bluuebunny/crossref_metadata_2025_split huggingface dataset:
A peptide containing the receptor binding site of insulin-like growth factor binding protein-2 enhances bone mass in ovariectomized rats
Authors: Xi Gang , Wai Christine , Rosen Clifford J. , Clemmons David R. 
Published: August 2018

AbstractMale Igfbp2−/− mice have a significant reduction in bone mass and administration of a peptide that contains the insulin-like growth factor binding protein-2(IGFBP-2) receptor-binding domain stimulates bone formation in these animals. Female Igfbp2−/− mice do not have this phenotype but following ovariectomy (OVX) lose more bone than OVX wild-type mice. This suggests that in the absence of estrogen, IGFBP-2 is required to maintain bone mass. Therefore these studies were undertaken to determine if this peptide could stimulate bone acquisition in OVX rats. OVX rats were divided into seven treatment groups: sham animals, OVX animals, OVX animals receiving a control scrambled peptide, or one of three doses of the active peptide termed PEG-HBD-1 (0.7, 2, and 6 mg·kg-1) and an OVX group receiving parathyroid hormone (PTH) (50 µg·kg-1 per day). The peptides were administered for 8 weeks. DXA revealed a significant reduction in femoral and tibial areal bone mineral density (aBMD) after OVX, whereas treatment with the high-dose peptide increased aBMD by 6.2% ± 2.4% (P < 0.01) compared to control peptide; similar to the increase noted with PTH (5.6% ± 3.0%, P < 0.01). Similar increases were noted with two lower doses of the peptide (3.8% ± 1.5%, P < 0.05 for low dose; 3.1% ± 1.6%, P = 0.07 for middle dose). Micro CT showed that the OVX control peptide animals had reductions of 41% and 64% in femoral trabecular BV/TV and trabecular number, respectively. All three doses of the peptide increased bone volume/total volume (BV/TV) significantly, while the low and middle doses increased trabecular number. Cortical BV/TV and thickness at the midshaft increased significantly with each dose of peptide (18.9% ± 9.8%, P < 0.01 and 14.2% ± 7.9%, P < 0.01 for low dose; 23.7% ± 10.7%, P < 0.001 and 15.8% ± 6.1%, P < 0.001 for middle dose; 19.0% ± 6.9%, P < 0.01 and 16.2% ± 9.7%, P < 0.001 for high dose) and with PTH (25.8% ± 9.2%, P < 0.001 and 19.4% ± 8.8%, P < 0.001). Histomorphometry showed that the lowest dose of peptide stimulated BV/TV, trabecular thickness, mineral apposition rate (MAR), bone formation rate/bone surface (BFR/BS), number of osteoblasts/bone perimeter (N.ob/B.pm), and decreased osteoclast surface/bone perimeter (Oc.S/B.Pm). The highest dose stimulated each of these parameters except MAR and BFR/BS. Thus, the heparin-binding domain receptor region of IGFBP-2 accounts for its anabolic activity in bone. Importantly, this peptide enhances bone mass in estrogen-deficient animals.
Regulation of the small GTPase Rab1 function by a bacterial glucosyltransferase
Authors: Wang Zhen , McCloskey Alix , Cheng Sen , Wu Mei , Xue Chenyu , Yu Zhengyou , Fu Jiaqi , Liu Yanhua , Luo Zhao-Qing , Liu Xiaoyun 
Published: August 2018

AbstractPosttranslational modification of key host proteins by virulence factors is an important theme in bacterial pathogenesis. A remarkable example is the reversible modifications of the small GTPase Rab1 by multiple effectors of the bacterial pathogen Legionella pneumophila. Previous studies have shown that the effector SetA, dependent on a functional glucosyltransferase domain, interferes with host secretory pathways. However, the enzymatic substrate(s) of SetA in host cells remains unknown. Here, by using cross-linking mass spectrometry we uncovered Rab1 as the target of SetA during L. pneumophila infection. Biochemical studies establish that SetA covalently attaches a glucose moiety to Thr75 within the switch II region of Rab1, inhibiting its intrinsic GTPase activity. Moreover, we found that SetA preferentially modifies the GDP-bound form of Rab1 over its GTP-associated state and the modification of Rab1 inhibits its interaction with the GDP dissociation inhibitor GDI1, allowing for Rab1 activation. Our results thus add an extra layer of regulation on Rab1 activity and provide a mechanistic understanding of its inhibition of the host secretory pathways as well as cellular toxicity.
Axoneme polyglutamylation regulated by Joubert syndrome protein ARL13B controls ciliary targeting of signaling molecules
Authors: He Kai , Ma Xiaoyu , Xu Tao , Li Yan , Hodge Allen , Zhang Qing , Torline Julia , Huang Yan , Zhao Jian , Ling Kun , Hu Jinghua 
Published: August 2018

