bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fyn Kinase regulates GluN2B subunit-dominant NMDA receptors in human induced pluripotent stem cell-derived neurons
Authors: Zhang Wen-Bo , Ross P. Joel , Tu YuShan , Wang Yongqian , Beggs Simon , Sengar Ameet S. , Ellis James , Salter Michael W. 
Published: April 2016

AbstractNMDA receptor (NMDAR)-mediated fast excitatory neurotransmission is implicated in a broad range of physiological and pathological processes in the mammalian central nervous system. The function and regulation of NMDARs have been extensively studied in neurons from rodents and other non-human species and in recombinant expression systems. Here, we investigated human NMDARs in situ by using neurons produced by directed differentiation of human induced pluripotent stem cells (iPSCs). The resultant cells showed electrophysiological characteristics demonstrating that they are bona fide neurons. In particular, human iPSC-derived neurons expressed functional ligand-gated ion channels, including NMDARs, AMPA receptors, GABAA receptors, as well as glycine receptors. Pharmacological and electrophysiological properties of NMDAR-mediated currents indicated that these were dominated by receptors containing GluN2B subunits. The NMDAR currents were suppressed by genistein, a broad-spectrum tyrosine kinase inhibitor. The NMDAR currents were also inhibited by a Fyn-interfering peptide, Fyn(39–57), but not a Src-interfering peptide, Src(40–58). Together, these findings are the first evidence that tyrosine phosphorylation regulates the function of NMDARs in human iPSC-derived neurons. Our findings provide a basis for utilizing human iPSC-derived neurons in screening for drugs targeting NMDARs in neurological disorders.
Pado, a fluorescent protein with proton channel activity can optically monitor membrane potential, intracellular pH, and map gap junctions
Authors: Kang Bok Eum , Baker Bradley J. 
Published: April 2016

AbstractAn in silico search strategy was developed to identify potential voltage-sensing domains (VSD) for the development of genetically encoded voltage indicators (GEVIs). Using a conserved charge distribution in the S2 α-helix, a single in silico search yielded most voltage-sensing proteins including voltage-gated potassium channels, voltage-gated calcium channels, voltage-gated sodium channels, voltage-gated proton channels, and voltage-sensing phosphatases from organisms ranging from mammals to bacteria and plants. A GEVI utilizing the VSD from a voltage-gated proton channel identified from that search was able to optically report changes in membrane potential. In addition this sensor was capable of manipulating the internal pH while simultaneously reporting that change optically since it maintains the voltage-gated proton channel activity of the VSD. Biophysical characterization of this GEVI, Pado, demonstrated that the voltage-dependent signal was distinct from the pH-dependent signal and was dependent on the movement of the S4 α-helix. Further investigation into the mechanism of the voltage-dependent optical signal revealed that inhibiting the dimerization of the fluorescent protein greatly reduced the optical signal. Dimerization of the FP thereby enabled the movement of the S4 α-helix to mediate a fluorescent response.
The “Vessel through Strait” Sign is a Signature Radiological Sign for the Diagnosis of Left Hepatic Artery Variation
Authors: Rong Guanghua , Wang Zhijun , Wang Ximing , Yu Qiang , Zhou Lin , Wang Huaming , Zhang Junhua , Dong Jinghui , Ma Wei , An Weimin , Ren Hui , Zeng Zhen , Lu Yinying , Li Yongwu 
Published: April 2016

AbstractAn aberrant artery (AA) can frequently be observed coursing through the fissure for the ligamentum venosum (FLV) which was termed the “vessel through strait” sign (VTSS) by us. Fundamental data including the incidence, anatomical composition and clinical significance of VTSS and the AAs composing VTSS are still lacking. We sought to give a systematic demonstration on this issue in the present study. VTSS was respectively analyzed in 2,275 patients and was observed in 357 of them. Interestingly, 319 (89.4%) out of the 357 patients exhibiting VTSS were proved to have left hepatic artery variation (LHAV) (247 with replaced left hepatic artery, 64 with accessory left hepatic artery and 8 with variant common hepatic artery). We therefore hypothesized that VTSS could be a sign that strongly associated with LHAV and could be used for its diagnosis. In the following validating analysis, VTSS gained a sensitivity of 96.3% and a specificity of 98.3% for the diagnosis of LHAV in another bicenter cohort consisted of 1,329 patients. In conclusion, VTSS is a signature radiological sign of LHAV which could be used as an easy and specific method for the diagnosis of LHAV.
Novel PKC-ζ to p47phox interaction is necessary for transformation from blebbishields
Authors: Jinesh Goodwin G. , Taoka Rikiya , Zhang Qiang , Gorantla Siddharth , Kamat Ashish M. 
Published: April 2016

