bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthetic antigen-binding fragments (Fabs) against S. mutans and S. sobrinus inhibit caries formation
Authors: Alam Md. Kausar , Zheng Li , Liu Ruirui , Papagerakis Silvana , Papagerakis Petros , Geyer C. Ronald 
Published: June 2018

AbstractStreptococcus mutansandStreptococcus sobrinusare the main causative agents of human dental caries. Current strategies for treating caries are costly and do not completely eradicate them completely. Passive immunization using nonhuman antibodies against Streptococcal surface antigens has shown success in human trials, however they often invoke immune reactions. We used phage display to generate human antigen-binding fragments (Fabs) againstS.mutansandS.sobrinus. These Fabs were readily expressed inE.coliand bound to the surfaceS.mutansandS.sobrinus. Fabs inhibited sucrose-inducedS.mutansandS.sobrinusbiofilm formationin vitroand a combination ofS.mutansandS.sobrinusFabs prevented dental caries formation in a rat caries model. These results demonstrated thatS.mutansandS.sobrinusFabs could be used in passive immunization strategies to prevent dental caries. In the future, this strategy may be applied towards a caries therapy, whereby Fabs are topically applied to the tooth surface.
Human IgM monoclonal antibodies block HIV-transmission to immune cells in cervico-vaginal tissues and across polarized epithelial cells in vitro
Authors: Devito Claudia , Ellegård Rada , Falkeborn Tina , Svensson Lennart , Ohlin Mats , Larsson Marie , Broliden Kristina , Hinkula Jorma 
Published: June 2018

AbstractThe importance of natural IgM antibodies in protection against infections is still emerging and these antibodies have a potential role in the maintenance of homeostasis through clearance of apoptotic bodies, complement-dependent mechanisms, inflammation and exclusion of misfolded proteins. Natural IgM act as a first line of defence against unknown hazardous factors and are present in most vertebrates. We investigated the functional capacity of anti-HIV-1 IgM monoclonal antibodies, from a combinatorial Fab library derived from healthy individuals, and evaluated their protective role in inhibiting HIV-1in vitrowhen passing across the human mucosal epithelial barrier. Primary HIV-1 isolates were efficiently transmitted over the tight polarized epithelial cells when added to their apical surface. Efficient inhibition of HIV-1 transmission was achieved when anti-HIV-1 IgM monoclonal antibodies were added to the basolateral side of the cells. Two of these human IgM MoAbs had the ability to neutralize HIV and reduced infection of dendritic cells in primary cervico-vaginal tissue biopsiesin vitro. This indicates a potential role of natural IgM antibodies in the reduction of HIV-1 transmission in mucosal tissues and improve our understanding of how natural IgM antibodies against a neutralizing epitope could interfere with viral transmission.
Using machine learning tools for protein database biocuration assistance
Authors: König Caroline , Shaim Ilmira , Vellido Alfredo , Romero Enrique , Alquézar René , Giraldo Jesús 
Published: June 2018

AbstractBiocuration in the omics sciences has become paramount, as research in these fields rapidly evolves towards increasingly data-dependent models. As a result, the management of web-accessible publicly-available databases becomes a central task in biological knowledge dissemination. One relevant challenge for biocurators is the unambiguous identification of biological entities. In this study, we illustrate the adequacy of machine learning methods as biocuration assistance tools using a publicly available protein database as an example. This database contains information on G Protein-Coupled Receptors (GPCRs), which are part of eukaryotic cell membranes and relevant in cell communication as well as major drug targets in pharmacology. These receptors are characterized according to subtype labels. Previous analysis of this database provided evidence that some of the receptor sequences could be affected by a case of label noise, as they appeared to be too consistently misclassified by machine learning methods. Here, we extend our analysis to recent and quite substantially modified new versions of the database and reveal their now extremely accurate labeling using several machine learning models and different transformations of the unaligned sequences. These findings support the adequacy of our proposed method to identify problematic labeling cases as a tool for database biocuration.
Neonatal corticosterone mitigates autoimmune neuropsychiatric disorders associated with streptococcus in mice
Authors: Macrì Simone , Spinello Chiara , Widomska Joanna , Magliozzi Roberta , Poelmans Geert , Invernizzi Roberto William , Creti Roberta , Roessner Veit , Bartolini Erika , Margarit Immaculada , Glennon Jeffrey , Laviola Giovanni 
Published: June 2018

