bluuebunny/crossref_metadata_2025_split huggingface dataset:
A dopaminergic mechanism of antipsychotic drug efficacy, failure, and failure reversal: the role of the dopamine transporter
Authors: Amato Davide , Canneva Fabio , Cumming Paul , Maschauer Simone , Groos Dominik , Dahlmanns Jana Katharina , Grömer Teja W. , Chiofalo Lisa , Dahlmanns Marc , Zheng Fang , Kornhuber Johannes , Prante Olaf , Alzheimer Christian , von Hörsten Stephan , Müller Christian P. 
Published: July 2018

AbstractAntipsychotic drugs are effective interventions in schizophrenia. However, the efficacy of these agents often decreases over time, which leads to treatment failure and symptom recurrence. We report that antipsychotic efficacy in rat models declines in concert with extracellular striatal dopamine levels rather than insufficient dopamine D2 receptor occupancy. Antipsychotic efficacy was associated with a suppression of dopamine transporter activity, which was reversed during failure. Antipsychotic failure coincided with reduced dopamine neuron firing, which was not observed during antipsychotic efficacy. Synaptic field responses in dopamine target areas declined during antipsychotic efficacy and showed potentiation during failure. Antipsychotics blocked synaptic vesicle release during efficacy but enhanced this release during failure. We found that the pharmacological inhibition of the dopamine transporter rescued antipsychotic drug treatment outcomes, supporting the hypothesis that the dopamine transporter is a main target of antipsychotic drugs and predicting that dopamine transporter blockers may be an adjunct treatment to reverse antipsychotic treatment failure.
Suppression of Notch1 and AKT mediated epithelial to mesenchymal transition by Verrucarin J in metastatic colon cancer
Authors: Pal Deeksha , Tyagi Ashish , Chandrasekaran Balaji , Alattasi Houda , Ankem Murali K. , Sharma Arun K. , Damodaran Chendil 
Published: July 2018

AbstractEpithelial to mesenchymal transition (EMT) in colorectal cancer (CRC) has been attributed to activation of AKT and Notch1 signaling pathways. As EMT corresponds to increased aggressiveness of CRC, approaches that prevent metastasis by targeting AKT/Notch1 pathways are at the forefront of current research paradigms. This study examined the anti-metastatic potential of Verrucarin J (VJ), a small molecule, in CRC cells overexpressing AKT and Notch1. VJ significantly inhibited AKT/HCT 116 cell growth by acting on the AKT/NFκB/Bcl-2 signaling axis and initiated apoptotic signaling as was evident from increased expression of pro-apoptotic markers such as cleaved PARP, cleaved caspase 3, and cleaved caspase 9. Also, VJ inhibited the cell growth in AKT/Notch1-overexpressing CRC cells and abrogated EMT. The down-regulation of AKT and Notch1 signaling was apparent in immunoblot analysis and corresponded with down-regulation of mesenchymal markers including Snail, and β-catenin. Intraperitoneal administration of VJ in control (pCMV/HCT 116) and AKT/HCT 116 mice significantly suppressed AKT-induced tumor growth in a xenograft model. In addition, down-regulation of prosurvival markers as well as AKT and Notch1 was observed in the immunohistochemical analysis of the xenografted tumors. In conclusion, our study substantiates the role of AKT and Notch1 in cell proliferation, angiogenesis, and EMT of CRC cells and demonstrates that VJ may be a viable therapeutic option to counter AKT-induced cell proliferation and tumor outgrowth in CRC.
Phase-field model of pitting corrosion kinetics in metallic materials
Authors: Ansari Talha Qasim , Xiao Zhihua , Hu Shenyang , Li Yulan , Luo Jing-Li , Shi San-Qiang 
Published: July 2018

AbstractPitting corrosion is one of the most destructive forms of corrosion that can lead to catastrophic failure of structures. This study presents a thermodynamically consistent phase field model for the quantitative prediction of the pitting corrosion kinetics in metallic materials. An order parameter is introduced to represent the local physical state of the metal within a metal-electrolyte system. The free energy of the system is described in terms of its metal ion concentration and the order parameter. Both the ion transport in the electrolyte and the electrochemical reactions at the electrolyte/metal interface are explicitly taken into consideration. The temporal evolution of ion concentration profile and the order parameter field is driven by the reduction in the total free energy of the system and is obtained by numerically solving the governing equations. A calibration study is performed to couple the kinetic interface parameter with the corrosion current density to obtain a direct relationship between overpotential and the kinetic interface parameter. The phase field model is validated against the experimental results, and several examples are presented for applications of the phase-field model to understand the corrosion behavior of closely located pits, stressed material, ceramic particles-reinforced steel, and their crystallographic orientation dependence.
Controlled study on Gamma nail and proximal femoral locking plate for unstable intertrochanteric femoral fractures with broken lateral wall
Authors: Han Lei , Liu Jing-jing , Hu Yun-gen , Quan Ren-fu , Fang Wei-li , Jin Bo , Lin Wei-long 
Published: July 2018

