bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone morphogenetic protein 2 and dexamethasone synergistically increase alkaline phosphatase levels through JAK/STAT signaling in C3H10T1/2 cells
Authors: Mikami Yoshikazu , Asano Masatake , Honda Masaki J. , Takagi Minoru 
Published: December 2009

AbstractAlkaline phosphatase (ALP) is generally believed to be a faithful marker of osteoblast differentiation, and its expression is induced by bone morphogenetic protein‐2 (BMP‐2) and dexamethasone (Dex). However, the effects of combined administration of BMP‐2 and Dex on ALP transcription have not been extensively examined. In this study, we found that BMP‐2 and Dex synergistically increase ALP levels in mouse C3H10T1/2 pluripotent stem cells. However, switching from one inducer to the other, by adding BMP‐2 or Dex to cell cultures at different times, was no more effective than continuous treatment with either inducer alone. A significant induction of ALP mRNA expression was observed only in cells continuously treated with both inducers. This result suggests that both BMP‐2 and Dex may act in the same pathway or at the same stage of differentiation. A luciferase assay using ALP promoter deletion constructs showed that a region of the promoter containing a putative signal transducer and activator of transcription 3 (STAT3) response element (SRE) responds to treatment with a combination of BMP‐2 and Dex. Furthermore, a ChIP assay indicated that STAT3 bound to the SRE. In addition, a STAT3 siRNA suppressed the synergistic effect of BMP‐2 and Dex on ALP levels. These results indicate that STAT3 may play an important role in regulating ALP expression. To our knowledge, this is the first time that STAT3 has been implicated in the regulation of ALP expression by BMP‐2 and Dex. These findings raise the possibility of developing new strategies for the enhancement of bone formation using a combination of BMPs and Dex. J. Cell. Physiol. 223: 123–133, 2010. © 2009 Wiley‐Liss, Inc.
Laminin‐332–β1 integrin interactions negatively regulate invadopodia
Authors: Liu Shanshan , Yamashita Hironobu , Weidow Brandy , Weaver Alissa M. , Quaranta Vito 
Published: December 2009

AbstractAdhesion of epithelial cells to basement membranes (BM) occurs through two major structures: actin‐associated focal contacts and keratin‐associated hemidesmosomes, both of which form on laminin‐332 (Ln‐332). In epithelial‐derived cancer cells, additional actin‐linked structures with putative adhesive properties, invadopodia, are frequently present and mediate BM degradation. A recent study proposed that BM invasion requires a proper combination of focal contacts and invadopodia for invading cells to gain traction through degraded BM, and suggested that these structures may compete for common molecular components such as Src kinase. In this study, we tested the role of the Ln‐332 in regulating invadopodia in 804G rat bladder carcinoma cells, a cell line that secretes Ln‐332 and forms all three types of adhesions. Expression of shRNA to Ln‐332 γ2 chain (γ2‐kd) led to increased numbers of invadopodia and enhanced extracellular matrix degradation. Replating γ2‐kd cells on Ln‐332 or collagen‐I fully recovered cell spreading and inhibition of invadopodia. Inhibition of α3 or β1, but not α6 or β4, phenocopied the effect of γ2‐kd, suggesting that α3β1‐mediated focal contacts, rather than α6β4‐mediated hemidesmosome pathways, intersect with invadopodia regulation. γ2‐kd cells exhibited alterations in focal contact‐type structures and in activation of focal adhesion kinase (FAK) and Src kinase. Inhibition of FAK also increased invadopodia number, which was reversible with Src inhibition. These data are consistent with a model whereby actin‐based adhesions can limit the availability of active Src that is capable of invadopodia initiation and identifies Ln‐332‐β1 interactions as a potent upstream regulator that limits cell invasion. J. Cell. Physiol. 223: 134–142, 2010. © 2009 Wiley‐Liss, Inc.
Downregulation and aberrant promoter methylation of p16INK4A: A possible novel heritable susceptibility marker to retinoblastoma
Authors: Indovina Paola , Acquaviva Antonio , De Falco Giulia , Rizzo Valeria , Onnis Anna , Luzzi Anna , Giorgi Francesca , Hadjistilianou Theodora , Toti Paolo , Tomei Valentina , Pentimalli Francesca , Carugi Alessandro , Giordano Antonio 
Published: December 2009

