bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profibrogenic effect of high-mobility group box protein-1 in human dermal fibroblasts and its excess in keloid tissues
Authors: Lee Won Jai , Song Seung Yong , Roh Hyun , Ahn Hyo Min , Na Youjin , Kim Jihee , Lee Ju Hee , Yun Chae Ok 
Published: May 2018

AbstractHigh-mobility group box 1 (HMGB1) protein acts as a DNA chaperone for nuclear homeostasis. It translocates into the cytosol and is secreted into extracellular spaces, triggering proinflammatory cytokines and acting as a mediator in fibrosis. We determined whether HMGB1 plays a role in normal dermal fibrosis and keloid, and is involved with transforming growth factor β. We investigated the translocation and active release of HMGB1 from normal dermal fibroblasts under lipopolysaccharide stimuli, and the redistribution of nuclear HMGB1 into the cytoplasm of keloid fibroblasts. HMGB1 and its effector toll-like receptors and receptors for advanced glycation end product proteins are actively expressed in keloid tissues. Exogenous HMGB1 can induce the proliferation of human dermal fibroblasts, and could act as a profibrogenic molecule to produce collagen, decrease MMP-1, and increase TIMP-1 mRNA expression. Moreover, administration of HMGB1 increased the expression level of TGF-β1 and internal signaling molecules, such as Smad 2 and 3, phosphorylated Smad 2/3 complex, Erk 1/2, Akt, and NF-κB. Collectively, we demonstrate that HMGB1 treatment increases the expression level of collagen types I and III, elastin, and fibronectin in dermal spheroid cultures, thus making HMGB1 a promising therapeutic target for treatment of profibrogenic diseases.
Engineered membrane protein antigens successfully induce antibodies against extracellular regions of claudin-5
Authors: Hashimoto Yosuke , Zhou Wei , Hamauchi Kohtaroh , Shirakura Keisuke , Doi Takefumi , Yagi Kiyohito , Sawasaki Tatsuya , Okada Yoshiaki , Kondoh Masuo , Takeda Hiroyuki 
Published: May 2018

AbstractThe production of antibodies against the extracellular regions (ECR) of multispanning membrane proteins is notoriously difficult because of the low productivity and immunogenicity of membrane proteins due to their complex structure and highly conserved sequences among species. Here, we introduce a new method to generate ECR-binding antibodies utilizing engineered liposomal immunogen prepared using a wheat cell-free protein synthesis system. We used claudin-5 (CLDN-5) as the target antigen, which is a notoriously difficult to produce and poorly immunogenic membrane protein with two highly conserved extracellular loops. We drastically improved the productivity of CLDN-5 in the cell-free system after suppressing and normalizing mRNA GC content. To overcome its low immunogenicity, two engineered antigens were designed and synthesized as proteoliposomes: a human/mouse chimeric CLDN-5, and a CLDN-5-based artificial membrane protein consisting of symmetrically arranged ECRs. Intraperitoneal immunization of both engineered CLDN-5 ECR antigens induced ECR-binding antibodies in mice with a high success rate. We isolated five monoclonal antibodies that specifically recognized CLDN-5 ECR. Antibody clone 2B12 showed high affinity (<10 nM) and inhibited CLDN-5-containing tight junctions. These results demonstrate the effectiveness of the methods for monoclonal antibody development targeting difficult-to-produce membrane proteins such as CLDNs.
The 13C hyperpolarized pyruvate generated by ParaHydrogen detects the response of the heart to altered metabolism in real time
Authors: Cavallari Eleonora , Carrera Carla , Sorge Matteo , Bonne Gisèle , Muchir Antoine , Aime Silvio , Reineri Francesca 
Published: May 2018

