bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of the urokinase receptor regulates focal adhesion assembly and cell migration in adenoid cystic carcinoma cells
Authors: Abu‐Ali Samah , Sugiura Tsuyoshi , Takahashi Miho , Shiratsuchi Toru , Ikari Tatsuya , Seki Katsuhiro , Hiraki Akimitsu , Matsuki Ryousuke , Shirasuna Kanemitsu 
Published: November 2004

AbstractAdenoid cystic carcinoma (AdCC) cell lines (ACCS and ACCT) showed higher migration responses and adhesion to the extracellular matrix (ECM), especially types I and IV collagen, than did the oral squamous cell carcinoma (SCC) lines (NA and TF). The response to collagens was largely and exclusively inhibited by anti‐α2 integrin antibody. Moreover, AdCC cell lines expressed higher surface levels of urokinase‐type plasminogen activator receptor (uPAR) than did SCC cell lines. When AdCC cells were plated on collagen, the surface level of uPAR was increased, and numerous focal adhesions consisting of uPAR, vinculin, and paxillin were assembled; whereas collagen‐stimulated SCC cell counterparts or AdCC cells plated on other types of ECM, such as fibronectin, failed to assemble such definite focal adhesions. In order to elucidate the association of uPAR with collagen‐induced events, an ACCS‐AS cell line transfected with a vector expressing antisense uPAR RNA was established and shown to have reduced uPAR (about 10% that of parental ACCS at both the protein and mRNA levels). ACCS‐AS showed a strong reduction of collagen‐stimulated migration and focal adhesion assembly of α2 integrin, vinculin, and paxillin. These findings suggest that AdCC has a proclivity for migrating to types I and IV collagens due to the overexpression of uPAR, which plays a key role in focal adhesion assembly and migration. © 2004 Wiley‐Liss, Inc.
Mitochondrial tissue specificity of substrates utilization in rat cardiac and skeletal muscles
Authors: Ponsot E. , Zoll J. , N'Guessan B. , Ribera F. , Lampert E. , Richard R. , Veksler V. , Ventura‐Clapier R. , Mettauer B. 
Published: November 2004

AbstractAs energetic metabolism is crucial for muscles, they develop different adaptations to respond to fluctuating demand among muscle types. Whereas quantitative characteristics are known, no study described simultaneously quantitative and qualitative differences among muscle types in terms of substrates utilization patterns. This study thus defined the pattern of substrates preferential utilization by mitochondria from glycolytic gastrocnemius (GAS) and oxidative soleus (SOL) skeletal muscles and from heart left ventrical (LV) in rats. We measured in situ, ADP (2 mM)‐stimulated, mitochondrial respiration rates from skinned fibers in presence of increasing concentrations of pyruvate (Pyr) + malate (Mal), palmitoyl‐carnitine (Palm‐C) + Mal, glutamate (Glut) + Mal, glycerol‐3‐phosphate (G3‐P), lactate (Lact) + Mal. Because the fibers oxygen uptake (Vs) followed Michaelis–Menten kinetics in function of substrates level we determined the Vs and Km, representing maximal oxidative capacity and the mitochondrial sensibility for each substrate, respectively. Vs were in the order GAS < SOL < LV for Pyr, Glu, and Palm‐C substrates, whereas in the order SOL = LV < GAS with G3‐P. Moreover, the relative capacity to oxidize Palm‐C is extremely higher in LV than in SOL. Vs was not stimulated by the Lact substrate. The Km was equal for Pyr among muscles, but much lower for G3‐P in GAS and lower for Palm‐C in LV. These results demonstrate qualitative mitochondrial tissue specificity for metabolic pathways. Mitochondria of glycolytic muscle fibers are well adapted to play a central role for maintaining a satisfactory cytosolic redox state in these fibers, whereas mitochondria of LV developed important capacities to use fatty acids. © 2004 Wiley‐Liss, Inc.
Transcriptional regulation of thioredoxin reductase 1 expression by cadmium in vascular endothelial cells: Role of NF‐E2‐related factor‐2
Authors: Sakurai Atsuko , Nishimoto Michie , Himeno Seiichiro , Imura Nobumasa , Tsujimoto Masafumi , Kunimoto Manabu , Hara Shuntaro 
Published: November 2004

