bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new inhibitor of the β-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling
Authors: Beautrait Alexandre , Paradis Justine S. , Zimmerman Brandon , Giubilaro Jenna , Nikolajev Ljiljana , Armando Sylvain , Kobayashi Hiroyuki , Yamani Lama , Namkung Yoon , Heydenreich Franziska M. , Khoury Etienne , Audet Martin , Roux Philippe P. , Veprintsev Dmitry B. , Laporte Stéphane A. , Bouvier Michel 
Published: April 2017

AbstractIn addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, β-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of β-arrestin recruitment to the receptor and β-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecule that selectively inhibits the interaction between β-arrestin and the β2-adaptin subunit of the clathrin adaptor protein AP2 without interfering with the formation of receptor/β-arrestin complexes. This selective β-arrestin/β2-adaptin inhibitor (Barbadin) blocks agonist-promoted endocytosis of the prototypical β2-adrenergic (β2AR), V2-vasopressin (V2R) and angiotensin-II type-1 (AT1R) receptors, but does not affect β-arrestin-independent (transferrin) or AP2-independent (endothelin-A) receptor internalization. Interestingly, Barbadin fully blocks V2R-stimulated ERK1/2 activation and blunts cAMP accumulation promoted by both V2R and β2AR, supporting the concept of β-arrestin/AP2-dependent signalling for both G protein-dependent and -independent pathways.
Facile measurement of single-crystal elastic constants from polycrystalline samples
Authors: Du Xinpeng , Zhao Ji-Cheng 
Published: April 2017

AbstractElastic constants are among the most fundamental properties of materials. Simulations of microstructural evolution and constitutive/micro-mechanistic modeling of materials properties require elastic constants that are predominately measured from single crystals that are labor intensive to grow. A facile technique is developed to measure elastic constants from polycrystalline samples. The technique is based upon measurements of the surface acoustic wave velocities with the help of a polydimethylsiloxane film grating that is placed on a polished surface of a polycrystalline sample to confine surface acoustic waves that are induced by a femtosecond laser and measured using pump-probe time-domain thermoreflectance. Electron backscatter diffraction is employed to measure the crystallographic orientation along which the surface acoustic wave propagates in each grain (perpendicular to the polydimethylsiloxane grating). Such measurements are performed on several grains. A robust mathematical solution was developed to compute the surface acoustic wave velocity along any crystallographic orientation of any crystal structure with given elastic constants and density. By inputting various starting values of elastic constants to compute the surface acoustic wave velocities to match experimental measurements in several distinct crystallographic orientations using an optimization algorithm, accurate elastic constant values have been obtained from seven polycrystalline metal samples to be within 6.8% of single-crystal measurements. This new technique can help change the current scenario that experimentally measured elastic constants are available for only about 1% of the estimated 160,000 distinct solid compounds, not to mention the significant need for elastic constants of various solid solution compositions that are the base of structural materials.
Mining the transcriptome for rare disease therapies: a comparison of the efficiencies of two data mining approaches and a targeted cell-based drug screen
Authors: Mears A. J. , Schock S. C. , Hadwen J. , Putos S. , Dyment D. , Boycott K. M. , MacKenzie Alex 
Published: April 2017

AbstractMost monogenic diseases can be viewed as conditions caused by dysregulated protein activity; therefore, drugs can be used to modulate gene expression, and thus protein level, possibly conferring clinical benefit. When considering repurposing drugs for loss of function diseases, there are three classes of genetic disease amenable to an increase of function; haploinsufficient dominant diseases, those secondary to hypomorphic recessive alleles, and conditions with rescuing paralogs. This therapeutic model then brings the questions: how frequently do such clinically useful drug–gene interactions occur and what is the most rapid and efficient route by which to identify them. Here we compare three approaches: (1) mining of pre-existing system-wide transcriptomal datasets such as Connectivity Map; (2) utilization of a proprietary causal reasoning engine knowledge base; and, (3) a targeted drug screen using clinically accepted agents tested against normal human fibroblasts. We have determined the validation rate of these approaches for 76 diseases (i.e., in vitro fibroblast mRNA increase); for the Connectivity Map, approximately 5% of tested putative drug–gene interactions validated, for causal reasoning engine knowledge base the rate was 10%, and for the targeted drug screen 9%. The degree of overlap between these methodologies was low suggesting they are complementary not redundant approaches to identify putative drug-gene interactions. Although the validation rate was low, a number of drug–gene interactions were successfully identified and are now being investigated for protein induction and in vivo effect. This analysis establishes potentially valuable therapeutic leads as well as useful benchmarks for the thousands of currently untreatable rare genetic conditions.
Drying-mediated patterns in colloid-polymer suspensions
Authors: Ryu Seul-a , Kim Jin Young , Kim So Youn , Weon Byung Mook 
Published: April 2017

