bluuebunny/crossref_metadata_2025_split huggingface dataset:
An integrated strategy by using target tissue metabolomics biomarkers as pharmacodynamic surrogate indices to screen antipyretic components of Qingkaikling injection
Authors: Zhang Zhixin , Lu Fang , Liu Haiyu , Zhao Huizhen , Liu Yuehong , Fu Shuang , Wang Meiling , Xie Ziye , Yu Honghong , Huang Zhenghai , Zhang Yanling , Gao Xiaoyan 
Published: July 2017

AbstractTraditional Chinese medicine (TCM) treatment can be valuable therapeutic strategies. However, the active components and action mechanisms that account for its therapeutic effects remain elusive. Based on the hypothesis that the components of a formula which exert effect would be measurable in target tissue, a target tissue metabolomics-based strategy was proposed for screening of antipyretic components in Qingkaikling injection (QKLI). First, we detected the components of QKLI which could reach its target tissue (hypothalamus) by determining the hypothalamus microdialysate and discovered that only baicalin and geniposide could be detected. Then, by conducting hypothalamus metabolomics studies, 14 metabolites were screened as the potential biomarkers that related to the antipyretic mechanisms of QKLI and were used as its pharmacodynamic surrogate indices. Subsequently, the dynamic concentration of baicalin and geniposide in hypothalamus microdialysates and biomarkers in hypothalamus were measured and correlated with each other. The results indicated that only baicalin shown a good correlation with these biomarkers. Finally, a network pharmacology approach was established to validate the antipyretic activity of baicalin and the results elucidated its antipyretic mechanisms as well. The integrated strategy proposed here provided a powerful means for identifying active components and mechanisms contributing to pharmacological effects of TCM.
Replication of H9 influenza viruses in the human ex vivo respiratory tract, and the influence of neuraminidase on virus release
Authors: Chan Renee W. Y. , Chan Louisa L. Y. , Mok Chris K. P. , Lai Jimmy , Tao Kin P. , Obadan Adebimpe , Chan Michael C. W. , Perez Daniel R. , Peiris J. S. Malik , Nicholls John M. 
Published: July 2017

AbstractH9N2 viruses are the most widespread influenza viruses in poultry in Asia. We evaluated the infection and tropism of human and avian H9 influenza virus in the human respiratory tract using ex vivo respiratory organ culture. H9 viruses infected the upper and lower respiratory tract and the majority of H9 viruses had a decreased ability to release virus from the bronchus rather than the lung. This may be attributed to a weak neuraminidase (NA) cleavage of carbon-6-linked sialic acid (Sia) rather than carbon-3-linked Sia. The modified cleavage of N-acetlylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) by NA in H9 virus replication was observed by reverse genetics, and recombinant H9N2 viruses with amino acids (38KQ) deleted in the NA stalk, and changing the amino acid at position 431 from Proline-to-Lysine. Using recombinant H9 viruses previously evaluated in the ferret, we found that viruses which replicated well in the ferret did not replicate to the same extent in the human ex vivo cultures. The existing risk assessment models for H9N2 viruses in ferrets may not always have a strong correlation with the replication in the human upper respiratory tract. The inclusion of the human ex vivo cultures would further strengthen the future risk-assessment strategies.
Functional and Transcriptomic Characterization of Peritoneal Immune-Modulation by Addition of Alanyl-Glutamine to Dialysis Fluid
Authors: Herzog Rebecca , Kuster Lilian , Becker Julia , Gluexam Tobias , Pils Dietmar , Spittler Andreas , Bhasin Manoj K. , Alper Seth L. , Vychytil Andreas , Aufricht Christoph , Kratochwill Klaus 
Published: July 2017

