bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling disease in the mouse: Lessons from DNA damage response and cell cycle control genes
Authors: Adelman Carrie A. , Petrini John H. J. , Attwooll Claire L. 
Published: November 2005

AbstractThe advent of gene targeting has allowed the dissection of many essential cellular pathways, including those involved in cell cycle regulation, signal transduction, and development. However, it is becoming increasingly clear that the simple gene deletion strategy may not be sufficient for the modeling of many cancer syndromes. In this Prospect article, we will discuss the strengths and weaknesses of mouse models, how they have advanced from gene deletions to truncations, point mutations, and conditional mouse models in which expression or loss of the gene of interest is controlled either temporally or spatially. We will also consider future directions for the use of mouse models in cancer. The vastness of the field necessitates focusing on a few specific examples with the unfortunate exclusion of many excellent studies from our discussion. As such, we focus on a few specific models of human cancer syndromes, however many of the themes discussed here are applicable to other systems of genetic manipulation and may be applied across fields. J. Cell. Biochem. © 2005 Wiley‐Liss, Inc.
Signaling roles of diacylglycerol kinases
Authors: Topham Matthew K. 
Published: November 2005

AbstractDiacylglycerol kinases (DGKs) attenuate diacylglycerol signaling by converting this lipid to phosphatidic acid (PA). The nine mammalian DGKs that have been identified are widely expressed, but each isoform has a unique tissue and subcellular distribution. Their kinase activity is regulated by mechanisms that modify their access to diacylglycerol, directly affect their kinase activity, or alter their ability to bind to other proteins. In many cases, these enzymes regulate the activity of proteins that are modulated by either diacylglycerol or PA. Experiments using cultured cells and model organisms have demonstrated that DGKs have prominent roles in neuronal transmission, lymphocyte signaling, and carcinogenesis. J. Cell. Biochem. © 2005 Wiley‐Liss, Inc.
Ascorbate depletion mediates up‐regulation of hypoxia‐associated proteins by cell density and nickel
Authors: Karaczyn Aldona , Ivanov Sergey , Reynolds Mindy , Zhitkovich Anatoly , Kasprzak Kazimierz S. , Salnikow Konstantin 
Published: November 2005

AbstractExposure of human lung cells to carcinogenic nickel compounds in the presence of oxygen up‐regulated carbonic anhydrase IX (CA IX) and NDRG1/Cap43, both known as intrinsic hypoxia markers and cancer‐associated genes. This suggests that factors other than a shortage of oxygen may be involved in this induction. Both proteins can also be induced in the presence of oxygen by culturing these cells to a high density without medium change. The intracellular ascorbate measurements revealed its rapid depletion in both metal‐ and density‐exposed cells. Nickel exposure caused strong activation of HIF‐1α and HIF‐2α proteins, underscoring activation of HIF‐1‐dependent transcription. In contrast, cell density‐dependent transcription was characterized by minor induction of HIF‐1α or HIF‐2α. Moreover, the up‐regulation of NDRG1/Cap43 in HIF‐1α deficient fibroblasts suggested the involvement of different transcription factor(s). The repletion of intracellular ascorbate reversed the induction of CA IX and NDRG1/Cap43 caused by cell density or nickel exposure. Thus, the loss of intracellular ascorbate triggered the induction of both tumor markers by two different conditions in the presence of oxygen. Ascorbate is delivered to lung cells via the SVCT2 ascorbate transporter, which was found to be sensitive to nickel or cell density. Collectively these findings establish the importance of intracellular ascorbate levels for the regulation of expression of CA IX and NDRG1/Cap43. We suggest, that, in addition to low oxygenation, insufficient supply of ascorbate or its excessive oxidation in tumors, can contribute to the induction of hypoxia‐associated proteins via both HIF‐dependent and independent mechanisms. J. Cell. Biochem. 97: 1025–1035, 2006. © 2005 Wiley‐Liss, Inc.
The α1 subunit of GABAA receptor is repressed by c‐Myc and is pro‐apoptotic
Authors: Vaknin Uri A. , Hann Stephen R. 
Published: November 2005