AbstractCancer stem cells are capable of transformation after apoptosis through the blebbishield emergency program. Reactive oxygen species (ROS) play an essential role in transformation. Understanding how ROS are linked to blebbishield-mediated transformation is necessary to develop efficient therapeutics that target the resurrection of cancer stem cells. Here we demonstrate that a novel PKC-ζ to p47phox interaction is required for ROS production in cancer cells. The combined use of the S6K inhibitor BI-D1870 with TNF-α inhibited the PKC-ζ to p47phox interaction, inhibited ROS production, degraded PKC-ζ and activated caspases-3 and -8 to block transformation from blebbishields. BI-D1870 also inhibited transformation from cycloheximide-generated blebbishields. Thus ROS and the PKC-ζ to p47phox interaction are valid therapeutic targets to block transformation from blebbishields.
Transcriptome sequencing reveals e-cigarette vapor and mainstream-smoke from tobacco cigarettes activate different gene expression profiles in human bronchial epithelial cells
Authors: Shen Yifei , Wolkowicz Michael J. , Kotova Tatyana , Fan Lonjiang , Timko Michael P. 
Published: April 2016

AbstractElectronic cigarettes (e-cigarettes) generate an aerosol vapor (e-vapor) thought to represent a less risky alternative to main stream smoke (MSS) of conventional tobacco cigarettes. RNA-seq analysis was used to examine the transcriptomes of differentiated human bronchial epithelial (HBE) cells exposed to air, MSS from 1R5F tobacco reference cigarettes, and e-vapor with and without added nicotine in an in vitro air-liquid interface model for cellular exposure. Our results indicate that while e-vapor does not elicit many of the cell toxicity responses observed in MSS-exposed HBE cells, e-vapor exposure is not benign, but elicits discrete transcriptomic signatures with and without added nicotine. Among the cellular pathways with the most significantly enriched gene expression following e-vapor exposure are the phospholipid and fatty acid triacylglycerol metabolism pathways. Our data suggest that alterations in cellular glycerophopholipid biosynthesis are an important consequences of e-vapor exposure. Moreover, the presence of nicotine in e-vapor elicits a cellular response distinct from e-vapor alone including alterations of cytochrome P450 function, retinoid metabolism, and nicotine catabolism. These studies establish a baseline for future analysis of e-vapor and e-vapor additives that will better inform the FDA and other governmental bodies in discussions of the risks and future regulation of these products.
Experimental Realisation of High-sensitivity Laboratory X-ray Grating-based Phase-contrast Computed Tomography
Authors: Birnbacher Lorenz , Willner Marian , Velroyen Astrid , Marschner Mathias , Hipp Alexander , Meiser Jan , Koch Frieder , Schröter Tobias , Kunka Danays , Mohr Jürgen , Pfeiffer Franz , Herzen Julia 
Published: April 2016

AbstractThe possibility to perform high-sensitivity X-ray phase-contrast imaging with laboratory grating-based phase-contrast computed tomography (gbPC-CT) setups is of great interest for a broad range of high-resolution biomedical applications. However, achieving high sensitivity with laboratory gbPC-CT setups still poses a challenge because several factors such as the reduced flux, the polychromaticity of the spectrum and the limited coherence of the X-ray source reduce the performance of laboratory gbPC-CT in comparison to gbPC-CT at synchrotron facilities. In this work, we present our laboratory X-ray Talbot-Lau interferometry setup operating at 40 kVp and describe how we achieve the high sensitivity yet unrivalled by any other laboratory X-ray phase-contrast technique. We provide the angular sensitivity expressed via the minimum resolvable refraction angle both in theory and experiment and compare our data with other differential phase-contrast setups. Furthermore, we show that the good stability of our high-sensitivity setup allows for tomographic scans, by which even the electron density can be retrieved quantitatively as has been demonstrated in several preclinical studies.
Extreme stiffness hyperbolic elastic metamaterial for total transmission subwavelength imaging
Authors: Lee Hyuk , Oh Joo Hwan , Seung Hong Min , Cho Seung Hyun , Kim Yoon Young 
Published: April 2016