AbstractDrying-mediated patterning of colloidal particles is a physical phenomenon that must be understood in inkjet printing technology to obtain crack-free uniform colloidal films. Here we experimentally study the drying-mediated patterns of a model colloid-polymer suspension and specifically observe how the deposit pattern appears after droplet evaporation by varying particle size and polymer concentration. We find that at a high polymer concentration, the ring-like pattern appears in suspensions with large colloids, contrary to suppression of ring formation in suspensions with small colloids thanks to colloid-polymer interactions. We attribute this unexpected reversal behavior to hydrodynamics and size dependence of colloid-polymer interactions. This finding would be very useful in developing control of drying-mediated self-assembly to produce crack-free uniform patterns from colloidal fluids.
Multidisciplinary study of the secondary immune response in grandparents re-exposed to chickenpox
Authors: Ogunjimi B. , Van den Bergh J. , Meysman P. , Heynderickx S. , Bergs K. , Jansens H. , Leuridan E. , Vorsters A. , Goossens H. , Laukens K. , Cools N. , Van Tendeloo Viggo , Hens N. , Van Damme P. , Smits Evelien , Beutels Ph. 
Published: April 2017

AbstractRe-exposure to chickenpox may boost varicella-zoster virus (VZV) immunity in the elderly. This secondary immune response is hypothesized to confer protection against herpes zoster. We longitudinally sampled 36 adults over the course of one year after re-exposure to chickenpox. The resulting 183 samples and those of 14 controls were assessed for VZV-specific T-cell immunity and antibody titres. The percentages of VZV-specific CD4+ IL-2-producing T-cells were increased in re-exposed grandparents compared to control participants up to 9 months after re-exposure. Using a longitudinal mixture modelling approach, we found that 25% and 17% of re-exposed grandparents showed a boosting of VZV-specific CD4+ IL-2-producing T-cells and VZV-specific antibodies, respectively. The antibody boosting occurred exclusively in cytomegalovirus (CMV) IgG-positive participants. CMV IgG-positive participants also had higher VZV IE62-specific CD4+ IFN-γ-producing T-cell percentages and VZV-specific antibody titres. The protective effect of re-exposure to chickenpox is likely limited, as boosting only occurred in 17–25% of the VZV re-exposed grandparents and for less than one year.
Limited genomic consequences of hybridization between two African clawed frogs, Xenopus gilli and X. laevis (Anura: Pipidae)
Authors: Furman Benjamin L. S. , Cauret Caroline M. S. , Colby Graham A. , Measey G. John , Evans Ben J. 
Published: April 2017

AbstractThe Cape platanna,Xenopus gilli, an endangered frog, hybridizes with the African clawed frog,X.laevis, in South Africa. Estimates of the extent of gene flow between these species range from pervasive to rare. Efforts have been made in the last 30 years to minimize hybridization between these two species in the west population ofX.gilli, but not the east populations. To further explore the impact of hybridization and the efforts to minimize it, we examined molecular variation in one mitochondrial and 13 nuclear genes in genetic samples collected recently (2013) and also over two decades ago (1994). Despite the presence ofF1hybrids, none of the genomic regions we surveyed had evidence of gene flow between these species, indicating a lack of extensive introgression. Additionally we found no significant effect of sampling time on genetic diversity of populations of each species. Thus, we speculate thatF1hybrids have low fitness and are not backcrossing with the parental species to an appreciable degree. WithinX.gilli, evidence for gene flow was recovered between eastern and western populations, a finding that has implications for conservation management of this species and its threatened habitat.
SLC10A4 regulates IgE-mediated mast cell degranulation in vitro and mast cell-mediated reactions in vivo
Authors: Pettersson Hanna , Zarnegar Behdad , Westin Annika , Persson Viktor , Peuckert Christiane , Jonsson Jörgen , Hallgren Jenny , Kullander Klas 
Published: April 2017