AbstractThioredoxin reductase (TrxR) is a selenoprotein that catalyzes the reduction of the active site disulfide of thioredoxin (Trx), which regulates the redox status of the cells. In the present study, we found that TrxR1, one of the three TrxR isozymes, was induced by cadmium as well as tumor necrosis factor α (TNFα) in bovine arterial endothelial cells (BAEC), and investigated the mechanism of cadmium‐induced TrxR1 expression. We here showed that cadmium, differently from TNFα, enhanced the promoter activity of the 5′‐flanking region of human TrxR1 gene (nucleotides −1692 to +49). Deletion and site‐directed mutation of antioxidant responsive element (ARE) (nucleotides −62 to −48) in this region abolished the response to cadmium. Overexpression of NF‐E2‐related factor‐2 (Nrf2) augmented the TrxR1 promoter activity. In contrast, overexpression of the dominant negative mutant of Nrf2 suppressed cadmium‐induced activation of TrxR1 promoter through the ARE. Chromatin immunoprecipitation (ChIP) assays showed that anti‐Nrf2 antibody precipitated ARE from the chromatin of the cadmium‐treated cells. These results indicated that cadmium‐induced TrxR1 gene expression is mediated by the activation of Nrf2 transcription factor and its binding to ARE in the TrxR1 gene promoter. We further found that in addition to cadmium, the activators of Nrf2, such as diethyl maleate (DEM) and arsenite, induced both TrxR1 and Trx gene expression in BAEC. Nrf2 might play an important role in the regulation of the cellular Trx system consisting of Trx and TrxR. © 2004 Wiley‐Liss, Inc.
Hedgehog signaling in normal urothelial cells and in urothelial carcinoma cell lines
Authors: Thievessen Ingo , Wolter Marietta , Prior Andrea , Seifert Hans‐Helge , Schulz Wolfgang A. 
Published: November 2004

AbstractConstitutive activation of hedgehog signaling, often caused byPTCH1inactivation and leading to inappropriate activation of GLI target genes, is crucial for the development of several human tumors including basal cell carcinoma of the skin and medulloblastoma. ThePTCH1gene at 9q22 is also considered as a candidate tumor suppressor in transitional cell carcinoma (TCC), of which >50% show LOH in this region. However, only rare mutations have been found inPTCH1. We have therefore investigated GLI‐dependent promoter activity and expression of hedgehog pathway components in TCC cell lines and proliferating normal urothelial cells. Normal urothelial cells cultured in serum‐free medium, but not TCC lines exhibited low, but significant promoter activity under standard growth conditions. Accordingly, GLI1‐3 andPTCH1mRNAs were expressed at moderate levels, and sonic hedgehog (SHH) mRNA expression was low to undetectable. In co‐transfection experiments GLI1 increased promoter activity significantly in one TCC line and further in normal urothelial cells, but less strongly in other TCC lines. Expression patterns of GLI factor mRNAs did not correlate with inducibility. No significant effects of SHH or cyclopamine on proliferation were observed, ruling out autocrine effects. However, SHH induced GLI‐dependent promoter activity in normal urothelial cells. Taken together, our data suggest that the hedgehog pathway is weakly active in normal adult urothelial cells and of limited importance in TCC. © 2004 Wiley‐Liss, Inc.
Requirement of protein phosphatase 2A for recruitment of IQGAP1 to Rac‐bound β1 integrin
Authors: Suzuki Katsuo , Chikamatsu Yasuhiro , Takahashi Kazuhide 
Published: November 2004

AbstractSerine/threonine protein phosphatase (PP) 2A is thought to dephosphorylate phosphorylated β1 integrin to link with actin filaments (F‐actin). However, whether PP2A participates in the regulation of F‐actin assembly to which β1 integrin is anchored is unclear. We report here that the core enzyme of PP2A (PP2A‐AC), consisting of the regulatory subunit A (PP2A‐A) and the catalytic subunit C (PP2A‐C), forms a complex with β1 integrin, a small GTPase Rac, and its effector IQGAP1 in non‐malignant human mammary epithelial (HME) cells. Treatment of HME cells with okadaic acid (OA), an inhibitor of PP2A, caused cell rounding, reduction in F‐actin assembly that links with β1 integrin, and dissociation of IQGAP1‐bound PP2A‐AC from Rac‐β1 integrin. The dissociation of IQGAP1‐PP2A‐AC was accompanied by loss of F‐actin gelating activity of Rac‐β1 integrin. In breast cancer MCF‐7 cells, which possess PP2A‐C but lack PP2A‐A, IQGAP1 was not associated with Rac‐β1 integrin but with PP2A‐C, with no distinct F‐actin assembly that linked to Rac‐β1 integrin even before treatment with OA. We therefore propose that PP2A, especially PP2A‐A, functions to maintain F‐actin assembly to which β1 integrin is anchored by recruitment of IQGAP1 to Rac‐β1 integrin. © 2004 Wiley‐Liss, Inc.
Birds have dinosaur wings: The molecular evidence
Authors: Vargas Alexander O. , Fallon John F. 
Published: November 2004

