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Sample records for anti-apoptotic molecule galectin-3

  1. Thyroid cancer imaging in vivo by targeting the anti-apoptotic molecule galectin-3.

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    Armando Bartolazzi

    Full Text Available BACKGROUND: The prevalence of thyroid nodules increases with age, average 4-7% for the U.S.A. adult population, but it is much higher (19-67% when sub-clinical nodules are considered. About 90% of these lesions are benign and a reliable approach to their preoperative characterization is necessary. Unfortunately conventional thyroid scintigraphy does not allow the distinction among benign and malignant thyroid proliferations but it provides only functional information (cold or hot nodules. The expression of the anti-apoptotic molecule galectin-3 is restricted to cancer cells and this feature has potential diagnostic and therapeutic implications. We show here the possibility to obtain thyroid cancer imaging in vivo by targeting galectin-3. METHODS: The galectin-3 based thyroid immuno-scintigraphy uses as radiotracer a specific (99mTc-radiolabeled mAb. A position-sensitive high-resolution mini-gamma camera was used as imaging capture device. Human galectin-3 positive thyroid cancer xenografts (ARO and galectin-3 knockout tumors were used as targets in different experiments in vivo. 38 mice with tumor mass of about 1 gm were injected in the tail vein with 100 microCi of (99mTc-labeled mAb to galectin-3 (30 microg protein/in 100 microl saline solution. Tumor images were acquired at 1 hr, 3 hrs, 6 hrs, 9 hrs and 24 hrs post injection by using the mini-gamma camera. FINDINGS: Results from different consecutive experiments show an optimal visualization of thyroid cancer xenografts between 6 and 9 hours from injection of the radiotracer. Galectin-3 negative tumors were not detected at all. At 6 hrs post-injection galectin-3 expressing tumors were correctly visualized, while the whole-body activity had essentially cleared. CONCLUSIONS: These results demonstrate the possibility to distinguish preoperatively benign from malignant thyroid nodules by using a specific galectin-3 radio-immunotargeting. In vivo imaging of thyroid cancer may allow a better

  2. Galectin 3

    DEFF Research Database (Denmark)

    Stoltze Gaborit, Freja; Bosselmann, Helle; Kistorp, Caroline;

    2016-01-01

    /é or LV global longitudinal strain (P > 0.05 for all). In multivariate analyses plasma concentrations of Gal-3 were significantly associated with the cardiac biomarkers: NT-proBNP (β: 0.047; 95 % CI: 0.008-0.086; P = 0.020), proANP (β: 0.137; 95 % CI: 0.067-0.207; P ...BACKGROUND: Galectin 3 (Gal-3) reflects cardiac fibrosis in heart failure HF, but has also been associated to renal fibrosis and impaired renal function. Previous research has suggested that Gal-3 could be a cardio-renal biomarker, but it has never been tested simultaneous in a single study whether...

  3. AT-101, a small molecule inhibitor of anti-apoptotic Bcl-2 family members, activates the SAPK/JNK pathway and enhances radiation-induced apoptosis

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    Rooswinkel Rogier

    2009-10-01

    Full Text Available Abstract Background Gossypol, a naturally occurring polyphenolic compound has been identified as a small molecule inhibitor of anti-apoptotic Bcl-2 family proteins. It induces apoptosis in a wide range of tumor cell lines and enhances chemotherapy- and radiation-induced cytotoxicity both in vitro and in vivo. Bcl-2 and related proteins are important inhibitors of apoptosis and frequently overexpressed in human tumors. Increased levels of these proteins confer radio- and chemoresistance and may be associated with poor prognosis. Consequently, inhibition of the anti-apoptotic functions of Bcl-2 family members represents a promising strategy to overcome resistance to anticancer therapies. Methods We tested the effect of (--gossypol, also denominated as AT-101, radiation and the combination of both on apoptosis induction in human leukemic cells, Jurkat T and U937. Because activation of the SAPK/JNK pathway is important for apoptosis induction by many different stress stimuli, and Bcl-XL is known to inhibit activation of SAPK/JNK, we also investigated the role of this signaling cascade in AT-101-induced apoptosis using a pharmacologic and genetic approach. Results AT-101 induced apoptosis in a time- and dose-dependent fashion, with ED50 values of 1.9 and 2.4 μM in Jurkat T and U937 cells, respectively. Isobolographic analysis revealed a synergistic interaction between AT-101 and radiation, which also appeared to be sequence-dependent. Like radiation, AT-101 activated SAPK/JNK which was blocked by the kinase inhibitor SP600125. In cells overexpressing a dominant-negative mutant of c-Jun, AT-101-induced apoptosis was significantly reduced. Conclusion Our data show that AT-101 strongly enhances radiation-induced apoptosis in human leukemic cells and indicate a requirement for the SAPK/JNK pathway in AT-101-induced apoptosis. This type of apoptosis modulation may overcome treatment resistance and lead to the development of new effective combination

  4. AT-101, a small molecule inhibitor of anti-apoptotic Bcl-2 family members, activates the SAPK/JNK pathway and enhances radiation-induced apoptosis

    International Nuclear Information System (INIS)

    Gossypol, a naturally occurring polyphenolic compound has been identified as a small molecule inhibitor of anti-apoptotic Bcl-2 family proteins. It induces apoptosis in a wide range of tumor cell lines and enhances chemotherapy- and radiation-induced cytotoxicity both in vitro and in vivo. Bcl-2 and related proteins are important inhibitors of apoptosis and frequently overexpressed in human tumors. Increased levels of these proteins confer radio- and chemoresistance and may be associated with poor prognosis. Consequently, inhibition of the anti-apoptotic functions of Bcl-2 family members represents a promising strategy to overcome resistance to anticancer therapies. We tested the effect of (-)-gossypol, also denominated as AT-101, radiation and the combination of both on apoptosis induction in human leukemic cells, Jurkat T and U937. Because activation of the SAPK/JNK pathway is important for apoptosis induction by many different stress stimuli, and Bcl-XL is known to inhibit activation of SAPK/JNK, we also investigated the role of this signaling cascade in AT-101-induced apoptosis using a pharmacologic and genetic approach. AT-101 induced apoptosis in a time- and dose-dependent fashion, with ED50 values of 1.9 and 2.4 μM in Jurkat T and U937 cells, respectively. Isobolographic analysis revealed a synergistic interaction between AT-101 and radiation, which also appeared to be sequence-dependent. Like radiation, AT-101 activated SAPK/JNK which was blocked by the kinase inhibitor SP600125. In cells overexpressing a dominant-negative mutant of c-Jun, AT-101-induced apoptosis was significantly reduced. Our data show that AT-101 strongly enhances radiation-induced apoptosis in human leukemic cells and indicate a requirement for the SAPK/JNK pathway in AT-101-induced apoptosis. This type of apoptosis modulation may overcome treatment resistance and lead to the development of new effective combination therapies

  5. Galectin-3 Determines Tumor Cell Adaptive Strategies in Stressed Tumor Microenvironments

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    Cardoso, Ana Carolina Ferreira; Andrade, Luciana Nogueira de Sousa; Bustos, Silvina Odete; Chammas, Roger

    2016-01-01

    Galectin-3 is a member of the β-galactoside-binding lectin family, whose expression is often dysregulated in cancers. While galectin-3 is usually an intracellular protein found in the nucleus and in the cytoplasm, under certain conditions, galectin-3 can be secreted by an yet unknown mechanism. Under stressing conditions (e.g., hypoxia and nutrient deprivation) galectin-3 is upregulated, through the activity of transcription factors, such as HIF-1α and NF-κB. Here, we review evidence that indicates a positive role for galectin-3 in MAPK family signal transduction, leading to cell proliferation and cell survival. Galectin-3 serves as a scaffold protein, which favors the spatial organization of signaling proteins as K-RAS. Upon secretion, extracellular galectin-3 interacts with a variety of cell surface glycoproteins, such as growth factor receptors, integrins, cadherins, and members of the Notch family, among other glycoproteins, besides different extracellular matrix molecules. Through its ability to oligomerize, galectin-3 forms lectin lattices that act as scaffolds that sustain the spatial organization of signaling receptors on the cell surface, dictating its maintenance on the plasma membrane or their endocytosis. Galectin-3 induces tumor cell, endothelial cell, and leukocyte migration, favoring either the exit of tumor cells from a stressed microenvironment or the entry of endothelial cells and leukocytes, such as monocytes/macrophages into the tumor organoid. Therefore, galectin-3 plays homeostatic roles in tumors, as (i) it favors tumor cell adaptation for survival in stressed conditions; (ii) upon secretion, galectin-3 induces tumor cell detachment and migration; and (iii) it attracts monocyte/macrophage and endothelial cells to the tumor mass, inducing both directly and indirectly the process of angiogenesis. The two latter activities are potentially targetable, and specific interventions may be designed to counteract the protumoral role of extracellular

  6. Galectin-3 Determines Tumor Cell Adaptive Strategies in Stressed Tumor Microenvironments.

    Science.gov (United States)

    Cardoso, Ana Carolina Ferreira; Andrade, Luciana Nogueira de Sousa; Bustos, Silvina Odete; Chammas, Roger

    2016-01-01

    Galectin-3 is a member of the β-galactoside-binding lectin family, whose expression is often dysregulated in cancers. While galectin-3 is usually an intracellular protein found in the nucleus and in the cytoplasm, under certain conditions, galectin-3 can be secreted by an yet unknown mechanism. Under stressing conditions (e.g., hypoxia and nutrient deprivation) galectin-3 is upregulated, through the activity of transcription factors, such as HIF-1α and NF-κB. Here, we review evidence that indicates a positive role for galectin-3 in MAPK family signal transduction, leading to cell proliferation and cell survival. Galectin-3 serves as a scaffold protein, which favors the spatial organization of signaling proteins as K-RAS. Upon secretion, extracellular galectin-3 interacts with a variety of cell surface glycoproteins, such as growth factor receptors, integrins, cadherins, and members of the Notch family, among other glycoproteins, besides different extracellular matrix molecules. Through its ability to oligomerize, galectin-3 forms lectin lattices that act as scaffolds that sustain the spatial organization of signaling receptors on the cell surface, dictating its maintenance on the plasma membrane or their endocytosis. Galectin-3 induces tumor cell, endothelial cell, and leukocyte migration, favoring either the exit of tumor cells from a stressed microenvironment or the entry of endothelial cells and leukocytes, such as monocytes/macrophages into the tumor organoid. Therefore, galectin-3 plays homeostatic roles in tumors, as (i) it favors tumor cell adaptation for survival in stressed conditions; (ii) upon secretion, galectin-3 induces tumor cell detachment and migration; and (iii) it attracts monocyte/macrophage and endothelial cells to the tumor mass, inducing both directly and indirectly the process of angiogenesis. The two latter activities are potentially targetable, and specific interventions may be designed to counteract the protumoral role of extracellular

  7. Galectin-3 silencing inhibits epirubicin-induced ATP binding cassette transporters and activates the mitochondrial apoptosis pathway via β-catenin/GSK-3β modulation in colorectal carcinoma.

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    Yung-Kuo Lee

    Full Text Available Multidrug resistance (MDR, an unfavorable factor compromising the treatment efficacy of anticancer drugs, involves the upregulation of ATP binding cassette (ABC transporters and induction of galectin-3 signaling. Galectin-3 plays an anti-apoptotic role in many cancer cells and regulates various pathways to activate MDR. Thus, the inhibition of galectin-3 has the potential to enhance the efficacy of the anticancer drug epirubicin. In this study, we examined the effects and mechanisms of silencing galectin-3 via RNA interference (RNAi on the β-catenin/GSK-3β pathway in human colon adenocarcinoma Caco-2 cells. Galectin-3 knockdown increased the intracellular accumulation of epirubicin in Caco-2 cells; suppressed the mRNA expression of galectin-3, β-catenin, cyclin D1, c-myc, P-glycoprotein (P-gp, MDR-associated protein (MRP 1, and MRP2; and downregulated the protein expression of P-gp, cyclin D1, galectin-3, β-catenin, c-Myc, and Bcl-2. Moreover, galectin-3 RNAi treatment significantly increased the mRNA level of GSK-3β, Bax, caspase-3, and caspase-9; remarkably increased the Bax-to-Bcl-2 ratio; and upregulated the GSK-3β and Bax protein expressions. Apoptosis was induced by galectin-3 RNAi and/or epirubicin as demonstrated by chromatin condensation, a higher sub-G1 phase proportion, and increased caspase-3 and caspase-9 activity, indicating an intrinsic/mitochondrial apoptosis pathway. Epirubicin-mediated resistance was effectively inhibited via galectin-3 RNAi treatment. However, these phenomena could be rescued after galectin-3 overexpression. We show for the first time that the silencing of galectin-3 sensitizes MDR cells to epirubicin by inhibiting ABC transporters and activating the mitochondrial pathway of apoptosis through modulation of the β-catenin/GSK-3β pathway in human colon cancer cells.

  8. How Microgravity Changes Galectin-3 in Thyroid Follicles

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    Elisabetta Albi

    2014-01-01

    Full Text Available After long-term exposure to real microgravity thyroid gland in vivo undergoes specific changes, follicles are made up of larger thyrocytes that produce more cAMP and express more thyrotropin-receptor, caveolin-1, and sphingomyelinase and sphingomyelin-synthase; parafollicular spaces lose C cells with consequent reduction of calcitonin production. Here we studied four immunohistochemical tumor markers (HBME-1, MIB-1, CK19, and Galectin-3 in thyroid of mice housed in the Mouse Drawer System and maintained for 90 days in the International Space Station. Results showed that MIB-1 proliferative index and CK19 are negative whereas HBME-1 and Galectin-3 are overexpressed. The positivity of Galectin-3 deserves attention not only for its expression but also and especially for its localization. Our results highlighted that, in microgravity conditions, Galectin-3 leaves thyrocytes and diffuses in colloid. It is possible that the gravity force contributes to the maintenance of the distribution of the molecules in both basal membrane side and apical membrane side and that the microgravity facilitates slippage of Galectin-3 in colloid probably due to membrane remodelling-microgravity induced.

  9. Nucleocytoplasmic shuttling of galectin-3.

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    Arnoys, Eric J; Ackerman, Cheri M; Wang, John L

    2015-01-01

    A large number of observations on the nuclear versus cytoplasmic distribution of galectin-3 have been reported, correlating the presence or absence of the protein in a particular compartment of the cell to various parameters such as source of the cells under study, specific cell type, culture conditions, proliferation status of the cell/culture, or neoplastic transformation. In fact, galectin-3 exhibits the phenomenon of nucleocytoplasmic shuttling, defined as the repeated bidirectional movement of a protein across the nuclear pore complex. Nevertheless, the finding that galectin-3 can show a predominantly nuclear localization under one set of conditions and a prominent cytoplasmic localization under other conditions suggests specific and regulated mechanisms of balance between cytoplasmic anchorage, nuclear import, nuclear retention, and nuclear export. One key consideration in the understanding of these processes is the definition of the signals and receptors that mediate the transport. In this chapter, we describe the experimental procedures that have allowed us to document the phenomenon of nucleocytoplasmic shuttling and the identification of the nuclear localization signal as well as the nuclear export signal. PMID:25253159

  10. Galectin-3 functions as an alarmin: pathogenic role for sepsis development in murine respiratory tularemia.

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    Bibhuti B Mishra

    Full Text Available Sepsis is a complex immune disorder with a mortality rate of 20-50% and currently has no therapeutic interventions. It is thus critical to identify and characterize molecules/factors responsible for its development. We have recently shown that pulmonary infection with Francisella results in sepsis development. As extensive cell death is a prominent feature of sepsis, we hypothesized that host endogenous molecules called alarmins released from dead or dying host cells cause a hyperinflammatory response culminating in sepsis development. In the current study we investigated the role of galectin-3, a mammalian β-galactoside binding lectin, as an alarmin in sepsis development during F. novicida infection. We observed an upregulated expression and extracellular release of galectin-3 in the lungs of mice undergoing lethal pulmonary infection with virulent strain of F. novicida but not in those infected with a non-lethal, attenuated strain of the bacteria. In comparison with their wild-type C57Bl/6 counterparts, F. novicida infected galectin-3 deficient (galectin-3(-/- mice demonstrated significantly reduced leukocyte infiltration, particularly neutrophils in their lungs. They also exhibited a marked decrease in inflammatory cytokines, vascular injury markers, and neutrophil-associated inflammatory mediators. Concomitantly, in-vitro pre-treatment of primary neutrophils and macrophages with recombinant galectin-3 augmented F. novicida-induced activation of these cells. Correlating with the reduced inflammatory response, F. novicida infected galectin-3(-/- mice exhibited improved lung architecture with reduced cell death and improved survival over wild-type mice, despite similar bacterial burden. Collectively, these findings suggest that galectin-3 functions as an alarmin by augmenting the inflammatory response in sepsis development during pulmonary F. novicida infection.

  11. Galectin-3 induces pulmonary artery endothelial cell morphogenesis and angiogenesis

    Institute of Scientific and Technical Information of China (English)

    ZHANG Li; LI Yu-mei; WANG Xiao-yan; ZHU Da-ling

    2016-01-01

    AIM:Increasing evidence suggests that carbohydrate-binding proteins play an essential role in tumor growth and metastasis .Ga-lectin-3, a multifunctional protein of an expanding family of β-galactoside-binding animal lectins , is the major nonintegrin cellular laminin-binding protein , and is implicated in a variety of biologic events , such as inflammation and angiogenesis .Because galectin-3 expression was shown to participate in mediating tumor angiogenesis and initiate signaling cascades in several diseases .We hypothe-sized that galectin-3 may promote pulmonary vascular endothelial neovascularization .METHODS:Hypoxic and MCT rat model of pul-monary artery remodeling was used .The mRNA and protein levels of galectin-3 in rats were measured by in situ hybrization and West-ern blot analysis.Endothelial cell (EC) proliferation, migration and tube formation were measured using MTT , cell scratch and Matri-gel assays, respectively.Protein expression was quantitated by Western blot analysis .LC 3A/B staining was detected with cellular im-munofluorescence staining .RESULTS:We found that galectin-3 was localized on the intima and adventitial wall .Galectin-3 was in-creased after rat hypoxia and MCT administration .Galectin-3 promoted EC proliferation , migration and tube formation , while its roles were reversed by RNA interference.Galectin-3 induced Atg 5, Beclin-1, LAMP-2, and LC 3A/B expression increases.Galectin-3 al-so increased LC 3A/B staining in ECs.Akt/mTOR and GSK-3βsignaling pathways were activated after galectin-3 treated ECs using its specific phosphorylation antibodies , while blocked it with LY294002 inhibited cell autophagy and EC dynamic alterations induced by galectin-3.CONCLUSION:These findings demonstrate that galectin-3 can induce an Akt signaling cascade leading to cell autoph-agy, and then the differentiation and angiogenesis of pulmonary artery endothelial cells .

  12. Galectin-3 in patients undergoing ablation of atrial fibrillation

    OpenAIRE

    Nicolas Clementy; Eric Piver; Nazih Benhenda; Anne Bernard; Bertrand Pierre; Edouard Siméon; Laurent Fauchier; Jean-Christophe Pagès; Dominique Babuty

    2014-01-01

    Background: Mechanisms of maintenance of atrial fibrillation are known to include fibrosis. Galectin-3, as a biomarker of fibrosis, may be a valuable marker of atrial remodeling. We sought to find whether there was a link between clinical features and higher galectin-3 levels in patients with atrial fibrillation. Methods: Serum concentrations of Galectin-3 were determined in a consecutive series of patients addressed for ablation of atrial fibrillation. Results: One-hundred-and-eighty-s...

  13. Role of galectin-3 in prion infections of the CNS

    International Nuclear Information System (INIS)

    Galectin-3 is a multi-functional protein and participates in mediating inflammatory reactions. The pronounced overexpression of galectin-3 in prion-infected brain tissue prompted us to study the role of this protein in a murine prion model. Immunofluorescence double-labelling identified microglia as the major cell type expressing galectin-3. Ablation of galectin-3 did not affect PrPSc-deposition and development of gliosis. However, galectin-3-/--mice showed prolonged survival times upon intracerebral and peripheral scrapie infections. Moreover, protein levels of the lysosomal activation marker LAMP-2 were markedly reduced in prion-infected galectin-3-/--mice suggesting a role of galectin-3 in regulation of lysosomal functions. Lower mRNA levels of Beclin-1 and Atg5 in prion-infected wild-type and galectin-3-/--mice indicated an impairment of autophagy although autophagosome formation was unchanged. The results point towards a detrimental role of galectin-3 in prion infections of the CNS and suggest that endo-/lysosomal dysfunction in combination with reduced autophagy may contribute to disease development

  14. EXPRESSION OF GALECTIN-3 IN GASTRIC CARCINOMA AND ITS SIGNIFICANCE

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    程春生; 董卫国; 罗和生; 余保平

    2004-01-01

    Objective: To study the expression of Galectin-3 in gastric cancerous tissues and the relationship between Galectin-3 expression and biological behave of gastric carcinoma. Methods: S-P immunohistochemistry method was used to examine Galectin-3 expression in 64 primary gastric cancerous tissues and 10 normal gastric mucosa as control. The expression of Galectin-3 was examined by HPIAS- 2000 image analysis software. Results: Positive Gaiectin-3 expression was observed in 85.9% of the gastric cancer cases. In gastric cancerous tissues, about 46% of cases showed strong nuclear immunoreactivity. The degree of enhancement of immunoreactivity was different in various histopathological subtypes in cancerous tissues. The readings of average absorbency of Galectin-3 in well, moderate and poorly differentiated adenocarcinoma tissues were 0.1713(0.02147, 0.1873(0.0313 and 0.2538(0.1216 respectively. A stronger expression of Galectin-3 in cancerous tissues was observed. When Galectin-3 expression in gastric cancerous tissues was compared with that in normal gastric tissues, there was a significant difference (P<0.001). Conclusion: A significantly stronger expression of Galectin-3 in gastric cancerous tissues was observed. Galectin-3 might be a useful tumor marker for gastric carcinomas with respects to tumor metastasis, proliferation, cancer progression, and tumor cell adhesion.

  15. Nucleoporin Nup98 mediates galectin-3 nuclear-cytoplasmic trafficking

    International Nuclear Information System (INIS)

    Highlights: •Nuclear pore protein Nup98 is a novel binding partner of galectin-3. •Nup98 transports galectin-3 into cytoplasm. •Nup98 depletion leads to galectin-3 nuclear transport and induces growth retardation. •Nup98 may involve in ß-catenin pathway through interaction with galectin-3. -- Abstract: Nucleoporin Nup98 is a component of the nuclear pore complex, and is important in transport across the nuclear pore. Many studies implicate nucleoporin in cancer progression, but no direct mechanistic studies of its effect in cancer have been reported. We show here that Nup98 specifically regulates nucleus–cytoplasm transport of galectin-3, which is a ß-galactoside-binding protein that affects adhesion, migration, and cancer progression, and controls cell growth through the ß-catenin signaling pathway in cancer cells. Nup98 interacted with galectin-3 on the nuclear membrane, and promoted galectin-3 cytoplasmic translocation whereas other nucleoporins did not show these functions. Inversely, silencing of Nup98 expression by siRNA technique localized galectin-3 to the nucleus and retarded cell growth, which was rescued by Nup98 transfection. In addition, Nup98 RNA interference significantly suppressed downstream mRNA expression in the ß-catenin pathway, such as cyclin D1 and FRA-1, while nuclear galectin-3 binds to ß-catenin to inhibit transcriptional activity. Reduced expression of ß-catenin target genes is consistent with the Nup98 reduction and the galectin-3–nucleus translocation rate. Overall, the results show Nup98’s involvement in nuclear–cytoplasm translocation of galectin-3 and ß-catenin signaling pathway in regulating cell proliferation, and the results depicted here suggest a novel therapeutic target/modality for cancers

  16. Nucleoporin Nup98 mediates galectin-3 nuclear-cytoplasmic trafficking

    Energy Technology Data Exchange (ETDEWEB)

    Funasaka, Tatsuyoshi, E-mail: funasaka@staff.kanazawa-u.ac.jp [Laboratory of Molecular and Cellular Biology, Department of Biology, Faculty of Natural Systems, Institute of Science and Engineering, Kanazawa University, Ishikawa (Japan); Balan, Vitaly; Raz, Avraham [Department of Oncology and Pathology, Karmanos Cancer Institute, Wayne State University, School of Medicine, Detroit, MI (United States); Wong, Richard W., E-mail: rwong@staff.kanazawa-u.ac.jp [Laboratory of Molecular and Cellular Biology, Department of Biology, Faculty of Natural Systems, Institute of Science and Engineering, Kanazawa University, Ishikawa (Japan); Bio-AFM Frontier Research Center, Kanazawa Kanazawa University, Ishikawa (Japan)

    2013-04-26

    Highlights: •Nuclear pore protein Nup98 is a novel binding partner of galectin-3. •Nup98 transports galectin-3 into cytoplasm. •Nup98 depletion leads to galectin-3 nuclear transport and induces growth retardation. •Nup98 may involve in ß-catenin pathway through interaction with galectin-3. -- Abstract: Nucleoporin Nup98 is a component of the nuclear pore complex, and is important in transport across the nuclear pore. Many studies implicate nucleoporin in cancer progression, but no direct mechanistic studies of its effect in cancer have been reported. We show here that Nup98 specifically regulates nucleus–cytoplasm transport of galectin-3, which is a ß-galactoside-binding protein that affects adhesion, migration, and cancer progression, and controls cell growth through the ß-catenin signaling pathway in cancer cells. Nup98 interacted with galectin-3 on the nuclear membrane, and promoted galectin-3 cytoplasmic translocation whereas other nucleoporins did not show these functions. Inversely, silencing of Nup98 expression by siRNA technique localized galectin-3 to the nucleus and retarded cell growth, which was rescued by Nup98 transfection. In addition, Nup98 RNA interference significantly suppressed downstream mRNA expression in the ß-catenin pathway, such as cyclin D1 and FRA-1, while nuclear galectin-3 binds to ß-catenin to inhibit transcriptional activity. Reduced expression of ß-catenin target genes is consistent with the Nup98 reduction and the galectin-3–nucleus translocation rate. Overall, the results show Nup98’s involvement in nuclear–cytoplasm translocation of galectin-3 and ß-catenin signaling pathway in regulating cell proliferation, and the results depicted here suggest a novel therapeutic target/modality for cancers.

  17. Targeting Hsp90 with small molecule inhibitors induces the over-expression of the anti-apoptotic molecule, survivin, in human A549, HONE-1 and HT-29 cancer cells

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    Lyu Kevin W

    2010-04-01

    Full Text Available Abstract Background Survivin is a dual functioning protein. It inhibits the apoptosis of cancer cells by inhibiting caspases, and also promotes cancer cell growth by stabilizing microtubules during mitosis. Since the molecular chaperone Hsp90 binds and stabilizes survivin, it is widely believed that down-regulation of survivin is one of the important therapeutic functions of Hsp90 inhibitors such as the phase III clinically trialed compound 17-AAG. However, Hsp90 interferes with a number of molecules that up-regulate the intracellular level of survivin, raising the question that clinical use of Hsp90 inhibitors may indirectly induce survivin expression and subsequently enhance cancer anti-drug responses. The purpose of this study is to determine whether targeting Hsp90 can alter survivin expression differently in different cancer cell lines and to explore possible mechanisms that cause the alteration in survivin expression. Results Here, we demonstrated that Hsp90 inhibitors, geldanamycin and 17-AAG, induced the over-expression of survivin in three different human cancer cell lines as shown by Western blotting. Increased survivin mRNA transcripts were observed in 17-AAG and geldanamycin-treated HT-29 and HONE-1 cancer cells. Interestingly, real-time PCR and translation inhibition studies revealed that survivin was over-expressed partially through the up-regulation of protein translation instead of gene transcription in A549 cancer cells. In addition, 17-AAG-treated A549, HONE-1 and HT-29 cells showed reduced proteasomal activity while inhibition of 26S proteasome activity further increased the amount of survivin protein in cells. At the functional level, down-regulation of survivin by siRNA further increased the drug sensitivity to 17-AAG in the tested cancer cell lines. Conclusions We showed for the first time that down-regulation of survivin is not a definite therapeutic function of Hsp90 inhibitors. Instead, targeting Hsp90 with small

  18. Galectin-3 guides intracellular trafficking of some human serotransferrin glycoforms

    DEFF Research Database (Denmark)

    Carlsson, Carl Michael; Bengtson, Per; Cucak, Helena;

    2013-01-01

    these transferrin glycoforms differently after preloading with exogenously added galectin-3. In all, this study provides the first evidence of a functional role for transferrin glycans, in intracellular trafficking after uptake. Moreover, the galectin-3 bound glycoform increased in cancer, suggesting...

