bluuebunny/crossref_metadata_2025 huggingface dataset:
Mathematical modelling of the impact of treating latent tuberculosis infection in the elderly in a city with intermediate tuberculosis burden
Authors: Chong Ka Chun , Leung Chi Chiu , Yew Wing Wai , Zee Benny Chung Ying , Tam Greta Chun Huen , Wang Maggie Haitian , Jia Katherine Min , Chung Pui Hong , Lau Steven Yuk Fai , Han Xiaoran , Yeoh Eng Kiong
Published: March 2019

Hong Kong is a high-income city with intermediate tuberculosis (TB) burden primarily driven by endogenous reactivations. A high proportion of remote latently infected people, particularly elderly, hinders the effectiveness of current strategies focusing on passive TB detection. In this study, we developed a mathematical model to evaluate the impact of treating latent TB infection (LTBI) in the elderly in addition to current TB control strategies. The model was calibrated using the annual age-stratified TB notifications from 1965–2013 in Hong Kong. Our results showed that at present, approximately 75% of annual new notifications were from reactivations. Given the present treatment completion rate, even if only a low to moderate proportion (approximately 20% to 40%) of elderly people were screened and treated for LTBI, the overall TB incidence could be reduced by almost 50%, to reach the 2025 milestone of the global End TB Strategy. Nevertheless, due to a high risk of hepatotoxicity in elderly population, benefit-risk ratios were mostly below unity; thus, intervention programs should be carefully formulated, including prioritising LTBI treatment for high-risk elderly groups who are closely monitored for possible adverse side effects.
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

Severe 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

ANP32B 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

The 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

We 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

The 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

Besides 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

A 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

There 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

Burning 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

Zebrafish 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

The 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

Pollens 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

Acute-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

We 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.
Genetic analysis of admixture and hybrid patterns of Populus hopeiensis and P. tomentosa
Authors: Wang Dongsheng , Wang Zhaoshan , Kang Xiangyang , Zhang Jianguo
Published: March 2019

Hybridization and introgression have resulted in reticulate evolution within the genusPopulus. Consequently, the origin and evolutionary history of some hybrids has become blurred.P.hopeiensisandP.tomentosaare endemic to China, and there is still controversy about their origin. We employ phylogeny, Bayesian estimation of admixture, and approximate Bayesian computation to investigate their origin with 10 nuclear DNA and 6 cpDNA regions. The combined evidences firmly support the hypothesis that they are hybrids and dominated by F1s.P.hopeiensiswas generated via hybridization between the paternal speciesP.albaand maternal speciesP.davidiana. Surprisingly,P.tomentosawas divided into two genetic types with different maternal parents.P.adenopodahybridized withP.albadirectly to generate the first genetic type (mb1) and hybridized withP.davidianafollowed byP.albato generate the second (mb2). In both genetic types,P.albaacted as the male parent. The maternal parent wasP.adenopodaandP.davidianafor mb1 and mb2, respectively. Hybridization not only generated these hybrids but also resulted in a unidirectional gene flow fromP.davidianatoP.adenopoda. ThePopulusspecies have maintained a delicate balance between their genetic integrity and gene exchange.
The Familial dementia gene ITM2b/BRI2 facilitates glutamate transmission via both presynaptic and postsynaptic mechanisms
Authors: Yao Wen , Yin Tao , Tambini Marc D. , D’Adamio Luciano
Published: March 2019

