundThe glial cell line‐derived neurotrophic factor has a potent neuroprotective action on mesencephalic dopamine neurons, which are progressively lost in Parkinson's disease. Intrastriatal administration of this factor is a promising therapy for Parkinson's disease. Glial cell line‐derived neurotrophic factor is naturally produced in restricted cerebral regions, such as the striatum, septum, and thalamus; however, its effects in the adult brain remain under debate.ObjectivesWe sought to clarify the physiologic role of endogenous glial cell line‐derived neurotrophic factor in the survival of catecholaminergic neurons of the substantia nigra pars compacta and the locus coeruleus in adult mice.MethodsWe used 2 new Cre recombinase‐based mouse models to delete a floxed–glial cell line‐derived neurotrophic factor gene. The first model had Cre expression in the parvalbumin expressing interneurons, as these cells represent the major source of striatal glial cell line‐derived neurotrophic factor. The second model was an estrogen receptor 2‐based inducible Cre triggered by tamoxifen at 2 months of age.ResultsWe found that the floxed–glial cell line‐derived neurotrophic factor gene was resilient to ablation by Cre‐induced recombination and that parvalbumin‐driven Cre was particularly inefficient to do so. The inducible‐Cre model allowed an average 70% to 80% reduction in glial cell line‐derived neurotrophic factor messenger ribonucleic acid and protein in striatum and septum with moderate significant loss of catecholamine neurons in the nigrostriatal pathway and, more markedly, in the locus coeruleus. This was accompanied with mild locomotor decline.ConclusionsOur data support qualitatively the view that brain glial cell line‐derived neurotrophic factor is needed for the maintenance of adult central catecholaminergic neurons. © 2020 International Parkinson and Movement Disorder Society
The Use of the Index of Ideality of Correlation to Build Up Models for Bioconcentration Factor
Authors: Toropova Alla P. , Duchowicz Pablo R. , Saavedra Laura M. , Castro Eduardo A. , Toropov Andrey A. 
Published: January 2020

AbstractWe establish a QSPR analysis for the bioconcentration factor of 851 heterogeneous structural compounds. Linear models are proposed via two different approaches: i. the optimal descriptor method implemented in CORAL, and ii. multivariable linear regressions on the best molecular descriptors found with the Replacement Method on 44,216 structural descriptors. Such variables are derived with different freely available softwares, such as PaDEL, PyDescriptor, Mold2, QuBiLs‐MAS and ISIDA/Fragmentor. The same validation set is employed in order to compare the predictive performance between the so‐obtained CORAL and RM based models. Finally, the comparison of several models for the bioconcentration factor confirms the ability of the so‐called index of ideality of correlation to be a criterion of predictive potential in Quantitative Structure‐Property Relationships.
Combined use of dbcAMP and IBMX minimizes the damage induced by a long‐term artificial meiotic arrest in mouse germinal vesicle oocytes
Authors: Wu Xue‐Chen , Han Zhe , Hao Xin , Zhao Yi‐Tong , Zhou Cheng‐Jie , Wen Xin , Liang Cheng‐Guang 
Published: January 2020

AbstractPhosphodiesterase (PDE)‐mediated reduction of cyclic adenosine monophosphate (cAMP) activity can initiate germinal vesicle (GV) breakdown in mammalian oocytes. It is crucial to maintain oocytes at the GV stage for a long period to analyze meiotic resumption in vitro. Meiotic resumption can be reversibly inhibited in isolated oocytes by cAMP modulator forskolin, cAMP analog dibutyryl cAMP (dbcAMP), or PDE inhibitors, milrinone (Mil), Cilostazol (CLZ), and 3‐isobutyl‐1‐methylxanthine (IBMX). However, these chemicals negatively affect oocyte development and maturation when used independently. Here, we used ICR mice to develop a model that could maintain GV‐stage arrest with minimal toxic effects on subsequent oocyte and embryonic development. We identified optimal concentrations of forskolin, dbcAMP, Mil, CLZ, IBMX, and their combinations for inhibiting oocyte meiotic resumption. Adverse effects were assessed according to subsequent development potential, including meiotic resumption after washout, first polar body extrusion, early apoptosis, double‐strand DNA breaks, mitochondrial distribution, adenosine triphosphate levels, and embryonic development. Incubation with a combination of 50.0 μM dbcAMP and 10.0 μM IBMX efficiently inhibited meiotic resumption in GV‐stage oocytes, with low toxicity on subsequent oocyte maturation and embryonic development. This work proposes a novel method with reduced toxicity to effectively arrest and maintain mouse oocytes at the GV stage.
Early Weaning Effects on Survival, Growth, and Histopathology of Larval Sterlet Acipenser ruthenus
Authors: Laczynska Beata , Siddique Mohammad Abdul Momin , Ziomek Elzbieta , Shelton William L , Fopp-Bayat Dorota 
Published: January 2020

