bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac spheroids as promising in vitro models to study the human heart microenvironment
Authors: Polonchuk Liudmila , Chabria Mamta , Badi Laura , Hoflack Jean-Christophe , Figtree Gemma , Davies Michael J. , Gentile Carmine
Published: July 2017

Three-dimensional in vitro cell systems are a promising alternative to animals to study cardiac biology and disease. We have generated three-dimensional in vitro models of the human heart (“cardiac spheroids”, CSs) by co-culturing human primary or iPSC-derived cardiomyocytes, endothelial cells and fibroblasts at ratios approximating those present in vivo. The cellular organisation, extracellular matrix and microvascular network mimic human heart tissue. These spheroids have been employed to investigate the dose-limiting cardiotoxicity of the common anti-cancer drug doxorubicin. Viability/cytotoxicity assays indicate dose-dependent cytotoxic effects, which are inhibited by the nitric oxide synthase (NOS) inhibitor L-NIO, and genetic inhibition of endothelial NOS, implicating peroxynitrous acid as a key damaging agent. These data indicate that CSs mimic important features of human heart morphology, biochemistry and pharmacology in vitro, offering a promising alternative to animals and standard cell cultures with regard to mechanistic insights and prediction of toxic effects in human heart tissue.
Folding driven self-assembly of a stimuli-responsive peptide-hyaluronan hybrid hydrogel
Authors: Selegård Robert , Aronsson Christopher , Brommesson Caroline , Dånmark Staffan , Aili Daniel
Published: July 2017

Protein-metal ion interactions are ubiquitous in nature and can be utilized for controlling the self-assembly of complex supramolecular architectures and materials. Here, a tunable supramolecular hydrogel is described, obtained by self-assembly of a Zn2+-responsive peptide-hyaluronic acid hybrid synthesized using strain promoted click chemistry. Addition of Zn2+ triggers folding of the peptides into a helix-loop-helix motif and dimerization into four-helix bundles, resulting in hydrogelation. Removal of the Zn2+ by chelators results in rapid hydrogel disassembly. Degradation of the hydrogels can also be time-programed by encapsulation of a hydrolyzing enzyme within the gel, offering multiple possibilities for modulating materials properties and release of encapsulated species. The hydrogel further shows potential antioxidant properties when evaluated using an in vitro model for reactive oxygen species.
Metal-Insulator Transition in Nanoparticle Solids: Insights from Kinetic Monte Carlo Simulations
Authors: Qu Luman , Vörös Márton , Zimanyi Gergely T.
Published: July 2017

Progress has been rapid in increasing the efficiency of energy conversion in nanoparticles. However, extraction of the photo-generated charge carriers remains challenging. Encouragingly, the charge mobility has been improved recently by driving nanoparticle (NP) films across the metal-insulator transition (MIT). To simulate MIT in NP films, we developed a hierarchical Kinetic Monte Carlo transport model. Electrons transfer between neighboring NPs via activated hopping when the NP energies differ by more than an overlap energy, but transfer by a non-activated quantum delocalization, if the NP energies are closer than the overlap energy. As the overlap energy increases, emerging percolating clusters support a metallic transport across the entire film. We simulated the evolution of the temperature-dependent electron mobility. We analyzed our data in terms of two candidate models of the MIT: (a) as a Quantum Critical Transition, signaled by an effective gap going to zero; and (b) as a Quantum Percolation Transition, where a sample-spanning metallic percolation path is formed as the fraction of the hopping bonds in the transport paths is going to zero. We found that the Quantum Percolation Transition theory provides a better description of the MIT. We also observed an anomalously low gap region next to the MIT. We discuss the relevance of our results in the light of recent experimental measurements.
Acceleration of Batch-type Heterogeneous Ligand-free Suzuki-Miyaura Reactions with Polymer Composite Supported Pd Catalyst
Authors: Wang Mian , Xue Han , Ju Fei , Yang Haijie
Published: July 2017

An efficient and recyclable palladium (II) catalyst supported on a double-structured amphiphilic polymer composite was reported previously containing a polymer hydrogel within macroporous polystyrene (PS) microspheres. However, some critical questions have been unaddressed. First, the catalyst accelerated the heterogeneous ligand-free batch Suzuki-Miyaura reaction in a H2O/EtOH mixture solution at room temperature in the presence of air, which could be ascribed to the “on-water” effect taking place at the interface of the aqueous–organic and basic-aqueous phases created by sodium carbonate in H2O/EtOH. To this acceleration, the double-structured amphiphilic polymer composite can also contribute by providing hydrogels inside the macroporous PS that served as a microreactor. This microreactor allowed the reactions to quickly proceed across the two immiscible (i.e. aqueous-organic and basic-aqueous) phases. Moreover, hydrogels containing hydroxyl groups can also serve as phase-transfer catalysts (PTC) to promote the Suzuki reaction. Second, the deactivated catalyst recovered its initial catalytic activity after overnight air exposure. This observation indicates the importance of oxygen in the activation/deactivation of Pd metals, as determined by X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) measurements which revealed different Pd oxidation states with various morphologies before and after Suzuki reactions.
Motorboat noise disrupts co-operative interspecific interactions
Authors: Nedelec Sophie L. , Mills Suzanne C. , Radford Andrew N. , Beldade Ricardo , Simpson Stephen D. , Nedelec Brendan , Côté Isabelle M.
Published: July 2017

