bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA defects, epigenetics, and gene expression in cancer-adjacent breast: a study from The Cancer Genome Atlas
Authors: Troester Melissa A , Hoadley Katherine A , D’Arcy Monica , Cherniack Andrew D , Stewart Chip , Koboldt Daniel C , Robertson A Gordon , Mahurkar Swapna , Shen Hui , Wilkerson Matthew D , Sandhu Rupninder , Johnson Nicole B , Allison Kimberly H , Beck Andrew H , Yau Christina , Bowen Jay , Sheth Margi , Hwang E Shelley , Perou Charles M , Laird Peter W , Ding Li , Benz Christopher C 
Published: May 2016

AbstractRecurrence rates after breast-conserving therapy may depend on genomic characteristics of cancer-adjacent, benign-appearing tissue. Studies have not evaluated recurrence in association with multiple genomic characteristics of cancer-adjacent breast tissue. To estimate the prevalence of DNA defects and RNA expression subtypes in cancer-adjacent, benign-appearing breast tissue at least 2 cm from the tumor margin, cancer-adjacent, pathologically well-characterized, benign-appearing breast tissue specimens from The Cancer Genome Atlas project were analyzed for DNA sequence, copy-number variation, DNA methylation, messenger RNA (mRNA) sequence, and mRNA/microRNA expression. Additional samples were also analyzed by at least one of these genomic data types and associations between genomic characteristics of normal tissue and overall survival were assessed. Approximately 40% of cancer-adjacent, benign-appearing tissues harbored genomic defects in DNA copy number, sequence, methylation, or in RNA sequence, although these defects did not significantly predict 10-year overall survival. Two mRNA/microRNA expression phenotypes were observed, including an active mRNA subtype that was identified in 40% of samples. Controlling for tumor characteristics and the presence of genomic defects, this active subtype was associated with significantly worse 10-year survival among estrogen receptor (ER)-positive cases. This multi-platform analysis of breast cancer-adjacent samples produced genomic findings consistent with current surgical margin guidelines, and provides evidence that extratumoral RNA expression patterns in cancer-adjacent tissue predict overall survival among patients with ER-positive disease.
Accurate Electron Affinity of Iron and Fine Structures of Negative Iron ions
Authors: Chen Xiaolin , Luo Zhihong , Li Jiaming , Ning Chuangang 
Published: May 2016

AbstractIonization potential (IP) is defined as the amount of energy required to remove the most loosely bound electron of an atom, while electron affinity (EA) is defined as the amount of energy released when an electron is attached to a neutral atom. Both IP and EA are critical for understanding chemical properties of an element. In contrast to accurate IPs and structures of neutral atoms, EAs and structures of negative ions are relatively unexplored, especially for the transition metal anions. Here, we report the accurate EA value of Fe and fine structures of Fe− using the slow electron velocity imaging method. These measurements yield a very accurate EA value of Fe, 1235.93(28) cm−1 or 153.236(34) meV. The fine structures of Fe− were also successfully resolved. The present work provides a reliable benchmark for theoretical calculations and also paves the way for improving the EA measurements of other transition metal atoms to the sub cm−1 accuracy.
Molecular Imaging of Activated Platelets Allows the Detection of Pulmonary Embolism with Magnetic Resonance Imaging
Authors: Heidt Timo , Ehrismann Simon , Hövener Jan-Bernd , Neudorfer Irene , Hilgendorf Ingo , Reisert Marco , Hagemeyer Christoph E. , Zirlik Andreas , Reinöhl Jochen , Bode Christoph , Peter Karlheinz , von Elverfeldt Dominik , von zur Muhlen Constantin 
Published: May 2016

AbstractEarly and reliable detection of pulmonary embolism (PE) is critical for improving patient morbidity and mortality. The desire for low-threshold screening for pulmonary embolism is contradicted by unfavorable radiation of currently used computed tomography or nuclear techniques, while standard magnetic resonance imaging still struggles to provide sufficient diagnostic sensitivity in the lung. In this study we evaluate a molecular-targeted contrast agent against activated platelets for non-invasive detection of murine pulmonary thromboembolism using magnetic resonance imaging. By intravenous injection of human thrombin, pulmonary thromboembolism were consistently induced as confirmed by immunohistochemistry of the lung. Magnetic resonance imaging after thrombin injection showed local tissue edema in "Equation missing" weighted images which co-localized with the histological presence of pulmonary thromboembolism. Furthermore, injection of a functionalized contrast agent targeting activated platelets provided sensitive evidence of focal accumulation of activated platelets within the edematous area, which, ex vivo, correlated well with the size of the pulmonary embolism. In summary, we here show delivery and specific binding of a functionalized molecular contrast agent against activated platelets for targeting pulmonary thromboembolism. Going forward, molecular imaging may provide new opportunities to increase sensitivity of magnetic resonance imaging for detection of pulmonary embolism.
Dislocation Majorana zero modes in perovskite oxide 2DEG
Authors: Chung Suk Bum , Chan Cheung , Yao Hong 
Published: May 2016