AbstractMany imaging methods have been proposed to act as surrogate markers of organ damage, yet for many candidates the essential biomarkers characteristics of the injured organ have not yet been described. Hyperpolarized [1-13C]pyruvate allows real time monitoring of metabolism in vivo. ParaHydrogen Induced Polarization (PHIP) is a portable, cost effective technique able to generate 13C MR hyperpolarized molecules within seconds. The introduction of the Side Arm Hydrogenation (SAH) strategy offered a way to widen the field of PHIP generated systems and to make this approach competitive with the currently applied dissolution-DNP (Dynamic Nuclear Polarization) method. Herein, we describe the first in vivo metabolic imaging study using the PHIP-SAH hyperpolarized [1-13C]pyruvate. In vivo maps of pyruvate and of its metabolic product lactate have been acquired on a 1 T MRI scanner. By comparing pyruvate/lactate 13C label exchange rate in a mouse model of dilated cardiomyopathy, it has been found that the metabolic dysfunction occurring in the cardiac muscle of the diseased mice can be detected well before the disease can be assessed by echocardiographic investigations.
eIF4A inhibition prevents the onset of cytokine-induced muscle wasting by blocking the STAT3 and iNOS pathways
Authors: Cramer Zvi , Sadek Jason , Vazquez Gabriela Galicia , Di Marco Sergio , Pause Arnim , Pelletier Jerry , Gallouzi Imed-Eddine 
Published: May 2018

AbstractCachexia is a deadly muscle wasting syndrome that arises under conditions linked to chronic inflammation, such as cancer. Cytokines, including interferon γ (IFNγ), tumor necrosis factor α (TNFα) and interleukin-6 (IL-6), and their downstream effectors such as Signal Transducer and Activator of Transcription 3 (STAT3), have been shown to play a prominent role in muscle wasting. Previously, we demonstrated that Pateamine A (PatA), a compound that targets eukaryotic initiation factor 4A (eIF4A), could prevent muscle wasting by modulating the translation of the inducible Nitric Oxide Synthase (iNOS) mRNA. Here we show that hippuristanol, a compound that impedes eIF4A in a manner distinct from PatA, similarly inhibits the iNOS/NO pathway and cytokine-induced muscle wasting. Furthermore, we show that hippuristanol perturbs the activation of the STAT3 pathway and expression of STAT3-gene targets such as IL-6. The decreased activation of STAT3, which resulted from a decrease in STAT3 protein expression, was due to the inhibition of STAT3 translation as there were no changes in STAT3 mRNA levels. These effects are likely dependent on the inhibition of eIF4A activity since we observed similar results using PatA. Our results identify the inhibition of eIF4A-responsive transcripts, such as STAT3, as a viable approach to alleviate cachexia.
Signatures of balancing selection in toll-like receptor (TLRs) genes – novel insights from a free-living rodent
Authors: Kloch Agnieszka , Wenzel Marius A. , Laetsch Dominik R. , Michalski Olek , Bajer Anna , Behnke Jerzy M. , Welc-Falęciak Renata , Piertney Stuart B. 
Published: May 2018

AbstractSelective pressure from pathogens is considered a key selective force driving the evolution of components of the immune system. Since single components of the immune system may interact with many pathogens, and single pathogens may be recognized by multiple components of the immune system, gaining a better understanding of the mechanisms of parasite-driven selection requires the study of multiple genes and pathogens. Toll-like receptors (TLRs) are a large gene family that code for antigen-presenting components of the innate immune response. In the present paper we characterize polymorphism and signatures of selection in seven TLRs in free-living bank volesMyodes glareolus. We report the first evidence of balancing selection in several TLR genes, supported by positive values of Fu and Li’s D* in TLR2 and TLR5, and positive values of Tajima’s D in LRR regions within TLR1 and TLR2. We further found significant associations between amino-acid alleles of TLR1 and TLR5 and susceptibility to infection with the blood pathogenBartonella. Interestingly, selection patterns in TLRs presenting virus-derived motifs (TLR7 and TLR9) differed considerably from those interacting with bacterial PAMPs. In contrast to the highly variable TLRs presenting bacterial motifs, TLR7 and TLR9 had low polymorphism and displayed signatures of directional selection. These findings suggest different functional responses across the TLR gene family and highlight the complexity of parasite-driven selection.
Polarons Explain Luminescence Behavior of Colloidal Quantum Dots at Low Temperature
Authors: Khosla Meenakshi , Rao Sravya , Gupta Shilpi 
Published: May 2018