Human-made noise is contributing increasingly to ocean soundscapes. Its physical, physiological and behavioural effects on marine organisms are potentially widespread, but our understanding remains largely limited to intraspecific impacts. Here, we examine how motorboats affect an interspecific cleaning mutualism critical for coral reef fish health, abundance and diversity. We conducted in situ observations of cleaning interactions between bluestreak cleaner wrasses (Labroides dimidiatus) and their fish clients before, during and after repeated, standardised approaches with motorboats. Cleaners inspected clients for longer and were significantly less cooperative during exposure to boat noise, and while motorboat disturbance appeared to have little effect on client behaviour, as evidenced by consistency of visit rates, clientele composition, and use of cleaning incitation signals, clients did not retaliate as expected (i.e., by chasing) in response to increased cheating by cleaners. Our results are consistent with the idea of cognitive impairments due to distraction by both parties. Alternatively, cleaners might be taking advantage of distracted clients to reduce their service quality. To more fully understand the importance of these findings for conservation and management, further studies should elucidate whether the efficacy of ectoparasite removal by cleaners is affected and explore the potential for habituation to boat noise in busy areas.
Role of Aortic Geometry on Stroke Propensity based on Simulations of Patient-Specific Models
Authors: Choi Hyo Won , Luo Tong , Navia Jose A. , Kassab Ghassan S.
Published: July 2017

Stroke is a life threatening event that is expected to more than double over the next 40 years. Atrial fibrillation (AF) has been reported as a strong independent risk factor for stroke. We have previously shown that a hemodynamic perturbation by AF or reduced cardiac output and cycle length may have a significant impact on clot trajectory and thus embolic stroke propensity through the left common carotid artery using an idealized aortic arch model. Here, we show the dependence of flow patterns and hence stroke propensity on geometry of patient-specific aortas. We performed computational fluid dynamics (CFD) simulations to determine the variations of AF-induced stroke propensity over various image-based patient-dependent aorta models. The results demonstrated that curvature pattern of aorta can play a determinant role in AF-induced stroke propensity alteration. Specifically, it was shown that the hemodynamic perturbation by AF considered led to substantial increase in stroke propensity (i.e., 2.5~3.8 fold elevation) for lower curvature angle <90° while the changes in stroke propensity by AF are negligible for higher curvature angle >90°. The present simulations suggest that aortic arch curvature is an important risk factor for embolic stroke which should be tested in future clinical trials.
The Voltage-Dependent Anion Channels (VDAC) of Mycobacterium avium phagosome are associated with bacterial survival and lipid export in macrophages
Authors: Danelishvili Lia , Chinison Jessica J. J. , Pham Tuan , Gupta Rashmi , Bermudez Luiz E.
Published: July 2017

Mycobacterium avium subsp. hominissuis is associated with infection of immunocompromised individuals as well as patients with chronic lung disease. M. avium infects macrophages and actively interfere with the host killing machinery such as apoptosis and autophagy. Bacteria alter the normal endosomal trafficking, prevent the maturation of phagosomes and modify many signaling pathways inside of the macrophage by secreting effector molecules into the cytoplasm. To investigate whether M. avium needs to attach to the internal surface of the vacuole membrane before releasing efferent molecules, vacuole membrane proteins were purified and binding to the surface molecules present in intracellular bacteria was evaluated. The voltage-dependent anion channels (VDAC) were identified as components of M. avium vacuoles in macrophages. M. avium mmpL4 proteins were found to bind to VDAC-1 protein. The inactivation of VDAC-1 function either by pharmacological means or siRNA lead to significant decrease of M. avium survival. Although, we could not establish a role of VDAC channels in the transport of known secreted M. avium proteins, we demonstrated that the porin channels are associated with the export of bacterial cell wall lipids outside of vacuole. Suppression of the host phagosomal transport systems and the pathogen transporter may serve as therapeutic targets for infectious diseases.
PRDX2 in Myocyte Hypertrophy and Survival is Mediated by TLR4 in Acute Infarcted Myocardium
Authors: Jin Xian , Chen Chengjun , Li Dandan , Su Qian , Hang Yanwen , Zhang Peng , Hu Wei
Published: July 2017

Peroxiredoxin 2 (PRDX2) is an antioxidant and molecular chaperone that can be secreted from tumor cells. But the role of PRDX2 in acute myocardial infarction (AMI) is not clear. In the current study, we demonstrate the role of PRDX2 from clinical trials, H9c2 cells and in a mouse model. ELISA analysis shows that serum concentrations of VEGF and inflammatory factor IL-1β, TNF-α and IL-6 were increased in AMI patients compared to a control group. The expression of PRDX2 was also upregulated. In vivo experiments show that the expression of PRDX2 inhibits hypoxia-induced oxidative stress injury to H9c2 cells. However, PRDX2 expression promotes TLR4 mediated inflammatory factor expression and VEGF expression under hypoxia conditions. PRDX2 overexpression in H9c2 cells also promotes human endothelial cell migration, vasculogenic mimicry formation and myocardial hypertrophy related protein expression. The overexpression of PRDX2 inhibits ROS level and myocardial injury after AMI but promotes inflammatory responses in vivo. Immunocytochemistry and immunofluorescence analysis show that overexpression of PRDX2 promotes angiogenesis and myocardial hypertrophy. Taken together, our results indicate that PRDX2 plays two roles in acute infarction – the promotion of cell survival and inflammatory myocardial hypertrophy.
Interplay between social influence and competitive strategical games in multiplex networks
Authors: Amato Roberta , Díaz-Guilera Albert , Kleineberg Kaj-Kolja
Published: July 2017

