bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glutathione-related substances maintain cardiomyocyte contractile function in hypoxic conditions
Authors: Poluektov Yuri M. , Petrushanko Irina Yu. , Undrovinas Nidas A. , Lakunina Valentina A. , Khapchaev Asker Y. , Kapelko Valery I. , Abramov Alexander A. , Lakomkin Vladimir L. , Novikov Mikhail S. , Shirinsky Vladimir P. , Mitkevich Vladimir A. , Makarov Alexander A. 
Published: March 2019

AbstractSevere hypoxia leads to decline in cardiac contractility and induces arrhythmic events in part due to oxidative damage to cardiomyocyte proteins including ion transporters. This results in compromised handling of Ca2+ ions that trigger heart contractile machinery. Here, we demonstrate that thiol-containing compounds such as N-acetylcysteine (NAC), glutathione ethyl ester (et-GSH), oxidized tetraethylglutathione (tet-GSSG), oxidized glutathione (GSSG) and S-nitrosoglutathione (GSNO) are capable of reducing negative effects of hypoxia on isolated rat cardiomyocytes. Preincubation of cardiomyocytes with 0.1 mM GSNO, 0.5 mM et-GSH, GSSG, tet-GSSG or with 10 mM NAC allows cells 5-times longer tolerate the hypoxic conditions and elicit regular Ca2+ transients in response to electric pacing. The shape of Ca2+ transients generated in the presence of GSNO, et-GSH and NAC was similar to that observed in normoxic control cardiomyocytes. The leader compound, GSNO, accelerated by 34% the recovery of normal contractile function of isolated rat heart subjected to ischemia-reperfusion. GSNO increased glutathionylation of Na,K-ATPase alpha-2 subunit, the principal ion-transporter of cardiac myocyte sarcolemma, which prevents irreversible oxidation of Na,K-ATPase and regulates its function to support normal Ca2+ ion handling in hypoxic cardiomyocytes. Altogether, GSNO appears effective cardioprotector in hypoxic conditions worth further studies toward its cardiovascular application.
The acidic protein rich in leucines Anp32b is an immunomodulator of inflammation in mice
Authors: Chemnitz Jan , Pieper Dorothea , Stich Lena , Schumacher Udo , Balabanov Stefan , Spohn Michael , Grundhoff Adam , Steinkasserer Alexander , Hauber Joachim , Zinser Elisabeth 
Published: March 2019

AbstractANP32B belongs to a family of evolutionary conserved acidic nuclear phosphoproteins (ANP32A-H). Family members have been described as multifunctional regulatory proteins and proto-oncogenic factors affecting embryonic development, cell proliferation, apoptosis, and gene expression at various levels. Involvement of ANP32B in multiple processes of cellular life is reflected by the previous finding that systemic gene knockout (KO) of Anp32b leads to embryonic lethality in mice. Here, we demonstrate that a conditional KO of Anp32b is well tolerated in adult animals. However, after immune activation splenocytes isolated from Anp32b KO mice showed a strong commitment towards Th17 immune responses. Therefore, we further analyzed the respective animals in vivo using an experimental autoimmune encephalomyelitis (EAE) model. Interestingly, an exacerbated clinical score was observed in the Anp32b KO mice. This was accompanied by the finding that animal-derived T lymphocytes were in a more activated state, and RNA sequencing analyses revealed hyperactivation of several T lymphocyte-associated immune modulatory pathways, attended by significant upregulation of Tfh cell numbers that altogether might explain the observed strong autoreactive processes. Therefore, Anp32b appears to fulfill a role in regulating adequate adaptive immune responses and, hence, may be involved in dysregulation of pathways leading to autoimmune disorders and/or immune deficiencies.
Honeybees disrupt the structure and functionality of plant-pollinator networks
Authors: Valido Alfredo , Rodríguez-Rodríguez María C. , Jordano Pedro 
Published: March 2019

