bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphorylation of NuMA by Aurora‐A kinase in PC‐3 prostate cancer cells affects proliferation, survival, and interphase NuMA localization
Authors: Toughiri Raheleh , Li Xiang , Du Quansheng , Bieberich Charles J. 
Published: October 2012

AbstractAurora‐A is a serine/threonine kinase that has oncogenic properties in vivo. The expression and kinase activity of Aurora‐A are up‐regulated in multiple malignancies. Aurora‐A is a key regulator of mitosis that localizes to the centrosome from the G2 phase through mitotic exit and regulates mitotic spindle formation as well as centrosome separation. Overexpression of Aurora‐A in multiple malignancies has been linked to higher tumor grade and poor prognosis through mechanisms that remain to be defined. Using an unbiased proteomics approach, we identified the protein nuclear mitotic apparatus (NuMA) as a robust substrate of Aurora‐A kinase. Using a small molecule Aurora‐A inhibitor in conjunction with a reverse in‐gel kinase assay (RIKA), we demonstrate that NuMA becomes hypo‐phosphorylated in vivo upon Aurora‐A inhibition. Using an alanine substitution strategy, we identified multiple Aurora‐A phospho‐acceptor sites in the C‐terminal tail of NuMA. Functional analyses demonstrate that mutation of three of these phospho‐acceptor sites significantly diminished cell proliferation. In addition, alanine mutation at these sites significantly increased the rate of apoptosis. Using confocal immunofluorescence microscopy, we show that the NuMA T1804A mutant mis‐localizes to the cytoplasm in interphase nuclei in a punctate pattern. The identification of Aurora‐A phosphorylation sites in NuMA that are important for cell cycle progression and apoptosis provides new insights into Aurora‐A function. J. Cell. Biochem. 114: 823–830, 2013. © 2012 Wiley Periodicals, Inc.
Sodium valproate potentiates staurosporine‐induced apoptosis in neuroblastoma cells via Akt/survivin independently of HDAC inhibition
Authors: Shah Reecha D. , Jagtap Jayashree C. , Mruthyunjaya S. , Shelke Ganesh V. , Pujari Radha , Das Gowry , Shastry Padma 
Published: October 2012

AbstractSodium valproate (VPA) has been recently identified as a selective class I histone deacetylase (HDAC) inhibitor and explored for its potential as an anti‐cancer agent. The anti‐cancer properties of VPA are generally attributed to its HDAC inhibitory activity indicating a clear overlap of these two actions, but the underlying mechanisms of its anti‐tumor effects are not clearly elucidated. The present study aimed to delineate the molecular mechanism of VPA in potentiating cytotoxic effects of anti‐cancer drugs with focus on inhibition of HDAC activity. Using human neuroblastoma cell lines, SK‐N‐MC, SH‐SY5Y, and SK‐N‐SH, we show that non‐toxic dose (2 mM) of VPA enhanced staurosporine (STS)‐induced cell death as assessed by MTT assay, PARP cleavage, hypodiploidy, and caspase 3 activity. Mechanistically, the effect of VPA was mediated by down regulation of survivin, an anti‐apoptotic protein crucial in resistance to STS‐mediated cytotoxicity, through Akt pathway. Knock down of class I HDAC isoforms remarkably inhibited HDAC activity comparable with that of VPA but had no effect on STS‐induced apoptosis. Moreover, MS‐275, a structurally distinct class I HDAC inhibitor did not affect STS‐mediated apoptosis, nor decrease the levels of survivin and Akt. Valpromide (VPM), an amide analog of VPA that does not inhibit HDAC also potentiated cell death in NB cells associated with decreased survivin and Akt levels suggesting that HDAC inhibition might not be crucial for STS‐induced apoptosis. The study provides new information on the possible molecular mechanism of VPA in apoptosis that can be explored in combination therapy in cancer. J. Cell. Biochem. 114: 854–863, 2013. © 2012 Wiley Periodicals, Inc.
Exendin‐4 inhibits iNOS expression at the protein level in LPS‐stimulated Raw264.7 macrophage by the activation of cAMP/PKA pathway
Authors: Chang Seo‐Yoon , Kim Dong‐Bin , Ryu Gyeong Ryul , Ko Seung‐Hyun , Jeong In‐Kyung , Ahn Yu‐Bae , Jo Yang‐Hyeok , Kim Myung‐Jun 
Published: October 2012