AbstractWithin developmental biology, the digits of the wing of birds are considered on embryological grounds to be digits 2, 3 and 4. In contrast, within paleontology, wing digits are named 1, 2, 3 as a result of phylogenetic analysis of fossil taxa indicating that birds descended from theropod dinosaurs that had lost digits 4 and 5. It has been argued that the development of the wing does not support the conclusion that birds are theropods, and that birds must have descended from ancestors that had lost digits 1 and 5. Here we use highly conserved gene expression patterns in the developing limbs of mouse and chicken, including the chicken talpid2mutant and polydactylous Silkie breed (Silkie mutant), to aid the assessment of digital identity in the wing. Digit 1 in developing limbs does not express Hoxd12, but expresses Hoxd13. All other digits express both Hoxd12and Hoxd13. We found this signature expression pattern identifies the anteriormost digit of the wing as digit 1, in accordance with the hypothesis these digits are 1, 2 and 3, as in theropod dinosaurs. Our evidence contradicts the long‐standing argument that the development of the wing does not support the hypothesis that birds are living dinosaurs. J. Exp. Zool. (Mol. Dev. Evol.) 304:000–000, 2004. © 2004 Wiley‐Liss, Inc.
Low‐pH‐sensitive poly(ethylene glycol) (PEG)‐stabilized plasmid nanolipoparticles: effects of PEG chain length, lipid composition and assembly conditions on gene delivery
Authors: Li Weijun , Huang Zhaohua , MacKay J. Andrew , Grube Stefan , Szoka Francis C. 
Published: November 2004

AbstractBackgroundWe have studied the effects of the poly(ethylene glycol) (PEG) chain length and acyl chain composition on the pH‐sensitivity of acid‐labile PEG‐diorthoester (POD) lipids. The optimal conditions are described for preparation of DNA plasmid encapsulated POD nanolipoparticles (NLPs) which mediate high gene delivery activity in vitro with moderate cytotoxicity.Methods and ResultsA series of POD lipids with various PEG chain lengths (750, 2000, and 5000 Da) or acyl chains (distearoyl 18 : 0 or dioleoyl 18 : 1) were incorporated into DNA containing NLPs or model liposomes as a stealth and bioresponsive component. We investigated the collapse kinetics of the POD‐stabilized liposomes when the PEG chain length was changed. We optimized a detergent dialysis method to encapsulate plasmid DNA into NLPs prepared from a mixture of the various POD lipids, cationic lipid and phosphatidylethanolamine lipid. A critical concentration (28 mM) of n‐octyl‐β‐D‐glucopyranoside (OG) enabled high encapsulation of DNA plasmid into 100 nm particles with a neutral surface charge. The POD NLPs are stable at pH 8.5 but rapidly collapse (∼10 min) into aggregates at pH 5.0. In the detergent solution there is a metastable DNA‐lipid intermediate that evolves into a stable NLP if the detergent is removed shortly after adding DNA to the lipid‐detergent mixture. The rank order of transfection activity from NLPs containing PEG‐lipid was POD 750 > POD 5000 = POD 2000 > non‐pH‐sensitive PEG‐lipid. The particle size stability was in the reverse order. Binding of the NLPs to cells reached a maximum level by 12 hours. The POD NLPs had slightly less transfection activity but considerably lower cytotoxicity than the PEI‐DNA polyplex.ConclusionsOf the PEG‐orthoester lipids tested, POD 2000 is the better choice for the preparation of sterically stabilized NLPs with a small particle diameter, good stability, low cytotoxicity, and satisfactory transfection activity. Copyright © 2004 John Wiley & Sons, Ltd.
Trend and variability of China precipitation in spring and summer: linkage to sea‐surface temperatures
Authors: Yang Fanglin , Lau K.‐M. 
Published: November 2004