AbstractThe honeybee is the primary managed species worldwide for both crop pollination and honey production. Owing to beekeeping activity, its high relative abundance potentially affects the structure and functioning of pollination networks in natural ecosystems. Given that evidences about beekeeping impacts are restricted to observational studies of specific species and theoretical simulations, we still lack experimental data to test for their larger-scale impacts on biodiversity. Here we used a three-year field experiment in a natural ecosystem to compare the effects of pre- and post-establishment stages of beehives on the pollination network structure and plant reproductive success. Our results show that beekeeping reduces the diversity of wild pollinators and interaction links in the pollination networks. It disrupts their hierarchical structural organization causing the loss of interactions by generalist species, and also impairs pollination services by wild pollinators through reducing the reproductive success of those plant species highly visited by honeybees. High-density beekeeping in natural areas appears to have lasting, more serious negative impacts on biodiversity than was previously assumed.
Conjugates of methylene blue with γ-carboline derivatives as new multifunctional agents for the treatment of neurodegenerative diseases
Authors: Bachurin Sergey O. , Makhaeva Galina F. , Shevtsova Elena F. , Boltneva Natalia P. , Kovaleva Nadezhda V. , Lushchekina Sofya V. , Rudakova Elena V. , Dubova Ludmila G. , Vinogradova Daria V. , Sokolov Vladimir B. , Aksinenko Alexey Yu. , Fisenko Vladimir P. , Richardson Rudy J. , Aliev Gjumrakch 
Published: March 2019

AbstractWe studied the inhibitory activity of methylene blue (MB) γ-carbolines (gC) conjugates (MB-gCs) against human erythrocyte acetylcholinesterase (AChE), equine serum butyrylcholinesterase (BChE), and a structurally related enzyme, porcine liver carboxylesterase (CaE). In addition, we determined the ability of MB-gCs to bind to the peripheral anionic site (PAS) of Electrophorus electricus AChE (EeAChE) and competitively displace propidium iodide from this site. Moreover, we examined the ability of MB-gCs to scavenge free radicals as well as their influence on mitochondrial potential and iron-induced lipid peroxidation. We found that MB-gCs effectively inhibited AChE and BChE with IC50 values in the range 1.73–10.5 μM and exhibited low potencies against CaE (9.8–26% inhibition at 20 μM). Kinetic studies showed that MB-gCs were mixed-type reversible inhibitors of both cholinesterases. Molecular docking results showed that the MB-gCs could bind both to the catalytic active site and to the PAS of human AChE and BChE. Accordingly, MB-gCs effectively displaced propidium from the peripheral anionic site of EeAChE. In addition, MB-gCs were extremely active in both radical scavenging tests. Quantum mechanical DFT calculations suggested that free radical scavenging was likely mediated by the sulfur atom in the MB fragment. Furthermore, the MB-gCs, in like manner to MB, can restore mitochondrial membrane potential after depolarization with rotenone. Moreover, MB-gCs possess strong antioxidant properties, preventing iron-induced lipid peroxidation in mitochondria. Overall, the results indicate that MB-gCs are promising candidates for further optimization as multitarget therapeutic agents for neurodegenerative diseases.
Covalent Modification by Glyoxals Converts Cytochrome c Into its Apoptotically Competent State
Authors: Sharma Gurumayum Suraj , Warepam Marina , Bhattacharya Reshmee , Singh Laishram Rajendrakumar 
Published: March 2019

AbstractThe effects of glycation by glyoxal (Gly) and methylglyoxal (MGly) on the early and late conformational alterations in Cytochrome c (Cyt c) were studied. Spectroscopic measurements revealed that Cyt c undergo certain conformational alterations and exposure of heme upon overnight incubation with Gly and MGly. These were followed by the reduction of heme centre and activation of its peroxidase-like, which is crucial for initiation of the intrinsic apoptotic pathway. An extended incubation resulted in appearance of AGE-like fluorescence, with significant alterations in secondary structural compositions. However, no amyloidogenic conversions were observed as suggested by TEM analyses. The study provides an insight to the role of glycating agents, elevated under oxidative stress in inducing Cyt c release and apoptosis.
Development of live attenuated Enterovirus 71 vaccine strains that confer protection against lethal challenge in mice
Authors: Yee Pinn Tsin Isabel , Tan Soon Hao , Ong Kien Chai , Tan Kuan Onn , Wong Kum Thong , Hassan Sharifah Syed , Poh Chit Laa 
Published: March 2019

