bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Avian Influenza Virus NS1 ESEV PDZ Binding Motif Associates with Dlg1 and Scribble To Disrupt Cellular Tight Junctions
Authors: Golebiewski Lisa , Liu Hongbing , Javier Ronald T. , Rice Andrew P. 
Published: August 2011

ABSTRACT
The influenza A virus NS1 protein contains a conserved 4-amino-acid-residue PDZ-ligand binding motif (PBM) at the carboxyl terminus that can function as a virulence determinant by targeting cellular PDZ proteins. The NS1 proteins from avian and human viral isolates have consensus PBM sequences ESEV and RSKV, respectively. Currently circulating highly pathogenic H5N1 viruses contain the ESEV PBM which specifically associates with the PDZ proteins Scribble, Dlg1, MAGI-1, MAGI-2, and MAGI-3. In this study, we found NS1 proteins from viral isolates that contain the PBM sequence RSKV, KSEV, or EPEV are unable to associate with these PDZ proteins. Other results showed that the ESEV PBM mediates an indirect association with PDZ protein, Lin7C, via an interaction with Dlg1. Infection with a virus that expresses a NS1 protein with the ESEV PBM results in colocalization of NS1, Scribble, and Dlg1 within perinuclear puncta and mislocalization of plasma membrane-associated Lin7C to the cytoplasm. Infection of polarized MDCK cells with the ESEV virus additionally results in functional disruption of the tight junction (TJ) as measured by altered localization of TJ markers ZO-1 and Occludin, decreased transepithelial electrical resistance, and increased fluorescein isothiocyanate (FITC)-inulin diffusion across the polarized cell monolayer. A similar effect on the TJ was observed in MDCK cells depleted for either Scribble or Dlg1 by small interfering RNA (siRNA). These findings indicate that ESEV PBM-mediated binding of NS1 to Scribble and Dlg1 functions to disrupt the cellular TJ and that this effect likely contributes to the severe disease associated with highly pathogenic H5N1 influenza A viruses.
Novel Reassortment of Eurasian Avian-Like and Pandemic/2009 Influenza Viruses in Swine: Infectious Potential for Humans
Authors: Zhu Huachen , Zhou Boping , Fan Xiaohui , Lam Tommy T. Y. , Wang Jia , Chen Antony , Chen Xinchun , Chen Honglin , Webster Robert G. , Webby Richard , Peiris Joseph S. M. , Smith David K. , Guan Yi 
Published: August 2011

ABSTRACT

Pigs are considered to be intermediate hosts and “mixing vessels,” facilitating the genesis of pandemic influenza viruses, as demonstrated by the emergence of the 2009 H1N1 pandemic (pdm/09) virus. The prevalence and repeated introduction of the pdm/09 virus into pigs raises the possibility of generating novel swine influenza viruses with the potential to infect humans. To address this, an active influenza surveillance program was conducted with slaughtered pigs in abattoirs in southern China. Over 50% of the pigs tested were found to be seropositive for one or more H1 influenza viruses, most commonly pdm/09-like viruses. Out of 36 virus isolates detected, one group of novel reassortants had Eurasian avian-like swine H1N1 surface genes and pdm/09 internal genes. Animal experiments showed that this virus transmitted effectively from pig to pig and from pig to ferret, and it could also replicate in
ex vivo
human lung tissue. Immunization against the 2009 pandemic virus gave only partial protection to ferrets. The continuing prevalence of the pdm/09 virus in pigs could lead to the genesis of novel swine reassortant viruses with the potential to infect humans.
A Cluster of Basic Amino Acids in the Factor X Serine Protease Mediates Surface Attachment of Adenovirus/FX Complexes
Authors: Duffy Margaret R. , Bradshaw Angela C. , Parker Alan L. , McVey John H. , Baker Andrew H. 
Published: August 2011

ABSTRACT
Hepatocyte transduction following intravenous administration of adenovirus 5 (Ad5) is mediated by interaction between coagulation factor X (FX) and the hexon. The FX serine protease (SP) domain tethers the Ad5/FX complex to hepatocytes through binding heparan sulfate proteoglycans (HSPGs). Here, we identify the critical HSPG-interacting residues of FX. We generated an FX mutant by modifying seven residues in the SP domain. Surface plasmon resonance demonstrated that mutations did not affect binding to Ad5. FX-mediated, HSPG-associated cell binding and transduction were abolished. A cluster of basic amino acids in the SP domain therefore mediates surface interaction of the Ad/FX complex.
Interaction of Reverse Transcriptase (RT) Mutations Conferring Resistance to Lamivudine and Etravirine: Effects on Fitness and RT Activity of Human Immunodeficiency Virus Type 1
Authors: Hu Zixin , Kuritzkes Daniel R. 
Published: August 2011