AbstractIncreased glucocorticoid concentrations have been shown to favor resilience towards autoimmune phenomena. Here, we addressed whether experimentally induced elevations in circulating glucocorticoids mitigate the abnormalities exhibited by an experimental model of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS). This is a pathogenic hypothesis linking repeated exposures to Group-A-beta-hemolytic streptococcus (GAS), autoantibodies targeting selected brain nuclei and neurobehavioral abnormalities. To persistently elevate glucocorticoid concentrations, we supplemented lactating SJL/J mice with corticosterone (CORT; 80 mg/L) in the drinking water. Starting in adolescence (postnatal day 28), developing offspring were exposed to four injections - at bi-weekly intervals - of a GAS homogenate and tested for behavioral, immunological, neurochemical and molecular alterations. GAS mice showed increased perseverative behavior, impaired sensorimotor gating, reduced reactivity to a serotonergic agonist and inflammatory infiltrates in the anterior diencephalon. Neonatal CORT persistently increased circulating glucocorticoids concentrations and counteracted these alterations. Additionally, neonatal CORT increased peripheral and CNS concentrations of the anti-inflammatory cytokine IL-9. Further, upstream regulator analysis of differentially expressed genes in the striatum showed that the regulatory effect of estradiol is inhibited in GAS-treated mice and activated in GAS-treated mice exposed to CORT. These data support the hypothesis that elevations in glucocorticoids may promote central immunomodulatory processes.
Structural determination of bilayer graphene on SiC(0001) using synchrotron radiation photoelectron diffraction
Authors: Razado-Colambo I. , Avila J. , Vignaud D. , Godey S. , Wallart X. , Woodruff D. P. , Asensio M. C. 
Published: June 2018

AbstractIn recent years there has been growing interest in the electronic properties of ‘few layer’ graphene films. Twisted layers, different stacking and register with the substrate result in remarkable unconventional couplings. These distinctive electronic behaviours have been attributed to structural differences, even if only a few structural determinations are available. Here we report the results of a structural study of bilayer graphene on the Si-terminated SiC(0001) surface, investigated using synchrotron radiation-based photoelectron diffraction and complemented by angle-resolved photoemission mapping of the electronic valence bands. Photoelectron diffraction angular distributions of the graphene C 1s component have been measured at different kinetic energies and compared with the results of multiple scattering simulations for model structures. The results confirm that bilayer graphene on SiC(0001) has a layer spacing of 3.48 Å and an AB (Bernal) stacking, with a distance between the C buffer layer and the first graphene layer of 3.24 Å. Our work generalises the use of a versatile and precise diffraction method capable to shed light on the structure of low-dimensional materials.
Innate and adaptive immune dysregulation in critically ill ICU patients
Authors: Duggal Niharika Arora , Snelson Catherine , Shaheen Ulfath , Pearce Victoria , Lord Janet M. 
Published: June 2018

AbstractThis study aimed to evaluate whether ICU patients who developed persistent critical illness displayed an immune profile similar to an aged immune phenotype and any associations with patient outcomes. Twenty two critically ill ICU patients (27–76 years, 15 males), at day 5 of mechanical ventilation, and 22 healthy age-matched controls (27–77 years, 13 males) were recruited. Frequency and phenotype of innate and adaptive immune cells and telomere length in peripheral blood mononuclear cells (PBMCs) were measured. An elevated granulocyte count (p < 0.0001), increased numbers of immature granulocytes (p < 0.0001), increased CD16++ve monocytes (p = 0.003) and CD14+ve HLADRdim/low monocytes (p = 0.004) and lower NK cell numbers (p = 0.007) were observed in ICU patients compared to controls. Critically ill patients also had lower numbers of total T lymphocytes (p = 0.03), naïve CD4 T cells (p = 0.003) and PTK7+ve recent thymic emigrants (p = 0.002), and increased senescent CD28−ve CD57+ve CD4 T cells (p = 0.02), but there was no difference in PBMC telomere length. Regulatory immune cell frequency was affected with reduced circulating CD19+veCD24hiCD38hi regulatory B cells (p = 0.02). However, only a raised neutrophil:lymphocyte ratio and reduced frequency of CD14+ve HLADRdim/low monocytes were associated with poor outcomes. We conclude that persistent critical illness results in changes to immune cell phenotype only some of which are similar to that seen in physiological ageing of the immune system.
Metastable phase formation of Pt-X (X = Ir, Au) thin films
Authors: Saksena Aparna , Chien Yu-Chuan , Chang Keke , Kümmerl Pauline , Hans Marcus , Völker Bernhard , Schneider Jochen M. 
Published: June 2018