AbstractRB loss has long been recognized as the causative genetic alteration underlying retinoblastoma but it is increasingly evident that other alterations are required for the tumor to develop. Therefore, we set out to identify additional inheritable susceptibility markers and new potential preventive and therapeutic targets for retinoblastoma. We focused on the p16INK4A tumor suppressor gene because of its possible role in retinoblastoma pathogenesis and its involvement in predisposition to familial cancer. p16INK4A expression was analyzed in tumor samples from retinoblastoma patients by immunohistochemistry and in peripheral blood cells from both patients and their parents by real‐time quantitative reverse transcription‐PCR (qRT‐PCR). Since promoter methylation is a common mechanism regulating p16INK4A expression, the methylation status of its promoter was also analyzed in blood samples from patients and their parents by methylation‐specific PCR. A downregulation of p16INK4A was observed in 55% of retinoblastoma patients. Interestingly, in 56% of the cases showing p16INK4A downregulation at least one of the patients' parents bore the same alteration in blood cells. Analysis of p16INK4A promoter methylation showed hypermethylation in most patients with p16INK4A downregulation and in the parents with the same alteration in p16INK4A expression. The finding that p16INK4A was downregulated both in patients and their parents suggests that this alteration could be a novel inheritable susceptibility marker to retinoblastoma. The observation that p16INK4A downregulation seems to be due to its promoter hypermethylation opens the way for the development of new preventive and therapeutic strategies using demethylating agents. J. Cell. Physiol. 223: 143–150, 2010. © 2009 Wiley‐Liss, Inc.
Integrated methodology for the evaluation of cleaning effectiveness in two Russian icons (16th–17th centuries)
Authors: Anca Sandu Irina Crina , Bracci Susanna , Lobefaro Mariella , Sandu Ion 
Published: December 2009

AbstractThis article covers a methodology for evaluating the effectiveness of cleaning two Russian icons. The icons belong to a group of five from the same iconographic school, dating from the 16th to 17th centuries. An integrated and complementary approach to varnish and overpaint removal involved microscopic techniques (optical and scanning electron microscopy) and colorimetry (CIE L*a*b* system). The materials and techniques used in these icons have been characterized previously. Cleaning revealed extensive overpainting that had not only dramatically changed the original appearance, but also the meaning and attribution of one of the two icons. The analyses carried out were useful in determining the extent of the overpainting and led to a better assessment of the results and effectiveness of the restoration. Microsc. Res. Tech. 73:752–760, 2010. © 2009 Wiley‐Liss, Inc.
How a heavy‐bodied snake strikes quickly: high‐power axial musculature in the puff adder (Bitis arietans)
Authors: Young Bruce A. 
Published: December 2009

AbstractDespite being large, heavy‐bodied snakes, puff adders (Bitis arietans) are capable of achieving strike velocities and accelerations similar to, or greater than, those of much smaller snakes (means of 2.6 and 72 m/sec2, respectively). The mechanistic basis of the strike was examined using high‐speed digital videography, coupled with electromyographic (EMG) analysis, of the two main extensors of the vertebral column, the semispinalis and longissimus. Although the strike involves the rapid extension of preformed body curves, the extensor muscles were not electrically active during body extension. The vertebral extensor muscles exhibited bursts of electrical activity before the onset of movement—and quantified features of these EMG signals were significantly related to kinematic aspects of the strike (e.g., acceleration)—however, this electrical activity terminated shortly (∼50 msec) before the onset of movement. It is hypothesized that the prestrike activity of the extensor muscles functions to place the (extensive) musculo‐tendon complex of the snake's epaxial muscles under tension, and that the displacement of the body during the strike is due to the elastic recoil of this musculo‐tendon complex. Incorporation of this type of elastic recoil would increase the power output of the vertebral extensors. Power amplification of the vertebral extensors may be an evolutionary necessity if a large, heavy‐bodied snake, like B. arietans, is going to achieve rapid acceleration during the strike. J. Exp. Zool. 313A:114–121, 2010. © 2009 Wiley‐Liss, Inc.
Efficient synthesis of benzothieno[3,2‐d]‐imidazo[1,2‐a]pyrimidine‐2,5‐(1H, 3H)‐diones via a tandem aza‐wittig/heterocumulene‐mediated annulation
Authors: Xu Sheng‐Zhen , Wu Jing , Cao Min‐Hui , Ding Ming‐Wu 
Published: December 2009

