bluuebunny/crossref_metadata_2025_split huggingface dataset:
ATP-dependent substrate transport by the ABC transporter MsbA is proton-coupled
Authors: Singh Himansha , Velamakanni Saroj , Deery Michael J. , Howard Julie , Wei Shen L. , van Veen Hendrik W. 
Published: August 2016

AbstractATP-binding cassette transporters mediate the transbilayer movement of a vast number of substrates in or out of cells in organisms ranging from bacteria to humans. Current alternating access models for ABC exporters including the multidrug and Lipid A transporter MsbA from Escherichia coli suggest a role for nucleotide as the fundamental source of free energy. These models involve cycling between conformations with inward- and outward-facing substrate-binding sites in response to engagement and hydrolysis of ATP at the nucleotide-binding domains. Here we report that MsbA also utilizes another major energy currency in the cell by coupling substrate transport to a transmembrane electrochemical proton gradient. The dependence of ATP-dependent transport on proton coupling, and the stimulation of MsbA-ATPase by the chemical proton gradient highlight the functional integration of both forms of metabolic energy. These findings introduce ion coupling as a new parameter in the mechanism of this homodimeric ABC transporter.
Disorder engineering and conductivity dome in ReS2 with electrolyte gating
Authors: Ovchinnikov Dmitry , Gargiulo Fernando , Allain Adrien , Pasquier Diego José , Dumcenco Dumitru , Ho Ching-Hwa , Yazyev Oleg V. , Kis Andras 
Published: August 2016

AbstractAtomically thin rhenium disulphide (ReS2) is a member of the transition metal dichalcogenide family of materials. This two-dimensional semiconductor is characterized by weak interlayer coupling and a distorted 1T structure, which leads to anisotropy in electrical and optical properties. Here we report on the electrical transport study of mono- and multilayer ReS2 with polymer electrolyte gating. We find that the conductivity of monolayer ReS2 is completely suppressed at high carrier densities, an unusual feature unique to monolayers, making ReS2 the first example of such a material. Using dual-gated devices, we can distinguish the gate-induced doping from the electrostatic disorder induced by the polymer electrolyte itself. Theoretical calculations and a transport model indicate that the observed conductivity suppression can be explained by a combination of a narrow conduction band and Anderson localization due to electrolyte-induced disorder.
Synthetic viability by BRCA2 and PARP1/ARTD1 deficiencies
Authors: Ding Xia , Chaudhuri Arnab Ray , Callen Elsa , Pang Yan , Biswas Kajal , Klarmann Kimberly D. , Martin Betty K. , Burkett Sandra , Cleveland Linda , Stauffer Stacey , Sullivan Teresa , Dewan Aashish , Marks Hanna , Tubbs Anthony T. , Wong Nancy , Buehler Eugen , Akagi Keiko , Martin Scott E. , Keller Jonathan R. , Nussenzweig André , Sharan Shyam K. 
Published: August 2016

AbstractPoly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) olaparib has been approved for treatment of advanced ovarian cancer associated with BRCA1 and BRCA2 mutations. BRCA1- and BRCA2-mutated cells, which are homologous recombination (HR) deficient, are hypersensitive to PARPi through the mechanism of synthetic lethality. Here we examine the effect of PARPi on HR-proficient cells. Olaparib pretreatment, PARP1 knockdown or Parp1 heterozygosity of Brca2cko/ko mouse embryonic stem cells (mESCs), carrying a null (ko) and a conditional (cko) allele of Brca2, results in viable Brca2ko/ko cells. PARP1 deficiency does not restore HR in Brca2ko/ko cells, but protects stalled replication forks from MRE11-mediated degradation through its impaired recruitment. The functional consequence of Parp1 heterozygosity on BRCA2 loss is demonstrated by a significant increase in tumorigenesis in Brca2cko/cko mice. Thus, while olaparib efficiently kills BRCA2-deficient cells, we demonstrate that it can also contribute to the synthetic viability if PARP is inhibited before BRCA2 loss.
Polyphenol-rich strawberry extract (PRSE) shows in vitro and in vivo biological activity against invasive breast cancer cells
Authors: Amatori Stefano , Mazzoni Luca , Alvarez-Suarez Josè Miguel , Giampieri Francesca , Gasparrini Massimiliano , Forbes-Hernandez Tamara Yuliett , Afrin Sadia , Errico Provenzano Alfredo , Persico Giuseppe , Mezzetti Bruno , Amici Augusto , Fanelli Mirco , Battino Maurizio 
Published: August 2016