AbstractPeritonitis remains a major cause of morbidity and mortality during chronic peritoneal dialysis (PD). Glucose-based PD fluids reduce immunological defenses in the peritoneal cavity. Low concentrations of peritoneal extracellular glutamine during PD may contribute to this immune deficit. For these reasons we have developed a clinical assay to measure the function of the immune-competent cells in PD effluent from PD patients. We then applied this assay to test the impact on peritoneal immune-competence of PD fluid supplementation with alanyl-glutamine (AlaGln) in 6 patients in an open-label, randomized, crossover pilot trial (EudraCT 2012-004004-36), and related the functional results to transcriptome changes in PD effluent cells. Ex-vivo stimulation of PD effluent peritoneal cells increased release of interleukin (IL) 6 and tumor necrosis factor (TNF) α. Both IL-6 and TNF-α were lower at 1 h than at 4 h of the peritoneal equilibration test but the reductions in cytokine release were attenuated in AlaGln-supplemented samples. AlaGln-supplemented samples exhibited priming of IL-6-related pathways and downregulation of TNF-α upstream elements. Results from measurement of cytokine release and transcriptome analysis in this pilot clinical study support the conclusion that suppression of PD effluent cell immune function in human subjects by standard PD fluid is attenuated by AlaGln supplementation.
A new marine-derived sulfoglycolipid triggers dendritic cell activation and immune adjuvant response
Authors: Manzo Emiliano , Cutignano Adele , Pagano Dario , Gallo Carmela , Barra Giusi , Nuzzo Genoveffa , Sansone Clementina , Ianora Adrianna , Urbanek Konrad , Fenoglio Daniela , Ferrera Francesca , Bernardi Cinzia , Parodi Alessia , Pasquale Giuseppe , Leonardi Antonio , Filaci Gilberto , De Palma Raffaele , Fontana Angelo 
Published: July 2017

AbstractDendritic Cells (DCs) recognize infectious non-self molecules and engage the adaptive immune system thereby initiating long lasting, antigen-specific responses. As such, the ability to activate DCs is considered a key tool to enhance the efficacy and quality of vaccination. Here we report a novel immunomodulatory sulfolipid named β-SQDG18 that prototypes a class of natural-derived glycolipids able to prime human DCs by a TLR2/TLR4-independent mechanism and trigger an efficient immune responsein vivo. β-SQDG18 induces maturation of DC with the upregulation of MHC II molecules and co-stimulatory proteins (CD83, CD86), as well as pro-inflammatory cytokines (IL-12 and INF-γ). Mice immunized with OVA associated to β-SQDG18 (1:500) produced a titer of anti-OVA Ig comparable to traditional adjuvants. In an experimental model of melanoma, vaccination of C57BL/6 mice with β-SQDG18-adjuvanted hgp10 peptide elicited a protective response with a reduction in tumour growth and increase in survival.
Exploring the binding sites and proton diffusion on insulin amyloid fibril surfaces by naphthol-based photoacid fluorescence and molecular simulations
Authors: Amdursky Nadav , Rashid M. Harunur , Stevens Molly M. , Yarovsky Irene 
Published: July 2017

AbstractThe diffusion of protons along biological surfaces and the interaction of biological structures with water are fundamental areas of interest in biology and chemistry. Here, we examine the surface of insulin amyloid fibrils and follow the binding of small molecules (photoacids) that differ according to the number and location of their sulfonic groups. We use transient fluorescence combined with a spherically-symmetric diffusion theory to show that the binding mode of different photoacids determines the efficiency of proton dissociation from the photoacid and the dimensionality of the proton’s diffusion. We use molecular dynamics simulations to examine the binding mode and mechanism of the photoacids and its influence on the unique kinetic rates and diffusion properties of the photoacid’s dissociated proton, where we also suggest a proton transfer process between one of the photoacids to proximal histidine residues. We show that the photoacids can be used as fluorescent markers for following the progression of amyloidogenic processes. The detailed characterisation of different binding modes to the surface of amyloid fibrils paves the way for better understanding of the binding mechanism of small molecules to amyloid fibrils.
Homeostatic Left Heart integration and disintegration links atrio-ventricular covariation’s dyshomeostasis in Hypertrophic Cardiomyopathy
Authors: Piras Paolo , Torromeo Concetta , Evangelista Antonietta , Gabriele Stefano , Esposito Giuseppe , Nardinocchi Paola , Teresi Luciano , Madeo Andrea , Schiariti Michele , Varano Valerio , Puddu Paolo Emilio 
Published: July 2017