We present a model that takes into account the coupling between evolutionary game dynamics and social influence. Importantly, social influence and game dynamics take place in different domains, which we model as different layers of a multiplex network. We show that the coupling between these dynamical processes can lead to cooperation in scenarios where the pure game dynamics predicts defection. In addition, we show that the structure of the network layers and the relation between them can further increase cooperation. Remarkably, if the layers are related in a certain way, the system can reach a polarized metastable state. These findings could explain the prevalence of polarization observed in many social dilemmas.
High Mobility Group Box 1 Protein Level as a Novel Biomarker for the Development of Peri-Implant Disease
Authors: Liu Jinpan , Li Ronghui , Liu Tongjun , Rausch-Fan Xiaohui , Wang Mingguo
Published: July 2017

Peri-implant disease is a chronic inflammation of the soft and hard tissues around a dental implant, resulting from bacterial infection. Recent evidence indicates that some pro-inflammatory cytokines and chemokines released by immunocytes are substantially responsible for the progress and consequence of inflammation. High mobility group box 1 (HMGB1) is released into the extracellular matrix and acts as a key pro-inflammatory factor during injury, necrosis and inflammation. A higher concentration of HMGB1 has been found in gingival crevicular fluid from inflammatory gingival tissue than from healthy sites. HMGB1 mRNA and protein are overexpressed in murine periodontal ligament fibroblasts stimulated with lipopolysaccharide (LPS) and IL-1β. Thus, this study sought to assess HMGB1 expression in peri-implant crevicular fluid (PICF) at each stage of peri-implant disease and to investigate the correlation between HMGB1 and peri-implant disease progress. The results demonstrated that the HMGB1 expression level in PICF is indicative of the progress of peri-implant disease and hence may be a useful diagnostic and prognostic biomarker for peri-implant tissue.
Physarum machines imitating a Roman road network: the 3D approach
Authors: Evangelidis Vasilis , Jones Jeff , Dourvas Nikolaos , Tsompanas Michail-Antisthenis , Sirakoulis Georgios Ch. , Adamatzky Andrew
Published: July 2017

Physarum Polycephalum is a single cell visible by unaided eye. This is a plasmodial, vegetative stage of acellular slime mould. This single cell has myriad of nuclei which contribute to a network of bio-chemical oscillators responsible for the slime mould’s distributed sensing, concurrent information processing and decision making, and parallel actuation. When presented with a spatial configuration of sources of nutrients, the slime mould spans the sources with networks of its protoplasmic tube. These networks belong to a family of planar proximity graphs. The protoplasmic networks also show a degree of similarity to vehicular transport networks. Previously, we have shown that the foraging behaviour of the slime mould can be applied in archaeological research to complement and enhance conventional geographic information system tools. The results produced suffered from limitation of a flat substrate: transport routes imitated by the slime mould did not reflect patterns of elevations. To overcome the limitation of the ‘flat world’ we constructed a three-dimensional model of Balkans. In laboratory experiments and computer modelling we uncovered patterns of the foraging behaviour that might shed a light onto development of Roman roads in the Balkans during the imperial period (1st century BC – 4th century AD).
Linearly polarized GHz magnetization dynamics of spin helix modes in the ferrimagnetic insulator Cu2OSeO3
Authors: Stasinopoulos I. , Weichselbaumer S. , Bauer A. , Waizner J. , Berger H. , Garst M. , Pfleiderer C. , Grundler D.
Published: July 2017

Linear dichroism — the polarization dependent absorption of electromagnetic waves— is routinely exploited in applications as diverse as structure determination of DNA or polarization filters in optical technologies. Here filamentary absorbers with a large length-to-width ratio are a prerequisite. For magnetization dynamics in the few GHz frequency regime strictly linear dichroism was not observed for more than eight decades. Here, we show that the bulk chiral magnet Cu2OSeO3 exhibits linearly polarized magnetization dynamics at an unexpectedly small frequency of about 2 GHz at zero magnetic field. Unlike optical filters that are assembled from filamentary absorbers, the magnet is shown to provide linear polarization as a bulk material for an extremely wide range of length-to-width ratios. In addition, the polarization plane of a given mode can be switched by 90° via a small variation in width. Our findings shed a new light on magnetization dynamics in that ferrimagnetic ordering combined with antisymmetric exchange interaction offers strictly linear polarization and cross-polarized modes for a broad spectrum of sample shapes at zero field. The discovery allows for novel design rules and optimization of microwave-to-magnon transduction in emerging microwave technologies.
Visualization of Synthetic Vascular Smooth Muscle Cells in Atherosclerotic Carotid Rat Arteries by F-18 FDG PET
Authors: Pahk Kisoo , Joung Chanmin , Jung Se-Mi , Young Song Hwa , Yong Park Ji , Woo Byun Jung , Lee Yun-Sang , Chul Paeng Jin , Kim Chunsook , Kim Sungeun , Kim Won-Ki
Published: July 2017