AbstractBesides causing mild hand, foot and mouth infections, Enterovirus A71 (EV-A71) is associated with neurological complications and fatality. With concerns about rising EV-A71 virulence, there is an urgency for more effective vaccines. The live attenuated vaccine (LAV) is a more valuable vaccine as it can elicit both humoral and cellular immune responses. A miRNA-based vaccine strain (pIY) carrying let-7a and miR-124a target genes in the EV-A71 genome which has a partial deletion in the 5′NTR (∆11 bp) and G64R mutation (3Dp°l) was designed. The viral RNA copy number and viral titers of the pIY strain were significantly lower in SHSY-5Y cells that expressed both let-7a and miR-124a. Inhibition of the cognate miRNAs expressed in RD and SHSY-5Y cells demonstrated de-repression of viral mRNA translation. A previously constructed multiply mutated strain, MMS and the pIY vaccine strain were assessed in their ability to protect 4-week old mice from hind limb paralysis. The MMS showed higher amounts of IFN-γex vivothan the pIY vaccine strain. There was absence of EV-A71 antigen in the skeletal muscles and spinal cord micrographs of mice vaccinated with the MMS and pIY strains. The MMS and pIY strains are promising LAV candidates developed against severe EV-A71 infections.
Elevated pretreatment platelet-to-lymphocyte ratio is associated with poor survival in stage IV non-small cell lung cancer with malignant pleural effusion
Authors: Lim Jeong Uk , Yeo Chang Dong , Kang Hye Seon , Park Chan Kwon , Kim Ju Sang , Kim Jin Woo , Kim Seung Joon , Lee Sang Haak 
Published: March 2019

AbstractA higher platelet-to-lymphocyte ratio (PLR) has a clinical correlation with shorter survival in non-small cell lung cancer (NSCLC). The present study evaluated the association between the PLR and survival in patients with advanced NSCLC with malignant pleural effusion (MPE). Between January 2012 and July 2016, 237 patients with stage IV NSCLC were selected for evaluation. Receiver operating characteristic analysis was used to determine a cutoff for the PLR. Clinicopathological characteristics were compared between the high and low PLR groups, and the role of PLR as a predictive/prognostic maker was investigated. Among the 237 patients, 122 were assigned to the low PLR group and the other 115 to the high PLR group. According to multivariate analysis, male sex, not receiving active anticancer treatment, low hemoglobin level, low albumin level, high C-reactive protein level, and high PLR were identified as significant risk factors for shorter overall survival (OS) (p = 0.010, <0.001, 0.011, 0.004, 0.003, and <0.001, respectively). In the subgroup multivariate analysis of driver mutation-negative NSCLC, high Eastern Cooperative Oncology Group score, not receiving active anticancer treatment, low hemoglobin level, high C-reactive protein level, and high PLR were identified as significant risk factors for shorter OS (p = 0.047, <0.001, = 0.036, = 0.003, and <0.001, respectively). A high pretreatment PLR is independently associated with poor survival in stage IV NSCLC with MPE and in a subgroup of epidermal growth factor receptor and anaplastic lymphoma kinase wild-type NSCLC.
Transsphenoidal versus Transcranial Approach for Treatment of Tuberculum Sellae Meningiomas: A Systematic Review and Meta-analysis of Comparative Studies
Authors: Yang Chengxian , Fan Yanghua , Shen Zhiwei , Wang Renzhi , Bao Xinjie 
Published: March 2019

AbstractThere is controversy regarding the surgical route selection for tuberculum sellae meningiomas (TSMs): the transsphenoidal (TS) or transcranial (TC) approach? We conducted a systematic review and meta-analysis to compare clinical outcomes and postoperative complications between two surgical approaches. Literature search was performed. Relevant articles were selected and evaluated. Data were extracted and analyzed. Eight articles comprising 550 patients met the inclusion criteria. Traditionally, the rates of gross total resection, tumor recurrence, visual improvement, and cerebrospinal fluid leakage were the most common outcomes of interest. We demonstrated that the TS approach was significantly associated with better visual outcomes but more frequent cerebrospinal fluid leakage, while the rates of tumor resection and recurrence showed no significant difference between groups. In addition to surgical results that were consistent with previous studies, we further evaluated the impact of approach selection on common postoperative complications, which were closely related to the recovery course and quality of life. We revealed that the risk of dysosmia was significantly higher in the TS group. There was no significant difference between groups regarding infection, intracranial hemorrhage, and endocrine disorders. Because of the relatively low evidence levels of included retrospective studies, it was difficult to reach a categorical conclusion about the optimal surgical approach for TSMs. Finally, we recommended that the TS approach was an alternative option in patients with smaller TSMs (<30 mm) and limited invasion of optic canals in experienced neurosurgical centers.
Proteomic profiling of whole-saliva reveals correlation between Burning Mouth Syndrome and the neurotrophin signaling pathway
Authors: Krief Guy , Haviv Yaron , Deutsch Omer , Keshet Naama , Almoznino Galit , Zacks Batia , Palmon Aaron , Aframian Doron J. 
Published: March 2019

