bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experimental assessment of the safety and potential efficacy of high irradiance photostimulation of brain tissues
Authors: Senova Suhan , Scisniak Ilona , Chiang Chih-Chieh , Doignon Isabelle , Palfi Stéphane , Chaillet Antoine , Martin Claire , Pain Frédéric 
Published: March 2017

AbstractOptogenetics is widely used in fundamental neuroscience. Its potential clinical translation for brain neuromodulation requires a careful assessment of the safety and efficacy of repeated, sustained optical stimulation of large volumes of brain tissues. This study was performed in rats and not in non-human primates for ethical reasons. We studied the spatial distribution of light, potential damage, and non-physiological effects in vivo, in anesthetized rat brains, on large brain volumes, following repeated high irradiance photo-stimulation. We generated 2D irradiance and temperature increase surface maps based on recordings taken during optical stimulation using irradiance and temporal parameters representative of common optogenetics experiments. Irradiances of 100 to 600 mW/mm2 with 5 ms pulses at 20, 40, and 60 Hz were applied during 90 s. In vivo electrophysiological recordings and post-mortem histological analyses showed that high power light stimulation had no obvious phototoxic effects and did not trigger non-physiological functional activation. This study demonstrates the ability to illuminate cortical layers to a depth of several millimeters using pulsed red light without detrimental thermal damages.
NV Proteins of Fish Novirhabdovirus Recruit Cellular PPM1Bb Protein Phosphatase and Antagonize RIG-I-Mediated IFN Induction
Authors: Biacchesi Stéphane , Mérour Emilie , Chevret Didier , Lamoureux Annie , Bernard Julie , Brémont Michel 
Published: March 2017

AbstractNon virion (NV) protein expression is critical for fish Novirhabdovirus, viral hemorrhagic septicemia virus (VHSV) and infectious hematopoietic necrosis virus (IHNV), in vivo pathogenesis. However, the mechanism by which NV promotes the viral replication is still unclear. We developed an approach based on reverse genetics and interactomic and identified several NV-associated cellular partners underlying cellular pathways as potential viral targets. Among these cell partners, we showed that NV proteins specifically interact with a protein phosphatase, Mg2+/Mn2+-dependent, 1Bb (PPM1Bb) and recruit it in the close vicinity of mitochondria, a subcellular compartment important for retinoic acid-inducible gene-I- (RIG-I)-mediated interferon induction pathway. PPM1B proteins belong to the PP2C family of serine/threonine (Ser/Thr) protein phosphatase and have recently been shown to negatively regulate the host antiviral response via dephosphorylating Traf family member-associated NF-κB activator (TANK)-binding kinase 1 (TBK1). We demonstrated that NV proteins and PPM1Bb counteract RIG-I- and TBK1-dependent interferon (IFN) and IFN-stimulated gene promoter induction in fish cells and, hence, the establishment of an antiviral state. Furthermore, the expression of VHSV NV strongly reduced TBK1 phosphorylation and thus its activation. Our findings provide evidence for a previously undescribed mechanism by which a viral protein recruits PPM1Bb protein phosphatase to subvert innate immune recognition.
Identification of berberine as a direct thrombin inhibitor from traditional Chinese medicine through structural, functional and binding studies
Authors: Wang Xing , Zhang Yuxin , Yang Ying , Wu Xia , Fan Hantian , Qiao Yanjiang 
Published: March 2017

AbstractThrombin acts as a key enzyme in the blood coagulation cascade and represents a potential drug target for the treatment of several cardiovascular diseases. The aim of this study was to identify small-molecule direct thrombin inhibitors from herbs used in traditional Chinese medicine (TCM). A pharmacophore model and molecular docking were utilized to virtually screen a library of chemicals contained in compositions of traditional Chinese herbs, and these analyses were followed by in vitro bioassay validation and binding studies. Berberine (BBR) was first confirmed as a thrombin inhibitor using an enzymatic assay. The BBR IC50 value for thrombin inhibition was 2.92 μM. Direct binding studies using surface plasmon resonance demonstrated that BBR directly interacted with thrombin with a KD value of 16.39 μM. Competitive binding assay indicated that BBR could bind to the same argartroban/thrombin interaction site. A platelet aggregation assay demonstrated that BBR had the ability to inhibit thrombin-induced platelet aggregation in washed platelets samples. This study proved that BBR is a direct thrombin inhibitor that has activity in inhibiting thrombin-induced platelet aggregation. BBR may be a potential candidate for the development of safe and effective thrombin-inhibiting drugs.
Engineering a vascularised 3D in vitro model of cancer progression
Authors: Magdeldin Tarig , López-Dávila Víctor , Pape Judith , Cameron Grant W. W. , Emberton Mark , Loizidou Marilena , Cheema Umber 
Published: March 2017