Synthetic vascular smooth muscle cells (VSMCs) play important roles in atherosclerosis, in-stent restenosis, and transplant vasculopathy. We investigated the synthetic activity of VSMCs in the atherosclerotic carotid artery using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Atherosclerosis was induced in rats by partial ligation of the right carotid artery coupled with an atherogenic diet and vitamin D injections (2 consecutive days, 600,000 IU/day). One month later, rats were imaged by F-18 FDG PET. The atherosclerotic right carotid arteries showed prominent luminal narrowing with neointimal hyperplasia. The regions with neointimal hyperplasia were composed of α-smooth muscle actin-positive cells with decreased expression of smooth muscle myosin heavy chain. Surrogate markers of synthetic VSMCs such as collagen type III, cyclophilin A, and matrix metallopeptidase-9 were increased in neointima region. However, neither macrophages nor neutrophils were observed in regions with neointimal hyperplasia. F-18 FDG PET imaging and autoradiography showed elevated FDG uptake into the atherosclerotic carotid artery. The inner vessel layer showed higher tracer uptake than the outer layer. Consistently, the expression of glucose transporter 1 was highly increased in neointima. The present results indicate that F-18 FDG PET may be a useful tool for evaluating synthetic activities of VSMCs in vascular remodeling disorders.
Antitumoral effects of γCdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 breast cancer cell
Authors: Gimenes Sarah N. C. , Lopes Daiana S. , Alves Patrícia T. , Azevedo Fernanda V. P. V. , Vecchi Lara , Goulart Luiz R. , Rodrigues Thais C. S. , Santos André L. Q. , Brites Vera L. de C. , Teixeira Thaise L. , da Silva Cláudio V. , Dias Matheus H. , Teixeira Samuel C. , Rodrigues Renata S. , Yoneyama Kelly A. G. , Oliveira Ricardo A. , Rodrigues Veridiana de M.
Published: July 2017

Phospholipases A2(PLA2s) overexpression is closely associated with the malignant potential of breast cancers. Here, we showed for the first the antitumoral effects of γCdcPLI, a PLA2 inhibitor from Crotalus durissus collilineatus via PI3K/Akt pathway on MDA-MB-231 cell. Firstly, γCdcPLI was more cytotoxic to MDA-MB-231 breast cancer cells than other cell lines (MCF-7, HeLa, PC3 and A549) and did not affect the viability of non-tumorigenic breast cell (MCF 10A). In addition, γCdcPLI induced modulation of important mediators of apoptosis pathways such as p53, MAPK-ERK, BIRC5 and MDM2. γCdcPLI decreased MDA-MB-231 adhesion, migration and invasion. Interestingly, the γCdcPLI also inhibited the adhesion and migration of endothelial cells and blocked angiogenesis by inhibiting tube formation by HUVECs in vitro and sprouting elongation on aortic ring assay ex vivo. Furthermore, γCdcPLI reduced the production of vascular endothelial growth factor (VEGF). γCdcPLI was also able to decrease PGE2 levels in MDA-MB-231 and inhibited gene and protein expression of the PI3K/Akt pathway. In conclusion, γCdcPLI showed in vitro antitumoral, antimestatatic and anti-angiogenic potential effects and could be an attractive approach for futures studies in cancer therapy.
Fabrication of Epitaxial Fe3O4 Film on a Si(111) Substrate
Authors: Takahashi Nozomi , Huminiuc Teodor , Yamamoto Yuta , Yanase Takashi , Shimada Toshihiro , Hirohata Atsufumi , Nagahama Taro
Published: July 2017

The application of magnetic oxides in spintronics has recently attracted much attention. The epitaxial growth of magnetic oxide on Si could be the first step of new functional spintronics devices with semiconductors. However, epitaxial spinel ferrite films are generally grown on oxide substrates, not on semiconductors. To combine oxide spintronics and semiconductor technology, we fabricated Fe3O4 films through epitaxial growth on a Si(111) substrate by inserting a γ-Al2O3 buffer layer. Both of γ-Al2O3 and Fe3O4 layer grew epitaxially on Si and the films exhibited the magnetic and electronic properties as same as bulk. Furthermore, we also found the buffer layer dependence of crystal structure of Fe3O4 by X-ray diffraction and high-resolution transmission electron microscope. The Fe3O4 films on an amorphous-Al2O3 buffer layer grown at room temperature grew uniaxially in the (111) orientation and had a textured structure in the plane. When Fe3O4 was deposited on Si(111) directly, the poly-crystal Fe3O4 films were obtained due to SiOx on Si substrate. The epitaxial Fe3O4 layer on Si substrates enable us the integration of highly functional spintoronic devices with Si technology.
ARC is essential for maintaining pancreatic islet structure and β-cell viability during type 2 diabetes
Authors: McKimpson Wendy M. , Zheng Min , Chua Streamson C. , Pessin Jeffrey E. , Kitsis Richard N.
Published: July 2017

Pancreatic β-cell loss through apoptosis is an important disease mechanism in type 2 diabetes. Apoptosis Repressor with CARD (ARC) is a cell death inhibitor that antagonizes multiple death programs. We previously reported that ARC is abundant in pancreatic β-cells and modulates survival of these cells in vitro. Herein we assessed the importance of endogenous ARC in maintaining islet structure and function in vivo. While generalized loss of ARC did not result in detectable abnormalities, its absence in ob/ob mice, a model of type 2 diabetes, induced a striking pancreatic phenotype: marked β-cell death, loss of β-cell mass, derangements of islet architecture, and impaired glucose-stimulated insulin secretion in vivo. These abnormalities contributed to worsening of hyperglycemia and glucose-intolerance in these mice. Mechanistically, the absence of ARC increased levels of C/EBP homologous protein (CHOP) in wild type isolated islets stimulated with ER stress and in ob/ob isolated islets at baseline. Deletion of CHOP in ob/ob; ARC −/− mice led to reversal of β-cell death and abnormalities in islet architecture. These data indicate that suppression of CHOP by endogenous levels of ARC is critical for β-cell viability and maintenance of normal islet structure in this model of type 2 diabetes.
CDHR1 mutations in retinal dystrophies
Authors: Stingl Katarina , Mayer Anja K. , Llavona Pablo , Mulahasanovic Lejla , Rudolph Günther , Jacobson Samuel G. , Zrenner Eberhart , Kohl Susanne , Wissinger Bernd , Weisschuh Nicole
Published: July 2017