Abstract
magnified imageCarbodiimide 2, obtained from aza‐Wittig reaction of iminophosphorane 1 with aromaic isocyanate, reacted with α‐amino ester in the presence of catalytic amount of sodium ethoxide to give selectively new tetracyclic benzothieno[3,2‐d]‐imidazo[1,2‐a]pyrimidine‐2,5‐(1H, 3H)‐diones 5 in good yields. X‐Ray structure analysis of 5b verified the proposed structure and the reaction selectivity. J. Heterocyclic Chem., 2010.
The anion binding properties bearing neutral cycle amine recognition sites
Authors: Shang Xuefang , Xu Xiufang 
Published: December 2009

Abstract
magnified imageO‐phenylene‐diamine derivative containing colorimetric dinitroquinoxaline has been synthesized. Its UV‐vis spectroscopy and 1H NMR investigation reveal that the receptor shows the strong binding ability for AcO−, F−, and H2PO, moderate binding abilities for OH− and almost no binding abilities for Cl−, Br−, and I−. The interaction of the receptor with studied anions achieving the recognition of anions is proposed to come from the NH…F and potential CH…F hydrogen bonding in its neutral form. The results indicate that it is well suitable for the anion complexation, which is presumably contributed to its ring topology possessing a rigidity conjugation system. Moreover, the molecular orbital level of this receptor and its tautomer were further determined by means of theoretical investigations. J. Heterocyclic Chem., 2010.
Regioselective synthesis of pyrimido[5,4‐c][2,1]benzothiazines by reactions of β‐chloroaldehydes with n‐c‐n binucleophiles
Authors: Popov Kirill , Volovnenko Tatyana , Turov Alexander , Volovenko Yulian 
Published: December 2009

Abstract
magnified imageThe method of pyrimidine ring fusion at the [c] side of benzothiazines based on the reaction of their chloroaldehyde derivatives with amidines is described. Formation of the structural isomers of reaction products was investigated, and regioselectivity of heterocyclization reactions was shown. A number of novel pyrimidobenzothiazines were synthesized. J. Heterocyclic Chem., 2010.
A diagnostics approach to economic growth and employment policy in low income economies: The case of Kosovo
Authors: Sen Kunal , Kirkpatrick Colin 
Published: December 2009

AbstractThe economic challenges facing Kosovo in 2008 are considerable. Economic growth has been below the rate achieved in neighbouring countries and more than one‐third of the work force is unemployed. The paper applies a ‘diagnostics’ analytical framework to identify the most binding constraints on economic growth and job creation. The binding constraints to growth are found to be the costs and access to finance, poor provision of public goods and weaknesses in the rule of law. The analysis also suggests that policy options for job creation must focus on increasing both economic growth and the employment intensity of growth. Copyright © 2009 John Wiley & Sons, Ltd.
Ionizing radiation enhances tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)‐induced apoptosis through up‐regulations of death receptor 4 (DR4) and death receptor 5 (DR5) in human osteosarcoma cells
Authors: Hori Takeshi , Kondo Takashi , Kanamori Masahiko , Tabuchi Yoshiaki , Ogawa Ryohei , Zhao Qing‐Li , Ahmed Kanwal , Yasuda Taketoshi , Seki Shoji , Suzuki Kayo , Kimura Tomoatsu 
Published: December 2009

AbstractDespite improvements in chemotherapy and surgery in the treatment of osteosarcoma (OS), satisfactory results are still difficult to achieve. Novel therapeutic modalities need to be developed for osteosarcoma treatment. The combined effects of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and ionizing radiation (IR) on human OS cells were investigated. IR and TRAIL treatment synergistically decreased the cell viability and enhanced apoptosis in OS cell lines. IR pretreatment enhances TRAIL‐induced Bid and caspase‐3 activations. Decreases in the expression levels of the antiapoptotic proteins c‐FLIP and XIAP also associated with apoptosis enhancement. Furthermore, IR pretreatment enhanced DR4 and DR5 expressions at the transcription stage. These results can become the basic lines of evidence for the future treatment of OS using TRAIL with IR. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:739–745, 2010
Chondrogenic differentiation of human subchondral progenitor cells is impaired by rheumatoid arthritis synovial fluid
Authors: Krüger Jan Philipp , Endres Michaela , Neumann Katja , Häupl Thomas , Erggelet Christoph , Kaps Christian 
Published: December 2009