AbstractObservational records in the past 50 years show an upward trend of boreal‐summer precipitation over central eastern China and a downward trend over northern China. During boreal spring, the trend is upward over southeastern China and downward over central eastern China. This study explores the forcing mechanism of these trends in association with the global sea‐surface temperature (SST) variations on the interannual and interdecadal time scales.Results based on singular value decomposition (SVD) analyses show that the interannual variability of China precipitation in boreal spring and summer can be well defined by two centres of action for each season, which are covarying with two interannual modes of SSTs. The first SVD modes of precipitation in spring and summer, which are centred in southeastern China and northern China respectively, are linked to an El Niño–southern oscillation (ENSO)‐like mode of SSTs. The second SVD modes of precipitation in both seasons are confined to central eastern China, and are primarily linked to SST variations over the warm pool and the Indian Ocean. Features of the anomalous 850 hPa winds and 700 hPa geopotential height corresponding to these modes support a physical mechanism that explains the causal links between the modal variations of precipitation and SSTs.On the decadal and longer time scale, similar causal links are found between the same modes of precipitation and SSTs, except for the case of springtime precipitation over central eastern China. For this case, while the interannual mode of precipitation is positively correlated with the interannual variations of SSTs over the warm pool and Indian Ocean, the interdecadal mode is negatively correlated with a different SST mode, i.e. the North Pacific mode. The latter is responsible for the observed downward trend of springtime precipitation over central eastern China. For all other cases, both the interannual and interdecadal variations of precipitation can be explained by the same mode of SSTs. The upward trend of springtime precipitation over southeastern China and downward trend of summertime precipitation over northern China are attributable to the warming trend of the ENSO‐like mode. The recent frequent summertime floods over central eastern China are linked to the warming trend of SSTs over the warm pool and Indian Ocean. Copyright © 2004 Royal Meteorological Society
Spatial pattern in the precipitation regime of Nepal
Authors: Kansakar Sunil R. , Hannah David M. , Gerrard John , Rees Gwyn 
Published: November 2004

AbstractA large‐scale perspective is provided upon the nature of precipitation regimes across Nepal by classifying long‐term mean monthly precipitation data for 222 stations. The classification methodology is shown to be a useful tool for identifying underlying spatial structure in precipitation regime shape (seasonal variability) and magnitude (size) in an extreme physical environment where climatological patterns are complex and poorly known. Four precipitation regime shape classes are identified: (a) July–August peaks are typical of western regions; (b) marked July peaks are characteristic of the central region and eastern lowlands; (c) July peaks with gradual onset are mainly concentrated in eastern Middle Mountains; and (d) July–August peaks with winter precipitation are confined to western higher mountains, particularly the Trans‐Himalayan region. Four precipitation regime magnitude classes are found: (a) low regimes clearly dominate western high‐mountain areas but occur more widely across the High Mountains and High Himalaya; (b) intermediate regimes are distributed from east to west at low altitude, dominating the western Terai/Siwaliks; (c) moderately high regimes are widespread but most evident in the Terai (plains) to Middle Mountains of central and eastern parts and eastern high mountains; and (d) high precipitation zones are situated near Pokhara and northeast of the Kathmandu Valley around Langtang. A composite (shape and magnitude) regime classification indicates the key controls upon spatial patterns in Nepalese precipitation to be: length and timing of the summer monsoon (duration decreases east to west with later onset and earlier withdrawal in the west); successively higher altitude, east–west‐trending mountain ranges causing rainfall to decline broadly south–north; topographic barriers that induce local rain shadows (lee) and precipitation hotspots (windward side); and westerly weather systems supplying winter precipitation to the northwest mountains. Although general patterns relating to zonal movement of the summer monsoon and physiographic (mountain ranges) controls upon precipitation may be identified, the role of mountainous relief in yielding localized precipitation patterns is significant. Copyright © 2004 Royal Meteorological Society
Anti‐apoptotic action of stem cell factor on oocytes in primordial follicles and its signal transduction
Authors: Jin Xuan , Han Chun‐Sheng , Yu Fu‐Qing , Wei Peng , Hu Zhao‐Yuan , Liu Yi‐Xun 
Published: November 2004