We report ophthalmic and genetic findings in patients with autosomal recessive retinitis pigmentosa (RP), cone-rod dystrophy (CRD) or cone dystrophy (CD) harboring potential pathogenic variants in the CDHR1 gene. Detailed ophthalmic examination was performed in seven sporadic and six familial subjects. Mutation screening was done using a customized next generation sequencing panel targeting 105 genes implicated in inherited retinal disorders. In one family, homozygosity mapping with subsequent candidate gene analysis was performed. Stringent filtering for rare and potentially disease causing variants following a model of autosomal recessive inheritance led to the identification of eleven different CDHR1 variants in nine index cases. All variants were novel at the time of their identification. In silico analyses confirmed their pathogenic potential. Minigene assays were performed for two non-canonical splice site variants and revealed missplicing for the mutant alleles. Mutations in CDHR1 are a rare cause of retinal dystrophy. Our study further expands the mutational spectrum of this gene and the associated clinical presentation.
Hypomethylation of CNTFRα is associated with proliferation and poor prognosis in lower grade gliomas
Authors: Fan Kun , Wang Xiaowen , Zhang Jingwen , Ramos Romela Irene , Zhang Haibo , Li Chunjie , Ye Dan , Kang Jiansheng , Marzese Diego M. , Hoon Dave S. B. , Hua Wei
Published: July 2017

Ciliary neurotrophic factor receptor α subunit (CNTFRα) and CNTF play important roles in neuron survival, glial differentiation and brain tumor growth. However, the molecular mechanisms of CNTFRα regulation and its clinical significance in glioma remain largely unknown. Here, we found CNTFRα was overexpressed in lower grade gliomas (LGG) compared with glioblastoma (GBM) and normal brain specimens in TCGA datasets and in an independent cohort. Bioinformatics analysis revealed a CpG shore of the CNTFRα gene regulated its mRNA expression in TCGA datasets. This observation was further validated with clinical specimens and functionally verified using demethylating agents. Additionally, we observed that independent of IDH mutation status, methylation of CNTFRα was significantly correlated with down-regulated CNTFRα gene expression and longer LGG patient survival. Interestingly, combination of CNTFRα methylation and IDH mutation significantly (p < 0.05) improved the prognostic prediction in LGG patients. Furthermore, the role of CNTFRα in glioma proliferation and apoptosis through the PI3K/AKT pathways was demonstrated by supplementation with exogenous CNTF  in vitro and siRNA knockdown in vivo. Our study demonstrated that hypomethylation leading to CNTFRα up-regulation, together with autocrine expression of CNTF, was involved in glioma growth regulation. Importantly, DNA methylation of CNTFRα might serve as a potential epigenetic theranostic target for LGG patients.
Quantitative Proteomics of Cerebrospinal Fluid in Paediatric Pneumococcal Meningitis
Authors: Gómez-Baena Guadalupe , Bennett Richard J. , Martínez-Rodríguez Carmen , Wnęk Małgorzata , Laing Gavin , Hickey Graeme , McLean Lynn , Beynon Robert J. , Carrol Enitan D.
Published: July 2017

Streptococcus pneumoniae is responsible for diseases causing major global public health problems, including meningitis, pneumonia and septicaemia. Despite recent advances in antimicrobial therapy, pneumococcal meningitis remains a life-threatening disease. Furthermore, long-term sequelae are a major concern for survivors. Hence, a better understanding of the processes occurring in the central nervous system is crucial to the development of more effective management strategies. We used mass spectrometry based quantitative proteomics to identify protein changes in cerebrospinal fluid from children with Streptococcus pneumoniae infection, compared with children admitted to hospital with bacterial meningitis symptoms but negative diagnosis. Samples were analysed, by label free proteomics, in two independent cohorts (cohort 1: cases (n = 8) and hospital controls (n = 4); cohort 2: cases (n = 8), hospital controls (n = 8)). Over 200 human proteins were differentially expressed in each cohort, of which 65% were common to both. Proteins involved in the immune response and exosome signalling were significantly enriched in the infected samples. For a subset of proteins derived from the proteome analysis, we corroborated the proteomics data in a third cohort (hospital controls (n = 15), healthy controls (n = 5), cases (n = 20)) by automated quantitative western blotting, with excellent agreement with our proteomics findings. Proteomics data are available via ProteomeXchange with identifier PXD004219.
The potential of using semitendinosus tendon as autograft in rabbit meniscus reconstruction
Authors: Li Chenxi , Hu Xiaoqing , Meng Qingyang , Zhang Xin , Zhu Jingxian , Dai Linghui , Cheng Jin , Zhong Mingjin , Shi Weili , Ren Bo , Zhang Jiying , Fu Xin , Duan Xiaoning , Ao Yingfang
Published: July 2017