  19. Pathogenic roles of CD14, galectin-3, and OX40 during experimental cerebral malaria in mice.

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    Miranda S Oakley

    Full Text Available An in-depth knowledge of the host molecules and biological pathways that contribute towards the pathogenesis of cerebral malaria would help guide the development of novel prognostics and therapeutics. Genome-wide transcriptional profiling of the brain tissue during experimental cerebral malaria (ECM caused by Plasmodium berghei ANKA parasites in mice, a well established surrogate of human cerebral malaria, has been useful in predicting the functional classes of genes involved and pathways altered during the course of disease. To further understand the contribution of individual genes to the pathogenesis of ECM, we examined the biological relevance of three molecules -- CD14, galectin-3, and OX40 that were previously shown to be overexpressed during ECM. We find that CD14 plays a predominant role in the induction of ECM and regulation of parasite density; deletion of the CD14 gene not only prevented the onset of disease in a majority of susceptible mice (only 21% of CD14-deficient compared to 80% of wildtype mice developed ECM, p<0.0004 but also had an ameliorating effect on parasitemia (a 2 fold reduction during the cerebral phase. Furthermore, deletion of the galectin-3 gene in susceptible C57BL/6 mice resulted in partial protection from ECM (47% of galectin-3-deficient versus 93% of wildtype mice developed ECM, p<0.0073. Subsequent adherence assays suggest that galectin-3 induced pathogenesis of ECM is not mediated by the recognition and binding of galectin-3 to P. berghei ANKA parasites. A previous study of ECM has demonstrated that brain infiltrating T cells are strongly activated and are CD44(+CD62L(- differentiated memory T cells [1]. We find that OX40, a marker of both T cell activation and memory, is selectively upregulated in the brain during ECM and its distribution among CD4(+ and CD8(+ T cells accumulated in the brain vasculature is approximately equal.

  20. Galectin-3: a novel protein in cerebellar hemangioblastoma.

    Science.gov (United States)

    Al-Salam, Suhail; Al-Salam, Mohammed; Al Ashari, Moueid

    2013-01-01

    Hemangioblastoma (HB), a rare neoplasm of uncertain histogenesis, is characterized histologically by the presence of vacuolated; lipid-containing cells 'stromal cells' and a well developed, fine capillary network. Stromal cells are the neoplastic component of this tumor. Five-um sections were stained using streptavidin- biotin immunoperoxidase and immunofluorescent techniques. The stromal cells were uniformly "HIF-1α, Galectin-3, VEGF, VEGFR, WT-1, and bcl2," positive. Endothelial cells but not stromal cells were uniformly immunoreactive to CD31. Co-localization of HIF-1α with galectin-3 and VEGF as well as galectin-3 with VEGF in stromal cells is confirmed by immunofluorescent technique. In conclusion, the development of HB is multi-factorial and the expression of galectin-3 correlates with the expression of HIF-1α and VEGF. Galectin-3 can be used as a marker for the diagnosis of HB as well as it can be a valuable candidate for future targeting immunotherapy. PMID:23638216

  1. Galectin-3 In Obesity And Type 2 Diabetes

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    Pejnovic Nada

    2015-12-01

    Full Text Available Galectin-3 is an important regulator of inflammation and acts as a receptor for advanced-glycation (AGE and lipoxidation end-products (ALE. Evidence indicates a significant upregulation in circulating levels and visceral adipose tissue production of Galectin-3 in obesity and type 2 diabetes. Recent studies demonstrate development of obesity and dysregulation of glucose metabolism in Galectin-3 “knockout” (KO mice, which also develop accelerated and more severe pathology in models of atherosclerosis and metabolically-induced kidney damage. Thus, evidence that Galectin-3 is an important player in metabolic disease is accumulating. This review discusses current evidence on the connection between Galectin-3 and metabolic disease, focusing on mechanisms by which this galectin modulates adiposity, glucose metabolism and obesity-associated inflammatory responses.

  2. Research Progress of Galectin-3,Bcl-2 and Embryo Development Termination%Galectin-3和Bcl-2与胚胎停育研究进展

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    徐耀辉

    2012-01-01

    Galectin-3 is a member of galectin family,which interacts with intracellular glycoprotein,cell surface molecules and extracellular matrix proteins by its carbohydrate recognition domains, participates the progress of embryo implantation,embryogenesis and placenta formation,and establishes and maintains a close relationship with pregnancy. Inhibitors of apoptosis protein Bcl-2 and Galectin-3 have significant sequence similarity,and may have the same apoptosis pathway,which participates in the growth and differentiation of villous trophoblast cells in people's earlier pregnancy and the process of decidualization of endometrium,in addition,playing a critical role in the villous production,growth,placenta formation and in its tissue structure rebuilding and functional perfection.%Galectin-3 是半乳糖凝集素家族中的一员,能通过其糖识别域与细胞内糖蛋白、细胞表面分子和细胞外基质蛋白相互作用,参与胚胎着床、胚胎发生和胎盘形成等过程,与妊娠成功建立和维持密切相关.凋亡抑制蛋白Bcl-2与Galectin-3有明显的序列相似性,可能存在共同细胞凋亡通路,在人早孕过程中参与了绒毛滋养层细胞的增殖和分化、子宫内膜蜕膜化的过程,在绒毛的发生、发育、胎盘形成和组织结构改建及功能完善等方面发挥着重要作用.

  3. Multivalent scaffolds induce galectin-3 aggregation into nanoparticles

    Directory of Open Access Journals (Sweden)

    Candace K. Goodman

    2014-07-01

    Full Text Available Galectin-3 meditates cell surface glycoprotein clustering, cross linking, and lattice formation. In cancer biology, galectin-3 has been reported to play a role in aggregation processes that lead to tumor embolization and survival. Here, we show that lactose-functionalized dendrimers interact with galectin-3 in a multivalent fashion to form aggregates. The glycodendrimer–galectin aggregates were characterized by dynamic light scattering and fluorescence microscopy methodologies and were found to be discrete particles that increased in size as the dendrimer generation was increased. These results show that nucleated aggregation of galectin-3 can be regulated by the nucleating polymer and provide insights that improve the general understanding of the binding and function of sugar-binding proteins.

  4. The role of galectin-3 in cancer drug resistance

    OpenAIRE

    Fukumori, Tomoharu; Kanayama, Hiro-omi; Raz, Avraham

    2007-01-01

    The galectins comprise a family of 14 members of β-galactoside-binding proteins, characterized by their affinity for β-galactosides and by a conserved sequence in the carbohydrate recognition domain that bind to the carbohydrate portion of cell surface glycoproteins or glycolipids. Galectin-3, a 31 kDa gene product, is a multifunctional oncogenic protein which regulates cell growth, cell adhesion, cell proliferation, angiogenesis, and apoptosis. Recent studies have revealed that galectin-3 de...

  5. Expression of antigen tf and galectin-3 in fibroadenoma

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    Gallegos Itandehui Belem

    2012-12-01

    Full Text Available Abstract Background Fibroadenomas are benign human breast tumors, characterized by proliferation of epithelial and stromal components of the terminal ductal unit. They may grow, regress or remain unchanged, as the hormonal environment of the patient changes. Expression of antigen TF in mucin or mucin-type glycoproteins and of galectin-3 seems to contribute to proliferation and transformations events; their expression has been reported in ductal breast cancer and in aggressive tumors. Findings Lectin histochemistry, immunohistochemistry, and immunofluorescence were used to examine the expression and distribution of antigen TF and galectin-3. We used lectins from Arachis hypogaea, Artocarpus integrifolia, and Amaranthus lecuocarpus to evaluate TF expression and a monoclonal antibody to evaluate galectin-3 expression. We used paraffin-embedded blocks from 10 breast tissues diagnosed with fibroadenoma and as control 10 healthy tissue samples. Histochemical and immunofluorescence analysis showed positive expression of galectin-3 in fibroadenoma tissue, mainly in stroma, weak interaction in ducts was observed; whereas, in healthy tissue samples the staining was also weak in ducts. Lectins from A. leucocarpus and A. integrifolia specificaly recognized ducts in healthy breast samples, whereas the lectin from A. hypogaea recognized ducts and stroma. In fibroadenoma tissue, the lectins from A. integrifolia, A. Hypogaea, and A. leucocarpus recognized mainly ducts. Conclusions Our results suggest that expression of antigen TF and galectin-3 seems to participate in fibroadenoma development.

  6. Renal Handling of Galectin-3 in the General Population, Chronic Heart Failure, and Hemodialysis

    NARCIS (Netherlands)

    Meijers, Wouter C.; van der Velde, A. Rogier; Ruifrok, Willem P.; Schroten, Nicolas F.; Dokter, Martin M.; Damman, Kevin; Assa, Solmaz; Franssen, Casper F.; Gansevoort, Ron T.; van Gilst, Wiek; Sillje, Herman H.; de Boer, Rudolf A.

    2014-01-01

    Background-Galectin-3 is a biomarker for prognostication and risk stratification of patients with heart failure (HF). It has been suggested that renal function strongly relates to galectin-3 levels. We aimed to describe galectin-3 renal handling in HF. Methods and Results-In Sprague-Dawley rats, we

  7. Galectin-3 in patients undergoing ablation of atrial fibrillation

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    Nicolas Clementy

    2014-11-01

    Conclusions: Persistent type of atrial fibrillation is an independent predictor of higher Galectin-3 concentration. This biomarker of fibrosis may be implied in the mechanisms of atrial remodeling and maintenance of atrial fibrillation, and thus be helpful for the design of therapeutic strategy in patients with atrial fibrillation.

  8. Galectin-3 and post-myocardial infarction cardiac remodeling

    NARCIS (Netherlands)

    Meijers, Wouter C.; van der Velde, A. Rogier; Pascual-Figal, Domingo A.; de Boer, Rudolf A.

    2015-01-01

    This review summarizes the current literature regarding the involvement and the putative role(s) of galectin-3 in post-myocardial infarction cardiac remodeling. Post-myocardial infarction remodeling is characterized by acute loss of myocardium, which leads to structural and biomechanical changes in

  9. Galectin-3: a novel protein in cerebellar hemangioblastoma

    OpenAIRE

    Al-Salam, Suhail; Al-Salam, Mohammed; Ashari, Moueid Al

    2013-01-01

    Hemangioblastoma (HB), a rare neoplasm of uncertain histogenesis, is characterized histologically by the presence of vacuolated; lipid-containing cells ‘stromal cells’ and a well developed, fine capillary network. Stromal cells are the neoplastic component of this tumor. Five-um sections were stained using streptavidin- biotin immunoperoxidase and immunofluorescent techniques. The stromal cells were uniformly “HIF-1α, Galectin-3, VEGF, VEGFR, WT-1, and bcl2,” positive. Endothelial cells but n...

  10. Galectin 3 acts as an enhancer of survival responses in H. pylori-infected gastric cancer cells.

    Science.gov (United States)

    Subhash, Vinod Vijay; Ho, Bow

    2016-02-01

    Galectin 3 (Gal-3) is upregulated in gastric epithelial cells as a host response to Helicobacter pylori infection. However, the significance of Gal-3 expression in H. pylori-infected cells is not well established. We analyzed Gal-3 intracellular expression, localization, and its effects in H. pylori-infected gastric epithelial cells. The predominantly nuclear confined Gal-3 was shown to be upregulated and exported out to the cytoplasm in H. pylori-infected AGS cells. The nuclear export was channeled through CRM-1 (exportin-1) protein. Interestingly, knock down of Gal-3 expression led to reduced NF-κB promoter activity and interleukin-8 (IL-8) secretion, suggesting its pro-inflammatory roles. Furthermore, Gal-3 was found to be pro-proliferative and anti-apoptotic in nature, as its knock down caused a reduction in cell proliferation and an increase in apoptosis, respectively. Taken together, our data suggest the expression and upregulation of Gal-3 as a critical endogenous event in H. pylori infection that interferes with various intracellular events, causing prolonged cell survival, which is characteristic in carcinogenesis. PMID:27044250

  11. Labeling galectin-3 for the assessment of myocardial infarction in rats

    OpenAIRE

    Arias, Teresa; Petrov, Artiom; Chen, Jiqiu; de Haas, Hans; Pérez-Medina, Carlos; Strijkers, Gustav J.; Hajjar, Roger J; Fayad, Zahi A.; Fuster,Valentín; Narula, Jagat

    2014-01-01

    Background Galectin-3 is a ß-galactoside-binding lectin expressed in most of tissues in normal conditions and overexpressed in myocardium from early stages of heart failure (HF). It is an established biomarker associated with extracellular matrix (ECM) turnover during myocardial remodeling. The aim of this study is to test the ability of 123I-galectin-3 (IG3) to assess cardiac remodeling in a model of myocardial infarction (MI) using imaging techniques. Methods Recombinant galectin-3 was labe...

  12. Serum Galectin-3 Levels Predict Recurrences after Ablation of Atrial Fibrillation

    Science.gov (United States)

    Clementy, Nicolas; Benhenda, Nazih; Piver, Eric; Pierre, Bertrand; Bernard, Anne; Fauchier, Laurent; Pages, Jean-Christophe; Babuty, Dominique

    2016-01-01

    Galectin-3 is a biomarker of fibrosis and atrial remodeling, involved in the mechanisms of initiation and maintenance of atrial fibrillation (AF). We sought to study the accuracy of galectin-3 level in predicting recurrences of AF after ablation. Serum concentrations of galectin-3 were determined in a consecutive series of patients addressed for AF ablation in our center. After a 3-month blanking period, recurrences of atrial arrhythmias were collected during the first year in all patients, using Holter monitoring at 3, 6 months and 12 months. A total of 160 patients were included, with a mean galectin-3 rate was 14.4 ± 5.6 ng/mL. At 12-month, 55 patients (34%) had reexperienced sustained atrial arrhythmia. Only higher galectin-3 level (HR = 1.07 [1.01–1.12], p = 0.02) and larger left atrial diameter (HR = 1.07 [1.03–1.12], p = 0.001) independently predicted recurrence. Patients with both galectin-3 level drug − of 91%, as compared with 41% in patients with galectin-3 ≥ 15 and left trial diameter ≥40 (p < 0.0001), whether AF was paroxysmal or persistent. Galectin-3 and left atrial diameters, rather than clinical presentation of AF, predict recurrences after ablation. PMID:27677964

  13. Galectin-3 : a new biomarker for heart failure progression and prognosis

    NARCIS (Netherlands)

    de Boer, Rudolf A.; van der Velde, A. Rogier

    2013-01-01

    Galectin-3 is a carbohydrate-binding protein involved in inflammatory and fibrotic processes in various tissues. In the heart, galectin-3 activation has been associated with progression of cardiac fibrosis leading to cardiac remodeling and heart failure development. Clinical studies have shown that

  14. Hypoxia Up-Regulates Galectin-3 in Mammary Tumor Progression and Metastasis.

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    de Oliveira, Joana T; Ribeiro, Cláudia; Barros, Rita; Gomes, Catarina; de Matos, Augusto J; Reis, Celso A; Rutteman, Gerard R; Gärtner, Fátima

    2015-01-01

    The tumor microenvironment encompasses several stressful conditions for cancer cells such as hypoxia, oxidative stress and pH alterations. Galectin-3, a well-studied member of the beta-galactoside-binding animal family of lectins has been implicated in multiple steps of metastasis as cell-cell and cell-ECM adhesion, promotion of angiogenesis, cell proliferation and resistance to apoptosis. However, both its aberrantly up- and down-regulated expression was observed in several types of cancer. Thus, the mechanisms that regulate galectin-3 expression in neoplastic settings are not clear. In order to demonstrate the putative role of hypoxia in regulating galectin-3 expression in canine mammary tumors (CMT), in vitro and in vivo studies were performed. In malignant CMT cells, hypoxia was observed to induce expression of galectin-3, a phenomenon that was almost completely prevented by catalase treatment of CMT-U27 cells. Increased galectin-3 expression was confirmed at the mRNA level. Under hypoxic conditions the expression of galectin-3 shifts from a predominant nuclear location to cytoplasmic and membrane expressions. In in vivo studies, galectin-3 was overexpressed in hypoxic areas of primary tumors and well-established metastases. Tumor hypoxia thus up-regulates the expression of galectin-3, which may in turn increase tumor aggressiveness. PMID:26222311

  15. Hypoxia Up-Regulates Galectin-3 in Mammary Tumor Progression and Metastasis.

    Directory of Open Access Journals (Sweden)

    Joana T de Oliveira

    Full Text Available The tumor microenvironment encompasses several stressful conditions for cancer cells such as hypoxia, oxidative stress and pH alterations. Galectin-3, a well-studied member of the beta-galactoside-binding animal family of lectins has been implicated in multiple steps of metastasis as cell-cell and cell-ECM adhesion, promotion of angiogenesis, cell proliferation and resistance to apoptosis. However, both its aberrantly up- and down-regulated expression was observed in several types of cancer. Thus, the mechanisms that regulate galectin-3 expression in neoplastic settings are not clear. In order to demonstrate the putative role of hypoxia in regulating galectin-3 expression in canine mammary tumors (CMT, in vitro and in vivo studies were performed. In malignant CMT cells, hypoxia was observed to induce expression of galectin-3, a phenomenon that was almost completely prevented by catalase treatment of CMT-U27 cells. Increased galectin-3 expression was confirmed at the mRNA level. Under hypoxic conditions the expression of galectin-3 shifts from a predominant nuclear location to cytoplasmic and membrane expressions. In in vivo studies, galectin-3 was overexpressed in hypoxic areas of primary tumors and well-established metastases. Tumor hypoxia thus up-regulates the expression of galectin-3, which may in turn increase tumor aggressiveness.

  16. Galectin-3与垂体泌乳素瘤侵袭性的关系%Relationship between Expression of Galectin-3 and Invasiveness of Prolactinoma

    Institute of Scientific and Technical Information of China (English)

    蒲建章; 赵洪洋; 苏群

    2006-01-01

    目的探讨Galectin-3表达和人脑垂体泌乳素(PRL)腺瘤侵袭性的关系.方法应用免疫组织化学技术SP法检测38例垂体PRL腺瘤Galectin-3的表达.结果①侵袭PRL腺瘤与非侵袭PRL腺瘤组的Galectin-3阳性表达率分别为92.0%(23/25)和38.46%(5/13),两组之间差异显著(P<0.01).②Galectin-3表达与PRL肿瘤的大小及海绵窦侵袭有关(P<0.05),但与年龄和性别无明显关系(P>0.05).结论Galectin-3与垂体PRL腺瘤侵袭性密切相关,Galectin-3可能在PRL腺瘤的侵袭性生长过程中起重要作用.

  17. Serum galectin-3: a risk factor for vascular complications in type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    JIN Qi-hui; LOU Yu-feng; LI Tian-lang; CHEN Huai-hong; LIU Qiang; HE Xiao-jun

    2013-01-01

    Background Plasma galectin-3,a mediator of fibrogenesis and inflammation,its potential to associate with type 2 diabetes (T2DM) is poorly investigated.Here,we explored its interaction with the serum galectin-3 and vascular complications.Methods We conducted a population-based cross-sectional survey in Zhejiang,China involving 165 men and 119 women (age range,43-84 years),investigating the relationship between serum galectin-3 and vascular disease in patients with T2DM.Results Serum galectin-3 was higher in subjects with T2DM than that in control participants (27.4 vs.17.6 ng/ml,P <0.001).Compared with subjects with galectin-3 values in the lowest quartile,those with values in the highest quartile had an increased likelihood of vascular complications (4th quartile odds ratio (OR) 2.52,95% confidence interval (CI),1.25-4.07).Increased risk of micro-or macrovascular complications corrrelated with serum galectin-3 concentration (ORs 11.4and 8.5,respectively).An increased number of vascular complications was associated with high serum galectin-3 levels (P<0.05).Patients with serum galectin-3 levels >25 ng/ml had an elevated risk of diabetes relative to patients with levels <10ng/ml (OR for any vascular complication 2.64,for heart failure 3.97,for nephropathy 4.09,for peripheral arterial disease (PAD) 4.18; all P <0.05).Complication risk was higher in patients with neurogenic,stroke,or retinopathy complications,but this difference was not significant after risk factor adjustment.Serum galectin-3 levels correlated with diabetes duration,C-reactive protein (CRP) levels,and albuminuria.Conclusion High galectin-3 values were associated with increased odds of developing heart failure,nephropathy,and peripheral arterial disease in patients with T2DM.

  18. Bisphosphonate-associated osteonecrosis of the jaw is linked to suppressed TGFβ1-signaling and increased Galectin-3 expression: A histological study on biopsies

    Directory of Open Access Journals (Sweden)

    Schlegel Karl A

    2011-07-01

    Full Text Available Abstract Background Bisphosphonate associated osteonecrosis of the jaw (BRONJ implies an impairment in oral hard- and soft tissue repair. An understanding of the signal transduction alterations involved can inform therapeutic strategies. Transforming growth factor β1 (TGFβ1 is a critical regulator of tissue repair; galectin-3 mediates tissue differentiation and specifically modulates periodontopathic bacterial infection. The aim of this study was to compare the expression of TGFβ1-related signaling molecules and Galectin-3 in BRONJ-affected and healthy mucosal tissues. To discriminate between BRONJ-specific impairments in TGFβ1 signaling and secondary inflammatory changes, the results were compared to the expression of TGFβ1 and Galectin-3 in mucosal tissues with osteoradionecrosis. Methods Oral mucosal tissue samples with histologically-confirmed BRONJ (n = 20, osteoradionecrosis (n = 20, and no lesions (normal, n = 20 were processed for immunohistochemistry. Automated staining with an alkaline phosphatase-anti-alkaline phosphatase kit was used to detect TGFβ1, Smad-2/3, Smad-7, and Galectin-3. We semiquantitatively assessed the ratio of stained cells/total number of cells (labeling index, Bonferroni-adjustment. Results TGFβ1 and Smad-2/3 were significantly decreased (p Conclusion Our results showed that disrupted TGFβ1 signaling was associated with delayed periodontal repair in BRONJ samples. The findings also indicated that impairments in TGFβ1-signaling were different in BRONJ compared to osteoradionecrosis. BRONJ appeared to be associated with increased terminal osseous differentiation and decreased soft tissue proliferation. The increase in Galectin-3 reflected the increase in osseous differentiation of mucoperiosteal progenitors, and this might explain the inflammatory anergy observed in BRONJ-affected soft tissues. The results substantiated the clinical success of treating BRONJ with sequestrectomy, followed by strict mucosa

  19. Nitric oxide as a pro-apoptotic as well as anti-apoptotic modulator.

    Science.gov (United States)

    Choi, Byung-Min; Pae, Hyun-Ock; Jang, Seon Il; Kim, Young-Myeong; Chung, Hun-Taeg

    2002-01-31

    Nitric oxide (NO), synthesized from L-arginine by NO synthases, is a small, lipophilic, diffusible, highly reactive molecule with dichotomous regulatory roles in many biological events under physiological and pathological conditions. NO can promote apoptosis (pro-apoptosis) in some cells, whereas it inhibits apoptosis (anti-apoptosis) in other cells. This complexity is a consequence of the rate of NO production and the interaction with biological molecules such as metal ion, thiol, protein tyrosine, and reactive oxygen species. Long-lasting overproduction of NO acts as a pro-apoptotic modulator, activating caspase family proteases through the release of mitochondrial cytochrome c into cytosol, up-regulation of the p53 expression, and alterations in the expression of apoptosis-associated proteins, including the Bcl-2 family. However, low or physiological concentrations of NO prevent cells from apoptosis that is induced by the trophic factor withdrawal, Fas, TNFalpha/ActD, and LPS. The anti-apoptotic mechanism is understood on the basis of gene transcription of protective proteins. These include: heat shock protein, hemeoxygenase, or cyclooxygenase-2 and direct inhibition of the apoptotic executive effectors caspase family protease by S-nitrosylation of the cysteine thiol group in their catalytic site in a cell specific way. Our current understanding of the mechanisms by which NO exerts both pro- and anti-apototic action is discussed in this review article. PMID:16248976

  20. Serum Galectin-9 and Galectin-3-Binding Protein in Acute Dengue Virus Infection.

    Science.gov (United States)

    Liu, Kuan-Ting; Liu, Yao-Hua; Chen, Yen-Hsu; Lin, Chun-Yu; Huang, Chung-Hao; Yen, Meng-Chi; Kuo, Po-Lin

    2016-01-01

    Dengue fever is a serious threat for public health and induces various inflammatory cytokines and mediators, including galectins and glycoproteins. Diverse immune responses and immunological pathways are induced in different phases of dengue fever progression. However, the status of serum galectins and glycoproteins is not fully determined. The aim of this study was to investigate the serum concentration and potential interaction of soluble galectin-1, galectin-3, galectin-9, galectin-3 binding protein (galectin-3BP), glycoprotein 130 (gp130), and E-, L-, and P-selectin in patients with dengue fever in acute febrile phase. In this study, 317 febrile patients (187 dengue patients, 150 non-dengue patients that included 48 patients with bacterial infection and 102 patients with other febrile illness) who presented to the emergency department and 20 healthy controls were enrolled. Our results showed the levels of galectin-9 and galectin-3BP were significantly higher in dengue patients than those in healthy controls. Lower serum levels of galectin-1, galectin-3, and E-, L-, and P-selectin in dengue patients were detected compared to bacteria-infected patients, but not to healthy controls. In addition, strong correlation between galectin-9 and galectin-3BP was observed in dengue patients. In summary, our study suggested galectin-9 and galectin-3BP might be critical inflammatory mediators in acute dengue virus infection. PMID:27240351

  1. Methodology and technical requirements of the galectin-3 test for the preoperative characterization of thyroid nodules.

    Science.gov (United States)

    Bartolazzi, Armando; Bellotti, Carlo; Sciacchitano, Salvatore

    2012-01-01

    In the last decade, the β-galactosyl binding protein galectin-3 has been the object of extensive molecular, structural, and functional studies aimed to clarify its biological role in cancer. Multicenter studies also contributed to discover the potential clinical value of galectin-3 expression analysis in distinguishing, preoperatively, benign from malignant thyroid nodules. As a consequence galectin-3 is receiving significant attention as tumor marker for thyroid cancer diagnosis, but some conflicting results mostly owing to methodological problems have been published. The possibility to apply preoperatively a reliable galectin-3 test method on fine needle aspiration biopsy (FNA)-derived thyroid cells represents an important achievement. When correctly applied, the method reduces consistently the gray area of thyroid FNA cytology, contributing to avoid unnecessary thyroid surgery. Although the efficacy and reliability of the galectin-3 test method have been extensively proved in several studies, its translation in the clinical setting requires well-standardized reagents and procedures. After a decade of experimental work on galectin-3-related basic and translational research projects, the major methodological problems that may potentially impair the diagnostic performance of galectin-3 immunotargeting are highlighted and discussed in detail. A standardized protocol for a reliable galectin-3 expression analysis is finally provided. The aim of this contribution is to improve the clinical management of patients with thyroid nodules, promoting the preoperative use of a reliable galectin-3 test method as ancillary technique to conventional thyroid FNA cytology. The final goal is to decrease unnecessary thyroid surgery and its related social costs. PMID:21691201

  2. Galectin-3 and cyclin D1 expression in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Gołecki Marcin

    2011-10-01

    Full Text Available Abstract Introduction Lung cancer is a major cause of mortality and morbidity worldwide. Galectin-3 is multifunctional protein, which is involved in regulation of cell growth, cell adhesion, cell proliferation, angiogenesis and apoptosis. Cyclin D1 together with other cyclin plays an important role in cell cycle control. Cyclin D1 regulates the G1-to-S phase transition. The aim of this study was the evaluation of correlations between clinicopathological findings and cyclin D1 and galectin-3 expression in non-small cell lung cancer (NSCLC. We wanted also to analyze the prognostic value of cyclin D1 and galectin-3 expression. Moreover we tried to evaluate the correlations between galectin-3 and cyclin D1 expression in tumor tissue. Materials and methods We used the immunochemistry method to investigate the expression of galectin-3 and cyclin D1 in the paraffin-embedded tumor tissue of 47 patients (32 men and 15 women; mean age 59.34 ± 8.90. years. We used monoclonal antibodies to cyclin D1 (NCL-L-cyclin D1-GM clone P2D11F11 NOVO CASTRA and to galectin-3 (mouse monoclonal antibody NCL-GAL3 NOVO CASTRA. Results Galectin-3 expression was positive in 18 cases (38.29% and cyclin D1 in 39 (82.97%. We showed only weak trend, that galectin-3 expression was lower in patients without lymph node involvement (p = 0.07 and cyclin D1 expression was higher in this group (p = 0.080. We didn't reveal differences in cyclin D1 and galectin-3 expression in SCC and adenocarcinoma patients. We didn't demonstrated also differences in galectin-3 and cyclin D1 expression depending on disease stage. Moreover we analyzed the prognostic value of cyclin D1 expression and galectin-3 in all examinated patients and separately in SCC and in adenocarcinoma and in all stages, but we didn't find any statistical differences. We demonstrated that in galectin-3 positive tumors cyclin D1 expression was higher (96.55% vs 61.11%, Chi2 Yatesa 7.53, p = 0.0061 and we revealed negative

  3. BAG1: the guardian of anti-apoptotic proteins in acute myeloid leukemia.

    Directory of Open Access Journals (Sweden)

    Sanja Aveic

    Full Text Available BCL2 associated Athano-Gene 1 (BAG1 is a multifunctional protein that has been described to be involved in different cell processes linked to cell survival. It has been reported as deregulated in diverse cancer types. Here, BAG1 protein was found highly expressed in children with acute myeloid leukemia at diagnosis, and in a cohort of leukemic cell lines. A silencing approach was used for determining BAG1's role in AML, finding that its down-regulation decreased expression of BCL2, BCL-XL, MCL1, and phospho-ERK1/2, all proteins able to sustain leukemia, without affecting the pro-apoptotic protein BAX. BAG1 down-regulation was also found to increase expression of BAG3, whose similar activity was able to compensate the loss of function of BAG1. BAG1/BAG3 co-silencing caused an enhanced cell predisposition to death in cell lines and also in primary AML cultures, affecting the same proteins. Cell death was CASPASE-3 dependent, was accompanied by PARP cleavage and documented by an increased release of pro-apoptotic molecules Smac/DIABLO and Cytochrome c. BAG1 was found to directly maintain BCL2 and to protect MCL1 from proteasomal degradation by controlling USP9X expression, which appeared to be its novel target. Finally, BAG1 was found able to affect leukemia cell fate by influencing the expression of anti-apoptotic proteins crucial for AML maintenance.

