bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective effect of mangiferin on myocardial ischemia-reperfusion injury in streptozotocin-induced diabetic rats: role of AGE-RAGE/MAPK pathways
Authors: Suchal Kapil , Malik Salma , Khan Sana Irfan , Malhotra Rajiv Kumar , Goyal Sameer N. , Bhatia Jagriti , Kumari Santosh , Ojha Shreesh , Arya Dharamvir Singh 
Published: February 2017

AbstractHyperglycemia induced advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) activation is thought to involve in the development of cardiovascular disease in diabetics. Activation of AGE-RAGE axis results in the oxidative stress and inflammation. Mangiferin is found in the bark of mango tree and is known to treat diseases owing to its various biological activities. Thus, this study was designed to evaluate the effect of mangiferin in ischemia-reperfusion (IR) induced myocardial injury in diabetic rats. A single injection of STZ (70 mg/kg; i.p.) was injected to male albino Wistar rats to induce diabetes. After confirmation of diabetes, rats were administered vehicle (2 ml/kg; i.p.) and mangiferin (40 mg/kg; i.p.) for 28 days. On 28th day, left anterior descending coronary artery was ligated for 45 min and then reperfused for 60 min. Mangiferin treatment significantly improved cardiac function, restored antioxidant status, reduced inflammation, apoptosis and maintained myocardial architecture. Furthermore, mangiferin significantly inhibited the activation of AGE-RAGE axis, c-Jun N-terminal kinase (JNK) and p38 and increased the expression of extracellular regulated kinase 1/2 (ERK1/2) in the myocardium. Thus, mangiferin attenuated IR injury in diabetic rats by modulation of AGE-RAGE/MAPK pathways which further prevented oxidative stress, inflammation and apoptosis in the myocardium.
Differences in the transcriptome of medullary thyroid cancer regarding the status and type of RET gene mutations
Authors: Oczko-Wojciechowska Malgorzata , Swierniak Michal , Krajewska Jolanta , Kowalska Malgorzata , Kowal Monika , Stokowy Tomasz , Wojtas Bartosz , Rusinek Dagmara , Pawlaczek Agnieszka , Czarniecka Agnieszka , Szpak-Ulczok Sylwia , Gawlik Tomasz , Chmielik Ewa , Tyszkiewicz Tomasz , Nikiel Barbara , Lange Dariusz , Jarzab Michal , Wiench Malgorzata , Jarzab Barbara 
Published: February 2017

AbstractMedullary thyroid cancer (MTC) can be caused by germline mutations of theRETproto-oncogene or occurs as a sporadic form. It is well known thatRETmutations affecting the cysteine-rich region of the protein (MEN2A-like mutations) are correlated with different phenotypes than those in the kinase domain (MEN2B-like mutations). Our aim was to analyse the whole-gene expression profile of MTC with regard to the type ofRETgene mutation and the cancer genetic background (hereditary vs sporadic). We studied 86 MTC samples. We demonstrated that there were no distinct differences in the gene expression profiles of hereditary and sporadic MTCs. This suggests a homogeneous nature of MTC. We also noticed that the site of theRETgene mutation slightly influenced the gene expression profile of MTC. We found a significant association between the localization ofRETmutations and the expression of three genes:NNAT(suggested to be a tumour suppressor gene),CDC14B(involved in cell cycle control) andNTRK3(tyrosine receptor kinase that undergoes rearrangement in papillary thyroid cancer). This study suggests that these genes are significantly deregulated in tumours with MEN2A-like and MEN2B-like mutations; however, further investigations are necessary to demonstrate any clinical impact of these findings.
Using information of relatives in genomic prediction to apply effective stratified medicine
Authors: Lee S. Hong , Weerasinghe W. M. Shalanee P. , Wray Naomi R. , Goddard Michael E. , van der Werf Julius H. J. 
Published: February 2017

AbstractGenomic prediction shows promise for personalised medicine in which diagnosis and treatment are tailored to individuals based on their genetic profiles for complex diseases. We present a theoretical framework to demonstrate that prediction accuracy can be improved by targeting more informative individuals in the data set used to generate the predictors (“discovery sample”) to include those with genetically close relationships with the subjects put forward for risk prediction. Increase of prediction accuracy from closer relationships is achieved under an additive model and does not rely on any family or interaction effects. Using theory, simulations and real data analyses, we show that the predictive accuracy or the area under the receiver operating characteristic curve (AUC) increased exponentially with decreasing effective size (Ne), i.e. when individuals are closely related. For example, with the sample size of discovery set N = 3000, heritability h2 = 0.5 and population prevalence K = 0.1, AUC value approached to 0.9 and the top percentile of the estimated genetic profile scores had 23 times higher proportion of cases than the general population. This suggests that there is considerable room to increase prediction accuracy by using a design that does not exclude closer relationships.
Open-source algorithm for automatic choroid segmentation of OCT volume reconstructions
Authors: Mazzaferri Javier , Beaton Luke , Hounye Gisèle , Sayah Diane N. , Costantino Santiago 
Published: February 2017

