bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic inflammation induced by lipopolysaccharide aggravates inherited retinal dystrophy
Authors: Noailles Agustina , Maneu Victoria , Campello Laura , Lax Pedro , Cuenca Nicolás 
Published: March 2018

AbstractRetinal neurodegenerative diseases involve a scenario of inflammation and cell death that leads to morphological alterations and visual impairment. Non-ocular inflammatory processes could affect neurodegenerative retinal disorders and their progression, at least in part by activating microglial cells and releasing pro-inflammatory cytokines. Our purpose was to study the consequences of a systemic inflammatory process in the progression of retinal degeneration in P23H rats, a retinitis pigmentosa (RP) model. In order to induce a mild chronic systemic inflammation, we administered low doses of lipopolysaccharide (LPS) from age P20 to P60 to dystrophic P23H rats and healthy SD rats. Visual responsiveness was assessed by electroretinography (ERG). The morphological state of the retinas was analyzed by fluorescent immunohistochemistry (IHC), evaluating the number, morphology, and connectivity of different neuronal populations by means of cell type-specific markers. Microglia density, distribution, and degree of activation were evaluated by IHC and flow cytometry. The expression levels of inflammation- and apoptosis-related genes were analyzed by qRT-PCR arrays. Low-dose LPS administration did not induce significant functional or morphological changes in the retina of SD rats, although at the molecular level, we detected expression changes in genes related to apoptosis. Otherwise, systemic injection of LPS into P23H rats induced a further deterioration in the ERG response, with greater loss of photoreceptors and worsening of synaptic connectivity, accompanied by increasing numbers of microglial cells, which also showed a more intense activation state. Several inflammation- and apoptosis-related genes were upregulated. Our results indicate that chronic exacerbation of the inflammatory response in response to LPS accelerates neurodegeneration in dystrophic P23H rats, suggesting that in patients with ocular neurodegenerative diseases, peripheral damage, as a systemic infection or chronic inflammatory process, could accelerate disease progression, and should be taken into account in order to select an appropriate therapy to revert, block or slow-down the degenerative process.
Assisted delivery of antisense therapeutics in animal models of heritable neurodegenerative and neuromuscular disorders: a systematic review and meta-analysis
Authors: van der Bent M. Leontien , Paulino da Silva Filho Omar , van Luijk Judith , Brock Roland , Wansink Derick G. 
Published: March 2018

AbstractAntisense oligonucleotide (AON)-based therapies hold promise for a range of neurodegenerative and neuromuscular diseases and have shown benefit in animal models and patients. Success in the clinic is nevertheless still limited, due to unfavourable biodistribution and poor cellular uptake of AONs. Extensive research is currently being conducted into the formulation of AONs to improve delivery, but thus far there is no consensus on which of those strategies will be the most effective. This systematic review was designed to answer in an unbiased manner which delivery strategies most strongly enhance the efficacy of AONs in animal models of heritable neurodegenerative and neuromuscular diseases. In total, 95 primary studies met the predefined inclusion criteria. Study characteristics and data on biodistribution and toxicity were extracted and reporting quality and risk of bias were assessed. Twenty studies were eligible for meta-analysis. We found that even though the use of delivery systems provides an advantage over naked AONs, it is not yet possible to select the most promising strategies. Importantly, standardisation of experimental procedures is warranted in order to reach conclusions about the most efficient delivery strategies. Our best practice guidelines for future experiments serve as a step in that direction.
Effects of low molecular weight heparin on the polarization and cytokine profile of macrophages and T helper cells in vitro
Authors: Bruno Valentina , Svensson-Arvelund Judit , Rubér Marie , Berg Göran , Piccione Emilio , Jenmalm Maria C. , Ernerudh Jan 
Published: March 2018