Abstract
Weaning of fish is a critical stage during larval rearing and could cause high mortality. Therefore, proper larval weaning period selection is crucial for the success of larviculture. This study aimed to find the effect of weaning on growth performance, histopathological features, and mortality rates in larvae of Sterlet Acipenser ruthenus. The experimental rearing was conducted from 7 to 38 d posthatch (dph) at a mean temperature of 18°C in a recirculating system. The experiment was carried out in three groups (each with three replicates) and placed in nine tanks (22 L) at a density of 10 individuals/L. The diet groups were made up of group C in which larvae were fed with nauplii of brine shrimp Artemia spp., group F7 in which larvae were weaned to dry feed 15 dph, and group F that was fed with dry feed throughout the experimental trial. During 15–38 dph, total wet body weight and total length were lowest in the group fed with formulated feed. Survival rate of larvae in group F7 was 90.45% and 70.05% during 7–14 and 15–22 dph, respectively. On the other hand, the survival rate of larvae fed only Artemia nauplii (group C) or formulated feed (group F) was 86.14% and 70.45% during 7–14 dph and 84.55% and 78.41% during 15–22 dph, respectively. The maximum height of the enterocytic epithelium was found in the individuals in group F7 (mean ± SD = 33.80 ± 2.56 μm). The average height of enterocytes of group F7 (n =30 fish) larvae were significantly increased at 15, 23, and 38 dph compared with the larvae fed with formulated feed and live feed, but no significant changes were observed in the liver cells, including in the diameter of hepatocytes and their nuclei. This study provides evidence that Sterlet larvae should be fed with Artemia nauplii at 7–15 dph because fish gain a higher wet body weight and total length and develop a better liver and digestive tract.
Voluntary exercise improves voiding function and bladder hyperalgesia in an animal model of stress‐induced visceral hypersensitivity: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome research network study
Authors: Sanford Melissa T. , Yeh Jih‐chao , Mao Jackie J. , Guo Yumei , Wang Zhuo , Zhang Rong , Holschneider Daniel P. , Rodriguez Larissa V. 
Published: January 2020

AbstractObjectiveThe underlying mechanism of interstitial cystitis/bladder pain syndrome (IC/BPS) is not well understood and evaluation of current therapeutic interventions has not identified any generally effective treatments. Physical activity has shown beneficial effects on individuals suffering from chronic pain. Anxiety‐prone rats exposed to water avoidance stress (WAS) develop urinary frequency and lower bladder sensory thresholds with high face and construct validity for the study of IC/BPS. The aim of this study was to evaluate the role of chronic voluntary exercise on urinary frequency, voiding function, and hyperalgesia in animals exposed to WAS.Materials and MethodsTwenty‐six female Wistar‐Kyoto rats were exposed to WAS and thereafter randomized to either voluntary exercise for 3 weeks or sedentary groups. Voiding parameters were assessed at baseline, post‐WAS, and weekly for 3 weeks. Before euthanasia, the animals underwent cystometrogram (CMG), external urinary sphincter electromyography, and assessment of visceromotor response (VMR) to isotonic bladder distension (IBD).ResultsWAS exposure resulted in adverse changes in voiding parameters. Compared with sedentary animals, animals in the voluntary exercise group had improved voiding parameters during metabolic cage and CMG testing, as well as improved bladder sensory thresholds as determined by VMR during IBD.ConclusionVoluntary exercise in an animal model of chronic stress leads to improvement in voiding function and visceral bladder hyperalgesia.
Global cracking elements: A novel tool for Galerkin‐based approaches simulating quasi‐brittle fracture
Authors: Zhang Yiming , Mang Herbert A. 
Published: January 2020

SummaryFollowing the so‐called cracking elements method (CEM), we propose a novel Galerkin‐based numerical approach for simulating quasi‐brittle fracture, named global cracking elements method (GCEM). For this purpose the formulation of the original CEM is reorganized. The new approach is embedded in the standard framework of the Galerkin‐based finite‐element method (FEM), which uses disconnected element‐wise crack openings for capturing crack initiation and propagation. The similarity between the proposed global cracking elements (GCEs) and the standard nine‐node quadrilateral element (Q9) suggests a special procedure: the degrees of freedom of the center node of the Q9, originally defining the displacements, are “borrowed” to describe the crack openings of the GCE. The proposed approach does not need remeshing, enrichment, or a crack‐tracking strategy, and it avoids a precise description of the crack tip. Several benchmark tests provide evidence that the new approach inherits from the CEM most of the advantages. The numerical stability and robustness of the GCEM are better than the ones of the CEM. However, presently only quadrilateral elements with nonlinear interpolations of the displacement field can be used.
Emerging Roles and Research Tools of Atypical Ubiquitination
Authors: Huang Qiuling , Zhang Xiaofei 
Published: January 2020