AbstractThe hallmark of tumours is the ability of cancerous cells to promote vascular growth, to disseminate and invade to distant organs. The metastatic process is heavily influenced by the extracellular matrix (ECM) density and composition of the surrounding tumour microenvironment. These microenvironmental cues, which include hypoxia, also regulate the angiogenic processes within a tumour, facilitating the spread of cancer cells. We engineered compartmentalized biomimetic colorectal tumouroids with stromal surrounds that comprised a range of ECM densities, composition and stromal cell populations. Recapitulating tissue ECM composition and stromal cell composition enhanced cancer cell invasion. Manipulation of ECM density was associated with an altered migration pattern from glandular buds (cellular aggregates) to epithelial cell sheets. Laminin appeared to be a critical component in regulating endothelial cell morphology and vascular network formation. Interestingly, the disruption of vascular networks by cancer cells was driven by changes in expression of several anti-angiogenic genes. Cancer cells cultured in our biomimetic tumouroids exhibited intratumoural heterogeneity that was associated with increased tumour invasion into the stroma. These findings demonstrate that our 3D in vitro tumour model exhibits biomimetic attributes that may permit their use in studying microenvironment clues of tumour progression and angiogenesis.
Meprin Metalloproteases Generate Biologically Active Soluble Interleukin-6 Receptor to Induce Trans-Signaling
Authors: Arnold Philipp , Boll Inga , Rothaug Michelle , Schumacher Neele , Schmidt Frederike , Wichert Rielana , Schneppenheim Janna , Lokau Juliane , Pickhinke Ute , Koudelka Tomas , Tholey Andreas , Rabe Björn , Scheller Jürgen , Lucius Ralph , Garbers Christoph , Rose-John Stefan , Becker-Pauly Christoph 
Published: March 2017

AbstractSoluble Interleukin-6 receptor (sIL-6R) mediated trans-signaling is an important pro-inflammatory stimulus associated with pathological conditions, such as arthritis, neurodegeneration and inflammatory bowel disease. The sIL-6R is generated proteolytically from its membrane bound form and A Disintegrin And Metalloprotease (ADAM) 10 and 17 were shown to perform ectodomain shedding of the receptorin vitroandin vivo. However, under certain conditions not all sIL-6R could be assigned to ADAM10/17 activity. Here, we demonstrate that the IL-6R is a shedding substrate of soluble meprin α and membrane bound meprin β, resulting in bioactive sIL-6R that is capable of inducing IL-6 trans-signaling. We determined cleavage within the N-terminal part of the IL-6R stalk region, distinct from the cleavage site reported for ADAM10/17. Interestingly, meprin β can be shed from the cell surface by ADAM10/17 and the observation that soluble meprin β is not capable of shedding the IL-6R suggests a regulatory mechanism towards trans-signaling. Additionally, we observed a significant negative correlation of meprin β expression and IL-6R levels on human granulocytes, providing evidence forin vivofunction of this proteolytic interaction.
Processing of fair and unfair offers in the ultimatum game under social observation
Authors: Peterburs Jutta , Voegler Rolf , Liepelt Roman , Schulze Anna , Wilhelm Saskia , Ocklenburg Sebastian , Straube Thomas 
Published: March 2017