AbstractLeft ventricle and left atrium are and have been practically always analyzed separately in common clinically and non-clinically oriented cardiovascular investigations. Both classic and speckle tracking echocardiographic data contributed to the knowledge about deformational impairments occurring in systo-diastolic differences. Recently new trajectory based approaches allowed a greater awareness about the entire left ventricle or left atrium revolution and on their deficiencies that take place in presence of hypertrophic cardiomyopathy. However, surprisingly, the concomitant function of the two left heart chambers has not been analyzed for their geometrical/mechanical relationship. For the first time we study here, by acquiring left ventricle and left atrial geometries on the same heartbeat, the trajectory attributes of the entire left heart treated as a whole shape and the shape covariation of its two subunits. We contrasted healthy subjects with patients affected by hypertrophic cardiomyopathy. We found impaired left heart trajectory mainly in terms of orientation and size. More importantly, we found profound differences in the direction of morphological covariation of left ventricle and left atrium. These findings open to new perspectives in pathophysiological evaluation of different diseases by allowing the appreciation of concomitant functioning of both left heart whole geometry and of its two chambers.
Establishing a yeast-based screening system for discovery of human GLUT5 inhibitors and activators
Authors: Tripp Joanna , Essl Christine , Iancu Cristina V. , Boles Eckhard , Choe Jun-yong , Oreb Mislav 
Published: July 2017

AbstractHuman GLUT5 is a fructose-specific transporter in the glucose transporter family (GLUT, SLC2 gene family). Its substrate-specificity and tissue-specific expression make it a promising target for treatment of diabetes, metabolic syndrome and cancer, but few GLUT5 inhibitors are known. To identify and characterize potential GLUT5 ligands, we developed a whole-cell system based on a yeast strain deficient in fructose uptake, in which GLUT5 transport activity is associated with cell growth in fructose-based media or assayed by fructose uptake in whole cells. The former method is convenient for high-throughput screening of potential GLUT5 inhibitors and activators, while the latter enables detailed kinetic characterization of identified GLUT5 ligands. We show that functional expression of GLUT5 in yeast requires mutations at specific positions of the transporter sequence. The mutated proteins exhibit kinetic properties similar to the wild-type transporter and are inhibited by established GLUT5 inhibitors N-[4-(methylsulfonyl)-2-nitrophenyl]-1,3-benzodioxol-5-amine (MSNBA) and (−)-epicatechin-gallate (ECG). Thus, this system has the potential to greatly accelerate the discovery of compounds that modulate the fructose transport activity of GLUT5.
Uncovering Offshore Financial Centers: Conduits and Sinks in the Global Corporate Ownership Network
Authors: Garcia-Bernardo Javier , Fichtner Jan , Takes Frank W. , Heemskerk Eelke M. 
Published: July 2017

AbstractMultinational corporations use highly complex structures of parents and subsidiaries to organize their operations and ownership. Offshore Financial Centers (OFCs) facilitate these structures through low taxation and lenient regulation, but are increasingly under scrutiny, for instance for enabling tax avoidance. Therefore, the identification of OFC jurisdictions has become a politicized and contested issue. We introduce a novel data-driven approach for identifying OFCs based on the global corporate ownership network, in which over 98 million firms (nodes) are connected through 71 million ownership relations. This granular firm-level network data uniquely allows identifying both sink-OFCs and conduit-OFCs. Sink-OFCs attract and retain foreign capital while conduit-OFCs are attractive intermediate destinations in the routing of international investments and enable the transfer of capital without taxation. We identify 24 sink-OFCs. In addition, a small set of five countries – the Netherlands, the United Kingdom, Ireland, Singapore and Switzerland – canalize the majority of corporate offshore investment as conduit-OFCs. Each conduit jurisdiction is specialized in a geographical area and there is significant specialization based on industrial sectors. Against the idea of OFCs as exotic small islands that cannot be regulated, we show that many sink and conduit-OFCs are highly developed countries.
Bridging the gap between measurements and modelling: a cardiovascular functional avatar
Authors: Casas Belén , Lantz Jonas , Viola Federica , Cedersund Gunnar , Bolger Ann F. , Carlhäll Carl-Johan , Karlsson Matts , Ebbers Tino 
Published: July 2017

AbstractLumped parameter models of the cardiovascular system have the potential to assist researchers and clinicians to better understand cardiovascular function. The value of such models increases when they are subject specific. However, most approaches to personalize lumped parameter models have thus far required invasive measurements or fall short of being subject specific due to a lack of the necessary clinical data. Here, we propose an approach to personalize parameters in a model of the heart and the systemic circulation using exclusively non-invasive measurements. The personalized model is created using flow data from four-dimensional magnetic resonance imaging and cuff pressure measurements in the brachial artery. We term this personalized model the cardiovascular avatar. In our proof-of-concept study, we evaluated the capability of the avatar to reproduce pressures and flows in a group of eight healthy subjects. Both quantitatively and qualitatively, the model-based results agreed well with the pressure and flow measurements obtained in vivo for each subject. This non-invasive and personalized approach can synthesize medical data into clinically relevant indicators of cardiovascular function, and estimate hemodynamic variables that cannot be assessed directly from clinical measurements.
The lipid peroxidation product 4-hydroxynonenal contributes to oxidative stress-mediated deterioration of the ageing oocyte
Authors: Mihalas Bettina P. , De Iuliis Geoffry N. , Redgrove Kate A. , McLaughlin Eileen A. , Nixon Brett 
Published: July 2017