AbstractTubulin polyglutamylation is a predominant axonemal post-translational modification. However, if and how axoneme polyglutamylation is essential for primary cilia and contribute to ciliopathies are unknown. Here, we report that Joubert syndrome protein ARL13B controls axoneme polyglutamylation, which is marginally required for cilia stability but essential for cilia signaling. ARL13B interacts with RAB11 effector FIP5 to promote cilia import of glutamylase TTLL5 and TTLL6. Hypoglutamylation caused by a deficient ARL13B-RAB11-FIP5 trafficking pathway shows no effect on ciliogenesis, but promotes cilia disassembly and, importantly, impairs cilia signaling by disrupting the proper anchoring of sensory receptors and trafficking of signaling molecules. Remarkably, depletion of deglutamylase CCP5, the predominant cilia deglutamylase, effectively restores hypoglutamylation-induced cilia defects. Our study reveals a paradigm that tubulin polyglutamylation is a major contributor for cilia signaling and suggests a potential therapeutic strategy by targeting polyglutamylation machinery to promote ciliary targeting of signaling machineries and correct signaling defects in ciliopathies.
A combination of TLR-4 agonist and saponin adjuvants increases antibody diversity and protective efficacy of a recombinant West Nile Virus antigen
Authors: Van Hoeven Neal , Wiley Steven , Gage Emily , Fiore-Gartland Andrew , Granger Brian , Gray Sean , Fox Christopher , Clements David E. , Parks D. Elliot , Winram Scott , Stinchcomb Dan T. , Reed Steven G. , Coler Rhea N. 
Published: August 2018

AbstractMembers of the Flaviviridae family are the leading causes of mosquito-borne viral disease worldwide. While dengue virus is the most prevalent, the recent Zika virus outbreak in the Americas triggered a WHO public health emergency, and yellow fever and West Nile viruses (WNV) continue to cause regional epidemics. Given the sporadic nature of flaviviral epidemics both temporally and geographically, there is an urgent need for vaccines that can rapidly provide effective immunity. Protection from flaviviral infection is correlated with antibodies to the viral envelope (E) protein, which encodes receptor binding and fusion functions. TLR agonist adjuvants represent a promising tool to enhance the protective capacity of flavivirus vaccines through dose and dosage reduction and broadening of antiviral antibody responses. This study investigates the ability to improve the immunogenicity and protective capacity of a promising clinical-stage WNV recombinant E-protein vaccine (WN-80E) using a novel combination adjuvant, which contains a potent TLR-4 agonist and the saponin QS21 in a liposomal formulation (SLA-LSQ). Here, we show that, in combination with WN-80E, optimized SLA-LSQ is capable of inducing long-lasting immune responses in preclinical models that provide sterilizing protection from WNV challenge, reducing viral titers following WNV challenge to undetectable levels in Syrian hamsters. We have investigated potential mechanisms of action by examining the antibody repertoire generated post-immunization. SLA-LSQ induced a more diverse antibody response to WNV recombinant E-protein antigen than less protective adjuvants. Collectively, these studies identify an adjuvant formulation that enhances the protective capacity of recombinant flavivirus vaccines.
Indibulin dampens microtubule dynamics and produces synergistic antiproliferative effect with vinblastine in MCF-7 cells: Implications in cancer chemotherapy
Authors: Kapoor Sonia , Srivastava Shalini , Panda Dulal 
Published: August 2018