AbstractMuch of the current experimental efforts for detecting Majorana zero modes have been centered on probing the boundary of quantum wires with strong spin-orbit coupling. The same type of Majorana zero mode can also be realized at crystalline dislocations in 2D superconductors with the nontrivial weak topological indices. Unlike at an Abrikosov vortex, at such a dislocation, there is no other low-lying midgap state than the Majorana zero mode so that it avoids usual complications encountered in experimental detections such as scanning tunneling microscope (STM) measurements. We will show that, using the anisotropic dispersion of the t2g orbitals of Ti or Ta atoms, such a weak topological superconductivity can be realized when the surface two-dimensional electronic gas (2DEG) of SrTiO3 or KTaO3 becomes superconducting, which can occur through either intrinsic pairing or proximity to existing s-wave superconductors.
New Hosts of The Lassa Virus
Authors: Olayemi Ayodeji , Cadar Daniel , Magassouba N’Faly , Obadare Adeoba , Kourouma Fode , Oyeyiola Akinlabi , Fasogbon Samuel , Igbokwe Joseph , Rieger Toni , Bockholt Sabrina , Jérôme Hanna , Schmidt-Chanasit Jonas , Garigliany Mutien , Lorenzen Stephan , Igbahenah Felix , Fichet Jean-Nicolas , Ortsega Daniel , Omilabu Sunday , Günther Stephan , Fichet-Calvet Elisabeth 
Published: May 2016

AbstractLassa virus (LASV) causes a deadly haemorrhagic fever in humans, killing several thousand people in West Africa annually. For 40 years, the Natal multimammate rat, Mastomys natalensis, has been assumed to be the sole host of LASV. We found evidence that LASV is also hosted by other rodent species: the African wood mouse Hylomyscus pamfi in Nigeria, and the Guinea multimammate mouse Mastomys erythroleucus in both Nigeria and Guinea. Virus strains from these animals were isolated in the BSL-4 laboratory and fully sequenced. Phylogenetic analyses of viral genes coding for glycoprotein, nucleoprotein, polymerase and matrix protein show that Lassa strains detected in M. erythroleucus belong to lineages III and IV. The strain from H. pamfi clusters close to lineage I (for S gene) and between II & III (for L gene). Discovery of new rodent hosts has implications for LASV evolution and its spread into new areas within West Africa.
An effective colorimetric and ratiometric fluorescent probe based FRET with a large Stokes shift for bisulfite
Authors: Wu Wen-Li , Wang Zhao-Yang , Dai Xi , Miao Jun-Ying , Zhao Bao-Xiang 
Published: May 2016

AbstractBisulfite plays crucial roles in diverse physiological processes. Therefore, the efficient detection of bisulfite is very important. In this study, we report a colorimetric and ratiometric fluorescent probe (CPT) with a large Stokes shift (162 nm) for bisulfite (HSO3−) based FRET mechanism. The probe can quantitatively detect HSO3− with low detection limit (45 nM) and high specificity over other common anions and biothiols. A nucleophilic addition reaction was proposed for the sensing mechanism, which was confirmed by HRMS spectra. The test strips of the probe were made and used easily. Moreover, probe CPT was used to ratiometric fluorescent imaging of exogenous and endogenous HSO3− in living cells.
Combined sodium ion sensitivity in agonist binding and internalization of vasopressin V1b receptors
Authors: Koshimizu Taka-aki , Kashiwazaki Aki , Taniguchi Junichi 
Published: May 2016