ABSTRACTResistance to the nonnucleoside reverse transcriptase inhibitors etravirine and rilpivirine (RPV) is conferred by the E138K mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Clinical trials of RPV administered with lamivudine or emtricitabine showed the emergence of E138K together with M184I, which confers lamivudine and emtricitabine resistance in most patients with virologic failure. To understand why M184I was favored over M184V, we determined the drug susceptibility, infectivity, relative fitness, and reverse transcriptase activity of HIV-1 carrying E138K/M184I or E138K/M184V mutations. Whereas the replication capacity (RC) of the single mutants was reduced compared to that of the wild type (WT), the RC of the two double mutants was comparable to that of the WT in the absence of drug. The RC of the E138K/M184I mutant in the presence of etravirine was significantly greater than that of the E138K and E138K/M184V mutants; the RC of the double mutants was greater than that of the M184I or M184V mutant. Fitness profiles and growth competition experiments showed that the E138K/M184I mutant had a significant replicative advantage over the E138K/M184V mutant in the presence of etravirine and lamivudine. The virion-associated RT activity of the E138K, M184I, or M184V virus was significantly reduced compared to that of the WT, whereas the RT activity of the E138K/M184I virus was significantly greater than that of the WT or E138K/M184V virus. These results suggest that the E138K and M184I/V mutations are mutually compensatory and may explain the frequent occurrence of E138K/M184I after the virologic failure of rilpivirine-, lamivudine-, and emtricitabine-containing regimens.
The ability of a behaviour-specific patient questionnaire to identify poorly performing doctors
Authors: Fossli Jensen Bård , Dahl Fredrik A , Safran Dana Gelb , Garratt Andrew M , Krupat Edward , Finset Arnstein , Gulbrandsen Pål 
Published: August 2011

BackgroundDoctors' ability to communicate with patients varies. Patient questionnaires are often used to assess doctors' communication skills.ObjectiveTo investigate whether the Four Habits Patient Questionnaire (4HPQ) can be used to assess the different skill levels of doctors.DesignA cross-sectional study of 497 hospital encounters with 71 doctors. Encounters were videotaped and patients completed three post-visit questionnaires.SettingA 500-bed general teaching hospital in Norway.Main outcomeThe proportion of video-observed between-doctor variance that could be predicted by 4HPQ.ResultsThere were strong correlations between all patient-reported outcomes (range 0.71–0.80 at the doctor level, p<0.01). 4HPQ correlated significantly with video-observed behaviour at the doctor level (Pearson's r=0.42, p<0.01) and the encounter level (Pearson's r=0.27, p<0.01). The proportion of between-doctor variance not detectable by 4HPQ was 88%. The reason for this discordance was large within-doctor between-encounter variance observed in the videos, and small between-patient variance in patient reports. The maximum positive predictive value for the identification of poorly performing doctors (92%) was achieved with a cut-off score for 4HPQ of 82% (ie, patient assessments were concordant with expert observers for these doctors).ConclusionUsing a patient-reported questionnaire of doctors' communication skills, favourable assessments of doctors by patients were mostly discordant with the views of expert observers. Only very poor performance identified by patients was in agreement with the views of expert observers. The results suggest that patient reports alone may not be sufficient to identify all doctors whose communication skills need improvement training.
Cationic ruthenium(III) maltolato–imidazole complexes — Synthesis, characterization, and antiproliferatory activity*Adapted from the Ph.D. thesis of D.C. Kennedy (see the References section).
Authors: Kennedy David C. , Patrick Brian O. , James Brian R. 
Published: August 2011

The cationic RuIII complexes, trans-[Ru(ma)2(L)2]CF3SO3, where Hma = maltol = 3-hydroxy-2-methyl-4-pyrone; L = imidazole (Im) (complex 2), 1(N)-methylimidazole (N-MeIm) (3), 2-methylimidazole (2-MeIm) (4), and 4-methylimidazole (4-MeIm) (5), were synthesized via the known L = EtOH (complex 1a), and characterized by elemental analysis, 1H NMR and IR spectroscopies, mass spectrometry, cyclic voltammetry, and (for 3 and 4) by X-ray crystallography. The trans-[Ru(ma)2(H2O)2]CF3SO3 complex (1b) was inadvertently isolated and characterized crystallographically, and the monomaltolato species [Ru(ma)(N-MeIm)4][CF3SO3]2 (6) was also isolated and characterized. In vitro antiproliferatory activity of complexes 2−6 against human breast cancer cells (MDA-MB-435S) was tested using an MTT assay: 4 and 5 exhibit the lowest IC50 values, ~5 and ~15 µmol/L, respectively, whereas cisplatin exhibits an IC50 value of ~35 µmol/L against this cell line.
Theoretical investigation of the conformational intricacies and thermodynamic functions of noradrenaline
Authors: Lee DongJin R. , Galant Natalie J. , Lee Donghoon M. , Dawson Sean S.H. , Ding Vanna Z.Y. , Setiadi David H. , Viskolcz Bela , Csizmadia Imre G. 
Published: August 2011