AbstractThe dependence of phase formation and mechanical properties on the chemical composition has been investigated for Pt-Ir and Pt-Au combinatorial thin films. The formation of a single, metastable Pt-Ir solid solution has been observed for all experimental compositions and temperatures. Upon Ir addition to Pt the experimentally determined changes in lattice parameter and Young’s modulus display rule of mixture behavior which is in good agreement with ourab initiodata. Whereas, in the Pt-Au system, the single metastable solid solution decomposes into two phases as the growth temperature is raised to ≥600 °C. The lattice parameters in the dual phase region are independent of chemical composition. The substrate temperature and chemical composition dependent phase formation in Pt-Ir and Pt-Au thin films can be rationalized based on CALPHAD (CALculation of PHAse Diagrams) results combined with estimations of the activation energy required for surface diffusion: The metastable phase formation during film growth is caused by kinetic limitations, where Ir atoms (in Pt-Ir) need to overcome an up to factor 6 higher activation energy barrier than Au (in Pt-Au) to enable surface diffusion.
The multidomain flavodiiron protein from Clostridium difficile 630 is an NADH:oxygen oxidoreductase
Authors: Folgosa Filipe , Martins Maria C. , Teixeira Miguel 
Published: June 2018

AbstractFlavodiiron proteins (FDPs) are enzymes with a minimal core of two domains: a metallo-β-lactamase-like, harbouring a diiron center, and a flavodoxin, FMN containing, domains. FDPs are O2 or NO reducing enzymes; for many pathogens, they help mitigate the NO produced by the immune system of the host, and aid survival during fluctuating concentrations concentrations of oxygen. FDPs have a mosaic structure, being predicted to contain multiple extra domains. Clostridium difficile, a threatening human pathogen, encodes two FDPs: one with the two canonical domains, and another with a larger polypeptide chain of 843 amino acids, CD1623, with two extra domains, predicted to be a short-rubredoxin-like and an NAD(P)H:rubredoxin oxidoreductase. This multi-domain protein is the most complex FDP characterized thus far. Each of the predicted domains was characterized and the presence of the predicted cofactors confirmed by biochemical and spectroscopic analysis. Results show that this protein operates as a standalone FDP, receiving electrons directly from NADH, and reducing oxygen to water, precluding the need for extra partners. CD1623 displayed negligible NO reductase activity, and is thus considered an oxygen selective FDP, that may contribute to the survival of C. difficile in the human gut and in the environment.
Ventromedial hypothalamic nucleus in regulation of stress-induced gastric mucosal injury in rats
Authors: Sun Haiji , Zhao Pan , Liu Wenkai , Li Lei , Ai Hongbin , Ma Xiaoli 
Published: June 2018

AbstractPrevious studies showed that restraint water-immersion stress (RWIS) increases the expression of Fos protein in the ventromedial hypothalamic nucleus (VMH), indicating the VMH involving in the stress-induced gastric mucosal injury (SGMI). The present study was designed to investigate its possible neuro-regulatory mechanisms in rats receiving either VMH lesions or sham surgery. The model for SGMI was developed by restraint and water (21 ± 1 °C) immersion for 2 h. Gastric mucosal injury index, gastric motility, gastric acid secretion and Fos expression in the hypothalamus and brainstem were examined on the 15th postoperative day in RWIS rats. Gastric mucosal injury in VMH-lesioned rats was obviously aggravated compared to the control. Gastric acidity under RWIS was obviously higher in VMH-lesioned rats than that in sham rats. Meantime, the VMH-lesioned rats exhibited marked increases in the amplitude of gastric motility in the VMH lesions group after RWIS. In VMH-lesioned rats, Fos expression significantly increased in the dorsal motor nucleus of the vagus (DMV), the nucleus of the solitary tract (NTS), the area postrema (AP), the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) in response to RWIS. These results indicate that VMH lesions can aggravate the stress-induced gastric mucosal injury through the VMH-dorsal vagal complex (DVC)-vagal nerve pathway.
Integument CYP genes of the largest genome-wide cytochrome P450 expansions in triatomines participate in detoxification in deltamethrin-resistant Triatoma infestans
Authors: Dulbecco Andrea B. , Moriconi Débora E. , Calderón-Fernández Gustavo M. , Lynn Soledad , McCarthy Andrés , Roca-Acevedo Gonzalo , Salamanca-Moreno Jhon A. , Juárez M. Patricia , Pedrini Nicolás 
Published: June 2018