AbstractGlucagon‐like peptide‐1 (GLP‐1) and its potent agonists have been widely studied in pancreatic islet β‐cells. However, GLP‐1 receptors are present in many extrapancreatic tissues including macrophages, and thus GLP‐1 may have diverse actions in these tissues and cells. Therefore, we examined the mechanism by which exendin‐4 (EX‐4), a potent GLP‐1 receptor agonist, inhibits lipopolysaccharide (LPS)‐induced iNOS expression in Raw264.7 macrophage cells. EX‐4 significantly inhibited LPS‐induced iNOS protein expression and nitrite production. However, Northern blot and promoter analyses demonstrated that EX‐4 did not inhibit LPS‐induced iNOS mRNA expression and iNOS promoter activity. Electrophoretic mobility shift assay (EMSA) showed that EX‐4 did not alter the binding activity of NF‐κB to the iNOS promoter. Consistent with the result of EMSA, LPS‐induced IκBα phosphorylation and nuclear translocation of p65 were not inhibited by EX‐4. Also, actinomycin D chase study and the promoter assay using the construct containing 3′‐untranslated region of iNOS showed that EX‐4 did not affect iNOS mRNA stability. Meanwhile, cycloheximide chase study demonstrated that EX‐4 significantly accelerated iNOS protein degradation. The EX‐4 inhibition of LPS‐induced iNOS protein was significantly reversed by adenylate cyclase inhibitors (MDL‐12330A and SQ 22536), a PKA inhibitor (H‐89) and PKAα gene silencing. These findings suggest that EX‐4 inhibited LPS‐induced iNOS expression at protein level, but not at transcriptional mechanism of iNOS gene and this inhibitory effect of EX‐4 was mainly dependent on cAMP/PKA system. J. Cell. Biochem. 114: 844–853, 2013. © 2012 Wiley Periodicals, Inc.
Stem cells as promising therapeutic options for neurological disorders
Authors: Yoo Jongman , Kim Han‐Soo , Hwang Dong‐Youn 
Published: October 2012

AbstractDue to the limitations of pharmacological and other current therapeutic strategies, stem cell therapies have emerged as promising options for treating many incurable neurologic diseases. A variety of stem cells including pluripotent stem cells (i.e., embryonic stem cells and induced pluripotent stem cells) and multipotent adult stem cells (i.e., fetal brain tissue, neural stem cells, and mesenchymal stem cells from various sources) have been explored as therapeutic options for treating many neurologic diseases, and it is becoming obvious that each type of stem cell has pros and cons as a source for cell therapy. Wise selection of stem cells with regard to the nature and status of neurologic dysfunctions is required to achieve optimal therapeutic efficacy. To this aim, the stem cell‐mediated therapeutic efforts on four major neurological diseases, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and stroke, will be introduced, and current problems and future directions will be discussed. J. Cell. Biochem. 114: 743–753, 2013. © 2012 Wiley Periodicals, Inc.
Multilayer appearance on contrast‐enhanced susceptibility‐weighted images on patients with brain abscesses: Possible origins and effects of postprocessing
Authors: Chang Hing‐Chiu , Chuang Tzu‐Chao , Chung Hsiao‐Wen , Lin Huey‐Shyan , Lai Ping‐Hong , Weng Mei‐Jui , Fu Jui‐Hsun , Wang Po‐Chin , Li Shang‐Chieh , Pan Huay‐Ben 
Published: October 2012

AbstractPurpose:To demonstrate the presence of a multilayer appearance of the capsule on contrast‐enhanced (CE) susceptibility‐weighted imaging (SWI) in patients with pyogenic brain abscesses. Possible origins for the appearance and effects of postprocessing settings are discussed.Materials and Methods:Fourteen patients with pyogenic brain abscesses underwent post gadolinium‐enhanced SWI at 1.5 T. All SWI images were postprocessed with various filter and mask settings to compare the image appearance. Computer simulations using a paramagnetic spherical shell model were performed to verify the clinical findings.Results:Pyogenic brain abscesses demonstrated a multilayer appearance with a darkened ring within the enhanced capsule on CE‐SWI in all patients. The multilayer appearance was slice‐orientation‐dependent, decreased with larger widths of the high‐pass filter, and increased with larger numbers of phase mask multiplication operations, consistently on both simulation results and the clinical images.Conclusion:CE‐SWI shows the multilayer appearance of the capsule in pyogenic brain abscesses, which may arise from postprocessing procedures originally designed to enhance susceptibility contrast. Although SWI may provide additional information valuable in the diagnosis of pyogenic brain abscesses, image interpretation should be exercised with caution, particularly for CE‐SWI. J. Magn. Reson. Imaging 2012; 36:1353–1361. © 2012 Wiley Periodicals, Inc.
High performance of a new PCR‐based urine assay for HPV‐DNA detection and genotyping
Authors: Tanzi Elisabetta , Bianchi Silvia , Fasolo Maria Michela , Frati Elena R. , Mazza Francesca , Martinelli Marianna , Colzani Daniela , Beretta Rosangela , Zappa Alessandra , Orlando Giovanna 
Published: October 2012

