bluuebunny/crossref_metadata_2025_split huggingface dataset:
A displaced PAG enhances proximal signaling and SDF‐1‐induced T cell migration
Authors: Posevitz‐Fejfár Anita , Šmída Michal , Kliche Stefanie , Hartig Roland , Schraven Burkhart , Lindquist Jonathan A. 
Published: December 2007

AbstractPAG, the phosphoprotein associated with glycosphingolipid‐enriched microdomains (GEM), negatively regulates Src family kinases by recruiting C‐terminal Src kinase (Csk) to the membrane, where Csk phosphorylates the inhibitory tyrosine of the Src kinases. S‐acylation of a CxxC motif juxtaposed to the transmembrane domain within PAG has been proposed to be responsible for targeting PAG to the lipid rafts. Here, we present the characterization of a mutant PAG molecule lacking the palmitoylation motif. We demonstrate that the mutant protein is expressed at the plasma membrane, but does not localize within the GEM. Despite being displaced, the mutant PAG molecule still binds the Src kinase Fyn and the cytoskeletal adaptor ezrin‐radixin‐moesin‐binding phosphoprotein of 50 kDa, becomes tyrosine‐phosphorylated, and recruits Csk to the membrane. Functional characterization of the mutant shows that, unlike WT PAG, it does not block proximal TCR signaling, and surprisingly enhances stromal cell‐derived factor 1 (CXCL12)‐induced migration. The mutant functions by depleting Csk from the GEM fractions, as apparent by changes in the phosphorylation of the inhibitory tyrosines within the Src kinases. Indeed this mechanism is supported by RNA interference of PAG, which results in enhanced migration and Src kinase activity. Our results therefore support a functional role for the compartmentalization of Src kinases within the membrane.
The orally‐active and selective c‐Fms tyrosine kinase inhibitor Ki20227 inhibits disease progression in a collagen‐induced arthritis mouse model
Authors: Ohno Hiroaki , Uemura Yasunori , Murooka Hideko , Takanashi Hiromi , Tokieda Takemi , Ohzeki Yumiko , Kubo Kazuo , Serizawa Isao 
Published: December 2007

AbstractMacrophage colony‐stimulating factor (M‐CSF) is important in the development of macrophages and osteoclasts. Previous studies have also shown that CD11b+ myeloblasts and osteoclasts play key roles during inflammation and bone destruction in arthritic lesions. In this study, we investigated whether N‐{4‐[(6,7‐dimethoxy‐4‐quinolyl)oxy]‐2‐methoxyphenyl}‐N′‐[1‐(1,3‐thiazole‐2‐yl)ethyl] urea (Ki20227), an inhibitor of the M‐CSF receptor (c‐Fms), suppressed disease progression in a type II collagen (CII)‐induced arthritis (CIA) mouse model. We found that Ki20227 inhibited M‐CSF‐dependent reactions, such as lipopolysaccharide‐induced tumor necrosis factor‐α production, which were enhanced by M‐CSF in vitro. Oral administration of Ki20227 in vivo prevented inflammatory cell infiltration and bone destruction, and consequently suppressed disease progression. In addition, the number of CD11b+, Gr‐1+, and Ly‐6G+ cells in the spleen decreased in the Ki20227‐treated mice, and the CII‐induced cytokine production in splenocytes isolated from the Ki20227‐treated arthritic mice was also reduced. These observations indicate that Ki20227 might exert its therapeutic effects in the CIA mouse model by suppressing the M‐CSF‐dependent accumulation of both inflammatory and osteoclast cells, as well as by inhibiting inflammatory cytokine production. Hence, inhibitors of the c‐Fms tyrosine kinase might act as anti‐inflammatory or anti‐osteolytic agents against arthritis.
Retinoid receptor‐activating ligands are produced within the mouse thymus during postnatal development
Authors: Kiss Ildikó , Rühl Ralph , Szegezdi Éva , Fritzsche Britta , Tóth Beáta , Pongrácz Judit , Perlmann Thomas , Fésüs László , Szondy Zsuzsa 
Published: December 2007

