bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of bone resorption and sealing zone formation in osteoclasts occurs through protein kinase b–mediated microtubule stabilization
Authors: Matsumoto Takumi , Nagase Yuichi , Hirose Jun , Tokuyama Naoto , Yasui Tetsuro , Kadono Yuho , Ueki Kohjiro , Kadowaki Takashi , Nakamura Kozo , Tanaka Sakae 
Published: December 2012

Abstract
We investigated the role of protein kinase B (Akt), a downstream effector of phosphatidylinositol 3-kinase, in bone-resorbing activity of mature osteoclasts. Treatment with a specific Akt inhibitor disrupted sealing zone formation and decreased the bone-resorbing activity of osteoclasts. The normal microtubule structures were lost and the Akt inhibitor reduced the amount of acetylated tubulin, which reflects stabilized microtubules, whereas forced Akt activation by adenovirus vectors resulted in the opposite effect. Forced Akt activation increased the binding of the microtubule-associated protein adenomatous polyposis coli (APC), the APC-binding protein end-binding protein 1 (EB1) and dynactin, a dynein activator complex, with microtubules. Depletion of Akt1 and Akt2 resulted in a disconnection of APC/EB1 and a decrease in bone-resorbing activity along with reduced sealing zone formation, both of which were recovered upon the addition of LiCl, a glycogen synthase kinase-3β (GSK-3β) inhibitor. The Akt1 and Akt2 double-knockout mice exhibited osteosclerosis due to reduced bone resorption. These findings indicate that Akt controls the bone-resorbing activity of osteoclasts by stabilizing microtubules via a regulation of the binding of microtubule associated proteins. © 2013 American Society for Bone and Mineral Research.
CaMKII activity is reduced in skeletal muscle during sepsis
Authors: Aversa Zaira , Alamdari Nima , Castillero Estibaliz , Muscaritoli Maurizio , Fanelli Filippo Rossi , Hasselgren Per‐Olof 
Published: December 2012

AbstractExercise‐induced muscle hypertrophy is associated with increased calcium/calmodulin‐dependent protein kinase II (CaMKII) expression and activity. In contrast, the influence of muscle atrophy‐related conditions on CaMKII is poorly understood. Here, we tested the hypothesis that sepsis‐induced muscle wasting is associated with reduced CaMKII expression and activity. Sepsis, induced by cecal ligation and puncture in rats, and treatment of rats with TNFα, resulted in reduced total CaMKII activity in skeletal muscle whereas autonomous CaMKII activity was unaffected. The expression of CaMKIIδ, but not β and γ, was reduced in septic muscle. In additional experiments, treatment of cultured myotubes with TNFα resulted in reduced total CaMKII activity and decreased levels of phosphorylated glycogen synthase kinase (GSK)‐3β, a downstream target of CaMKII. The present results suggest that sepsis‐induced muscle wasting is associated with reduced CaMKII activity and that TNFα may be involved in the regulation of CaMKII activity in skeletal muscle. Decreased phosphorylation (consistent with activation) of GSK‐3β may be a consequence of reduced CaMKII activity, indicating that inhibited CaMKII activity may be involved in the catabolic response to sepsis. J. Cell. Biochem. 114: 1294–1305, 2013. © 2012 Wiley Periodicals, Inc.
Differential effects of exogenous and autocrine growth hormone on LNCaP prostate cancer cell proliferation and survival
Authors: Nakonechnaya Alona O. , Jefferson Holly S. , Chen Xiaofei , Shewchuk Brian M. 
Published: December 2012