AbstractInsect resistance to chemical insecticides is attributed to a combination of different mechanisms, such as metabolic resistance, knockdown resistance, and the cuticular resistance or penetration factor. The insect integument offers an efficient barrier against contact insecticides and its role as penetration factor has been previously reported; however, there is no information about its potential function in the metabolic resistance. Cytochrome P450 genes (CYP) are highly expressed in the fat body of several insects and thus play a key role in their metabolic resistance. Here, we describe new members that belong to the highly genome-wide expanded CYP3093A and CYP4EM subfamilies in the Chagas disease vectors Rhodnius prolixus and Triatoma infestans. We modeled the docking of deltamethrin in their active site and detected differences in some amino acids between both species that are critical for a correct interaction with the substrate. We also knocked down the two constitutively most expressed genes in the integument of resistant T. infestans nymphs (CYP3093A11 and CYP4EM10) in order to find clues on their participation in deltamethrin resistance. This is the first report on the role of the insect integument in detoxification events; although these two CYP genes do not fully explain the resistance observed in T. infestans.
Phasic and sustained interactions of multisensory interplay and temporal expectation
Authors: Ball Felix , Fuehrmann Fabienne , Stratil Fenja , Noesselt Toemme 
Published: June 2018

AbstractEvery moment organisms are confronted with complex streams of information which they use to generate a reliable mental model of the world. There is converging evidence for several optimization mechanisms instrumental in integrating (or segregating) incoming information; among them are multisensory interplay (MSI) and temporal expectation (TE). Both mechanisms can account for enhanced perceptual sensitivity and are well studied in isolation; how these two mechanisms interact is currently less well-known. Here, we tested in a series of four psychophysical experiments for TE effects in uni- and multisensory contexts with different levels of modality-related and spatial uncertainty. We found that TE enhanced perceptual sensitivity for the multisensory relative to the best unisensory condition (i.e. multisensory facilitation according to the max-criterion). In the latter TE effects even vanished if stimulus-related spatial uncertainty was increased. Accordingly, computational modelling indicated that TE, modality-related and spatial uncertainty predict multisensory facilitation. Finally, the analysis of stimulus history revealed that matching expectation at trial n-1 selectively improves multisensory performance irrespective of stimulus-related uncertainty. Together, our results indicate that benefits of multisensory stimulation are enhanced by TE especially in noisy environments, which allows for more robust information extraction to boost performance on both short and sustained time ranges.
Synergy of AERONET and MODIS AOD products in the estimation of PM2.5 concentrations in Beijing
Authors: Fu Disong , Xia Xiangao , Wang Jun , Zhang Xiaoling , Li Xiaojing , Liu Jianzhong 
Published: June 2018

AbstractSatellite aerosol optical depth (AOD) is widely used to estimate particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5) mass concentrations. Polar orbiting satellite retrieval 1–2 times each day is frequently affected by cloud, snow cover or misclassification of heavy pollution. Novel methods are therefore required to improve AOD sampling. Sunphotometer provides much more AODs than satellite at a fixed point. Furthermore, much of the aerosol pollution is regional. Both factors indicate that sunphotometer has great potential for PM2.5 concentration estimation. The spatial representativeness of the Aerosol Robotic Network (AERONET) AOD at Beijing site is investigated by linear regression analysis of 13-year daily paired AODs at each grid from Moderate Resolution Imaging Spectroradiometer (MODIS) on Aqua and Beijing AERONET. The result suggests a good correlation for the whole Beijing Administrative region, with regional mean correlation coefficient exceeding 0.73. Pixel AODs are then estimated from AERONET AOD using linear equations, which are verified to have the same accuracy as that of MODIS AOD. Either AOD from MODIS retrieval or estimation from AERONET AOD in the absence of MODIS pixel AOD is finally used to predict PM2.5 concentration. Daily AOD sampling in average is enhanced by 59% in winter when MODIS AODs are very limited. More importantly, synergy of AERONET and MODIS AOD is able to improve the estimation of regional mean PM2.5 concentrations, which indicates this method would play a significant role in monitoring regional aerosol pollution.
A multifunctional DNA nano-scorpion for highly efficient targeted delivery of mRNA therapeutics
Authors: Li Dandan , Mo Fei , Wu Jiangling , Huang Yong , Zhou Huihao , Ding Shijia , Chen Weixian 
Published: June 2018