AbstractSocial context influences social decisions and outcome processing, partially depending on inter-individual differences. The present study investigated social context-dependent modulation of behavior and feedback processing in the ultimatum game (UG) in relation to inter-individual differences in social anxiety. Thirty-two healthy adults completed the UG both under social observation and without observation. Offers were allegedly either randomly generated by the computer or drawn from a pool of offers from previous human players. Overall, fewer unfair than fair offers were accepted. Observation decreased acceptance rates for unfair offers. The feedback-locked feedback-related negativity (FRN) but not the P3 was modulated by observation and fairness, with stronger differential coding of unfair/fair under observation. This effect was strongly correlated with individual levels of social anxiety, with higher levels associated with stronger differential fairness coding in the FRN under observation. Behavioral findings support negative reciprocity in the UG, suggesting that (implicit) social norms overwrite explicit task instructions even in the absence of (alleged) social interaction. Observation enhances this effect. Fairness coding in the FRN was modulated by observation as a function of social anxiety, supporting the notion that altered sensitivity to equality in a social context may contribute to social avoidance in socially anxious individuals.
Significant improvement in Mn2O3 transition metal oxide electrical conductivity via high pressure
Authors: Hong Fang , Yue Binbin , Hirao Naohisa , Liu Zhenxian , Chen Bin 
Published: March 2017

AbstractHighly efficient energy storage is in high demand for next-generation clean energy applications. As a promising energy storage material, the application of Mn2O3 is limited due to its poor electrical conductivity. Here, high-pressure techniques enhanced the electrical conductivity of Mn2O3 significantly. In situ synchrotron micro X-Ray diffraction, Raman spectroscopy and resistivity measurement revealed that resistivity decreased with pressure and dramatically dropped near the phase transition. At the highest pressure, resistivity reduced by five orders of magnitude and the sample showed metal-like behavior. More importantly, resistivity remained much lower than its original value, even when the pressure was fully released. This work provides a new method to enhance the electronic properties of Mn2O3 using high-pressure treatment, benefiting its applications in energy-related fields.
Modulation of p-eIF2α cellular levels and stress granule assembly/disassembly by trehalose
Authors: Dimasi Pasquale , Quintiero Annamaria , Shelkovnikova Tatyana A. , Buchman Vladimir L. 
Published: March 2017

AbstractStress granules (SGs) are an important component of cellular stress response. Compromised assembly of SGs as well as their premature or delayed disassembly affect physiology and survival of cells under stress or during recovery from stress. Consequently, abnormal turnover of SGs has been implicated in the development of various pathologies, including neurodegeneration. We found that pretreatment of cells with a natural disaccharide trehalose, a known autophagy enhancer, delays SG assembly and facilitates their premature post-stress disassembly. Mechanistically, the effect of trehalose on SGs is mediated via the p-eIF2α rather than autophagosome pathway. Trehalose increases pre-stress levels of p-eIF2α and its phosphatase subunits and promotes post-stress translational recovery. Upon prolonged treatment, trehalose impairs basal translation affecting production of transiently expressed proteins. Early translational recovery and SG disassembly induced by trehalose pretreatment can sensitise cells to stress and impair survival. Our study has important implications for the use of trehalose in studies of autophagic clearance of misfolded proteins and for targeting SGs as a possible therapeutic approach in neurodegenerative and other diseases.
Growth Mechanism for Low Temperature PVD Graphene Synthesis on Copper Using Amorphous Carbon
Authors: Narula Udit , Tan Cher Ming , Lai Chao Sung 
Published: March 2017

AbstractGrowth mechanism for synthesizing PVD based Graphene using Amorphous Carbon, catalyzed by Copper is investigated in this work. Different experiments with respect to Amorphous Carbon film thickness, annealing time and temperature are performed for the investigation. Copper film stress and its effect on hydrogen diffusion through the film grain boundaries are found to be the key factors for the growth mechanism, and supported by our Finite Element Modeling. Low temperature growth of Graphene is achieved and the proposed growth mechanism is found to remain valid at low temperatures.
A randomized trial and novel SPR technique identifies altered lipoprotein-LDL receptor binding as a mechanism underlying elevated LDL-cholesterol in APOE4s
Authors: Calabuig-Navarro M. V. , Jackson K. G. , Kemp C. F. , Leake D. S. , Walden C. M. , Lovegrove J. A. , Minihane A. M. 
Published: March 2017