AbstractThe use of optical coherence tomography (OCT) to study ocular diseases associated with choroidal physiology is sharply limited by the lack of available automated segmentation tools. Current research largely relies on hand-traced, single B-Scan segmentations because commercially available programs require high quality images, and the existing implementations are closed, scarce and not freely available. We developed and implemented a robust algorithm for segmenting and quantifying the choroidal layer from 3-dimensional OCT reconstructions. Here, we describe the algorithm, validate and benchmark the results, and provide an open-source implementation under the General Public License for any researcher to use (https://www.mathworks.com/matlabcentral/fileexchange/61275-choroidsegmentation).
Analysis of drought-responsive signalling network in two contrasting rice cultivars using transcriptome-based approach
Authors: Borah Pratikshya , Sharma Eshan , Kaur Amarjot , Chandel Girish , Mohapatra Trilochan , Kapoor Sanjay , Khurana Jitendra P. 
Published: February 2017

AbstractTraditional cultivars of rice in India exhibit tolerance to drought stress due to their inherent genetic variations. Here we present comparative physiological and transcriptome analyses of two contrasting cultivars, drought tolerant Dhagaddeshi (DD) and susceptible IR20. Microarray analysis revealed several differentially expressed genes (DEGs) exclusively in DD as compared to IR20 seedlings exposed to 3 h drought stress. Physiologically, DD seedlings showed higher cell membrane stability and differential ABA accumulation in response to dehydration, coupled with rapid changes in gene expression. Detailed analyses of metabolic pathways enriched in expression data suggest interplay of ABA dependent along with secondary and redox metabolic networks that activate osmotic and detoxification signalling in DD. By co-localization of DEGs with QTLs from databases or published literature for physiological traits of DD and IR20, candidate genes were identified including those underlying major QTL qDTY1.1 in DD. Further, we identified previously uncharacterized genes from both DD and IR20 under drought conditions including OsWRKY51, OsVP1 and confirmed their expression by qPCR in multiple rice cultivars. OsFBK1 was also functionally validated in susceptible PB1 rice cultivar and Arabidopsis for providing drought tolerance. Some of the DEGs mapped to the known QTLs could thus, be of potential significance for marker-assisted breeding.
Non-patchy strategy for inter-atomic distances from Extended X-ray Absorption Fine Structure
Authors: Xu Gu , Li Guifang , LI Xianya , Liang Yi , Feng Zhechuan 
Published: February 2017

AbstractExtended X-ray Absorption Fine Structure (EXAFS) has been one of the few structural probes available for crystalline, non-crystalline and even highly disordered specimens. However, the data analysis involves a patchy and tinkering process, including back-and-forth fitting and filtering, leading to ambiguous answers sometimes. Here we try to resolve this long standing problem, to extract the inter-atomic distances from the experimental data by a single step minimization, in order to replace the tedious and tinkering process. The new strategy is built firmly by the mathematical logic, and made straightforward and undeniable. The finding demonstrates that it is possible to break off from the traditional patchy model fitting, and to remove the logical confusion of a priori prediction of the structure to be matched with experimental data, making it a much more powerful technique than the existing methods. The new method is expected to benefit EXAFS users covering all disciplines. Also, it is anticipated that the current work to be the motivation and inspiration to the further efforts.
Bigelovin triggered apoptosis in colorectal cancer in vitro and in vivo via upregulating death receptor 5 and reactive oxidative species
Authors: Li Mingyue , Song Li-Hua , Yue Grace Gar-Lee , Lee Julia Kin-Ming , Zhao Li-Mei , Li Lin , Zhou Xunian , Tsui Stephen Kwok-Wing , Ng Simon Siu-Man , Fung Kwok-Pui , Tan Ning-Hua , Lau Clara Bik-San 
Published: February 2017