AbstractUbiquitination is a posttranslational modification characterized by the covalent attachment of ubiquitin molecules to protein substrates. The ubiquitination modification process is reversible, dynamic, and involved in the regulation of various biological processes, such as autophagy, inflammatory responses, and DNA damage responses. The forms of ubiquitin modification are very diverse, incorporating either a single ubiquitin molecule or a complicated ubiquitin polymer, and different types of ubiquitination usually elicit corresponding cellular responses. The development of research tools and strategies has afforded more detailed insight into atypical ubiquitin signaling pathways that were previously poorly understood. Here, an update on the understanding of atypical ubiquitin chain signaling pathways is provided and the recent development of representative research tools for ubiquitin systems is discussed. In addition, the future challenges in ubiquitin research are reflected on and summarized.
A complex interprofessional intervention to improve the management of painful procedures in neonates
Authors: Balice‐Bourgois Colette , Newman Christopher J. , Simonetti Giacomo D. , Zumstein‐Shaha Maya 
Published: January 2020

AbstractDuring hospitalization, neonates are exposed to a stressful environment and a high number of painful procedures. If pain is not treated adequately, short‐ and long‐term complications may develop. Despite evidence about neonatal pain and available guidelines, procedural pain remains undertreated. This gap between research and practice is mostly due to limited implementation of evidence‐based knowledge and time constraints. This study describes in detail the development process of a complex interprofessional intervention to improve the management of procedural pain in neonates called NEODOL© (NEOnato DOLore). The framework of the Medical Research Council (MRC) for the development and evaluation of complex interventions was used as a methodological guide for the design of the NEODOL© intervention. The development of the intervention is based on several steps and multiple methods. To report this process, we used the Criteria for Reporting the Development of Complex Interventions in Healthcare (CReDECI 2). Additionally, we evaluated the content of the intervention using a Delphi method to obtain consensus from experts, stakeholders, and parents. The complex interprofessional intervention, NEODOL©, is developed and designed for three groups: healthcare professionals, parents, and neonates for a level IIb neonatal unit at a regional hospital in southern Switzerland. A total of 16 panelists participated in the Delphi process. At the end of the Delphi process, the panelists endorsed the NEODOL© intervention as important and feasible. Following the MRC guidelines, a multimethod process was used to develop a complex interprofessional intervention to improve the management of painful procedures in newborns. Complex interprofessional interventions need theoretical bases, careful development, and integration of stakeholders to provide a comprehensive approach. The NEODOL intervention consists of promising components and has the potential to improve the management of painful procedures and should facilitate the knowledge translation into practice.
Site‐specific rapid deamidation and isomerization in human lens αA‐crystallin in vitro
Authors: Takata Takumi , Ha Seongmin , Koide Tamaki , Fujii Noriko 
Published: January 2020

AbstractRecent studies have suggested that the isomerization/racemization of aspartate residues in proteins increases in aged tissues. One such residue is Asp151 in lens‐specific αA‐crystallin. Although many isomerization/racemization sites have been reported in various proteins, the factors that lead to those modifications in proteins in vivo remain obscure. Therefore, an in vitro system is needed to assess the mechanisms of modifications of Asp under various conditions. Deamidation of Asn to Asp in proteins occurs more rapidly than isomerization/racemization of Asp, although the reaction passes through the same intermediate in both pathways. Here, therefore, we replaced Asp151 in human lens αA‐crystallin with Asn by using site‐directed mutagenesis. The recombinant protein was expressed in Escherichia coli and used to investigate the deamidation/isomerization/racemization of Asn151 after incubation at 50°C for various durations and under different pH. After incubation, the mutant αA‐crystallin was subjected to enzymatic digestion followed by liquid chromatography–MS/MS to evaluate the ratio of modifications in Asn151‐containing peptides. The Asp151Asn αA‐crystallin mutant showed rapid deamidation to Asp with the formation of specific Asp isomers. In particular, deamidation increased greatly under basic conditions. By contrast, subunit–subunit interactions between αA‐crystallin and αB‐crystallin had little effect on the modification of Asn151. Our findings suggest that the Asp151Asn αA‐crystallin mutant represents a good in vitro model protein to assess deamidation, isomerization, and the racemization intermediates. Furthermore, our in vitro results show a different trend from in vivo data, implying the presence of specific factors that induce racemization from L‐Asp to D‐Asp residues in vivo.
Allosteric inhibitors of Mycobacterium tuberculosis tryptophan synthase
Authors: Michalska Karolina , Chang Changsoo , Maltseva Natalia I. , Jedrzejczak Robert , Robertson Gregory T. , Gusovsky Fabian , McCarren Patrick , Schreiber Stuart L. , Nag Partha P. , Joachimiak Andrzej 
Published: January 2020