AbstractThe highly efficient cancer cell targeted delivery plays an important role in precise targeted therapies. Herein, a multifunctional DNA nano-scorpion nanostructure (termed AptDzy-DNS) functioned with aptamers and DNAzyme is developed for highly efficient targeted delivery of mRNA therapeutics in gene therapy. The designed AptDzy-DNS is self-assembled with specific aptamers as “scorpion stingers” for targeting tumor cell and DNAzymes as “scorpion pincers” for targeted gene therapy by cleaving mRNA into fragments. The as-prepared AptDzy-DNS can effectively distinguish cancer cells from normal cells by specific cross-talking between aptamers on AptDzy-DNS and overexpressed cell-surface receptors. In the process of gene therapy, by reacting with Mg2+-dependent DNAzyme on AptDzy-DNS, the mRNA oligonucleotide in cancer cell is auto-cleaved into broken strand, failing to be translated into corresponding protein. Following, the downregulation protein can block cancer cell growth and realize highly efficient targeted therapies. The results demonstrate that the multifunctional AptDzy-DNS shows promise for targeted cancer cell discrimination, highly efficient targeted delivery of mRNA therapeutics in gene therapy. Thus, this developed strategy provides impressive improvement on gene targeted therapy and paves the way for application of AptDzy-DNS in human cancer targeted therapies.
Exposure to podophyllotoxin inhibits oocyte meiosis by disturbing meiotic spindle formation
Authors: Hu Lin-Lin , Zhou Xin , Zhang Hao-Lin , Wu Lan-Lan , Tang Lian-Sheng , Chen Ling-Li , Duan Jin-Liang 
Published: June 2018

AbstractPodophyllotoxin is used as medical cream which is widely applied to genital warts and molluscum contagiosum. Although previous study showed that podophyllotoxin had minimal toxicity, it was forbidden to use during pregnancy since it might be toxic to the embryos. In present study we used mouse as the model and tried to examine whether podophyllotoxin exposure was toxic to oocyte maturation, which further affected embryo development. Our results showed that podophyllotoxin exposure inhibited mouse oocyte maturation, showing with the failure of polar body extrusion, and the inhibitory effects of podophyllotoxin on oocytes was dose-depended. Further studies showed that the meiotic spindle formation was disturbed, the chromosomes were misaligned and the fluorescence signal of microtubule was decreased, indicating that podophyllotoxin may affect microtubule dynamics for spindle organization. Moreover, the oocytes which reached metaphase II under podophyllotoxin exposure also showed aberrant spindle morphology and chromosome misalignment, and the embryos generated from these oocytes showed low developmental competence. We also found that the localization of p44/42 MAPK and gamma-tubulin was disrupted, which further confirmed the effects of podophyllotoxin on meiotic spindle formation. In all, our results indicated that podophyllotoxin exposure could affect mouse oocyte maturation by disturbing microtubule dynamics and meiotic spindle formation.
Chronotype and social jetlag influence human circadian clock gene expression
Authors: Takahashi Masaki , Tahara Yu , Tsubosaka Miku , Fukazawa Mayuko , Ozaki Mamiho , Iwakami Tamao , Nakaoka Takashi , Shibata Shigenobu 
Published: June 2018

AbstractWe examined the relationships between chronotype or social jetlag and clock gene expression. Twenty-four young men [Chronotype: morningness, n = 8; intermediate, n = 8, eveningness, n = 8], aged 27 ± 2 years old (mean ± SE), completed two trials in a randomized order: (1) a Friday trial and (2) a Monday trial. In both trials, hair follicle cells were collected to evaluate the expression of clock genes over a 24-hour period at 4-hour intervals. There was a significant main effect of time on the expression of NR1D1, NR1D2, and PER3 (P < 0.001) in the morningness group, but not in the eveningness group. Changes in the peak time of expression of NR1D1 (r = 0.434, P = 0.034), NR1D2 (r = 0.481, P = 0.017), and PER3 (r = 0.457, P = 0.025) from the Friday to Monday trials were positively correlated with social jetlag (SJL) time. Our findings indicate that there was no change in the patterns of clock gene expression between workdays and the day after the holiday in the morningness group, and that SJL time influences the peak time of clock gene expression, moving it from the early to late workday, after a holiday.