AbstractHuman papillomavirus (HPV) testing has been proposed as a means of replacing or supporting conventional cervical screening (Pap test). However, both methods require the collection of cervical samples. Urine sample is easier and more acceptable to collect and could be helpful in facilitating cervical cancer screening. The aim of this study was to evaluate the sensitivity and specificity of urine testing compared to conventional cervical smear testing using a PCR‐based method with a new, designed specifically primer set. Paired cervical and first voided urine samples collected from 107 women infected with HIV were subjected to HPV‐DNA detection and genotyping using a PCR‐based assay and a restriction fragment length polymorphism method. Sensitivity, specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) were calculated using the McNemar's test for differences. Concordance between tests was assessed using the Cohen's unweighted Kappa (k). HPV DNA was detected in 64.5% (95% CI: 55.1–73.1%) of both cytobrush and urine samples. High concordance rates of HPV‐DNA detection (k = 0.96; 95% CI: 0.90–1.0) and of high risk‐clade and low‐risk genotyping in paired samples (k = 0.80; 95% CI: 0.67–0.92 and k = 0.74; 95% CI: 0.60–0.88, respectively) were observed. HPV‐DNA detection in urine versus cervix testing revealed a sensitivity of 98.6% (95% CI: 93.1–99.9%) and a specificity of 97.4% (95% CI: 87.7–99.9%), with a very high NPV (97.4%; 95% CI: 87.7–99.9%). The PCR‐based assay utilized in this study proved highly sensitive and specific for HPV‐DNA detection and genotyping in urine samples. These data suggest that a urine‐based assay would be a suitable and effective tool for epidemiological surveillance and, most of all, screening programs. J. Med. Virol. 85:91–98, 2012. © 2012 Wiley Periodicals, Inc.
Human metapneumovirus associated with community‐acquired pneumonia in children in Beijing, China
Authors: Lu Guilan , Li Jianguo , Xie Zhengde , Liu Chunyan , Guo Li , Vernet Guy , Shen Kunling , Wang Jianwei 
Published: October 2012

AbstractCommunity‐acquired pneumonia is a major cause of morbidity and mortality in children worldwide. However, few studies have been conducted on the infection of human metapneumovirus (hMPV) associated with pediatric community‐acquired pneumonia in China. Nasopharyngeal aspirates were collected between July 2008 and June 2010 from 1,028 children, aged ≤16.5 years, who were diagnosed with community‐acquired pneumonia in Beijing, China. Reverse‐transcriptase polymerase chain reaction was used to screen the samples for hMPV and common respiratory viruses. hMPV was detected in 6.3% of the patients with community‐acquired pneumonia. This detection rate is the third highest for a respiratory virus in children with community‐acquired pneumonia, after that of rhinovirus (30.9%) and respiratory syncytial virus (30.7%). The detection rate of hMPV in 2008/2009 (42/540, 7.8%) was significantly higher than in 2009/2010 (23/488, 4.7%; χ2 = 4.065, P = 0.044). The hMPV subtypes A2, B1, and B2 were found to co‐circulate, with A2 being most prevalent. These results indicate that hMPV plays a substantial role in pediatric community‐acquired pneumonia in China. Overall, these findings provide a better understanding of the epidemiological and clinical features of hMPV infections. J. Med. Virol. 85:138–143, 2012. © 2012 Wiley Periodicals, Inc.
In vivo implant fixation of carbon fiber‐reinforced PEEK hip prostheses in an ovine model
Authors: Nakahara Ichiro , Takao Masaki , Bandoh Shunichi , Bertollo Nicky , Walsh William R , Sugano Nobuhiko 
Published: October 2012