AbstractGlobal dispersion of multidrug resistant bacteria is very common and evolution of antibiotic‐resistance is occurring at an alarming rate, presenting a formidable challenge for humanity. The development of new therapeuthics with novel molecular targets is urgently needed. Current drugs primarily affect protein, nucleic acid, and cell wall synthesis. Metabolic pathways, including those involved in amino acid biosynthesis, have recently sparked interest in the drug discovery community as potential reservoirs of such novel targets. Tryptophan biosynthesis, utilized by bacteria but absent in humans, represents one of the currently studied processes with a therapeutic focus. It has been shown that tryptophan synthase (TrpAB) is required for survival of Mycobacterium tuberculosis in macrophages and for evading host defense, and therefore is a promising drug target. Here we present crystal structures of TrpAB with two allosteric inhibitors of M. tuberculosis tryptophan synthase that belong to sulfolane and indole‐5‐sulfonamide chemical scaffolds. We compare our results with previously reported structural and biochemical studies of another, azetidine‐containing M. tuberculosis tryptophan synthase inhibitor. This work shows how structurally distinct ligands can occupy the same allosteric site and make specific interactions. It also highlights the potential benefit of targeting more variable allosteric sites of important metabolic enzymes.
Effects of an engineered log jam on spatial variability of the flow field across submergence depths
Authors: L'Hommedieu William , Tullos Desirée , Jones Julia 
Published: January 2020

AbstractEngineered log jams (ELJs) are commonly implemented in rivers to diversify fish habitat, but few studies have verified the hydraulic benefits of ELJs by assessing their effects on the spatial variability and turbulence structure of the flow field. This field and modelling study assessed the effects of an ELJ on various characteristics of the flow field with increasing submergence. A 2‐D hydrodynamic model was applied to simulate flow conditions of the Calapooia River, Oregon, with an ELJ installed at the upstream end of a meander. Output was analyzed using coherent flow structure identification, maps of turbulence measures, and wavelet analysis along linear transects. At the highest discharge (62% ELJ submergence), more and smaller coherent flow structures were identified than in the no ELJ model run, but the magnitudes of turbulence metrics were unaffected. At low flow (1% jam submergence), the presence of the ELJ did not affect the number of coherent flow structures identified and produced only small and localized effects on turbulence measures. Taken together, results indicate that the ELJ primarily affected the flow field by increasing the number of flow structures at higher discharges and submergence depths. However, these changes were small and local to the ELJ. The limited effects of this wood jam over limited spatial scales raise questions about the conditions under which such structures increase hydraulic diversity and highlight the need for more detailed understanding on spatial variability around habitat structures with complex shapes.
Asymptotic normality in random graphs with given vertex degrees
Authors: Janson Svante 
Published: January 2020

AbstractWe consider random graphs with a given degree sequence and show, under weak technical conditions, asymptotic normality of the number of components isomorphic to a given tree, first for the random multigraph given by the configuration model and then, by a conditioning argument, for the simple uniform random graph with the given degree sequence. Such conditioning is standard for convergence in probability, but much less straightforward for convergence in distribution as here. The proof uses the method of moments, and is based on a new estimate of mixed cumulants in a case of weakly dependent variables. The result on small components is applied to give a new proof of a recent result by Barbour and Röllin on asymptotic normality of the size of the giant component in the random multigraph; moreover, we extend this to the random simple graph.
Evolutionary analysis on structural characteristics of water resource system in basins of Northern China
Authors: Lu Shibao , Zhang Xiaoling , Tang Yao 
Published: January 2020

AbstractThe overdevelopment of water resources has caused the deterioration of the river ecology and environment, resulting in increasing water shortages. This has become one of the key factors that restricts the sustainable development of the social economy and ecological environment of the region. The water network system of the Songhua, Liaohe, Yellow, and Haihe river basins is analyzed by using ecological network analysis for the period 2004–2017. According to our findings, the network structures of various river basins present a relevant gap from its equilibrium value; thus, the water resources have not reached the state of sustainable use. By comparing the value of the water system in Songliao, Yellow, and Haihe river basins with aopt, we found that only the water network structure of the Songliao River Basin is close to the point of equilibrium. Therefore, we recommend to improve water‐use efficiency and reduce production and domestic water consumption by adjusting water prices, carrying out agricultural water‐saving irrigation, and increasing the use of industrial circulating water. This set of measures would ensure sufficient ecological water consumption in the basin, in order to meet the needs of a healthy and sustainable development of the ecological environment.