bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct Responses of Chloroplasts to Blue and Green Laser Microbeam Irradiations in the Centric Diatom Pleurosira laevis
Authors: Shihira‐Ishikawa Ikuko , Nakamura Takanori , Higashi Sho‐ichi , Watanabe Masakatsu 
Published: July 2007

AbstractThe centric diatomPleurosira laevis is a large unicellular alga, in which ca 200 chloroplasts migrate toward the nuclear cytoplasm through the transvacuolar cytoplasmic strands in response to blue‐light irradiation and, on the contrary, toward the cortical cytoplasm in response to green‐light irradiation. We analyzed these light‐induced chloroplast migrations using a scanning laser microbeam provided by a confocal microscope for intracellular irradiation. Spot irradiation of a blue laser microbeam induced rapid assemblage of chroloplasts into the nuclear cytoplasm regardless of the spot position and spot number. On the other hand, one or two spots of green laser microbeam induced chloroplast accumulation at the spots, although increasing spot numbers suppressed chloroplast accumulation at each spot. In our experimental condition, ca 1 min of blue‐light irradiation was sufficient to stimulate movement, whereas green‐light irradiation required uninterrupted and longer irradiation time (ca 15 min). Chloroplast assemblage induced by blue‐light required extracellular Ca2+, and was inhibited by Ca2+channel antagonists. Furthermore, higher efficiencies of chloroplast migration were obtained when a single beam spot was fragmented and scattered over wider area of plasma membrane. These observations suggested that blue‐light induced a response at the plasma membrane, which subsequently activated Ca2+permeable channels. This sequence of physiological events is identical to what was previously observed with chloroplast movement in response to mechanical stimulation. Furthermore, experiments with the cytoskeleton‐disrupting agents, colchicine and cytochalasin D, indicated that blue‐light‐induced chloroplast movement required microtubules whereas the green‐light‐induced response to beam spot required actin filaments.
Study of UV Radiation Dose Received by the Spanish Population
Authors: Gurrea Gonzalo , Cañada Javier 
Published: July 2007

AbstractExcess exposure to UV radiation can affect our health by causing sunburn, skin cancer, etc. It is therefore useful to determine the UV dosage received by people as a way of protecting them from the possible negative effects that this kind of radiation can cause. In this work, the personal outdoor percentage, which shows the time spent in outdoor activities, as well as personal UV doses, has been calculated by means of global UV radiation on a horizontal plane. A database of average daily UVB radiation on the horizontal plane given by the National Institute of Meteorology has been used. In this work we evaluate the standard erythema dose of the Spanish population throughout the year.
Ratiometric Analysis of Fluorescence Lifetime for Probing Binding Sites in Albumin with Near‐Infrared Fluorescent Molecular Probes
Authors: Berezin Mikhail Y. , Lee Hyeran , Akers Walter , Nikiforovich Gregory , Achilefu Samuel 
Published: July 2007

AbstractA number of diseases have been linked to abnormal conformation of albumin, a major extracellular protein in blood. Current protein structural analysis requires pure isolated samples, thereby limiting their use for albumin analysis in blood. In this study, we report a new approach for high‐throughput structure‐related analysis of albumin by using the fluorescence lifetime properties of near‐infrared (NIR) polymethine dyes. Based on molecular modeling, polymethine dyes are bound to two binding sites with different polarities on albumin. As a result, an NIR molecular probe exhibits two distinct lifetimes with two corresponding fluorescent fractional contributions. The distribution of fractional contributions along with individual fluorescence lifetimes represents unique parameters for characterizing albumin architecture by ratiometric analysis. After screening a small library of NIR polymethine dyes, we identified and used a polymethine dye with optimal fluorescence lifetime properties to assess structure‐related differences in commercially available bovine serum albumin as model systems. The results show that changes in the lifetime of NIR dyes reflect the perturbation of the tertiary structures of albumin and that albumin prepared by different methods has slightly altered tertiary structures. Because of the reduced absorption of light by blood in the NIR region, the method developed can be used to determine structural changes in albumin in whole blood without prior isolation of the pure protein.
Frequency and fidelity of alien chromosome transmission inGossypiumhexaploid bridging populations
Authors: Becerra Lopez-Lavalle L. Augusto , Brubaker Curt L. 
Published: July 2007