  4. Overexpression of the anti-apoptotic protein AVEN contributes to increased malignancy in hematopoietic neoplasms.

    Science.gov (United States)

    Eißmann, M; Melzer, I M; Fernández, S B M; Michel, G; Hrabě de Angelis, M; Hoefler, G; Finkenwirth, P; Jauch, A; Schoell, B; Grez, M; Schmidt, M; Bartholomae, C C; Newrzela, S; Haetscher, N; Rieger, M A; Zachskorn, C; Mittelbronn, M; Zörnig, M

    2013-05-16

    AVEN has been identified as an inhibitor of apoptosis, which binds to the adaptor protein, APAF-1, and thereby prevents apoptosome formation and mitochondrial apoptosis. Recent data have demonstrated high expression levels of AVEN messenger RNA in acute leukemias as well as a positive correlation between AVEN mRNA overexpression and poor prognosis in childhood acute lymphoblastic leukemia. On the basis of these data, we investigated the potential involvement of AVEN in tumorigenesis. First, we confirmed the overexpression of AVEN in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) patient samples. We then established a transgenic mouse model with T-cell-specific overexpression of AVEN, with which we demonstrated the oncogenic cooperation of AVEN with heterozygous loss of p53. Finally, we used a subcutaneous xenograft mouse model to show that AVEN knockdown in the T-ALL cell lines, MOLT-4 and CCRF-CEM, and in the acute myeloblastic leukemia cell line, Kasumi-1, leads to a halt in tumor growth owing to the increased apoptosis and decreased proliferation of tumor cells. Collectively, our data demonstrate that the anti-apoptotic molecule, AVEN, functions as an oncoprotein in hematopoietic neoplasms. PMID:22751129

  5. G3-C12 Peptide Reverses Galectin-3 from Foe to Friend for Active Targeting Cancer Treatment.

    Science.gov (United States)

    Sun, Wei; Li, Lian; Yang, Qingqing; Shan, Wei; Zhang, Zhirong; Huang, Yuan

    2015-11-01

    Galectin-3 is overexpressed by numerous carcinomas and is a potential target for active tumor treatments. On the other hand, galectin-3 also plays a key role in cancer progression and prevents cells from undergoing apoptosis, thereby offsetting the benefits of active targeting drugs. However, the relative contribution of the protective antiapoptotic effects of galectin-3 and the proapoptotic effects of galectin-3-targeted therapies has remained yet unrevealed. Here, we show that a galectin-3-binding peptide G3-C12 could reverse galectin-3 from foe to friend for active targeting delivery system. Results showed G3-C12 modified N-(2-hydroxypropyl)methacrylamide copolymer doxorubicin conjugates (G3-C12-HPMA-Dox) could internalize into galectin-3 overexpressed PC-3 cells via a highly specific ligand-receptor pathway (2.2 times higher cellular internalization than HPMA-Dox). The internalized Dox stimulated the translocation of galectin-3 to the mitochondria to prevent from apoptosis. In turn, this caused G3-C12-HPMA-Dox to concentrate into the mitochondria after binding to galectin-3 intracellularly. Initially, mitochondrial galectin-3 weakened Dox-induced mitochondrial damage; however, as time progressed, G3-C12 active-mediation allowed increasing amounts of Dox to be delivered to the mitochondria, which eventually induced higher level of apoptosis than nontargeted copolymers. In addition, G3-C12 downregulates galectin-3 expression, 0.43 times lower than control cells, which could possibly be responsible for the suppressed cell migration. Thus, G3-C12 peptide exerts sequential targeting to both cell membrane and mitochondria via regulating galectin-3, and eventually reverses and overcomes the protective effects of galectin-3; therefore, it could be a promising agent for the treatment of galectin-3-overexpressing cancers. PMID:26393405

  6. Serum Galectin-3 Levels Predict Recurrences after Ablation of Atrial Fibrillation

    Science.gov (United States)

    Clementy, Nicolas; Benhenda, Nazih; Piver, Eric; Pierre, Bertrand; Bernard, Anne; Fauchier, Laurent; Pages, Jean-Christophe; Babuty, Dominique

    2016-01-01

    Galectin-3 is a biomarker of fibrosis and atrial remodeling, involved in the mechanisms of initiation and maintenance of atrial fibrillation (AF). We sought to study the accuracy of galectin-3 level in predicting recurrences of AF after ablation. Serum concentrations of galectin-3 were determined in a consecutive series of patients addressed for AF ablation in our center. After a 3-month blanking period, recurrences of atrial arrhythmias were collected during the first year in all patients, using Holter monitoring at 3, 6 months and 12 months. A total of 160 patients were included, with a mean galectin-3 rate was 14.4 ± 5.6 ng/mL. At 12-month, 55 patients (34%) had reexperienced sustained atrial arrhythmia. Only higher galectin-3 level (HR = 1.07 [1.01–1.12], p = 0.02) and larger left atrial diameter (HR = 1.07 [1.03–1.12], p = 0.001) independently predicted recurrence. Patients with both galectin-3 level <15 ng/mL and left atrial diameter <40 millimeters had a 1-year arrhythmia-free survival rate − after a single procedure without anti-arrhythmic drug − of 91%, as compared with 41% in patients with galectin-3 ≥ 15 and left trial diameter ≥40 (p < 0.0001), whether AF was paroxysmal or persistent. Galectin-3 and left atrial diameters, rather than clinical presentation of AF, predict recurrences after ablation. PMID:27677964

  7. Acute hantavirus infection induces galectin-3-binding protein.

    Science.gov (United States)

    Hepojoki, Jussi; Strandin, Tomas; Hetzel, Udo; Sironen, Tarja; Klingström, Jonas; Sane, Jussi; Mäkelä, Satu; Mustonen, Jukka; Meri, Seppo; Lundkvist, Ake; Vapalahti, Olli; Lankinen, Hilkka; Vaheri, Antti

    2014-11-01

    Hantaviruses are zoonotic viruses that cause life-threatening diseases when transmitted to humans. Severe hantavirus infection is manifested by impairment of renal function, pulmonary oedema and capillary leakage. Both innate and adaptive immune responses contribute to the pathogenesis, but the underlying mechanisms are not fully understood. Here, we showed that galectin-3-binding protein (Gal-3BP) was upregulated as a result of hantavirus infection both in vitro and in vivo. Gal-3BP is a secreted glycoprotein found in human serum, and increased Gal-3BP levels have been reported in chronic viral infections and in several types of cancer. Our in vitro experiments showed that, whilst Vero E6 cells (an African green monkey kidney cell line) constitutively expressed and secreted Gal-3BP, this protein was detected in primary human cells only as a result of hantavirus infection. Analysis of Gal-3BP levels in serum samples of cynomolgus macaques infected experimentally with hantavirus indicated that hantavirus infection induced Gal-3BP also in vivo. Finally, analysis of plasma samples collected from patients hospitalized because of acute hantavirus infection showed higher Gal-3BP levels during the acute than the convalescent phase. Furthermore, the Gal-3BP levels in patients with haemorrhagic fever with renal syndrome correlated with increased complement activation and with clinical variables reflecting the severity of acute hantavirus infection. PMID:25013204

  8. Multiple approaches to assess pectin binding to galectin-3.

    Science.gov (United States)

    Zhang, Tao; Zheng, Yi; Zhao, Dongyang; Yan, Jingmin; Sun, Chongliang; Zhou, Yifa; Tai, Guihua

    2016-10-01

    Although several approaches have been used to evaluate binding of carbohydrates to lectins, results are not always comparable, especially with larger polysaccharides. Here, we quantitatively assessed and compared binding of pectin-derived polysaccharides to galectin-3 (Gal-3) using five methods: surface plasmon resonance (SPR), bio-layer interferometry (BLI), fluorescence polarization (FP), competitive fluorescence-linked immunosorbance (cFLISA), and the well-known cell-based hemagglutination assay (G3H). Our studies revealed that whereas Gal-3-pectin binding parameters determined by SPR and BLI were comparable and correlated with inhibitory potencies from the G3H assay, results using FP and cFLISA assays were highly variable and depended greatly on the probe and mass of the polysaccharide. In the cFLISA assay, for example, pectins showed no inhibition when using the DTAF-labeled asialofetuin probe, but did when using a DTAF-labeled pectin probe. And the FP approach with the DTAF-lactose probe did not work on polysaccharides and large galactan chains, although it did work well with smaller galactans. Nevertheless, even though results derived from all of these methods are in general agreement, derived KD, IC50, and MIC values do differ. Our results reflect the variability using various techniques and therefore will be useful to investigators who are developing pectin-derived Gal-3 antagonists as anti-cancer agents. PMID:27328612

  9. Galectin-3, Renal Function, and Clinical Outcomes: Results from the LURIC and 4D Studies.

    Science.gov (United States)

    Drechsler, Christiane; Delgado, Graciela; Wanner, Christoph; Blouin, Katja; Pilz, Stefan; Tomaschitz, Andreas; Kleber, Marcus E; Dressel, Alexander; Willmes, Christoph; Krane, Vera; Krämer, Bernhard K; März, Winfried; Ritz, Eberhard; van Gilst, Wiek H; van der Harst, Pim; de Boer, Rudolf A

    2015-09-01

    Galectin-3 has been linked to incident renal disease, experimental renal fibrosis, and nephropathy. However, the association among galectin-3, renal function, and adverse outcomes has not been described. We studied this association in two large cohorts of patients over a broad range of renal function. We measured galectin-3 concentrations in baseline samples from the German Diabetes mellitus Dialysis (4D) study (1168 dialysis patients with type 2 diabetes mellitus) and the Ludwigshafen Risk and Cardiovascular Health (LURIC) study (2579 patients with coronary angiograms). Patients were stratified into three groups: eGFR of ≥90 ml/min per 1.73 m(2), 60-89 ml/min per 1.73 m(2), and <60 ml/min per 1.73 m(2). We correlated galectin-3 concentrations with demographic, clinical, and biochemical parameters. The association of galectin-3 with clinical end points was assessed by Cox proportional hazards regression within 10 years (LURIC) or 4 years (4D) of follow-up. Mean±SD galectin-3 concentrations were 12.8±4.0 ng/ml (eGFR≥90 ml/min per 1.73 m(2)), 15.6±5.4 ng/ml (eGFR 60-89 ml/min per 1.73 m(2)), 23.1±9.9 ng/ml (eGFR<60 ml/min per 1.73 m(2)), and 54.1±19.6 ng/ml (dialysis patients of the 4D study). Galectin-3 concentration was significantly associated with clinical end points in participants with impaired kidney function, but not in participants with normal kidney function. Per SD increase in log-transformed galectin-3 concentration, the risks of all-cause mortality, cardiovascular mortality, and fatal infection increased significantly. In dialysis patients, galectin-3 was associated with the combined end point of cardiovascular events. In conclusion, galectin-3 concentrations increased with progressive renal impairment and independently associated with cardiovascular end points, infections, and all-cause death in patients with impaired renal function. PMID:25568176

  10. A functional yeast survival screen of tumor-derived cDNA libraries designed to identify anti-apoptotic mammalian oncogenes.

    Directory of Open Access Journals (Sweden)

    Moritz Eißmann

    Full Text Available Yeast cells can be killed upon expression of pro-apoptotic mammalian proteins. We have established a functional yeast survival screen that was used to isolate novel human anti-apoptotic genes overexpressed in treatment-resistant tumors. The screening of three different cDNA libraries prepared from metastatic melanoma, glioblastomas and leukemic blasts allowed for the identification of many yeast cell death-repressing cDNAs, including 28% of genes that are already known to inhibit apoptosis, 35% of genes upregulated in at least one tumor entity and 16% of genes described as both anti-apoptotic in function and upregulated in tumors. These results confirm the great potential of this screening tool to identify novel anti-apoptotic and tumor-relevant molecules. Three of the isolated candidate genes were further analyzed regarding their anti-apoptotic function in cell culture and their potential as a therapeutic target for molecular therapy. PAICS, an enzyme required for de novo purine biosynthesis, the long non-coding RNA MALAT1 and the MAST2 kinase are overexpressed in certain tumor entities and capable of suppressing apoptosis in human cells. Using a subcutaneous xenograft mouse model, we also demonstrated that glioblastoma tumor growth requires MAST2 expression. An additional advantage of the yeast survival screen is its universal applicability. By using various inducible pro-apoptotic killer proteins and screening the appropriate cDNA library prepared from normal or pathologic tissue of interest, the survival screen can be used to identify apoptosis inhibitors in many different systems.

  11. DIAGNOSTIC VALUE OF GALECTIN-3 LEVEL IN PATIENTS WITH CHRONIC HEART FAILURE AND TYPE 2 DIABETES

    Directory of Open Access Journals (Sweden)

    A. A. Snetkova

    2015-01-01

    Full Text Available Currently, a greater emphasis is placed on the search for additional biomarkers of chronic heart failure (CHF. Galectin-3, a marker of fibrosis and inflammation, has shown himself as a biomarker of CHF in many studies, but the dynamics of its levels in patients with concomitant diabetes mellitus (DM type 2 is not well-studied.Aim. To identify diagnostic significance of galectin-3 plasma level evaluation and its correlations with echocardiographic criteria for patients with CHF and DM type 2.Material and methods. The study included 33 patients with ischemic CHF (all patients had a history of myocardial infarction and DM type 2. The patients were divided into two groups according to the left ventricle (LV ejection fraction (EF: a group with CHF and preserved ejection fraction (PEF (EF≥50% and with CHF and reduced ejection fraction (EF<50%. Patients underwent clinical laboratory tests and Doppler echocardiography; moreover, the levels of brain natriuretic peptide (BNP and galeсtin-3 were measured.Results. The mean level of galectin-3 in blood plasma in the group with CHF and PEF was significantly higher than in the group with CHF and reduced EF (p=0.007. In the group with CHF and PEF a positive correlation between the level of galectin-3 and diastolic LV function E/E' was found (r=0.620, p=0.01. A significant correlation between galectin-3 level and LV systolic function was stated in the group with reduced EF (r=0.53; p<0.05, while in the group with PEF, the correlation was not significant (p=0.225. In the group of patients with reduced EF a negative correlation between galectin-3 and the volume of left atrium was revealed (r=-0.53; p<0.05.Conclusion. Galectin-3 can be used as a diagnostic biomarker primarily in patients with CHF and PEF.

  12. DIAGNOSTIC VALUE OF GALECTIN-3 LEVEL IN PATIENTS WITH CHRONIC HEART FAILURE AND TYPE 2 DIABETES

    Directory of Open Access Journals (Sweden)

    A. A. Snetkova

    2015-09-01

    Full Text Available Currently, a greater emphasis is placed on the search for additional biomarkers of chronic heart failure (CHF. Galectin-3, a marker of fibrosis and inflammation, has shown himself as a biomarker of CHF in many studies, but the dynamics of its levels in patients with concomitant diabetes mellitus (DM type 2 is not well-studied.Aim. To identify diagnostic significance of galectin-3 plasma level evaluation and its correlations with echocardiographic criteria for patients with CHF and DM type 2.Material and methods. The study included 33 patients with ischemic CHF (all patients had a history of myocardial infarction and DM type 2. The patients were divided into two groups according to the left ventricle (LV ejection fraction (EF: a group with CHF and preserved ejection fraction (PEF (EF≥50% and with CHF and reduced ejection fraction (EF<50%. Patients underwent clinical laboratory tests and Doppler echocardiography; moreover, the levels of brain natriuretic peptide (BNP and galeсtin-3 were measured.Results. The mean level of galectin-3 in blood plasma in the group with CHF and PEF was significantly higher than in the group with CHF and reduced EF (p=0.007. In the group with CHF and PEF a positive correlation between the level of galectin-3 and diastolic LV function E/E' was found (r=0.620, p=0.01. A significant correlation between galectin-3 level and LV systolic function was stated in the group with reduced EF (r=0.53; p<0.05, while in the group with PEF, the correlation was not significant (p=0.225. In the group of patients with reduced EF a negative correlation between galectin-3 and the volume of left atrium was revealed (r=-0.53; p<0.05.Conclusion. Galectin-3 can be used as a diagnostic biomarker primarily in patients with CHF and PEF.

  13. Galectin-3 Binds to Lubricin and Reinforces the Lubricating Boundary Layer of Articular Cartilage

    Science.gov (United States)

    Reesink, Heidi L.; Bonnevie, Edward D.; Liu, Sherry; Shurer, Carolyn R.; Hollander, Michael J.; Bonassar, Lawrence J.; Nixon, Alan J.

    2016-05-01

    Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. Extensive O-linked glycosylation within lubricin’s mucin-rich domain is critical for its boundary lubricating function; however, it is unknown exactly how glycosylation facilitates cartilage lubrication. Here, we find that the lubricin glycome is enriched with terminal β-galactosides, known binding partners for a family of multivalent lectins called galectins. Of the galectin family members present in synovial fluid, we find that galectin-3 is a specific, high-affinity binding partner for lubricin. Considering the known ability of galectin-3 to crosslink glycoproteins, we hypothesized that galectins could augment lubrication via biomechanical stabilization of the lubricin boundary layer. We find that competitive inhibition of galectin binding results in lubricin loss from the cartilage surface, and addition of multimeric galectin-3 enhances cartilage lubrication. We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. Together, our results suggest that galectin-3 reinforces the lubricin boundary layer; which, in turn, enhances cartilage lubrication and may delay the onset and progression of arthritis.

  14. Myocardial Galectin-3 Expression Is Associated with Remodeling of the Pressure-Overloaded Heart and May Delay the Hypertrophic Response without Affecting Survival, Dysfunction, and Cardiac Fibrosis.

    Science.gov (United States)

    Frunza, Olga; Russo, Ilaria; Saxena, Amit; Shinde, Arti V; Humeres, Claudio; Hanif, Waqas; Rai, Vikrant; Su, Ya; Frangogiannis, Nikolaos G

    2016-05-01

    The β-galactoside-binding animal lectin galectin-3 is predominantly expressed by activated macrophages and is a promising biomarker for patients with heart failure. Galectin-3 regulates inflammatory and fibrotic responses; however, its role in cardiac remodeling remains unclear. We hypothesized that galectin-3 may be up-regulated in the pressure-overloaded myocardium and regulate hypertrophy and fibrosis. In normal mouse myocardium, galectin-3 was constitutively expressed in macrophages and was localized in atrial but not ventricular cardiomyocytes. In a mouse model of transverse aortic constriction, galectin-3 expression was markedly up-regulated in the pressure-overloaded myocardium. Early up-regulation of galectin-3 was localized in subpopulations of macrophages and myofibroblasts; however, after 7 to 28 days of transverse aortic constriction, a subset of cardiomyocytes in fibrotic areas contained large amounts of galectin-3. In vitro, cytokine stimulation suppressed galectin-3 synthesis by macrophages and cardiac fibroblasts. Correlation studies revealed that cardiomyocyte- but not macrophage-specific galectin-3 localization was associated with adverse remodeling and dysfunction. Galectin-3 knockout mice exhibited accelerated cardiac hypertrophy after 7 days of pressure overload, whereas female galectin-3 knockouts had delayed dilation after 28 days of transverse aortic constriction. However, galectin-3 loss did not affect survival, systolic and diastolic dysfunction, cardiac fibrosis, and cardiomyocyte hypertrophy in the pressure-overloaded heart. Despite its potential role as a prognostic biomarker, galectin-3 is not a critical modulator of cardiac fibrosis but may delay the hypertrophic response. PMID:26948424

  15. Targeting the Anti-Apoptotic Protein c-FLIP for Cancer Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Safa, Ahmad R., E-mail: asafa@iupui.edu [Department of Pharmacology and Toxicology, Indiana University School of Medicine, 980 W. Walnut Street, R3-C524, Indianapolis, IN 46202 (United States); Indiana University Simon Cancer Center, Indiana University School of Medicine, 980 W. Walnut Street, R3-C524, Indianapolis, IN 46202 (United States); Pollok, Karen E. [Department of Pharmacology and Toxicology, Indiana University School of Medicine, 980 W. Walnut Street, R3-C524, Indianapolis, IN 46202 (United States); Indiana University Simon Cancer Center, Indiana University School of Medicine, 980 W. Walnut Street, R3-C524, Indianapolis, IN 46202 (United States); Herman B. Wells Center for Pediatric Research, 980 W. Walnut Street, R3-C524, Indianapolis, IN 46202 (United States)

    2011-03-29

    Cellular FLICE (FADD-like IL-1beta-converting enzyme)-inhibitory protein (c-FLIP) is a major resistance factor and critical anti-apoptotic regulator that inhibits tumor necrosis factor-alpha (TNF-alpha), Fas-L, and TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis as well as chemotherapy-triggered apoptosis in malignant cells. c-FLIP is expressed as long (c-FLIP{sub L}), short (c-FLIP{sub S}), and c-FLIP{sub R} splice variants in human cells. c-FLIP binds to FADD and/or caspase-8 or -10 in a ligand-dependent and-independent fashion, which in turn prevents death-inducing signaling complex (DISC) formation and subsequent activation of the caspase cascade. Moreover, c-FLIP{sub L} and c-FLIP{sub S} are known to have multifunctional roles in various signaling pathways, as well as activating and/or upregulating several cytoprotective signaling molecules. Upregulation of c-FLIP has been found in various tumor types, and its downregulation has been shown to restore apoptosis triggered by cytokines and various chemotherapeutic agents. Hence, c-FLIP is an important target for cancer therapy. For example, small interfering RNAs (siRNAs) that specifically knockdown the expression of c-FLIP{sub L} in diverse human cancer cell lines augmented TRAIL-induced DISC recruitment and increased the efficacy of chemotherapeutic agents, thereby enhancing effector caspase stimulation and apoptosis. Moreover, small molecules causing degradation of c-FLIP as well as decreasing mRNA and protein levels of c-FLIP{sub L} and c-FLIP{sub S} splice variants have been found, and efforts are underway to develop other c-FLIP-targeted cancer therapies. This review focuses on (1) the functional role of c-FLIP splice variants in preventing apoptosis and inducing cytokine and drug resistance; (2) the molecular mechanisms that regulate c-FLIP expression; and (3) strategies to inhibit c-FLIP expression and function.

  16. Anti-apoptotic signaling and failure of apoptosis in the ischemic rat hippocampus

    DEFF Research Database (Denmark)

    Müller, Georg Johannes; Lassmann, Hans; Johansen, Flemming Fryd

    2007-01-01

    colchicine injection severed as a reference for classical apoptosis. Heat shock protein 70 (Hsp70), neuronal apoptosis inhibitory protein (NAIP) and manganese superoxide dismutase (MnSOD) were upregulated in the majority of intact CA1 neurons paralleling the occurrence of CA1 neuronal death (days 3-7) as...... well as in a proportion of apoptosis-(<50%) and necrosis-like (<30%) CA1 neurons. Colchicine did not provoke an anti-apoptotic response in DGC at all. In addition, more than 70% of apoptosis- and necrosis-like CA1 neurons had completely lost their RCC subunits suggesting bioenergetic failure; by...... contrast, following colchicine injection, 88% of all apoptotic DGC presented RCC subunits. Thus, anti-apoptotic proteins may, in a subset of ischemic CA1 neurons, prevent cell death, while in others, affected by pronounced energy failure, they may cause secondary necrosis....

  17. Dynamics and prognostic role of galectin-3 in patients with advanced heart failure, during left ventricular assist device support and following heart transplantation

    OpenAIRE

    Coromilas, Ellie; Que-Xu, Em-Claire; Moore, D’Vesharronne; Kato, Tomoko S.; Wu, Christina; Ji, Ruiping; Givens, Raymond; Jorde, Ulrich P.; Takayama, Hiroo; NAKA, YOSHIFUMI; George, Isaac; Mancini, Donna; Schulze, P. Christian

    2016-01-01

    Background Galectin-3 is a marker of myocardial inflammation and fibrosis shown to correlate with morbidity and mortality in heart failure (HF). We examined the utility of galectin-3 as a marker of the severity of HF, the response of galectin-3 levels to ventricular assist device (LVAD) implantation or heart transplantation (HTx), and its use as a prognostic indicator. Methods Plasma galectin-3 was measured using a commercially available ELISA assay in patients with stable HF (n = 55), severe...

  18. Relaxin has anti-apoptotic effects on human trophoblast-derived HTR-8/SV neo cells.

    Science.gov (United States)

    Lodhi, Romana S Z; Nakabayashi, Koji; Suzuki, Kaho; Yamada, Ai Y; Hazama, Rhoichi; Ebina, Yasuhiko; Yamada, Hideto

    2013-12-01

    The study was conducted to evaluate the effects of human relaxin on apoptosis in the human trophoblast derived HTR-8/SV neo cell line, which is a possible model of human extravillous trophoblasts (EVTs). HTR-8/SV neo cells, cultured in phenol red free RPMI1640 medium, were treated with different doses of human recombinant (rH2) relaxin in serum-deprived conditions. RT-PCR was used for evaluating relaxin receptor: RXFP1 and RXFP2 expression in HTR-8/SV neo cells. The cell death was examined by TUNEL assay. Furthermore, we investigated caspase-3, cleaved PARP and Bcl-2 expressions by Western blot analysis to recognize the translational effects of anti-apoptotic and pro-apoptotic proteins. RXFP1 and RXFP2 mRNA expression was observed in HTR-8/SV neo cells. Compared with untreated control cultures, treatment with rH2 relaxin, decreased TUNEL-positive rate in HTR-8/SV neo cells was observed. Western blot analysis revealed that treatment with rH2 relaxin decreased the expression of caspase-3 and cleaved PARP, but in contrast increased Bcl-2 expression in those cells. These results suggest that rH2 relaxin has anti-apoptotic effects on HTR8/SV neo cells by decreasing pro-apoptotic caspase-3 and cleaved PARP expression and up-regulating anti-apoptotic Bcl-2 expression. PMID:24070111

  19. Free fatty acids and IL-6 induce adipocyte galectin-3 which is increased in white and brown adipose tissues of obese mice.

    Science.gov (United States)

    Krautbauer, Sabrina; Eisinger, Kristina; Hader, Yvonne; Buechler, Christa

    2014-10-01

    Galectin-3 regulates immune cell function and clearance of advanced glycation end products. Galectin-3 is increased in serum of obese humans and mice and most studies suggest that this protein protects from inflammation in metabolic diseases. Current data show that galectin-3 is markedly elevated in the liver, subcutaneous and intra-abdominal fat depots of mice fed a high fat diet and ob/ob mice. Galectin-3 is also increased in brown adipose tissues of these animals and immunohistochemistry confirms higher levels in adipocytes. Raised galectin-3 in obese white adipocytes has been described in the literature and regulation of adipocyte galectin-3 by metabolites with a role in obesity has been analyzed. Galectin-3 is expressed in 3T3-L1 fibroblasts and human preadipocytes and is modestly induced in mature adipocytes. In 3T3-L1 adipocytes galectin-3 is localized in the cytoplasm and is also detected in cell supernatants. Glucose does not alter soluble galectin-3. Lipopolysaccharide has no effect while TNF reduces and IL-6 raises this lectin in cell supernatants. Palmitate and oleate modestly elevate soluble galectin-3. Differentiation of 3T3-L1 cells in the presence of 100 μM and 200 μM linoleate induces soluble galectin-3 and cellular levels are upregulated by the higher concentration. Current data suggest that free fatty acids and IL-6 increase galectin-3 in adipocytes and thereby may contribute to higher levels in obesity.