AbstractSubwavelength imaging by metamaterials and extended work to pursue total transmission has been successfully demonstrated with electromagnetic and acoustic waves very recently. However, no elastic counterpart has been reported because earlier attempts suffer from considerable loss. Here, for the first time, we realize an elastic hyperbolic metamaterial lens and experimentally show total transmission subwavelength imaging with measured wave field inside the metamaterial lens. The main idea is to compensate for the decreased impedance in the perforated elastic metamaterial by utilizing extreme stiffness, which has not been independently actualized in a continuum elastic medium so far. The fabricated elastic lens is capable of directly transferring subwavelength information from the input to the output boundary. In the experiment, this intriguing phenomenon is confirmed by scanning the elastic structures inside the lens with laser scanning vibrometer. The proposed elastic metamaterial lens will bring forth significant guidelines for ultrasonic imaging techniques.
Insight into the feeding behavior of predatory mites on Beauveria bassiana, an arthropod pathogen
Authors: Wu Shengyong , Zhang Ye , Xu Xuenong , Lei Zhongren 
Published: April 2016

AbstractInteractions between fungal entomopathogens and pest predators are particularly relevant in control of agricultural insect pests. In a laboratory study, we confirmed that the predatory mite, Neoseiulus barkeri, exhibited feeding behavior on the entomopathogenic fungus Beauveria bassiana conidia through DNA extracts. Using transmission electron microscopy, we determined that the majority of conidia found in the mite gut tended to dissolve within 24 h post ingestion, suggesting that the conidia had probably lost their viability. To our knowledge this is the first report of feeding behavior of phytoseiid mites on entomopathogenic fungus. The findings expand our knowledge of fungus–predator interactions.
Using Language Sample Analysis to Assess Spoken Language Production in Adolescents
Authors: Miller Jon F. , Andriacchi Karen , Nockerts Ann 
Published: April 2016

Purpose
This tutorial discusses the importance of language sample analysis and how Systematic Analysis of Language Transcripts (SALT) software can be used to simplify the process and effectively assess the spoken language production of adolescents.

Method
Over the past 30 years, thousands of language samples have been collected from typical speakers, aged 3–18 years, in conversational and narrative contexts. These samples have been formatted as reference databases included with SALT. Using the SALT software, individual samples are compared with age- and grade-matched samples selected from these databases.

Results
Two case studies illustrate that comparison with database samples of typical adolescents, matched by grade and elicitation context, highlights language measures that are higher or lower than the database mean values. Differences in values are measured in standard deviations.

Conclusion
Language sample analysis remains a powerful method of documenting language use in everyday speaking situations. A sample of talking reveals an individual's ability to meet specific speaking demands. These demands vary across contexts, and speakers can have difficulty in any one or all of these communication tasks. Language use for spoken communication is a foundation for literacy attainment and contributes to success in navigating relationships for school, work, and community participation.
Large-Animal Biventricular Working Heart Perfusion System with Low Priming Volume—Comparison between in vivo and ex vivo Cardiac Function
Authors: Mayr Tanja , Jauch Judith , Guethoff Sonja , Buchholz Stefan , Reichart Bruno , Bauer Andreas , Abicht Jan-Michael 
Published: April 2016

Background Existing large-animal, ex vivo, cardiac perfusion models are restricted in their ability to establish an ischemia/reperfusion condition as seen in cardiac surgery or transplantation. Other working heart systems only challenge one ventricle or require a substantially larger priming volume. We describe a novel biventricular cardiac perfusion system with reduced priming volume.
Methods Juvenile pig hearts were cardiopleged, explanted, and reperfused ex vivo after 150 minutes of cold ischemia. Autologous whole blood was used as perfusate (minimal priming volume 350 mL). After 15 minutes of Langendorff perfusion (LM), the system was switched into a biventricular working mode (WM) and studied for 3 hours.
Results During reperfusion, complete unloading of both ventricles and constant-pressure coronary perfusion was achieved. During working mode perfusion, the preload and afterload pressure of both ventricles was controlled within the targeted physiologic range. Functional parameters such as left ventricular work index were reduced in ex vivo working mode (in vivo: 787 ± 186 vs. 1 h WM 498 ± 66 mm Hg·mL/g·min; p < 0.01), but remained stable throughout the following study period (3 h WM 517 ± 103 mm Hg·mL/g·min; p = 0.63). Along with the elevated workload during WM, myocardial metabolism and oxygen consumption increased compared with LM (0.021 ± 0.08 vs. 0.06 ± 0.01 mL/min/g; 1 h after reperfusion). Histologic examination of the myocardium revealed no structural damage.
Conclusion In the ex vivo perfusion system, stable hemodynamic and metabolic conditions can be established for a period of 3 hours while functional and blood parameters are easily accessible. Moreover, because of the minimal priming volume, the novel ex vivo cardiac perfusion circuit allows for autologous perfusion, using the limited amount of blood available from the organ donating animal.
Application of Continuous Wound-Infusion Catheters in Lung Transplantation: A Retrospective Data Analysis
Authors: Lenz Nils , Roehrig Rainer , Menges Thilo , Mueller Matthias , Padberg Winfried , Mann Valesco , Hirschburger Markus 
Published: April 2016