AbstractColorectal cancer (CRC) is the third most prevalent cancer and the third highest cancer-related mortality in the United States. Bigelovin, a sesquiterpene lactone isolated from Inula helianthus aquatica, has been proven to induce apoptosis and exhibit anti-inflammatory and anti-angiogenic activities. However, the effects of bigelovin on CRC and underlying mechanisms have not been explored. The present study demonstrated that bigelovin exhibited potent anti-tumor activities against CRC in vitro and in vivo. Bigelovin suppressed cell proliferation and colony formation and induced apoptosis in human colorectal cancer HT-29 and HCT 116 cells in vitro. Results also revealed that bigelovin activated caspases, caused the G2/M cell cycle arrest and induced DNA damage through up-regulation of death receptor (DR) 5 and increase of ROS. In HCT 116 xenograft model, bigelovin treatment resulted in suppression of tumor growth. Bigelovin at 20 mg/kg showed more significant tumor suppression and less side effects than conventional FOLFOX (containing folinic acid, 5-fluorouracil and oxaliplatin) treatment. In addition, in vivo data confirmed that anti-tumor activity of bigelovin in CRC was through induction of apoptosis by up-regulating DR5 and increasing ROS. In conclusion, these results strongly suggested that bigelovin has potential to be developed as therapeutic agent for CRC patients.
High expression of AKR1B10 predicts low risk of early tumor recurrence in patients with hepatitis B virus-related hepatocellular carcinoma
Authors: Wang Yan-Yan , Qi Lu-Nan , Zhong Jian-Hong , Qin Hong-Gui , Ye Jia-Zhou , Lu Shi-Dong , Ma Liang , Xiang Bang-De , Li Le-Qun , You Xue-Mei 
Published: February 2017

AbstractTo clarify the relationship between aldo-keto reductase family 1 member B10 (AKR1B10) expression and early hepatocellular carcinoma (HCC) recurrence, this study detected AKR1B10 expression in tumor and adjacent non-tumor tissues from 110 patients with hepatitis B virus (HBV)-related HCC underwent liver resection and analyzed its correlations with clinicopathological characteristics and prognosis of these patients. Detected by quantitative reverse transcription polymerase chain reaction, AKR1B10 mRNA expression showed significantly higher in HCC tissues than in adjacent non-tumor tissues, with a low level in normal liver tissues. Similar results was confirmed at the protein level using immunohistochemistry and Western blotting. High AKR1B10 expression was negatively correlated with serum alpha-fetoprotein level and positively correlated with HBV-DNA level. Patients with high AKR1B10 expression had significantly higher disease-free survival than those with low expression within 2 years after liver resection. Multivariate analysis also confirmed high AKR1B10 expression to be a predictor of low risk of early HCC recurrence. In addition, high AKR1B10 expression was found to be a favorable factor of overall survival. These results suggest that AKR1B10 is involved in HBV-related hepatocarcinogenesis, but its high expression could predict low risk of early tumor recurrence in patients with HBV-related HCC after liver resection.
Effects of Taxol on Regeneration in a Rat Sciatic Nerve Transection Model
Authors: Hsu Shih-Tien , Yao Chun-Hsu , Hsu Yuan-Man , Lin Jia-Horng , Chen Yung-Hsiang , Chen Yueh-Sheng 
Published: February 2017

AbstractRecent studies describe taxol as a candidate treatment for promoting central nerve regeneration. However, taxol has serious side effects including peripheral neurotoxicity, and little information is known about the effect of taxol on peripheral nerve regeneration. We investigated the effects of taxol on regeneration in a rat sciatic nerve transection model. Rats were divided into four groups (n = 10): normal saline (i.p.) as the control, Cremophor EL vehicle, and 2 or 6 mg/kg of taxol in the Cremophor EL solution (four times in day-2, 4, 6, and 8), respectively. We evaluated neuronal electrophysiology, animal behaviour, neuronal connectivity, macrophage infiltration, location and expression levels of calcitonin gene-related peptide (CGRP), and expression levels of both nerve growth factors and immunoregulatory factors. In the high-dose taxol group (6 mg/kg), neuronal electrophysiological function was significantly impaired. Licking latencies were significantly changed while motor coordination was unaffected. Neuronal connectivity, macrophage density, and expression levels of CGRP was dramatically reduced. Expression levels of nerve growth factors and immunoregulatory factors was also reduced, while it was increased in the low-dose taxol group (2 mg/kg). These results indicate that taxol can modulate local inflammatory conditions, impair nerve regeneration, and impede recovery of a severe peripheral nerve injury.
Predictive Modeling of Physician-Patient Dynamics That Influence Sleep Medication Prescriptions and Clinical Decision-Making
Authors: Beam Andrew L. , Kartoun Uri , Pai Jennifer K. , Chatterjee Arnaub K. , Fitzgerald Timothy P. , Shaw Stanley Y. , Kohane Isaac S. 
Published: February 2017