AbstractThe gamma nail and proximal femoral locking plate (PFLP) are both used for fractures. A controlled study was performed to determine the optimal implant. To assess and analyze the clinical effects of gamma nails and PFLPs for patients with unstable intertrochanteric femoral fractures, specifically with broken lateral walls. Thirty-six patients with unstable intertrochanteric femoral fractures and broken lateral walls were treated with gamma nails or PFLPs and retrospectively studied. The clinical data were compared. Duration of surgery and early full weight-bearing time were significantly longer in the PFLP group compared to the gamma nail group (P < 0.05). However, intraoperative fluoroscopy frequency and total blood loss in the PFLP group were significantly less than those in the gamma nail group (P < 0.05). No significant differences were found in hospitalized days, Parker Palmer mobility scores, Harris hip scores, and complications between the two groups. No difference in hip-functional recovery was found between the gamma nail group and the PFLP group, indicating that both the gamma nail and PFLP were effective for unstable intertrochanteric femoral fractures with a broken lateral wall. However, early weight bearing on the fractures was not encouraged in patients treated with PFLP.
Biomechanical Texture Coding in Rat Whiskers
Authors: Oladazimi Maysam , Brendel Wieland , Schwarz Cornelius 
Published: July 2018

AbstractClassically, texture discrimination has been thought to be based on ‘global’ codes, i.e. frequency (signal analysis based on Fourier analysis) or intensity (signal analysis based on averaging), which both rely on integration of the vibrotactile signal across time and/or space. Recently, a novel ‘local’ coding scheme based on the waveform of frictional movements, discrete short lasting kinematic events (i.e. stick-slip movements called slips) has been formulated. We performed biomechanical measurements of relative movements of a rat vibrissa across sandpapers of different roughness. We find that the classic global codes convey some information about texture identity, but are consistently outperformed by the slip-based local code. Moreover, the slip code also surpasses the global ones in coding for active scanning parameters. This is remarkable as it suggests that the slip code would explicitly allow the whisking rat to optimize perception by selecting goal-specific scanning strategies.
Actin cytoskeleton dynamics in stem cells from autistic individuals
Authors: Griesi-Oliveira Karina , Suzuki Angela May , Alves Aline Yasuda , Mafra Ana Carolina Cintra Nunes , Yamamoto Guilherme Lopes , Ezquina Suzana , Magalhães Yuli Thamires , Forti Fabio Luis , Sertie Andrea Laurato , Zachi Elaine Cristina , Vadasz Estevão , Passos-Bueno Maria Rita 
Published: July 2018

AbstractSeveral lines of indirect evidence, such as mutations or dysregulated expression of genes related to cytoskeleton, have suggested that cytoskeletal dynamics, a process essential for axons and dendrites development, is compromised in autism spectrum disorders (ASD). However, no study has yet examined whether cytoskeleton dynamics is functionally altered in cells from ASD patients. Here we investigated the regulation of actin cytoskeleton dynamics in stem cells from human exfoliated deciduous teeth (SHEDs) of 13 ASD patients and 8 control individuals by inducing actin filament depolymerization and then measuing their reconstruction upon activation of the RhoGTPases Rac, Cdc42 or RhoA. We observed that stem cells from seven ASD individuals (53%) presented altered dymanics of filament reconstruction, including a patient recently studied by our group whose iPSC-derived neuronal cells show shorten and less arborized neurites. We also report potentially pathogenic genetic variants that might be related to the alterations in actin repolymerization dynamics observed in some patient-derived cells. Our results suggest that, at least for a subgroup of ASD patients, the dynamics of actin polymerization is impaired, which might be ultimately leading to neuronal abnormalities.
Inhibition of Tunneling Nanotube (TNT) Formation and Human T-cell Leukemia Virus Type 1 (HTLV-1) Transmission by Cytarabine
Authors: Omsland Maria , Pise-Masison Cynthia , Fujikawa Dai , Galli Veronica , Fenizia Claudio , Parks Robyn Washington , Gjertsen Bjørn Tore , Franchini Genoveffa , Andresen Vibeke 
Published: July 2018