AbstractReducing Na+ in the extracellular environment may lead to two beneficial effects for increasing agonist binding to cell surface G-protein coupled receptors (GPCRs): reduction of Na+-mediated binding block and reduce of receptor internalization. However, such combined effects have not been explored. We used Chinese Hamster Ovary cells expressing vasopressin V1b receptors as a model to explore Na+ sensitivity in agonist binding and receptor internalization. Under basal conditions, a large fraction of V1b receptors is located intracellularly and a small fraction is in the plasma membrane. Decreases in external Na+ increased cell surface [3H]AVP binding and decreased receptor internalization. Substitution of Na+ by Cs+ or NH4+ inhibited agonist binding. To suppress receptor internalization, the concentration of NaCl, but not of CsCl, had to be less than 50 mM, due to the high sensitivity of the internalization machinery to Na+ over Cs+. Iso-osmotic supplementation of glucose or NH4Cl maintained internalization of the V1b receptor, even in a low-NaCl environment. Moreover, iodide ions, which acted as a counter anion, inhibited V1b agonist binding. In summary, we found external ionic conditions that could increase the presence of high-affinity state receptors at the cell surface with minimum internalization during agonist stimulations.
Resveratrol Inhibition of Rac1-Derived Reactive Oxygen Species by AMPK Decreases Blood Pressure in a Fructose-Induced Rat Model of Hypertension
Authors: Cheng Pei-Wen , Lee Hui-Chieh , Lu Pei-Jung , Chen Hsin-Hung , Lai Chi-Cheng , Sun Gwo-Ching , Yeh Tung-Chen , Hsiao Michael , Lin Yu-Te , Liu Chun-Peng , Tseng Ching-Jiunn 
Published: May 2016

AbstractRecent studies have reported that the activation of AMP-activated protein kinase (AMPK) suppressed oxidative stress. The aim of this study was to examine whether the activation of AMPK in the brain decreased Rac1-induced ROS generation, thereby reducing blood pressure (BP) in rats with fructose-induced hypertension. The inhibition of ROS by treatment with an AMPK activator (oral resveratrol, 10 mg/kg/day) for 1 week decreased the BP and increased the NO production in the rostral ventrolateral medulla (RVLM) of fructose-fed rats but not in control Wistar-Kyoto (WKY) rats. In addition, resveratrol treatment abolished the Rac1-induced increases in the activity of the NADPH oxidase subunits p22-phox and reduced the activity of SOD2, while treatment with an AMPK inhibitor (compound C, 40 μM/day) had the opposite effect, in the fructose-fed rats. Interestingly, the activation of AMPK abolished Rac1 activation and decreased BP by inducing the activities of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and ribosomal protein S6 kinase (RSK) and nNOS phosphorylation in the fructose-fed rats. We conclude that the activation of AMPK decreased BP, abolished ROS generation and enhanced ERK1/2-RSK-nNOS pathway activity by negatively regulating Racl-induced NADPH oxidase levels in the RVLM during oxidative stress–associated hypertension.
Expression levels of ROS1/ALK/c-MET and therapeutic efficacy of cetuximab plus chemotherapy in advanced biliary tract cancer
Authors: Chiang Nai-Jung , Hsu Chiun , Chen Jen-Shi , Tsou Hsiao-Hui , Shen Ying-Ying , Chao Yee , Chen Ming-Huang , Yeh Ta-Sen , Shan Yan-Shen , Huang Shiu-Feng , Chen Li-Tzong 
Published: May 2016

AbstractAberrant expression of ROS1, ALK or c-MET (RAM) is implicated in carcinogenesis and cancer drug resistance. We retrospectively evaluated the effect of RAM expression on outcomes for advanced biliary tract cancer patients, who were treated with gemcitabine plus oxaliplatin (GEMOX), with or without cetuximab, in a randomized phase II trial. RAM expression levels on archived tissue sections were scored using immunohistochemistry (IHC). Of 110 tumors with IHC staining for all three markers, 18 were RAMhigh (IHC intensity 3+ for any markers). Ninety-two tumors were RAMlow (IHC intensity <3+ for all markers). All RAMhigh tumors were intra-hepatic cholangiocarcinomas (IHCC). Of the patients with IHCC (n = 80), median overall survival (OS) of RAMhigh group was inferior to that of the RAMlow group (5.7 vs. 11.7 months, p = 0.021). In multivariate analysis RAMhigh remained an independently adverse prognostic factor, with a hazard ratio of 2.01 (p = 0.039). In the RAMlow group, GEMOX treatment with cetuximab significantly improved the disease control rate (68% vs. 41%, p = 0.044), median progression-free survival (7.3 vs. 4.9 months, p = 0.026), and marginally prolonged median OS (14.1 vs 9.6 months, p = 0.056), compared to GEMOX treatment alone. Future trials of anti-EGFR inhibitors for IHCC may consider RAM expression as a patient stratification factor.
The Complex QT/RR Relationship in Mice
Authors: Roussel Julien , Champeroux Pascal , Roy Jérôme , Richard Sylvain , Fauconnier Jérémy , Le Guennec Jean-Yves , Thireau Jérôme 
Published: May 2016