  20. Anti-galectin-3 therapy: a new chance for multiple myeloma and ovarian cancer?

    Science.gov (United States)

    Mirandola, Leonardo; Nguyen, Diane D; Rahman, Rakhshanda L; Grizzi, Fabio; Yuefei, Yu; Figueroa, José A; Jenkins, Marjorie R; Cobos, Everardo; Chiriva-Internati, Maurizio

    2014-10-01

    Here we review the role of Galectins in the molecular pathogenesis of multiple myeloma and ovarian cancer, with a special focus on Glectin-3. Multiple myeloma is the second most common hematologic malignancy worldwide. Because the pathogenesis of multiple myeloma is still incompletely understood, there is no ultimately effective cure, and this cancer results fatal. Ovarian cancer is the most lethal gynecologic malignancy worldwide. Due to the lack of screening techniques for early detection, patients are mostly diagnosed with advanced disease, which results ultimately fatal. Multiple myeloma and ovarian cancer have different biologies, but they share a strong dependence on adhesion with extracellular matrix and other cells. Galectin-3 plays a key role in regulating such adhesive abilities of tumor cells. Here we discuss the outcomes and possible mechanism of action of a truncated, dominant negative form of Galectin-3, Galectin-3C, in these malignancies. Overall, we report that Galectin-3C is a promising new compound for effective adjuvant therapies in advanced, refractory multiple myeloma and ovarian cancer. PMID:24801755

  1. Hypoxia Up-Regulates Galectin-3 in Mammary Tumor Progression and Metastasis

    NARCIS (Netherlands)

    de Oliveira, Joana T; Ribeiro, Cláudia; Barros, Rita; Gomes, Catarina; de Matos, Augusto J; Reis, Celso A; Rutteman, Gerard R; Gärtner, Fátima

    2015-01-01

    The tumor microenvironment encompasses several stressful conditions for cancer cells such as hypoxia, oxidative stress and pH alterations. Galectin-3, a well-studied member of the beta-galactoside-binding animal family of lectins has been implicated in multiple steps of metastasis as cell-cell and c

  2. Utilization of Galectin-3 in Case Management Across the Spectrum of Heart Failure

    NARCIS (Netherlands)

    McCullough, Peter; de Boer, Rudolph; Edelmann, Frank; Lewis, Connie M.; Maisel, Alan S.

    2014-01-01

    In patients with heart failure as a result of mechanical and neurohormonal derangements, macrophages secrete galectin-3, which is a paracrine and endocrine factor that stimulates additional macrophages, pericytes, myofibroblasts, and fibroblasts to proliferate and secrete procollagen I, which is irr

  3. Assessment of Galectin-3 Polymorphism in Subjects with Chronic Chagas Disease

    Directory of Open Access Journals (Sweden)

    Gabriela da Silva Cruz

    2015-11-01

    Full Text Available AbstractBackground:Galectin-3, a β-galactoside binding lectin, has been described as a mediator of cardiac fibrosis in experimental studies and as a risk factor associated with cardiovascular events in subjects with heart failure. Previous studies have evaluated the genetic susceptibility to Chagas disease in humans, including the polymorphisms of cytokine genes, demonstrating correlations between the genetic polymorphism and cardiomyopathy development in the chronic phase. However, the relationship between the galectin-3 single nucleotide polymorphism (SNP and phenotypic variations in Chagas disease has not been evaluated.Objective:The present study aimed to determine whether genetic polymorphisms of galectin-3 may predispose to the development of cardiac forms of Chagas disease.Methods:Fifty-five subjects with Chagas disease were enrolled in this observational study. Real-time polymerase chain reaction (PCR was used for genotyping the variants rs4644 and rs4652 of the galectin-3 gene.Results:For the SNP rs4644, the relative risk for the cardiac form was not associated with the genotypes AA (OR = 0.79, p = 0.759, AC (OR = 4.38, p = 0.058, or CC (OR = 0.39, p = 0.127. Similarly, for the SNP rs4652, no association was found between the genotypes AA (OR = 0.64, p = 0.571, AC (OR = 2.85, p = 0.105, or CC (OR = 0.49, p = 0.227 and the cardiac form of the disease.Conclusion:Our results showed no association between the different genotypes for both SNPs of the galectin-3 gene and the cardiac form of Chagas disease. (Arq Bras Cardiol. 2015; [online].ahead print, PP.0-0

  4. Galectin-3 facilitates cell motility in gastric cancer by up-regulating protease-activated receptor-1 (PAR-1 and matrix metalloproteinase-1 (MMP-1.

    Directory of Open Access Journals (Sweden)

    Seok-Jun Kim

    Full Text Available BACKGROUND: Galectin-3 is known to regulate cancer metastasis. However, the underlying mechanism has not been defined. Through the DNA microarray studies after galectin-3 silencing, we demonstrated here that galectin-3 plays a key role in up-regulating the expressions of protease-activated receptor-1 (PAR-1 and matrix metalloproteinase-1 (MMP-1 PAR-1 thereby promoting gastric cancer metastasis. METHODOLOGY/PRINCIPAL FINDINGS: We examined the expression levels of Galectin-3, PAR-1, and MMP-1 in gastric cancer patient tissues and also the effects of silencing these proteins with specific siRNAs and of over-expressing them using specific lenti-viral constructs. We also employed zebrafish embryo model for analysis of in vivo gastric cancer cell invasion. These studies demonstrated that: a galectin-3 silencing decreases the expression of PAR-1. b galectin-3 over-expression increases cell migration and invasion and this increase can be reversed by PAR-1 silencing, indicating that galectin-3 increases cell migration and invasion via PAR-1 up-regulation. c galectin-3 directly interacts with AP-1 transcriptional factor, and this complex binds to PAR-1 promoter and drives PAR-1 transcription. d galectin-3 also amplifies phospho-paxillin, a PAR-1 downstream target, by increasing MMP-1 expression. MMP-1 silencing blocks phospho-paxillin amplification and cell invasion caused by galectin-3 over-expression. e Silencing of either galectin-3, PAR-1 or MMP-1 significantly reduced cell migration into the vessels in zebrafish embryo model. f Galectin-3, PAR-1, and MMP-1 are highly expressed and co-localized in malignant tissues from gastric cancer patients. CONCLUSIONS/SIGNIFICANCE: Galectin-3 plays the key role of activating cell surface receptor through production of protease and boosts gastric cancer metastasis. Galectin-3 has the potential to serve as a useful pharmacological target for prevention of gastric cancer metastasis.

  5. The gastroprotective effect of menthol: involvement of anti-apoptotic, antioxidant and anti-inflammatory activities.

    Directory of Open Access Journals (Sweden)

    Ariane Leite Rozza

    Full Text Available The aim of this research was to investigate the anti-apoptotic, antioxidant and anti-inflammatory properties of menthol against ethanol-induced gastric ulcers in rats. Wistar rats were orally treated with vehicle, carbenoxolone (100 mg/kg or menthol (50 mg/kg and then treated with ethanol to induce gastric ulcers. After euthanasia, stomach samples were prepared for histological slides and biochemical analyses. Immunohistochemical analyses of the cytoprotective and anti-apoptotic heat-shock protein-70 (HSP-70 and the apoptotic Bax protein were performed. The neutrophils were manually counted. The activity of the myeloperoxidase (MPO was measured. To determine the level of antioxidant functions, the levels of glutathione (GSH, glutathione peroxidase (GSH-Px, glutathione reductase (GR and superoxide dismutase (SOD were measured using ELISA. The levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6 and the anti-inflammatory cytokine interleukin-10 (IL-10 were assessed using ELISA kits. The menthol treated group presented 92% gastroprotection compared to the vehicle-treated group. An increased immunolabeled area was observed for HSP-70, and a decreased immunolabeled area was observed for the Bax protein in the menthol treated group. Menthol treatment induced a decrease in the activity of MPO and SOD, and the protein levels of GSH, GSH-Px and GR were increased. There was also a decrease in the levels of TNF-α and IL-6 and an increase in the level of IL-10. In conclusion, oral treatment with menthol displayed a gastroprotective activity through anti-apoptotic, antixidant and anti-inflammatory mechanisms.

  6. Long noncoding RNA-mediated anti-apoptotic activity in murine erythroid terminal differentiation.

    Science.gov (United States)

    Hu, Wenqian; Yuan, Bingbing; Flygare, Johan; Lodish, Harvey F

    2011-12-15

    Long noncoding RNAs (lncRNAs) are differentially expressed under both normal and pathological conditions, implying that they may play important biological functions. Here we examined the expression of lncRNAs during erythropoiesis and identified an erythroid-specific lncRNA with anti-apoptotic activity. Inhibition of this lncRNA blocks erythroid differentiation and promotes apoptosis. Conversely, ectopic expression of this lncRNA can inhibit apoptosis in mouse erythroid cells. This lncRNA represses expression of Pycard, a proapoptotic gene, explaining in part the inhibition of programmed cell death. These findings reveal a novel layer of regulation of cell differentiation and apoptosis by a lncRNA.

  7. Anti-apoptotic mechanism of Bacoside rich extract against reactive nitrogen species induced activation of iNOS/Bax/caspase 3 mediated apoptosis in L132 cell line.

    Science.gov (United States)

    Anand, T; Pandareesh, M D; Bhat, Pratiksha V; Venkataramana, M

    2014-10-01

    Nitric oxide is a highly reactive free radical gas that reacts with a wide range of bio-molecules to produce reactive nitrogen species and exerts nitrative stress. Bacopa monniera is a traditional folk and ayurvedic medicine known to alleviate a variety of disorders. Aim of the present study is to evaluate the protective propensity of Bacopa monniera extract (BME) through its oxido-nitrosative and anti-apoptotic mechanism to attenuate sodium nitroprusside (SNP)-induced apoptosis in a human embryonic lung epithelial cell line (L132). Our results elucidate that pre-treatment of L132 cells with BME ameliorates the mitochondrial and plasma membrane damage induced by SNP as evidenced by MTT and LDH leakage assays. BME pre-treatment inhibited NO generation by down-regulating inducible nitric oxide synthase expression. BME exhibited potent antioxidant activity by up-regulating the antioxidant enzymes. SNP-induced damage to cellular, nuclear and mitochondrial integrity was also restored by BME, which was confirmed by ROS estimation, comet assay and mitochondrial membrane potential assays respectively. BME pre-treatment efficiently attenuated the SNP-induced apoptotic biomarkers such as Bax, cytochrome-c and caspase-3, which orchestrate the proteolytic damage of the cell. By considering all these findings, we report that BME protects L132 cells against SNP-induced toxicity via its free radical scavenging and anti-apoptotic mechanism.

  8. A novel BH3 mimetic efficiently induces apoptosis in melanoma cells through direct binding to anti-apoptotic Bcl-2 family proteins, including phosphorylated Mcl-1.

    Science.gov (United States)

    Liu, Yubo; Xie, Mingzhou; Song, Ting; Sheng, Hongkun; Yu, Xiaoyan; Zhang, Zhichao

    2015-03-01

    The Bcl-2 family modulates sensitivity to chemotherapy in many cancers, including melanoma, in which the RAS/BRAF/MEK/ERK pathway is constitutively activated. Mcl-1, a major anti-apoptotic protein in the Bcl-2 family, is extensively expressed in melanoma and contributes to melanoma's well-documented chemoresistance. Here, we provide the first evidence that Mcl-1 phosphorylation at T163 by ERK1/2 and JNK is associated with the resistance of melanoma cell lines to the existing BH3 mimetics gossypol, S1 and ABT-737, and a novel anti-apoptotic mechanism of phosphorylated Mcl-1 (pMcl-1) is revealed. pMcl-1 antagonized the known BH3 mimetics by sequestering pro-apoptotic proteins that were released from Bcl-2/Mcl-1. Furthermore, an anthraquinone BH3 mimetic, compound 6, was identified to be the first small molecule to that induces endogenous apoptosis in melanoma cells by directly binding Bcl-2, Mcl-1, and pMcl-1 and disrupting the heterodimers of these proteins. Although compound 6 induced upregulation of the pro-apoptotic protein Noxa, its apoptotic induction was independent of Noxa. These data reveal the promising therapeutic potential of targeting pMcl-1 to treat melanoma. Compound 6 is therefore a potent drug that targets pMcl-1 in melanoma.

  9. The Protective Properties of the Strawberry (Fragaria ananassa) against Carbon Tetrachloride-Induced Hepatotoxicity in Rats Mediated by Anti-Apoptotic and Upregulation of Antioxidant Genes Expression Effects

    Science.gov (United States)

    Hamed, Sherifa S.; AL-Yhya, Nouf A.; El-Khadragy, Manal F.; Al-Olayan, Ebtesam M.; Alajmi, Reem A.; Hassan, Zeinab K.; Hassan, Salwa B.; Abdel Moneim, Ahmed E.

    2016-01-01

    The strawberry (Fragaria ananassa) has been extensively used to treat a wide range of ailments in many cultures. The present study was aimed at evaluating the hepatoprotective effect of strawberry juice on experimentally induced liver injury in rats. To this end, rats were introperitoneally injected with carbon tetrachloride (CCl4) with or without strawberry juice supplementation for 12 weeks and the hepatoprotective effect of strawberry was assessed by measuring serum liver enzyme markers, hepatic tissue redox status and apoptotic markers with various techniques including biochemistry, ELISA, quantitative PCR assays and histochemistry. The hepatoprotective effect of the strawberry was evident by preventing CCl4-induced increase in liver enzymes levels. Determination of oxidative balance showed that strawberry treatment significantly blunted CCl4-induced increase in oxidative stress markers and decrease in enzymatic and non-enzymatic molecules in hepatic tissue. Furthermore, strawberry supplementation enhanced the anti-apoptotic protein, Bcl-2, and restrained the pro-apoptotic proteins Bax and caspase-3 with a marked reduction in collagen areas in hepatic tissue. These findings demonstrated that strawberry (F. ananassa) juice possessed antioxidant, anti-apoptotic and anti-fibrotic properties, probably mediated by the presence of polyphenols and flavonoids compounds. PMID:27547187

  10. Expression of Galectin-3 As A Testis Inflammatory Marker in Vasectomised Mice

    Directory of Open Access Journals (Sweden)

    Homayoun Naderian

    2013-01-01

    Full Text Available Objective: Vasectomy, though in some cases are being confronted with irreversibility, has been accepted as an effective contraceptive method. It is estimated that near 2-6% of vasectomised men ultimately show a tendency to restore their fertility. In some cases, vasectomy has been considered as an irreversible procedure due to many post-vasectomy complications causing this debate. The aim of present study was to investigate the pattern of expression of galectin-3, an inflammatory factor secreted by macrophages and immune cells, following the vasectomy in mice testis tissue.Materials and Methods: In this experimental study, twenty mature male Balb/c mice, aged two months, were divided into two equal groups: sham and vasectomised groups (n=10. They were sacrificed four months after vasectomy, while the pattern of galectin-3 expression was investigated using a standard immunohistochemistry technique on testicular tissues. Stereological analyses of testes parameters in vasectomised and sham-operated groups were compared by mixed model analysis.Results: Based on observations, although galectin-3 was not expressed in sham-operated group, it was expressed in 40% of testicular tissues of vasectomised mice, like: seminiferous tubules, interstitial tissues and tunica albugina. Also, our result showed a significant alteration in number of germ and sertoli cells of testicular tissue in vasectomised group in comparison to sham-operated group. In addition, the result of mixed model method confirmed a significant reduction in germ and sertoli cells of vasectomised group.Conclusion: The expression of galectin-3 at different parts of testicular tissue in vasectomised group is higher than sham group. This express illustrates the increase of degenerative changes and inflammation reactions in testicular tissue, leading to chronic complications and infertility, after the vasovasostomy.

  11. Galectin-1 and Galectin-3 induce mitochondrial apoptotic pathway in Jurkat cells

    Science.gov (United States)

    Vasil'eva, O. A.; Isaeva, A. V.; Prokhorenko, T. S.; Zima, A. P.; Novitsky, V. V.

    2016-08-01

    Cellular malignant transformation is often accompanied by increased gene expression of low-molecular proteins of lectins family-galectins. But it is unknown how galectins promote tumor growth and malignization. Galectins-1 and galectin-3 are thought to be possible immunoregulators exerting their effects by regulating the balance of CD4+ lymphocytes. In addition it is known that tumor cells overexpressing galectins are capable of escaping immunological control, causing apoptosis of lymphocytes. The aim of the study is to investigate the role of galectin-1 and galectin-3 in the implementation of mitochondrial apoptotic pathway in Jurkat cells. Methods: Jurkat cells were used as a model for the study of T-lymphocytes. Jurkat cells were activated with antibodies to CD3 and CD28 and cultured with recombinant galectin-1 and -3. Apoptosis of Jurkat cells and depolarization of the mitochondrial membrane were assessed by flow cytometry. It was found that galectin-1 and galectin-3 have a dose-dependent pro-apoptotic effect on Jurkat cells in vitro and enlarge the number of cells with decreased mitochondrial membrane potential compared with intact cells.

  12. Galectin-3 coats the membrane of breast cells and makes a signature of tumours

    KAUST Repository

    Simone, Giuseppina

    2014-01-01

    Galectin-3, β-galactoside-binding lectin, coats the membrane of most cancer cells and is involved in metastasis and endothelium recognition as well as in evading immune surveillance through killing of activated T cells. To flag galectin as a biomarker of tumours and metastasis, it is pivotal to understand the role of this protein in different tumours and at different stages. Breast tumours have an anomalous behaviour of the galectin-3 compared to other tumour cells. Herein, FACS sorting and galactoside based assays were used to investigate the role of galectin-3 in metastasis and metastatisation of breast cancer cells. Breast galectin fingerprint at the FACS displayed a higher amount in healthy cells, compared to metastatic cells. The microfluidic assay was able to isolate tumour and metastatic cells more than healthy breast cells. Investigation was performed on samples from patients with breast tumours at stage I and stage III whilst MCF7 and EPH-4 cells were used to perform preliminary investigations. The readout of the conditioned medium (from culturing of stage I cells) fingerprint by FACS evidenced high expression of free galectin. Analysis of the results established that the galectin coating the membrane, by galactoside recognition of the breast cells, and engaged by the cells to form protein-carbohydrate complexes inside the microfluidic assay, resembled the tumour signature of tumours in breast cells whilst the galectin free is independent of those mechanisms. © 2014 The Royal Society of Chemistry.

  13. Expression of extracellular matrix proteins: tenascin-C, fibronectin and galectin-3 in prostatic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Monika Ulamec

    2015-12-01

    Full Text Available Introduction: The interchanged stromal-epithelial relations and altered expression profiles of various extracellular matrix (ECM proteins creates a suitable microenvironment for cancer development and growth. We support the opinion that remodeling of the extracellular matrix (ECM plays an important role in the cancer progression. The aim of this study was to examine the expression of ECM proteins tenascin-C, fibronectin and galectin-3 in prostatic adenocarcinoma. Methods: Glands and surrounding stroma were analyzed in randomly selected specimens from 52 patients with prostate cancer and 28 patients with benign prostatic hyperplasia (BHP. To evaluate the intensity of tenascin-C, fibronectin and galectin-3 expression the percentage of positively immunostained stromal cells was examined.Results: Compared to BPH, stroma of prostatic adenocarcinoma showed statistically significant increase in tenascin-C expression (p<0.001, predominantly around neoplastic glands, while fibronectin (p=0.001 and galectin-3 (p<0.001 expression in the same area was decreased.Conclusions: Our study confirms changes in the expression of ECM proteins of prostate cancer which may have important role in the cancer development.

  14. Skeletal muscle stem cells express anti-apoptotic ErbB receptors during activation from quiescence

    International Nuclear Information System (INIS)

    To be effective for tissue repair, satellite cells (the stem cells of adult muscle) must survive the initial activation from quiescence. Using an in vitro model of satellite cell activation, we show that erbB1, erbB2 and erbB3, members of the EGF receptor tyrosine kinase family, appear on satellite cells within 6 h of activation. We show that signalling via erbB2 provides an anti-apoptotic survival mechanism for satellite cells during the first 24 h, as they progress to a proliferative state. Inhibition of erbB2 signalling with AG825 reduced satellite cell numbers, concomitant with elevated caspase-8 activation and TUNEL labelling of apoptotic satellite cells. In serum-free conditions, satellite cell apoptosis could be largely prevented by a mixture of erbB1, erbB3 and erbB4 ligand growth factors, but not by neuregulin alone (erbB3/erbB4 ligand). Furthermore, using inhibitors specific to discrete intracellular signalling pathways, we identify MEK as a pro-apoptotic mediator, and the erbB-regulated factor STAT3 as an anti-apoptotic mediator during satellite cell activation. These results implicate erbB2 signalling in the preservation of a full compliment of satellite cells as they activate in the context of a damaged muscle

  15. Inhibition of mitochondria responsible for the anti-apoptotic effects of melatonin during ischemia-reperfusion

    Institute of Scientific and Technical Information of China (English)

    HAN Yi-xiang; ZHANG Sheng-hui; WANG Xi-ming; WU Jian-bo

    2006-01-01

    Objective: To investigate a possible mechanism responsible for anti-apoptotic effects of melatonin and provide theoretical evidences for clinical therapy. Methods: Ischemia-reperfusion mediated neuronal cell injury model was constructed in cerebellar granule neurons (CGNs) by deprivation of glucose, serum and oxygen in media. After ischemia, melatonin was added to the test groups to reach differential concentration during reperfusion. DNA fragmentation, mitochondrial transmembrane potential,mitochondrial cytochrome c release and caspase-3 activity were observed after subjecting cerebellar granule neurons to oxygen-glucose deprivation (OGD). Results: The results showed that OGD induced typical cell apoptosis change, DNA ladder and apoptosis-related alterations in mitochondrial functions including depression of mitochondrial transmembrane potential (its maximal protection ratio was 73.26%) and release of cytochrome c (its maximal inhibition ratio was 42.52%) and the subsequent activation of caspase-3 (its maximal protection ratio was 59.32%) in cytoplasm. Melatonin reduced DNA damage and inhibited release of mitochondrial cytochrome c and activation of caspase-3. Melatonin can strongly prevent the OGD-induced loss of the mitochondria membrane potential. Conclusion: Our findings suggested that the direct inhibition of mitochondrial pathway might essentially contribute to its anti-apoptotic effects in neuronal ischemia-reperfusion.

  16. Galectin-3C inhibits tumor growth and increases the anticancer activity of bortezomib in a murine model of human multiple myeloma.

    Directory of Open Access Journals (Sweden)

    Leonardo Mirandola

    Full Text Available Galectin-3 is a human lectin involved in many cellular processes including differentiation, apoptosis, angiogenesis, neoplastic transformation, and metastasis. We evaluated galectin-3C, an N-terminally truncated form of galectin-3 that is thought to act as a dominant negative inhibitor, as a potential treatment for multiple myeloma (MM. Galectin-3 was expressed at varying levels by all 9 human MM cell lines tested. In vitro galectin-3C exhibited modest anti-proliferative effects on MM cells and inhibited chemotaxis and invasion of U266 MM cells induced by stromal cell-derived factor (SDF-1α. Galectin-3C facilitated the anticancer activity of bortezomib, a proteasome inhibitor approved by the FDA for MM treatment. Galectin-3C and bortezomib also synergistically inhibited MM-induced angiogenesis activity in vitro. Delivery of galectin-3C intravenously via an osmotic pump in a subcutaneous U266 cell NOD/SCID mouse model of MM significantly inhibited tumor growth. The average tumor volume of bortezomib-treated animals was 19.6% and of galectin-3C treated animals was 13.5% of the average volume of the untreated controls at day 35. The maximal effect was obtained with the combination of galectin-3C with bortezomib that afforded a reduction of 94% in the mean tumor volume compared to the untreated controls at day 35. In conclusion, this is the first study to show that inhibition of galectin-3 is efficacious in a murine model of human MM. Our results demonstrated that galectin-3C alone was efficacious in a xenograft mouse model of human MM, and that it enhanced the anti-tumor activity of bortezomib in vitro and in vivo. These data provide the rationale for continued testing of galectin-3C towards initiation of clinical trials for treatment of MM.

  17. Evaluation of anti-apoptotic activity of different dietary antioxidants in renal cell carcinoma against hydrogen peroxide

    Institute of Scientific and Technical Information of China (English)

    Garg Neeraj K; Mangal Sharad; Sahu Tejram; Mehta Abhinav; Vyas Suresh P; Tyagi Rajeev K

    2011-01-01

    Objective: To evaluate the anti-apoptotic and radical scavenging activities of dietary phenolics, namely ascorbic acid, -tocopherol acetate, citric acid, salicylic acid, and estimate H2O2-induced apoptosis in renal cell carcinoma cells. Methods: The intracellular antioxidant potency of antioxidants was investigated. H2O2-induced apoptosis in RCC-26 was assayed with the following parameters: cell viability (% apoptosis), nucleosomal damage and DNA fragmentation, bcl-2 levels and flow cytometery analysis (ROS production evaluation). Results: The anticancer properties of antioxidants such as ascorbic acid, - tocopherol acetate, citric acid, salicylic acid with perdurable responses were investigated. It was observed that these antioxidants had protective effect (anti-apoptotic activity) against hydrogen peroxide (H2O2) in renal cell carcinoma (RCC-26) cell line. Conclusions: This study reveals and proves the anticancer properties. However, in cancer cell lines anti-apoptotic activity can indirectly reflect the cancer promoter activity through radicals scavenging, and significantly protect nucleus and bcl-2.

  18. Examination of a Viral Infection Mimetic Model in Human iPS Cell-Derived Insulin-Producing Cells and the Anti-Apoptotic Effect of GLP-1 Analogue.

    Directory of Open Access Journals (Sweden)

    Megu Yamaguchi Baden

    Full Text Available Viral infection is associated with pancreatic beta cell destruction in fulminant type 1 diabetes mellitus. The aim of this study was to investigate the acceleration and protective mechanisms of beta cell destruction by establishing a model of viral infection in pancreatic beta cells.Polyinosinic:polycytidylic acid was transfected into MIN6 cells and insulin-producing cells differentiated from human induced pluripotent stem cells via small molecule applications. Gene expression was analyzed by real-time PCR, and apoptosis was evaluated by caspase-3 activity and TUNEL staining. The anti-apoptotic effect of Exendin-4 was also evaluated.Polyinosinic:polycytidylic acid transfection led to elevated expression of the genes encoding IFNα, IFNβ, CXCL10, Fas, viral receptors, and IFN-inducible antiviral effectors in MIN6 cells. Exendin-4 treatment suppressed the elevated gene expression levels and reduced polyinosinic:polycytidylic acid-induced apoptosis both in MIN6 cells and in insulin-producing cells from human induced pluripotent stem cells. Glucagon-like peptide-1 receptor, protein kinase A, and phosphatidylinositol-3 kinase inhibitors counteracted the anti-apoptotic effect of Exendin-4.Polyinosinic:polycytidylic acid transfection can mimic viral infection, and Exendin-4 exerted an anti-apoptotic effect both in MIN6 and insulin-producing cells from human induced pluripotent stem cells.

  19. The anti-apoptotic members of the Bcl-2 family are attractive tumor-associated antigens

    DEFF Research Database (Denmark)

    Straten, Per thor; Andersen, Mads Hald

    2010-01-01

    Anti-apoptotic members of the Bcl-2 family (Bcl-2, Bcl-X(L) and Mcl-2) are pivotal regulators of apoptotic cell death. They are all highly overexpressed in cancers of different origin in which they enhance the survival of the cancer cells. Consequently, they represent prime candidates for anti......, spontaneous cellular immune responses against the Bcl-2 family proteins have been identified as frequent features in cancer patients underscoring that these proteins are natural targets for the immune system. Thus, Bcl-2 family may serve as an important and widely applicable target for anti......-cancer immunotherapeutic strategies, alone or in the combination with conventional therapy. Here, we summarize the current knowledge of Bcl-2 family proteins as T-cell antigens, which has set the stage for the first explorative trial using these antigens in therapeutic vaccinations against cancer, and discuss future...