AbstractVitamin A deficiency is known to be accompanied with immune deficiency and susceptibility to a wide range of infectious diseases. Experimental evidence suggests that the active metabolites of vitamin A that mediate its effects on the immune system are the retinoic acids (RA), which are ligands for the nuclear RA receptor (RAR) family. RA were previously shown both to promote proliferation and to regulate apoptosis of thymocytes. In this study we detected the age‐dependent mRNA expression of retinaldehyde dehydrogenases (RALDH1 and 2), cellular RA binding protein‐II and CYP26A, proteins responsible for the synthesis, nuclear transport and degradation of RA in the postnatally developing thymus. RALDH1 was located in thymic epithelial cells. However, the amount of all‐trans RA in thymic homogenates was close to the detection limit, suggesting that in this tissue all‐trans RA is not the main RAR‐regulating product of retinol metabolism. At the same time, by measuring the induction of a RAR‐responsive transgene in two independent transgenic mouse strains, we demonstrated the production of an RAR‐activating ligand, which was age and RALDH dependent. Our data provide evidence for the existence of endogenous retinoid synthesis in the thymus and suggest that retinoids similar to glucocorticoids might indeed be involved in the regulation of thymic proliferation and selection processes by being present in the thymus in functionally effective amounts.
RIP2 contributes to Nod signaling but is not essential for T cell proliferation, T helper differentiation or TLR responses
Authors: Hall Håkan T. L. , Wilhelm Margareta T. , Saibil Samuel D. , Mak Tak W. , Flavell Richard A. , Ohashi Pamela S. 
Published: December 2007

AbstractReceptor‐interacting protein 2 (RIP2), also known as CARDIAK and RICK, has been reported to play a role in both adaptive T cell responses and innate immunity as a mediator in TLR signaling and nucleotide‐binding oligomerization domain (Nod) signaling. Because initial reports remain controversial, we have further examined both innate and adaptive immune responses in RIP2‐deficient mice on the C57BL/6 background. Despite the up‐regulation of RIP2 after T cell activation, we could not detect any defect in T cell proliferation or Th1/Th2 responses in RIP2‐KO mice. Furthermore, we found that TLR responses in RIP2‐deficient macrophages were normal. However, our analysis showed that Nod signaling was impaired in macrophages from RIP2‐deficient mice. In conclusion, our data demonstrate a critical role for RIP2 in Nod signaling, while T cell proliferation, T helper differentiation and TLR responses were unaffected by the absence of RIP2.
Apoptosis differentially regulates mesenteric and subcutaneous lymph node immune responses to Trypanosoma cruzi
Authors: de Meis Juliana , Ferreira Lidia M. S. , Guillermo Landi V. C. , Silva Elisabeth M. , DosReis George A. , Lopes Marcela F. 
Published: December 2007

AbstractInfection with Trypanosoma cruzi causes expansion of subcutaneous (SLN) and atrophy of mesenteric (MLN) lymph nodes. Here we show that excision of MLN increased parasitemia in T. cruzi‐infected mice. We then studied how apoptosis of MLN cells affects immune responses to infection. T cell apoptosis increased in the MLN compared to SLN in T. cruzi‐infected mice. Absolute numbers of naïve T cells decreased, and activated T cells failed to accumulate in MLN during infection. In addition, activated T cells from MLN produced less IL‐2, IFN‐γ, IL‐4, and IL‐10 than T cells from SLN. Treatment with IL‐4 or with caspase‐9 inhibitor increased the recovery of viable T cells in vitro. Treatment with caspase‐9 inhibitor also increased the production of cytokines by MLN T cells from infected mice. Moreover, injection of a pan caspase inhibitor prevented MLN atrophy during T. cruzi infection. Caspase‐9, but not caspase‐8, inhibitor also reduced MLN atrophy and increased the recovery of naïve and activated T cells from MLN. These findings indicate that caspase‐mediated apoptosis and defective cytokine production are implicated in MLN atrophy and affect immune responses to T. cruzi infection.
Design and Synthesis of 1‐Benzazepine Derivatives by Strategic Utilization of Suzuki–Miyaura Cross‐Coupling, Aza‐Claisen Rearrangement and Ring‐Closing Metathesis
Authors: Kotha Sambasivarao , Shah Vrajesh R. 
Published: December 2007