AbstractIndibulin, a synthetic inhibitor of tubulin assembly, has shown promising anticancer activity with a minimal neurotoxicity in preclinical animal studies and in Phase I clinical trials for cancer chemotherapy. Using time-lapse confocal microscopy, we show that indibulin dampens the dynamic instability of individual microtubules in live breast cancer cells. Indibulin treatment also perturbed the localization of end-binding proteins at the growing microtubule ends in MCF-7 cells. Indibulin reduced inter-kinetochoric tension, produced aberrant spindles, activated mitotic checkpoint proteins Mad2 and BubR1, and induced mitotic arrest in MCF-7 cells. Indibulin-treated MCF-7 cells underwent apoptosis-mediated cell death. Further, the combination of indibulin with an anticancer drug vinblastine was found to exert synergistic cytotoxic effects on MCF-7 cells. Interestingly, indibulin displayed a stronger effect on the undifferentiated neuroblastoma (SH-SY5Y) cells than the differentiated neuronal cells. Unlike indibulin, vinblastine and colchicine produced similar depolymerizing effects on microtubules in both differentiated and undifferentiated SH-SY5Y cells. The data indicated a possibility that indibulin may reduce chemotherapy-induced peripheral neuropathy in cancer patients.
Arbitrary shaped beam scattering from a chiral-coated conducting object with arbitrary monochromatic illumination
Authors: Wang Mingjun , Zhang Huayong , Ke Xizheng , Liu Guosheng , Ouyang Xiaoping 
Published: August 2018

AbstractAn exact semi-analytical method of calculating the scattered fields from a chiral-coated conducting object under arbitrary shaped beam illumination is developed. The scattered fields and the fields within the chiral coating are expanded in terms of appropriate spherical vector wave functions. The unknown expansion coefficients are determined by solving an infinite system of linear equations derived using the method of moments technique and the boundary conditions. For incidence of a Gaussian beam, circularly polarized wave, zero-order Bessel beam and Hertzian electric dipole radiation on a chiral-coated conducting spheroid and a chiral-coated conducting circular cylinder of finite length, the normalized differential scattering cross sections are evaluated and discussed briefly.
Human esophageal myofibroblast secretion of bone morphogenetic proteins and GREMLIN1 and paracrine regulation of squamous epithelial growth
Authors: Zhang Chunying , Niu Chao , Yang Kevin , Shaker Anisa 
Published: August 2018

AbstractWe have previously shown myofibroblasts subjacent to the squamous epithelium in the normal human esophagus and an increase in esophagitis. Myofibroblast contribution to bone morphogenetic protein (BMP) signaling and to paracrine mediated epithelial-mesenchymal interactions in the human esophagus remains incompletely defined. We investigated BMP4 and BMP inhibitor GREM1 gene expression and protein levels in previously characterized human esophageal myofibroblast primary cultures and in a human esophageal myofibroblast cell line. We adapted human esophageal myofibroblast conditioned media into a 3D organotypic model to investigate the effect of myofibroblast secreted factors on squamous epithelial morphology, proliferation, differentiation and BMP signaling. Human esophageal myofibroblasts constitutively secrete GREM1 and increase BMP4 expression and BMP4 secretion in response to epithelial Hedgehog ligand SHH. Detection of secreted BMP4 is decreased in the presence of GREM1. Myofibroblast conditioned media increases epithelial proliferation and expression of basal markers p63 and CK14 leading to an overall increase in epithelial thickness. Epithelial BMP signaling increases with myofibroblast conditioned media. These findings were partially reversed with GREM1 inhibition. Our results demonstrate that myofibroblasts are potential sources of GREM1 and of BMP4 in the human esophagus and that human esophageal myofibroblast-epithelial paracrine interactions contribute in part to the regulation of epithelial growth.
Detoxification mechanisms involved in ivermectin resistance in the cattle tick, Rhipicephalus (Boophilus) microplus
Authors: Le Gall Valeria Lis , Klafke Guilherme Marcondes , Torres Tatiana Teixeira 
Published: August 2018

AbstractThe cattle tick Rhipicephalus microplus is one of the most important ectoparasites with great sanitary and economic impact for cattle rearing worldwide. Ivermectin is commonly used to control tick populations, but its use over the last 30 years has led to the development of resistant populations of R. microplus, and a concomitant loss of efficacy. In this context, we aimed to determine the metabolic mechanisms that contribute to ivermectin resistance in a resistant strain of this species. We performed lethal time bioassays with inhibitors of detoxifying enzymes and xenobiotic transporters (four detoxification pathways) using two strains of ticks: a susceptible strain, Mozo, and a resistant strain, Juarez. We used four inhibitors to test the involvement of different families of proteins responsible for detoxification of ivermectin, namely cytochrome P450, esterases, glutathione-S-transferase, and ATP Binding Cassette Transporters. We calculated the synergistic factor for each inhibitor and strain. To different degrees, all tested inhibitors altered the mortality rates in the strain Juarez, indicating that multiple mechanisms are responsible for the resistant phenotype. Detoxification mechanisms mediated by ABC transporters were observed to be the most important. Esterases, glutathione-S-transferases, and cytochrome-oxidases played less important roles in detoxification.
Carrier transfer efficiency and its influence on emission properties of telecom wavelength InP-based quantum dot – quantum well structures
Authors: Rudno-Rudziński Wojciech , Syperek Marcin , Andrzejewski Janusz , Rogowicz Ernest , Eisenstein Gadi , Bauer Sven , Sichkovskyi Vitalii I. , Reithmaier Johann P. , Sęk Grzegorz 
Published: August 2018