AbstractThe human T-cell leukemia virus type 1 (HTLV-1) is highly dependent on cell-to-cell interaction for transmission and productive infection. Cell-to-cell interactions through the virological synapse, biofilm-like structures and cellular conduits have been reported, but the relative contribution of each mechanism on HTLV-1 transmission still remains vastly unknown. The HTLV-1 protein p8 has been found to increase viral transmission and cellular conduits. Here we show that HTLV-1 expressing cells are interconnected by tunneling nanotubes (TNTs) defined as thin structures containing F-actin and lack of tubulin connecting two cells. TNTs connected HTLV-1 expressing cells and uninfected T-cells and monocytes and the viral proteins Tax and Gag localized to these TNTs. The HTLV-1 expressing protein p8 was found to induce TNT formation. Treatment of MT-2 cells with the nucleoside analog cytarabine (cytosine arabinoside, AraC) reduced number of TNTs and furthermore reduced TNT formation induced by the p8 protein. Intercellular transmission of HTLV-1 through TNTs provides a means of escape from recognition by the immune system. Cytarabine could represent a novel anti-HTLV-1 drug interfering with viral transmission.
Dual terahertz comb spectroscopy with a single free-running fibre laser
Authors: Hu Guoqing , Mizuguchi Tatsuya , Oe Ryo , Nitta Kazuki , Zhao Xin , Minamikawa Takeo , Li Ting , Zheng Zheng , Yasui Takeshi 
Published: July 2018

AbstractDual terahertz (THz) comb spectroscopy enables high spectral resolution, high spectral accuracy, and broad spectral coverage; however, the requirement for dual stabilized femtosecond lasers hampers its versatility. We here report the first demonstration of dual THz comb spectroscopy using a single free-running fibre laser. By tuning the cavity-loss-dependent gain profile with an intracavity Lyot filter together with precise management of the cavity length and dispersion, dual-wavelength comb light beams with slightly detuned repetition frequencies are generated in a single laser cavity. Due to sharing of the same cavity, such comb light beams suffer from common-mode fluctuation of the repetition frequency, and hence the corresponding frequency difference between them is passively stable around a few hundred hertz within millihertz fluctuation. While greatly reducing the size, complexity, and cost of the laser source by use of a single free-running fibre laser, the dual THz comb spectroscopy system maintains a spectral bandwidth and dynamic range of spectral power comparable to a system equipped with dual stabilized fibre lasers, and can be effectively applied to high-precision spectroscopy of acetonitrile gas at atmospheric pressure. The demonstrated results indicate that this system is an attractive solution for practical applications of THz spectroscopy and other applications.
The Impact of Compressed Femtosecond Laser Pulse Durations on Neuronal Tissue Used for Two-Photon Excitation Through an Endoscope
Authors: Sibai Mira , Mehidine Hussein , Poulon Fanny , Ibrahim Ali , Varlet P. , Juchaux M. , Pallud J. , Devaux B. , Kudlinski A. , Abi Haidar Darine 
Published: July 2018

AbstractAccurate intraoperative tumour margin assessment is a major challenge in neurooncology, where sparse tumours beyond the bulk tumour are left undetected under conventional resection. Non-linear optical imaging can diagnose tissue at the sub-micron level and provide functional label-free histopathology in vivo. For this reason, a non-linear endomicroscope is being developed to characterize brain tissue intraoperatively based on multiple endogenous optical contrasts such as spectrally- and temporally-resolved fluorescence. To produce highly sensitive optical signatures that are specific to a given tissue type, short femtosecond pulsed lasers are required for efficient two-photon excitation. Yet, the potential of causing bio-damage has not been studied on neuronal tissue. Therefore, as a prerequisite to clinically testing the non-linear endomicroscope in vivo, the effect of short laser pulse durations (40–340 fs) on ex vivo brain tissue was investigated by monitoring the intensity, the spectral, and the lifetime properties of endogenous fluorophores under 800 and 890 nm two-photon excitation using a bi-modal non-linear endoscope. These properties were also validated by imaging samples on a benchtop multiphoton microscope. Our results show that under a constant mean laser power, excitation pulses as short as 40 fs do not negatively alter the biochemical/ biophysical properties of tissue even for prolonged irradiation.
An acidic model pro-peptide affects the secondary structure, membrane interactions and antimicrobial activity of a crotalicidin fragment
Authors: Júnior Nelson G. O. , Cardoso Marlon H. , Cândido Elizabete S. , van den Broek Daniëlle , de Lange Niek , Velikova Nadya , Kleijn J. Mieke , Wells Jerry M. , Rezende Taia M. B. , Franco Octávio Luiz , de Vries Renko 
Published: July 2018