  20. Anti-apoptotic peptides protect against radiation-induced cell death

    International Nuclear Information System (INIS)

    The risk of terrorist attacks utilizing either nuclear or radiological weapons has raised concerns about the current lack of effective radioprotectants. Here it is demonstrated that the BH4 peptide domain of the anti-apoptotic protein Bcl-xL can be delivered to cells by covalent attachment to the TAT peptide transduction domain (TAT-BH4) and provide protection in vitro and in vivo from radiation-induced apoptotic cell death. Isolated human lymphocytes treated with TAT-BH4 were protected against apoptosis following exposure to 15 Gy radiation. In mice exposed to 5 Gy radiation, TAT-BH4 treatment protected splenocytes and thymocytes from radiation-induced apoptotic cell death. Most importantly, in vivo radiation protection was observed in mice whether TAT-BH4 treatment was given prior to or after irradiation. Thus, by targeting steps within the apoptosis signaling pathway it is possible to develop post-exposure treatments to protect radio-sensitive tissues

  1. Anti-apoptotic treatment in mouse models of age-related hearing loss

    Institute of Scientific and Technical Information of China (English)

    Fengchan Han; Oumei Wang; Quanxiang Cai

    2016-01-01

    Age-related hearing loss (AHL), or presbycusis, is the most common neurodegenerative disorder and top communication deficit of the aged population. Genetic predisposition is one of the major factors in the development of AHL. Generally, AHL is associated with an age-dependent loss of sensory hair cells, spiral ganglion neurons and stria vascularis cells in the inner ear. Although the mechanisms leading to genetic hearing loss are not completely understood, caspase-family proteases function as important signals in the inner ear pathology. It is now accepted that mouse models are the best tools to study the mechanism of genetic hearing loss or AHL. Here, we provide a brief review of recent studies on hearing improvement in mouse models of AHL by anti-apoptotic treatment.

  2. Methane attenuates retinal ischemia/reperfusion injury via anti-oxidative and anti-apoptotic pathways.

    Science.gov (United States)

    Liu, Lin; Sun, Qinglei; Wang, Ruobing; Chen, Zeli; Wu, Jiangchun; Xia, Fangzhou; Fan, Xian-Qun

    2016-09-01

    Retinal ischemia/reperfusion injury (IRI) may cause incurable visual impairment due to neural regeneration limits. Methane was shown to exert a protective effect against IRI in many organs. This study aims to explore the possible protective effects of methane-rich saline against retinal IRI in rat. Retinal IRI was performed on the right eyes of male Sprague-Dawley rats, which were immediately injected intraperitoneally with methane-saturated saline (25ml/kg). At one week after surgery, the number of retinal ganglion cells (RGCs), total retinal thickness, visual function were measured by hematoxylin and eosin staining, FluoroGold anterograde labeling and flash visual evoked potentials. The levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), 4-Hydroxy-2-nonenal (4-HNE), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), caspase-3, caspase-9, B cell lymphoma/leukemia-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in retinas were assessed by immunofluorescence staining, enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. As expected, methane treatment significantly improved the retinal IRI-induced RGC loss, total retinal layer thinning and visual dysfunction. Moreover, methane treatment significantly reduced the levels of oxidative stress biomarkers (8-OHdG, 4-HNE, MDA) and increased the antioxidant enzyme activities (SOD, CAT, GPx) in the retinas with IRI. Meanwhile, methane treatment significantly increased the anti-apoptotic gene (Bcl-2) expression and decreased the pro-apoptotic gene (Bax) expression, accompanied by the suppression of caspase-3 and caspase-9 activity. Thus, these data demonstrated that methane can exert a neuroprotective role against retinal IRI through anti-oxidative and anti-apoptotic pathways. PMID:27208496

  3. The CORM ALF-186 Mediates Anti-Apoptotic Signaling via an Activation of the p38 MAPK after Ischemia and Reperfusion Injury in Retinal Ganglion Cells

    Science.gov (United States)

    Ulbrich, Felix; Kaufmann, Kai B.; Meske, Alexander; Lagrèze, Wolf A.; Augustynik, Michael; Buerkle, Hartmut; Ramao, Carlos C.; Biermann, Julia

    2016-01-01

    Purpose Ischemia and reperfusion injury may induce apoptosis and lead to sustained tissue damage and loss of function, especially in neuronal organs. While carbon monoxide is known to exert protective effects after various harmful events, the mechanism of carbon monoxide releasing molecules in neuronal tissue has not been investigated yet. We hypothesize that the carbon monoxide releasing molecule (CORM) ALF-186, administered after neuronal ischemia-reperfusion injury (IRI), counteracts retinal apoptosis and its involved signaling pathways and consecutively reduces neuronal tissue damage. Methods IRI was performed in rat´s retinae for 1 hour. The water-soluble CORM ALF-186 (10 mg/kg) was administered intravenously via a tail vein after reperfusion. After 24 and 48 hours, retinal tissue was harvested to analyze mRNA and protein expression of Bcl-2, Bax, Caspase-3, ERK1/2, p38 and JNK. Densities of fluorogold pre-labeled retinal ganglion cells (RGC) were analyzed 7 days after IRI. Immunohistochemistry was performed on retinal cross sections. Results ALF-186 significantly reduced IRI mediated loss of RGC. ALF-186 treatment differentially affected mitogen-activated protein kinases (MAPK) phosphorylation: ALF-186 activated p38 and suppressed ERK1/2 phosphorylation, while JNK remained unchanged. Furthermore, ALF-186 treatment affected mitochondrial apoptosis, decreasing pro-apoptotic Bax and Caspase-3-cleavage, but increasing anti-apoptotic Bcl-2. Inhibition of p38-MAPK using SB203580 reduced ALF-186 mediated anti-apoptotic effects. Conclusion In this study, ALF-186 mediated substantial neuroprotection, affecting intracellular apoptotic signaling, mainly via MAPK p38. CORMs may thus represent a promising therapeutic alternative treating neuronal IRI. PMID:27764224

  4. Effects of advanced glycosylation end products and rosiglitazone on the expression and secretion of galectin-3 in human renal mesangial cells

    Institute of Scientific and Technical Information of China (English)

    SUN Zi-lin; MA Chan-juan; JIN Hui; YUAN Yang; LIU Nai-feng

    2009-01-01

    Background Galectin-3 is the most recently identified advanced glycosylation end products (AGEs) binding protein. This study aimed to investigate the effects of AGEs and rosiglitazone on the expression and secretion of galectin-3 in cultured human renal mesangial cells (HRMCs).Methods HRMCs were incubated with different concentrations of AGE-bovine serum albumin (BSA) (0, 50, 100, 200, and 400 mg/L) for different time (0, 24, 36, 48, and 72 hours), and exposed to AGE-BSA in the presence of different concentrations of rosiglitazone (1, 10, and 100 μmol/L). The mRNA and protein expression of galectin-3 in HRMCs were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and Westem blotting. The culture medium of HRMCs was collected and concentrated, and the content of galectin-3 in the medium was detected by Western blotting. Results Both RT-PCR and Western blotting revealed that AGE-BSA up-regulated the expression of galectin-3 in HRMCs in a concentration- (P<0.05) and time-dependent (P<0.05) manner compared with the control. Compared with the control, AGE-BSA elevated the content of galectin-3 in the culture medium of HRMCs time- and concentration-dependently (P<0.05, respectively). Both protein and mRNA expression of galectin-3, and its content in the medium of HRMCs exposed to different concentrations of rosiglitazone in the presence of AGE-BSA were increased compared with those of cells exposed to AGE-BSA alone (P<0.05). Rosiglitazone increased the expression and secretion of galectin-3 in a dose-dependent manner (P<0.05).Conclusions AGEs up-regulates the expression and secretion of galectin-3 in HRMCs. Rosiglitazone further enhances the upregulation of galectin-3 in HRMCs induced by AGEs, which suggests that rosiglitazone may play a role of reno-protection via up-regulation of galectin-3.

  5. Leptin is an anti-apoptotic effector in placental cells involving p53 downregulation.

    Directory of Open Access Journals (Sweden)

    Ayelén Rayen Toro

    Full Text Available Leptin, a peripheral signal synthetized by the adipocyte to regulate energy metabolism, can also be produced by placenta, where it may work as an autocrine hormone. We have previously demonstrated that leptin promotes proliferation and survival of trophoblastic cells. In the present work, we aimed to study the molecular mechanisms that mediate the survival effect of leptin in placenta. We used the human placenta choriocarcinoma BeWo and first trimester Swan-71 cell lines, as well as human placental explants. We tested the late phase of apoptosis, triggered by serum deprivation, by studying the activation of Caspase-3 and DNA fragmentation. Recombinant human leptin added to BeWo cell line and human placental explants, showed a decrease on Caspase-3 activation. These effects were dose dependent. Maximal effect was achieved at 250 ng leptin/ml. Moreover, inhibition of endogenous leptin expression with 2 µM of an antisense oligonucleotide, reversed Caspase-3 diminution. We also found that the cleavage of Poly [ADP-ribose] polymerase-1 (PARP-1 was diminished in the presence of leptin. We analyzed the presence of low DNA fragments, products from apoptotic DNA cleavage. Placental explants cultivated in the absence of serum in the culture media increased the apoptotic cleavage of DNA and this effect was prevented by the addition of 100 ng leptin/ml. Taken together these results reinforce the survival effect exerted by leptin on placental cells. To improve the understanding of leptin mechanism in regulating the process of apoptosis we determined the expression of different intermediaries in the apoptosis cascade. We found that under serum deprivation conditions, leptin increased the anti-apoptotic BCL-2 protein expression, while downregulated the pro-apoptotic BAX and BID proteins expression in Swan-71 cells and placental explants. In both models leptin augmented BCL-2/BAX ratio. Moreover we have demonstrated that p53, one of the key cell cycle

  6. An increase in galectin-3 causes cellular unresponsiveness to IFN-γ-induced signal transduction and growth inhibition in gastric cancer cells

    Science.gov (United States)

    Tseng, Po-Chun; Chen, Chia-Ling; Shan, Yan-Shen; Lin, Chiou-Feng

    2016-01-01

    Glycogen synthase kinase (GSK)-3β facilitates interferon (IFN)-γ signaling by inhibiting Src homology-2 domain-containing phosphatase (SHP) 2. Mutated phosphoinositide 3-kinase (PI3K) and phosphatase and tensin homolog (PTEN) cause AKT activation and GSK-3β inactivation to induce SHP2-activated cellular unresponsiveness to IFN-γ in human gastric cancer AGS cells. This study investigated the potential role of galectin-3, which acts upstream of AKT/GSK-3β/SHP2, in gastric cancer cells. Increasing or decreasing galectin-3 altered IFN-γ signaling. Following cisplatin-induced galectin-3 upregulation, surviving cells showed cellular unresponsiveness to IFN-γ. Galectin-3 induced IFN-γ resistance independent of its extracellular β-galactoside-binding activity. Galectin-3 expression was not regulated by PI3K activation or by a decrease in PTEN. Increased galectin-3 may cause GSK-3β inactivation and SHP2 activation by promoting PDK1-induced AKT phosphorylation at a threonine residue. Overexpression of AKT, inactive GSK-3βR96A, SHP2, or active SHP2D61A caused cellular unresponsiveness to IFN-γ in IFN-γ-sensitive MKN45 cells. IFN-γ-induced growth inhibition and apoptosis in AGS cells were observed until galectin-3 expression was downregulated. These results demonstrate that an increase in galectin-3 facilitates AKT/GSK-3β/SHP2 signaling, causing cellular unresponsiveness to IFN-γ. PMID:26934444

  7. d-(+-Galactose-Conjugated Single-Walled Carbon Nanotubes as New Chemical Probes for Electrochemical Biosensors for the Cancer Marker Galectin-3

    Directory of Open Access Journals (Sweden)

    Young Key Shim

    2011-05-01

    Full Text Available d-(+-Galactose-conjugated single-walled carbon nanotubes (SWCNTs were synthesized for use as biosensors to detect the cancer marker galectin-3. To investigate the binding of galectin-3 to the d-(+-galactose-conjugated SWCNTs, an electrochemical biosensor was fabricated by using molybdenum electrodes. The binding affinities of the conjugated SWCNTs to galectin-3 were quantified using electrochemical sensitivity measurements based on the differences in resistance together with typical I-V characterization. The electrochemical sensitivity measurements of the d-(+-galactose-conjugated SWCNTs differed significantly between the samples with and without galectin-3. This indicates that d-(+-galactose-conjugated SWCNTs are potentially useful electrochemical biosensors for the detection of cancer marker galectin-3.

  8. Within-day variation and influence of physical exercise on circulating Galectin-3 in patients with rheumatoid arthritis and healthy individuals

    DEFF Research Database (Denmark)

    Issa, S F; Christensen, A F; Lottenburger, T;

    2015-01-01

    Galectin-3 has been suggested as a pro-inflammatory mediator in rheumatoid arthritis (RA). Previous studies have reported overexpression of Galectin-3 in RA synovitis and increased levels in synovial fluid and serum in long-standing RA compared with osteoarthritis and healthy controls. Our...... objectives were to study whether serum Galectin-3 (1) exhibits circadian variation and/or (2) responds to exercise in RA and controls. The study on circadian patterns (1) comprised eleven patients with newly diagnosed RA, disease duration less than 6 months (ERA), 10 patients with long-standing RA [5...... controls. The participants underwent a standardized exercise programme and four blood samples were drawn before, during and after exercise. Serum Galectin-3 was quantified by ELISA (R&D systems). (1) Galectin-3 was increased at baseline in both RA subsets (P = 0.08). There were no diurnal oscillations (P...

  9. An anti-apoptotic peptide improves survival in lethal total body irradiation.

    Science.gov (United States)

    McDunn, Jonathan E; Muenzer, Jared T; Dunne, Benjamin; Zhou, Anthony; Yuan, Kevin; Hoekzema, Andrew; Hilliard, Carolyn; Chang, Katherine C; Davis, Christopher G; McDonough, Jacquelyn; Hunt, Clayton; Grigsby, Perry; Piwnica-Worms, David; Hotchkiss, Richard S

    2009-05-15

    Cell penetrating peptides (CPPs) have been used to deliver the anti-apoptotic Bcl-xL-derived BH4 peptide to prevent injury-induced apoptosis both in vitro and in vivo. Here we demonstrate that the nuclear localization sequence (NLS) from the SV40 large T antigen has favorable properties for BH4 domain delivery to lymphocytes compared to sequences based on the HIV-1 TAT sequence. While both TAT-BH4 and NLS-BH4 protected primary human mononuclear cells from radiation-induced apoptotic cell death, TAT-BH4 caused persistent membrane damage and even cell death at the highest concentrations tested (5-10 microM) and correlated with in vivo toxicity as intravenous administration of TAT-BH4 caused rapid death. The NLS-BH4 peptide has significantly attenuated toxicity compared to TAT-BH4 and we established a dosing regimen of NLS-BH4 that conferred a significant survival advantage in a post-exposure treatment model of LD90 total body irradiation.

  10. Anti-apoptotic role of retinoic acid in the inner ear of noise-exposed mice

    International Nuclear Information System (INIS)

    Exposure to loud noise can induce temporary or permanent hearing loss, and acoustic trauma is the major cause of hearing impairment in industrial nations. However, the mechanisms underlying the death of hair cells after acoustic trauma remain unclear. In addition to its involvement in cellular stress and apoptosis, the c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase family, is involved in cell survival, transformation, embryonic morphogenesis, and differentiation. JNK is primarily activated by various environmental stresses including noise, and the phenotypic result appears be to cell death. All-trans retinoic acid (ATRA) is an active metabolite of vitamin A that regulates a wide range of biological processes, including cell proliferation, differentiation, and morphogenesis. We evaluated the role of ATRA in preserving hearing in mice exposed to noise that can induce permanent hearing loss. Mice fed with ATRA before and during 3 consecutive days of noise exposure had a more preserved hearing threshold than mice fed sesame oil or saline. Histological and TUNEL staining of the cochlea showed significantly enhanced preservation of the organ of Corti, including outer hair cells and relatively low apoptotic nuclei, in mice-fed ATRA than in mice-fed sesame oil or saline. Phospho-JNK immunohistochemistry showed that ATRA inhibited the activation of JNK. These results suggest that ATRA has an anti-apoptotic effect on cochleae exposed to noise

  11. Anti-apoptotic effects of Z alpha1-antitrypsin in human bronchial epithelial cells.

    LENUS (Irish Health Repository)

    Greene, C M

    2010-05-01

    alpha(1)-antitrypsin (alpha(1)-AT) deficiency is a genetic disease which manifests as early-onset emphysema or liver disease. Although the majority of alpha(1)-AT is produced by the liver, it is also produced by bronchial epithelial cells, amongst others, in the lung. Herein, we investigate the effects of mutant Z alpha(1)-AT (ZAAT) expression on apoptosis in a human bronchial epithelial cell line (16HBE14o-) and delineate the mechanisms involved. Control, M variant alpha(1)-AT (MAAT)- or ZAAT-expressing cells were assessed for apoptosis, caspase-3 activity, cell viability, phosphorylation of Bad, nuclear factor (NF)-kappaB activation and induced expression of a selection of pro- and anti-apoptotic genes. Expression of ZAAT in 16HBE14o- cells, like MAAT, inhibited basal and agonist-induced apoptosis. ZAAT expression also inhibited caspase-3 activity by 57% compared with control cells (p = 0.05) and was a more potent inhibitor than MAAT. Whilst ZAAT had no effect on the activity of Bad, its expression activated NF-kappaB-dependent gene expression above control or MAAT-expressing cells. In 16HBE14o- cells but not HEK293 cells, ZAAT upregulated expression of cIAP-1, an upstream regulator of NF-kappaB. cIAP1 expression was increased in ZAAT versus MAAT bronchial biopsies. The data suggest a novel mechanism by which ZAAT may promote human bronchial epithelial cell survival.

  12. Heparin exerts anti-apoptotic effects on uterine explants by targeting the endocannabinoid system.

    Science.gov (United States)

    Salazar, Ana Inés; Vercelli, Claudia; Schiariti, Victoria; Davio, Carlos; Correa, Fernando; Franchi, Ana María

    2016-09-01

    Miscarriage caused by Gram-negative bacteria infecting the female genital tract is one of the most common complications of human pregnancy. Intraperitoneal administration of LPS to 7-days pregnant mice induces embryo resorption after 24 h. Here, we show that LPS induced apoptosis on uterine explants from 7-days pregnant mice and that CB1 receptor was involved in this effect. On the other hand, heparin has been widely used for the prevention of pregnancy loss in women with frequent miscarriage with or without thrombophilia. Besides its anticoagulant properties, heparin exerts anti-inflammatory, immunomodulatory and anti-apoptotic effects. Here, we sought to investigate whether the administration of heparin prevented LPS-induced apoptosis in uterine explants from 7-days pregnant mice. We found that heparin enhanced cell survival in LPS-treated uterine explants and that this effect was mediated by increasing uterine FAAH activity. Taken together, our results point towards a novel mechanism involved in the protective effects of heparin. PMID:27364950

  13. Host cell Golgi anti-apoptotic protein (GAAP) and growth of Chlamydia pneumoniae.

    Science.gov (United States)

    Markkula, Eveliina; Hulkkonen, Jaakko; Penttilä, Tuula; Puolakkainen, Mirja

    2013-01-01

    Chlamydia pneumoniae protein CPn0809 is a type three secretion system substrate, the exact function of which in infection pathogenesis has remained unknown. In this study, we identified by yeast two-hybrid screening a potential host cell interaction partner of CPn0809, Golgi anti-apoptotic protein (GAAP), a conserved protein found in eukaryotic cells. GAAP gene is expressed at relatively constant levels and its expression remained stable also after C. pneumoniae infection. The interaction between GAAP and C. pneumoniae was suggested by transfection studies. GAAP knock-down by siRNA in infected A549 cells resulted in an increased number of C. pneumoniae genomes and growth of the bacteria as judged by quantitative PCR and inclusion counts, respectively. Silencing of GAAP did not make the A549 cells more susceptible to apoptosis per se, and infection with C. pneumoniae prevented staurosporin-induced apoptosis also in transfected cultures. Taken together, the proposed interaction between C. pneumoniae and GAAP modulates bacterial growth in A549 cells. PMID:23000903

  14. Galectin-3 Deletion Enhances Visceral Adipose Tissue Inflammation and Dysregulates Glucose Metabolism in Mice on a High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Jeftic Ilija

    2016-09-01

    Full Text Available Obesity and type 2 diabetes mellitus (T2DM constitute major health problems worldwide. Increased visceral adiposity enhances the risk of insulin resistance and type 2 diabetes. The mechanisms involved in obesity-associated chronic inflammation in metabolic tissues (metaflammation that lead to insulin resistance and dysregulated glucose metabolism are incompletely defined. Galectin-3 (Gal-3, a β-galactoside-binding lectin, modulates immune/inflammatory responses and specifically binds to metabolic danger molecules. To dissect the role of Gal-3 in obesity and diabetes, Gal-3-deficient (LGALS3-/- and wild-type (WT C57Bl/6 male mice were placed on a high-fat diet (HFD, 60% kcal fat or a standard chow diet (10% kcal fat for 6 months and metabolic, histological and immunophenotypical analyses of the visceral adipose tissue were performed. HFD-fed LGALS3-/- mice had higher body weights and more body weight gain, visceral adipose tissue (VAT, hyperglycaemia, hyperinsulinemia, insulin resistance and hyperlipidemia than diet-matched WT mice. Compared to WT mice, the enlarged VAT in obese LGALS3-/- mice contained larger adipocytes. Additionally, we demonstrate enhanced inflammation in the VAT of LGALS3-/- mice compared with diet-matched WT mice. The VAT of LGALS3-/- mice fed a HFD contained more numerous dendritic cells and proinflammatory F4/80+CD11c+CD11b+ and F4/80high macrophages. In contrast to WT mice, the numbers of CXCR3+ and CD8+ T cells were increased in the VAT of Gal-3-deficient mice after 6 months of high-fat feeding. We provide evidence that Gal-3 ablation results in enhanced HFD-induced adiposity, inflammation in the adipose tissue, insulin resistance and hyperglycaemia. Thus, Gal-3 represents an important regulator of obesity-associated immunometabolic alterations.

  15. Carbohydrate-based chemical probes for the proteomic profiling of glucosidases and the emerging cancer marker galectin-3

    NARCIS (Netherlands)

    van Scherpenzeel, M.

    2010-01-01

    This thesis describes the synthesis of carbohydrate-based chemical probes to either profile glucosidases, or specifically label the emerging cancer marker galectin-3 in cell lysates. In general, chemical probe based methods can tag certain classes of proteins, and covalently label a protein or a pro

  16. Immune-mediated beta-cell destruction in vitro and in vivo-A pivotal role for galectin-3

    DEFF Research Database (Denmark)

    Karlsen, Allan E; Størling, Zenia M; Sparre, Thomas;

    2006-01-01

    Pro-apoptotic cytokines are toxic to the pancreatic beta-cells and have been associated with the pathogenesis of Type 1 diabetes (T1D). Proteome analysis of IL-1beta exposed isolated rat islets identified galectin-3 (gal-3) as the most up-regulated protein. Here analysis of human and rat islets a...

  17. Galectin-3 binding protein links circulating microparticles with electron dense glomerular deposits in lupus nephritis

    DEFF Research Database (Denmark)

    Nielsen, C T; Østergaard, O; Rekvig, O P;

    2015-01-01

    OBJECTIVE: A high level of galectin-3-binding protein (G3BP) appears to distinguish circulating cell-derived microparticles in systemic lupus erythematosus (SLE). The aim of this study is to characterize the population of G3BP-positive microparticles from SLE patients compared to healthy controls......, explore putative clinical correlates, and examine if G3BP is present in immune complex deposits in kidney biopsies from patients with lupus nephritis. METHODS: Numbers of annexin V-binding and G3BP-exposing plasma microparticles from 56 SLE patients and 36 healthy controls were determined by flow...... in kidney biopsies from one non-SLE control and from patients with class IV (n = 2) and class V (n = 1) lupus nephritis using co-localization immune electron microscopy. RESULTS: Microparticle-G3BP, microparticle-C1q and microparticle-immunoglobulins were significantly (P 

  18. Human Milk Galectin-3 Binding Protein and Breastfeeding-Associated HIV Transmission

    Science.gov (United States)

    Chan, Christina S.; Kim, Hae-Young; Autran, Chloe; Kim, Jae H.; Sinkala, Moses; Kankasa, Chipepo; Mwiya, Mwiya; Thea, Donald M.; Aldrovandi, Grace M.; Kuhn, Louise; Bode, Lars

    2013-01-01

    Analysis of milk from 247 HIV-infected Zambian mothers showed that Galectin-3 Binding Protein (Gal3BP) concentrations were significantly higher among HIV-infected mothers who transmitted HIV through breastfeeding (6.51±2.12 ug/mL) than among non-transmitters but were also correlated with higher milk and plasma HIV RNA copies/ml and lower CD4+ cell counts. The association between Gal3BP and postnatal transmission was attenuated after adjustment for milk and plasma HIV load and CD4+ cell counts. This suggests that although milk Gal3BP is a marker of advanced maternal disease, it does not independently modify transmission risk. PMID:23899964

  19. Galectin-3 is upregulated in activated glia during Junin virus-induced murine encephalitis.

    Science.gov (United States)

    Jaquenod De Giusti, Carolina; Alberdi, Lucrecia; Frik, Jesica; Ferrer, María F; Scharrig, Emilia; Schattner, Mirta; Gomez, Ricardo M

    2011-09-01

    Argentine haemorrhagic fever (AHF) is a systemic febrile syndrome characterized by several haematological and neurological alterations caused by Junín virus (JUNV), a member of the Arenaviridae family. Newborn mice are highly susceptible to JUNV and the course of infection has been associated with the viral strain used. Galectin-3 (Gal-3) is an animal lectin that has been proposed to play an important role in some central nervous system (CNS) diseases. In this study, we analysed Gal-3 expression at the transcriptional and translational expression levels during JUNV-induced CNS disease. We found that Candid 1 strain induced, with relatively low mortality, a subacute/chronic CNS disease with significant glia activation and upregulation of Gal-3 in microglia cells as well as in reactive astrocytes that correlated with viral levels. Our results suggest an important role for Gal-3 in viral-induced CNS disease.

  20. Evaluation of anti-apoptotic activity of different dietary antioxidants in renal cell carcinoma against hydrogen peroxide

    Institute of Scientific and Technical Information of China (English)

    Garg; Neeraj; K; Mangal; Sharad; Sahu; Tejram; Mehta; Abhinav; Vyas; Suresh; P; Tyagi; Rajeev; K

    2011-01-01

    Objective:To evaluate the anti-apoptotic and radical scavenging activities of dietary phenolics, namely ascorbic acid,a-tocopherol acetate,citric acid,salicylic acid,and estimate H2O2induced apoptosis in renal cell carcinoma cells.Methods:The intracellular antioxidant potency of antioxidants was investigated.H2O-2-induced apoptosis in RCC-26 was assayed with the following parameters:cell viability(%apoptosis),nucleosomal damage and DNA fragmentation, bcl-2 levels and flow cytometery analysis(ROS production evaluation).Results:Ine anticancer properties of antioxidants such as ascorbic acid,a- tocopherol acetate,citric acid,salicylic acid with perdurable responses were investigated.It was observed that these antioxidants had protective effect(anti-apoptotic activity) against hydrogen peroxide(H2O2) in renal cell carcinoma(RCC-26) cell line.Conclusions:This study reveals and proves the anticancer properties.However,in cancer cell lines anti-apoptotic activity can indirectly reflect the cancer promoter activity through radicals scavenging,and significantly protect nucleus and bcl-2.

  1. Structure-based redesign of the binding specificity of anti-apoptotic Bcl-x(L).

    Science.gov (United States)

    Chen, T Scott; Palacios, Hector; Keating, Amy E

    2013-01-01

    Many native proteins are multi-specific and interact with numerous partners, which can confound analysis of their functions. Protein design provides a potential route to generating synthetic variants of native proteins with more selective binding profiles. Redesigned proteins could be used as research tools, diagnostics or therapeutics. In this work, we used a library screening approach to reengineer the multi-specific anti-apoptotic protein Bcl-x(L) to remove its interactions with many of its binding partners, making it a high-affinity and selective binder of the BH3 region of pro-apoptotic protein Bad. To overcome the enormity of the potential Bcl-x(L) sequence space, we developed and applied a computational/experimental framework that used protein structure information to generate focused combinatorial libraries. Sequence features were identified using structure-based modeling, and an optimization algorithm based on integer programming was used to select degenerate codons that maximally covered these features. A constraint on library size was used to ensure thorough sampling. Using yeast surface display to screen a designed library of Bcl-x(L) variants, we successfully identified a protein with ~1000-fold improvement in binding specificity for the BH3 region of Bad over the BH3 region of Bim. Although negative design was targeted only against the BH3 region of Bim, the best redesigned protein was globally specific against binding to 10 other peptides corresponding to native BH3 motifs. Our design framework demonstrates an efficient route to highly specific protein binders and may readily be adapted for application to other design problems. PMID:23154169

  2. Inhibition of Wnt signaling by cucurbitacin B in breast cancer cells: reduction of Wnt-associated proteins and reduced translocation of galectin-3-mediated β-catenin to the nucleus.