AbstractLuminescence properties of colloidal quantum dots have found applications in imaging, displays, light-emitting diodes and lasers, and single photon sources. Despite wide interest, several experimental observations in low-temperature photoluminescence of these quantum dots, such as the short lifetime on the scale of microseconds and a zero-longitudinal optical phonon line in spectrum, both attributed to a dark exciton in literature, remain unexplained by existing models. Here we propose a theoretical model including the effect of solid-state environment on luminescence. The model captures both coherent and incoherent interactions of band-edge exciton with phonon modes. Our model predicts formation of dressed states by coupling of the exciton with a confined acoustic phonon mode, and explains the short lifetime and the presence of the zero-longitudinal optical phonon line in the spectrum. Accounting for the interaction of the exciton with bulk phonon modes, the model also explains the experimentally observed temperature-dependence of the photoluminescence decay dynamics and temperature-dependence of the photoluminescence spectrum.
Combining micro-RNA and protein sequencing to detect robust biomarkers for Graves’ disease and orbitopathy
Authors: Zhang Lei , Masetti Giulia , Colucci Giuseppe , Salvi Mario , Covelli Danila , Eckstein Anja , Kaiser Ulrike , Draman Mohd Shazli , Muller Ilaria , Ludgate Marian , Lucini Luigi , Biscarini Filippo 
Published: May 2018

AbstractGraves’ Disease (GD) is an autoimmune condition in which thyroid-stimulating antibodies (TRAB) mimic thyroid-stimulating hormone function causing hyperthyroidism. 5% of GD patients develop inflammatory Graves’ orbitopathy (GO) characterized by proptosis and attendant sight problems. A major challenge is to identify which GD patients are most likely to develop GO and has relied on TRAB measurement. We screened sera/plasma from 14 GD, 19 GO and 13 healthy controls using high-throughput proteomics and miRNA sequencing (Illumina’s HiSeq2000 and Agilent-6550 Funnel quadrupole-time-of-flight mass spectrometry) to identify potential biomarkers for diagnosis or prognosis evaluation. Euclidean distances and differential expression (DE) based on miRNA and protein quantification were analysed by multidimensional scaling (MDS) and multinomial regression respectively. We detected 3025 miRNAs and 1886 proteins and MDS revealed good separation of the 3 groups. Biomarkers were identified by combined DE and Lasso-penalized predictive models; accuracy of predictions was 0.86 (±0:18), and 5 miRNA and 20 proteins were found including Zonulin, Alpha-2 macroglobulin, Beta-2 glycoprotein 1 and Fibronectin. Functional analysis identified relevant metabolic pathways, including hippo signaling, bacterial invasion of epithelial cells and mRNA surveillance. Proteomic and miRNA analyses, combined with robust bioinformatics, identified circulating biomarkers applicable to diagnose GD, predict GO disease status and optimize patient management.
Birth weight variants are associated with variable fetal intrauterine growth from 20 weeks of gestation
Authors: Engelbrechtsen L. , Gybel-Brask D. , Mahendran Y. , Crusell M. , Hansen T. H. , Schnurr T. M. , Hogdall E. , Skibsted L. , Hansen T. , Vestergaard H. 
Published: May 2018

AbstractFetal intrauterine growth is influenced by complex interactions between the maternal genes, environment and fetal genes. The aim of this study was to assess the effect of GWAS-identified genetic variants associated with birth weight on intrauterine fetal growth in 665 children. Fetal growth was estimated by two-dimensional ultrasound scans at 20, 25 and 32 weeks of gestation and growth trajectories were modeled using mixed linear regression. A genetic risk score (GRS) of birth weight-raising variants was associated with intrauterine growth showing an attenuating effect on the unconditional daily reduction in proportional weight gain of 8.92 × 10−6 percentage points/allele/day (p = 2.0 × 10−4), corresponding to a mean difference of 410 g at 40 weeks of gestation between a child with lowest and highest GRS. Eight variants were independently associated with intrauterine growth throughout the pregnancy, while four variants were associated with fetal growth in the periods 20–25 or 25–32 weeks of gestation, indicating that some variants may act in specific time windows during pregnancy. Four of the intrauterine growth variants were associated with type 2 diabetes, hypertension or BMI in the UK Biobank, which may provide basis for further understanding of the link between intrauterine growth and later risk of metabolic disease.
Deciphering the functional role of spatial and temporal muscle synergies in whole-body movements
Authors: Delis Ioannis , Hilt Pauline M. , Pozzo Thierry , Panzeri Stefano , Berret Bastien 
Published: May 2018