AbstractThe c‐myc oncoprotein plays a critical role in the regulation of cellular proliferation and apoptosis. To mediate these biological functions, a variety of target genes are activated or repressed by c‐myc, but few genes have yet been identified that directly mediate c‐myc's role in proliferation or apoptosis. During a screen for genes that are repressed by c‐myc, we identified the α1 subunit of γ aminobutyric acid receptor (GABAAR‐α1) as a novel target of c‐myc. GABAAR is the major inhibitory neurotransmitter receptor in the mammalian central nervous system and is involved in developmental events in the brain, such as neurite outgrowth, neuronal survival, neuronal migration, and proliferation. We show here that GABAAR‐α1 expression is rapidly and directly repressed by c‐myc. GABAAR‐α1 expression is elevated in c‐myc null cells and upregulation of GABAAR‐α1 correlates with downregulation of c‐myc protein expression during neuronal cell differentiation. We also show that overexpression of GABAAR‐α1 causes apoptosis, which is blocked by the coexpression of Bcl‐2 or Bcl‐XL. Induction of apoptosis is specific for the α1 subunit, since neither the β1 or β2 subunits of GABAAR induced apoptosis. Derepression of GABAAR‐α1 expression upon downregulation of c‐myc represents a unique apoptotic mechanism and a distinct function for the α1 subunit, independent of its role as a component of the GABAAR in the plasma membrane. In addition, the regulation of GABAAR‐α1 expression by c‐myc provides a potential direct role for the Myc proteins in neurological processes and neurodegenerative disorders. J. Cell. Biochem. 97: 1094–1103, 2006. © 2005 Wiley‐Liss, Inc.
Beyond the cell cycle: A new role for Cdk6 in differentiation
Authors: Grossel Martha J. , Hinds Philip W. 
Published: November 2005

AbstractOver 10 years ago, cdk6 was identified as a new member in a family of vertebrate cdc‐2 related kinases. This novel kinase was found to partner with the D‐type cyclins and to possess pRb kinase activity in vitro and has since been understood to function solely as a pRb kinase in the regulation of the G1 phase of the cell cycle. In the past 2 years, several independent studies in multiple cell types have indicated a novel role for cdk6 in differentiation. For example, cdk6 expression must be reduced to allow proper osteoblast and osteoclast differentiation, forced cdk6 expression blocked differentiation of mouse erythroid leukemia cells and cdk6 expression in primary astrocytes favors the expression of progenitor cell markers. Since exit from the cell cycle is a necessary step in terminal differentiation, down‐regulation of a mitogenic factor may be expected in this process, however it is surprising that this association has not been previously uncovered and that it is apparently not shared with cdk4, long understood to be a functional homolog of cdk6. The mechanism of cdk6 function in differentiation is not understood, but it may extend beyond the established role of cdk6 as a pRb kinase. As this story unfolds it will be important to discover if the function of cdk6 in differentiation is pRb‐dependent or pRb‐independent, since pRb has long been established as a key factor in initiating and maintaining cell cycle exit during differentiation. © 2005 Wiley‐Liss, Inc.
Transcriptional regulation of VCAM‐1 expression by tumor necrosis factor‐α in human tracheal smooth muscle cells: Involvement of MAPKs, NF‐κB, p300, and histone acetylation
Authors: Lee Chiang‐Wen , Lin Wei‐Ning , Lin Chih‐Chung , Luo Shue‐Fen , Wang Jong‐Shyan , Pouyssegur Jacques , Yang Chuen‐Mao 
Published: November 2005

AbstractTumor necrosis factor‐α (TNF‐α) has been shown to induce the expression of adhesion molecules in airway resident cells and contribute to inflammatory responses. Here, the roles of mitogen‐activated protein kinases (MAPKs) and NF‐κB in TNF‐α‐induced expression of vascular cell adhesion molecule (VCAM)‐1 were investigated in human tracheal smooth muscle cells (HTSMCs). TNF‐α‐enhanced expression of VCAM‐1 protein and mRNA as well as phosphorylation of p42/p44 MAPK, p38, and JNK were significantly attenuated by inhibitors of MEK1/2 (U0126), p38 (SB202190), and JNK (SP600125). Transfection with dominant negative mutants of MEK1/2, ERK1, ERK2, p38, and JNK attenuated TNF‐α‐induced VCAM‐1 expression. Furthermore, TNF‐α‐induced VCAM‐1 expression was significantly blocked by a selective NF‐κB inhibitor helenalin. TNF‐α‐stimulated translocation of NF‐κB into the nucleus and degradation of IκB‐α was blocked by helenalin, but not by U0126, SB202190, or SP600125. VCAM‐1 promoter activity was enhanced by TNF‐α in HTSMCs transfected with VCAM‐1‐Luc, which was inhibited by helenalin, U0126, SB202190, and SP600125. Most surprisingly, VCAM‐1 expression was also significantly blocked by a selective inhibitor of p300, curcumin. NF‐κB transcription factor and p300 were associated with the VCAM‐1 promoter, which was dynamically linked to histone H3 acetylation stimulated by TNF‐α, as determined by chromatin immunoprecipitation assay. Moreover, the resultant enhancement of VCAM‐1 expression increased the adhesion of polymorphonuclear cells (PMNs) to monolayer of HTSMCs, which was blocked by helenalin, U0126, SB202190, or SP600125. These results suggest that in HTSMCs, activation of MAPK pathways, NF‐κB, and p300 is essential for TNF‐α‐induced VCAM‐1 expression. J. Cell. Physiol. 207: 174–186, 2006. © 2005 Wiley‐Liss, Inc.
Comparative analysis of antitumor activity of CD40L, RANKL, and 4‐1BBL in vivo following intratumoral administration of viral vectors or transduced dendritic cells
Authors: Yurkovetsky Zoya R. , Shurin Galina V. , Barry Denise A. , Schuh Andre C. , Shurin Michael R. , Robbins Paul D. 
Published: November 2005