Background Lung transplantation is the only treatment option for many patients with end-stage pulmonary disease. Therefore, postthoracotomy pain therapy is of vital interest. Thoracic epidural analgesia (EPI) is the “gold standard” for postthoracotomy pain, but especially in lung transplantation contraindications, and potential infectious complications limit its advantages. Under these circumstances surgically placed postthoracotomy catheter-assisted continuous paravertebral intercostal nerve block (PVB) could be of advantage.
Methods We performed a retrospective cohort study of patients who underwent lung transplantation between 2005 and 2012. Groups were defined according to the type of postoperative pain therapy: PVB, EPI, and SYS (systemic analgesia). Total 44 patients were eligible.
Results Postoperative opioid requirement of the PVB and EPI group was comparable and less than that of the SYS group. Patients of the PVB group were weaned earlier from mechanical ventilation after lung transplantation.
Conclusion The potency of postoperative pain therapy of EPI and PVB seemed to be comparable and superior to SYS. Considering the risks and benefits, PVB could be a better choice than EPI for postthoracotomy pain therapy, especially in lung transplantation.
Designing Biomaterials Systems for the Disc Pathology
Authors: Pandit Abhay 
Published: April 2016

Biomaterials are no longer considered innate structures and using functionalisation strategies to modulate a desired response whether it is a host or implant is currently an important focus in current research paradigms. Fundamentally, a thorough understanding the host response will enable to design propoer functionalisation strategies. Using functionalisation strategies such as enzymatic and hyperbranched linking systems, we have been able to link biomolecules to different structural moieties. The programmed assembly of biomolecules into higher-order self-organized systems is central to innumerable biological processes and development of the next generation of functionalized scaffolds. Recent design efforts have utilized a bottom-up approach toward both understanding and engineering supramolecular protein assemblies. These include functionalisation of micro and nanoparticles with biomolecules that include designed peptide motifs, growth factors and a multitude of gene vector systems. Structural moieties have taken a variety of different forms such as nanofibers and nanoparticulate. The talk will elucidate some of these ongoing strategies in our laboratory. Disclosures: None
Novel Carriers for Growth Factors for Enhancing Spinal Fusion
Authors: Li Xudong Joshua , Jin Li , Shen Francis 
Published: April 2016

Spinal fusion is a well-accepted surgical treatment for many spinal diseases; the costs amount to ~34 billion annually in the US alone, with significant increases projected due to an aging population. Non-unions are a notable complication of spinal fusion surgery. To promote bone regeneration, the FDA has approved rhBMP-2 with a rebsorbable collagen sponge as an alternative to the standard bone graft for spinal fusion. However, adverse events associated with supraphysiological doses, and burst release of rhBMP-2 is a recurring problem for clinicians. Formulations that help regulate the delivery and release profile of growth factors are needed to achieve consistent clinical outcomes. Numerous approaches have been tested, and some of them have shown promising results. Strategies tested for achieving this endeavor include: 1) optimization of cytokine kinetics, 2) combination of different growth factors, 3) utilization of osteoinductive and osteoconductive scaffolds, 4) incorporation of progenitor cells, 5) augmentation of biological activity with tropic bone factors, and, 6) reduction of the endogenous BMP antagonists. Disclosures: None
A Nanotechnology-Based Therapy to Target Inflammation in Degenerated Intervertebral Disc: First Results from an ex vivo Disc Organ Culture
Authors: Teixeira Graciosa Q. , Boldt Antje , Nagl Ines , Molinos Maria , Pereira Catarina Leite , Benz Karin , Wilke Hans-Joachim , Ignatius Anita , Barbosa Mário A. , Neidlinger-Wilke Cornelia , Gonçalves Raquel M. 
Published: April 2016