AbstractA new and simple methodology has been realized for the synthesis of 7‐substituted 2,3,4,5‐tetrahydro‐1‐benzazepine derivatives with Suzuki–Miyaura cross‐coupling, aza‐Claisen rearrangement and ring‐closing metathesis (RCM) the key steps. Here,o‐allylacetanilide derivatives were obtained by Suzuki–Miyaura cross‐coupling of the correspondingo‐iodoacetanilides. Theo‐allylacetanilides, onN‐allylation under phase‐transfter catalysis conditions, provided diallyl derivatives as suitable precursors for RCM. These diallyl derivatives, on treatment with Grubbs' second‐generation catalyst, gave the 1‐benzazepine derivatives in moderate‐to‐good yields. These RCM products were found to be unstable and so they were hydrogenated to provide stable tetahydro‐1‐benzazepine derivatives25–28. 1H‐1‐Benzazepin‐2‐one derivatives44and45were synthesized following a similar sequence. In addition, the aza‐Claisen rearrangement was utilized as a key step in the preparation of RCM precursor17. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Response surface examination of the relationship between experimental conditions and product distribution in electrophoretically mediated microanalysis
Authors: Montes Ruth E. , Gomez Frank A. , Hanrahan Grady 
Published: December 2007

AbstractThis work presents the first known use of response surface methodology (RSM) in electrophoretically mediated microanalysis. This concept is demonstrated by examining the optimization of reaction conditions for the conversion of nicotinamide adenine dinucleotide to nicotinamide adenine dinucleotide, reduced form by glucose‐6‐phosphate dehydrogenase (G6PDH, EC 1.1.1.49) in the conversion of glucose‐6‐phosphate to 6‐phosphogluconate. Experimental factors including voltage, enzyme concentration, and mixing time of reaction at the applied voltage were selected at three levels and tested in a Box–Behnken response surface design. Upon migration in a capillary under CE conditions, plugs of substrate and enzyme are injected separately in buffer and allowed to react at variable conditions. Extent of reaction and product ratios were subsequently determined by CE. The model predicted results are shown to be in good agreement (7.1% discrepancy difference) with experimental data. The use of chemometric RSM provides a direct relationship between electrophoretic conditions and product distribution of microscale reactions using CE, thereby offering a new and versatile approach to optimizing enzymatic experimental conditions.
A comparison of preconditioners for incompressible Navier–Stokes solvers
Authors: ur Rehman M. , Vuik C. , Segal G. 
Published: December 2007

AbstractWe consider solution methods for large systems of linear equations that arise from the finite element discretization of the incompressible Navier–Stokes equations. These systems are of the so‐called saddle point type, which means that there is a large block of zeros on the main diagonal. To solve these types of systems efficiently, several block preconditioners have been published. These types of preconditioners require adaptation of standard finite element packages. The alternative is to apply a standard ILU preconditioner in combination with a suitable renumbering of unknowns. We introduce a reordering technique for the degrees of freedom that makes the application of ILU relatively fast. We compare the performance of this technique with some block preconditioners. The performance appears to depend on grid size, Reynolds number and quality of the mesh. For medium‐sized problems, which are of practical interest, we show that the reordering technique is competitive with the block preconditioners. Its simple implementation makes it worthwhile to implement it in the standard finite element method software. Copyright © 2007 John Wiley & Sons, Ltd.
A rough morphology of the adsorbed fibronectin layer favors adhesion of neuronal cells
Authors: Dekeyser C. M. , Zuyderhoff E. , Giuliano R. E. , Federoff H. J. , Dupont‐Gillain Ch. C. , Rouxhet P. G. 
Published: December 2007