AbstractLow molecular weight heparin (LMWH) is widely used in recurrent miscarriage treatment. The anti-coagulant effects are established, while immunological effects are not fully known. Our aim was to assess LMWH effects on activation and polarization of central regulatory immune cells from healthy women, and on placenta tissues from women undergoing elective abortions. Isolated blood monocytes and T helper (Th) cells under different activation and polarizing conditions were cultured with or without LMWH. Flow cytometry showed that LMWH exposure induced increased expression of HLA-DR and CD206 in macrophages. This phenotype was associated with increased secretion of Th17-associated CCL20, and decreased secretion of CCL2 (M2-associated) and CCL22 (Th2), as measured by multiplex bead array. In accordance, LMWH exposure to Th cells reduced the proportion of CD25highFoxp3+ regulatory T-cells, intensified IFN-γ secretion and showed a tendency to increase the lymphoblast proportions. Collectively, a mainly pro-inflammatory effect was noted on two essential tolerance-promoting cells. Although the biological significancies of these in vitro findings are uncertain and need to be confirmed in vivo, they suggest the possibility that immunological effects of LMWH may be beneficial mainly at an earlier gestational age to provide an appropriate implantation process in women with recurrent miscarriage.
Single molecule real time sequencing in ADTKD-MUC1 allows complete assembly of the VNTR and exact positioning of causative mutations
Authors: Wenzel Andrea , Altmueller Janine , Ekici Arif B. , Popp Bernt , Stueber Kurt , Thiele Holger , Pannes Alois , Staubach Simon , Salido Eduardo , Nuernberg Peter , Reinhardt Richard , Reis André , Rump Patrick , Hanisch Franz-Georg , Wolf Matthias T. F. , Wiesener Michael , Huettel Bruno , Beck Bodo B. 
Published: March 2018

AbstractRecently, the Mucin-1 (MUC1) gene has been identified as a causal gene of autosomal dominant tubulointerstitial kidney disease (ADTKD). Most causative mutations are buried within a GC-rich 60 basepair variable number of tandem repeat (VNTR), which escapes identification by massive parallel sequencing methods due to the complexity of the VNTR. We established long read single molecule real time sequencing (SMRT) targeted to the MUC1-VNTR as an alternative strategy to the snapshot assay. Our approach allows complete VNTR assembly, thereby enabling the detection of all variants residing within the VNTR and simultaneous determination of VNTR length. We present high resolution data on the VNTR architecture for a cohort of snapshot positive (n = 9) and negative (n = 7) ADTKD families. By SMRT sequencing we could confirm the diagnosis in all previously tested cases, reconstruct both VNTR alleles and determine the exact position of the causative variant in eight of nine families. This study demonstrates that precise positioning of the causative mutation(s) and identification of other coding and noncoding sequence variants in ADTKD-MUC1 is feasible. SMRT sequencing could provide a powerful tool to uncover potential factors encoded within the VNTR that associate with intra- and interfamilial phenotype variability of MUC1 related kidney disease.
Cabozantinib Affects Osteosarcoma Growth Through A Direct Effect On Tumor Cells and Modifications In Bone Microenvironment
Authors: Fioramonti M. , Fausti V. , Pantano F. , Iuliani M. , Ribelli G. , Lotti F. , Pignochino Y. , Grignani G. , Santini D. , Tonini G. , Vincenzi B. 
Published: March 2018

AbstractOsteosarcoma (OS) is the most common primary malignant tumor of the bone. Due to its high heterogeneity and to survival signals from bone microenvironment, OS can resist to standard treatments, therefore novel therapies are needed. c-MET oncogene, a tyrosine-kinase receptor, plays a crucial role in OS initiation and progression. The present study aimed to evaluate the effect of c-MET inhibitor cabozantinib (CBZ) on OS both directly and through its action on bone microenvironment. We tested different doses of CBZ in in vitro models of OS alone or in co-culture with bone cells in order to reproduce OS-tumor microenvironment interactions. CBZ is able to decrease proliferation and migration of OS cells, inhibiting ERK and AKT signaling pathways. Furthermore, CBZ leads to the inhibition of the proliferation of OS cells expressing receptor activator of nuclear factor κB (RANK), due to its effect on bone microenvironment, where it causes an overproduction of osteoprotegerin and a decrease of production of RANK ligand by osteoblasts. Overall, our data demonstrate that CBZ might represent a new potential treatment against OS, affecting both OS cells and their microenvironment. In this scenario, RANK expression in OS cells could represent a predictive factor of better response to CBZ treatment.
Comparative Proteomic Profiling and Biomarker Identification of Traditional Chinese Medicine-Based HIV/AIDS Syndromes
Authors: Wen Li , Liu Ye-Fang , Jiang Cen , Zeng Shao-Qian , Su Yue , Wu Wen-Jun , Liu Xi-Yang , Wang Jian , Liu Ying , Su Chen , Li Bai-Xue , Feng Quan-Sheng 
Published: March 2018