AbstractWe describe the biological effects of a polyphenol-rich strawberry extract (PRSE), obtained from the “Alba” variety, on the highly aggressive and invasive basal-like breast cancer cell line A17. Dose-response and time-course experiments showed that PRSE is able to decrease the cellular viability of A17 cells in a time- and dose-dependent manner. PRSE effect on cell survival was investigated in other tumor and normal cell lines of both mouse and human origin, demonstrating that PRSE is more active against breast cancer cells. Cytofluorimetric analysis of A17 cells demonstrated that sub-lethal doses of PRSE reduce the number of cells in S phase, inducing the accumulation of cells in G1 phase of cell cycle. In addition, the migration of A17 cells was studied monitoring the ability of PRSE to inhibit cellular mobility. Gene expression analysis revealed the modulation of 12 genes playing different roles in the cellular migration, adhesion and invasion processes. Finally,in vivoexperiments showed the growth inhibition of A17 cells orthotopically transplanted into FVB syngeneic mice fed with PRSE. Overall, we demonstrated that PRSE exerts important biological activities against a highly invasive breast cancer cell line bothin vitroandin vivosuggesting the strawberry extracts as preventive/curative food strategy.
Distinct interacting core taxa in co-occurrence networks enable discrimination of polymicrobial oral diseases with similar symptoms
Authors: Shiba Takahiko , Watanabe Takayasu , Kachi Hirokazu , Koyanagi Tatsuro , Maruyama Noriko , Murase Kazunori , Takeuchi Yasuo , Maruyama Fumito , Izumi Yuichi , Nakagawa Ichiro 
Published: August 2016

AbstractPolymicrobial diseases, which can be life threatening, are caused by the presence and interactions of multiple microbes. Peri-implantitis and periodontitis are representative polymicrobial diseases that show similar clinical symptoms. To establish a means of differentiating between them, we compared microbial species and functional genes in situ by performing metatranscriptomic analyses of peri-implantitis and periodontitis samples obtained from the same subjects (n = 12 each). Although the two diseases differed in terms of 16S rRNA-based taxonomic profiles, they showed similarities with respect to functional genes and taxonomic and virulence factor mRNA profiles. The latter—defined as microbial virulence types—differed from those of healthy periodontal sites. We also showed that networks based on co-occurrence relationships of taxonomic mRNA abundance (co-occurrence networks) were dissimilar between the two diseases. Remarkably, these networks consisted mainly of taxa with a high relative mRNA-to-rRNA ratio, with some showing significant co-occurrence defined as interacting core taxa, highlighting differences between the two groups. Thus, peri-implantitis and periodontitis have shared as well as distinct microbiological characteristics. Our findings provide insight into microbial interactions in polymicrobial diseases with unknown etiologies.
Differentiation of malignant cervical lymphadenopathy by dual-energy CT: a preliminary analysis
Authors: Yang Liang , Luo Dehong , Li Lin , Zhao Yanfeng , Lin Meng , Guo Wei , Zhou Chunwu 
Published: August 2016

AbstractThe accurate diagnosis of malignant cervical lymphadenopathy remains challenging. In this study, we determined the value of quantitative parameters derived from dual-energy computed tomography (DECT) for differentiating malignant cervical lymphadenopathy caused by thyroid carcinoma (TC), salivary gland carcinoma (SC), squamous cell carcinoma (SCC) and lymphoma. We retrospectively analysed 92 patients with pathologically confirmed cervical lymphadenopathy due to TC, SC, SCC and lymphoma. All patients received a DECT scan before therapy. Using GSI (gemstone spectral imaging) Volume Viewer software, we analysed the enhanced monochromatic data and the quantitative parameters we acquired included the iodine concentration (IC), water concentration (WC) and the slope of the spectral HU curve (λHU). One-way ANOVA showed significant differences in the IC and λHU among different groups (P < 0.05). Post-hoc pairwise comparisons demonstrated the IC and λHU of TC group were significantly higher than those of SC, SCC and lymphoma groups (P < 0.05). In addition, the IC and λHU of SC group were significantly higher than those of the SCC and lymphoma groups (P < 0.05). Other comparisons of IC and λHU values showed no significant differences (P > 0.05). The quantitative parameters derived from DECT were useful supplements to conventional computed tomography images and were helpful for distinguishing different malignant cervical lymphadenopathies.
Developmental Validation of the Huaxia Platinum System and application in 3 main ethnic groups of China
Authors: Wang Zheng , Zhou Di , Jia Zhenjun , Li Luyao , Wu Wei , Li Chengtao , Hou Yiping 
Published: August 2016