AbstractInsomnia remains under-diagnosed and poorly treated despite its high economic and social costs. Though previous work has examined how patient characteristics affect sleep medication prescriptions, the role of physician characteristics that influence this clinical decision remains unclear. We sought to understand patient and physician factors that influence sleep medication prescribing patterns by analyzing Electronic Medical Records (EMRs) including the narrative clinical notes as well as codified data. Zolpidem and trazodone were the most widely prescribed initial sleep medication in a cohort of 1,105 patients. Some providers showed a historical preference for one medication, which was highly predictive of their future prescribing behavior. Using a predictive model (AUC = 0.77), physician preference largely determined which medication a patient received (OR = 3.13; p = 3 × 10−37). In addition to the dominant effect of empirically determined physician preference, discussion of depression in a patient’s note was found to have a statistically significant association with receiving a prescription for trazodone (OR = 1.38, p = 0.04). EMR data can yield insights into physician prescribing behavior based on real-world physician-patient interactions.
Ultra-wideband, Wide Angle and Polarization-insensitive Specular Reflection Reduction by Metasurface based on Parameter-adjustable Meta-Atoms
Authors: Su Jianxun , Lu Yao , Zhang Hui , Li Zengrui , Yang Yaoqing , Che Yongxing , Qi Kainan 
Published: February 2017

AbstractIn this paper, an ultra-wideband, wide angle and polarization-insensitive metasurface is designed, fabricated, and characterized for suppressing the specular electromagnetic wave reflection or backward radar cross section (RCS). Square ring structure is chosen as the basic meta-atoms. A new physical mechanism based on size adjustment of the basic meta-atoms is proposed for ultra-wideband manipulation of electromagnetic (EM) waves. Based on hybrid array pattern synthesis (APS) and particle swarm optimization (PSO) algorithm, the selection and distribution of the basic meta-atoms are optimized simultaneously to obtain the ultra-wideband diffusion scattering patterns. The metasurface can achieve an excellent RCS reduction in an ultra-wide frequency range under x- and y-polarized normal incidences. The new proposed mechanism greatly extends the bandwidth of RCS reduction. The simulation and experiment results show the metasurface can achieve ultra-wideband and polarization-insensitive specular reflection reduction for both normal and wide-angle incidences. The proposed methodology opens up a new route for realizing ultra-wideband diffusion scattering of EM wave, which is important for stealth and other microwave applications in the future.
Developmental stage-dependent effects of cardiac fibroblasts on function of stem cell-derived engineered cardiac tissues
Authors: Liau Brian , Jackman Christopher P. , Li Yanzhen , Bursac Nenad 
Published: February 2017

AbstractWe investigated whether the developmental stage of mouse cardiac fibroblasts (CFs) influences the formation and function of engineered cardiac tissues made of mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs). Engineered cardiac tissue patches were fabricated by encapsulating pure mESC-CMs, mESC-CMs + adult CFs, or mESC-CMs + fetal CFs in fibrin-based hydrogel. Tissue patches containing fetal CFs exhibited higher velocity of action potential propagation and contractile force amplitude compared to patches containing adult CFs, while pure mESC-CM patches did not form functional syncytium. The functional improvements in mESC-CM + fetal CF patches were associated with differences in structural remodeling and increased expression of proteins involved in cardiac function. To determine role of paracrine signaling, we cultured pure mESC-CMs within miniature tissue “micro-patches” supplemented with media conditioned by adult or fetal CFs. Fetal CF-conditioned media distinctly enhanced CM spreading and contractile activity, which was shown by pathway inhibitor experiments and Western blot analysis to be mediated via MEK-ERK signaling. In mESC-CM monolayers, CF-conditioned media did not alter CM spreading or MEK-ERK activation. Collectively, our studies show that 3D co-culture of mESC-CMs with embryonic CFs is superior to co-culture with adult CFs for in vitro generation of functional myocardium. Ensuring consistent developmental stages of cardiomyocytes and supporting non-myocytes may be a critical factor for promoting functional maturation of engineered cardiac tissues.
An air-liquid interphase approach for modeling the early embryo-maternal contact zone
Authors: Chen S. , Palma-Vera S. E. , Langhammer M. , Galuska S. P. , Braun B. C. , Krause E. , Lucas-Hahn A. , Schoen J. 
Published: February 2017