AbstractAt a population level APOE4 carriers (~25% Caucasians) are at higher risk of cardiovascular diseases. The penetrance of genotype is however variable and influenced by dietary fat composition, with the APOE4 allele associated with greater LDL-cholesterol elevation in response to saturated fatty acids (SFA). The etiology of this greater responsiveness is unknown. Here a novel surface plasmon resonance technique (SPR) is developed and used, along with hepatocyte (with the liver being the main organ modulating lipoprotein metabolism and plasma lipid levels) uptake studies to establish the impact of dietary fatty acid composition on, lipoprotein-LDL receptor (LDLR) binding, and hepatocyte uptake, according to APOE genotype status. In men prospectively recruited according to APOE genotype (APOE3/3 common genotype, or APOE3/E4), triglyceride-rich lipoproteins (TRLs) were isolated at fasting and 4–6 h following test meals rich in SFA, unsaturated fat and SFA with fish oil. In APOE4s a greater LDLR binding affinity of postprandial TRL after SFA, and lower LDL binding and hepatocyte internalization, provide mechanisms for the greater LDL-cholesterol raising effect. The SPR technique developed may be used for the future study of the impact of genotype, and physiological and behavioral variables on lipoprotein metabolism. Trial registration number NCT01522482.
Magnetically controlled ferromagnetic swimmers
Authors: Hamilton Joshua K. , Petrov Peter G. , Winlove C. Peter , Gilbert Andrew D. , Bryan Matthew T. , Ogrin Feodor Y. 
Published: March 2017

AbstractMicroscopic swimming devices hold promise for radically new applications in lab-on-a-chip and microfluidic technology, diagnostics and drug delivery etc. In this paper, we demonstrate the experimental verification of a new class of autonomous ferromagnetic swimming devices, actuated and controlled solely by an oscillating magnetic field. These devices are based on a pair of interacting ferromagnetic particles of different size and different anisotropic properties joined by an elastic link and actuated by an external time-dependent magnetic field. The net motion is generated through a combination of dipolar interparticle gradient forces, time-dependent torque and hydrodynamic coupling. We investigate the dynamic performance of a prototype (3.6 mm) of the ferromagnetic swimmer in fluids of different viscosity as a function of the external field parameters (frequency and amplitude) and demonstrate stable propulsion over a wide range of Reynolds numbers. We show that the direction of swimming has a dependence on both the frequency and amplitude of the applied external magnetic field, resulting in robust control over the speed and direction of propulsion. This paves the way to fabricating microscale devices for a variety of technological applications requiring reliable actuation and high degree of control.
A norm knockout method on indirect reciprocity to reveal indispensable norms
Authors: Yamamoto Hitoshi , Okada Isamu , Uchida Satoshi , Sasaki Tatsuya 
Published: March 2017

AbstractAlthough various norms for reciprocity-based cooperation have been suggested that are evolutionarily stable against invasion from free riders, the process of alternation of norms and the role of diversified norms remain unclear in the evolution of cooperation. We clarify the co-evolutionary dynamics of norms and cooperation in indirect reciprocity and also identify the indispensable norms for the evolution of cooperation. Inspired by the gene knockout method, a genetic engineering technique, we developed the norm knockout method and clarified the norms necessary for the establishment of cooperation. The results of numerical investigations revealed that the majority of norms gradually transitioned to tolerant norms after defectors are eliminated by strict norms. Furthermore, no cooperation emerges when specific norms that are intolerant to defectors are knocked out.
Multiunit Activity-Based Real-Time Limb-State Estimation from Dorsal Root Ganglion Recordings
Authors: Han Sungmin , Chu Jun-Uk , Kim Hyungmin , Park Jong Woong , Youn Inchan 
Published: March 2017

AbstractProprioceptive afferent activities could be useful for providing sensory feedback signals for closed-loop control during functional electrical stimulation (FES). However, most previous studies have used the single-unit activity of individual neurons to extract sensory information from proprioceptive afferents. This study proposes a new decoding method to estimate ankle and knee joint angles using multiunit activity data. Proprioceptive afferent signals were recorded from a dorsal root ganglion with a single-shank microelectrode during passive movements of the ankle and knee joints, and joint angles were measured as kinematic data. The mean absolute value (MAV) was extracted from the multiunit activity data, and a dynamically driven recurrent neural network (DDRNN) was used to estimate ankle and knee joint angles. The multiunit activity-based MAV feature was sufficiently informative to estimate limb states, and the DDRNN showed a better decoding performance than conventional linear estimators. In addition, processing time delay satisfied real-time constraints. These results demonstrated that the proposed method could be applicable for providing real-time sensory feedback signals in closed-loop FES systems.
Calcium isotope fractionation between aqueous compounds relevant to low-temperature geochemistry, biology and medicine
Authors: Moynier Frédéric , Fujii Toshiyuki 
Published: March 2017