AbstractThe tumor necrosis factor (TNF) family comprises a group of ligands that regulate cell proliferation, differentiation, activation, maturation and apoptosis through interaction with the corresponding TNF receptor family members. In this study, we have evaluated whether adenovirus‐mediated intratumoral gene transfer of CD40L, RANKL, or 4‐1BBL elicits an immune response to established murine MC38 and TS/A tumors. Intratumoral administration of the recombinant adenoviral vectors expressing CD40L, RANKL or 4‐1BBL 7 days post‐tumor cell inoculation resulted in significant inhibition of MC38 tumor growth for all three ligands when compared with control groups treated with either saline or control adenovirus. However, intratumoral injection of Ad‐4‐1BBL or Ad‐CD40L resulted in a significantly stronger inhibition of TS/A tumor progression than did Ad‐RANKL treatment. We also demonstrated that intratumoral administration of dendritic cells (DC) transduced with adenoviral vectors encoding the TNF‐related ligands resulted in a significant inhibition of MC38 tumor growth as compared with control groups treated with Ad‐LacZ‐transduced DC or saline‐treated DC. In addition, DC overexpressing CD40L secreted considerably more IL‐12 and expressed higher levels of the co‐stimulatory molecules, CD80, CD86 and CD40, than did DC overexpressing LacZ, 4‐1BBL or RANKL. We have also demonstrated that DC/CD40L, DC/4‐1BBL, and DC/RANKL survived significantly longer than control DC or DC infected with the LacZ vector. Taken together, these results demonstrate that adenoviral gene transfer of CD40L, RANKL or 4‐1BBL elicit a significant antitumor effect in two different tumor models, with CD40L gene transfer inducing the strongest antitumor effect. Copyright © 2005 John Wiley & Sons, Ltd.
A system for efficient generation of adenovirus protein IX‐producing helper cell lines
Authors: Vellinga Jort , Uil Taco G. , de Vrij Jeroen , Rabelink Martijn J. W. E. , Lindholm Leif , Hoeben Rob C. 
Published: November 2005

AbstractBackgroundThe adenovirus 14.3 kDa hexon‐associated protein IX (pIX) functions in the viral capsid as ‘cement’ and assembles the hexons in stable groups‐of‐nine (GONs). Although viruses lacking pIX do not form GONs, and are less heat‐stable than wild‐type (wt) viruses, they can be propagated with the same kinetics and yields as the wt viruses. To facilitate ‘pseudotyping’ of adenoviral vectors we have set up an efficient system for the generation of pIX‐producing helper cell lines.MethodsWith a lentiviral pIX‐expression cassette, monoclonal and polyclonal helper cell lines were generated, which express wt or modified pIX genes at levels equivalent to wt HAdV‐5 infected cells. The incorporation efficiency into pIX gene deleted viruses was examined by Western analysis, immuno‐affinity electron microscopy, and heat‐stability assays.ResultsImmuno‐affinity electron microscopy on viruses lacking the pIX gene demonstrated that more than 96% of the particles contain pIX protein in their capsids after propagation on the pIX‐expressing helper cell lines. In addition, the pIX level in the helper cells was sufficient to generate heat‐stable particles. Finally, the ratio between pIX and fiber was equivalent to that found in wt particles. The pIX‐producing cell lines are very stable, demonstrating that pIX is not toxic to cells.ConclusionThese data demonstrate that lentivirus vectors can be used for the establishment of pIX‐complementing helper cell lines. Copyright © 2005 John Wiley & Sons, Ltd.
Efficient cold transfection of pea ferredoxin‐NADP(H) oxidoreductase into rat hepatocytes
Authors: Mediavilla María Gabriela , Krapp Adriana , Carrillo Néstor , Rodríguez Joaquín V. , Tiribelli Claudio , Guibert Edgardo E. 
Published: November 2005