AbstractBurning mouth syndrome (BMS) is characterized by a spontaneous and chronic sensation of burning in the oral mucosa, with no apparent signs. The underlying pathophysiological and neuropathic mechanisms remain unclear. Here, we attempt to elucidate some of these mechanisms using proteomic profiling and bioinformatic analyses of whole-saliva (WS) from BMS patients compared to WS from healthy individuals. Qualitative and quantitative proteomic profiling was performed using two dimensional gel electrophoresis (2-DE) and quantitative mass spectrometry (q-MS). In order to improve protein visibility, 21 high abundance proteins were depleted before proteomic profiling. Quantitative proteomic analysis revealed 100 BMS specific proteins and an additional 158 proteins up-regulated by more than threefold in those with BMS. Bioinformatic analyses of the altered protein expression profile of BMS group indicated high correlations to three cellular mechanisms including the neurotrophin signaling pathway. Based on this finding, we suggest that neurotrophin signaling pathway is involved in the pathophysiology of BMS by amplifying P75NTR activity, which in turn increases neural apoptosis thereby reducing sub-papillary nerve fiber density in the oral mucosa.
Regeneration associated transcriptional signature of retinal microglia and macrophages
Authors: Mitchell Diana M. , Sun Chi , Hunter Samuel S. , New Daniel D. , Stenkamp Deborah L. 
Published: March 2019

AbstractZebrafish have the remarkable capacity to regenerate retinal neurons following a variety of damage paradigms. Following initial tissue insult and a period of cell death, a proliferative phase ensues that generates neuronal progenitors, which ultimately regenerate damaged neurons. Recent work has revealed that Müller glia are the source of regenerated neurons in zebrafish. However, the roles of another important class of glia present in the retina, microglia, during this regenerative phase remain elusive. Here, we examine retinal tissue and perform QuantSeq. 3′mRNA sequencing/transcriptome analysis to reveal localization and putative functions, respectively, ofmpeg1expressing cells (microglia/macrophages) during Müller glia-mediated regeneration, corresponding to a time of progenitor proliferation and production of new neurons. Our results indicate that in this regenerative state,mpeg1-expressing cells are located in regions containing regenerative Müller glia and are likely engaged in active vesicle trafficking. Further,mpeg1+ cells congregate at and around the optic nerve head. Our transcriptome analysis reveals several novel genes not previously described in microglia. This dataset represents the first report, to our knowledge, to use RNA sequencing to probe the microglial transcriptome in such context, and therefore provides a resource towards understanding microglia/macrophage function during successful retinal (and central nervous tissue) regeneration.
Modelling of stress distribution and fracture in dental occlusal fissures
Authors: Wan Boyang , Shahmoradi Mahdi , Zhang Zhongpu , Shibata Yo , Sarrafpour Babak , Swain Michael , Li Qing 
Published: March 2019

AbstractThe aim of this study was to investigate the fracture behaviour of fissural dental enamel under simulated occlusal load in relation to various interacting factors including fissure morphology, cuspal angle and the underlying material properties of enamel. Extended finite element method (XFEM) was adopted here to analyse the fracture load and crack length in tooth models with different cusp angles (ranging from 50° to 70° in 2.5° intervals), fissural morphologies (namely U shape, V shape, IK shape, I shape and Inverted-Y shape) and enamel material properties (constant versus graded). The analysis results showed that fissures with larger curved morphology, such as U shape and IK shape, exhibit higher resistance to fracture under simulated occlusal load irrespective of cusp angle and enamel properties. Increased cusp angle (i.e. lower cusp steepness), also significantly enhanced the fracture resistance of fissural enamel, particularly for the IK and Inverted-Y shape fissures. Overall, the outcomes of this study explain how the interplay of compositional and structural features of enamel in the fissural area contribute to the resistance of the human tooth against masticatory forces. These findings may provide significant indicators for clinicians and technicians in designing/fabricating extra-coronal dental restorations and correcting the cuspal inclinations and contacts during clinical occlusal adjustment.
Pollens destroy respiratory epithelial cell anchors and drive alphaherpesvirus infection
Authors: Van Cleemput Jolien , Poelaert Katrien C. K. , Laval Kathlyn , Impens Francis , Van den Broeck Wim , Gevaert Kris , Nauwynck Hans. J. 
Published: March 2019