AbstractThe QT interval reflects the time between the depolarization of ventricles until their repolarization and is usually used as a predictive marker for the occurrence of arrhythmias. This parameter varies with the heart rate, expressed as the RR interval (time between two successive ventricular depolarizations). To calculate the QT independently of the RR, correction formulae are currently used. In mice, the QT-RR relationship as such has never been studied in conscious animals, and correction formulas are mainly empirical. In the present paper we studied how QT varies when the RR changes physiologically (comparison of nocturnal and diurnal periods) or after dosing mice with tachycardic agents (norepinephrine or nitroprusside). Our results show that there is significant variability of QT and RR in a given condition, resulting in the need to average at least 200 consecutive complexes to accurately compare the QT. Even following this method, no obvious shortening of the QT was observed with increased heart rate, regardless of whether or not this change occurs abruptly. In conclusion, the relationship between QT and RR in mice is weak, which renders the use of correction formulae inappropriate and misleading in this species.
Epigenetically regulated miR-449a enhances hepatitis B virus replication by targeting cAMP-responsive element binding protein 5 and modulating hepatocytes phenotype
Authors: Zhang Xiaoyong , Liu Hongyan , Xie Zhanglian , Deng Wangyu , Wu Chunchen , Qin Bo , Hou Jinlin , Lu Mengji 
Published: May 2016

AbstractCellular microRNAs (miRNAs) are able to influence hepatitis B virus (HBV) replication directly by binding to HBV transcripts or indirectly by targeting cellular factors. Here, we investigate the effect of epigenetically regulated miR-449a on HBV replication and the underlying mechanisms. miR-449a expression was lower in human hepatocellular carcinoma (HCC) cells than in primary hepatocytes and could be induced by trichostatin A. Ectopic miR-449a expression in HCC cells strongly enhanced HBV replication, transcription, progeny virions secretion and antigen expression in a dose-dependent manner. miR-449a directly targeted cAMP-responsive element binding protein 5 (CREB5), which in turn induced the expression of farnesoid X receptor α (FXRα), a transcription factor that facilitates HBV replication. CREB5 knockdown and overexpression demonstrated that it is a negative regulator of HBV replication. Additionally, miR-449a overexpression inhibited proliferation, caused cell cycle arrest and promoted HCC cell differentiation. The results indicated that epigenetically regulated miR-449a targets CREB5 to increase FXRα expression, thereby promoting HBV replication and gene expression. Our findings provide a new understanding of the role of miRNAs in HBV replication.
A clinically applicable molecular classification for high-grade serous ovarian cancer based on hormone receptor expression
Authors: Feng Zheng , Wen Hao , Bi Rui , Ju Xingzhu , Chen Xiaojun , Yang Wentao , Wu Xiaohua 
Published: May 2016

AbstractTo establish an effective hormone receptor-based molecular classification of high-grade serous ovarian cancer (HGSC), we retrospectively examined 875 consecutive HGSC patients who underwent primary surgery at our hospital and constructed tissue microarrays from these specimens. The expression levels of the hormone receptors were as follows: ER 64.4%, PR 12.6%, AR 35.6%, FSHR 54.5%, LHR 34.8%, and GnRHR 88.3%. Based on clustering of their expression patterns, we classified patients into five subgroups with distinctive clinical features (PR+, PR − ER + AR+, PR − ER + AR−, PR − ER − AR+, and PR − ER − AR−). Patients in the PR + group were younger compared to those in the other groups (p < 0.001). More patients were of advanced stage in the PR − ER + AR− group than the other groups (p = 0.020). A greater proportion of patients were sensitive to platinum-based chemotherapy in the PR − ER − AR + group compared with the other groups (p = 0.034). A trend of increasing risk of death was observed among these subgroups (p < 0.001). In the multivariate analysis, patients also had orderly increased hazard ratios for death in the PR + (HR = 2.256, 95% CI, 0.983–5.175), PR − ER + AR + (HR = 2.188, 95% CI, 1.004–4.796), PR − ER − AR− (HR = 2.316, 95% CI, 1.097–5.082) and PR − ER + AR− (HR = 2.928, 95% CI, 1.366–6.276) subgroups compared to the PR − ER − AR+ subgroup. Our classification could help predict patient clinical outcomes, guide individual treatments and stratify patients in future clinical trials.
Sex, offspring and carcass determine antimicrobial peptide expression in the burying beetle
Authors: Jacobs Chris G. C. , Steiger Sandra , Heckel David G. , Wielsch Natalie , Vilcinskas Andreas , Vogel Heiko 
Published: May 2016