AbstractStem cell factor (SCF) is essential for the development of primordial follicles. One of its functions is to prevent oocytes from apoptosis. However, the underlying mechanism remains largely unknown. By using cultured ovaries that are rich in primordial follicles, the anti‐apoptotic action of SCF and the potential signal transduction pathways were investigated. The apoptosis was evaluated by means of in situ 3′‐end labeling. The expressions of proteins were analyzed with immunohistochemistry and Western blot. The data showed that SCF significantly prevented oocytes from apoptosis in the cultured organs. Addition of a specific pharmacological inhibitor of PI3K abolished the anti‐apoptotic action of SCF while that of a MEK inhibitor did not. The phosphorylation of two mitogen activated protein kinases (MAPKs) (p42 and p44) and AKT, the respective substrates of MEK and PI3K, were enhanced by SCF treatment. Not surprisingly, the MAPK activation occurred only in theca cells. The expressions of apoptosis‐related gene products, the Bcl‐2 family proteins, in response to SCF treatment were also investigated. While SCF up‐regulated the expression of the anti‐apoptotic proteins Bcl‐2 and Bcl‐xL, it did the opposite to the pro‐apoptotic factor Bax. The PI3K inhibitor reversed the regulation of SCF on Bcl‐xL and Bax but not on Bcl‐2. Therefore, it seemed that SCF initiated an anti‐apoptotic signal starting from its membrane receptor c‐kit to Bcl‐2 family members through PI3K/AKT and other signaling cascades in the oocytes of primordial follicles. Mol. Reprod. Dev. 70: 82–90, 2004. © 2004 Wiley‐Liss, Inc.
C‐kit receptor and its possible function in human spermatozoa
Authors: Feng Huai L. , Sandlow J.I. , Zheng L.J. 
Published: November 2004

AbstractThe presence and role of the c‐kit proto‐oncogene protein was investigated in the mature sperm of the human. A polyclonal antibody against the c‐kit peptide was used to perform immunohistochemical (IHC) staining, electron microscopy (EM) studies, and Western blot analysis. The acrosomal region of fresh sperm specifically stained with the antibody. No acrosomal staining or staining limited to the equatorial region was noted in the acrosome‐reacted (AR) sperm. EM studies demonstrated immunogold label on the plasma membrane (PM) of the acrosome, and confirmed the lack of binding following the acrosome reaction. A 150 kDa band was detected by Western blot analysis. This protein was released from the sperm surface during sperm capacitation and the acrosome reaction. Antibody against the c‐kit receptor significantly inhibited the acrosome reaction and increased sperm agglutination, but did not significantly inhibit sperm motility. These results suggest that the c‐kit receptor protein is present in mature human sperm and is released during capacitation and/or the acrosome reaction. The assessment of the c‐kit receptor may also be a useful assay for sperm function in male infertility. Mol. Reprod. Dev. 70: 103–110, 2004. © 2004 Wiley‐Liss, Inc.
Structural and molecular characterization of equine sperm‐binding fibronectin‐II module proteins
Authors: Ekhlasi‐Hundrieser Mahnaz , Schäfer Bettina , Kirchhoff Christiane , Hess Oliver , Bellair Simone , Müller Peter , Töpfer‐Petersen Edda 
Published: November 2004

AbstractPhospholipid‐binding proteins in the male genital tract are characterized by differing numbers Fn‐2 modules (B‐domain) carrying N‐terminal extensions (A‐domain) of variable length. In the stallion, three different proteins were identified, SP‐1, SP‐2, and EQ‐12. SP‐1 and SP‐2 of the AA'BB'‐ and ABB'‐type, respectively, are major proteins of the seminal plasma. Here we report the cDNA sequences of SP‐1, and of a new member of the SP‐2 family (SPnew) and the partial characterization of their iso‐ and glycoforms. The phosphorylcholine (PC)‐binding ability of the long Fn‐2 protein, EQ‐12, with four tandemly arranged Fn‐2 modules was determined by PC‐affinity chromatography. Expression patterns of EQ‐12, and the SP‐proteins were studied by means of RT‐PCR, Northern blot analysis and immunological approaches indicating differential expression along the male reproductive tract. The vast majority of the short SP‐1 and SP‐2 proteins are produced by the ampulla whereas EQ‐12 originates from the epididymis. Indirect immunofluorescence microscopy of sperm isolated from different regions of the epididymis and Western blot analysis indicate that both, the long and the short Fn‐2 proteins associate to the sperm surface during post‐testicular maturation. Sperm binding of Fn‐2 proteins at the post‐acrosome and midpiece was at first detected in the corpus epididymis. Enhanced fluorescence intensity after ejaculation point to an increased number of molecules bound to the sperm surface. The function of these proteins is discussed in regard to their structure–function relationships. Mol. Reprod. Dev. 70: 45–57, 2004. © 2004 Wiley‐Liss, Inc.