Mutations in the Integral membrane protein 2B (ITM2b/BRI2) gene, which codes for a protein called BRI2, cause familial British and Danish dementia (FBD and FDD). Loss of BRI2 function and/or accumulation of amyloidogenic mutant BRI2-derived peptides have been proposed to mediate FDD and FBD pathogenesis by impairing synaptic Long-term potentiation (LTP). However, the precise site and nature of the synaptic dysfunction remain unknown. Here we use a genetic approach to inactivate Itm2b in either presynaptic (CA3), postsynaptic (CA1) or both (CA3 + CA1) neurons of the hippocampal Schaeffer-collateral pathway in both female and male mice. We show that after CA3 + CA1 Itm2b inactivation, spontaneous glutamate release and AMPAR-mediated responses are decreased, while short-term synaptic facilitation is increased. Moreover, AMPAR-mediated responses are decreased after postsynaptic but not presynaptic deletion of Itm2b. In contrast, the probability of spontaneous glutamate release is decreased, while short-term synaptic facilitation is increased, primarily after presynaptic deletion of Itm2b. Collectively, these results indicate a dual physiological role of Itm2b in the regulation of excitatory synaptic transmission at both presynaptic termini and postsynaptic termini and suggest that presynaptic and postsynaptic dysfunctions may be a pathogenic event leading to dementia and neurodegeneration in FDD and FBD.
Tracing recombinant bovine somatotropin ab(use) through transcriptomics: the potential of bovine somatic cells in a multi-dose longitudinal study
Authors: Lamas Alexandre , Regal Patricia , Vázquez Beatriz , Miranda José Manuel , Cepeda Alberto , Franco Carlos Manuel
Published: March 2019

In the European Union, the use of recombinant bovine somatotropin (rbST) in dairy cattle is forbidden. Monitoring rbST (ab)use by its direct detection in animal matrices still remains a challenging task. New monitoring methods based on indirect detection of the substance are necessary. A new transcriptomic system based on the use of high-throughput real-time PCR in combination with somatic cells was developed to control rbST administration in dairy animals. A total of nine cows, separated into control and rbST-treated groups, were included in the study. A subcutaneous injection containing 500 mg of rbST was administered to the treated group every 14 days, up to a total of 12 doses. Milk somatic cells (MSCs) were sampled from each animal at different time points throughout 8 months of study. It was possible to obtain the transcriptomic profile of 18 genes in MSCs of rbST-treated and control groups, and using univariate and multivariate statistical analysis control and treated animals were discriminated. The transcription of CCND1, IGF-1R, TNF and IL-1β genes resulted strongly influenced by rbST treatment. The combination of MSCs, transcriptomic tools and statistical analysis has allowed the selection of four genes as potential biomarkers that could be used in a transcriptomic panel for monitoring rbST administration in cows.
Prospectively reinstated memory drives conscious access of matching visual input
Authors: Gayet Surya , Moorselaar Dirk van , Olivers Christian N. L. , Paffen Chris L. E. , Stigchel Stefan Van der
Published: March 2019

Maintaining information in visual working memory (VWM) biases attentional selection of concurrent visual input, by favoring VWM-matching over VWM-mismatching visual input. Recently, it was shown that this bias disappears when the same item is memorized on consecutive occasions (as memoranda presumably transit from VWM to long-term memory), but reemerges when observers anticipate to memorize a novel item on a subsequent trial. Here, we aimed to conceptually replicate and extend this intriguing finding, by investigating whether prospectively reinstated memory drives conscious access of memory-matching visual input. We measured the time it took for participants to detect interocularly suppressed target stimuli, which were either from the same color category as a concurrently memorized color or not. Our results showed that the advantage of memory-matching targets in overcoming suppression progresses non-monotonically across consecutive memorizations of the same color (‘repetitions’): the advantage for memory-matching visual input initially declined to asymptote, before being fully revived on the last repetition. This revival was not observed in a control experiment in which targets were not interocularly suppressed. The results suggest that, as observers anticipate to memorize a novel item imminently, VWM usage is prospectively reinstated, causing memory-matching visual input to gain accelerated access to consciousness again.
New Therapeutic Approach for Targeting Hippo Signalling Pathway
Authors: Dominguez-Berrocal Leticia , Cirri Erica , Zhang Xiguang , Andrini Laura , Marin Gustavo H. , Lebel-Binay Sophie , Rebollo Angelita
Published: March 2019

Nuclear localization signals are short amino acid sequences that target proteins for nuclear import. In this manuscript, we have generated a chimeric tri-functional peptide composed of a cell penetrating peptide (CPP), a nuclear localization sequence and an interfering peptide blocking the interaction between TEAD and YAP, two transcription factors involved in the Hippo signalling pathway, whose deregulation is related to several types of cancer. We have validated the cell penetration and nuclear localization by flow cytometry and fluorescence microscopy and shown that the new generated peptide displays an apoptotic effect in tumor cell lines thanks to the specific nuclear delivery of the cargo, which targets a protein/protein interaction in the nucleus. In addition, the peptide has an anti-tumoral effect in vivo in xenograft models of breast cancer. The chimeric peptide designed in the current study shows encouraging prospects for developing nuclear anti- neoplastic drugs.
Integrated transcriptome and in vitro analysis revealed anti-proliferative effect of citral in human stomach cancer through apoptosis
Authors: Balusamy Sri Renukadevi , Ramani Sivasubramanian , Natarajan Sathishkumar , Kim Yeon Ju , Perumalsamy Haribalan
Published: March 2019