AbstractGiven the challenges in exploring lifelong therapy with little side effect for human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) cases, there is increasing interest in developing traditional Chinese medicine (TCM) treatments based on specific TCM syndrome. However, there are few objective and biological evidences for classification and diagnosis of HIV/AIDS TCM syndromes to date. In this study, iTRAQ-2DLC-MS/MS coupled with bioinformatics were firstly employed for comparative proteomic profiling of top popular TCM syndromes of HIV/AIDS: accumulation of heat-toxicity (AHT) and Yang deficiency of spleen and kidney (YDSK). It was found that for the two TCM syndromes, the identified differential expressed proteins (DEPs) as well as their biological function distributions and participation in signaling pathways were significantly different, providing biological evidence for the classification of HIV/AIDS TCM syndromes. Furthermore, the TCM syndrome-specific DEPs were confirmed as biomarkers based on western blot analyses, including FN1, GPX3, KRT10 for AHT and RBP4, ApoE, KNG1 for YDSK. These biomarkers also biologically linked with the specific TCM syndrome closely. Thus the clinical and biological basis for differentiation and diagnosis of HIV/AIDs TCM syndromes were provided for the first time, providing more opportunities for stable exertion and better application of TCM efficacy and superiority in HIV/AIDS treatment.
A novel standardized deep sequencing-based assay for hepatitis C virus genotype determination
Authors: Rodriguez Christophe , Soulier Alexandre , Demontant Vanessa , Poiteau Lila , Mercier-Darty Mélanie , Bouvier-Alias Magali , Pawlotsky Jean-Michel , Chevaliez Stéphane 
Published: March 2018

AbstractHepatitis C virus (HCV) genotype and subtype (1a/1b) identification is needed to tailor anti-HCV therapy. Currently available methods accurately identify the genotype and differentiate subtypes 1a from 1b. However, these assays have not been designed to identify other HCV subtypes, nor to recognize mixed genotype/subtype infections, emphasizing the need for a high-resolution system based on phylogenetic analysis of reads obtained by deep sequencing of a relevant genome region. The aim of this study was to evaluate the performance of the Sentosa SQ HCV Genotyping Assay, a novel deep sequencing-based assay targeting the HCV nonstructural 5B (NS5B) region, in clinical samples from patients with an indication for anti-HCV therapy. A high concordance rate with Sanger sequencing of the NS5B region, the reference method, was found for genotype 1 to 6 determination, 1a/1b subtype identification, and genotype 4, 5 and 6 subtyping. Discrepancies were seen essentially for HCV genotype 2 subtyping. Overall, the performance of the deep sequencing-based assay in generating the genotypes/subtype information needed to tailor anti-HCV treatment was adequate in this study. Further improvements, such as a longer NS5B fragment analyzed and enriching the database of reference prototype strains used for subtype assignment would make it a method of choice for HCV genotyping and subtyping for future clinical practice and research.
Low-temperature synthesis and investigation into the formation mechanism of high quality Ni-Fe layered double hydroxides hexagonal platelets
Authors: Jaśkaniec Sonia , Hobbs Christopher , Seral-Ascaso Andrés , Coelho João , Browne Michelle P. , Tyndall Daire , Sasaki Takayoshi , Nicolosi Valeria 
Published: March 2018

AbstractThis paper describes the wet-chemistry synthesis of highly crystalline hexagonal flakes of Ni-Fe layered double hydroxide (LDH) produced at temperature as low as 100 °C. The flakes with diameter in the range of 0.5–1.5 μm and the thickness between 15 and 20 nm were obtained by homogeneous precipitation method with the use of triethanolamine (TEA) and urea. By analyzing the intermediate products, it is suggested that, differently from previous reports, a thermodynamically metastable iron oxyhydroxide and Ni-TEA complex are firstly formed at room temperature. Subsequently, when the mixture is heated to 100 °C and the pH increases due to the thermal decomposition of urea, Ni2+and Fe3+are slowly released and then recombine, thus leading to formation of pure, highly-crystalline Ni-Fe LDH flakes. This material showed promising results as an electrocatalyst in oxygen evolution reaction (OER) providing an overpotential value of 0.36 V.
High-speed photon-counting laser ranging for broad range of distances
Authors: Du Bingcheng , Pang Chengkai , Wu Di , Li Zhaohui , Peng Huan , Tao Yuliang , Wu E. , Wu Guang 
Published: March 2018