AbstractThe prostate gland is regulated by multiple hormones and growth factors that may also affect prostate tumorigenesis. Growth hormone (GH) contributes to prostate development and function, but the direct effects of GH on prostate cancer cells are not well understood. The expression of endogenous GH in prostate cancer cell lines has also been observed, suggesting the potential for an effect of autocrine GH. In the present study, we measure the levels of GH and GH receptor (GHR) mRNA in multiple prostate cancer and normal prostate‐derived cell lines, and compare the effects of exogenous and autocrine GH on LNCaP prostate cancer cell proliferation and apoptosis, and the associated signal transduction pathways. We found that GHR and GH expression were higher in the prostate cancer cell lines, and that exogenous GH increased LNCaP cell proliferation, but had no effect on apoptosis. In contrast, autocrine GH overexpression reduced LNCaP cell proliferation and increased apoptosis. The distinct actions of exogenous and autocrine GH were accompanied by differences in the involvement of GHR‐associated signal transduction pathways, and were paralleled by an alteration in the subcellular localization of GHR, in which autocrine GH appeared to sequester GHR in the Golgi and endoplasmic reticulum. This alteration of GHR trafficking may underlie a distinct mode of GH‐mediated signaling associated with the effect of autocrine GH. These findings clarify the potential effects of GH on prostate cancer cell function, and indicate that the activity of autocrine GH may be distinct from that of endocrine GH in prostate cancer cells. J. Cell. Biochem. 114: 1322–1335, 2013. © 2012 Wiley Periodicals, Inc.
Hyperglycemia accelerates ATP‐binding cassette transporter A1 degradation via an ERK‐dependent pathway in macrophages
Authors: Chang Yu‐Cheng , Sheu Wayne H.‐H. , Chien Yi‐Shen , Tseng Pei‐Chi , Lee Wen‐Jane , Chiang An‐Na 
Published: December 2012

AbstractAn elevation in blood glucose concentration leads to increased risk of developing diabetes‐associated atherosclerotic cardiovascular disease due to an excessive accumulation of cholesterol in arterial macrophages. ATP‐binding cassette transporter A1 (ABCA1) is an atheroprotective protein that mediates the export of cholesterol from macrophages. The present study aims to investigate the effect of hyperglycemia on the regulation of ABCA1 expression and to explore its underlying mechanisms of regulation in macrophages. Our results show that high glucose activates the extracellular signal‐regulated kinases (ERK) signaling pathway via reactive oxygen species (ROS) production, which in turn down‐regulates ABCA1 mRNA and protein expression. This down‐regulation is mediated by accelerating ABCA1 mRNA and protein degradation in macrophages exposed to high concentrations of glucose. Our results provide evidence for the first time that hyperglycemia inhibits ABCA1 expression by ERK‐modulated ABCA1 mRNA and protein stability. Overall, these results provide a mechanism for hyperglycemia‐induced reduction in ABCA1 expression, which suggests a promising strategy for the treatment of diabetes‐associated atherosclerosis. J. Cell. Biochem. 114: 1364–1373, 2013. © 2012 Wiley Periodicals, Inc.
The MM2QM tool for combining docking, molecular dynamics, molecular mechanics, and quantum mechanics†
Authors: Nowosielski Marcin , Hoffmann Marcin , Kuron Aneta , Korycka‐Machala Malgorzata , Dziadek Jaroslaw 
Published: December 2012

AbstractThe use of the MM2QM tool in a combined docking + molecular dynamics (MD) + molecular mechanics (MM) + quantum mechanical (QM) binding affinity prediction study is presented, and the tool itself is discussed. The system of interest is Mycobacterium tuberculosis (MTB) pantothenate synthetase in complexes with three highly similar sulfonamide inhibitors, for which crystal structures are available. Starting from the structure of MTB pantothenate synthetase in the “open” conformation and following the combined docking + MD + MM + QM procedure, we were able to capture the closing of the enzyme binding pocket and to reproduce the position of the ligands with an average root mean square deviation of 1.6 Å. Protein–ligand interaction energies were reproduced with an average error lower than 10%. The discussion on the MD part and a protein flexibility importance is carried out. The presented approach may be useful especially for finding analog inhibitors or improving drug candidates. © 2012 Wiley Periodicals, Inc.
Notes on quantitative structure–property relationships (QSPR), part 3: Density functions origin shift as a source of quantum QSPR algorithms in molecular spaces
Authors: Carbó‐Dorca Ramon 
Published: December 2012