The Australian diploid Gossypium species possess traits of potential agronomical value, such as gossypol-free seeds and Fusarium wilt resistance. However, they belong to the tertiary germplasm pool, which is the most difficult group of species from which to introgress genes into G. barbadense L. and G. hirsutum L. Interspecific triploid hybrids can be generated but they are sterile. The sterility barrier can be overcome using synthetic polyploids as introgression bridges, but whether there is sufficient homoeologous chromosome interaction at meiosis to allow recombination is still an open question. To ascertain, genetically, observable levels of homoeologous introgression, 2 synthetic hexaploid lines (2x G. hirsutum × G. australe and 2x G. hirsutum × G. sturtianum) were crossed to G. hirsutum to generate pentaploid F1plants that, in turn, were backcrossed to G. hirsutum to generate BC1and BC2multiple alien chromosome addition lines (MACALs). Gossypium australe F. Muell. and G. sturtianum Willis chromosome-specific markers were used to track the frequency and fidelity of chromosome transmission to the BC1and BC2MACALs. The chromosomal location of the AFLP markers was determined by their distribution among the MACALs and confirmed in parental F2families. Roughly half the available chromosomes were transmitted to the G. hirsutum × G. australe (54%) and G. hirsutum × G. sturtianum (52%) BC1MACALs. The BC2MACAL families again inherited about half of the available chromosomes. There were, however, notable exceptions for specific chromosomes. Some chromosomes were preferentially eliminated, while others were preferentially transmitted. Consistent with the genomic stability of Gossypium synthetic polyploids, the de novo loss or gain of AFLP fragments was rarely observed. While restructuring of the donor G. australe and G. sturtianum chromosomes was observed, this is more likely the result of chromatin loss, and no clear cases of introgression of donor chromatin into the recipient G. hirsutum genome were observed.
Circulating stromal osteonectin-positive progenitor cells and stenotic coronary atherosclerosisThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.
Authors: Gabbasov Zufar A. , Agapov Alexander A. , Saburova Olga S. , Komlev Alexei E. , Soboleva Emma L. , Akchurin Renat S. , Smirnov Vladimir N. 
Published: July 2007

The level of circulating stromal progenitor cells carrying osteonectin (ON), a marker of osteogenic differentiation, was evaluated by flow cytometry in blood of patients with coronary artery disease (CAD). Ninety-nine patients with CAD were included into the study. Coronary angiography of all patients showed critical stenosis of at least 2 coronary arteries or their major branches. The control groups included 8 patients without CAD and 19 healthy volunteers. In control patients, no lesions of the coronary bed were found by angiography. The absence of CAD in the volunteers was confirmed by bicycle stress test. The content of ON-positive cells in blood was examined in various populations of lymphocyte-like cells. It was found that the number of ON+ lymphocyte-like cells with CD41 positivity in blood of patients without coronary stenosis (0.27% ± 0.11%, mean ± SD) did not differ significantly from corresponding value in healthy volunteers (0.26% ± 0.07%, p = 0.94). In CAD patients, the percent of these ON+ cells was 1.01% ± 0.49% and was significantly higher than in blood of healthy volunteers (p < 0.0001) and patients without CAD (p < 0.0001). High content of ON+ lymphocyte-like cells with CD41 positivity in blood may serve as noninvasive marker of arterial atherosclerosis.
Retinoblastoma Tumor Suppressor Status Is a Critical Determinant of Therapeutic Response in Prostate Cancer Cells
Authors: Sharma Ankur , Comstock Clay E.S. , Knudsen Erik S. , Cao Khanh H. , Hess-Wilson Janet K. , Morey Lisa M. , Barrera Jason , Knudsen Karen E. 
Published: July 2007

Abstract
The retinoblastoma tumor suppressor protein (RB), a critical mediator of cell cycle progression, is functionally inactivated in the majority of human cancers, including prostatic adenocarcinoma. The importance of RB tumor suppressor function in this disease is evident because 25% to 50% of prostatic adenocarcinomas harbor aberrations in RB pathway. However, no previous studies challenged the consequence of RB inactivation on tumor cell proliferation or therapeutic response. Here, we show that RB depletion facilitates deregulation of specific E2F target genes, but does not confer a significant proliferative advantage in the presence of androgen. However, RB-deficient cells failed to elicit a cytostatic response (compared with RB proficient isogenic controls) when challenged with androgen ablation, AR antagonist, or combined androgen blockade. These data indicate that RB deficiency can facilitate bypass of first-line hormonal therapies used to treat prostate cancer. Given the established effect of RB on DNA damage checkpoints, these studies were then extended to determine the impact of RB depletion on the response to cytotoxic agents used to treat advanced disease. In this context, RB-deficient prostate cancer cells showed enhanced susceptibility to cell death induced by only a selected subset of cytotoxic agents (antimicrotubule agents and a topoisomerase inhibitor). Combined, these data indicate that RB depletion dramatically alters the cellular response to therapeutic intervention in prostate cancer cells and suggest that RB status could potentially be developed as a marker for effectively directing therapy. [Cancer Res 2007;67(13):6192–203]
Effects of Phenylethyl Isothiocyanate on Early Molecular Events in N-Nitrosomethylbenzylamine–Induced Cytotoxicity in Rat Esophagus
Authors: Reen Rashmeet K. , Dombkowski Alan A. , Kresty Laura A. , Cukovic Daniela , Mele Jennifer M. , Salagrama Sridevi , Nines Ronald , Stoner Gary D. 
Published: July 2007