AbstractSTRs, scattered throughout the genome with higher mutation rate, are attractive to genetic application like forensic, anthropological and population genetics studies. STR profiling has now been applied in various aspects of human identification in forensic investigations. This work described the developmental validation of a novel and universal assay, the Huaxia Platinum System, which amplifies all markers in the expanded CODIS core loci and the Chinese National Database in one single PCR system. Developmental validation demonstrated that this novel assay is accurate, sensitive, reproducible and robust. No discordant calls were observed between the Huaxia Platinum System and other STR systems. Full genotypes could be achieved even with 250 pg of human DNA. Additionally, 402 unrelated individuals from 3 main ethnic groups of China (Han, Uygur and Tibetan) were genotyped to investigate the effectiveness of this novel assay. The CMP were 2.3094 × 10−27, 4.3791 × 10−28 and 6.9118 × 10−27, respectively and the CPE were 0.99999999939059, 0.99999999989653 and 0.99999999976386, respectively. Aforementioned results suggested that the Huaxia Platinum System is polymorphic and informative, which provides efficient tool for national DNA database and facilitate international data sharing.
A VEGF-dependent gene signature enriched in mesenchymal ovarian cancer predicts patient prognosis
Authors: Yin Xia , Wang Xiaojie , Shen Boqiang , Jing Ying , Li Qing , Cai Mei-Chun , Gu Zhuowei , Yang Qi , Zhang Zhenfeng , Liu Jin , Li Hongxia , Di Wen , Zhuang Guanglei 
Published: August 2016

AbstractWe have previously reported surrogate biomarkers of VEGF pathway activities with the potential to provide predictive information for anti-VEGF therapies. The aim of this study was to systematically evaluate a new VEGF-dependent gene signature (VDGs) in relation to molecular subtypes of ovarian cancer and patient prognosis. Using microarray profiling and cross-species analysis, we identified 140-gene mouse VDGs and corresponding 139-gene human VDGs, which displayed enrichment of vasculature and basement membrane genes. In patients who received bevacizumab therapy and showed partial response, the expressions of VDGs (summarized to yield VDGs scores) were markedly decreased in post-treatment biopsies compared with pre-treatment baselines. In contrast, VDGs scores were not significantly altered following bevacizumab treatment in patients with stable or progressive disease. Analysis of VDGs in ovarian cancer showed that VDGs as a prognostic signature was able to predict patient outcome. Correlation estimation of VDGs scores and molecular features revealed that VDGs was overrepresented in mesenchymal subtype and BRCA mutation carriers. These findings highlighted the prognostic role of VEGF-mediated angiogenesis in ovarian cancer and proposed a VEGF-dependent gene signature as a molecular basis for developing novel diagnostic strategies to aid patient selection for VEGF-targeted agents.
Elevated progesterone on the trigger day does not impair the outcome of Human Menotrophins Gonadotrophin and Medroxyprogesterone acetate treatment cycles
Authors: Lu Xuefeng , Chen Qiuju , Fu Yonglun , Ai Ai , Lyu Qifeng , Kuang Yan Ping 
Published: August 2016