Cancer is the second leading cause of death globally, particularly stomach cancer is third most common causes of cancer death worldwide. Citral possesses anti-tumor activity in various cancer cell lines, However its effect toward stomach cancer and its mechanism of action is have yet to be elucidated. The goal of the present study is to elucidate the role of citral in stomach cancer using transcriptome and in vitro approaches. We performed transcriptome analysis using RNA-seq and explored its capability to persuade apoptosis in AGS human stomach cancer cell lines in vitro. Furthermore, the enrichment and KEGG pathway results suggested that there are several genes involved to induce apoptosis pathway. Furthermore, our study also demonstrated that citral arrested colony formation and migration of cancer cells significantly than that of untreated cells. RNA-seq revealed a total of 125 million trimmed reads obtained from both control and citral treated groups respectively. A total number of 612 differentially expressed genes (DEGs) were identified which includes 216 genes up-regulated and 396 genes down-regulated genes after treatment. The enrichment analysis identified DEGs genes from transcriptome libraries including cell death, cell cycle, apoptosis and cell growth. The present study showed the significant inhibition effect upon citral by regulating various genes involved in signaling pathways, inhibits metastasis, colony formation and induced apoptosis both in silico and in vitro.
Elucidation of in vitro cellular steps induced by antitumor treatment with plasma-activated medium
Authors: Chauvin Julie , Gibot Laure , Griseti Elena , Golzio Muriel , Rols Marie-Pierre , Merbahi Nofel , Vicendo Patricia
Published: March 2019

Numerous studies have reported cold atmospheric plasma cytotoxic activities in various cancer cell lines, either by direct exposure to non-thermal plasma or indirectly by activating a medium (plasma-activated medium, PAM) prior to cell treatment. We suggested the use of in vitro 3D tumor model spheroids to determine the potential of PAM for cancer therapy at the tissue scale, especially in human tumor tissue. This work aimed to better understand the effect of PAM on human colorectal tumor spheroids by describing the in vitro-induced-cell death kinetics and associated mechanisms to further improve its therapeutic potential. Tumor spheroid growth was delayed depending on contact time with PAM. Medium osmolarity was increased by activation with low temperature Helium plasma jet but it did not fully explain the observed growth delay. PAM impaired tumor cell viability through intracellular ATP depletion, leading within hours to both cell apoptosis and necrosis as well as mitochondrial oxidative stress. When successive treatments were spaced over time, cumulative effects on the growth delay of spheroids were observed. Taken together, these results demonstrated that plasma-activated liquids may represent a novel and efficient therapeutic method for the treatment of tumors, especially when successive treatments are applied.
Photoacoustic F-Mode imaging for scale specific contrast in biological systems
Authors: Moore Michael J. , Hysi Eno , Fadhel Muhannad N. , El-Rass Suzan , Xiao Yongliang , Wen Xiao-Yan , Kolios Michael C.
Published: March 2019

In photoacoustic (PA) imaging, time domain reconstruction techniques are the current gold standard for image formation. While these techniques provide high-resolution spatial maps of optical absorption, they neglect the structural information encoded in the frequency domain of the broadband PA signals. In this work, we introduce a frequency domain technique for PA image formation, termed F-Mode. By leveraging information contained in the frequency content of PA signals, F-Mode can be used to generate images with scale-specific contrast. To demonstrate the robustness of our technique, we apply F-Mode to datasets acquired using both PA tomography and PA microscopy systems, utilizing linear array and single-element transducers with central frequencies ranging from 40–400 MHz. Here we show that the technique can be used to: differentiate between vessels and microspheres of different size in phantoms, enhance visualization of organelles in cultured cells, and selectively display single blood vessels in vivo in zebrafish larvae.
Lean and rich aging of a Cu/SSZ-13 catalyst for combined lean NOx trap (LNT) and selective catalytic reduction (SCR) concept
Authors: Auvray Xavier , Grant Ann , Lundberg Björn , Olsson Louise
Published: March 2019