Since transplantation of meniscal allograft or artificial menisci is limited by graft sources and a series of adverse events, substitution for meniscus reconstruction still needs to be explored. Natural biomaterials, which can provide a unique 3-D microenvironment, remain a promising alternative for tissue engineering. Among them, autograft is a preferred option for its safety and excellent biocompatibility. In this study, we utilized semitendinosus tendon autograft in meniscus reconstruction to investigate its fibrochondrogenic metaplasticity potential and chondroprotective effect. Tendon-derived stem cells (TDSCs) and synovial-derived mesenchymal stem cells (SMSCs), two most important stem cell sources in our strategy, exhibited excellent viability, distribution, proliferation and fibrochondrogenic differentiation ability in decellularized semitendinosus tendon (DST) scaffolds in vitro. Histologic evaluation of the tendon grafts in vivo suggested endogenous stem cells differentiated into fibrochondrocytes, synthesized proteoglycan, type II collagen and radial type I collagen at 12 weeks and 24 weeks post-surgery. As for elastic modulus and hardness of the grafts, there were no significant differences between native meniscus and regenerated meniscus at 24 weeks. The protection of condylar cartilage from degeneration was significantly better in the reconstruction group comparing to control group. Overall, semitendinosus tendon autograft seems to be a promising substitution in meniscus reconstruction.
Thermal conductivity measurements of proton-heated warm dense aluminum
Authors: McKelvey A. , Kemp G. E. , Sterne P. A. , Fernandez-Panella A. , Shepherd R. , Marinak M. , Link A. , Collins G. W. , Sio H. , King J. , Freeman R. R. , Hua R. , McGuffey C. , Kim J. , Beg F. N. , Ping Y.
Published: July 2017

Thermal conductivity is one of the most crucial physical properties of matter when it comes to understanding heat transport, hydrodynamic evolution, and energy balance in systems ranging from astrophysical objects to fusion plasmas. In the warm dense matter regime, experimental data are very scarce so that many theoretical models remain untested. Here we present the first thermal conductivity measurements of aluminum at 0.5–2.7 g/cc and 2–10 eV, using a recently developed platform of differential heating. A temperature gradient is induced in a Au/Al dual-layer target by proton heating, and subsequent heat flow from the hotter Au to the Al rear surface is detected by two simultaneous time-resolved diagnostics. A systematic data set allows for constraining both thermal conductivity and equation-of-state models. Simulations using Purgatorio model or Sesame S27314 for Al thermal conductivity and LEOS for Au/Al release equation-of-state show good agreement with data after 15 ps. Discrepancy still exists at early time 0–15 ps, likely due to non-equilibrium conditions.
Implication of REDD1 in the activation of inflammatory pathways
Authors: Pastor Faustine , Dumas Karine , Barthélémy Marie-Astrid , Regazzetti Claire , Druelle Noémie , Peraldi Pascal , Cormont Mireille , Tanti Jean-François , Giorgetti-Peraldi Sophie
Published: July 2017

In response to endotoxemia, the organism triggers an inflammatory response, and the visceral adipose tissue represents a major source of proinflammatory cytokines. The regulation of inflammation response in the adipose tissue is thus of crucial importance. We demonstrated that Regulated in development and DNA damage response-1 (REDD1) is involved in inflammation. REDD1 expression was increased in response to lipopolysaccharide (LPS) in bone marrow derived macrophages (BMDM) and in epidydimal adipose tissue. Loss of REDD1 protected the development of inflammation, since the expression of proinflammatory cytokines (TNFα, IL-6, IL-1β) was decreased in adipose tissue of REDD1−/− mice injected with LPS compared to wild-type mice. This decrease was associated with an inhibition of the activation of p38MAPK, JNK, NF-κB and NLRP3 inflammasome leading to a reduction of IL-1β secretion in response to LPS and ATP in REDD1−/− BMDM. Although REDD1 is an inhibitor of mTORC1, loss of REDD1 decreased inflammation independently of mTORC1 activation but more likely through oxidative stress regulation. Absence of REDD1 decreases ROS associated with a dysregulation of Nox-1 and GPx3 expression. Absence of REDD1 in macrophages decreases the development of insulin resistance in adipocyte-macrophage coculture. Altogether, REDD1 appears to be a key player in the control of inflammation.
Telomerase reverse transcriptase promotes chemoresistance by suppressing cisplatin-dependent apoptosis in osteosarcoma cells
Authors: Zhang Zhengpei , Yu Ling , Dai Guo , Xia Kezhou , Liu Gaiwei , Song Qi , Tao Chunjie , Gao Tian , Guo Weichun
Published: July 2017

Cisplatin is one of the most efficacious antimitotic drugs used in the treatment of a range of malignant tumors. However, treatment failures are common due to the development of chemoresistance. In addition to its telomere maintenance function, telomerase plays a pro-survival role, inducing decreased apoptosis and increased resistance against DNA damage. Elucidation of the molecular mechanisms underlying this effect is critical to improve treatment outcomes. Previously, our group showed higher telomerase reverse transcriptase(TERT) expression in cisplatin resistant osteosarcoma cells. In this study, confocal fluorescence microscopy experiments revealed that TERT translocates from the nucleus to mitochondria in cisplatin treated osteosarcoma cells. We observed decreased apoptosis rate and improved mitochondrial function in TERT-overexpressing cells following cisplatin treatment. Based on these results, we further established that TERT inhibits cisplatin-induced apoptosis independently of telomerase reverse transcriptase activity. Moreover, TERT suppressed cisplatin-induced apoptosis and improved mitochondrial function via alleviating intracellular ROS in osteosarcoma cells. Our finding that TERT shuttles from the nucleus to the mitochondrion in response to cisplatin treatment and inhibits cisplatin-induced apoptosis in osteosarcoma cells may be especially important to overcome drug resistance.
Transferring arbitrary d-dimensional quantum states of a superconducting transmon qudit in circuit QED
Authors: Liu Tong , Su Qi-Ping , Yang Jin-Hu , Zhang Yu , Xiong Shao-Jie , Liu Jin-Ming , Yang Chui-Ping
Published: July 2017