AbstractTo demonstrate the incidence and effects of elevated progesterone (P) on the trigger day on the outcome of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles using Medroxyprogesterone acetate (MPA) co-treated with Human Menotrophins Gonadotrophin (hMG + MPA), we performed a retrospective analysis including 4106 IVF/ICSI cycles. The cycles were grouped according to the P level on the trigger day: <1 ng/mL, between 1–1.5 ng/ml (including 1), between 1.5–2 ng/mL (including 1.5) and ≥2 ng/mL. The primary outcome measure was live birth rate. The prevalence of P level categories was 12.93% (531/4106), 2.92% (120/4106) and 1.92% (79/4106) in women with P between 1–1.5 ng/mL, between 1.5–2 ng/mL and ≥2 ng/mL, respectively. The mean stimulation duration, total hMG dose, serum follicle stimulating hormone (FSH), estrogen(E2) on the trigger day and the number of oocytes in patients with elevated P were significantly higher than patients with P < 1 ng/mL (P < 0.05). However, there were no significant differences in the oocyte retrieval rates, fertilization rates, implantation rates, clinical pregnancy rates and live birth rates between the groups based on frozen embryo transfer (FET). We concluded that elevated P on the trigger day had no negative effect on the final outcome of the hMG + MPA treatment cycles based on FET.
Structure of a Highly Active Cephalopod S-crystallin Mutant: New Molecular Evidence for Evolution from an Active Enzyme into Lens-Refractive Protein
Authors: Tan Wei-Hung , Cheng Shu-Chun , Liu Yu-Tung , Wu Cheng-Guo , Lin Min-Han , Chen Chiao-Che , Lin Chao-Hsiung , Chou Chi-Yuan 
Published: August 2016

AbstractCrystallins are found widely in animal lenses and have important functions due to their refractive properties. In the coleoid cephalopods, a lens with a graded refractive index provides good vision and is required for survival. Cephalopod S-crystallin is thought to have evolved from glutathione S-transferase (GST) with various homologs differentially expressed in the lens. However, there is no direct structural information that helps to delineate the mechanisms by which S-crystallin could have evolved. Here we report the structural and biochemical characterization of novel S-crystallin-glutathione complex. The 2.35-Å crystal structure of a S-crystallin mutant from Octopus vulgaris reveals an active-site architecture that is different from that of GST. S-crystallin has a preference for glutathione binding, although almost lost its GST enzymatic activity. We’ve also identified four historical mutations that are able to produce a “GST-like” S-crystallin that has regained activity. This protein recapitulates the evolution of S-crystallin from GST. Protein stability studies suggest that S-crystallin is stabilized by glutathione binding to prevent its aggregation; this contrasts with GST-σ, which do not possess this protection. We suggest that a tradeoff between enzyme activity and the stability of the lens protein might have been one of the major driving force behind lens evolution.
Hydrogen prevents corneal endothelial damage in phacoemulsification cataract surgery
Authors: Igarashi Tsutomu , Ohsawa Ikuroh , Kobayashi Maika , Igarashi Toru , Suzuki Hisaharu , Iketani Masumi , Takahashi Hiroshi 
Published: August 2016

AbstractIn phacoemulsification, ultrasound induces hydroxyl radical (·OH) formation, damaging corneal endothelium. Whether H2 can prevent such oxidative damage in phacoemulsification was examined by in vitro and in vivo studies. H2 was dissolved in a commercial irrigating solution. The effects of H2 against ·OH generation were first confirmed in vitro by electron-spin resonance (ESR) and hydroxyphenyl fluorescein (HPF). ESR showed a significantly decreased signal magnitude and fluorescence intensity by oxidized HPF was significantly less in the H2-dissolved solution. The effects of H2 in phacoemulsification were evaluated in rabbits, comparing H2-dissolved and control solutions. Five hours after the procedure, the whole cornea was excised and subjected to image analysis for corneal edema, real-time semiquantitative PCR (qPCR) for heme oxygenase (HO)-1, catalase (CAT), superoxide dismutase 1 (SOD1) and SOD2 mRNA and immunohistochemistry. Corneal edema was significantly less and the increases in anti-oxidative HO-1, CAT and SOD2 mRNA expressions were significantly suppressed in the H2 group. In addition, corneal endothelial cell expressions of two oxidative stress markers, 4-HNE and 8-OHdG, were significantly lower in the H2 group. In conclusion, H2 dissolved in the ocular irrigating solution protected corneal endothelial cells from phacoemulsification-induced oxidative stress and damage.
Adipocyte in vascular wall can induce the rupture of abdominal aortic aneurysm
Authors: Kugo Hirona , Zaima Nobuhiro , Tanaka Hiroki , Mouri Youhei , Yanagimoto Kenichi , Hayamizu Kohsuke , Hashimoto Keisuke , Sasaki Takeshi , Sano Masaki , Yata Tatsuro , Urano Tetsumei , Setou Mitsutoshi , Unno Naoki , Moriyama Tatsuya 
Published: August 2016