AbstractAn increase in intraovarian reactive oxygen species (ROS) has long been implicated in the decline in oocyte quality associated with maternal ageing. Oxidative stress (OS)-induced lipid peroxidation and the consequent generation of highly electrophilic aldehydes, such as 4-hydroxynonenal (4-HNE), represents a potential mechanism by which ROS can inflict damage in the ageing oocyte. In this study, we have established that aged oocytes are vulnerable to damage by 4-HNE resulting from increased cytosolic ROS production within the oocyte itself. Further, we demonstrated that the age-related induction of OS can be recapitulated by exposure of germinal vesicle (GV) oocytes to exogenous H2O2. Such treatments stimulated an increase in 4-HNE generation, which remained elevated during in vitro oocyte maturation to metaphase II. Additionally, exposure of GV oocytes to either H2O2 or 4-HNE resulted in decreased meiotic completion, increased spindle abnormalities, chromosome misalignments and aneuploidy. In seeking to account for these data, we revealed that proteins essential for oocyte health and meiotic development, namely α-, β-, and γ-tubulin are vulnerable to adduction via 4-HNE. Importantly, 4-HNE-tubulin adduction, as well as increased aneuploidy rates, were resolved by co-treatment with the antioxidant penicillamine, demonstrating a possible therapeutic mechanism to improve oocyte quality in older females.
Ryanodine receptors are part of the myospryn complex in cardiac muscle
Authors: Benson Matthew A. , Tinsley Caroline L. , Waite Adrian J. , Carlisle Francesca A. , Sweet Steve M. M. , Ehler Elisabeth , George Christopher H. , Lai F. Anthony , Martin-Rendon Enca , Blake Derek J. 
Published: July 2017

AbstractThe Cardiomyopathy–associated gene 5 (Cmya5) encodes myospryn, a large tripartite motif (TRIM)-related protein found predominantly in cardiac and skeletal muscle. Cmya5 is an expression biomarker for a number of diseases affecting striated muscle and may also be a schizophrenia risk gene. To further understand the function of myospryn in striated muscle, we searched for additional myospryn paralogs. Here we identify a novel muscle-expressed TRIM-related protein minispryn, encoded by Fsd2, that has extensive sequence similarity with the C-terminus of myospryn. Cmya5 and Fsd2 appear to have originated by a chromosomal duplication and are found within evolutionarily-conserved gene clusters on different chromosomes. Using immunoaffinity purification and mass spectrometry we show that minispryn co-purifies with myospryn and the major cardiac ryanodine receptor (RyR2) from heart. Accordingly, myospryn, minispryn and RyR2 co-localise at the junctional sarcoplasmic reticulum of isolated cardiomyocytes. Myospryn redistributes RyR2 into clusters when co-expressed in heterologous cells whereas minispryn lacks this activity. Together these data suggest a novel role for the myospryn complex in the assembly of ryanodine receptor clusters in striated muscle.
Downregulation of ALAS1 by nicarbazin treatment underlies the reduced synthesis of protoporphyrin IX in shell gland of laying hens
Authors: Samiullah Sami , Roberts Juliet , Wu Shu-Biao 
Published: July 2017