Abstract
There is little information on early molecular events in the development of N-nitrosomethylbenzylamine (NMBA)–induced rat esophageal tumorigenesis and of the effects of chemopreventive agents on these events. In this study, we identified genes in rat esophagus that were differentially expressed in response to short-term NMBA treatment and modulated by cotreatment with phenylethyl isothiocyanate (PEITC). Rats were fed AIN-76A diet or AIN-76A diet containing PEITC for 3 weeks. During the 3rd week of dietary treatment, they were administered three s.c. doses of NMBA (0.5 mg/kg body weight). Rats were sacrificed 24 h after the last treatment; esophagi were excised and processed for histologic grading, microarray and real-time PCR analysis. Histopathologic analysis showed that treatment of rats with PEITC had a protective effect on NMBA-induced preneoplastic lesions in the rat esophagus. We identified 2,261 genes that were differentially expressed in the NMBA-treated versus control esophagi and 1,936 genes in the PEITC + NMBA versus NMBA-treated esophagi. The intersection of these two sets resulted in the identification of 1,323 genes in NMBA-treated esophagus, the vast majority of which were modulated by PEITC to near-normal levels of expression. Measured changes in the expression levels of eight selected genes were validated using real-time PCR. Results from 12 microarrays indicated that PEITC treatment had a genome-wide modulating effect on NMBA-induced gene expression. Samples obtained from animals treated with PEITC alone or cotreated with PEITC + NMBA were more similar to controls than to samples treated with NMBA alone. [Cancer Res 2007;67(13):1–9]
The Inhibitory Effect of (−)-Epigallocatechin Gallate on Activation of the Epidermal Growth Factor Receptor Is Associated with Altered Lipid Order in HT29 Colon Cancer Cells
Authors: Adachi Seiji , Nagao Tomokazu , Ingolfsson Helgi I. , Maxfield Frederick R. , Andersen Olaf S. , Kopelovich Levy , Weinstein I. Bernard 
Published: July 2007

Abstract
(−)-Epigallocatechin gallate (EGCG), a major biologically active constituent of green tea, inhibits activation of the epidermal growth factor (EGF) receptor (EGFR) and downstream signaling pathways in several types of human cancer cells, but the precise mechanism is not known. Because several plasma membrane-associated receptor tyrosine kinases (RTK) including EGFR are localized in detergent-insoluble ordered membrane domains, so-called “lipid rafts,” we examined whether the inhibitory effect of EGCG on activation of the EGFR is associated with changes in membrane lipid order in HT29 colon cancer cells. First, we did cold Triton X-100 solubility assays. Phosphorylated (activated) EGFR was found only in the Triton X-100–insoluble (lipid raft) fraction, whereas total cellular EGFR was present in the Triton X-100–soluble fraction. Pretreatment with EGCG inhibited the binding of Alexa Fluor 488–labeled EGF to the cells and also inhibited EGF-induced dimerization of the EGFR. To examine possible effects of EGCG on membrane lipid organization, we labeled the cells with the fluorescent lipid analogue 1, 1′-dihexadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate, which preferentially incorporates into ordered membrane domains in cells and found that subsequent treatment with EGCG caused a marked reduction in the Triton X-100–resistant membrane fraction. Polyphenon E, a mixture of green tea catechins, had a similar effect but (−)-epicatechin (EC), the biologically inactive compound, did not significantly alter the Triton X-100 solubility properties of the membrane. Furthermore, we found that EGCG but not EC caused dramatic changes in the function of bilayer-incorporated gramicidin channels. Taken together, these findings suggest that EGCG inhibits the binding of EGF to the EGFR and the subsequent dimerization and activation of the EGFR by altering membrane organization. These effects may also explain the ability of EGCG to inhibit activation of other membrane-associated RTKs, and they may play a critical role in the anticancer effects of this and related compounds. [Cancer Res 2007;67(13):6493–501]
A Novel Epidermal Growth Factor Receptor Inhibitor Promotes Apoptosis in Non–Small Cell Lung Cancer Cells Resistant to Erlotinib
Authors: de La Motte Rouge Thibault , Galluzzi Lorenzo , Olaussen Ken A. , Zermati Yael , Tasdemir Ezgi , Robert Thomas , Ripoche Hugues , Lazar Vladimir , Dessen Philippe , Harper Francis , Pierron Gerard , Pinna Guillaume , Araujo Natalia , Harel-Belan Annick , Armand Jean-Pierre , Wong Tai Wai , Soria Jean Charles , Kroemer Guido 
Published: July 2007