    Science.gov (United States)

    Dakeng, Sumana; Duangmano, Suwit; Jiratchariyakul, Weena; U-Pratya, Yaowalak; Bögler, Oliver; Patmasiriwat, Pimpicha

    2012-01-01

    The cucurbitacins are tetracyclic triterpenes found in plants of the family Cucurbitaceae. Cucurbitacins have been shown to have anti-cancer and anti-inflamatory activities. We investigated the anti-cancer activity of cucurbitacin B extracted from Thai medicinal plant Trichosanthes cucumerina Linn. Cell viability was assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Results indicated that cucurbitacin B from T. cucumerina Linn. has a cytotoxic effect on breast cancer cell lines SKBR-3 and MCF-7 with an IC50 of 4.60 and 88.75 µg/ml, respectively. Growth inhibition was attributed to G2/M phase arrest and apoptosis. Cyclin D1, c-Myc, and β-catenin expression levels were reduced. Western blot analysis showed increased PARP cleavage and decreased Wnt-associated signaling molecules β-catenin, galectin-3, cyclin D1 and c-Myc, and corresponding changes in phosphorylated GSK-3β levels. Cucurbitacin B treatment inhibited translocation to the nucleus of β-catenin and galectin-3. The depletion of β-catenin and galectin-3 in the nucleus was confirmed by cellular protein fractionation. T-cell factor (TCF)/lymphoid enhancer factor (LEF)-dependent transcriptional activity was disrupted in cucurbitacin B treated cells as tested by a TCF reporter assay. The relative luciferase activity was reduced when we treated cells with cucurbitacin B compound for 24 h. Our data suggest that cucurbitacin B may in part induce apoptosis and exert growth inhibitory effect via interruption the Wnt signaling.

  3. Anti-apoptotic effects of aspirin following cerebral ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Liying Qiu; Bin Du; Ying Li; Hongbin Fan; Zhiyong Yang

    2008-01-01

    /kg aspirin decreased MDA content and increased ATP levels. However, 6 mg/kg aspirin did not have the same effect. CONCLUSION: Aspirin reduced the number of apoptotic cells following CIRI. These results suggest that the neuroprotective mechanism of aspirin could be related to elevated Bcl-2 protein levels or decreased Bax protein expression. The increase in the ratio of Bcl-2 to Bax appears to be a common anti-apoptotic mechanism of aspirin.

  4. Galectin-3 is a marker of myocardial and vascular fibrosis in Kawasaki disease patients with giant aneurysms

    OpenAIRE

    Numano, F; Shimizu, C.; Jimenez-Fernandez, S; Vejar, M; Oharaseki, T; K. Takahashi; Salgado, A; Tremoulet, AH; Gordon, JB; Burns, JC; Daniels, LB

    2015-01-01

    © 2015 Elsevier Ireland Ltd. Backgrounds Galectin-3 (Gal-3) is a multifunctional matricellular protein associated with heart failure and cardiovascular events. Gal-3 is required for transforming growth factor-β pathway-mediated myofibroblast activation that is a key process in coronary artery aneurysm formation in Kawasaki Disease (KD). Autopsies from young adults late after KD onset (AKD) have demonstrated bridging fibrosis throughout the myocardium and arteries. In this study, we postulated...

  5. NG2 Proteoglycan Promotes Endothelial Cell Motility and Angiogenesis via Engagement of Galectin-3 and α3β1 Integrin

    Science.gov (United States)

    Fukushi, Jun-ichi; Makagiansar, Irwan T.; Stallcup, William B.

    2004-01-01

    The NG2 proteoglycan is expressed by microvascular pericytes in newly formed blood vessels. We have used in vitro and in vivo models to investigate the role of NG2 in cross-talk between pericytes and endothelial cells (EC). Binding of soluble NG2 to the EC surface induces cell motility and multicellular network formation in vitro and stimulates corneal angiogenesis in vivo. Biochemical data demonstrate the involvement of both galectin-3 and α3β1 integrin in the EC response to NG2 and show that NG2, galectin-3, and α3β1 form a complex on the cell surface. Transmembrane signaling via α3β1 is responsible for EC motility and morphogenesis in this system. Galectin-3–dependent oligomerization may potentiate NG2-mediated activation of α3β1. In conjunction with recent studies demonstrating the early involvement of pericytes in angiogenesis, these data suggest that pericyte-derived NG2 is an important factor in promoting EC migration and morphogenesis during the early stages of neovascularization. PMID:15181153

  6. Metabolism under hypoxia in Tm1 murine melanoma cells is affected by the presence of galectin-3, a metabolomics approach.

    Science.gov (United States)

    Bacchi, Pedro Starzynski; Bloise, Antonio Carlos; Bustos, Silvina Odete; Zimmermann, Lara; Chammas, Roger; Rabbani, Said Rahnamaye

    2014-01-01

    Metabolomics has proven an useful tool for systems biology. Here we have used a metabolomics approach to identify conditions in which de novo expression of an established tumor marker, galectin-3, would confer a potential selective advantage for melanoma growth and survival. A murine melanoma cell line (Tm1) that lacks galectin-3 was modified to express it or not (Tm1.G2 and Tm1.N3, respectively). These variant cell line were then exposed to conditions of controlled oxygen tensions and glucose levels. Metabolic profiling of intracellular metabolites of cells exposed to these conditions was obtained in steady state using high resolution (1)H Magnetic Resonance Spectroscopy ((1)H-MRS) and multivariate statistical analysis. The Nuclear Magnetic Resonance (NMR) spectra contained a large number of absorption lines from which we were able to distinguish 20 metabolites, 3 fatty acids and some absorption lines and clusters were not identified. Principal Components Analysis (PCA) allowed for the discrimination of 2 experimental conditions in which expression of the tumor marker galectin-3 may play a significant role, namely exposure of cells to hypoxia under high glucose. Interestingly, under all other experimental conditions tested, the cellular system was quite robust. Our results suggest that the Metabolomics approach can be used to access information about changes in many metabolic pathways induced in tumorigenic cells and to allow the evaluation of their behavior in controlled environmental conditions or selective pressures.

  7. Extracellular galectin-3 counteracts adhesion and exhibits chemoattraction in Helicobacter pylori-infected gastric cancer cells.

    Science.gov (United States)

    Subhash, Vinod Vijay; Ling, Samantha Shi Min; Ho, Bow

    2016-08-01

    Galectin-3 (Gal-3) is a β-galactoside lectin that is upregulated and rapidly secreted by gastric epithelial cells in response to Helicobacter pylori infection. An earlier study reported the involvement of H. pylori cytotoxin-associated gene A (cagA) in the expression of intracellular Gal-3. However, the role of extracellular Gal-3 and its functional significance in H. pylori-infected cells remains uncharacterized. Data presented here demonstrate secretion of Gal-3 is an initial host response event in gastric epithelial cells during H. pylori infection and is independent of CagA. Previously, Gal-3 was shown to bind to H. pylori LPS. The present study elaborates the significance of this binding, as extracellular recombinant Gal-3 (rGal-3) was shown to inhibit the adhesion of H. pylori to the gastric epithelial cells. Interestingly, a decrease in H. pylori adhesion to host cells also resulted in a decrease in apoptosis. Furthermore, the study also demonstrated a chemoattractant role of extracellular rGal-3 in the recruitment of THP-1 monocytes. This study outlines the previously unidentified roles of extracellular Gal-3 where it acts as a negative regulator of H. pylori adhesion and apoptosis in gastric epithelial cells, and as a chemoattractant to THP-1 monocytes. Our findings could contribute to the better understanding of how Gal-3 acts as a modulator under H. pylori-induced pathological conditions. PMID:27283429

  8. Galectin-3 in bone tumor microenvironment: a beacon for individual skeletal metastasis management.

    Science.gov (United States)

    Nakajima, Kosei; Kho, Dong Hyo; Yanagawa, Takashi; Zimel, Melissa; Heath, Elisabeth; Hogan, Victor; Raz, Avraham

    2016-06-01

    The skeleton is frequently a secondary growth site of disseminated cancers, often leading to painful and devastating clinical outcomes. Metastatic cancer distorts bone marrow homeostasis through tumor-derived factors, which shapes different bone tumor microenvironments depending on the tumor cells' origin. Here, we propose a novel insight on tumor-secreted Galectin-3 (Gal-3) that controls the induction of an inflammatory cascade, differentiation of osteoblasts, osteoclasts, and bone marrow cells, resulting in bone destruction and therapeutic failure. In the approaching era of personalized medicine, the current treatment modalities targeting bone metastatic environments are provided to the patient with limited consideration of the cancer cells' origin. Our new outlook suggests delivering individual tumor microenvironment treatments based on the expression level/activity/functionality of tumor-derived factors, rather than utilizing a commonly shared therapeutic umbrella. The notion of "Gal-3-associated bone remodeling" could be the first step toward a specific personalized therapy for each cancer type generating a different bone niche in patients afflicted with non-curable bone metastasis. PMID:27067726

  9. Pancreatic stellate cells promote proliferation and invasiveness of human pancreatic cancer cells via galectin-3

    Institute of Scientific and Technical Information of China (English)

    Hai-Biao Jiang; Ming Xu; Xing-Peng Wang

    2008-01-01

    AIM: To investigate the role of pancreatic stellate cells (PSCs) and galectin-3 (GAL-3) in the proliferation and infiltration of pancreatic cancer cell line SW1990.METHODS: Human pancreatic cancer cell line SW1990 and PSCs were cultured in vitro. Supernatant fluid of cultured PSCs and SW1990 cells was collected. Expression of GAL-3 in SW1990 cells and PSCs was detected by ELISA, RT-PCR and Western blotting. Proliferation of cultured PSCs and SW1990 cells was measured by 3-(4, 5-methylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. Infiltration of SW1990 cells was detected by a cell infiltration kit.RESULTS: SW1990 cells expressed GAL-3 and this was up-regulated by the supernatant fluid of cultured PSCs. PSCs did not express GAL-3. SW1990 cells stimulated proliferation of PSCs via GAL-3. GAL-3 antibody inhibited SW1990 cell proliferation, while the supernatant fluid of PSCs stimulated proliferation of SW1990 cells through interaction with GAL-3 protein. The supernatant fluid of PSCs enhanced the invasiveness of SW1990 cells through interaction with GAL-3.CONCLUSION: GAL-3 and PSCs were involved in the proliferation and infiltration process of pancreatic cancer cells.

  10. Galectin-3 in bone tumor microenvironment: a beacon for individual skeletal metastasis management.

    Science.gov (United States)

    Nakajima, Kosei; Kho, Dong Hyo; Yanagawa, Takashi; Zimel, Melissa; Heath, Elisabeth; Hogan, Victor; Raz, Avraham

    2016-06-01

    The skeleton is frequently a secondary growth site of disseminated cancers, often leading to painful and devastating clinical outcomes. Metastatic cancer distorts bone marrow homeostasis through tumor-derived factors, which shapes different bone tumor microenvironments depending on the tumor cells' origin. Here, we propose a novel insight on tumor-secreted Galectin-3 (Gal-3) that controls the induction of an inflammatory cascade, differentiation of osteoblasts, osteoclasts, and bone marrow cells, resulting in bone destruction and therapeutic failure. In the approaching era of personalized medicine, the current treatment modalities targeting bone metastatic environments are provided to the patient with limited consideration of the cancer cells' origin. Our new outlook suggests delivering individual tumor microenvironment treatments based on the expression level/activity/functionality of tumor-derived factors, rather than utilizing a commonly shared therapeutic umbrella. The notion of "Gal-3-associated bone remodeling" could be the first step toward a specific personalized therapy for each cancer type generating a different bone niche in patients afflicted with non-curable bone metastasis.

  11. Identification of peptides in human Hsp20 and Hsp27 that possess molecular chaperone and anti-apoptotic activities

    Science.gov (United States)

    Nahomi, Rooban B.; DiMauro, Michael A.; Wang, Benlian; Nagaraj, Ram H.

    2015-01-01

    Previous studies have identified peptides in the ‘crystallin-domain’ of the small heat-shock protein (sHSP) α-crystallin with chaperone and anti-apoptotic activities. We found that peptides in heat-shock protein Hsp20 (G71HFSVLLDVKHFSPEEIAVK91) and Hsp27 (D93RWRVSLDVNHFAPDELTVK113) with sequence homology to α-crystallin also have robust chaperone and anti-apoptotic activities. Both peptides inhibited hyperthermic and chemically induced aggregation of client proteins. The scrambled peptides of Hsp20 and Hsp27 showed no such effects. The chaperone activities of the peptides were better than those from αA- and αB-crystallin. HeLa cells took up the FITC-conjugated Hsp20 peptide and, when the cells were thermally stressed, the peptide was translocated from the cytoplasm to the nucleus. The two peptides inhibited apoptosis in HeLa cells by blocking cytochrome c release from the mitochondria and caspase-3 activation. We found that scrambling the last four amino acids in the two peptides (KAIV in Hsp20 and KTLV in Hsp27) made them unable to enter cells and ineffective against stress-induced apoptosis. Intraperitoneal injection of the peptides prevented sodium-selenite-induced cataract formation in rats by inhibiting protein aggregation and oxidative stress. Our study has identified peptides from Hsp20 and Hsp27 that may have therapeutic benefit in diseases where protein aggregation and apoptosis are contributing factors. PMID:25332102

  12. Neuroglobin in Breast Cancer Cells: Effect of Hypoxia and Oxidative Stress on Protein Level, Localization, and Anti-Apoptotic Function.

    Directory of Open Access Journals (Sweden)

    Marco Fiocchetti

    Full Text Available The over-expression of human neuroglobin (NGB, a heme-protein preferentially expressed in the brain, displays anti-apoptotic effects against hypoxic/ischemic and oxidative stresses enhancing neuron survival. As hypoxic and oxidative stress injury frequently occurs in fast proliferating neoplastic tissues, here, the effect of these stressors on the level, localization, and anti-apoptotic function of NGB in wild type and NGB-stable-silenced MCF-7 breast cancer cells has been assessed. The well-known endogenous NGB inducer 17β-estradiol (E2 has been used as positive control. The median pO2 present in tumor microenvironment of breast cancer patients (i.e., 2% O2 does not affect the NGB level in breast cancer cells, whereas hydrogen peroxide and lead(IV acetate, which increase intracellular reactive oxygen species (ROS level, enhance the NGB levels outside the mitochondria and still activate apoptosis. However, E2-induced NGB up-regulation in mitochondria completely reverse lead(IV acetate-induced PARP cleavage. These results indicate that the NGB level could represent a marker of oxidative-stress in MCF-7 breast cancer cells; however, the NGB ability to respond to injuring stimuli by preventing apoptosis requires its re-allocation into the mitochondria. As a whole, present data might lead to a new direction in understanding NGB function in cancer opening new avenues for the therapeutic intervention.

  13. Neuroglobin in Breast Cancer Cells: Effect of Hypoxia and Oxidative Stress on Protein Level, Localization, and Anti-Apoptotic Function

    Science.gov (United States)

    Fiocchetti, Marco; Cipolletti, Manuela; Leone, Stefano; Naldini, Antonella; Carraro, Fabio; Giordano, Daniela; Verde, Cinzia; Ascenzi, Paolo; Marino, Maria

    2016-01-01

    The over-expression of human neuroglobin (NGB), a heme-protein preferentially expressed in the brain, displays anti-apoptotic effects against hypoxic/ischemic and oxidative stresses enhancing neuron survival. As hypoxic and oxidative stress injury frequently occurs in fast proliferating neoplastic tissues, here, the effect of these stressors on the level, localization, and anti-apoptotic function of NGB in wild type and NGB-stable-silenced MCF-7 breast cancer cells has been assessed. The well-known endogenous NGB inducer 17β-estradiol (E2) has been used as positive control. The median pO2 present in tumor microenvironment of breast cancer patients (i.e., 2% O2) does not affect the NGB level in breast cancer cells, whereas hydrogen peroxide and lead(IV) acetate, which increase intracellular reactive oxygen species (ROS) level, enhance the NGB levels outside the mitochondria and still activate apoptosis. However, E2-induced NGB up-regulation in mitochondria completely reverse lead(IV) acetate-induced PARP cleavage. These results indicate that the NGB level could represent a marker of oxidative-stress in MCF-7 breast cancer cells; however, the NGB ability to respond to injuring stimuli by preventing apoptosis requires its re-allocation into the mitochondria. As a whole, present data might lead to a new direction in understanding NGB function in cancer opening new avenues for the therapeutic intervention. PMID:27149623

  14. Multitasking Human Lectin Galectin-3 Interacts with Sulfated Glycosaminoglycans and Chondroitin Sulfate Proteoglycans.

    Science.gov (United States)

    Talaga, Melanie L; Fan, Ni; Fueri, Ashli L; Brown, Robert K; Bandyopadhyay, Purnima; Dam, Tarun K

    2016-08-16

    Glycosaminoglycan (GAG) binding proteins (GAGBPs), including growth factors, cytokines, morphogens, and extracellular matrix proteins, interact with both free GAGs and those covalently linked to proteoglycans. Such interactions modulate a variety of cellular and extracellular events, such as cell growth, metastasis, morphogenesis, neural development, and inflammation. GAGBPs are structurally and evolutionarily unrelated proteins that typically recognize internal sequences of sulfated GAGs. GAGBPs are distinct from the other major group of glycan binding proteins, lectins. The multifunctional human galectin-3 (Gal-3) is a β-galactoside binding lectin that preferentially binds to N-acetyllactosamine moieties on glycoconjugates. Here, we demonstrate through microcalorimetric and spectroscopic data that Gal-3 possesses the characteristics of a GAGBP. Gal-3 interacts with unmodified heparin, chondroitin sulfate-A (CSA), -B (CSB), and -C (CSC) as well as chondroitin sulfate proteoglycans (CSPGs). While heparin, CSA, and CSC bind with micromolar affinity, the affinity of CSPGs is nanomolar. Significantly, CSA, CSC, and a bovine CSPG were engaged in multivalent binding with Gal-3 and formed noncovalent cross-linked complexes with the lectin. Binding of sulfated GAGs was completely abolished when Gal-3 was preincubated with β-lactose. Cross-linking of Gal-3 by CSA, CSC, and the bovine CSPG was reversed by β-lactose. Both observations strongly suggest that GAGs primarily occupy the lactose/LacNAc binding site of Gal-3. Hill plot analysis of calorimetric data reveals that the binding of CSA, CSC, and a bovine CSPG to Gal-3 is associated with progressive negative cooperativity effects. Identification of Gal-3 as a GAGBP should help to reveal new functions of Gal-3 mediated by GAGs and proteoglycans. PMID:27427828

  15. Extracellular galectin-3 programs multidrug resistance through Na+/K+-ATPase and P-glycoprotein signaling.

    Science.gov (United States)

    Harazono, Yosuke; Kho, Dhong Hyo; Balan, Vitaly; Nakajima, Kosei; Hogan, Victor; Raz, Avraham

    2015-08-14

    Galectin-3 (Gal-3, LGALS3) is a pleotropic versatile, 29-35 kDa chimeric gene product, and involved in diverse physiological and pathological processes, including cell growth, homeostasis, apoptosis, pre-mRNA splicing, cell-cell and cell-matrix adhesion, cellular polarity, motility, adhesion, activation, differentiation, transformation, signaling, regulation of innate/adaptive immunity, and angiogenesis. In multiple diseases, it was found that the level of circulating Gal-3 is markedly elevated, suggesting that Gal-3-dependent function is mediated by specific interaction with yet an unknown ubiquitous cell-surface protein. Recently, we showed that Gal-3 attenuated drug-induced apoptosis, which is one of the mechanisms underlying multidrug resistance (MDR). Here, we document that MDR could be mediated by Gal-3 interaction with the house-keeping gene product e.g., Na+/K+-ATPase, and P-glycoprotein (P-gp). Gal-3 interacts with Na+/K+-ATPase and induces the phosphorylation of P-gp. We also find that Gal-3 binds P-gp and enhances its ATPase activity. Furthermore Gal-3 antagonist suppresses this interaction and results in a decrease of the phosphorylation and the ATPase activity of P-gp, leading to an increased sensitivity to doxorubicin-mediated cell death. Taken together, these findings may explain the reported roles of Gal-3 in diverse diseases and suggest that a combined therapy of inhibitors of Na+/K+-ATPase and Gal-3, and a disease specific drug(s) might be superior to a single therapeutic modality.

  16. Increased adiposity, dysregulated glucose metabolism and systemic inflammation in Galectin-3 KO mice.

    Directory of Open Access Journals (Sweden)

    Jingbo Pang

    Full Text Available Obesity and type 2 diabetes are associated with increased production of Galectin-3 (Gal-3, a protein that modulates inflammation and clearance of glucose adducts. We used Lean and Diet-induced Obese (DIO WT and Gal-3 KO mice to investigate the role of Gal-3 in modulation of adiposity, glucose metabolism and inflammation. Deficiency of Gal-3 lead to age-dependent development of excess adiposity and systemic inflammation, as indicated by elevated production of acute-phase proteins, number of circulating pro-inflammatory Ly6C(high monocytes and development of neutrophilia, microcytic anemia and thrombocytosis in 20-week-old Lean and DIO male Gal-3 KO mice. This was associated with impaired fasting glucose, heightened response to a glucose tolerance test and reduced adipose tissue expression of adiponectin, Gal-12, ATGL and PPARγ, in the presence of maintained insulin sensitivity and hepatic expression of gluconeogenic enzymes in 20-week-old Gal-3 KO mice compared to their diet-matched WT controls. Expression of PGC-1α and FGF-21 in the liver of Lean Gal-3 KO mice was comparable to that observed in DIO animals. Impaired fasting glucose and altered responsiveness to a glucose load preceded development of excess adiposity and systemic inflammation, as demonstrated in 12-week-old Gal-3 KO mice. Finally, a role for the microflora in mediating the fasting hyperglycemia, but not the excessive response to a glucose load, of 12-week-old Gal-3 KO mice was demonstrated by administration of antibiotics. In conclusion, Gal-3 is an important modulator of glucose metabolism, adiposity and inflammation.

  17. Within-day variation and influence of physical exercise on circulating Galectin-3 in patients with rheumatoid arthritis and healthy individuals.

    Science.gov (United States)

    Issa, S F; Christensen, A F; Lottenburger, T; Junker, K; Lindegaard, H; Hørslev-Petersen, K; Junker, P

    2015-07-01

    Galectin-3 has been suggested as a pro-inflammatory mediator in rheumatoid arthritis (RA). Previous studies have reported overexpression of Galectin-3 in RA synovitis and increased levels in synovial fluid and serum in long-standing RA compared with osteoarthritis and healthy controls. Our objectives were to study whether serum Galectin-3 (1) exhibits circadian variation and/or (2) responds to exercise in RA and controls. The study on circadian patterns (1) comprised eleven patients with newly diagnosed RA, disease duration less than 6 months (ERA), 10 patients with long-standing RA [5-15 years (LRA)] and 16 self-reportedly healthy control subjects. During 24 h, 7 blood samples were drawn at 3-h intervals starting at 10 a.m. through 10 p.m. and at 7 and 10 a.m. on the following day. The study on the effect of physical activity (2) included 10 patients with ERA, 10 with LRA and 14 controls. The participants underwent a standardized exercise programme and four blood samples were drawn before, during and after exercise. Serum Galectin-3 was quantified by ELISA (R&D systems). (1) Galectin-3 was increased at baseline in both RA subsets (P = 0.08). There were no diurnal oscillations (P = 0.85). Day-to-day variation amounted to 3%. (2) Baseline Galectin-3 was increased in LRA versus controls and ERA (P exercise induced 10-15% Galectin-3 increments in RA and controls (P Exercise elicited comparable increments in patients with RA of short and long duration and controls, approaching normal after 1-3 h.

  18. Anti-apoptotic effects of recombinant human granulocyte colony-stimulating factor in focal cerebral ischemic rats

    Institute of Scientific and Technical Information of China (English)

    Xia Yuan; Shiming Zhang; Wanli Dong; Qi Fang

    2011-01-01

    The neuroprotective effects of granulocyte colony-stimulating factor in cerebral ischemia/reperfusion injury are currently contentious. The present study examined the effects of subcutaneous injection of recombinant human granulocyte colony-stimulating factor (50 μg/kg) over 5 days in a model of cerebral ischemia/reperfusion with intraluminal filament occlusion in rats. The results indicated that recombinant human granulocyte colony-stimulating factor reduced brain infarct volume following cerebral ischemia/reperfusion injury in rats, down-regulated the expression of caspase-3 mRNA (a key protease for apoptosis in the cerebral ischemia zone), lowered the rate of neuronal apoptosis in the cerebral ischemia zone, and notably ameliorated neurological function. These results indicate that recombinant human granulocyte colony-stimulating factor has anti-apoptotic effects on neurons following focal cerebral ischemia/reperfusion injury, and exerts neuroprotective effects.

  19. Anti-Apoptotic Protein Bcl-xL Expression in the Midbrain Raphe Region Is Sensitive to Stress and Glucocorticoids.

    Directory of Open Access Journals (Sweden)

    Galina T Shishkina

    Full Text Available Anti-apoptotic proteins are suggested to be important for the normal health of neurons and synapses as well as for resilience to stress. In order to determine whether stressful events may influence the expression of anti-apoptotic protein Bcl-xL in the midbrain and specifically in the midbrain serotonergic (5-HT neurons involved in neurobehavioral responses to adverse stimuli, adult male rats were subjected to short-term or chronic forced swim stress. A short-term stress rapidly increased the midbrain bcl-xl mRNA levels and significantly elevated Bcl-xL immunoreactivity in the midbrain 5-HT cells. Stress-induced increase in glucocorticoid secretion was implicated in the observed effect. The levels of bcl-xl mRNA were decreased after stress when glucocorticoid elevation was inhibited by metyrapone (MET, 150 mg/kg, and this decrease was attenuated by glucocorticoid replacement with dexamethasone (DEX; 0.2 mg/kg. Both short-term stress and acute DEX administration, in parallel with Bcl-xL, caused a significant increase in tph2 mRNA levels and slightly enhanced tryptophan hydroxylase immunoreactivity in the midbrain. The increasing effect on the bcl-xl expression was specific to the short-term stress. Forced swim repeated daily for 2 weeks led to a decrease in bcl-xl mRNA in the midbrain without any effects on the Bcl-xL protein expression in the 5-HT neurons. In chronically stressed animals, an increase in tph2 gene expression was not associated with any changes in tryptophan hydroxylase protein levels. Our findings are the first to demonstrate that both short-term stress and acute glucocorticoid exposures induce Bcl-xL protein expression in the midbrain 5-HT neurons concomitantly with the activation of the 5-HT synthesis pathway in these neurons.

  20. Galectin-3, a biomarker linking oxidative stress and inflammation with the clinical outcomes of patients with atherothrombosis

    DEFF Research Database (Denmark)

    Madrigal-Matute, Julio; Lindholt, Jes Sandal; Fernandez-Garcia, Carlos Ernesto;

    2014-01-01

    BACKGROUND: Galectin-3 (Gal-3) participates in different mechanisms involved in atherothrombosis, such as inflammation, proliferation, or macrophage chemotaxis. Thus, there have been committed intensive efforts to elucidate the function of Gal-3 in cardiovascular (CV) diseases. The role of Gal-3...... subjects (n=115; 14.3 [10.7 to 16.9] vs. 10.4 [8.6 to 12.5] ng/mL; Pdisease, Gal-3 concentrations are significantly and independently associated with an increased risk for CV mortality (hazard ratio=2.24, 95% confidence...... interval: 1.06 to 4.73, Pstress. Moreover, circulating Gal-3 concentrations...

  1. Cod glycopeptide with picomolar affinity to galectin-3 suppresses T-cell apoptosis and prostate cancer metastasis

    OpenAIRE

    Guha, Prasun; Kaptan, Engin; Bandyopadhyaya, Gargi; Kaczanowska, Sabina; Davila, Eduardo; Thompson, Keyata; Martin, Stuart S.; Dhananjaya V Kalvakolanu; Vasta, Gerardo R; Ahmed, Hafiz

    2013-01-01

    Cancer metastasis and immune suppression are critical issues in cancer therapy. Here, we show that a β-galactoside–binding lectin [galectin-3 (gal3)] that recognizes the Thomsen-Friedenreich disaccharide (TFD, Galβ1,3GalNAc) present on the surface of most cancer cells is involved in promoting angiogenesis, tumor-endothelial cell adhesion, and metastasis of prostate cancer cells, as well as evading immune surveillance through killing of activated T cells. To block gal3-mediated interactions, w...