AbstractWe demonstrate a high-speed photon-counting laser ranging system with laser pulses of multiple repetition rates to extend the unambiguous range. In the experiment, the laser pulses of three different repetition rates around 10 MHz were employed to enlarge the maximum unambiguous range from 15 m to 165 km. Moreover, the range of distances was increased as well, enabling the measurement on different targets of large separation distance with high depth resolution. An outdoor photon-counting laser ranging up to 21 km was realized with high repetition rate, which is beneficial for the airborne and satellite-based topographic mapping.
Arc temperature profile measurement and characteristic analysis on an SF6 high‐voltage CB
Authors: Bai Su , Guan Yonggang , Luo Haiyun , Liu Weidong 
Published: March 2018

The arc temperature profile in an interrupter, which determines the extinguishing characteristic of an SF6 circuit breaker (CB), is of interest to designers and developers. In this investigation, optical fibres and spectrograph were employed to measure the arc temperature profiles in a 252 kV SF6 CB during short current interrupting. The temperature profiles of the upstream, throat, and downstream of the nozzle have been measured. The optical fibres can transfer the arc light from the measuring points in the nozzle to the spectrograph. Moreover, the spectral line intensities of copper (Cu) 510.5, Cu 515.3, and Cu 521.8 nm were obtained by the spectrograph. The condition in CB can be treated as a local thermal equilibrium system, and the temperature profiles can be calculated by two‐line method and Abel inverse method. The arc temperature profiles of the interrupter under 15–50 kA root mean square current have been analysed through the method established in this investigation.
PSO of power cable performance in complex surroundings
Authors: Al‐Saud Mamdooh S. 
Published: March 2018

Underground cable performance indices such as maximum cable temperature and ampacity are non‐continuous functions of the configuration parameters such as depth and width of various trench layers. In this respect, existing traditional gradient‐type methods cannot be used to optimise such performance indices. This study presents an efficient methodology for optimising power cable thermal performance with respect to configuration parameters involving cable spacing, depth of burial and size of backfill. The new methodology integrates the powerful features of the finite elements (FEs) technique coupled with the flexibility and effectiveness of the particle swarm optimisation (PSO) algorithm in order to handle various geometrical parameters in the complex surrounding operating environment. The introduced methodology is tested using a commercial FE simulation package used in conjunction with developed PSO code. The integrated methodology can be employed to minimise the maximum cable temperature, minimise installation cost or maximise cable ampacity. Practical applications are presented for 15 kV cables, which demonstrate the usefulness and versatility of the presented methodology. Notable improvements have been achieved by optimising the cable trench configuration parameters. For example, the cable ampacity was maximised, optimising the cable spacing, barrier depth and backfill thermal conductivity, which resulted in an appreciable increase of 4.5%.
Model simulation of jet precession in quasar PG 1302-102
Authors: Qian S. J. , Britzen S. , Witzel A. , Krichbaum T. P. , Kun E. 
Published: March 2018

Context. The study of periodic (or quasi-periodic) variabilities in optical and radio bands and quasi-periodic radio-jet swings are important to further our understanding of the physical processes in blazars. Among these the correlation between the periodic or quasi-periodic phenomena in radio and optical bands is particularly significant, because it can provide unique information about the relativistic jets and central engines in the nuclei of blazars.
Aims. We aim to investigate the possibility that the radio jet swing on parsec scales observed in PG 1302-102 (z = 0.278) is a quasi-periodic phenomenon and study its correlation with the periodic optical variability claimed in a recently published work, seeking evidence for a binary black hole system.
Methods. The precessing jet-nozzle model proposed in our previous works was applied to simulate the kinematics of the superluminal components. It is shown that the inner-jet kinematic features can well be explained in terms of the precessing nozzle model.
Results. Based on the model simulation (model fitting) of the inner kinematics for its six superluminal components, a precession period of ~5.1583 ± 0.5 yr is derived for the radio jet swing and the kinematics of all the six components are consistently interpreted. The similarity between the radio jet precession period and the optical period found in its optical light curve may be physically significant. Both periodic behaviors in radio and optical bands could be explained in terms of the orbital motion of a black hole binary, if the orbital plane makes large inclinations to the sky plane: the orbital motion of the primary hole produces the periodic jet swing and the orbital motion of the secondary hole produces the periodic optical variability as suggested in the literature. Thus the total mass and the mass ratio of the binary are estimated.
Conclusions. Based on this analysis, we show that PG 1302-102 might have a supermassive black hole binary existing in its nucleus and it is starting to enter its inspiral phase of merging. Gravitational radiation would start to dominate the energy-momentum loss for its orbital shrinkage.
Hyperforin and Miquelianin from St. Johnʼs Wort Attenuate Gene Expression in Neuronal Cells After Dexamethasone-Induced Stress
Authors: Verjee Sheela , Weston Anna , Kolb Christiane , Kalbhenn-Aziz Heba , Butterweck Veronika 
Published: March 2018