AbstractIn order to study how acidic pro-peptides inhibit the antimicrobial activity of antimicrobial peptides, we introduce a simple model system, consisting of a 19 amino-acid long antimicrobial peptide, and an N-terminally attached, 10 amino-acid long acidic model pro-peptide. The antimicrobial peptide is a fragment of the crotalicidin peptide, a member of the cathelidin family, from rattlesnake venom. The model pro-peptide is a deca (glutamic acid). Attachment of the model pro-peptide only leads to a moderately large reduction in the binding to- and induced leakage of model liposomes, while the antimicrobial activity of the crotalicidin fragment is completely inhibited by attaching the model pro-peptide. Attaching the pro-peptide induces a conformational change to a more helical conformation, while there are no signs of intra- or intermolecular peptide complexation. We conclude that inhibition of antimicrobial activity by the model pro-peptide might be related to a conformational change induced by the pro-peptide domain, and that additional effects beyond induced changes in membrane activity must also be involved.
Expanding the Arterivirus Host Spectrum: Olivier’s Shrew Virus 1, A Novel Arterivirus Discovered in African Giant Shrews
Authors: Vanmechelen Bert , Vergote Valentijn , Laenen Lies , Koundouno Fara Raymond , Bore Joseph Akoi , Wada Jiro , Kuhn Jens H. , Carroll Miles W. , Maes Piet 
Published: July 2018

AbstractThe family Arteriviridae harbors a rapidly expanding group of viruses known to infect a divergent group of mammals, including horses, pigs, possums, primates, and rodents. Hosts infected with arteriviruses present with a wide variety of (sub) clinical symptoms, depending on the virus causing the infection and the host being infected. In this study, we determined the complete genome sequences of three variants of a previously unknown virus found in Olivier’s shrews (Crocidura olivieri guineensis) sampled in Guinea. On the nucleotide level, the three genomes of this new virus, named Olivier’s shrew virus 1 (OSV-1), are 88–89% similar. The genome organization of OSV-1 is characteristic of all known arteriviruses, yet phylogenetic analysis groups OSV-1 separately from all currently established arterivirus lineages. Therefore, we postulate that OSV-1 represents a member of a novel arterivirus genus. The virus described here represents the first discovery of an arterivirus in members of the order Eulipotyphla, thereby greatly expanding the known host spectrum of arteriviruses.
The Dynamics of Nanoparticle-enhanced Fluid Displacement in Porous Media - A Pore-scale Study
Authors: Pak Tannaz , Archilha Nathaly Lopes , Mantovani Iara Frangiotti , Moreira Anderson Camargo , Butler Ian B. 
Published: July 2018

AbstractThis work provides new insights into the dynamics of silica nanoparticle-based removal of organic fluids (here oil) from naturally occurring porous media. We have used 4D (time-resolved 3D) imaging at pore-scale using X-ray computed micro-tomography (μCT) technique. The captured 3D tomographic time-series data reveal the dynamics of immiscible oil displacement from a carbonate rock upon injection of nanoparticle (NP) suspensions (0.06 and 0.12 wt% SiO2in deionised water). Our analysis shows significant pore-scale remobilisation of initially trapped oil upon injection of the NP suspensions, specifically, at higher concentration. Our data shows that oil clusters become significantly smaller with larger fluid/fluid interface as a result of the higher concentration NP injection. This paper demonstrates that use of 2D radiograms collected during fluid injections allows monitoring flow dynamics at time resolutions down to a few seconds using conventional laboratory-based μCT scanners. Here, as an underlying mechanism for oil remobilisation, we present the first 4D evidence ofin-situformation of an oil in water emulsion induced by nanoparticles.
Engineered Protein Model of the ATP synthase H+- Channel Shows No Salt Bridge at the Rotor-Stator Interface
Authors: Pierson Hannah E. , Kaler Mandeep , O’Grady Christopher , Uhlemann Eva-Maria E. , Dmitriev Oleg Y. 
Published: July 2018