Noradrenaline is a neurotransmitter that is involved in various psychological processes. In the neurotransmission process, noradrenaline binds to an adrenergic receptor by forming a complex of hydrogen bonds between its two catechol ring hydroxyl groups and the amino acid residues of adrenergic receptors. Although the two catechol ring hydroxyl groups play a crucial role in making hydrogen bonds to the binding site of the adrenergic receptor, the contribution of the catechol ring hydroxyl groups to the intramolecular stability that may affect docking has not been fully studied. To reveal the specific role that the catechol ring hydroxyl groups might play in stabilizing noradrenaline, the quantum chemical computations of geometry optimization and thermodynamic functions of N-protonated noradrenaline conformers were performed at both the B3LYP/6–31G(d,p) and G3MP2B3 levels of theory, using the Gaussian 03 program. The results were compared with those of N-protonated β-hydroxy-β-phenylethylamine, which is identical to noradrenaline except it lacks two catechol ring hydroxyl groups. For the first time, post-Hartree–Fock computations were used to obtain thermodynamic functions to establish relative stabilities of all possible conformers of N-protonated noradrenaline. In this study, 18 distinct structures of N-protonated noradrenaline were revealed, and the catechol ring hydroxyl groups were found to affect noradrenaline stability positively or negatively depending on the conformational orientations. On the basis of available experimental results, the issue that the least stable conformation of two catechol ring hydroxyl groups may be involved in the docking process has been raised. These findings may be useful in synthesis of derivatives of noradrenaline in drug design.
Adjacent land-use affects amphibian community composition and species richness in managed forests in New Brunswick, Canada
Authors: Jacobs Lee , Houlahan Jeff E. 
Published: August 2011

Here, we examine the effects of adjacent land use in a managed forest on pond-breeding amphibian species richness and community composition at 34 New Brunswick, Canada, ponds. Amphibian species richness was negatively correlated with the proportion of roads, precommercial thinning, and hardwood forest and positively correlated with the proportion of wetlands in adjacent lands. These land-use effects peak at 180 m from the ponds. Road density was negatively correlated with Lithobates catesbeiana and Lithobates septentrionalis presence. Precommercial thinning was negatively correlated with Ambystoma spp. presence and positively correlated with Anaxyrus americanus presence. Wetlands were positively correlated with L. septentrionalis and Notopthalamus viridescens presence. Correlations were also found between water table height and A. americanus, Lithobates palustris , and Ambystoma spp. presence. In addition, L. catesbeiana and N. viridescens presence–absence was positively correlated with the proportion of mature and overmature forest on the landscape (at scales of 500 and 1000 m, respectively). Lastly, the proportion of regenerating and sapling forest on the landscape was negatively correlated with L. palustris presence–absence but, by contrast, was positively correlated with A. americanus. These results suggest that the effects of adjacent land use may significantly impact amphibian populations in managed eastern Canadian forests.
Deriving forest canopy fuel parameters for loblolly pine forests in eastern Texas
Authors: Agca Muge , Popescu Sorin C. , Harper Clinton W. 
Published: August 2011

Crown fires, the fastest spreading of all forest fires, can occur in any forest type throughout the world. The overall aim of this study was to estimate forest canopy fuel parameters including canopy bulk density and canopy base height for loblolly pines ( Pinus taeda L.) at the plot level using both allometric equations and CrownMass/FMAPlus software. Allometric equation results were compared with the CrownMass outputs for validation. According to our results, the calculated average canopy bulk density values, across all 50 plots, were 0.18 and 0.07 kg/m3 for the allometric equation and the CrownMass program, respectively. Lorey’s mean height approach was used in this study to calculate canopy base height at the plot level. The average height values of canopy base height obtained from the Lorey height approach was 10.6 m and from the CrownMass program was 9.1 m. The results obtained for the two methods are relatively close to each other, with the estimate of canopy base height being 1.16 times larger than the CrownMass value. This study provides a practical method for quantifying these parameters and making them directly available to fire managers. The accuracy of these parameters is very important for realistic predictions of wildfire initiation and growth.
Temporal dynamics of nonstructural carbohydrates and xylem growth inPinus sylvestrisexposed to drought
Authors: Oberhuber Walter , Swidrak Irene , Pirkebner Daniela , Gruber Andreas 
Published: August 2011