AbstractDysregulation of the hypothalamic-pituitary-adrenal (HPA) axis plays an important part in the development of depressive symptoms. In this study, the effects of a commercial St. Johnʼs wort extract (STW3-VI), hyperforin, miquelianin, and the selective serotonin reuptake inhibitor citalopram on the expression of genes relevant to HPA axis function were investigated in human neuronal cells. SH-SY5Y cells were treated with STW3-VI (20 µg/mL), hyperforin (1 µM), miquelianin (10 µM), or citalopram (10 µM) in the presence of the glucocorticoid receptor agonist dexamethasone (DEX,10 µM) for 6 h and 48 h, respectively. Quantitative real-time polymerase chain reaction was used to determine the expression of FKBP5 (FK506 binding protein 51), CREB (cAMP responsive element binding protein), GRIK4 (glutamate ionotropic receptor kainate type subunit 4), VEGF (vascular endothelial growth factor), NET (norepinephrine transporter), and ARRB (β-arrestins), promising biomarkers of antidepressant therapy. Using DEX to mimic stress conditions, it was shown that the gene expression pattern of FKBP5, CREB, GRIK4, VEGF, NET, and ARRB2 in SH-SY5Y cells is time- and treatment-dependent. Most pronounced effects were observed for FKBP5: after 6 h of co-incubation, only STW3-VI could reverse the DEX-induced increase in FKBP5 expression, and after 48 h, citalopram, miquelianin, and hyperforin also reversed the glucocorticoid-induced increase in FKBP5 mRNA expression. The effects observed on FKBP5, CREB, GRIK4, VEGF, NET, and ARRB2 are in good correlation with published data, suggesting that this in vitro model could be used to screen the responsiveness of antidepressants under stress conditions.
Zum Zusammenhang zwischen Körperschema und sozio-emotionalem Verhalten bei umschriebenen
Entwicklungsstörungen der Wahrnehmung und Motorik
Authors: Reinersmann Annika , Lücke Thomas 
Published: March 2018

ZusammenfassungDiese Übersichtsarbeit diskutiert mögliche Zusammenhänge zwischen der übergeordneten neuronalen Repräsentation
des Körpers, dem „Körperschema“, und Störungen der sensorischen Wahrnehmung, motorischen Funktionen und
sozio-emotionalen Entwicklung. Die Erforschung der neurophysiologischen Grundlagen und Funktionen des
Körperschemas konzentrierte sich bisher vorwiegend auf das Erwachsenenalter. Es ist wenig bekannt darüber, wie
sich bestimmte Körperschemafunktionen im Kindesalter entwickeln, wie räumliche Aspekte der taktilen
Verarbeitung mit der Bewegungsplanung interagieren und in Wechselwirkung mit Meilensteinen der emotionalen und
sozial-emotionalen Entwicklung stehen. In diesem Beitrag werden die existierenden Befunde zur Entwicklung des
Körperschemas mit Fokus auf multisensorische Verarbeitungs- und Integrationsprozesse und Wechselwirkungen für
Störungen der sozio-emotionalen Entwicklung diskutiert.
Erbliche Sehnerverkrankungen
Authors: Rüther Klaus 
Published: March 2018

ZusammenfassungTrotz der Seltenheit haben die erblichen Sehnerverkrankungen den Vorteil, dass sie oftmals durch die Anamnese erkannt werden können und die Diagnosesicherung heute sicher durch eine molekulargenetische Untersuchung geleistet werden kann. Als isolierte erbliche Sehnerverkrankungen sind im augenheilkundlichen Alltag die Leberʼsche hereditäre Optikusneuropathie (LHON) und die autosomal-dominante Optikusatrophie (ADOA) relevant.