AbstractCarbon fiber‐reinforced polyetheretherketone (CFR/PEEK) is theoretically suitable as a material for use in hip prostheses, offering excellent biocompatibility, mechanical properties, and the absence of metal ions. To evaluate in vivo fixation methods of CFR/PEEK hip prostheses in bone, we examined radiographic and histological results for cementless or cemented CFR/PEEK hip prostheses in an ovine model with implantation up to 52 weeks. CFR/PEEK cups and stems with rough‐textured surfaces plus hydroxyapatite (HA) coatings for cementless fixation and CFR/PEEK cups and stems without HA coating for cement fixation were manufactured based on ovine computed tomography (CT) data. Unilateral total hip arthroplasty was performed using cementless or cemented CFR/PEEK hip prostheses. Five cementless cups and stems and six cemented cups and stems were evaluated. On the femoral side, all cementless stems demonstrated bony ongrowth fixation and all cemented stems demonstrated stable fixation without any gaps at both the bone‐cement and cement‐stem interfaces. All cementless cases and four of the six cemented cases showed minimal stress shielding. On the acetabular side, two of the five cementless cups demonstrated bony ongrowth fixation. Our results suggest that both cementless and cemented CFR/PEEK stems work well for fixation. Cup fixation may be difficult for both cementless and cemented types in this ovine model, but bone ongrowth fixation on the cup was first seen in two cementless cases. Cementless fixation can be achieved using HA‐coated CFR/PEEK implants, even under load‐bearing conditions. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 485–492, 2013
Mechanical effectiveness of lateral foot wedging in medial knee osteoarthritis after 1 year of wear
Authors: Barrios Joaquin A. , Butler Robert J. , Crenshaw Jeremy R. , Royer Todd D. , Davis Irene S. 
Published: October 2012

AbstractThe use of lateral foot wedging in the management of medial knee osteoarthritis is under scrutiny. Interestingly, there have been minimal efforts to evaluate biomechanical effectiveness with long‐term use. Therefore, we aimed to evaluate dynamic knee loading (assessed using the knee adduction moment) and other secondary gait parameters in patients with medial knee osteoarthritis wearing lateral foot wedging at a baseline visit and after 1 year of wear. Three‐dimensional gait data were captured in an intervention group of 19 patients with symptomatic medial knee osteoarthritis wearing their prescribed laterally wedged foot orthoses at 0 and 12 months. Wedge amounts were prescribed based on symptom response to a step‐down test. A control group of 19 patients wearing prescribed neutral orthoses were also captured at 0 and 12 months. The gait of the intervention group wearing neutral orthoses was additionally captured. Walking speed and shoes were controlled. Analyses of variance were conducted to examine for group‐by‐time (between the groups in their prescribed orthoses) and condition‐by‐time (within the intervention group) interactions, main effects, and simple effects. We observed increased knee adduction moments and frontal plane motion over time in the control group but not the intervention group. Further, within the intervention group, the mechanical effectiveness of the lateral wedging did not decrease. In patients with medial knee osteoarthritis, the effects of lateral foot wedging on pathomechanics associated with medial knee osteoarthritis were favorable and sustained over time. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 659–664, 2013
Radically Crosslinkable Poly(acrylic acid)s From Poly[(tert‐butyl acrylate)‐co‐(3‐aminopropyl vinyl ether)]: Synthesis and Rheological Properties
Authors: Maier Maximilian , Dollendorf Christian , Ritter Helmut , Klee Joachim E. 
Published: October 2012

AbstractAcrylic acid copolymers bearing radically polymerizable methacrylic and itaconic moieties are synthesized. Starting from copolymers of tBA and APVE, prepared at different ratios, methacrylic or itaconic amides are obtained via polymer‐analogous reaction. After acidic elimination of isobutylene, polymers with free carbon acids and staggered reactivity can be prepared. Varying amounts of attached acrylamide moieties allow the adjustment of network densities. Rheological properties in HEMA/water matrices during curing are evaluated.
Antidepressant use, serotonin transporter affinity, and reinfarction among patients receiving clopidogrel: a population‐based study
Authors: Fnais Naif , Alshaikh Mashael , Yao Zhan , Gomes Tara , Juurlink David , Mamdani Muhammad 
Published: October 2012