AbstractWe investigate a hybrid system containing an In0.53Ga0.47As quantum well (QW), separated by a thin 2 nm In0.53Ga0.23Al0.24As barrier from 1.55 µm emitting InAs quantum dots (QDs), grown by molecular beam epitaxy on an InP substrate. Photoreflectance and photoluminescence (PL) spectroscopies are used to identify optical transitions in the system, with support of 8-band kp modelling. The main part of the work constitute the measurements and analysis of thermal quenching of PL for a set of samples with different QW widths (3–6 nm). Basing on Arrhenius plots, carrier escape channels from the dots are identified, pointing at the importance of carrier escape into the QW. A simple two level rate equations model is proposed and solved, exhibiting qualitative agreement with experimental observations. We show that for a narrow QW the escape process is less efficient than carrier supply via the QW due to the narrow barrier, resulting in improved emission intensity at room temperature. It proves that with carefully designed energy level structure, a hybrid QW/QD system can be used as an active region in telecom lasers with improved efficiencies.
Genomic analysis of Sparus aurata reveals the evolutionary dynamics of sex-biased genes in a sequential hermaphrodite fish
Authors: Pauletto Marianna , Manousaki Tereza , Ferraresso Serena , Babbucci Massimiliano , Tsakogiannis Alexandros , Louro Bruno , Vitulo Nicola , Quoc Viet Ha , Carraro Roberta , Bertotto Daniela , Franch Rafaella , Maroso Francesco , Aslam Muhammad L. , Sonesson Anna K. , Simionati Barbara , Malacrida Giorgio , Cestaro Alessandro , Caberlotto Stefano , Sarropoulou Elena , Mylonas Costantinos C. , Power Deborah M. , Patarnello Tomaso , Canario Adelino V. M. , Tsigenopoulos Costas , Bargelloni Luca 
Published: August 2018

AbstractSexual dimorphism is a fascinating subject in evolutionary biology and mostly results from sex-biased expression of genes, which have been shown to evolve faster in gonochoristic species. We report here genome and sex-specific transcriptome sequencing ofSparus aurata, a sequential hermaphrodite fish. Evolutionary comparative analysis reveals that sex-biased genes inS. aurataare similar in number and function, but evolved following strikingly divergent patterns compared with gonochoristic species, showing overall slower rates because of stronger functional constraints. Fast evolution is observed only for highly ovary-biased genes due to female-specific patterns of selection that are related to the peculiar reproduction mode ofS. aurata, first maturing as male, then as female. To our knowledge, these findings represent the first genome-wide analysis on sex-biased loci in a hermaphrodite vertebrate species, demonstrating how having two sexes in the same individual profoundly affects the fate of a large set of evolutionarily relevant genes.
Growing a Bibliography
Authors: Winkelman Sherry , Rots Arnold , D’Abrusco Raffaele , Becker Glenn , Thong Sinh , McCollough Michael 
Published: August 2018

The Chandra Data Archive (CDA) has been tracking publications based on Chandra observations in journals and on-line conference proceedings since early in the mission. Our goals are two-fold: 1) provide a means for Chandra users to search literature on Chandra-related papers to further their scientific research; and 2) provide a means for measuring the science produced from Chandra data. Over the years the database and its associated tools have expanded dramatically. In this paper I will give a history of the development of the bibliography with a focus on the human capital involved, along with the skill sets and management structures developed which allow us to maintain a very rich and extensive bibliography with a limited number of full time employees (FTEs). I will also cover how the diverse metadata collected has made the Chandra bibliography an essential resource in managing the Chandra X-ray Center.
This work has been supported by NASA under contract NAS 8-03060 to the Smithsonian Astrophysical Observatory for operation of the Chandra X-ray Center. It depends critically on the services provided by the ADS.
Genotype-Phenotype Association and Impact on Outcomes following Guided De-Escalation of Anti-Platelet Treatment in Acute Coronary Syndrome Patients: The TROPICAL-ACS Genotyping Substudy
Authors: Gross Lisa , Trenk Dietmar , Jacobshagen Claudius , Krieg Anne , Gawaz Meinrad , Massberg Steffen , Baylacher Monika , Aradi Daniel , Stimpfle Fabian , Hromek Julia , Vogelgesang Anja , Hadamitzky Martin , Sibbing Dirk , Geisler Tobias 
Published: August 2018