A qudit (d-level quantum system) has a large Hilbert space and thus can be used to achieve many quantum information and communication tasks. Here, we propose a method to transfer arbitrary d-dimensional quantum states (known or unknown) between two superconducting transmon qudits coupled to a single cavity. The state transfer can be performed by employing resonant interactions only. In addition, quantum states can be deterministically transferred without measurement. Numerical simulations show that high-fidelity transfer of quantum states between two superconducting transmon qudits (d ≤ 5) is feasible with current circuit QED technology. This proposal is quite general and can be applied to accomplish the same task with natural or artificial atoms of a ladder-type level structure coupled to a cavity or resonator.
The East Asian summer monsoon variability over the last 145 years inferred from the Shihua Cave record, North China
Authors: Li Xianglei , Cheng Hai , Tan Liangcheng , Ban Fengmei , Sinha Ashish , Duan Wuhui , Li Hanying , Zhang Haiwei , Ning Youfeng , Kathayat Gayatri , Edwards R. Lawrence
Published: July 2017

The precipitation variability associated with the East Asian summer monsoon (EASM) has profound societal implications. Here, we use precisely dated and seasonally-resolved stalagmite oxygen isotope (δ18O) records from Shihua Cave, North China to reconstruct the EASM variability over the last 145 years. Our record shows a remarkable weakening of the EASM strength since the 1880s, which may be causally linked to the warming of the tropical Pacific and Indian Oceans. The δ18O record also exhibits a significant ~30-year periodicity, consistent with the instrumental, historical and proxy-based rainfall records from North China, plausibly driven by the Pacific Decadal Oscillation (PDO). Together, these observations imply that ~30-year periodicity is a persistent feature of the EASM, which remains significant with or without anthropogenic forcing. If indeed, the EASM rainfall in North China might decline significantly in the near future, which may affect millions of people in this region.
Bacterial membrane vesicles transport their DNA cargo into host cells
Authors: Bitto Natalie J. , Chapman Ross , Pidot Sacha , Costin Adam , Lo Camden , Choi Jasmine , D’Cruze Tanya , Reynolds Eric C. , Dashper Stuart G. , Turnbull Lynne , Whitchurch Cynthia B. , Stinear Timothy P. , Stacey Katryn J. , Ferrero Richard L.
Published: July 2017

Bacterial outer membrane vesicles (OMVs) are extracellular sacs containing biologically active products, such as proteins, cell wall components and toxins. OMVs are reported to contain DNA, however, little is known about the nature of this DNA, nor whether it can be transported into host cells. Our work demonstrates that chromosomal DNA is packaged into OMVs shed by bacteria during exponential phase. Most of this DNA was present on the external surfaces of OMVs, with smaller amounts located internally. The DNA within the internal compartments of Pseudomonas aeruginosa OMVs were consistently enriched in specific regions of the bacterial chromosome, encoding proteins involved in virulence, stress response, antibiotic resistance and metabolism. Furthermore, we demonstrated that OMVs carry DNA into eukaryotic cells, and this DNA was detectable by PCR in the nuclear fraction of cells. These findings suggest a role for OMV-associated DNA in bacterial-host cell interactions and have implications for OMV-based vaccines.
Theoretical isotopic fractionation of magnesium between chlorophylls
Authors: Moynier Frédéric , Fujii Toshiyuki
Published: July 2017

Magnesium is the metal at the center of all types of chlorophyll and is thus crucial to photosynthesis. When an element is involved in a biosynthetic pathway its isotopes are fractionated based on the difference of vibrational frequency between the different molecules. With the technical advance of multi-collectors plasma-mass-spectrometry and improvement in analytical precision, it has recently been found that two types of chlorophylls (a and b) are isotopically distinct. These results have very significant implications with regards to the use of Mg isotopes to understand the biosynthesis of chlorophyll. Here we present theoretical constraints on the origin of these isotopic fractionations through ab initio calculations. We present the fractionation factor for chlorphyll a, b, d, and f. We show that the natural isotopic variations among chlorophyll a and b are well explained by isotopic fractionation under equilibrium, which implies exchanges of Mg during the chlorophyll cycle. We predict that chlorophyll d and f should be isotopically fractionated compared to chlorophyll a and that this could be used in the future to understand the biosynthesis of these molecules.
Model representations of kerogen structures: An insight from density functional theory calculations and spectroscopic measurements
Authors: Weck Philippe F. , Kim Eunja , Wang Yifeng , Kruichak Jessica N. , Mills Melissa M. , Matteo Edward N. , Pellenq Roland J.-M.
Published: July 2017

Molecular structures of kerogen control hydrocarbon production in unconventional reservoirs. Significant progress has been made in developing model representations of various kerogen structures. These models have been widely used for the prediction of gas adsorption and migration in shale matrix. However, using density functional perturbation theory (DFPT) calculations and vibrational spectroscopic measurements, we here show that a large gap may still remain between the existing model representations and actual kerogen structures, therefore calling for new model development. Using DFPT, we calculated Fourier transform infrared (FTIR) spectra for six most widely used kerogen structure models. The computed spectra were then systematically compared to the FTIR absorption spectra collected for kerogen samples isolated from Mancos, Woodford and Marcellus formations representing a wide range of kerogen origin and maturation conditions. Limited agreement between the model predictions and the measurements highlights that the existing kerogen models may still miss some key features in structural representation. A combination of DFPT calculations with spectroscopic measurements may provide a useful diagnostic tool for assessing the adequacy of a proposed structural model as well as for future model development. This approach may eventually help develop comprehensive infrared (IR)-fingerprints for tracing kerogen evolution.
Synthesis and Multi Scale Tribological Behavior of WC-Co/Nanodiamond Nanocomposites
Authors: Nieto Andy , Jiang Lin , Kim Jaekang , Kim Dae-Eun , Schoenung Julie M.
Published: July 2017