AbstractAbdominal aortic aneurysm (AAA) is a vascular disease involving the gradual dilation of the abdominal aorta. It has been reported that development of AAA is associated with inflammation of the vascular wall; however, the mechanism of AAA rupture is not fully understood. In this study, we investigated the mechanism underlying AAA rupture using a hypoperfusion-induced animal model. We found that the administration of triolein increased the AAA rupture rate in the animal model and that the number of adipocytes was increased in ruptured vascular walls compared to non-ruptured walls. In the ruptured group, macrophage infiltration and the protein levels of matrix metalloproteinases 2 and 9 were increased in the areas around adipocytes, while collagen-positive areas were decreased in the areas with adipocytes compared to those without adipocytes. The administration of fish oil, which suppresses adipocyte hypertrophy, decreased the number and size of adipocytes, as well as decreased the risk of AAA rupture ratio by 0.23 compared to the triolein administered group. In human AAA samples, the amount of triglyceride in the adventitia was correlated with the diameter of the AAA. These results suggest that AAA rupture is related to the abnormal appearance of adipocytes in the vascular wall.
Miniaturizing VEGF: Peptides mimicking the discontinuous VEGF receptor-binding site modulate the angiogenic response
Authors: De Rosa Lucia , Finetti Federica , Diana Donatella , Di Stasi Rossella , Auriemma Sara , Romanelli Alessandra , Fattorusso Roberto , Ziche Marina , Morbidelli Lucia , D’Andrea Luca Domenico 
Published: August 2016

AbstractThe angiogenic properties of VEGF are mediated through the binding of VEGF to its receptor VEGFR2. The VEGF/VEGFR interface is constituted by a discontinuous binding region distributed on both VEGF monomers. We attempted to reproduce this discontinuous binding site by covalently linking into a single molecular entity two VEGF segments involved in receptor recognition. We designed and synthesized by chemical ligation a set of peptides differing in length and flexibility of the molecular linker joining the two VEGF segments. The biological activity of the peptides was characterized in vitro and in vivo showing a VEGF-like activity. The most biologically active mini-VEGF was further analyzed by NMR to determine the atomic details of its interaction with the receptor.
Microstructural and mechanical features of aluminium semi-solid alloys made by rheocasting technique
Authors: Ragab Kh. A. , Bouazara M. , Bouaicha A. , Allaoui O. 
Published: August 2016

The rheocasting process applied by Swirled Enthalpy Equilibration Device (SEED) technique relies on rapid extraction of a controlled quantity of heat from the liquid aluminium alloy via mechanical agitation to form the semi-solid slurry that can be formed under pressure. Microstructural characteristics of both conventional and semi-solid A357 castings under T6 heat treatment conditions were examined using optical and scanning electron microscopy. The fatigue and tensile experiments were applied to evaluate the effect of SEED technique on the mechanical properties of T6-A357 semi-solid alloys and conventional castings. The results showed that the rheocasting–SEED technique has proved successful in producing optimum microstructure of Al–Si–Mg semi-solid alloys providing an excellent combination of quality and mechanical performance as compared to conventional technique. This paper is part of a Themed Issue on Aluminium-based materials: processing, microstructure, properties, and recycling.
Voluntary exercise increases IgA concentration and polymeric Ig receptor expression in the rat submandibular gland
Authors: Kurimoto Yuki , Saruta Juri , To Masahiro , Yamamoto Yuko , Kimura Koji , Tsukinoki Keiichi 
Published: August 2016

AbstractSalivary IgA—a primary factor in local immunity of the oral cavity—plays an important role in maintaining local immune function in the oral cavity and prevent upper respiratory tract infections. Oral IgA levels are known to fluctuate in an exercise-dependent manner; thus, we investigated the effects of voluntary exercise on salivary IgA secretion in rats to better understand the mechanism by which this occurs. Six-week-old male Wistar rats were placed in individual cages with or without access to exercise wheels for three weeks. Notably, animals who engaged in voluntary exercise demonstrated significant increases in IgA concentration in saliva and submandibular gland tissue, as well as a markedly higher salivary IgA flow rate. Moreover, active rats also exhibited elevated polymeric Ig receptor (pIgR) mRNA expression in submandibular gland tissue. Collectively, these results suggest that voluntary exercise may increase salivary IgA concentration and boost immune function in the oral cavity.