Wood formation requires a continuous supply of carbohydrates for structural growth and metabolism. In the montane belt of the central Austrian Alps, we monitored the temporal dynamics of xylem growth and nonstructural carbohydrates (NSC) in stem sapwood of Scots pine ( Pinus sylvestris L.) during the growing season of 2009, which was characterized by exceptional soil dryness within the study area. Soil water content dropped below 10% at the time of maximum xylem growth at the end of May. Histological analyses have been used to describe cambial activity and xylem growth. Determination of NSC was performed using specific enzymatic assays revealing that total NSC ranged from 0.8% to 1.7% dry matter throughout the year. Significant variations (P < 0.05) of the size of the NSC pool were observed during the growing season. Starch showed persistent abundance throughout the year, reaching a maximum shortly before onset of late wood formation in mid-July. Seasonal dynamics of NSC and xylem growth suggest that (i) high sink activity occurred at the start of the growing season in spring and during late wood formation in summer and (ii) there was no particular shortage in NSC, which caused P. sylvestris to draw upon stem reserves more heavily during the drought in 2009.
Linking climate, gross primary productivity, and site index across forests of the western United States
Authors: Weiskittel Aaron R. , Crookston Nicholas L. , Radtke Philip J. 
Published: August 2011

Assessing forest productivity is important for developing effective management regimes and predicting future growth. Despite some important limitations, the most common means for quantifying forest stand-level potential productivity is site index (SI). Another measure of productivity is gross primary production (GPP). In this paper, SI is compared with GPP estimates obtained from 3-PG and NASA’s MODIS satellite. Models were constructed that predict SI and both measures of GPP from climate variables. Results indicated that a nonparametric model with two climate-related predictor variables explained over 68% and 76% of the variation in SI and GPP, respectively. The relationship between GPP and SI was limited (R2 of 36%–56%), while the relationship between GPP and climate (R2 of 76%–91%) was stronger than the one between SI and climate (R2 of 68%–78%). The developed SI model was used to predict SI under varying expected climate change scenarios. The predominant trend was an increase of 0–5 m in SI, with some sites experiencing reductions of up to 10 m. The developed model can predict SI across a broad geographic scale and into the future, which statistical growth models can use to represent the expected effects of climate change more effectively.
Identification of Epstein-Barr Virus–Induced Gene 3 as a Novel Serum and Tissue Biomarker and a Therapeutic Target for Lung Cancer
Authors: Nishino Ryohei , Takano Atsushi , Oshita Hideto , Ishikawa Nobuhisa , Akiyama Hirohiko , Ito Hiroyuki , Nakayama Haruhiko , Miyagi Yohei , Tsuchiya Eiju , Kohno Nobuoki , Nakamura Yusuke , Daigo Yataro 
Published: August 2011

AbstractPurpose: This study aims to identify novel biomarkers and therapeutic targets for lung cancer.Experimental Design: We carried out gene expression profile analysis of 120 lung cancers to screen for genes encoding transmembrane/secretory molecules that are commonly transactivated in lung cancers. Epstein-Barr virus–induced gene 3 (EBI3), which encodes a secretory glycoprotein, was selected as a good candidate. Immunohistochemical staining using tissue microarray consisting of 414 non–small cell lung cancers was applied to examine the expression level and prognostic value of EBI3. Serum EBI3 levels in 400 individuals for training assays (274 lung cancers and 126 healthy volunteers) and those in 173 individuals for validation analysis (132 lung cancers and 41 healthy volunteers) were measured by ELISA. The role of EBI3 in cancer cell growth was examined by siRNA and cell growth assays, using cells stably expressing exogenous EBI3.Results: Immunohistochemical staining of EBI3 using tissue microarrays revealed that a high level of EBI3 expression was associated with a poor prognosis of lung cancer (P = 0.0014) and multivariate analysis confirmed it to be an independent prognostic factor (P = 0.0439). Serum levels of EBI3 in the training set were found to be significantly higher in lung cancer patients than in healthy volunteers; this result was also observed in the validation set. Furthermore, reduction in EBI3 expression by siRNA suppressed cancer cell proliferation whereas induction of exogenous EBI3 conferred growth-promoting activity.Conclusions: EBI3 is a potential serum and tissue biomarker as well as therapeutic target for lung cancer. Clin Cancer Res; 17(19); 6272–86. ©2011 AACR.
BAD Phosphorylation Determines Ovarian Cancer Chemosensitivity and Patient Survival
Authors: Marchion Douglas C. , Cottrill Hope M. , Xiong Yin , Chen Ning , Bicaku Elona , Fulp William J. , Bansal Nisha , Chon Hye Sook , Stickles Xiaomang B. , Kamath Siddharth G. , Hakam Ardeshir , Li Lihua , Su Dan , Moreno Carolina , Judson Patricia L. , Berchuck Andrew , Wenham Robert M. , Apte Sachin M. , Gonzalez-Bosquet Jesus , Bloom Gregory C. , Eschrich Steven A. , Sebti Said , Chen Dung-Tsa , Lancaster Johnathan M. 
Published: August 2011