AbstractPollens are well-known triggers of respiratory allergies and asthma. The pollen burden in today’s ambient air is constantly increasing due to rising climate change and air pollution. How pollens interact with the respiratory mucosa remains largely unknown due to a lack of representative model systems. We here demonstrate how pollen proteases of Kentucky bluegrass, white birch and hazel selectively destroy integrity and anchorage of columnar respiratory epithelial cells, but not of basal cells, in bothex vivorespiratory mucosal explants andin vitroprimary equine respiratory epithelial cells (EREC). In turn, this pollen protease-induced damage to respiratory epithelial cell anchorage resulted in increased infection by the host-specific and ancestral alphaherpesvirus equine herpesvirus type 1 (EHV1). Pollen proteases of all three plant species were characterized by zymography and those of white birch were fully identified for the first time as serine proteases of the subtilase family and meiotic prophase aminopeptidase 1 using mass spectrometry-based proteomics. Together, our findings demonstrate that pollen proteases selectively and irreversibly damage integrity and anchorage of columnar respiratory epithelial cells. In turn, alphaherpesviruses benefit from this partial loss-of-barrier function, resulting in increased infection of the respiratory epithelium.
Acute-phase proteins during inflammatory reaction by bacterial infection: Fish-model
Authors: Charlie-Silva Ives , Klein Andre , Gomes Juliana M. M. , Prado Ed J. R. , Moraes Alessandra C. , Eto Silas F. , Fernandes Dayanne C. , Fagliari José J. , Junior José D. Corrêa , Lima Carla , Lopes-Ferreira Mônica , Conceição Katia , Manrique Wilson G. , Belo Marco A. A. 
Published: March 2019

AbstractAcute-phase protein (APPs) serum levels have been studied in many human diseases, and their components contribute to host defense during the evolution of infectious diseases by acting as part of the innate immune system. Based on the importance of establishing new experimental models, the present investigation evaluated the modulation of APPs following inflammatory stimulus by the inoculation ofAeromonas hydrophilain tilapias. Fish were sampled 6 and 24 hours post-infection. Tilapias presented increase of positive APPs such as ceruloplasmin, haptoglobin, alpha-2-macroglobulin and complement C3, as well as decrease of negative APPs such as albumin and transferrin. The protein response of tilapias during the course of bacterial infection showed correlation with the kinetics of cellular accumulation in the inflamed focus with significant increase of granulocytes, thrombocytes, lymphocytes and macrophages. However, granulocytes were the predominant cells, associated with increment in the reactive oxygen species (ROS) production. Showing responses similar to those observed in humans, the modulation of APPs and the kinetics of cellular accumulation in the exudate demonstrate the feasibility of this alternative experimental model for advances and studies to understand changes in pathophysiological mechanisms of acute inflammatory reaction due to bacterial infection.
Novel Data Transformations for RNA-seq Differential Expression Analysis
Authors: Zhang Zeyu , Yu Danyang , Seo Minseok , Hersh Craig P. , Weiss Scott T. , Qiu Weiliang 
Published: March 2019

AbstractWe propose eight data transformations (r, r2, rv, rv2, l, l2, lv, and lv2) for RNA-seq data analysis aiming to make the transformed sample mean to be representative of the distribution center since it is not always possible to transform count data to satisfy the normality assumption. Simulation studies showed that for data sets with small (e.g., nCases = nControls = 3) or large sample size (e.g., nCases = nControls = 100) limma based on data from the l, l2, and r2 transformations performed better than limma based on data from the voom transformation in term of accuracy, FDR, and FNR. For datasets with moderate sample size (e.g., nCases = nControls = 30 or 50), limma with the rv and rv2 transformations performed similarly to limma with the voom transformation. Real data analysis results are consistent with simulation analysis results: limma with the r, l, r2, and l2 transformation performed better than limma with the voom transformation when sample sizes are small or large; limma with the rv and rv2 transformations performed similarly to limma with the voom transformation when sample sizes are moderate. We also observed from our data analyses that for datasets with large sample size, the gene-selection via the Wilcoxon rank sum test (a non-parametric two sample test method) based on the raw data outperformed limma based on the transformed data.