Background Phenotype-guided de-escalation (PGDE) of P2Y12-inhibitor treatment with an early switch from prasugrel to clopidogrel was identified as an effective alternative treatment strategy in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). The Testing Responsiveness to Platelet Inhibition on Chronic Antiplatelet Treatment for Acute Coronary Syndromes (TROPICAL-ACS) Genotyping Substudy aimed to investigate whether CYP2C19 genotypes correlate with on-treatment platelet reactivity (PR) in ACS patients treated with clopidogrel or prasugrel and thus might be useful for guidance of early de-escalation of anti-platelet treatment.
Methods and Results A total of 603 ACS consecutive patients were enrolled in four centres (23.1% of the overall TROPICAL-ACS population). Rapid genotyping (Spartan RX) for CYP2C19*2, *3 and *17 alleles was performed. Associations between PR and the primary and secondary endpoints of the TROPICAL-ACS trial and CYP2C19*2 and CYP2C19*17 carrier status were evaluated.For the PGDE group, the on-clopidogrel PR significantly differed across CYP2C19*2 (p < 0.001) and CYP2C19*17 genotypes (p = 0.05). Control group patients were not related (p = 0.90, p = 0.74) to on-prasugrel PR. For high PR versus non-high PR patients within the PGDE group, significant differences were observed for the rate of CYP2C19*2 allele carriers (43% vs. 28%, p = 0.007).
Conclusion CYP2C19*2 and CYP2C19*17 carrier status correlates with PR in ACS patients treated with clopidogrel and thus might be useful for pre-selecting patients who will and who may not be suitable for PGDE of anti-platelet treatment. Regarding phenotype-guided treatment, we did not observe added benefit of genotyping to predict ischaemic and bleeding risk in patients who underwent a PGDE approach.
Clinical Trial Registration URL: https//www.clinicaltrials.gov. Unique Identifier: NCT: 01959451.
Risk Score for Prediction of 10-Year Atrial Fibrillation: A Community-Based Study
Authors: Aronson Doron , Shalev Varda , Katz Rachel , Chodick Gabriel , Mutlak Diab 
Published: August 2018

Purpose We used a large real-world data from community settings to develop and validate a 10-year risk score for new-onset atrial fibrillation (AF) and calculate its net benefit performance.
Methods Multivariable Cox proportional hazards model was used to estimate effects of risk factors in the derivation cohort (n = 96,778) and to derive a risk equation. Measures of calibration and discrimination were calculated in the validation cohort (n = 48,404).
Results Cumulative AF incidence rates for both the derivation and validation cohorts were 5.8% at 10 years. The final models included the following variables: age, sex, body mass index, history of treated hypertension, systolic blood pressure ≥ 160 mm Hg, chronic lung disease, history of myocardial infarction, history of peripheral arterial disease, heart failure and history of an inflammatory disease. There was a 27-fold difference (1.0% vs. 27.2%) in AF risk between the lowest (–1) and the highest (9) sum score. The c-statistic was 0.743 (95% confidence interval [CI], 0.737–0.749) for the derivation cohort and 0.749 (95% CI, 0.741–0.759) in the validation cohort. The risk equation was well calibrated, with predicted risks closely matching observed risks. Decision curve analysis displayed consistent positive net benefit of using the AF risk score for decision thresholds between 1 and 25% 10-year AF risk.
Conclusion We provide a simple score for the prediction of 10-year risk for AF. The score can be used to select patients at highest risk for treatments of modifiable risk factors, monitoring for sub-clinical AF detection or for clinical trials of primary prevention of AF.
Effects of environmental stressors on daily governance
Authors: Obradovich Nick , Tingley Dustin , Rahwan Iyad 
Published: August 2018

Significance
Public servants are often first responders to disasters, and the day-to-day completion of their jobs aids public health and safety. However, with respect to their individual psychological and physiological responses to environmental stressors, public sector workers may be harmed in much the same way as other citizens in society. We find that exposure to hotter temperatures reduces the activity of two groups of regulators—police officers and food safety inspectors—at times that the risks they are tasked with overseeing are highest. Given that we observe these effects in a country with high political institutionalization, our findings may have implications for the impacts of climate change on the functioning of regulatory governance in countries with lower political and economic development.