AbstractIn microfracture, subchondral progenitors enter the cartilage defect and form cartilage repair tissue. We hypothesize that synovial fluid (SF) from rheumatoid arthritis (RA) donors affects chondrogenesis of human subchondral progenitors stimulated with transforming growth factor‐β3 (TGFB3), whereas SF from normal and osteoarthritis (OA) donors do not. Human progenitors from subchondral cortico‐spongious bone (pool of n = 4) were cultured in micromasses under serum‐free conditions and were stimulated with 10 ng/mL TGFB3 and with 5% SF from normal, OA, and RA donors (pool of n = 7, each). Histological staining of proteoglycan and immunostaining of type II collagen showed that progenitors stimulated with SF from RA donors show significantly reduced cartilage matrix formation compared to progenitors treated with TGFB3 or with SF from normal and OA donors (n = 3, each). Gene expression analysis of typical chondrocyte marker genes and genes encoding matrix modifying enzymes showed that SF from OA and RA donors influence the onset of TGFB3‐mediated chondrogenesis (pool of 20 micromasses), but had no effect on the gene expression profile after prolonged culture in micromasses. These results suggest that SF from RA patients may impair the chondrogenic development of mesenchymal progenitors in microfracture, whereas osteoarthritic SF may has no negative effect on the cartilage matrix formation. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:819–827, 2010
Action of IL‐1β during fracture healing
Authors: Lange Jeffrey , Sapozhnikova Anna , Lu Chuanyong , Hu Diane , Li Xin , Miclau Theodore , Marcucio Ralph S. 
Published: December 2009

AbstractAfter bone injury, developmental processes such as endochondral and intramembranous ossification are recapitulated as the skeleton regenerates. In contrast to development, skeletal healing involves inflammation. During the early stages of healing a variety of inflammatory cells infiltrate the injured site, debride the wound, and stimulate the repair process. Little is known about the inflammatory process during bone repair. In this work, we examined the effect of a pro‐inflammatory cytokine, Interleukin‐1 beta (IL‐1β), on osteoblast and stem cell differentiation and on intramembranous and endochondral ossification, because IL‐1β exerts effects on skeletal homeostasis and is upregulated in response to fracture. We determined that IL‐1β stimulated proliferation of osteoblasts and production of mineralized bone matrix, but suppressed proliferation and inhibited differentiation of bone marrow derived MSCs. We next performed loss‐ and gain‐of‐function experiments to determine if altering IL‐1β signaling affects fracture healing. We did not detect any differences in callus, cartilage, and bone matrix production during healing of nonstabilized or stabilized fractures in mice that lacked the IL‐1β receptor compared to wild‐type animals. We observed subtle alterations in the healing process after administering IL‐1β during the early phases of repair. At day 10 after injury, the ratio of cartilage to callus was increased, and by day 14, the proportion of cartilage to total callus and to bone was reduced. These changes could reflect a slight acceleration of endochondral ossification, or direct effects on cartilage and bone formation. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:778–784, 2010
Mapping the human record in the British early Palaeolithic: evidence from the Solent River system
Authors: Ashton Nick , Hosfield Rob 
Published: December 2009

AbstractThe lithic record from the Solent River and its tributaries is re‐examined in the light of recent interpretations about the changing demography of Britain during the Lower and early Middle Palaeolithic. Existing models of the terrace stratigraphies in the Solent and its tributary areas are reviewed and the corresponding archaeological record (specifically handaxes) for each terrace is assessed to provide models for the relative changes in human occupation through time. The Bournemouth area is studied in detail to examine the effects of quarrying and urbanisation on collection history and on the biases it introduces to the record. In addition, the effects of reworking of artefacts from higher into lower terraces are assessed, and shown to be a significant problem. Although there is very little absolute dating available for the Solent area, a cautious interpretation of the results from these analyses would suggest a pre‐Marine Isotope Stage (MIS) 12 date for the first appearance of humans, a peak in population between MIS 12 and 10, and a decline in population during MIS 9 and 8. Owing to poor contextual data and small sample sizes, it is not clear when Levallois technology was introduced. This record is compared and contrasted to that from the Thames Valley. It is suggested that changes in the palaeogeography of Britain, in particular land connections to the continent, might have contributed to differences in the archaeological records from the Solent and Thames regions. Copyright © 2009 John Wiley & Sons, Ltd.
Lake‐level changes in central Patagonia (Argentina): crossing environmental thresholds for Lateglacial and Holocene human occupation
Authors: Ariztegui Daniel , Gilli Adrian , Anselmetti Flavio S. , Goñi Rafael A. , Belardi Juan B. , Espinosa Silvana 
Published: December 2009