AbstractWe describe the use of a non‐viral, polyethylenimine‐based vector to transfect rat hepatocytes preserved under hypothermic storage. DNA sequences encoding Escherichia coli β‐galactosidase and pea ferredoxin‐NADP(H) oxidoreductase (FNR), cloned into plasmids pCH110 and pKM4 respectively, were used. FNR was detected in the liver of animals transplanted with transfected cells; no reactivity was observed in endogenous parenchyma. The expression of the transgene was transient as it was detectable up to 96 h subsequently declining to undetectable levels. In contrast to non‐transfected cells, the engraftment of FNR‐positive cells was not associated with inflammatory reaction. The percentage of FNR‐positive implanted hepatocytes was at least five times higher than the original transfection efficiency measured in vitro, while the percentage of β‐galactosidase‐positive cells was similar for both methods. These data indicate that the transfection system is effective in the transfer of plasmid DNA into hepatocytes under cold preservation and suggest the advantage of pKM4‐transfected hepatocytes on engraftment in the recipient parenchyma. Copyright © 2005 John Wiley & Sons, Ltd.
Feeling bad: antecedents and consequences of negative emotions in ongoing change
Authors: Kiefer Tina 
Published: November 2005

AbstractThis paper examines how and why ongoing organizational change is experienced emotionally on an everyday basis and identifies important consequences of such emotional experiences. Three main antecedents to negative emotions in ongoing change are proposed: perceptions of an insecure future; perceptions of inadequate working conditions; and perceptions of inadequate treatment by the organization. Two outcome variables are identified: trust in the organization and withdrawal from the organization. The model is tested with cross‐sectional and follow‐up data from a field study. Regression and path analysis reveal that: a) ongoing changes are associated with negative emotions; b) this relationship between ongoing changes and emotions is mediated by the three proposed antecedents; and c) negative emotions predict employee lack of trust and employee withdrawal, both immediately and one month later. Copyright © 2005 John Wiley & Sons, Ltd.
Is it pay levels or pay raises that matter to fairness and turnover?
Authors: Tekleab Amanuel G. , Bartol Kathryn M. , Liu Wei 
Published: November 2005

AbstractTwo studies examined the relationship between actual pay and distributive and procedural justice, and the extent to which these perceptions were related to two important pay satisfaction dimensions, pay level and pay raise, and ultimately, impacted turnover. For each study the measures of pay and justice variables were obtained on a cross‐sectional basis, while the measure of turnover was necessarily lagged. Results showed that distributive justice mediated the relationship between pay and both pay level satisfaction and pay raise satisfaction. Furthermore, distributive justice was a stronger predictor of pay level satisfaction; whereas procedural justice was a stronger predictor of pay raise satisfaction. Procedural justice also played a moderating role in Study 2. The study also showed that only pay raise satisfaction was significantly and negatively related to turnover in Study 1, and to turnover via turnover intention in Study 2. Results support the value of considering pay satisfaction as multidimensional when evaluating justice issues in a compensation context. Copyright © 2005 John Wiley & Sons, Ltd.
Self‐interest: defining and understanding a human motive
Authors: Cropanzano Russell , Goldman Barry , Folger Robert 
Published: November 2005

AbstractThis paper explores the concept of self‐interest. Taking a multi‐disciplinary perspective, we discuss and critique various definitions of this phenomenon. We argue that self‐interest is an important human motive. However, we also emphasize that other human motives exist. These include empathy toward others and adherence to moral duty. Copyright © 2005 John Wiley & Sons, Ltd.
Flexible work bundles and organizational competitiveness: a cross‐national study of the European work context
Authors: Stavrou Eleni T. 
Published: November 2005

AbstractThe present study explores the categorization of flexible work arrangements (FWAs) into bundles and their connection to organizational competitiveness in the European Union. The measures of competitiveness were performance, turnover, and absenteeism. Four moderators were used in the study, organization sector, industry sector, organization size, and organizational women‐supportiveness. The analyses revealed four FWA Bundles, namely Non‐Standard Work Patterns, Work Away from the Office, Non‐Standard Work Hours and Work Outsourced. Non‐Standard Work Patterns were found to be related to decreased turnover (in the private sector), while Work Away from the Office was related to improved performance and reduced absenteeism. Non‐Standard Work Hours and Work Outsourced (within the public sector) were positively related to turnover, suggesting that these types are possibly not being used as true flexibility arrangements. Finally, post‐hoc analysis revealed that Non‐Standard Work Hours was related to increased performance only among Swedish organizations. Implications for management and future research are discussed. Copyright © 2005 John Wiley & Sons, Ltd.
Core self‐evaluations in Japan: relative effects on job satisfaction, life satisfaction, and happiness
Authors: Piccolo Ronald F. , Judge Timothy A. , Takahashi Koji , Watanabe Naotaka , Locke Edwin A. 
Published: November 2005