AbstractA general algorithm implementing a useful variant of quantum quantitative structure–property relationships (QQSPR) theory is described. Based on quantum similarity framework and previous theoretical developments on the subject, the present QQSPR procedure relies on the possibility to perform geometrical origin shifts over molecular density function sets. In this way, molecular collections attached to known properties can be easily used over other quantum mechanically well‐described molecular structures for the estimation of their unknown property values. The proposed procedure takes quantum mechanical expectation value as provider of causal relation background and overcomes the dimensionality paradox, which haunts classical descriptor space QSPR. Also, contrarily to classical procedures, which are also attached to heavy statistical gear, the present QQSPR approach might use a geometrical assessment only or just some simple statistical outline or both. From an applied point of view, several easily reachable computational levels can be set up. A Fortran 95 program: QQSPR‐n is described with two versions, which might be downloaded from a dedicated web site. Various practical examples are provided, yielding excellent results. Finally, it is also shown that an equivalent molecular space classical QSPR formalism can be easily developed. © 2012 Wiley Periodicals, Inc.
Purification of arabitol from fermentation broth of Debaryomyces hansenii using glycerol as substrate
Authors: Loman Abdullah Al , Ju Lu‐Kwang 
Published: December 2012

AbstractBACKGROUNDArabitol has many potential industrial applications and it can be produced by fermentation from glycerol, a major byproduct of biodiesel industry. This work aims at developing a new process for collecting and purifying arabitol from the broth of osmophilic Debaryomyces hansenii containing arabitol, unconsumed glycerol, and other minor impurities. RESULTS: The process developed and optimized in this study had the following steps: first, the broth supernatant was treated with 8 g L−1 activated carbon at 30°C and pH 6 for removal of colored organics and some impurities. Then glycerol was selectively removed by acetone extraction at 30°C. The acetone amount was optimized according to the measured solubility data of simulative glycerol‐xylitol‐acetone systems and real fermentation broth. The glycerol‐removed remainder was next extracted for arabitol with butanol (90% of supernatant volume) at 90 °C. White arabitol crystals were collected from the cooled butanol extract. The overall recovery and purity of arabitol crystals were 66% and 95%, respectively.CONCLUSIONSuccessful arabitol purification was achieved with an optimized process. Fundamental phase equilibrium data of glycerol‐xylitol‐acetone systems were obtained. The process developed would prove valuable for arabitol production and potentially for separation of other polyols. © 2012 Society of Chemical Industry
The yield of EUS‐FNA in undiagnosed upper abdominal adenopathy is very high
Authors: Coe Adam , Conway Jason , Evans Jerry , Goebel Michael , Mishra Girish 
Published: December 2012

AbstractPurpose:Endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) allows sampling of abdominal adenopathy easily and safely from locations that were previously deemed too risky and inaccessible. The efficacy of EUS‐FNA in a large cohort of patients with abdominal adenopathy has not been previously described in the literature.Methods:We conducted a large retrospective study at a tertiary referral center. Two hundred twenty‐five consecutive patients undergoing EUS‐FNA for only abdominal adenopathy between 2004 through August 2009 were included in our study. Patient demographics, indications, EUS findings, and final cytologic diagnoses were recorded.Results:A total of 230 lymph nodes were biopsied in 225 patients. Common locations of nodes included peripancreatic (19%), porta hepatis (18%), and celiac axis (18%). Adequate specimens were obtained in 200/230 nodes (87%) and the most common diagnoses based on cytology were: benign/reactive (50%), adenocarcinoma (20%), lymphoma (8%). The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were 71%, 99%, 99%, 78%, and 85%, respectively, for EUS‐FNA. Based on EUS imaging alone, malignant nodes were more likely to be larger in diameter (17 mm versus 26 mm, p < 0.001), have a round shape (p = 0.002), well‐defined borders (p = 0.04), and hypoechic echotexture (p < 0.001).Conclusions:EUS‐FNA allows for excellent tissue acquisition in abdominal lymphadenopathy. Our study supports the use of traditional EUS imaging criteria to identify suspected malignant adenopathy. The results from our large cohort of patients show that EUS‐FNA should be considered as a first‐line diagnostic modality for ascertaining the etiology of abdominal lymphadenopathy. © 2012 Wiley Periodicals, Inc. J Clin Ultrasound, 2013
Effects of gadoxetic acid on quantitative diffusion‐weighted imaging of the liver
Authors: Colagrande Stefano , Mazzoni Lorenzo Nicola , Mazzoni Elisa , Pradella Silvia 
Published: December 2012