AbstractMast cells act as sensors in innate immunity and as effector cells in adaptive immune reactions. Here we demonstrate that SLC10A4, also referred to as the vesicular aminergic-associated transporter, VAAT, modifies mast cell degranulation. Strikingly, Slc10a4−/− bone marrow-derived mast cells (BMMCs) had a significant reduction in the release of granule-associated mediators in response to IgE/antigen-mediated activation, whereas the in vitro development of mast cells, the storage of the granule-associated enzyme mouse mast cell protease 6 (mMCP-6), and the release of prostaglandin D2 and IL-6 were normal. Slc10a4-deficient mice had a strongly reduced passive cutaneous anaphylaxis reaction and a less intense itching behaviour in response to the mast cell degranulator 48/80. Live imaging of the IgE/antigen-mediated activation showed decreased degranulation and that ATP was retained to a higher degree in mast cell granules lacking SLC10A4. Furthermore, ATP was reduced by two thirds in Slc10a4−/− BMMCs supernatants in response to IgE/antigen. We speculate that SLC10A4 affects the amount of granule-associated ATP upon IgE/antigen-induced mast cell activation, which affect the release of granule-associated mast cell mediators. In summary, SLC10A4 acts as a regulator of degranulation in vitro and of mast cell-related reactions in vivo.
Clinical and microbiological characteristics, and impact of therapeutic strategies on the outcomes of children with candidemia
Authors: Tsai Ming-Horng , Hsu Jen-Fu , Chu Shih-Ming , Chang Pey-Jium , Lai Mei-Yin , Wu I-Hsyuan , Huang Hsuan-Rong , Chiang Ming-Chou , Fu Ren-Huei , Lu Jang-Jih 
Published: April 2017

AbstractWe aimed to determine the clinical and microbiological characteristics of Candida bloodstream infections in children and the impact of therapeutic strategies on outcomes. All pediatric patients with candidemia from a medical center in Taiwan over a 13-year period (2003–2015) were included and a total of 262 patients with 319 episodes of candidemia were analyzed. Overall susceptibility to fluconazole was 86.1%. Cumulative mortality at 7 and 30 days after the first episode of candidemia was 13.4% and 25.2%, respectively. The overall in-hospital mortality rate was 35.1%. The treatment outcomes did not change over the study period. Multivariate analysis showed that delayed catheter removal (odds ratio [OR], 5.52; 95% confidence interval [CI]: 2.97–10.25), septic shock (OR, 5.49; 95% CI: 2.85–10.57), and breakthrough candidemia (OR, 3.66; 95% CI: 1.43–9.35) were independently associated with clinical treatment failure. In children with candidemia, underlying renal insufficiency and hematological/oncological malignancy, delayed catheter removal, and septic shock at onset were independently associated final in-hospital mortality. Analyzing the subgroup of non-neonatal children did not change the findings. We concluded overall mortality of pediatric candidemia remains high during the past decade. Prompt early catheter removal and aggressive treatment strategy in patients with septic shock would be critical to improve outcomes.
Bioinformatic Approaches Including Predictive Metagenomic Profiling Reveal Characteristics of Bacterial Response to Petroleum Hydrocarbon Contamination in Diverse Environments
Authors: Mukherjee Arghya , Chettri Bobby , Langpoklakpam James S. , Basak Pijush , Prasad Aravind , Mukherjee Ashis K. , Bhattacharyya Maitree , Singh Arvind K. , Chattopadhyay Dhrubajyoti 
Published: April 2017

AbstractMicrobial remediation of oil polluted habitats remains one of the foremost methods for restoration of petroleum hydrocarbon contaminated environments. The development of effective bioremediation strategies however, require an extensive understanding of the resident microbiome of these habitats. Recent developments such as high-throughput sequencing has greatly facilitated the advancement of microbial ecological studies in oil polluted habitats. However, effective interpretation of biological characteristics from these large datasets remain a considerable challenge. In this study, we have implemented recently developed bioinformatic tools for analyzing 65 16S rRNA datasets from 12 diverse hydrocarbon polluted habitats to decipher metagenomic characteristics of the resident bacterial communities. Using metagenomes predicted from 16S rRNA gene sequences through PICRUSt, we have comprehensively described phylogenetic and functional compositions of these habitats and additionally inferred a multitude of metagenomic features including 255 taxa and 414 functional modules which can be used as biomarkers for effective distinction between the 12 oil polluted sites. Additionally, we show that significantly over-represented taxa often contribute to either or both, hydrocarbon degradation and additional important functions. Our findings reveal significant differences between hydrocarbon contaminated sites and establishes the importance of endemic factors in addition to petroleum hydrocarbons as driving factors for sculpting hydrocarbon contaminated bacteriomes.
ETS Related Gene mediated Androgen Receptor Aggregation and Endoplasmic Reticulum Stress in Prostate Cancer Development
Authors: Sreenath Taduru L. , Macalindong Shiela S. , Mikhalkevich Natallia , Sharad Shashwat , Mohamed Ahmed , Young Denise , Borbiev Talaibek , Xavier Charles , Gupta Rishita , Jamal Muhammad , Babcock Kevin , Tan Shyh-Han , Nevalainen Marja T. , Dobi Albert , Petrovics Gyorgy , Sesterhenn Isabell A. , Rosner Inger L. , Bieberich Charles J. , Nelson Peter , Vasioukhin Valeri , Srivastava Shiv 
Published: April 2017