AbstractWe developed an air-liquid interphase culture procedure for mammalian oviduct epithelial cells leading to the formation of functional epithelial tissues, which generate oviduct fluid surrogates. These in vitro oviduct epithelia can be co-cultured with living zygotes and enable embryonic development up to the blastocyst stage without addition of embryo culture medium. The described strategy is broadly applicable to analyze early embryo-maternal interactions under standardized in vitro conditions.
Structural variability of E. coli thioredoxin captured in the crystal structures of single-point mutants
Authors: Noguera Martín E. , Vazquez Diego S. , Ferrer-Sueta Gerardo , Agudelo William A. , Howard Eduardo , Rasia Rodolfo M. , Manta Bruno , Cousido-Siah Alexandra , Mitschler André , Podjarny Alberto , Santos Javier 
Published: February 2017

AbstractThioredoxin is a ubiquitous small protein that catalyzes redox reactions of protein thiols. Additionally, thioredoxin from E. coli (EcTRX) is a widely-used model for structure-function studies. In a previous paper, we characterized several single-point mutants of the C-terminal helix (CTH) that alter global stability of EcTRX. However, spectroscopic signatures and enzymatic activity for some of these mutants were found essentially unaffected. A comprehensive structural characterization at the atomic level of these near-invariant mutants can provide detailed information about structural variability of EcTRX. We address this point through the determination of the crystal structures of four point-mutants, whose mutations occurs within or near the CTH, namely L94A, E101G, N106A and L107A. These structures are mostly unaffected compared with the wild-type variant. Notably, the E101G mutant presents a large region with two alternative traces for the backbone of the same chain. It represents a significant shift in backbone positions. Enzymatic activity measurements and conformational dynamics studies monitored by NMR and molecular dynamic simulations show that E101G mutation results in a small effect in the structural features of the protein. We hypothesize that these alternative conformations represent samples of the native-state ensemble of EcTRX, specifically the magnitude and location of conformational heterogeneity.
The Multiple Roles of Small-Angle Tilt Grain Boundaries in Annihilating Radiation Damage in SiC
Authors: Jiang Hao , Wang Xing , Szlufarska Izabela 
Published: February 2017

AbstractLattice defects generated by radiation damage can diffuse to grain boundaries (GBs) and be annihilated at GBs. However, the precise role of GBs in annihilating the segregated defects remains unclear. Here, we employed multi-scale models to determine how interstitials are annihilated at small-angle tilt GBs (STGBs) in SiC. First of all, we found the pipe diffusion of interstitials in STGBs is slower than bulk diffusion. This is because the increased interatomic distance at dislocation cores raises the migration barrier of interstitial dumbbells. Furthermore, we found both the annihilation of interstitials at jogs and jog nucleation from clusters are diffusion-controlled and can occur under off-stoichiometric interstitial fluxes. Finally, a dislocation line model is developed to predict the role of STGBs in annihilating radiation damage. This model includes defect flux to GBs, pipe diffusion in STGBs, and the interaction of defects with jogs. The model predicts the role of STGBs in annihilating defects depends on the rate of defects segregation to and diffusion along STGBs. STGBs mainly serve as diffusion channel for defects to reach other sinks when defect diffusivity is high at boundaries. When defect diffusivity is low, most of the defects segregated to STGBs are annihilated by dislocation climb.
High-power dual-wavelength Ho-doped fiber laser at >2 μm tandem pumped by a 1.15 μm fiber laser
Authors: Jin Xiaoxi , Lou Zhaokai , Chen Yizhu , Zhou Pu , Zhang Hanwei , Xiao Hu , Liu Zejin 
Published: February 2017

AbstractWe demonstrated a high-power continuous-wave (CW) dual-wavelength Ho-doped fiber laser (HDFL) at 2049 nm and 2153 nm with a simple coupled-cavity configuration. A ~100 W laser diode-pumped fiber laser at 1150 nm served as the pump source. The maximum output power reached ~22.3 W and the slope efficiency was 23%. By altering the incident pump power, the power ratio of two signal wavelengths could be tuned in a large range due to gain competition. As far as we know, this is the first CW dual-wavelength HDFL with the power exceeding ten-watt-level, and the first dual-wavelength HDFL with the central wavelengths exceeding 2.0 μm and 2.15 μm respectively.