In the combined lean NOx trap (LNT) and selective catalytic reduction (SCR) concept, the SCR catalyst can be exposed to rich conditions during deSOx of the LNT.
Potato product form impacts in vitro starch digestibility and glucose transport but only modestly impacts 24 h blood glucose response in humans
Authors: Li Min , George Judy , Hunter Stephanie , Hamaker Bruce , Mattes Richard , Ferruzzi Mario G.
Published: March 2019

Potatoes are rich in phenolic compounds which have been reported to impact starch digestion and intestinal glucose transport in model systems through phenolic–starch interactions.
Soybean germ oil reduces blood cholesterol by inhibiting cholesterol absorption and enhancing bile acid excretion
Authors: Zhu Hanyue , Chen Jingnan , He Zouyan , Hao Wangjun , Liu Jianhui , Kwek Erika , Zhao Yimin , Ma Ka Ying , He Wen-Sen , Chen Zhen-Yu
Published: March 2019

Soybean germ oil is beneficial in management of hypercholesterolemia in hamsters fed a high cholesterol diet.
A new tool to attack biofilms: driving magnetic iron-oxide nanoparticles to disrupt the matrix
Authors: Li Jie , Nickel Rachel , Wu Jiandong , Lin Francis , van Lierop Johan , Liu Song
Published: March 2019

Removing robust MRSA biofilms using magnetic nanoparticles (MNPs) under AC and DC magnetic field is demonstrated. Despite being non-toxic to planktonic bacteria, MNPs can bring damage to the extracellular matrix of biofilms and remove them from surfaces without inducing bacterial resistance.
Excitonic channels from bio-inspired templated supramolecular assembly of J-aggregate nanowires
Authors: Anantharaman Surendra B. , Messmer Daniel , Sadeghpour Amin , Salentinig Stefan , Nüesch Frank , Heier Jakob
Published: March 2019

High quality J-aggregate nanowires obtained from complexation of dendronized polymers with J-aggregates.
Porous styryl-linked polyhedral oligomeric silsesquioxane (POSS) polymers used as a support for platinum catalysts
Authors: Liu Zhongshan , Ma Shujuan , Chen Lianfang , Xu Junwen , Ou Junjie , Ye Mingliang
Published: March 2019

Hierarchically porous styryl-linked POSS polymers that provide a delocalized π-electron environment allow for effective platinum loading via π-coordination interactions.
Titanium discs coated with 3,4-dihydroxy-l-phenylalanine promote osteogenic differentiation of human bone mesenchymal stem cells in vitro
Authors: Ma Ting , Ge Xi-Yuan , Hao Ke-Yi , Jiang Xi , Zheng Yan , Lin Ye , Zhang Yu
Published: March 2019

Titanium discs with simple 3,4-dihydroxy-l-phenylalanine coating enhanced BM-MSC adhesion, spreading, proliferation and differentiation, and upregulated expression of genes involved in focal adhesion in vitro.
Comparison of electrochemical performance of LiNi1−xCoxO2 cathode materials synthesized from coated (1−x)Ni(OH)2@xCo(OH)2 and doped Ni1−xCox(OH)2 precursors
Authors: Tang Lei , Li Gang , Xiao Peng , Chen Xu , Yang Wensheng
Published: March 2019

The effects of Co site and content on electrochemical performance of LiNi1−xCoxO2 cathodes materials were investigated.
Helical orbitals and circular currents in linear carbon wires
Authors: Garner Marc H. , Jensen Anders , Hyllested Louise O. H. , Solomon Gemma C.
Published: March 2019

Disubstituted odd-carbon cumulenes are linear carbon wires with helical π-orbitals, which results in circular current around the wire.
Highly efficient Ir-catalyzed asymmetric hydrogenation of benzoxazinones and derivatives with a Brønsted acid cocatalyst
Authors: Han Zhengyu , Liu Gang , Wang Rui , Dong Xiu-Qin , Zhang Xumu
Published: March 2019