PurposeTo prospectively evaluate the effect of gadoxetic acid (Gd‐EOB‐DTPA; Primovist, Bayer‐Schering, Berlin, Germany) on quantitative diffusion‐weighted imaging (DWI) using the Le Bihan IntraVoxel Incoherent Motion model and considering separately the following parameters: slow diffusion coefficient (D), fast diffusion coefficient (D*), perfusion fraction (PF), and apparent diffusion coefficient (ADC).Materials and MethodsTwenty‐four consecutive patients were submitted to the same magnetic resonance (MR)‐DWI acquisition before and after gadoxetic acid administration. Patients were divided into four groups according to the time at which the DW sequence was repeated, then 5, 10, 15, 20 minutes after contrast agent administration. A total of 48 manually drawn regions of interest (ROIs) of about 1200 pixels were placed in the middle right liver lobe. The mean and standard deviation (SD) were calculated in each group/patient for every DWI‐related parameter. Analysis of variance was performed (threshold P = 0.05). Bonferroni and Games‐Howell post‐hoc tests were applied if significant differences were found among groups; otherwise, data were averaged together.ResultsD, D*, PF, and ADC did not show any significant difference before and after contrast agent administration, at any time.ConclusionIt is possible to perform DW acquisitions after gadoxetic acid administration without any significant variation of the values of DW‐related parameters under consideration in this study. J. Magn. Reson. Imaging 2013;38:365–370. © 2013 Wiley Periodicals, Inc.
Determining the in vivo transverse relaxation time of GABA in the human brain at 7T
Authors: Intrapiromkul Jarunee , Zhu He , Cheng Ying , Barker Peter B. , Edden Richard A.E. 
Published: December 2012

PurposeTo measure in vivo transverse relaxation times (T2) of gamma‐aminobutyric acid (GABA) at 7T using the experimental spectral‐editing method.Materials and MethodsExperiments were performed at 7T in a 10 mM GABA phantom to determine the intrinsic TE‐dependence of the edited signal. Then the same method was applied with editing‐based suppression of coedited macromolecular signals to five healthy volunteers to determine T2 of GABA in vivo.ResultsFrom in vivo data acquired at multiple echo times, the in vivo GABA T2 relaxation time was estimated to be 63 ± 19 msec.ConclusionWe present a measurement of the T2 of edited GABA signal at 7T by first using phantom measurements to determine the echo time‐dependence of edited signal. The method is purely experimental and does not rely on prior knowledge of coupling constants or simulation of realistic experiments. J. Magn. Reson. Imaging 2013;38:1224–1229. © 2013 Wiley Periodicals, Inc.
Embolization therapy for benign prostatic hyperplasia: Influence of embolization particle size on gland perfusion
Authors: Brook Olga Rachel , Faintuch Salomao , Brook Alexander , Goldberg S. Nahum , Rofsky Neil M. , Lenkinski Robert E. 
Published: December 2012