AbstractMechanistic studies of deregulated ERG in prostate cancer and other cancers continue to enhance its role in cancer biology and its utility as a biomarker and therapeutic target. Here, we show that ERG, through its physical interaction with androgen receptor, induces AR aggregation and endoplasmic reticulum stress in the prostate glands of ERG transgenic mice. Histomorphological alterations and the expression of ER stress sensors Atf6, Ire1α, Perk, their downstream effectors Grp78/BiP and eIF2α in ERG transgenic mouse prostate glands indicate the presence of chronic ER stress. Transient activation of apoptotic cell death during early age correlated well with the differential regulation of ER stress sensors, in particular Perk. Epithelial cells derived from ERG transgenic mouse prostates have increased prostasphere formation with resistance to radiation induced cell death. Continued activation of cell survival factors, Atf6 and Ire1α during chronic ER stress due to presence of ERG in prostate epithelium induces survival pathways and provides a selection pressure in the continuum of ERG dependent neoplastic process. These novel insights will enhance the understanding of the mechanistic functions of ERG in prostate tumor biology and towards development of early targeted therapeutic strategies for prostate cancer.
Oxygen Vacancy-Tuned Physical Properties in Perovskite Thin Films with Multiple B-site Valance States
Authors: Enriquez Erik , Chen Aiping , Harrell Zach , Dowden Paul , Koskelo Nicholas , Roback Joseph , Janoschek Marc , Chen Chonglin , Jia Quanxi 
Published: April 2017

AbstractControlling oxygen content in perovskite oxides with ABO3 structure is one of most critical steps for tuning their functionality. Notably, there have been tremendous efforts to understand the effect of changes in oxygen content on the properties of perovskite thin films that are not composed of cations with multiple valance states. Here, we study the effect of oxygen vacancies on structural and electrical properties in epitaxial thin films of SrFeO3−δ (SFO), where SFO is a compound with multiple valance states at the B site. Various annealing treatments are used to produce different oxygen contents in the films, which has resulted in significant structural changes in the fully strained SFO films. The out-of-plane lattice parameter and tetragonality increase with decreasing oxygen concentration, indicating the crystal structure is closely related to the oxygen content. Importantly, variation of the oxygen content in the films significantly affects the dielectric properties, leakage conduction mechanisms, and the resistive hysteresis of the materials. These results establish the relationship between oxygen content and structural and functional properties for a range of multivalent transition metal oxides.
Exciton emission of quasi-2D InGaN in GaN matrix grown by molecular beam epitaxy
Authors: Ma Dingyu , Rong Xin , Zheng Xiantong , Wang Weiying , Wang Ping , Schulz Tobias , Albrecht Martin , Metzner Sebastian , Müller Mathias , August Olga , Bertram Frank , Christen Jürgen , Jin Peng , Li Mo , Zhang Jian , Yang Xuelin , Xu Fujun , Qin Zhixin , Ge Weikun , Shen Bo , Wang Xinqiang 
Published: April 2017

AbstractWe investigate the emission from confined excitons in the structure of a single-monolayer-thick quasi-two-dimensional (quasi-2D) InxGa1−xN layer inserted in GaN matrix. This quasi-2D InGaN layer was successfully achieved by molecular beam epitaxy (MBE), and an excellent in-plane uniformity in this layer was confirmed by cathodoluminescence mapping study. The carrier dynamics have also been investigated by time-resolved and excitation-power-dependent photoluminescence, proving that the recombination occurs via confined excitons within the ultrathin quasi-2D InGaN layer even at high temperature up to ~220 K due to the enhanced exciton binding energy. This work indicates that such structure affords an interesting opportunity for developing high-performance photonic devices.
Quantitative analyses of the global proteome and phosphoproteome reveal the different impacts of propofol and dexmedetomidine on HT22 cells
Authors: Zhang Honggang , Ye Juan , Shi Zhaomei , Bu Chen , Bao Fangping 
Published: April 2017