  2. Introduction of the anti-apoptotic baculovirus p35 gene in passion fruit induces herbicide tolerance, reduced bacterial lesions, but does not inhibits passion fruit woodiness disease progress induced by cowpea aphid-borne mosaic virus (CABMV

    NARCIS (Netherlands)

    Freitas, D.S.; Coelho, M.C.F.; Souza, M.T.; Marques, A.; Ribeiro, B.M.

    2007-01-01

    The introduction of anti-apoptotic genes into plants leads to resistance to environmental stress and broad-spectrum disease resistance. The anti-apoptotic gene (p35) from a baculovirus was introduced into the genome of passion fruit plants by biobalistics. Eleven regenerated plants showed the presen

  3. Tuberin and PRAS40 are anti-apoptotic gatekeepers during early human amniotic fluid stem-cell differentiation.

    Science.gov (United States)

    Fuchs, Christiane; Rosner, Margit; Dolznig, Helmut; Mikula, Mario; Kramer, Nina; Hengstschläger, Markus

    2012-03-01

    Embryoid bodies (EBs) are three-dimensional multicellular aggregates allowing the in vitro investigation of stem-cell differentiation processes mimicking early embryogenesis. Human amniotic fluid stem (AFS) cells harbor high proliferation potential, do not raise the ethical issues of embryonic stem cells, have a lower risk for tumor development, do not need exogenic induction of pluripotency and are chromosomal stable. Starting from a single human AFS cell, EBs can be formed accompanied by the differentiation into cells of all three embryonic germ layers. Here, we report that siRNA-mediated knockdown of the endogenous tuberous sclerosis complex-2 (TSC2) gene product tuberin or of proline-rich Akt substrate of 40 kDa (PRAS40), the two major negative regulators of mammalian target of rapamycin (mTOR), leads to massive apoptotic cell death during EB development of human AFS cells without affecting the endodermal, mesodermal and ectodermal cell differentiation spectrum. Co-knockdown of endogenous mTOR demonstrated these effects to be mTOR-dependent. Our findings prove this enzyme cascade to be an essential anti-apoptotic gatekeeper of stem-cell differentiation during EB formation. These data allow new insights into the regulation of early stem-cell maintenance and differentiation and identify a new role of the tumor suppressor tuberin and the oncogenic protein PRAS40 with the relevance for a more detailed understanding of the pathogenesis of diseases associated with altered activities of these gene products.

  4. The orphan adapter protein SLY1 as a novel anti-apoptotic protein required for thymocyte development

    Directory of Open Access Journals (Sweden)

    Beer-Hammer Sandra

    2009-07-01

    Full Text Available Abstract Background SH3 containing Lymphocyte Protein (SLY1 is a putative adapter protein exclusively expressed in lymphocytes which is involved in antigen receptor induced activation. We previously have generated SLY1Δ/Δ mice harbouring a partial deletion in the N-terminal region of SLY1 which revealed profound immunological defects in T and B cell functions. Results In this study, T cell development in SLY1-/- and SLY1Δ/Δ mice was analysed ex vivo and upon cultivation with the bone marrow stromal cell line OP9. SLY1-deficient thymocytes were compromised in inducing nutrient receptor expression and ribosomal protein S6 phosphorylation, indicating a defect in mTOR complex activation. Furthermore, SLY1 was identified as a novel anti-apoptotic protein required for developmental progression of T cell precursors to the CD4+CD8+ double-positive stage by protecting from premature programmed cell death initiation in developing CD4-CD8- double-negative thymocytes. In addition, SLY1 phosphorylation was differentially regulated upon Notch ligand-mediated stimulation and expression of the preTCR. Conclusion Thus, our results suggest a non-redundant role for SLY1 in integrating signals from both receptors in early T cell progenitors in the thymus.

  5. Piezometric biosensors for anti-apoptotic protein survivin based on buried positive-potential barrier and immobilized monoclonal antibodies.

    Science.gov (United States)

    Stobiecka, Magdalena; Chalupa, Agata; Dworakowska, Beata

    2016-10-15

    The anti-apoptotic protein survivin (Sur) plays an important role in the regulation of cell division and inducing the chemotherapeutic drug resistance. The Sur protein and its mRNA have recently been studied as cancer biomarkers and potential targets for cancer therapy. In this work, we have focused on the design of immunosensors for the detection of Sur based on buried positive-potential barrier layer structure and anti-survivin antibody. The modification of solid AuQC piezoelectrodes was monitored by recording the resonance frequency shift and electrochemical measurements during each step of the sensor preparation. Our results indicate that the immunosensor with covalently bound monoclonal anti-survivin antibody can detect Sur with the limit of detection, LOD=1.7nM (S/N=3σ). The immunosensor applicability for the analysis of real samples was assessed by testing samples of cell lysate solutions obtained from human astrocytoma (glioblastoma) U-87MG cell line, with the experiments performed using the standard addition method. The good linearity of the calibration curves for PBS and lysate solutions at low Sur concentrations confirm the high specificity of the proposed biosensor and good discrimination against nonspecific interactions with lysate components. The calculations indicate that there is still room to increase the Sur capture capacity for Sur while miniaturizing the sensor. The important advantage of the sensor is that it can be reused by a simple regeneration procedure. PMID:26507667

  6. Carnosine attenuates early brain injury through its antioxidative and anti-apoptotic effects in a rat experimental subarachnoid hemorrhage model.

    Science.gov (United States)

    Zhang, Zong-yong; Sun, Bao-liang; Yang, Ming-feng; Li, Da-wei; Fang, Jie; Zhang, Shuai

    2015-03-01

    Carnosine (β-alanyl-L-histidine) has been demonstrated to provide antioxidative and anti-apoptotic roles in the animal of ischemic brain injuries and neurodegenerative diseases. The aim of this study was to examine whether carnosine prevents subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) in rats. We found that intraperitoneal administration of carnosine improved neurobehavioral deficits, attenuated brain edema and blood-brain barrier permeability, and decreased reactive oxygen species level at 48 h following SAH in rat models. Carnosine treatment increased tissue copper/zinc superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px) enzymatic activities, and reduced post-SAH elevated lactate dehydrogenase (LDH) activity, the concentration of malondialdehyde (MDA), 3-nitrotyrosine (3-NT), 8-hydroxydeoxyguanosine (8-OHDG), interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in rats. Furthermore, carnosine treatment attenuated SAH-induced microglia activation and cortical neuron apoptosis. These results indicated that administration of carnosine may provide neuroprotection in EBI following SAH in rat models. PMID:25179154

  7. Anti-Apoptotic Gene Delivery with cyclo-(d-Trp-Tyr Peptide Nanotube via Eye Drop Following Corneal Epithelial Debridement

    Directory of Open Access Journals (Sweden)

    Yu-Hsing Lee

    2015-07-01

    Full Text Available Corneal keratocyte apoptosis triggered by cornel debridement is one mechanism of corneal disorders. In this study, the feasibility of cyclo-(d-Trp-Tyr peptide nanotubes (PNTs as carriers of caspase 3 silence shRNA delivery was assessed. A model of epithelial injury by epithelial debridement was applied to investigate the feasibility of PNTs as gene delivery carriers on corneal injury. First, the PNTs were found within 2 μm in length and 300 nm in width by an atomic force microscope and confocal laser microscope system. Plasmid DNAs were observed to be associated with PNTs by atomic force microscope and confocal laser scanning microscope. The plasmids were associated with tyrosine of PNTs with a binding constant of 2.7 × 108 M−1. The stability of plasmid DNA with PNTs against the DNase was found at 60 min. Using thioflavin T pre-stained PNTs on the corneal eye drop delivery, the distribution of PNTs was in the epithelial and stroma regions. After corneal debridement, the rhodamine-labeled plasmid DNA and thioflavin T pre-stained PNTs were also delivered and could be observed in the stroma of cornea. PNTs complexed with anti-apoptotic plasmid caspase 3 silencing shRNA eye drop delivery decreased 41% of caspase 3 activity after the first dose by caspase 3 activity and Western blot analysis.

  8. Microglia-Secreted Galectin-3 Acts as a Toll-like Receptor 4 Ligand and Contributes to Microglial Activation

    Directory of Open Access Journals (Sweden)

    Miguel Angel Burguillos

    2015-03-01

    Full Text Available Inflammatory response induced by microglia plays a critical role in the demise of neuronal populations in neuroinflammatory diseases. Although the role of toll-like receptor 4 (TLR4 in microglia’s inflammatory response is fully acknowledged, little is known about endogenous ligands that trigger TLR4 activation. Here, we report that galectin-3 (Gal3 released by microglia acts as an endogenous paracrine TLR4 ligand. Gal3-TLR4 interaction was further confirmed in a murine neuroinflammatory model (intranigral lipopolysaccharide [LPS] injection and in human stroke subjects. Depletion of Gal3 exerted neuroprotective and anti-inflammatory effects following global brain ischemia and in the neuroinflammatory LPS model. These results suggest that Gal3-dependent-TLR4 activation could contribute to sustained microglia activation, prolonging the inflammatory response in the brain.

  9. Acidosis Sensing Receptor GPR65 Correlates with Anti-Apoptotic Bcl-2 Family Member Expression in CLL Cells: Potential Implications for the CLL Microenvironment

    OpenAIRE

    Rosko, Ashley E.; McColl, Karen S.; Zhong, Fei; Ryder, Christopher B; Chang, Ming-Jin; Sattar, Abdus; Caimi, Paolo F.; Hill, Brian T; Al-harbi, Sayer; Almasan, Alexandru; Distelhorst, Clark W.

    2014-01-01

    The tumor microenvironment is generally an acidic environment, yet the effect of extracellular acidosis on chronic lymphocytic leukemia (CLL) is not well established. Here we are the first to report that the extracellular acid sensing G-protein coupled receptor, GPR65, is expressed in primary CLL cells where its level correlate strongly with anti-apoptotic Bcl-2 family member levels. GPR65 expression is found normally within the lymphoid lineage and has not been previously reported in CLL. We...

  10. Orphan Nuclear Receptor NR4A1 Binds a Novel Protein Interaction Site on Anti-apoptotic B Cell Lymphoma Gene 2 Family Proteins.

    Science.gov (United States)

    Godoi, Paulo H C; Wilkie-Grantham, Rachel P; Hishiki, Asami; Sano, Renata; Matsuzawa, Yasuko; Yanagi, Hiroko; Munte, Claudia E; Chen, Ya; Yao, Yong; Marassi, Francesca M; Kalbitzer, Hans R; Matsuzawa, Shu-Ichi; Reed, John C

    2016-07-01

    B cell lymphoma gene 2 (Bcl-2) family proteins are key regulators of programmed cell death and important targets for drug discovery. Pro-apoptotic and anti-apoptotic Bcl-2 family proteins reciprocally modulate their activities in large part through protein interactions involving a motif known as BH3 (Bcl-2 homology 3). Nur77 is an orphan member of the nuclear receptor family that lacks a BH3 domain but nevertheless binds certain anti-apoptotic Bcl-2 family proteins (Bcl-2, Bfl-1, and Bcl-B), modulating their effects on apoptosis and autophagy. We used a combination of NMR spectroscopy-based methods, mutagenesis, and functional studies to define the interaction site of a Nur77 peptide on anti-apoptotic Bcl-2 family proteins and reveal a novel interaction surface. Nur77 binds adjacent to the BH3 peptide-binding crevice, suggesting the possibility of cross-talk between these discrete binding sites. Mutagenesis of residues lining the identified interaction site on Bcl-B negated the interaction with Nur77 protein in cells and prevented Nur77-mediated modulation of apoptosis and autophagy. The findings establish a new protein interaction site with the potential to modulate the apoptosis and autophagy mechanisms governed by Bcl-2 family proteins. PMID:27129202

  11. Cytoplasmic and nuclear anti-apoptotic roles of αB-crystallin in retinal pigment epithelial cells.

    Directory of Open Access Journals (Sweden)

    Woo Jin Jeong

    Full Text Available In addition to its well-characterized role in the lens, αB-crystallin performs other functions. Methylglyoxal (MGO can alter the function of the basement membrane of retinal pigment epithelial (RPE cells. Thus, if MGO is not efficiently detoxified, it can induce adverse reactions in RPE cells. In this study, we examined the mechanisms underlying the anti-apoptotic activity of αB-crystallin in the human retinal pigment epithelial cell line ARPE-19 following MGO treatment using various assays, including nuclear staining, flow cytometry, DNA electrophoresis, pulse field gel electrophoresis, western blot analysis, confocal microscopy and co-immunoprecipitation assays. To directly assess the role of phosphorylation of αB-crystallin, we used site-directed mutagenesis to convert relevant serine residues to alanine residues. Using these techniques, we demonstrated that MGO induces apoptosis in ARPE-19 cells. Silencing αB-crystallin sensitized ARPE-19 cells to MGO-induced apoptosis, indicating that αB-crystallin protects ARPE-19 cells from MGO-induced apoptosis. Furthermore, we found that αB-crystallin interacts with the caspase subtypes, caspase-2L, -2S, -3, -4, -7, -8, -9 and -12 in untreated control ARPE-19 cells and that MGO treatment caused the dissociation of these caspase subtypes from αB-crystallin; transfection of S19A, S45A or S59A mutants caused the depletion of αB-crystallin from the nuclei of untreated control RPE cells leading to the release of caspase subtypes. Additionally, transfection of these mutants enhanced MGO-induced apoptosis in ARPE-19 cells, indicating that phosphorylation of nuclear αB-crystallin on serine residues 19, 45 and 59 plays a pivotal role in preventing apoptosis in ARPE-19 cells. Taken together, these results suggest that αB-crystallin prevents caspase activation by physically interacting with caspase subtypes in the cytoplasm and nucleus, thereby protecting RPE cells from MGO-induced apoptosis.

  12. Thymosin beta 4 protects cardiomyocytes from oxidative stress by targeting anti-oxidative enzymes and anti-apoptotic genes.

    Directory of Open Access Journals (Sweden)

    Chuanyu Wei

    Full Text Available BACKGROUND: Thymosin beta-4 (Tβ4 is a ubiquitous protein with many properties relating to cell proliferation and differentiation that promotes wound healing and modulates inflammatory mediators. The mechanism by which Tβ4 modulates cardiac protection under oxidative stress is not known. The purpose of this study is to dissect the cardioprotective mechanism of Tβ4 on H(2O(2 induced cardiac damage. METHODS: Rat neonatal cardiomyocytes with or without Tβ4 pretreatment were exposed to H(2O(2 and expression of antioxidant, apoptotic, and anti-inflammatory genes was evaluated by quantitative real-time PCR and western blotting. ROS levels were estimated by DCF-DA using fluorescent microscopy and fluorimetry. Selected antioxidant, anti-inflammatory and antiapoptotic genes were silenced by siRNA transfections in neonatal cardiomyocytes and effect of Tβ4 on H(2O(2-induced cardiac damage was evaluated. RESULTS: Pre-treatment of Tβ4 resulted in reduction of the intracellular ROS levels induced by H(2O(2 in cardiomyocytes. Tβ4 pretreatment also resulted in an increase in the expression of antiapoptotic proteins and reduction of Bax/BCl(2 ratio in the cardiomyocytes. Pretreatment with Tβ4 resulted in stimulating the expression of antioxidant enzymes copper/zinc SOD and catalase in cardiomyocytes at both transcription and translation levels. Tβ4 treatment resulted in the increased expression of anti-apoptotic and anti-inflammatory genes. Silencing of Cu/Zn SOD and catalase gene resulted in apoptotic cell death in the cardiomyocytes which was prevented by treatment with Tβ4. CONCLUSION: This is the first report that demonstrates the effect of Tβ4 on cardiomyocytes and its capability to selectively upregulate anti-oxidative enzymes, anti-inflammatory genes, and antiapoptotic enzymes in the neonatal cardiomyocytes thus preventing cell death thereby protecting the myocardium. Tβ4 treatment resulted in decreased oxidative stress and inflammation in the

  13. The anti-apoptotic factor Che-1/AATF links transcriptional regulation, cell cycle control, and DNA damage response

    Directory of Open Access Journals (Sweden)

    Fanciulli Maurizio

    2007-07-01

    Full Text Available Abstract Che-1 is a RNA polymerase II binding protein involved in the transcriptional regulation of E2F target genes and in cell proliferation. Recently, it has been shown that Che-1 accumulates in cells responding to genotoxic agents such as Doxorubicin and ionizing radiation. The DNA damage-activated checkpoint kinases ATM and Chk2 interact with and phosphorylate Che-1, enhancing its accumulation and stability, and promoting Che-1-mediated transcription of p53-responsive genes and of p53 itself, as evidenced by microarray analysis. This transcriptional response is suppressed by expression of a Che-1 mutant lacking ATM and Chk2 phosphorylation amino acid residues, or by depletion of Che-1 by RNA silencing. In addition, chromatin immunoprecipitation analysis has shown that Che-1 is released from E2F target genes and recruited to the p21 and p53 promoters after DNA damage. Che-1 contributes to the maintenance of the G2/M checkpoint in response to genotoxic stress. These findings identify a new mechanism by which the checkpoint kinases regulate, via the novel effector Che-1, the p53 pathway. Lastly, increasing evidence suggests that Che-1 may be involved in apoptotic signaling in neural tissues. In cortical neurons, Che-1 exhibits anti-apoptotic activity, protecting cells from neuronal damage induced by amyloid β-peptide. In cerebellar granule neurons, Che-1 interacts with Tau in the cytoplasmic compartment and this interaction is modulated during neuronal apoptosis. Finally, Che-1 directly interacts with the neuronal cell-death inducer "NRAGE" which downregulates endogenous Che-1 by targeting it for proteasome-dependent degradation. These findings identify Che-1 as a novel cytoprotective factor against apoptotic insults and suggest that Che-1 may represent a potential target for therapeutic application.

  14. Anti-apoptotic BFL-1 is the major effector in activation-induced human mast cell survival.

    Directory of Open Access Journals (Sweden)

    Maria Ekoff

    Full Text Available Mast cells are best known for their role in allergic reactions, where aggregation of FcεRI leads to the release of mast cell mediators causing allergic symptoms. The activation also induces a survival program in the cells, i.e., activation-induced mast cell survival. The aim of the present study was to investigate how the activation-induced survival is mediated. Cord blood-derived mast cells and the mast cell line LAD-2 were activated through FcεRI crosslinking, with or without addition of chemicals that inhibit the activity or expression of selected Bcl-2 family members (ABT-737; roscovitine. Cell viability was assessed using staining and flow cytometry. The expression and function of Bcl-2 family members BFL-1 and MCL-1 were investigated using real-time quantitative PCR and siRNA treatment. The mast cell expression of Bfl-1 was investigated in skin biopsies. FcεRI crosslinking promotes activation-induced survival of human mast cells and this is associated with an upregulation of the anti-apoptotic Bcl-2 family member Bfl-1. ABT-737 alone or in combination with roscovitine decreases viability of human mast cells although activation-induced survival is sustained, indicating a minor role for Bcl-X(L, Bcl-2, Bcl-w and Mcl-1. Reducing BFL-1 but not MCL-1 levels by siRNA inhibited activation-induced mast cell survival. We also demonstrate that mast cell expression of Bfl-1 is elevated in birch-pollen-provocated skin and in lesions of atopic dermatitis and psoriasis patients. Taken together, our results highlight Bfl-1 as a major effector in activation-induced human mast cell survival.

  15. Regulation of ozone-induced lung inflammation and injury by the β-galactoside-binding lectin galectin-3

    Energy Technology Data Exchange (ETDEWEB)

    Sunil, Vasanthi R., E-mail: sunilva@pharmacy.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Francis, Mary, E-mail: maryfranrutgers@gmail.com [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Vayas, Kinal N., E-mail: kinalv5@gmail.com [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Cervelli, Jessica A., E-mail: j.cervelli@pharmacy.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Choi, Hyejeong, E-mail: choi@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Laskin, Jeffrey D., E-mail: jlaskin@eohsi.rutgers.edu [Department of Environmental and Occupational Medicine, Rutgers University, Robert Wood Johnson Medical School, Piscataway, NJ (United States); Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ (United States)

    2015-04-15

    Macrophages play a dual role in ozone toxicity, contributing to both pro- and anti-inflammatory processes. Galectin-3 (Gal-3) is a lectin known to regulate macrophage activity. Herein, we analyzed the role of Gal-3 in the response of lung macrophages to ozone. Bronchoalveolar lavage (BAL) and lung tissue were collected 24–72 h after exposure (3 h) of WT and Gal-3{sup -/-} mice to air or 0.8 ppm ozone. In WT mice, ozone inhalation resulted in increased numbers of proinflammatory (Gal-3{sup +}, iNOS{sup +}) and anti-inflammatory (MR-1{sup +}) macrophages in the lungs. While accumulation of iNOS{sup +} macrophages was attenuated in Gal-3{sup -/-} mice, increased numbers of enlarged MR-1{sup +} macrophages were noted. This correlated with increased numbers of macrophages in BAL. Flow cytometric analysis showed that these cells were CD11b{sup +} and consisted mainly (> 97%) of mature (F4/80{sup +}CD11c{sup +}) proinflammatory (Ly6GLy6C{sup hi}) and anti-inflammatory (Ly6GLy6C{sup lo}) macrophages. Increases in both macrophage subpopulations were observed following ozone inhalation. Loss of Gal-3 resulted in a decrease in Ly6C{sup hi} macrophages, with no effect on Ly6C{sup lo} macrophages. CD11b{sup +}Ly6G{sup +}Ly6C{sup +} granulocytic (G) and monocytic (M) myeloid derived suppressor cells (MDSC) were also identified in the lung after ozone. In Gal-3{sup -/-} mice, the response of G-MDSC to ozone was attenuated, while the response of M-MDSC was heightened. Changes in inflammatory cell populations in the lung of ozone treated Gal-3{sup -/-} mice were correlated with reduced tissue injury as measured by cytochrome b5 expression. These data demonstrate that Gal-3 plays a role in promoting proinflammatory macrophage accumulation and toxicity in the lung following ozone exposure. - Highlights: • Multiple monocytic-macrophage subpopulations accumulate in the lung after ozone inhalation. • Galectin-3 plays a proinflammatory role in ozone-induced lung injury. • In the

  16. Regulation of ozone-induced lung inflammation and injury by the β-galactoside-binding lectin galectin-3

    International Nuclear Information System (INIS)

    Macrophages play a dual role in ozone toxicity, contributing to both pro- and anti-inflammatory processes. Galectin-3 (Gal-3) is a lectin known to regulate macrophage activity. Herein, we analyzed the role of Gal-3 in the response of lung macrophages to ozone. Bronchoalveolar lavage (BAL) and lung tissue were collected 24–72 h after exposure (3 h) of WT and Gal-3-/- mice to air or 0.8 ppm ozone. In WT mice, ozone inhalation resulted in increased numbers of proinflammatory (Gal-3+, iNOS+) and anti-inflammatory (MR-1+) macrophages in the lungs. While accumulation of iNOS+ macrophages was attenuated in Gal-3-/- mice, increased numbers of enlarged MR-1+ macrophages were noted. This correlated with increased numbers of macrophages in BAL. Flow cytometric analysis showed that these cells were CD11b+ and consisted mainly (> 97%) of mature (F4/80+CD11c+) proinflammatory (Ly6GLy6Chi) and anti-inflammatory (Ly6GLy6Clo) macrophages. Increases in both macrophage subpopulations were observed following ozone inhalation. Loss of Gal-3 resulted in a decrease in Ly6Chi macrophages, with no effect on Ly6Clo macrophages. CD11b+Ly6G+Ly6C+ granulocytic (G) and monocytic (M) myeloid derived suppressor cells (MDSC) were also identified in the lung after ozone. In Gal-3-/- mice, the response of G-MDSC to ozone was attenuated, while the response of M-MDSC was heightened. Changes in inflammatory cell populations in the lung of ozone treated Gal-3-/- mice were correlated with reduced tissue injury as measured by cytochrome b5 expression. These data demonstrate that Gal-3 plays a role in promoting proinflammatory macrophage accumulation and toxicity in the lung following ozone exposure. - Highlights: • Multiple monocytic-macrophage subpopulations accumulate in the lung after ozone inhalation. • Galectin-3 plays a proinflammatory role in ozone-induced lung injury. • In the absence of gal-3, inflammatory cells with a myeloid derived suppressor cell phenotype contribute to tissue repair

  17. Anti-apoptotic effect of morphine-induced delayed preconditioning on pulmonary artery endothelial cells with anoxia/reoxygenation injury

    Institute of Scientific and Technical Information of China (English)

    DING Weng-ang; ZHOU Hua-cheng; CUI Xiao-guang; LI Wen-zhi; GUO Yue-ping; ZHANG Bing; LIU Wei

    2008-01-01

    Background Opioid preconditioning (PC) reduces anoxiaJreoxygenation (NR) injury to various cells. However, it remains unclear whether opioid-induced delayed PC would show anti-apoptotic effects on pulmonary artery endothelial cells (PAECs) suffering from A/R injury. The present study was conducted to elucidate this issue and to investigate the potential mechanism of opioid-induced delayed PC.Methods Cultured porcine PAECs underwent 16-hour anoxia followed by 1-hour reoxygenation 24 hours after pretreatment with saline (NaCI; 0.9%) or morphine (1 μmol/L). To determine the underlying mechanism, a non-selective KATP channel inhibitor glibenclamide (Glib; 10 μmol/L), a nitric oxide (NO) synthase blocker NG-nitro-L-arginine methyl ester (L-NAME; 100 μmol/L), and an opioid receptor antagonist naloxone (Nal; 10 pmol/L) were given 30 minutes before the A/R load. The percentage of apoptotic cells was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, eNOS mRNA level was measured by real-time polymerase chain reaction (PCR). NO content of PAECs supernatants was measured with the Griess reagent.Results Compared to the A/R PAECs, morphine-induced delayed PC significantly reduced PAECs apoptosis ((18.1±1.9)% vs (5.5±0.3)%; P <0.05), increased NO release ((11.4±1.3) μmol/L vs (20.5±2.1) μmol/L, P <0.05), and up-regulated eNOS gene expression nearly 9 times (P<0.05). The anti-apoptosis effect of morphine was abolished by pretreatment with Glib, L-NAME and Nal, but the three agent-selves did not aggravate the A/R injury. Furthermore, L-NAME and Nal offset the enhanced release of NO caused by pretreatment with morphine.Conclusions Morphine-induced delayed PC prevents A/R injury of PAECs. This effect may be mediated by activation of KATP channel via opioid receptor and NO signaling pathways.

  18. Gene Expression Profiling in Lungs of Chronic Asthmatic Mice Treated with Galectin-3: Downregulation of Inflammatory and Regulatory Genes

    Directory of Open Access Journals (Sweden)

    Esther López

    2011-01-01

    Full Text Available Background. Asthma is a disorder characterized by a predominance of Th2 cells and eosinophilic inflammation. Suppressors of cytokine signaling (SOCS proteins act as negative regulators of cytokine signaling. In particular, SOCS1 and SOCS3 play an important role in immune response by controlling the balance between Th1 and Th2 cells. In a previous study, we demonstrated that treatment of chronic asthmatic mice with gene therapy using plasmid encoding galectin-3 (Gal-3 led to an improvement in Th2 allergic inflammation. Methods. Using a microarray approach, this study endeavored to evaluate the changes produced by therapeutic Gal-3 delivered by gene therapy in a well-characterized mouse model of chronic airway inflammation. Results were confirmed by real-time RT-PCR, Western blot and immunohistochemical analysis. Results. We identify a set of genes involved in different pathways whose expression is coordinately decreased/increased in mice treated with Gal-3 gene therapy. We report a correlation between Gal-3 treatment and inhibition of SOCS1 and SOCS3 expression in lungs. Conclusion. These results suggest that negative regulation of SOCS1 and 3 following Gal-3 treatment could be a valuable therapeutic approach in allergic disease.

  19. Cod glycopeptide with picomolar affinity to galectin-3 suppresses T-cell apoptosis and prostate cancer metastasis.

    Science.gov (United States)

    Guha, Prasun; Kaptan, Engin; Bandyopadhyaya, Gargi; Kaczanowska, Sabina; Davila, Eduardo; Thompson, Keyata; Martin, Stuart S; Kalvakolanu, Dhananjaya V; Vasta, Gerardo R; Ahmed, Hafiz

    2013-03-26

    Cancer metastasis and immune suppression are critical issues in cancer therapy. Here, we show that a β-galactoside-binding lectin [galectin-3 (gal3)] that recognizes the Thomsen-Friedenreich disaccharide (TFD, Galβ1,3GalNAc) present on the surface of most cancer cells is involved in promoting angiogenesis, tumor-endothelial cell adhesion, and metastasis of prostate cancer cells, as well as evading immune surveillance through killing of activated T cells. To block gal3-mediated interactions, we purified a glycopeptide from cod (designated TFD100) that binds gal3 with picomolar affinity. TFD100 blocks gal3-mediated angiogenesis, tumor-endothelial cell interactions, and metastasis of prostate cancer cells in mice at nanomolar levels. Moreover, apoptosis of activated T cells induced by either recombinant gal3 or prostate cancer patient serum-associated gal3 was inhibited at nanomolar concentration of TFD100. Because the gal3-TFD interaction is a key factor driving metastasis in most epithelial cancers, this high-affinity TFD100 should be a promising antimetastatic agent for the treatment of various cancers, including prostate adenocarcinoma. PMID:23479624

  20. Cell surface galectin-3 defines a subset of chemoresistant gastrointestinal tumor-initiating cancer cells with heightened stem cell characteristics.