PurposeTo assess the influence of embolic size on the therapy response of prostatic arterial embolization (PAE) based on perfusional changes seen on dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI).Materials and MethodsTwelve beagles underwent PAE, four dogs with each particle size: A: 100–300 μm; B: 300–500 μm; and C: 500–700 μm. Prior to and 1 month after the embolization all dogs underwent prostate DCE MRI.ResultsAfter embolization, time to maximal perfusion intensity for prostate parenchyma increased in B (188 vs. 135 sec, P = 0.023) and C (200 vs. 120 sec, P = 0.001), while it did not change for A (139 vs. 124 sec, P = 0.39). The maximal relative intensity increased after embolization in C (3.84 vs. 2.38, P < 0.001), while it did not change for A (2.50 vs. 2.44, P = 0.36) and B (3.23 vs. 2.9, P = 0.21). The extent of visualized intraprostatic urethral wall increased after embolization in B compared with A and C, 239.5 ± 138.1% vs. 56.1 ± 34.3, P = 0.04. Enhancement changes correlated with prostate volume changes: prostate volumes in A decreased less as compared with B and C (77 ± 34% vs. 56 ± 14%), P = 0.02.ConclusionThe enhancement and morphological data are useful to monitor response to therapy after embolization. Embolization with 300–500 and 500–700 μm particle may provide better results than with 100–300 μm particles in a canine model. J. Magn. Reson. Imaging 2013;38:380–387. © 2013 Wiley Periodicals, Inc.
Viral infections of the central nervous system in Spain: A prospective study
Authors: de Ory F. , Avellón A. , Echevarría J.E. , Sánchez‐Seco M.P. , Trallero G. , Cabrerizo M. , Casas I. , Pozo F. , Fedele G. , Vicente D. , Pena M.J. , Moreno A. , Niubo J. , Rabella N. , Rubio G. , Pérez‐Ruiz M. , Rodríguez‐Iglesias M. , Gimeno C. , Eiros J.M. , Melón S. , Blasco M. , López‐Miragaya I. , Varela E. , Martinez‐Sapiña A. , Rodríguez G. , Marcos M.Á. , Gegúndez M.I. , Cilla G. , Gabilondo I. , Navarro J.M. , Torres J. , Aznar C. , Castellanos A. , Guisasola M.E. , Negredo A.I. , Tenorio A. , Vázquez‐Morón S. 
Published: December 2012

AbstractThe aim of the study was to determine the incidence of viruses causing aseptic meningitis, meningoencephalitis, and encephalitis in Spain. This was a prospective study, in collaboration with 17 Spanish hospitals, including 581 cases (CSF from all and sera from 280): meningitis (340), meningoencephalitis (91), encephalitis (76), febrile syndrome (7), other neurological disorders (32), and 35 cases without clinical information. CSF were assayed by PCR for enterovirus (EV), herpesvirus (herpes simplex [HSV], varicella‐zoster [VZV], cytomegalovirus [CMV], Epstein–Barr [EBV], and human herpes virus‐6 [HHV‐6]), mumps (MV), Toscana virus (TOSV), adenovirus (HAdV), lymphocytic choriomeningitis virus (LCMV), West Nile virus (WNV), and rabies. Serology was undertaken when methodology was available. Amongst meningitis cases, 57.1% were characterized; EV was the most frequent (76.8%), followed by VZV (10.3%) and HSV (3.1%; HSV‐1: 1.6%; HSV‐2: 1.0%, HSV non‐typed: 0.5%). Cases due to CMV, EBV, HHV‐6, MV, TOSV, HAdV, and LCMV were also detected. For meningoencephalitis, 40.7% of cases were diagnosed, HSV‐1 (43.2%) and VZV (27.0%) being the most frequent agents, while cases associated with HSV‐2, EV, CMV, MV, and LCMV were also detected. For encephalitis, 27.6% of cases were caused by HSV‐1 (71.4%), VZV (19.1%), or EV (9.5%). Other positive neurological syndromes included cerebellitis (EV and HAdV), seizures (HSV), demyelinating disease (HSV‐1 and HHV‐6), myelopathy (VZV), and polyradiculoneuritis (HSV). No rabies or WNV cases were identified. EVs are the most frequent cause of meningitis, as is HSV for meningoencephalitis and encephalitis. A significant number of cases (42.9% meningitis, 59.3% meningoencephalitis, 72.4% encephalitis) still have no etiological diagnosis. J. Med. Virol. 85:554–562, 2013. © 2012 Wiley Periodicals, Inc.
Severe metapneumovirus infections among immunocompetent and immunocompromised patients admitted to hospital with respiratory infection
Authors: Souza Juliana Sinohara , Watanabe Aripuana , Carraro Emerson , Granato Celso , Bellei Nancy 
Published: December 2012