AbstractVoluntary movement is hypothesized to rely on a limited number of muscle synergies, the recruitment of which translates task goals into effective muscle activity. In this study, we investigated how to analytically characterize the functional role of different types of muscle synergies in task performance. To this end, we recorded a comprehensive dataset of muscle activity during a variety of whole-body pointing movements. We decomposed the electromyographic (EMG) signals using a space-by-time modularity model which encompasses the main types of synergies. We then used a task decoding and information theoretic analysis to probe the role of each synergy by mapping it to specific task features. We found that the temporal and spatial aspects of the movements were encoded by different temporal and spatial muscle synergies, respectively, consistent with the intuition that there should a correspondence between major attributes of movement and major features of synergies. This approach led to the development of a novel computational method for comparing muscle synergies from different participants according to their functional role. This functional similarity analysis yielded a small set of temporal and spatial synergies that describes the main features of whole-body reaching movements.
Optimality of the maximum likelihood estimator in astrometry
Authors: Espinosa Sebastian , Silva Jorge F. , Mendez Rene A. , Lobos Rodrigo , Orchard Marcos 
Published: May 2018

Context.Astrometry relies on the precise measurement of the positions and motions of celestial objects. Driven by the ever-increasing accuracy of astrometric measurements, it is important to critically assess the maximum precision that could be achieved with these observations.Aims.The problem of astrometry is revisited from the perspective of analyzing the attainability of well-known performance limits (the Cramér–Rao bound) for the estimation of the relative position of light-emitting (usually point-like) sources on a charge-coupled device (CCD)-like detector using commonly adopted estimators such as the weighted least squares and the maximum likelihood.Methods.Novel technical results are presented to determine the performance of an estimator that corresponds to the solution of an optimization problem in the context of astrometry. Using these results we are able to place stringent bounds on the bias and the variance of the estimators in close form as a function of the data. We confirm these results through comparisons to numerical simulations under a broad range of realistic observing conditions.Results.The maximum likelihood and the weighted least square estimators are analyzed. We confirm the sub-optimality of the weighted least squares scheme from medium to high signal-to-noise found in an earlier study for the (unweighted) least squares method. We find that the maximum likelihood estimator achieves optimal performance limits across a wide range of relevant observational conditions. Furthermore, from our results, we provide concrete insights for adopting an adaptive weighted least square estimator that can be regarded as a computationally efficient alternative to the optimal maximum likelihood solution.Conclusions.We provide, for the first time, close-form analytical expressions that bound the bias and the variance of the weighted least square and maximum likelihood implicit estimators for astrometry using a Poisson-driven detector. These expressions can be used to formally assess the precision attainable by these estimators in comparison with the minimum variance bound.
Circular polarization signals of cloudy (exo)planets
Authors: Rossi L. , Stam D. M. 
Published: May 2018

Context. The circular polarization of light that planets reflect is often neglected because it is very small compared to the linear polarization. It could, however, provide information on a planet’s atmosphere and surface, and on the presence of life, because homochiral molecules that are the building blocks of life on Earth are known to reflect circularly polarized light.
Aims. We compute Pc, the degree of circular polarization, of light that is reflected by rocky (exo)planets to provide insight into the viability of circular spectropolarimetry for characterizing (exo)planetary atmospheres.
Methods. We compute the Pc of light that is reflected by rocky (exo)planets with liquid water or sulfuric acid solution clouds, both spatially resolved across the planetary disk and, for planets with patchy clouds, integrated across the planetary disk, for various planetary phase angles α.
Results. The optical thickness and vertical distribution of the atmospheric gas and clouds, the size parameter and refractive index of the cloud particles, and α all influence Pc. Spatially resolved, Pc varies between ± 0.20% (the sign indicates the polarization direction). Only for small gas optical thicknesses above the clouds do significant sign changes (related to cloud particle properties) across the planets’ hemispheres occur. For patchy clouds, the disk-integrated Pc is typically smaller than ± 0.025%, with maximum for α between 40° and 70°, and 120° to 140°. As expected, the disk-integrated Pc is virtually zero at α = 0° and 180°. The disk-integrated Pc is also very small at α ≈ 100°.
Conclusions. Measuring circular polarization signals appears to be challenging with current technology. The small atmospheric circular polarization signal could, however, allow the detection of circular polarization due to homochiral molecules such as those associated with life on Earth. Confirmation of the detectability of such signals requires better knowledge of the strength of circular polarization signals of biological sources and in particular of the angular distribution of their scattering.
Psychosoziale Akuthilfen bei einem Massenanfall direkt oder indirekt betroffener Kinder
Authors: Karutz Harald , Fegert Ann-Katrin , Blank-Gorki Verena 
Published: May 2018