ABSTRACTPurposeConflicting evidence exists regarding the association between antidepressant use and reinfarction among high‐risk cardiovascular patients. Recent evidence suggests that clinical benefit associated with antidepressants may be related to serotonergic activity, suggesting that some antidepressants may offer greater advantages than others.MethodsWe conducted a population‐based nested case–control study among patients aged 66 years or older who commenced clopidogrel between April 1, 2002 and December 31, 2009, following hospital discharge for acute myocardial infarction (AMI). Cases were those who were readmitted for AMI, underwent percutaneous coronary intervention (PCI), or died within 90 days of discharge. Three controls were matched to each case on age, PCI, and the date of hospital discharge. We categorized exposure to antidepressants as current or no use within 120 days before the index date, and the serotonergic activity of antidepressants was further categorized as low, medium, and high according to their affinity for the serotonin transporter.ResultsAmong 24 090 patients who received clopidogrel following AMI, we identified 2494 cases. Of these, 2444 (98%) were successfully matched to 7045 controls. After extensive multivariable adjustment, antidepressant use was not associated with lower risk of the composite outcome (adjusted odds ratio [OR] 1.11 and 95% confidence interval [CI] 0.98–1.27). The absence of association was consistent across the different antidepressant groups categorized by serotonin transporter affinity.ConclusionIn high‐risk cardiovascular patients with a history of AMI and treated with clopidogrel, antidepressant use is associated with no additional reduction in risk of reinfarction irrespective of serotonin transporter affinity. Copyright © 2012 John Wiley & Sons, Ltd.
Proteomic workflow for analysis of archival formalin‐fixed and paraffin‐embedded clinical samples to a depth of 10 000 proteins
Authors: Wiśniewski Jacek R. , Duś Kamila , Mann Matthias 
Published: October 2012

PurposeArchival formalin‐fixed and paraffin‐embedded clinical samples represent a very diverse source of material for proteomic investigation of diseases, often with follow‐up patient information. Here, we describe an analytical workflow for analysis of laser‐capture microdissected formalin‐fixed and paraffin‐embedded samples that allows studying proteomes to a depth of 10 000 proteins per sample.Experimental designThe workflow involves lysis of tissue in SDS‐containing buffer, detergent removal, and consecutive digestion of the proteins with two enzymes by the multienzyme digestion filter‐aided sample preparation method. Resulting peptides are fractionated by pipette‐tip based strong anion exchange into six fractions and analyzed by LC‐MS/MS on a bench top quadrupole Orbitrap mass spectrometer.ResultsAnalysis of the data using the MaxQuant software resulted in the identification of 9502 ± 28 protein groups per a 110 nL sample of microdissected cells from human colonic adenoma. This depth of proteome analysis enables systemic insights into the organization of the adenoma cells and an estimation of the abundances of known biomarkers. It also allows the identification of proteins expressed from tumor suppressors, oncogenes, and other key players in the development and progression of the colorectal cancer.Conclusion and clinical relevanceOur proteomic platform can be used for quantitative comparisons between samples representing different stages of diseases and thus can be applied to the discovery of biomarkers or drug targets.
DFT investigation of the influence of ordered vacancies on elastic and magnetic properties of graphene and graphene‐like SiC and BN structures
Authors: Fedorov A. S. , Popov Z. I. , Fedorov D. A. , Eliseeva N. S. , Serjantova M. V. , Kuzubov A. A. 
Published: October 2012

AbstractInfluence of ordered monovacancies on elastic properties of graphene is theoretically investigated by density functional theory (DFT) calculations. Inverse linear dependence of the graphene Young's modulus on the concentration of vacancies has been revealed and migration rate of the vacancies has been calculated as a function of applied strain. It is shown that the migration rate can be controlled by applying various strains or temperatures. The influence of ordered monovacancies on magnetic properties of graphene as well as graphene‐like hexagonal carbon silicide (2D‐SiC) and the boron nitride (h‐BN) structures is investigated. It is established that the presence of vacancies in all systems yields the appearance of local magnetic moment. However, in 2D‐SiC structure the magnetic moment occurs only in the case of a Si vacancy. Influence of the distance between vacancies on the ferromagnetic or anti‐ferromagnetic ordering for all structures is established.
Sub‐nanometer thin single walled carbon nanotubes: Nitrogen does the trick
Authors: Kramberger Christian , Thurakitseree Therapool , Maruyama Shigeo 
Published: October 2012

AbstractThe mean diameter of single wall carbon nanotubes grown by chemical vapor deposition is demonstrated to be strongly affected by the relative concentrations of ethanol and acetonitrile in the liquid feedstock. We employ zeolite supported catalyst material which yields ∼1 nm thin nanotubes with pure ethanol. By adding acetonitrile the nanotube diameters can be reduced to ∼0.85 nm. The latter empirical lower bound points at the maximum curvature at which a free nanotube is still energetically favored.