AbstractPropofol and dexmedetomidine are both commonly used anaesthetics. Although they employ two different mechanisms to induce anaesthesia, both compounds influence the hippocampus and the HT22 cell line. HT22 cells are broadly used in neurobiological research. In this study, we assessed the effects of propofol and dexmedetomidine on signalling in HT22 cells. Using the SILAC (stable isotope labelling with amino acids in cell culture) labelling technique, IMAC (immobilized metal affinity chromatography) enrichment and high-resolution LC-MS/MS (liquid chromatography tandem mass spectrometry) analysis, we investigated the quantitative proteome and phosphoproteome in HT22 cells treated with propofol or dexmedetomidine. In total, 4,527 proteins and 6,824 phosphosites were quantified in cells treated with these two anaesthetics. With the assistance of intensive bioinformatics, the propofol and dexmedetomidine treatments were shown to induce distinct proteome and phosphoproteome profiles in HT22 cells. Consistent with our bioinformatics analysis, dexmedetomidine had a smaller effect than propofol on cell survival. These findings deepen our understanding of drug-induced anaesthesia.
Solution Process Synthesis of High Aspect Ratio ZnO Nanorods on Electrode Surface for Sensitive Electrochemical Detection of Uric Acid
Authors: Ahmad Rafiq , Tripathy Nirmalya , Ahn Min-Sang , Hahn Yoon-Bong 
Published: April 2017

AbstractThis study demonstrates a highly stable, selective and sensitive uric acid (UA) biosensor based on high aspect ratio zinc oxide nanorods (ZNRs) vertical grown on electrode surface via a simple one-step low temperature solution route. Uricase enzyme was immobilized on the ZNRs followed by Nafion covering to fabricate UA sensing electrodes (Nafion/Uricase-ZNRs/Ag). The fabricated electrodes showed enhanced performance with attractive analytical response, such as a high sensitivity of 239.67 μA cm−2 mM−1 in wide-linear range (0.01–4.56 mM), rapid response time (~3 s), low detection limit (5 nM), and low value of apparent Michaelis-Menten constant (Kmapp, 0.025 mM). In addition, selectivity, reproducibility and long-term storage stability of biosensor was also demonstrated. These results can be attributed to the high aspect ratio of vertically grown ZNRs which provides high surface area leading to enhanced enzyme immobilization, high electrocatalytic activity, and direct electron transfer during electrochemical detection of UA. We expect that this biosensor platform will be advantageous to fabricate ultrasensitive, robust, low-cost sensing device for numerous analyte detection.
An algorithm to predict advanced proximal colorectal neoplasia in Chinese asymptomatic population
Authors: Liwen Huang Jason , Chen Ping , Yuan Xiaoqin , Wu Yunlin , Haoxiang Wang Harry , Chisang Wong Martin 
Published: April 2017

AbstractThis study aims to develop and validate a new algorithm that incorporates distal colonoscopic findings to predict advanced proximal neoplasia (APN) in a Chinese asymptomatic population. We collected age, gender, and colonoscopic findings from a prospectively performed colonoscopy study between 2013 and 2015 in a large hospital-based endoscopy unit in Shanghai, China. Eligible subjects were allocated to a derivation group (n = 3,889) and validation group (n = 1,944) by random sampling. A new index for APN and its cut-off level were evaluated from the derivation cohort by binary logistic regression. The model performance was tested in the validation cohort using area under the curve (AUC). Age, gender, and distal finding were found to be independent predictors of APN in the derivation cohort (p < 0.001). Subjects were categorized into Average Risk (AR) and High Risk (HR) based on a cut-off score of 2. The AUC of the derivation and validation cohorts were 0.801 (0.754–0.847) and 0.722 (0.649–0.794), respectively. In the validation cohort, those in the HR group had a 3.57 fold higher risk of APN when compared with the AR group (P < 0.001), requiring 18 (95% CI = 12–28) follow-up colonoscopies to detect 1 APN. This new clinical index is useful to stratify APN risk in Chinese population.