AbstractStable Ca isotopes are fractionated between bones, urine and blood of animals and between soils, roots and leaves of plants by >1000 ppm for the 44Ca/40Ca ratio. These isotopic variations have important implications to understand Ca transport and fluxes in living organisms; however, the mechanisms of isotopic fractionation are unclear. Here we present ab initio calculations for the isotopic fractionation between various aqueous species of Ca and show that this fractionation can be up to 3000 ppm. We show that the Ca isotopic fractionation between soil solutions and plant roots can be explained by the difference of isotopic fractionation between the different first shell hydration degree of Ca2+ and that the isotopic fractionation between roots and leaves is controlled by the precipitation of Ca-oxalates. The isotopic fractionation between blood and urine is due to the complexation of heavy Ca with citrate and oxalates in urine. Calculations are presented for additional Ca species that may be useful to interpret future Ca isotopic measurements.
The Contrast Enhancement of Intracranial Arterial Wall on High-resolution MRI and Its Clinical Relevance in Patients with Moyamoya Vasculopathy
Authors: Wang Maoxue , Yang Yongbo , Zhou Fei , Li Ming , Liu Renyuan , Guan Maobin , Li Rui , He Le , Xu Yun , Zhang Bing , Zhu Bin , Zhao Xihai 
Published: March 2017

AbstractThe purpose of this study is to investigate the characteristics of intracranial vessel wall enhancement and its relationship with ischemic infarction in patients with Moyamoya vasculopathy (MMV). Forty-seven patients with MMV confirmed by angiography were enrolled in this study. The vessel wall enhancement of the distal internal carotid artery, anterior cerebral artery and middle cerebral artery was classified into eccentric and concentric patterns, as well as divided into three grades: grade 0, grade 1 and grade 2. The relationship between ischemic infarction and vessel wall enhancement was also determined. Fifty-six enhanced lesions were found in patients with (n = 25) and without acute infarction (n = 22). The incidence of lesions with grade 2 enhancement in patients with acute infarction was greater than that in those without acute infarction (p = 0.011). In addition, grade 2 enhancement of the intracranial vessel wall was significantly associated with acute ischemic infarction (Odds ratio, 26.7; 95% confidence interval: 2.8–258.2; p = 0.005). Higher-grade enhancement of the intracranial vessel wall is independently associated with acute ischemic infarction in patients with MMV. The characteristics of intracranial vessel wall enhancement may serve as a marker of its stability and provide important insight into ischemic stroke risk factors.
Preparation of a nanosilica cross‐linker and investigation of its effect on properties of guar gum fracturing fluid
Authors: Zhang Zifeng , Liu Peisong , Pan Hao , Zhao Mengyun , Li Xiaohong , Zhang Zhijun 
Published: March 2017

The development of hydraulic fracturing has created a huge demand for fracturing fluids with high performance and low formation damage in recent years. A nanosilica cross‐linker precursor (NCP) was prepared by introducing boric acid to the surface of organic silica compound (C9H23NO3Si, a silane coupling agent), the carrier. As‐obtained NCP was transformed into nanoparticles (NPs) with a diameter of 10–35 nm by self‐aggregation. The resultant NPs were used to crosslink low concentration of guar gum solution in order to improve the rheological and breaking properties of the fracturing fluid made of the NPs‐cross‐linked guar gum gels. Findings indicate that boric acid chemically reacts with the amino group of the silane coupling agent forming N–B bond via infrared analysis. The viscosity of NPs‐cross‐linked guar gum gels increases with the increase of particle size of NPs, which means that the particle size of NPs has a significant effect on the cross‐linking efficacy, the guar gum gels cross‐linked by a proper mass fractions of NPs exhibits good temperature resistance and shear resistance via rheometer. Moreover, the NPs‐cross‐linked guar gum gels possesses better breaking behaviour than the one cross‐linked by borate.