AbstractThe role and extent of climate as a cause of the expansion and decline of human cultures is still debatable. It is clear, however, that human–environment interactions are enhanced and interplay more closely in climatically sensitive areas such as around hydrologically closed basins. Lago Cardiel is located at 49° S in the very arid rain shadow east of the Andes, providing an exceptionally receptive system to changes in hydrological balance. Results of a geophysical survey combined with sedimentological and geochemical studies provide a continuous Lateglacial–Holocene record of substantial water‐level changes. These variations, combined with archaeological results from the catchment area, offer a unique possibility to explore the pattern of peopling within this remote area of the globe and its possible relation to climate change. Human occupation in Patagonia is well documented towards the Andes throughout the entire Holocene. Archaeological data from the Lago Cardiel basin, however, show an apparent lack of human activity during the first part of this period, which coincides with well‐constrained high lake levels. Our results show an intriguing coincidence between low lake level and increasing human occupation, suggesting that the Lago Cardiel basin has focused human use during intervals with relatively lower effective moisture such as during the Late Pleistocene, but its evidence may have been submerged. This interpretation is confirmed by archaeological remains from Lago Strobel, another perennial lake with a comparable catchment located in the same climatic region and thus sharing the same climatic history as Lago Cardiel. Copyright © 2009 John Wiley & Sons, Ltd.
Prostate stem cell antigen mRNA in peripheral blood as a potential predictor of biochemical recurrence in high‐risk prostate cancer
Authors: Joung Jae Young , Cho Kang Su , Kim Jeong Eun , Seo Ho Kyung , Chung Jinsoo , Park Weon Seo , Choi Moon Kyong , Lee Kang Hyun 
Published: December 2009

AbstractObjectiveTo determine whether the presence of prostate stem cell antigen (PSCA) mRNA in peripheral blood can predict biochemical recurrence (BCR) after radical prostatectomy in patients with high‐risk prostate cancer.MethodsHigh‐risk disease was defined based on the presence of any one of the following three risk factors: prostate‐specific antigen (PSA) ≥20 ng/ml, a biopsy Gleason score (GS) ≥8, or clinical stage ≥T2c. Nested reverse transcriptase‐polymerase chain reaction (RT‐PCR) was employed to detect PSCA mRNA‐bearing cells in peripheral blood. The relationship between PSCA detection and BCR after surgery was evaluated.ResultsOf the 250 patients, 103 (36.8%) with high‐risk disease were included in the analysis. PSCA‐mRNA was detected in 17 (16.5%) of these patients. Patients with high GS (≥7) tended to be PSCA‐mRNA positive status (P = 0.045). Over a median 23 months of follow‐up (range 3–47 months), BCR developed in 27 patients (26.2%). Cox regression hazards model analysis revealed that a RT‐PCR PSCA positivity (HR, 4.549; 95%CI, 1.685–12.279; P = 0.003) independently increased the risk of BCR.ConclusionsThe presence of PSCA mRNA in peripheral blood is a significant predictor of BCR after radical prostatectomy in high‐risk prostate cancer. J. Surg. Oncol. 2010;101:145–148. © 2009 Wiley‐Liss, Inc.
SCRN1 is a novel marker for prognosis in colorectal cancer
Authors: Miyoshi Norikatsu , Ishii Hideshi , Mimori Koshi , Sekimoto Mitsugu , Doki Yuichiro , Mori Masaki 
Published: December 2009

AbstractPurposeSecernin 1 (SCRN1) is a member of the secernin family and is reported to be a tumor‐associated antigen. Previous reports show that SCRN1 is upregulated in gastric cancer cell lines and may be a novel immunotherapy target, whereas its significance in colorectal cancer (CRC) is not fully understood.Materials and MethodsThe present study comprised 54 patients who underwent surgery for CRC, as well as two cell lines derived from human CRC. We assessed the correlation of gene expression with clinical parameters in the CRC patients, and knockdown was evaluated in the cell lines.ResultsThirty of the 54 (55.5%) cases exhibited a higher expression of the SCRN1 gene in cancerous regions than marginal non‐cancerous regions. Patients with high SCRN1 expression were statistically susceptible to a poor prognosis and showed poorer disease‐free survival than those with low expression. SCRN1 knockdown in the two cell lines demonstrated that the siRNA inhibition resulted in a statistically significant reduction in cell growth.ConclusionThe present data strongly suggest that SCRN1 expression is a prognostic factor in CRC patients. J. Surg. Oncol. 2010;101:156–159. © 2009 Wiley‐Liss, Inc.