Abstract
Purpose: Despite initial sensitivity to chemotherapy, ovarian cancers (OVCA) often develop drug resistance, which limits patient survival. Using specimens and/or genomic data from 289 patients and a panel of cancer cell lines, we explored genome-wide expression changes that underlie the evolution of OVCA chemoresistance and characterized the BCL2 antagonist of cell death (BAD) apoptosis pathway as a determinant of chemosensitivity and patient survival.
Experimental Design: Serial OVCA cell cisplatin treatments were performed in parallel with measurements of genome-wide expression changes. Pathway analysis was carried out on genes associated with increasing cisplatin resistance (EC50). BAD-pathway expression and BAD protein phosphorylation were evaluated in patient samples and cell lines as determinants of chemosensitivity and/or clinical outcome and as therapeutic targets.
Results: Induced in vitro OVCA cisplatin resistance was associated with BAD-pathway expression (P &lt; 0.001). In OVCA cell lines and primary specimens, BAD protein phosphorylation was associated with platinum resistance (n = 147, P &lt; 0.0001) and also with overall patient survival (n = 134, P = 0.0007). Targeted modulation of BAD-phosphorylation levels influenced cisplatin sensitivity. A 47-gene BAD-pathway score was associated with in vitro phosphorylated BAD levels and with survival in 142 patients with advanced-stage (III/IV) serous OVCA. Integration of BAD-phosphorylation or BAD-pathway score with OVCA surgical cytoreductive status was significantly associated with overall survival by log-rank test (P = 0.004 and P &lt; 0.0001, respectively).
Conclusion: The BAD apoptosis pathway influences OVCA chemosensitivity and overall survival, likely via modulation of BAD phosphorylation. The pathway has clinical relevance as a biomarker of therapeutic response, patient survival, and as a promising therapeutic target. Clin Cancer Res; 17(19); 6356–66. ©2011 AACR.
Oxidative Stress and Prostate Cancer Progression Are Elicited by Membrane-Type 1 Matrix Metalloproteinase
Authors: Nguyen Hoang-Lan , Zucker Stanley , Zarrabi Kevin , Kadam Pournima , Schmidt Cathleen , Cao Jian 
Published: August 2011

Abstract
Oxidative stress caused by high levels of reactive oxygen species (ROS) has been correlated with prostate cancer aggressiveness. Expression of membrane-type 1 matrix metalloproteinase (MT1-MMP), which has been implicated in cancer invasion and metastasis, is associated with advanced prostate cancer. We show here that MT1-MMP plays a key role in eliciting oxidative stress in prostate cancer cells. Stable MT1-MMP expression in less invasive LNCaP prostate cancer cells with low endogenous MT1-MMP increased activity of ROS, whereas MT1-MMP knockdown in DU145 cells with high endogenous MT1-MMP decreased activity of ROS. Expression of MT1-MMP increased oxidative DNA damage in LNCaP and in DU145 cells, indicating that MT1-MMP–mediated induction of ROS caused oxidative stress. MT1-MMP expression promoted a more aggressive phenotype in LNCaP cells that was dependent on elaboration of ROS. Blocking ROS activity using the ROS scavenger N-acetylcysteine abrogated MT1-MMP–mediated increase in cell migration and invasion. MT1-MMP–expressing LNCaP cells displayed an enhanced ability to grow in soft agar that required increased ROS. Using cells expressing MT1-MMP mutant cDNAs, we showed that ROS activation entails cell surface MT1-MMP proteolytic activity. Induction of ROS in prostate cancer cells expressing MT1-MMP required adhesion to extracellular matrix proteins and was impeded by anti-β1 integrin antibodies. These results highlight a novel mechanism of malignant progression in prostate cancer cells that involves β1 integrin–mediated adhesion, in concert with MT1-MMP proteolytic activity, to elicit oxidative stress and induction of a more invasive phenotype. Mol Cancer Res; 9(10); 1305–18. ©2011 AACR.