AbstractThe present study tested, in a non‐Western culture (Japan), the relative validity in predicting job satisfaction, life satisfaction, and happiness of core self‐evaluations (CSE), positive and negative affectivity (PA/NA), and the Neutral Objects Satisfaction Questionnaire (NOSQ). Consistent with previous results in primarily Western cultures, the four lower‐order traits that comprise CSE—self‐esteem, generalized self‐efficacy, locus of control, and neuroticism—indicated a higher‐order factor. While each lower‐order trait was itself related to the study's criteria, the CSE concept displayed in general, higher correlations with the dependent variables, and explained incremental variance in two of the study's three outcomes beyond PA, NA, and the NOSQ. These results indicate initial support for the generalizability of CSE in a culture that differs in many respects from Western cultures, and suggest that judgments of satisfaction and happiness in a non‐Western culture have a dispositional source. Copyright © 2005 John Wiley & Sons, Ltd.
Headspace single‐drop microextraction with in‐drop derivatization for aldehyde analysis
Authors: Deng Chunhui , Yao Ning , Li Ning , Zhang Xiangmin 
Published: November 2005

AbstractA new technique, headspace single‐drop microextraction (HS‐SDME) with in‐drop derivatization, was developed. Its feasibility was demonstrated by analysis of the model compounds, aldehydes in water. A hanging microliter drop of solvent containing the derivatization agent of O‐2,3,4,5,6‐(pentaflurobenzyl)hydroxylamine hydrochloride (PFBHA) was shown to be an excellent extraction, concentration, and derivatization medium for headspace analysis of aldehydes by GC‐MS. Using the microdrop solvent with PFBHA, acetaldehyde, propanal, butanal, hexanal, and heptanal in water were headspace extracted and simultaneously derivatized. The formed oximes in the microdrop were analyzed by GC‐MS. HS‐SDME and in‐drop derivatization parameters (extraction solvent, extraction temperature, extraction time, stirring rate microdrop volume, and the headspace volume) and the method validations (linearity, precision, detection limit, and recovery) were studied. Compared to liquid–liquid extraction and solid‐phase microextraction, HS‐SDME with in‐drop derivatization is a simple, rapid, convenient, and inexpensive sample technique.
Analysis of the disaccharides derived from hyaluronic acid and chondroitin sulfate by capillary electrophoresis with sample stacking
Authors: Yang Yifang , Breadmore Michael C. , Thormann Wolfgang 
Published: November 2005

AbstractCE conditions for monitoring the unsaturated disaccharides of hyaluronic acid (di‐HA) and chondroitin sulfate (di‐CS) using an alkaline tetraborate buffer, electrokinetic sample injection, and UV absorption detection at 232 nm are reported. Separations were performed in an uncoated fused‐silica capillary having reversed polarity and reversed electroosmosis generated with the addition of CTAB to the buffer. The influence of various separation parameters, including the concentration of CTAB, buffer pH, concentration of tetraborate, and applied voltage, on the resolution of the two disaccharides was investigated. Baseline separation was obtained with 25 mM tetraborate at pH 10.0 and having 0.05 mM CTAB. Chloride and phosphate in the sample are beneficial for the stacking of the disaccharides, with di‐HA forming a much sharper peak than di‐CS. Using samples prepared in 25 mM Tris‐HCl (pH 7.5) and electrokinetic injection at the cathode at –10 kV for 40 s, linear relationships between the corrected peak area and the concentration of the disaccharides have been found in the ranges of 1.0–400.0 and 0.1–1.0 μg/mL (0.2–1.0 μg/mL for di‐CS), with correlation coefficients being >0.9933 in all cases. The RSDs of detection times and corrected peak areas were between 1.13–1.24 and 1.57–2.13%, respectively. Applied to human serum samples that were prepared by ethanol precipitation and depolymerization of the two polysaccharides with chondroitinase ABC reveals comigration of endogenous compounds with di‐HA and a sample‐dependent detection time. The di‐HA content in the serum sample can be estimated via subtraction of the blank peak that is obtained without enzymatic hydrolysis.