AbstractA range of substrates made of polystyrene (PS) and poly(methyl methacrylate)–poly(methacrylic acid) copolymer (PMMA–PMAA) containing 98 and 80% PMMA (PA98, PA80) and presenting a homogeneous or a patterned surface were used to study fibronectin adsorption and neuronal cell behavior. Fibronectin adsorption showed weak differences regarding the adsorbed amount (evaluated by XPS), but large differences in adsorbed layer morphology as observed by AFM. A fine granular morphology, with dimensions up to 8 nm height and 50–150 nm width, was observed on top of a thin adsorbed layer in the case of PS, PA98, and of a surface made of nanoscale inclusions of the latter in PS. In contrast, the layer adsorbed on PA80, which carries more ionizable groups, showed a higher roughness on the PA80 zones with differences in height up to 30 nm and characteristic lateral dimensions of 400 nm. On substrates of the former category, the cells formed large clusters, revealing poor interactions with the substrate. On PA80, the cells formed large networks with only a few small clusters. The adsorbed layer roughness, resulting from aggregation of fibronectin upon adsorption and from the substrate surface chemical composition, is responsible for neuronal cell spreading and growth. Its effect is not prevented by the presence of inclusions (< 30% of the surface) responsible for smoother areas of adsorbed fibronectin and for protrusions below 40 nm. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Greater osteoblast long‐term functions on ionic plasma deposited nanostructured orthopedic implant coatings
Authors: Reising Alex , Yao Chang , Storey Dan , Webster Thomas J. 
Published: December 2007

AbstractBioactive coatings are in high demand to increase the functions of cells for numerous medical devices. The objective of this in vitro study was to characterize for the first time osteoblast (bone‐forming cell) long‐term functions (such as proliferation and deposition of calcium containing mineral) on several potential orthopedic implant polymeric materials [specifically, ultrahigh molecular weight polyethylene (UHMWPE) and polytetrafluoroethylene (PTFE)] coated with nanostructured titanium using a novel ionic plasma deposition (IPD) coating process. UHMWPE is a widely used polymer in total knee and hip replacements, while PTFE is not, but it has been used in other orthopedic applications. The IPD coating process creates a surface‐engineered nanostructure (with features usually below 100 nm) by first using a vacuum to remove all contaminants, and then guiding charged metallic ions or plasma to the surface of a medical device at ambient temperature. Results demonstrated that compared to currently used titanium and uncoated polymers, polymers coated with titanium using IPD significantly increased osteoblast proliferation and, most importantly, calcium deposition. In this manner, this study strongly suggests that IPD should be further studied for creating nanometer titanium surface feature coatings to enhance osteoblast functions necessary to increase orthopedic implant efficacy. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Mass spectrometry‐based survey of age‐associated protein carbonylation in rat brain mitochondria
Authors: Prokai Laszlo , Yan Liang‐Jun , Vera‐Serrano José L. , Stevens Stanley M. , Forster Michael J. 
Published: December 2007

AbstractThere is a body of evidence lending credence to the idea that oxidative stress may be responsible for age‐related deleterious changes in brain function, and that protein carbonylation is a potential marker for such changes. An investigation of oxidative damage to mitochondrial proteins from aged rat brains was done using gel electrophoresis coupled with carbonylation‐specific immunostaining. Six proteins that appeared to be susceptible to oxidative modification were identified by in‐gel trypsin digestion followed by matrix‐assisted laser desorption/ionization mass spectrometry and tandem mass spectrometry. Two subunits of the H+‐transporting ATP synthase, adenine nucleotide translocator, voltage‐dependent anion channel, glutamate oxaloacetate transaminase, and aconitase were identified as likely targets of age‐associated carbonylation. Copyright © 2007 John Wiley & Sons, Ltd.
Histopathological response after preoperative radiochemotherapy in rectal carcinoma is associated with improved overall survival
Authors: Rosenberg R. , Nekarda H. , Zimmermann F. , Becker K. , Lordick F. , Hofler H. , Molls M. , Siewert J.R. 
Published: December 2007