The Ir-catalyzed highly efficient asymmetric hydrogenation of benzoxazinones and derivatives was successfully developed with N-methylated ZhaoPhos L5 as the ligand, affording various chiral dihydrobenzoxazinones and derivatives with excellent results.
Designing pH-triggered drug release iron oxide nanocomposites for MRI-guided photothermal-chemoembolization therapy of liver orthotopic cancer
Authors: Liu Fengyong , Li Xin , Li Yangyang , Qi Yuchen , Yuan Hongjun , He Jian , Li Wanlin , Zhou Min
Published: March 2019

In an orthotopic liver cancer model, non-toxic versatile theranostic NPs consisting of an MRI contrast agent and a pH-sensitive and photothermal functional coating were delivered to improve tumor targeting efficacy.
New insights into the effect of nitrogen incorporation in Mo: catalytic hydrogenation vs. hydrogenolysis
Authors: Perret Noémie , Lamey Daniel , Kiwi-Minsker Lioubov , Cárdenas-Lizana Fernando , Keane Mark A.
Published: March 2019

The incorporation of nitrogen into bulk Mo has a contrasting effect on hydrogenation (nitrobenzene) and hydrogenolysis (benzaldehyde) processes.
Heterobimetallic Ba/Li and Ca/Li amides and diphenylmethanide
Authors: le Coz Erwann , Roueindeji Hanieh , Dorcet Vincent , Roisnel Thierry , Carpentier Jean-François , Sarazin Yann
Published: March 2019

Rare examples of stable heterobimetallic Ca/Li and Ba/Li amido polymeric species, as well as an ate Ca/Li diphenylmethanide compound stable in ethers, have been structurally characterised. Intra- and intermolecular metal⋯H–Si interactions are shown to play a key role.
Removal of dimethyl phthalate in water by non-thermal air plasma treatment
Authors: Qi Zhi Hua , Yang Liu , Xia Yang , Ding Zhen Feng , Niu Jin Hai , Liu Dong Ping , Zhao Yao , Ji Long Fei , Song Ying , Lin Xue Song
Published: March 2019

In this study, the effect of a non-thermal microplasma array on the degradation of dimethyl phthalate (DMP) solution was investigated using a high pressure liquid chromatograph and mass spectrometer (LC-MS).
Manifestation of dipole-induced disorder in self-assembly of ferroelectric and ferromagnetic nanocubes
Authors: Zablotsky Dmitry , Rusevich Leonid L. , Zvejnieks Guntars , Kuzovkov Vladimir , Kotomin Eugene
Published: March 2019

Long-range positional and orientational correlations of nanocubes in self-assembled mesocrystals are highly sensitive to the presence of dipoles.
Carbon nanodot-based heterostructures for improving the charge separation and the photocurrent generation
Authors: Bettini Simona , Sawalha Shadi , Carbone Luigi , Giancane Gabriele , Prato Maurizio , Valli Ludovico
Published: March 2019

The possibility to employ carbon nanodots (CNDs) in solar devices was exploited by combining them with a fulleropyrrolidine derivative (FP2).
A liquid PEDOT:PSS electrode-based stretchable triboelectric nanogenerator for a portable self-charging power source
Authors: Shi Jihong , Chen Xiaoping , Li Gengfei , Sun Na , Jiang Hongxue , Bao Dequan , Xie Lingjie , Peng Mingfa , Liu Yina , Wen Zhen , Sun Xuhui
Published: March 2019

A liquid electrode-based TENG has been fabricated to effectively harvest mechanical energy under various deformations and harsh environments.
(Photo)electrocatalysis of molecular oxygen reduction by S-doped graphene decorated with a star-shaped oligothiophene
Authors: Stergiou Anastasios , Perivoliotis Dimitris K. , Tagmatarchis Nikos
Published: March 2019

The high (photo)electrocatalytic activity and stability towards the oxygen reduction reaction of a star-shaped oligothiophene/S-doped graphene ensemble is presented.
Atmosphere-dependent stability and mobility of catalytic Pt single atoms and clusters on γ-Al2O3
Authors: Dessal Caroline , Sangnier Alexis , Chizallet Céline , Dujardin Christophe , Morfin Franck , Rousset Jean-Luc , Aouine Mimoun , Bugnet Matthieu , Afanasiev Pavel , Piccolo Laurent
Published: March 2019