AbstractThe burying beetle Nicrophorus vespilloides has emerged as a model system for the investigation of adaptations that allow the utilization of carrion as a diet and as a resource for reproduction. The survival of beetles and their offspring given their exposure to soil-dwelling and cadaver-borne microbes requires mechanisms that reduce bacterial contamination in the diet and that achieve sanitation of the microhabitat. To explore the role of antimicrobial peptides (AMPs) in this context, we analyzed burying beetle males and females at different stages of their breeding cycle using the RNA-Seq and proteomics approaches. To address variation in immune functions, we investigated the impact of adult sex, the presence or absence of offspring (social context), and the presence of carrion (environmental context) on the expression of the identified immune effector genes. We found that particular AMPs are sex-specific and tightly regulated by the presence of a carcass or offspring and identified the two most context-dependent antimicrobial proteins in anal secretions. The context-specific expression dynamics of particular AMPs and lysozymes reveals a complex regulatory system, reflecting adaptations to specific ecological niches. This study highlights how burying beetles cope with microorganisms found on carrion and identifies candidates for both internal and external immunity.
Multi-Order Investigation of the Nonlinear Susceptibility Tensors of Individual Nanoparticles
Authors: Schmidt Cédric , Riporto Jérémy , Uldry Aline , Rogov Andrii , Mugnier Yannick , Dantec Ronan Le , Wolf Jean-Pierre , Bonacina Luigi 
Published: May 2016

AbstractWe use Hyper Rayleigh Scattering and polarization resolved multiphoton microscopy to investigate simultaneously the second and third-order nonlinear response of Potassium Niobate and Bismuth Ferrite harmonic nanoparticles. We first derive the second-to-third harmonic intensity ratio for colloidal ensembles and estimate the average third-order efficiency of these two materials. Successively, we explore the orientation dependent tensorial response of individual nanoparticles fixed on a substrate. The multi-order polarization resolved emission curves are globally fitted with an analytical model to retrieve individual elements of susceptibility tensors.
Surface fractal dimension, water adsorption efficiency and cloud nucleation activity of insoluble aerosol
Authors: Laaksonen Ari , Malila Jussi , Nenes Athanasios , Hung Hui-Ming , Chen Jen-Ping 
Published: May 2016

AbstractSurface porosity affects the ability of a substance to adsorb gases. The surface fractal dimension D is a measure that indicates the amount that a surface fills a space and can thereby be used to characterize the surface porosity. Here we propose a new method for determining D, based on measuring both the water vapour adsorption isotherm of a given substance and its ability to act as a cloud condensation nucleus when introduced to humidified air in aerosol form. We show that our method agrees well with previous methods based on measurement of nitrogen adsorption. Besides proving the usefulness of the new method for general surface characterization of materials, our results show that the surface fractal dimension is an important determinant in cloud drop formation on water insoluble particles. We suggest that a closure can be obtained between experimental critical supersaturation for cloud drop activation and that calculated based on water adsorption data, if the latter is corrected using the surface fractal dimension of the insoluble cloud nucleus.
Financial difficulties but not other types of recent negative life events show strong interactions with 5-HTTLPR genotype in the development of depressive symptoms
Authors: Gonda X , Eszlari N , Kovacs D , Anderson I M , Deakin J F W , Juhasz G , Bagdy G 
Published: May 2016

AbstractSeveral studies indicate that 5-HTTLPR mediates the effect of childhood adversity in the development of depression, while results are contradictory for recent negative life events. For childhood adversity the interaction with genotype is strongest for sexual abuse, but not for other types of childhood maltreatment; however, possible interactions with specific recent life events have not been investigated separately. The aim of our study was to investigate the effect of four distinct types of recent life events in the development of depressive symptoms in a large community sample. Interaction between different types of recent life events measured by the List of Threatening Experiences and the 5-HTTLPR genotype on current depression measured by the depression subscale and additional items of the Brief Symptom Inventory was investigated in 2588 subjects in Manchester and Budapest. Only a nominal interaction was found between life events overall and 5-HTTLPR on depression, which failed to survive correction for multiple testing. However, subcategorising life events into four categories showed a robust interaction between financial difficulties and the 5-HTTLPR genotype, and a weaker interaction in the case of illness/injury. No interaction effect for the other two life event categories was present. We investigated a general non-representative sample in a cross-sectional approach. Depressive symptoms and life event evaluations were self-reported. The 5-HTTLPR polymorphism showed a differential interaction pattern with different types of recent life events, with the strongest interaction effects of financial difficulties on depressive symptoms. This specificity of interaction with only particular types of life events may help to explain previous contradictory findings.