AbstractBackgroundRecent studies showed improved local control after preoperative radiochemotherapy (RCTX) in patients with locally advanced rectal carcinoma, but failed to demonstrate a survival benefit. Our aims were to determine outcome and impact of histopathological response after preoperative RCTX.MethodsOne hundred four patients with uT3 rectal carcinoma were treated with preoperative RCTX of 45 Gy and continuous 5‐FU infusion between 1997 and 2001 (group I). Histopathological response was evaluated in all specimens after tumor resection. Group II consisted of 114 patients with uT3 rectal carcinoma treated with postoperative RCTX between 1988 and 1997.ResultsGroup I showed a 6.1% 5‐year local recurrence rate compared to 15.3% in group II (P = 0.023). Overall survival rates did not differ significantly between both groups (P = 0.225). Histopathological responders had a significantly improved 5‐year overall survival with 89.1 (7.8)% compared to 68.7 (6.7)% of the non‐responders (P = 0.008) and were identified as an independent prognostic factor.ConclusionsSignificant improvement of overall survival was observed for histopathological tumor responders after neoadjuvant radiochemotherapy. Our protocol of preoperative radiochemotherapy confirms the results of the multi‐center studies in regard to local control and overall survival. J. Surg. Oncol. 2008;97:8–13. © 2007 Wiley‐Liss, Inc.
1,1‐bis(3′‐indolyl)‐1‐(p‐substituted phenyl)methanes decrease mitochondrial membrane potential and induce apoptosis in endometrial and other cancer cell lines
Authors: Hong Jun , Samudio Ismael , Chintharlapalli Sudhakar , Safe Stephen 
Published: December 2007

Abstract1,1‐Bis(3′‐indolyl)‐1‐(p‐substituted phenyl)methanes, containing p‐t‐butyl (DIM‐C‐pPhtBu) and phenyl (DIM‐C‐pPhC6H5) substituents, are peroxisome proliferator‐activated receptor γ (PPARγ) agonists; however, DIM‐C‐pPhtBu‐induced growth inhibition and cell death in human HEC1A endometrial cancer cells is PPARγ‐independent. DIM‐C‐pPhtBu decreased mitochondrial membrane potential (MMP) and promoted the release of cytochrome c and caspase activation and nuclear uptake of endonuclease G leading to apoptosis of HEC1A cells. DIM‐C‐pPhtBu specifically targeted the mitochondrial permeability transition pore complex (PTPC) because the DIM‐C‐pPhtBu‐induced pro‐apoptotic responses were inhibited by atractyloside (Atra), a compound that specifically interacts with the inner mitochondrial membrane adenine nucleotide transport (ANT) proteins. At the dose of Atra used in this study (300 µM), this compound alone did not alter the PTPC but inhibited the mitochondriotoxic effects of DIM‐C‐pPhtBu. DIM‐C‐pPhtBu/DIM‐C‐pPhC6H5 and Atra also differentially affected the ability of eosin‐5‐maleimide (EMA) to alkylate Cys160 in the ANT protein and Atra, but not DIM‐C‐pPhtBu, inhibited the exchange of ATP/ADP in isolated mitochondria suggesting that these pharmacophores act on different sites on the ANT protein. Results of this study show that the receptor‐independent proapoptotic activity of DIM‐C‐pPhtBu and DIM‐C‐pPhC6H5 were related to novel mitochondriotoxic activities involving inner mitochondrial ANT proteins. © 2007 Wiley‐Liss, Inc.
Measuring fatigue among women with Sjögren's syndrome or rheumatoid arthritis: A comparison of the Profile of Fatigue (ProF) and the Multidimensional Fatigue Inventory (MFI)
Authors: Goodchild C. E. , Treharne G. J. , Booth D. A. , Kitas G. D. , Bowman S. J. 
Published: December 2007