Introduction Resolution of intervertebral disc (IVD) degeneration-associated inflammation is a pre-requisite for tissue regeneration. Here, a pro-inflammatory disc organ culture model from bovine origin was established,1 and a therapy based on the intra-discal delivery of an anti-inflammatory drug (diclofenac). Material and Methods Bovine caudal IVD punches were needle-punctured and additionally stimulated with lipopolysaccharide (10 µg/mL) or interleukin-1β (IL-1β, 10–100 ng/mL) for 48 hours. An intradiscal therapeutic approach was tested based on a non-steroidal anti-inflammatory drug, diclofenac (Df), alone or incorporated into nanoparticles, previously developed.2 Results IL-1β-treated IVD organ cultures showed a statistically significant up-regulation of pro-inflammatory markers (IL-6, IL-8, PGE2) and metalloproteases (MMP1, MMP3) expression while ECM proteins (Collagen II, Aggrecan) were significantly down-regulated. The injection of the anti-inflammatory drug was able to reduce the levels of pro-inflammatory cytokines and MMPs and surprisingly increased ECM protein levels. Conclusion These results point the intradiscal application of anti-inflammatory drugs as promising therapeutics for disc degeneration. Moreover, the organ culture model established could be used to address cellular/molecular mechanisms that regulate inflammation and IVD degeneration, and moreover to test novel therapeutic drugs, thus reducing the number of animals in in vivo experimentation. Acknowledgments This work was supported by European funds from FP7-EU-project GENODISC (HEALTH-F2–2008–201626), by German funds from the German Spine Foundation (Deutsche Wirbelsäulenstitung), by the Luso-German Integrated Actions Program (DAAD/CRUP, ref. A20/12), by FEDER funds through the Programa Operacional Factores de Competitividade – COMPETE, by Portuguese funds through QREN (project NORTE-07–0124-FEDER-000005) co-financed by North Portugal Regional Operational (ON.2-O Novo Norte). Graciosa Q. Teixeira and Catarina L. Pereira also acknowledge FCT for their PhD grants (SFRH/BD/88429/2012 and SFRH/BD/85779/2012, respectively). References Teixeira GQ, et al. Tissue Eng 2015; (Part C). Accepted for publication Gonçalves RM, et al. J Mater Sci Mater Med 2015
The Effect of Iodixanol on Human Intervertebral Disc Cells in vitro
Authors: Gradisnik Lidija , Maver Uros , Bunc Gorazd , Velnar Tomaz 
Published: April 2016

Introduction The diagnostics of discogenic low back pain may employ also radioopaque contrast agents, such as iodixanol, which may cause cytotoxicity to intervertebral disc cells following the intradiscal injections, provoking or accelerating the degeneration process. As many studies so far have been accomplished on animal cells, the potential effects of these agents in humans still remain unclear. The study aim was to evaluate the effect of iodixanol on human intervertebral disc cells in vitro and to compare its cytotoxicity to saline solution control. Material and Methods From human lumbar intervertebral disc fragments obtained during discectomis, annulus fibrosus and nucleus pulposus cells were isolated, cultured on the microtiter plates and exposed to various concentrations of iodixanol. Saline was used as a control. Three different dilutions (undiluted, 1:2 and 1:4) of iodixanol were tested. After 6, 24 and 48 hours, viability was determined. Results A time and dose depended response to iodixanol exposure was observed. The nulceus pulposus cells were more susceptible than annulus fibrosus cells to its toxic effects. Iodixanol was cytotoxic in all three tested concentrations (undiluted, 1:2 and 1:4) with the cell survival of 0%, 8% and 14%, respectively. Necrosis, rather than apoptosis, was the main reason for such devastating effects. Conclusion In iodixanol, commonly used for discography, the cytotoxic effects were observed in a dose- and time-dependent manner. According to our study, concentrated iodixanol is best avoided due to its high toxicity. Although 1:4 dilution was least toxic and may be thus recommended for the intradiscal diagnostics, the high dilutions are questionable due to loss of resolution yield. We assume the toxic effects of the contrast agents used may also contribute to disc degeneration, culminating to progressive tissue damage after the diagnostic measures.