AbstractShell colour is an important trait for eggs and an understanding of pigment deposition will assist potential management of egg shell colour loss. We demonstrated that nicarbazin feeding down-regulated ALAS1 and reduced protoporphyrin IX (PP IX) in both shell gland and eggshell, indicating the role of nicarbazin in inhibiting the synthesis of PP IX. Additionally, the expression levels of the genes did not show sequential upregulation in the same order of diurnal time-points (TP) during egg formation. The gene SLC25A38, responsible for transporting glycine from cytoplasm to mitochondria, and the gene ALAS1, encoding rate-limiting enzyme (delta-aminolevulinic acid synthase 1), had higher expression at 15 hr, as compared with 2, 5 and 23.5 hrs postoviposition. Interestingly, ABCB6, a gene encoding an enzyme responsible for transporting coproporphyrinogen III, showed higher expression level at 2 and 5 hrs. However, the expression of CPOX that converts coproporphyrinogen III to protoporphyrinogen III, and ABCG2 that transports PP IX out from mitochondria did not alter. Nevertheless, mitochondrial count per cell did not show consistent change in response to time-points postoviposition and nicarbazin feeding. The information obtained in the study sheds light on how nicarbazin disrupts the synthesis of PP IX.
Associations of Coffee, Diet Drinks, and Non-Nutritive Sweetener Use with Depression among Populations in Eastern Canada
Authors: Yu Zhijie M. , Parker Louise , Dummer Trevor J. B. 
Published: July 2017

AbstractConsumption of coffee and diet drinks and the use of non-nutritive sweeteners is commonplace worldwide. We conducted a cross-sectional analysis to investigate the associations between coffee consumption and non-nutritive sweetener use and depression among populations in Atlantic Canada. During 2009 to 2013, we recruited 18838 participants aged 35–69 years (5854 men and 12984 women) for the baseline survey of the Atlantic Partnership for Tomorrow’s Health cohort study. Coffee consumption, sweetener use, and major depression were assessed using a set of standardized questionnaires. We utilized multiple logistic regression models to assess the associations of coffee drinking and non-nutritive sweetener use with major depression. Compared with non-coffee drinkers, female participants who drank coffee ≥4 cups/day had an odds ratio of 1.38 (95% confidence interval, 1.15–1.64) for major depression with adjustment for sociodemographic and behavioral factors, chronic disease status, and body mass index. We found a significant association between depression and consumption of sweeteners and diet drinks, which was more apparent among women than men. We conclude that heavy coffee drinking and non-nutritive sweetener use were associated with depression among populations in Atlantic Canada. Further studies are warranted to investigate the underlying biological mechanisms.
Incremental benefit of late gadolinium cardiac magnetic resonance imaging for risk stratification in patients with hypertrophic cardiomyopathy
Authors: Doesch Christina , Tülümen Erol , Akin Ibrahim , Rudic Boris , Kuschyk Juergen , El-Battrawy Ibrahim , Becher Tobias , Budjan Johannes , Smakic Arman , Schoenberg Stefan O. , Borggrefe Martin , Papavassiliu Theano 
Published: July 2017

AbstractHypertrophic cardiomyopathy (HCM) has a low risk for sudden cardiac death (SCD). The ESC clinical risk prediction model estimates the risk of SCD using clinical and echocardiographical parameters without taking into account cardiac magnetic resonance (CMR) parameters. Therefore, we compared the CMR characteristics of 149 patients with low, intermediate and high ESC risk scores. In these patients left and right ventricular ejection fraction and volumes were comparable. Patients with a high ESC risk score revealed a significantly higher extent of late gadolinium enhancement (LGE) compared to patients with intermediate or a low risk scores. During follow-up of 4 years an extent of LGE ≥20% identified patients at a higher risk for major adverse cardiac arrhythmic events in the low and intermediate ESC risk group whereas an extent of LGE <20% was associated with a low risk of major adverse cardiac arrhythmic events despite a high ESC risk score ≥6%. Hence, we hypothesize that the extent of fibrosis might be an additional risk marker.
An adaptive image enhancement method for a recirculating aquaculture system
Authors: Zhou Chao , Yang Xinting , Zhang Baihai , Lin Kai , Xu Daming , Guo Qiang , Sun Chuanheng 
Published: July 2017

AbstractDue to the low and uneven illumination that is typical of a recirculating aquaculture system (RAS), visible and near infrared (NIR) images collected from RASs always have low brightness and contrast. To resolve this issue, this paper proposes an image enhancement method based on the Multi-Scale Retinex (MSR) algorithm and a greyscale nonlinear transformation. First, the images are processed using the MSR algorithm to eliminate the influence of low and uneven illumination. Then, the normalized incomplete Beta function is used to perform a greyscale nonlinear transformation. The function’s optimal parameters (α and β) are automatically selected by the particle swarm optimization (PSO) algorithm based on an image contrast measurement function. This adaptive image enhancement method is compared with other classic enhancement methods. The results show that the proposed method greatly improves the image contrast and highlights dark areas, which is helpful during further analysis of these images.