AbstractBackground: Fatigue is common in both Sjögren's syndrome (SS) and rheumatoid arthritis (RA) and can restrict functioning.Aims: We tested the convergent validity of the Profile of Fatigue (ProF) using the Multidimensional Fatigue Inventory (MFI) in SS and RA.Methods: The 16‐item ProF and the 20‐item MFI were completed by 82 White‐British women aged 35–79 years (mean 60.4 years). Thirty‐four had been diagnosed with SS for a mean of 7.0 years and 48 had been diagnosed with RA for a mean of 14.5 years. The ProF measures four somatic facets of fatigue and two mental facets; the MFI contains one mental and four somatic facets. The structures of the items from both measures were tested by principal component factor analysis using varimax rotation.Results: No significant differences in fatigue were found between the women with SS or RA. Five factors explained a total of 76% of the variance of the MFI; six factors explained 94% of the variance of the ProF. Mental fatigue items from both questionnaires loaded onto separate factors from somatic fatigue items; the two original facets of mental fatigue in the ProF were replicated. The four somatic fatigue facets of the ProF were generally replicated but the somatic facets of the MFI did not replicate as clearly. Equivalent facets correlated well between the two questionnaires (r ≥ 0.65).Conclusions: Both the ProF and the MFI distinguish between somatic and mental fatigue in SS and RA but the ProF appears better at resolving somatic facets of fatigue. Copyright © 2007 John Wiley & Sons, Ltd.
Solving a fourth‐order fractional diffusion‐wave equation in a bounded domain by decomposition method
Authors: Jafari Hossein , Dehghan Mehdi , Sayevand Khosro 
Published: December 2007

AbstractIn this article, the Adomian decomposition method has been used to obtain solutions of fourth‐order fractional diffusion‐wave equation defined in a bounded space domain. The fractional derivative is described in the Caputo sense. Convergence of the method has been discussed with some illustrative examples. © 2007 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2008
Insulin‐like growth factor binding protein‐5 (IGFBP‐5) suppresses the tumourigenesis of head and neck squamous cell carcinoma
Authors: Hung P‐S , Kao S‐Y , Shih Y‐H , Chiou S‐H , Liu C‐J , Chang K‐W , Lin S‐C 
Published: December 2007

AbstractHead and neck squamous cell carcinoma (HNSCC) is a global malignancy. The insulin‐like growth factor (IGF) signalling axis plays a critical role in tumourigenesis. This study defined the clinical and functional roles of insulin‐like growth factor binding protein‐5 (IGFBP‐5) in HNSCC. Down‐regulation of IGFBP‐5 mRNA expression was found during the progression from pre‐cancer to HNSCC. The down‐regulation in HNSCC was associated with a higher propensity to nodal metastasis. SAS and OECM‐1 are HNSCC cells that do, or do not, express IGFBP‐5, respectively. Recombinant IGFBP‐5 reduced the proliferation of OECM‐1 cells and this was exerted mainly through blockade of the IGF pathways. Either IGFBP‐5 or IGF‐I treatment alone promoted OECM‐1 migration, but a combination of treatments generated antagonistic effects. Overexpression of IGFBP‐5 reduced the proliferation and anchorage‐independent growth of both OECM‐1 and SAS cells. Conversely, knockdown of IGFBP‐5 expression significantly induced the proliferation and anchorage‐independent growth of SAS cells. It also induced the growth of xenografted SAS tumours. SAS transfectants that expressed mutant or truncated IGFBP‐5, which lack IGF binding activity, exhibited significantly lower anchorage‐independent growth than vector control. This suggests that IGFBP‐5 possesses an IGF‐independent suppressor function. The suppressive effects of IGFBP‐5 on the tumourigenesis of HNSCC might be invaluable to future neoplastic intervention. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.