AbstractHuman metapneumovirus (hMPV) is considered an important cause of acute respiratory infections. hMPV can cause morbidity in hematopoietic stem cell transplant recipients and recent research has demonstrated that it is an important virus in patients admitted to hospital with respiratory infections and suspected of having pandemic 2009 influenza A (H1N1pdm09) virus. The purpose of this study was to investigate infections caused by hMPV in two groups of patients admitted to hospital: Immunocompromized patients with a potential risk of severe outcomes and immunocompetent patients with severe acute respiratory syndrome. A total of 288 samples were tested: 165 samples were collected from patients with suspected influenza A (H1N1) pdm09 infection during the first pandemic wave in 2009; and 123 samples were collected from patients of a hematopoietic stem cell transplantation program in 2008–2009. Amplification of the hMPV genes was performed by polymerase chain reaction. This was followed by sequencing and phylogenetic analysis. hMPV was detected in 14.2% (41/288) of all samples: 17% (28/165) of immunocompetent patients with suspected H1N1 infection and 10.6% (13/123) among hematopoietic stem cell transplant recipients. hMPV accounted for 12.1% (8/66) of immunocompetent adults patients with severe respiratory infections (median age, 55.9 years). Two hMPV subtypes were identified, A2 (26.9%; 7/26) and B2 (73.1%; 19/26) but no difference was observed between the patient groups in terms of age or immunosuppression level. This study highlights the significance of hMPV in immunocompetent adult patients with severe infections and further investigations are recommended for understanding the impact of this virus. J. Med. Virol. 85:530–536, 2013. © 2012 Wiley Periodicals, Inc.
BMP‐2 stimulated non‐tenogenic differentiation and promoted proteoglycan deposition of tendon‐derived stem cells (TDSCs) in vitro
Authors: Rui Yun Feng , Lui Pauline Po Yee , Wong Yin Mei , Tan Qi , Chan Kai Ming 
Published: December 2012

AbstractWe hypothesized that BMP‐2 might induce non‐tenocyte differentiation and increase production of proteoglycans of tendon‐derived stem cells (TDSCs). This study investigated the effects of BMP‐2 on the differentiation and production of proteoglycans in TDSCs in vitro. Rat patellar TDSCs were treated without or with BMP‐2. The osteogenic, adipogenic, chondrogenic, and tenogenic differentiation of TDSCs were assessed by (1) Alizarin red‐S staining assay; (2) Oil Red‐O staining assay; (3) haematoxylin–eosin staining, Safranin‐O staining, immunohistochemical staining of Sox9, and collagen type II; and (4) qRT‐PCR analysis of lineage‐specific markers. The production of glycoaminoglycans (GAG) in the BMP‐2‐treated TDSCs was assessed by alcian blue staining. The mRNA expression of aggrecan (Acan), decorin (Dcn), biglycan (Bgn), and fibromodulin (Fmod) in TDSCs after BMP‐2 treatment was assessed by qRT‐PCR. BMP‐2 promoted the osteogenic, adipogenic, and chondrogenic differentiation but inhibited tenogenic marker expression of TDSCs. GAG production and Acan increased while Dcn, Bgn, and Fmod decreased in TDSCs after BMP‐2 stimulation. In conclusion, BMP‐2 promoted GAG deposition, aggrecan expression, and enhanced non‐tenocyte differentiation of TDSCs in vitro. The effect of BMP‐2 on TDSCs might provide insights into the histopathological changes of tendinopathy. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 746–753, 2013