AbstractNon–small cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) responds to EGFR tyrosine kinase inhibitors such as erlotinib. However, secondary somatic EGFR mutations (e.g., T790M) confer resistance to erlotinib. BMS-690514, a novel panHER/vascular endothelial growth factor receptor (VEGFR) inhibitor described here, exerted antiproliferative and proapoptotic effects on NSCLC cell lines, with prominent efficacy on H1975 cells expressing the T790M mutation. In this model, BMS-690514 induced a G1 cell cycle arrest, as well as ultrastructural hallmarks of apoptosis, mitochondrial release of cytochrome c, and activation of caspases involved in the intrinsic (e.g., caspase-2, caspase-3, caspase-7, and caspase-9), but not in the extrinsic (e.g., caspase-8), pathway. Caspase inhibition conferred partial protection against BMS-690514 cytotoxicity, pointing to the involvement of both caspase-dependent and caspase-independent effector mechanisms. Transcriptome analyses revealed the up-regulation of proapoptotic (e.g., Bim, Puma) and cell cycle inhibitory (e.g., p27Kip1, p57Kip2) factors, as well as the down-regulation of antiapoptotic (e.g., Mcl1), heat shock (e.g., HSP40, HSP70, HSP90), and cell cycle promoting [e.g., cyclins B1, D1, and D3; cyclin-dependent kinase 1 (CDK1); MCM family proteins; proliferating cell nuclear antigen (PCNA)] proteins. BMS-690514–induced death of H1975 cells was modified in a unique fashion by a panel of small interfering RNAs targeting apoptosis modulators. Down-regulation of components of the nuclear factor-κB survival pathway (e.g., p65, Nemo/IKKγ, TAB2) sensitized cells to BMS-690514, whereas knockdown of proapoptotic factors (e.g., Puma, Bax, Bak, caspase-2, etc.) and DNA damage–related proteins (e.g., ERCC1, hTERT) exerted cytoprotective effects. BMS-690514 is a new pan-HER/VEGFR inhibitor that may become an alternative to erlotinib for the treatment of NSCLC. [Cancer Res 2007;67(13):6253–62]
The Unhydrolyzable Fenretinide Analogue 4-Hydroxybenzylretinone Induces the Proapoptotic Genes GADD153 (CHOP) and Bcl-2–Binding Component 3 (PUMA) and Apoptosis that Is Caspase- Dependent and Independent of the Retinoic Acid Receptor
Authors: Anding Allyson L. , Chapman Jason S. , Barnett Derek W. , Curley Robert W. , Clagett-Dame Margaret 
Published: July 2007

Abstract
The synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) induces apoptosis in a variety of cell lines and has shown promise as an anticancer agent both in vitro and in vivo. The clinical dose of 4-HPR, however, is limited by residual-associated toxicities, indicating a need for a less toxic drug. In this study, we show that 4-hydroxybenzylretinone (4-HBR), the unhydrolyzable analogue of 4-HPR, is effective in producing apoptosis in a variety of 4-HPR–sensitive cell lines, including breast cancer, neuroblastoma, and leukemia cells. We also show through the use of a pan-caspase inhibitor that this 4-HBR–induced apoptosis is dependent, at least in part, on caspase activity. 4-HBR is shown to exhibit binding to the retinoic acid receptors (RAR) at concentrations necessary to induce cell death and induces expression of all-trans-retinoic acid–responsive genes that can be blocked by a RAR pan-antagonist. However, through the use of this RAR pan-antagonist, 4-HBR–induced apoptosis and cell death is shown to be independent of the RAR signaling pathway. To further characterize the mechanism of action of 4-HBR, expression of the endoplasmic reticulum stress–induced genes GADD153 and Bcl-2–binding component 3 was examined. These mRNAs are shown to be rapidly induced in 4-HBR–treated and 4-HPR–treated breast cancer cells, and this up-regulation is also shown to be independent of the RARs. These results suggest that a stress-mediated apoptotic cascade is involved in the mechanism of action of these retinoids. [Cancer Res 2007;67(13):6270–7]
Effects of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate, on thrombus formation and bleeding time in rats
Authors: Stassen Jean-Marie , Priepke Henning , Ries Uwe Joerg , Hauel Norbert , Wienen Wolfgang 
Published: July 2007