Pt single atoms, stable on alumina under O2, form mobile clusters under H2, due to adsorbate- and nuclearity-dependent metal-support interaction.
Metal- and chloride reagent-free synthesis of mixed thiophosphates
Authors: Ash Jeffrey , Huang Hai , Kang Jun Yong
Published: March 2019

Systematic synthesis of mixed thiophosphates from thiophosphates was developed.
Modular design for fluorophore homodimer probes using diethylentriamine as a common spacer
Authors: Kusano Shuhei , Matsumoto Keisuke , Hayashida Osamu
Published: March 2019

7-Aminooumarin and 1,8-naphthalimide homodimers have been developed to demonstrate the validity of our modular probe design on the basis of a triamine-based spacer.
The synthesis of cyanoformamides via a CsF-promoted decyanation/oxidation cascade of 2-dialkylamino-malononitriles
Authors: Lei Lin-Sheng , Xue Cao-Gen , Xu Xue-Tao , Jin Da-Ping , Wang Shao-Hua , Bao Wen , Liang Huan , Zhang Kun , Asiri Abdullah M.
Published: March 2019

The synthesis of cyanoformamides via a CsF-promoted decyanation/oxidation cascade of N,N-disubstituted aminomalononitriles.
Recent advances in colloidal nanocomposite designviaheterogeneous polymerization techniques
Authors: Thickett Stuart C. , Teo Guo Hui
Published: March 2019

Recent advances in colloidal nanocomposite design by heterogeneous polymerization are reviewed, with a specific focus on encapsulation and particle-based stabilization for specific materials applications.
Biomass carbon derived from pine nut shells decorated with NiO nanoflakes for enhanced microwave absorption properties
Authors: Wang Huiya , Zhang Yanlin , Wang Qiuyue , Jia Chaowei , Cai Pan , Chen Gang , Dong Chengjun , Guan Hongtao
Published: March 2019

A facile strategy was applied to synthesize NiO/biomass carbon composites with excellent microwave absorption properties.
Influence of low temperature conditions on lithium-ion batteries and the application of an insulation material
Authors: Ouyang Dongxu , He Yaping , Weng Jingwen , Liu Jiahao , Chen Mingyi , Wang Jian
Published: March 2019

In the current work, a series of experiments were carried out under low and normal temperature conditions (0 and 20 °C) to research the influence of low temperature on the performance of lithium-ion batteries (LIBs).
Room-temperature solution synthesis of ZnMn2O4 nanoparticles for advanced electrochemical lithium storage
Authors: Wang Chunhui , Zhou Chunxian , Zhang Bao , Ou Xing , Cao Liang , Peng Chunli , Zhang Jiafeng
Published: March 2019

ZnMn2O4 nanoparticles were fabricated via a low-cost and ecofriendly one-step approach at room temperature. The particles exhibited excellent structure stability and superior lithium storage.
Mulberry-like heterostructure (Fe–O–Ti): a novel sensing material for ethanol gas sensors
Authors: Li Min , Shen Jianxing , Cheng Chuanbing , Wang Tailin , Shen Yan , Wang Shuai , Chen Pan
Published: March 2019

The gas sensors have been widely used in various fields, to protect the safety of life and property.
Factors that determine thione(thiol)–disulfide interconversion in a bis(thiosemicarbazone) copper(ii) complex
Authors: Jeong Haewon , Kang Yeji , Kim Jin , Kim Byung-Kwon , Hong Seungwoo
Published: March 2019

Solvent-, acidity-, and redox-responsive thione(thiol)–disulfide interconversion were achieved by a dinuclear copper(ii) complex bearing a bis(thiosemicarbazone) (bTSC) ligand.
Reversible perovskite electrocatalysts for oxygen reduction/oxygen evolution
Authors: Bradley Kieren , Giagloglou Kyriakos , Hayden Brian E. , Jungius Hugo , Vian Chris
Published: March 2019

Reversible (bi-functional) ORR/OER electrocatalysts identified with the creation of mixed valent Mn perovskites and the Mn3+/Mn4+ surface redox couple.