Nanodiamonds (ND) present a unique combination of desirable mechanical, functional, and chemical characteristics that are ideally suited for reinforcing and enhancing the wear resistance of carbide based materials. Tungsten carbide cobalt (WC-Co) matrix nanocomposites reinforced with varying amounts of ND (2 – 10 vol.%) were synthesized here by spark plasma sintering. The rapid thermal consolidation route enabled attainment of dense samples with a significant retention of the metastable diamond phase. NDs affected the microstructural evolution, chemistry, and mechanical properties of WC-Co. Macroscale reciprocating pin-on-disk tests were conducted to assess wear behavior under conditions relevant to service environments, e.g., high cycles and high contact pressure. Microscale tribological properties were assessed using microscratch tests in order to investigate the intrinsic effects of ND on the localized mechanical and tribological response of WC-Co-ND composites. The incorporation of 10 vol.% ND enhanced wear resistance at both the micro- and macroscale, by 28% and 35%, respectively.
2-Oxoesters: A Novel Class of Potent and Selective Inhibitors of Cytosolic Group IVA Phospholipase A2
Authors: Kokotou Maroula G. , Galiatsatou Gerasimia , Magrioti Victoria , Koutoulogenis Giorgos , Barbayianni Efrosini , Limnios Dimitris , Mouchlis Varnavas D. , Satpathy Banita , Navratil Aaron , Dennis Edward A. , Kokotos George
Published: July 2017

Cytosolic phospholipase A2(GIVA cPLA2) is the only PLA2that exhibits a marked preference for hydrolysis of arachidonic acid containing phospholipid substrates releasing free arachidonic acid and lysophospholipids and giving rise to the generation of diverse lipid mediators involved in inflammatory conditions. Thus, the development of potent and selective GIVA cPLA2inhibitors is of great importance. We have developed a novel class of such inhibitors based on the 2-oxoester functionality. This functionality in combination with a long aliphatic chain or a chain carrying an appropriate aromatic system, such as the biphenyl system, and a free carboxyl group leads to highly potent and selective GIVA cPLA2inhibitors (XI(50) values 0.00007–0.00008) and docking studies aid in understanding this selectivity. A methyl 2-oxoester, with a short chain carrying a naphthalene ring, was found to preferentially inhibit the other major intracellular PLA2, the calcium-independent PLA2. In RAW264.7 macrophages, treatment with the most potent 2-oxoester GIVA cPLA2inhibitor resulted in over 50% decrease in KLA-elicited prostaglandin D2production. The novel, highly potent and selective GIVA cPLA2inhibitors provide excellent tools for the study of the role of the enzyme and could contribute to the development of novel therapeutic agents for the treatment of inflammatory diseases.
Risk factors for postoperative haemorrhage after total thyroidectomy: clinical results based on 2,678 patients
Authors: Zhang Xu , Du Wei , Fang Qigen
Published: July 2017

The aim of this study was to analyse postoperative haemorrhage (POH) after a total thyroidectomy and explore the possible risk factors. Records of patients receiving a total thyroidectomy were reviewed and analysed for risk factors of POH. From the 2,678 patients in this study, a total of 39 patients had POH, representing an incidence of 1.5%. The majority (59.0%) of POH events occurred within four hours after surgery. Arterial haemorrhage was the primary cause of POH and was identifiable prior to venous bleeding, making it the first sign of POH. A univariate analysis revealed an association between POH, certain disease factors and BMI, but only a BMI greater than 30 was found to significantly increase the risk of POH (almost 6-fold). At the first sign of POH, all patients showed an obvious red drainage, and 92.3% of the patients had neck swelling. In summary, arterial bleeding is the main cause and first sign of postoperative haemorrhage, as it starts earlier than venous bleeding. A BMI greater than 30 significantly increases the risk of neck haematoma.
Structure of the C-terminal domain of TRADD reveals a novel fold in the death domain superfamily
Authors: Zhang Ning , Yuan Wensu , Fan Jing-Song , Lin Zhi
Published: July 2017

The TNFR1-associated death domain protein (TRADD) is an intracellular adaptor protein involved in various signaling pathways, such as antiapoptosis. Its C-terminal death domain (DD) is responsible for binding other DD-containing proteins including the p75 neurotrophin receptor (p75NTR). Here we present a solution structure of TRADD DD derived from high-resolution NMR spectroscopy. The TRADD DD comprises two super-secondary structures, an all-helix Greek key motif and a β-hairpin motif flanked by two α helices, which make it unique among all known DD structures. The β-hairpin motif is essential for TRADD DD to fold into a functional globular domain. The highly-charged surface suggests a critical role of electrostatic interactions in TRADD DD-mediated signaling. This novel structure represents a new class within the DD superfamily and provides a structural basis for studying homotypic DD interactions. NMR titration revealed a direct weak interaction between TRADD DD and p75NTR DD monomers. A binding site next to the p75NTR DD homodimerization interface indicates that TRADD DD recruitment to p75NTR requires separation of the p75NTR DD homodimer, explaining the mechanism of NGF-dependent activation of p75NTR-TRADD-mediated antiapoptotic pathway in breast cancer cell.