AbstractATP synthase is powered by the flow of protons through the molecular turbine composed of two α-helical integral membrane proteins, subunita, which makes a stator, and a cylindrical rotor assembly made of multiple copies of subunitc. Transient protonation of a universally conserved carboxylate on subunitc(D61 inE. coli) gated by the electrostatic interaction with arginine on subunita(R210 inE. coli) is believed to be a crucial step in proton transfer across the membrane. We used a fusion protein consisting of subunitaand the adjacent helices of subunitcto test by NMR spectroscopy ifcD61 andaR210 are involved in an electrostatic interaction with each other, and found no evidence of such interaction. We have also determined that R140 does not form a salt bridge with either D44 or D124 as was suggested previously by mutation analysis. Our results demonstrate the potential of using arginines as NMR reporter groups for structural and functional studies of challenging membrane proteins.
Partial migration in savanna elephant populations distributed across southern Africa
Authors: Purdon Andrew , Mole Michael A. , Chase Michael J. , van Aarde Rudi J. 
Published: July 2018

AbstractMigration is an important, but threatened ecological process. Conserving migration requires the maintenance of functional connectivity across sufficiently large areas. Therefore, we need to know if, where and why species migrate. Elephants are highly mobile and can travel long distances but we do not know if they migrate. Here, we analysed the movement trajectories of 139 savanna elephants (Loxodonta africana) within eight clusters of protected areas across southern Africa to determine if elephants migrate, and if so, where, how and why they migrate. Only 25 of these elephants migrated. Elephants are a facultative partially migratory species, where only some individuals in a population migrate opportunistically, and not every year. Elephants migrated between distinct seasonal ranges corresponding to southern Africa’s dry and wet seasons. The timing of wet season migrations was associated with the onset of rainfall and the subsequent greening up of forage. Conversely, the duration, distance, and the timing of dry season migrations varied idiosyncratically. The drivers of elephant migration are likely a complex interaction between individual traits, density, and the distribution and availability of resources. Despite most migrations crossing administrative boundaries, conservation networks provided functional space for elephants to migrate.
Primary human nasal epithelial cells: a source of poly (I:C) LMW-induced IL-6 production
Authors: Ramezanpour Mahnaz , Bolt Harrison , Psaltis Alkis James , Wormald Peter-John , Vreugde Sarah 
Published: July 2018

AbstractInfection plays a significant role in the relapse of chronic rhinosinusitis (CRS), however, the role of primary human nasal epithelial cells (HNECs) in this process is largely unknown. Here, we determined the effect of Toll-like receptor (TLR) agonists and inflammatory cytokines on mucosal barrier integrity and immune response of HNECs. TLR 1–9 agonists and inflammatory cytokines were applied to submerged and/or air-liquid interface (ALI) cultures of HNECs from CRS patients and controls for 24 hours. Interleukin-6 (IL-6) protein levels were determined by ELISA. Mucosal barrier integrity was measured via Transepithelial Electrical Resistance and passage of fluorescently-labelled dextrans. IL-1β and IFN- γ significantly increased IL-6 production in HNECs derived from CRS patients and controls, however, a dose-dependent effect was observed in CRS-derived HNECs only. Stimulation with Poly (I:C) LMW induced a 15 to 17 fold increase in IL-6 production by HNEC-ALI control cells (p < 0.05) and HNEC-ALI-CRS cells (p = 0.004) whilst a 2.5 fold increase was observed in CRS HNEC submerged cultures. Priming of cells with Poly (I:C) LMW reduced subsequent IL-6 secretion upon stimulation with TLR 2–4 agonists. Poly (I:C) LMW exerts a potent pro-inflammatory effect on HNECs and reduces a subsequent immune activation by TLR agonists.
Erkältungsmittel aus der Klosterapotheke
Authors: Gottfried Mayer Johannes , Will Heike 
Published: July 2018

SummaryPflanzen der Klostermedizin, ergänzt durch wenige moderne Phytotherapeutika, bieten bei Erkältungskrankheiten bis heute den größten Therapieerfolg. Entzündungslindernde Pflanzen wie Süßholz, Ringelblume und Kamille lassen sich geschickt mit Expektoranzien wie Thymian und wärmenden Mitteln wie Senföl-Lieferanten kombinieren. Schleimdrogen wie Eibisch und Malve ergänzen klassische Hustenpflanzen wie Fenchel, Schlüsselblume, Andorn und Königskerze.
Alter neuer Königsweg: Die Durchspülungstherapie
Authors: Johannes Gottfried Mayer , Katharina Mantel 
Published: July 2018

SummaryZu den wichtigen Indikationen der Durchspülungstherapie zählen Harnwegsinfekte, Reizblase und Nierengrieß. Traditionelle Heilpflanzen wie Birke, Wacholder und Schachtelhalm zeigen durchspülende Effekte. In jüngster Zeit wurden Senfölen zum Beispiel in Meerrettich und Kapuzinerkresse deutlich antibiotische Effekte bei Harnwegsinfekten bescheinigt.