SummaryDabigatran is a reversible direct, selective thrombin inhibitor, undergoing clinical development as its orally active prodrug, dabigatran etexilate. The objective of this trial was to assess the antithrombotic and anticoagulant effects of dabigatran and dabigatran etexilate in a rat model of venous thrombosis. In order to do this a modifiedWessler model was used to assess the antithrombotic and anticoagulant effects of intravenous (i.v.) dabigatran and oral dabigatran etexilate administration. In addition, a rat tail bleeding time model was used to investigate the antihemostatic effect of dabigatran.The study demonstrated that bolus administration of dabigatran (0.01–0.1 mg/kg) reduced thrombus formation dose-dependently,with an ED50 (50% of the effective dose) of 0.033 mg/kg and complete inhibition at 0.1 mg/kg. By comparison,ED50 values for heparin (0.03–0.3 mg/kg),hirudin (0.01–0.5 mg/kg) and melagatran (0.1–0.5 mg/kg) were 0.07, 0.15 and 0.12 mg/kg, respectively. Oral administration of dabigatran etexilate (5–30 mg/kg) inhibited thrombus formation in a dose- and time-dependent manner, with maximum inhibition within 30 min of pretreatment, suggesting a rapid onset of action. Following i.v. administration of dabigatran (0.1–1.0 mg/kg), a statistically significant prolongation of bleeding time was observed at doses at least 15- and 5-fold greater than ED50 and ED100 (100% of the effective dose) doses, respectively; there was no significant increase in bleeding tendency at the maximum therapeutically effective dose (0.1 mg/kg). It can be concluded that dabigatran and its oral prodrug, dabigatran etexilate, show promise in the management of thromboembolic disease.
Cardiovascular regeneration in non-mammalian model systems: What are the differences between newts and man?
Authors: Braun Thomas , Borchardt Thilo 
Published: July 2007

SummaryThe mammalian heart cannot regenerate substantial cardiac injuries, while certain non-mammalian vertebrates such as certain fish (Danio rerio) and amphibiae (Notophthalmus viridescens) are able to repair the heart without functional impairment. In mammalians, the prevailing repair process is accompanied by fibrosis and scarring, while zebrafish and newts can replace lost contractile tissue by newly formed cardiac muscle with only little or no scar formation.A better understanding of cardiac regeneration in non-mammalian vertebrates might provide new insights for the manipulation of regenerative pathways in the human heart. Here, we summarize the current knowledge in cardiac regeneration of newts and the principal differences to repair processes in mammalian hearts.
Microfluidic reveals generation of platelet-strings on tumoractivated endothelium
Authors: Kleinerüschkamp Felix , Barg Alexej , Schnaeker Eva-Maria , Huck Volker , Schneider Matthias , Steinhoff Martin , Goerge Tobias , Schneider Stefan 
Published: July 2007

SummaryNeoplastic diseases are often associated with thromboembolic events,however the precise mechanism underlying this observation is a matter of ongoing investigation. It is known that matrixmetalloproteinase- 1 (MMP-1) canonically activates the thrombin receptor (PAR-1) and we recently reported that highly metastatic tumor cells of melanoma and colon cancer are secreting matrixmetalloproteinase-1. This tumor-derived MMP1 was shown to be a major activator of endothelial PAR-1, thus leading to endothelial cell activation. As tumor-induced thrombosis is a characteristic of metastazing tumors, we investigated whether tumor-derived supernatant (TUSN) from melanoma and colon cancer may induce adhesion of circulating platelets,an initial step in thrombus formation.A time-course study revealed that TU-SN induces a rapid secretion of von Willebrand factor (VWF) within minutes. Using a novel microfluidic device we analyzed platelet-endothelial interactions in a closed circuit. Immunofluorescence imaging showed that TU-SN rapidly induces platelet- string formation via secreted VWF. We demonstrated that tumor-derived supernatant is a potent agonist inducing platelet adhesion under flow conditions.