ZusammenfassungIn Großschadenslagen mit vielen direkt oder indirekt beteiligten Kindern muss nicht nur eine notfallmedizinische Hilfeleistung, sondern auch eine Psychosoziale Notfallversorgung (PSNV) sichergestellt werden. In diesem Zusammenhang werden konkrete Hinweise zu psychosozialen Akuthilfen, zur Einsatztaktik sowie zu Führungs- und Funktionsstrukturen unmittelbar am Ort des Geschehens gegeben. Der Beitrag greift dabei die allgemein bekannten Leitlinien des Konsensusprozesses zur PSNV in Deutschland auf, ergänzt und konkretisiert diese jedoch auch.
Obere Altersgrenze bei ambulanter Anästhesie: Möglichkeiten und Risiken
Authors: Hüppe Tobias , Kneller Nicole , Raddatz Alexander 
Published: May 2018

ZusammenfassungZahlreiche Operationen werden heute auch noch in höherem Lebensalter ambulant durchgeführt. Dieser Übersichtsartikel stellt die Vorteile der ambulanten Anästhesie bei älteren Patienten dar, zeigt aber auch die Risiken einer zu frühen Entlassung auf. Für den klinischen Alltag werden praktische Hilfestellungen für die Patientenauswahl gegeben und Risikofaktoren für eine ungeplante stationäre Aufnahme identifiziert.
Weekday–weekend variations in mother‐/father–child physical activity and screen time relationship: A cross‐sectional study in a random sample of Czech families with 5‐ to 12‐year‐old children
Authors: Sigmundová Dagmar , Badura Petr , Sigmund Erik , Bucksch Jens 
Published: May 2018

AbstractThis study assessed the associations between these factors in a random sample of Czech families with preschool and school‐aged children. A nationally representative sample comprised 185 families with preschool children and 649 families with school‐aged children (dyads; both parents and child n = 365, mother and child n = 730, and father and child n = 469). The participants wore Yamax Digiwalker SW‐200 pedometers at least four weekdays and both weekend days and completed family logbooks (anthropometric parameters, daily step counts (SC), and screen time (ST)). When a parent (fathers at weekends and mothers both on weekdays and at weekends) achieved 10,000 SC per day, their children were also significantly (OR = 2.93–6.06, 95% CI = 2.02–9.26) more likely to meet the daily SC recommendation. On the contrary, the involvement of fathers in organized leisure‐time PA reduced their children's odds of meeting the SC recommendation on weekdays (OR = 0.53, 95% CI = 0.31–0.89) and at weekends (OR = 0.41, 95% CI = 0.24–0.72). The excessive ST of parents at weekends reduced the odds of their children meeting the SC recommendation (mother–child dyads: OR = 0.44, 95% CI = 0.26–0.72; father–child dyads: OR = 0.63, 95% CI = 0.37–1.06). High levels of parents’ PA contribute to the achievement of the recommended daily PA in children on weekdays and at weekends. Excessive weekend ST of parents reduces their odds of their children achieving the recommended daily PA; however, the influence of parents’ PA on their children's achieving the recommended daily PA is stronger than the inhibitory effect of ST.
Information Hiding In Digital Video Using DCT, DWT and CvT
Authors: Shukur Wisam Abed , Abdullah Wathiq Najah , Qurban Luheb Kareem 
Published: May 2018

Abstract
The type of video that used in this proposed hiding a secret information technique is .AVI; the proposed technique of a data hiding to embed a secret information into video frames by using Discrete Cosine Transform (DCT), Discrete Wavelet Transform (DWT) and Curvelet Transform (CvT). An individual pixel consists of three color components (RGB), the secret information is embedded in Red (R) color channel. On the receiver side, the secret information is extracted from received video. After extracting secret information, robustness of proposed hiding a secret information technique is measured and obtained by computing the degradation of the extracted secret information by comparing it with the original secret information via calculating the Normalized cross Correlation (NC). The experiments shows the error ratio of the proposed technique is (8%) while accuracy ratio is (92%) when the Curvelet Transform (CvT) is used, but compared with Discrete Wavelet Transform (DWT) and Discrete Cosine Transform (DCT), the error rates are 11% and 14% respectively, while the accuracy ratios are (89%) and (86%) respectively. So, the experiments shows the Poisson noise gives better results than other types of noises, while the speckle noise gives worst results compared with other types of noises. The proposed technique has been established by using MATLAB R2016a programming language.