    Science.gov (United States)

    Ilmer, Matthias; Mazurek, Nachman; Byrd, James C; Ramirez, Karen; Hafley, Margarete; Alt, Eckhard; Vykoukal, Jody; Bresalier, Robert S

    2016-01-01

    Recurrence of gastrointestinal adenocarcinomas after surgery and chemotherapy may be attributed, in part, to the presence of a small population of tumor-initiating cancer stem cells (CSC). The expression of galectin-3 (Gal3), a multifunctional oncolectin, has been associated with biological behaviors associated with CSC. We examined the ability of Gal3 to characterize the CSC phenotype, and to identify a clinically important gastrointestinal cancer CSC population. Human colorectal and pancreatic cancer cell lines were sorted to identify subpopulations expressing commonly used CSC markers, and Gal3-positive CSC subpopulations. The association of Gal3 with the stem cell properties and alterations of these phenotypes by manipulation of Gal3 expression was examined. Gastrointestinal cancer cell lines contain both Gal3-positive and Gal3-negative subpopulations. Gal3-positive CSCs are characterized by high ALDH activity, enhanced self-renewal ability in vitro (sphere formation) and tumor forming ability in vivo, and resistance to chemotherapeutic agents and death-receptor-mediated apoptosis compared to Gal3-negative CSCs. Silencing Gal3 modifies this behavior. Cell surface Gal3 expression identifies a subset of CSCs in gastrointestinal cancers with high levels of stem cell characteristics, including chemoresistance. This may provide a platform for developing treatment strategies that target CSC. PMID:27512958

  1. ROLE OF PANCREATIC STELLATE CELLS AND GALECTIN-3 ON PROLIFERATION AND INFILTRATION OF HUMAN PANCREATIC CANCER CELL LINE SW1990

    Institute of Scientific and Technical Information of China (English)

    JIANG Hai-biao; XU Ming; WANG Xing-peng

    2008-01-01

    Objective To investigate the role of pancreatic stellate cells (PSCs) and galectin-3 (GAL-3)on the proliferation and infiltration of pancreatic cancer cell line SW1990. Methods Human pancreatic cancercell line SW1990 and PSCs were cultured in vitro. Supernatant of cultured PSCs and SW1990 cells was collected.Expressions of GAL-3 in SW1990 cells and PSCs were detected by ELISA, RT-PCR and Western blot. Theproliferation of those cultured PSCs and SW1990 cells were measured by MTT assay and flowcytometry. Infiltrationof SW1990 cells was detected by cell infiltration kit. Results SW1990 cells expressed GAL-3 and the expressionwas up-regulated by the supernatant fluid of cultured PSCs. PSCs did not express GAL-3. SW1990 cells couldstimulate the proliferation of PSCs via GAL-3. GAL-3 antibody could inhibit SW1990 cells proliferation andinfiltration, which indicated that supernatant of PSCs might stimulate the proliferation of SW1990 cells through theinteraction with GAL-3 protein. The supernatant fluid of PSCs could enhance the invasiveness of SW1990 cellsthrough the interaction with GAL-3. Conclusion GAL-3 and PSCs was involved in the proliferation andinfiltration process of pancreatic cancer.

  2. Expressions of D2-40, CK19, galectin-3, VEGF and EGFR in papillary thyroid carcinoma and their clinical significances%D2-40,CK19,galectin-3,VEGF和EGFR在甲状腺乳头状癌中的表达及其临床意义

    Institute of Scientific and Technical Information of China (English)

    巩雷; 陈萍; 刘宪军; 韩影; 周艳萍; 张卫东; 李红; 李传甲; 谢江

    2011-01-01

    目的 研究甲状腺乳头状癌中D2-40,CK19,galectin-3,VEGF和EGFR的表达及其临床意义.方法 应用免疫组化法检测38例甲状腺乳头状癌和12例甲状腺乳头状增生组织中D2-40,CK19,galectin-3,VEGF和EGFR的表达水平.结果 D2-40,CK19,galectin-3,VEGF和EGFR在甲状腺乳头状癌中的阳性表达率明显高于甲状腺乳头状增生组织(P<0.05);D2-40,VEGF,EGFR在甲状腺乳头状癌组织中有淋巴结转移组的表达高于无淋巴结转移组(P<0.05);CK19,galectin-3在甲状腺乳头状癌中的表达在有、无淋巴结转移组之间无统计学差异(P>0.05).结论 D2-40,CK19,galectin-3,VEGF及EGFR的检测有助于甲状腺乳头状癌与甲状腺乳头状增生的诊断和鉴别诊断;D2-40,VEGF和EGFR的表达与甲状腺乳头状癌淋巴结转移有关,对预测淋巴结的转移与否可能有帮助.%Objective To investigate the expressions of D2-40, CK19, galectin-3 , VEGF and EGFR in papillary thyroid carcinoma and their clinical significances. Methods The expressions of D2-40, CK19, galectin-3, VEGF and EGFR in 38 cases of papillary thyroid carcinoma and 12 cases of thyroid papillary hyperplasia were detected by immunohistochemical staining. Results The positive expression rates of D2-40 , CK19 , Galectin-3 , VEGF and EGFR in patients with papillary thyroid carcinoma were all significantly higher than those in patients with thyroid papillary hyperplasia (all P < 0. 05 ) . The expressions of D2-40, VEGF and EGFR in papillary thyroid carcinoma with lymph node metastasis were significantly higher than those without lymph node metastasis (P<0.05). The expressions of CK19 and galectin-3 showed no significant differences between the papillary thyroid carcinomas with and without lymph node metastasis ( P > 0. 05 ). Conclusions The detection of D2-40, CK19, galectin-3, VEGF and EGFR is helpful to diagnosis and differential diagnosis of papillary thyroid carcinoma and thyroid papillary hyperplasia

  3. 半乳糖凝集素-3与垂体泌乳素瘤细胞增殖的关系%Relationship between the expression of galectin-3 and proliferation of prolactinoma

    Institute of Scientific and Technical Information of China (English)

    蒲建章; 赵洪洋; 苏群

    2006-01-01

    目的探讨半乳糖凝集素-3(Galectin-3)表达和人脑垂体泌乳素腺瘤细胞增殖的关系.方法应用免疫组化SP法检测38例垂体泌乳素腺瘤组织中Galectin-3及增殖细胞核抗原(PCNA)表达.结果侵袭组的Galectin-3阳性表达率极显著高于非侵袭组(P《0.01).侵袭组的PCNA阳性表达率显著高于非侵袭组(P《0.05).Galectin-3与PCNA表达之间呈正相关(r=0.33,P《0.05).结论 Galectin-3与垂体泌乳素腺瘤细胞增殖密切相关,Galectin-3可能在垂体PRL腺瘤的细胞增殖和侵袭过程中起重要作用.

  4. Histone deacetylase inhibitors strongly sensitise neuroblastoma cells to TRAIL-induced apoptosis by a caspases-dependent increase of the pro- to anti-apoptotic proteins ratio

    International Nuclear Information System (INIS)

    Neuroblastoma (NB) is the second most common solid childhood tumour, an aggressive disease for which new therapeutic strategies are strongly needed. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in most tumour cells, but not in normal tissues and therefore represents a valuable candidate in apoptosis-inducing therapies. Caspase-8 is silenced in a subset of highly malignant NB cells, which results in full TRAIL resistance. In addition, despite constitutive caspase-8 expression, or its possible restoration by different strategies, NB cells remain weakly sensitive to TRAIL indicating a need to develop strategies to sensitise NB cells to TRAIL. Histone deacetylase inhibitors (HDACIs) are a new class of anti-cancer agent inducing apoptosis or cell cycle arrest in tumour cells with very low toxicity toward normal cells. Although HDACIs were recently shown to increase death induced by TRAIL in weakly TRAIL-sensitive tumour cells, the precise involved sensitisation mechanisms have not been fully identified. NB cell lines were treated with various doses of HDACIs and TRAIL, then cytotoxicity was analysed by MTS/PMS proliferation assays, apoptosis was measured by the Propidium staining method, caspases activity by colorimetric protease assays, and (in)activation of apoptotic proteins by immunoblotting. Sub-toxic doses of HDACIs strongly sensitised caspase-8 positive NB cell lines to TRAIL induced apoptosis in a caspases dependent manner. Combined treatments increased the activation of caspases and Bid, and the inactivation of the anti-apoptotic proteins XIAP, Bcl-x, RIP, and survivin, thereby increasing the pro- to anti-apoptotic protein ratio. It also enhanced the activation of the mitochondrial pathway. Interestingly, the kinetics of caspases activation and inactivation of anti-apoptotic proteins is accelerated by combined treatment with TRAIL and HDACIs compared to TRAIL alone. In contrast, cell surface expression of TRAIL

  5. PACS-2 mediates the ATM and NF-κB-dependent induction of anti-apoptotic Bcl-xL in response to DNA damage.

    Science.gov (United States)

    Barroso-González, J; Auclair, S; Luan, S; Thomas, L; Atkins, K M; Aslan, J E; Thomas, L L; Zhao, J; Zhao, Y; Thomas, G

    2016-09-01

    Nuclear factor kappa B (NF-κB) promotes cell survival in response to genotoxic stress by inducing the expression of anti-apoptotic proteins including Bcl-xL, which protects mitochondria from stress-induced mitochondrial outer membrane permeabilization (MOMP). Here we show that the multifunctional sorting protein Pacs-2 (phosphofurin acidic cluster sorting protein-2) is required for Bcl-xL induction following DNA damage in primary mouse thymocytes. Consequently, in response to DNA damage, Pacs-2(-/-) thymocytes exhibit a blunted induction of Bcl-xL, increased MOMP and accelerated apoptosis. Biochemical studies show that cytoplasmic PACS-2 promotes this DNA damage-induced anti-apoptotic pathway by interacting with ataxia telangiectasia mutated (ATM) to drive NF-κB activation and induction of Bcl-xL. However, Pacs-2 was not required for tumor necrosis factor-α-induced NF-κB activation, suggesting a role for PACS-2 selectively in NF-κB activation in response to DNA damage. These findings identify PACS-2 as an in vivo mediator of the ATM and NF-κB-dependent induction of Bcl-xL that promotes cell survival in response to DNA damage. PMID:26943323

  6. High-quality NMR structure of human anti-apoptotic protein domain Mcl-1(171-327 for cancer drug design.

    Directory of Open Access Journals (Sweden)

    Gaohua Liu

    Full Text Available A high-quality NMR solution structure is presented for protein hMcl-1(171-327 which comprises residues 171-327 of the human anti-apoptotic protein Mcl-1 (hMcl-1. Since this construct contains the three Bcl-2 homology (BH sequence motifs which participate in forming a binding site for inhibitors of hMcl-1, it is deemed to be crucial for structure-based design of novel anti-cancer drugs blocking the Mcl1 related anti-apoptotic pathway. While the coordinates of an NMR solution structure for a corresponding construct of the mouse homologue (mMcl-1 are publicly available, our structure is the first atomic resolution structure reported for the 'apo form' of the human protein. Comparison of the two structures reveals that hMcl-1(171-327 exhibits a somewhat wider ligand/inhibitor binding groove as well as a different charge distribution within the BH3 binding groove. These findings strongly suggest that the availability of the human structure is of critical importance to support future design of cancer drugs.

  7. Tumor targeting and SPECT imaging properties of an {sup 111}In-labeled galectin-3 binding peptide in prostate carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Deutscher, Susan L. [Department of Biochemistry, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States); Research Division, Harry S. Truman Veterans Hospital, Columbia, MO 65201 (United States); Figueroa, Said D. [Research Division, Harry S. Truman Veterans Hospital, Columbia, MO 65201 (United States); Kumar, Senthil R. [Department of Biochemistry, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States)], E-mail: kumars@missouri.edu

    2009-02-15

    Introduction: Galectin-3 (gal-3) is a carbohydrate binding protein that has been implicated in cell adhesion, tumor invasion and metastasis. The objective of this study was to evaluate the tumor targeting and imaging properties of a gal-3 binding peptide selected by phage display in a mouse model of metastatic human prostate carcinoma expressing gal-3. Methods: A gal-3 binding peptide, ANTPCGPYTHDCPVKR, was synthesized with a Gly-Ser-Gly (GSG) spacer and 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) and then radiolabeled with {sup 111}In. The in vitro cell binding properties of {sup 111}In-DOTA-(GSG)-ANTPCGPYTHDCPVKR were determined in metastatic human PC3-M prostate carcinoma cells. The pharmacokinetics and single-photon emission computed tomographic (SPECT/CT) imaging with the radiolabeled peptide were evaluated in SCID mice bearing human PC3-M prostate carcinoma tumor xenografts. Results: The radiolabeled peptide bound with a 50% inhibitory concentration of 191{+-}10.2 nM to cultured PC3-M prostate carcinoma cells. In vivo tumor uptake and retention coupled with fast whole-body clearance of the peptide were demonstrated in PC3-M tumor-bearing SCID mice. The tumor uptake rates of the radiolabeled peptide were 1.27{+-}0.10%ID/g at 30 min, 0.82{+-}0.15%ID/g at 1 h and 0.57{+-}0.09%ID/g at 2 h. MicroSPECT/CT studies revealed good tumor uptake of {sup 111}In-DOTA-(GSG)-ANTPCGPYTHDCPVKR 2 h postinjection, while uptake in normal organs was low, with the exception of the kidneys. Conclusions: In vitro cell binding along with tumor uptake of {sup 111}In-DOTA-(GSG)-ANTPCGPYTHDCPVKR in PC3-M human prostate carcinoma tumor-bearing SCID mice suggests the potential of this peptide as a radiopharmaceutical for imaging of gal-3-expressing prostate tumors.

  8. Analysis of effects by CK19, TPO, galectin-3 and HBME-1 protein expression for pathological diagnosis of thyroid tumor%CK19、TPO、Galectin-3与 HBME-1蛋白表达对甲状腺肿瘤病理诊断作用分析

    Institute of Scientific and Technical Information of China (English)

    郭健; 张世豪; 延丽雅; 陈辉娥

    2015-01-01

    Objective To investigate the expressions of cytokeratin 19 (CK19), thyroid peroxidase (TPO), Galectin-3, and human bone marrow endothelial cell markers (HBME-1) in thyroid lesions and their effects for pathological diagnosis of thyroid tumor. Methods Pathological samples were collected in 134 cases of thyroid cancer (123 cases of papillary carcinoma and 11 cases of follicular carcinoma), 34 cases of thyroid adenoma, 20 cases of nodositas goiter and 10 cases of Hashimoto thyroiditis. Their expressions of CK19, TPO, Galectin-3, and HBME-1 were detected. Results The difference of CK19, TPO, Galectin-3, and HBME-1 expressions between benign and malignant tissues in thyroid tumor had statistical significance (P<0.05). Combined detection of four indicators had the sensitivity and specificity as 96.3% and 100.0% for diagnosis of benign and malignant thyroid tumor. Conclusion In malignant thyroid tumor, the positive expressions of CK19, Galectin-3, and HBME-1 were increased, while that of TPO was deficient. Combined detection of four indicators provides important diagnostic value for benign and malignant thyroid tumor.%目的:探讨甲状腺病变中的细胞角蛋白19(CK19)、甲状腺过氧化物酶(TPO)、半乳糖凝集素-3(Galectin-3)与人骨髓内皮细胞标记物(HBME-1)表达及其对甲状腺肿瘤病理诊断的价值。方法收集134例甲状腺癌(123例乳头状癌和11例滤泡癌)、34例甲状腺腺瘤、20例结节性甲状腺腺肿以及10例桥本甲状腺炎患者的病理标本,检测其 CK19、TPO、Galectin-3与 HBME-1的表达情况。结果CK19、TPO、Galectin-3与 HBME-1在甲状腺肿瘤良性组织和恶性组织中的阳性表达率比较,差异有统计学意义(P<0.05);四项指标联合检测对于甲状腺肿瘤良恶性诊断的敏感度和特异度分别为96.3%和100.0%。结论甲状腺恶性肿瘤中 CK19、Galectin-3与 HBME-1阳性表达增高,而 TPO 表达缺失,四项指标联合检测对于甲状腺肿瘤良恶

  9. Targeting anti-apoptotic Bcl-2 by AT-101 to increase radiation efficacy: data from in vitro and clinical pharmacokinetic studies in head and neck cancer

    International Nuclear Information System (INIS)

    Pro-survival Bcl-2 family members can promote cancer development and contribute to treatment resistance. Head and neck squamous cell carcinoma (HNSCC) is frequently characterized by overexpression of anti-apoptotic Bcl-2 family members. Increased levels of these anti-apoptotic proteins have been associated with radio- and chemoresistance and poor clinical outcome. Inhibition of anti-apoptotic Bcl-2 family members therefore represents an appealing strategy to overcome resistance to anti-cancer therapies. The aim of this study was to evaluate combined effects of radiation and the pan-Bcl-2 inhibitor AT-101 in HNSCC in vitro. In addition, we determined human plasma levels of AT-101 obtained from a phase I/II trial, and compared these with the effective in vitro concentrations to substantiate therapeutic opportunities. We examined the effect of AT-101, radiation and the combination on apoptosis induction and clonogenic survival in two HNSCC cell lines that express the target proteins. Apoptosis was assessed by bis-benzimide staining to detect morphological nuclear changes and/or by propidium iodide staining and flow-cytometry analysis to quantify sub-diploid apoptotic nuclei. The type of interaction between AT-101 and radiation was evaluated by calculating the Combination Index (CI) and by performing isobolographic analysis. For the pharmacokinetic analysis, plasma AT-101 levels were measured by HPLC in blood samples collected from patients enrolled in our clinical phase I/II study. These patients with locally advanced HNSCC were treated with standard cisplatin-based chemoradiotherapy and received dose-escalating oral AT-101 in a 2-weeks daily schedule every 3 weeks. In vitro results showed that AT-101 enhances radiation-induced apoptosis with CI’s below 1.0, indicating synergy. This effect was sequence-dependent. Clonogenic survival assays demonstrated a radiosensitizing effect with a DEF37 of 1.3 at sub-apoptotic concentrations of AT-101. Pharmacokinetic analysis

  10. CK19、Galectin-3在甲状腺良恶性肿瘤中的表达及其临床意义%The Expression of CK19,Galectin-3 in Benign and Malignant Thyroid Tumor and Its Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    杜岗; 马艳波

    2014-01-01

    目的:检测细胞角蛋白-19(CK19)、半乳糖凝集素-3(Galectin-3)在甲状腺良恶性肿瘤中的表达情况,探讨其在鉴别诊断甲状腺良恶性肿瘤中的临床意义。方法:收集2012年1月-2013年12月在山西医科大学第一附属医院行手术切除并且经病理证实的80例甲状腺肿瘤组织标本,包括40例甲状腺癌手术标本、40例甲状腺瘤手术标本,采用免疫组化技术检测CK19、Galectin-3在甲状腺良恶性肿瘤中的表达情况,实验结果根据阳性细胞的百分率和染色强度进行评价,两组间样本率的比较用独立样本字2检验(检验水准α=0.0167),应用灵敏度、特异度及诊断符合率评价CK19、Galectin-3在鉴别诊断甲状腺良恶性肿瘤中的价值。结果:CK19在甲状腺癌和甲状腺瘤中的阳性率分别为100%(40/40)、37.50%(15/40),差异具有统计学意义(P<0.001),CK19在鉴别诊断甲状腺良恶性肿瘤中的评价结果显示:灵敏度为100%、特异度为62.50%、诊断符合率为81.25%;Galectin-3在甲状腺癌和甲状腺瘤中的阳性率分别为80.00%(32/40)、25.00%(10/40),差异具有统计学意义(P<0.001),Galectin-3在鉴别诊断甲状腺良恶性肿瘤中的评价结果显示:灵敏度为80.00%、特异度为75.00%、诊断符合率为77.50%。结论:CK19、Galectin-3在甲状腺癌中的阳性表达明显增强,可作为鉴别诊断甲状腺良恶性肿瘤的重要辅助指标,联合检测可提高甲状腺癌的诊断率。%Objective:To detect the expression of CK19,Galectin-3 in benign and malignant thyroid tumor,and to investigate the clinical significance in the differential diagnosis of benign and malignant thyroid tumor.Method:80 cases of thyroid tumor tissue specimens between January 2012 to December 2013 were collected from the first affiliated hospital of Shanxi Medical University.All specimens had been proved by pathology,including 40 cases of

  11. Inhibition of Advanced Glycation and Absence of Galectin-3 Prevent Blood-Retinal Barrier Dysfunction during Short-Term Diabetes

    Directory of Open Access Journals (Sweden)

    Paul Canning

    2007-01-01

    Full Text Available Breakdown of the inner blood-retinal barrier (iBRB occurs early in diabetes and is central to the development of sight-threatening diabetic macular edema (DME as retinopathy progresses. In the current study, we examined how advanced glycation end products (AGEs forming early in diabetes could modulate vasopermeability factor expression in the diabetic retina and alter inter-endothelial cell tight junction (TJ integrity leading to iBRB dysfunction. We also investigated the potential for an AGE inhibitor to prevent this acute pathology and examined a role of the AGE-binding protein galectin-3 (Gal-3 in AGE-mediated cell retinal pathophysiology. Diabetes was induced in C57/BL6 wild-type (WT mice and in Gal-3−/− transgenic mice. Blood glucose was monitored and AGE levels were quantified by ELISA and immunohistochemistry. The diabetic groups were subdivided, and one group was treated with the AGE-inhibitor pyridoxamine (PM while separate groups of WT and Gal-3−/− mice were maintained as nondiabetic controls. iBRB integrity was assessed by Evans blue assay alongside visualisation of TJ protein complexes via occludin-1 immunolocalization in retinal flat mounts. Retinal expression levels of the vasopermeability factor VEGF were quantified using real-time RT-PCR and ELISA. WT diabetic mice showed significant AGE -immunoreactivity in the retinal microvasculature and also showed significant iBRB breakdown (P<.005. These diabetics had higher VEGF mRNA and protein expression in comparison to controls (P<.01. PM-treated diabetics had normal iBRB function and significantly reduced diabetes-mediated VEGF expression. Diabetic retinal vessels showed disrupted TJ integrity when compared to controls, while PM-treated diabetics demonstrated near-normal configuration. Gal-3−/− mice showed significantly less diabetes-mediated iBRB dysfunction, junctional disruption, and VEGF expression changes than their WT counterparts. The data suggests an AGE

  12. Kaurene diterpene induces apoptosis in U87 human malignant glioblastoma cells by suppression of anti-apoptotic signals and activation of cysteine proteases

    Energy Technology Data Exchange (ETDEWEB)

    Lizarte, F.S. Neto; Tirapelli, D.P.C. [Universidade de São Paulo, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Ambrosio, S.R. [Universidade de Franca, Núcleo de Pesquisa em Ciências e Tecnologia, Franca, SP (Brazil); Tirapelli, C.R. [Universidade de São Paulo, Laboratório de Farmacologia, Departamento de Enfermagem Psiquiátrica e Ciências Humanas, Escola de Enfermagem de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Oliveira, F.M. [Universidade de São Paulo, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Novais, P.C. [Universidade de São Paulo, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Peria, F.M.; Oliveira, H.F. [Universidade de São Paulo, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Carlotti, C.G. Junior; Tirapelli, L.F. [Universidade de São Paulo, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP (Brazil)

    2013-01-11

    Gliomas are the most common and malignant primary brain tumors in humans. Studies have shown that classes of kaurene diterpene have anti-tumor activity related to their ability to induce apoptosis. We investigated the response of the human glioblastoma cell line U87 to treatment with ent-kaur-16-en-19-oic acid (kaurenoic acid, KA). We analyzed cell survival and the induction of apoptosis using flow cytometry and annexin V staining. Additionally, the expression of anti-apoptotic (c-FLIP and miR-21) and apoptotic (Fas, caspase-3 and caspase-8) genes was analyzed by relative quantification (real-time PCR) of mRNA levels in U87 cells that were either untreated or treated with KA (30, 50, or 70 µM) for 24, 48, and 72 h. U87 cells treated with KA demonstrated reduced viability, and an increase in annexin V- and annexin V/PI-positive cells was observed. The percentage of apoptotic cells was 9% for control cells, 26% for cells submitted to 48 h of treatment with 50 µM KA, and 31% for cells submitted to 48 h of treatment with 70 µM KA. Similarly, in U87 cells treated with KA for 48 h, we observed an increase in the expression of apoptotic genes (caspase-8, -3) and a decrease in the expression of anti-apoptotic genes (miR-21 and c-FLIP). KA possesses several interesting properties and induces apoptosis through a unique mechanism. Further experiments will be necessary to determine if KA may be used as a lead compound for the development of new chemotherapeutic drugs for the treatment of primary brain tumors.

  13. Anti-apoptotic activity of caffeic acid, ellagic acid and ferulic acid in normal human peripheral blood mononuclear cells: a Bcl-2 independent mechanism.

    Science.gov (United States)

    Khanduja, Krishan Lal; Avti, Pramod Kumar; Kumar, Surender; Mittal, Nidhi; Sohi, Kiranjit Kaur; Pathak, Chander Mohan

    2006-02-01

    Polyphenols have been shown to induce apoptosis in a variety of tumor cells including leukemia both in vitro and in vivo. However, their action on normal human peripheral blood mononuclear cells (PBMCs) during oxidative stress remains to be explored. In this study, we have evaluated the anti-apoptotic and radical scavenging activities of dietary phenolics, namely caffeic acid (CA), ellagic acid (EA) and ferulic acid (FA). H2O2-induced apoptosis in normal human PBMCs was assayed by phosphotidylserine externalization, nucleosomal damage and DNA fragmentation. Incubation of PBMCs with 5 mM H2O2 led to increased Annexin-V binding to externalized phosphatidyl serine (PS), an event of pre-apoptotic stage of the cell. Peripheral blood mononuclear cells pretreated with phenolics could resist H2O2-induced apoptotic damage. Caffeic acid (60 and 120 microM) and EA (100 and 200 microM) caused no change in externalization of PS, whereas FA (100 and 200 microM) increased externalization of PS in PBMCs treated with H2O2. The effects of phenolics were abolished to a large extent by culturing the PBMCs for 24 h after washing the phenolics from the medium. Inhibitory activities of these phenolics on lipid peroxidation were in the order of EAanti-apoptotic effect of EA, CA and FA in PBMCs seems to be through the Bcl-2 independent mechanism. PMID:16459021

  14. C-terminal clipping of chemokine CCL1/I-309 enhances CCR8-mediated intracellular calcium release and anti-apoptotic activity.

    Science.gov (United States)

    Denis, Catherine; Deiteren, Kathleen; Mortier, Anneleen; Tounsi, Amel; Fransen, Erik; Proost, Paul; Renauld, Jean-Christophe; Lambeir, Anne-Marie

    2012-01-01

    Carboxypeptidase M (CPM) targets the basic amino acids arginine and lysine present at the C-terminus of peptides or proteins. CPM is thought to be involved in inflammatory processes. This is corroborated by CPM-mediated trimming and modulation of inflammatory factors, and expression of the protease in inflammatory environments. Since the function of CPM in and beyond inflammation remains mainly undefined, the identification of natural substrates can aid in discovering the (patho)physiological role of CPM. CCL1/I-309, with its three C-terminal basic amino acids, forms a potential natural substrate for CPM. CCL1 plays a role not only in inflammation but also in apoptosis, angiogenesis and tumor biology. Enzymatic processing differently impacts the biological activity of chemokines thereby contributing to the complex regulation of the chemokine system. The aim of the present study was to investigate whether (i) CCL1/I-309 is prone to trimming by CPM, and (ii) the biological activity of CCL1 is altered after C-terminal proteolytic processing. CCL1 was identified as a novel substrate for CPM in vitro using mass spectrometry. C-terminal clipping of CCL1 augmented intracellular calcium release mediated by CCR8 but reduced the binding of CCL1 to CCR8. In line with the higher intracellular calcium release, a pronounced increase of the anti-apoptotic activity of CCL1 was observed in the BW5147 cellular model. CCR8 signaling, CCR8 binding and anti-apoptotic activity were unaffected when CPM was exposed to the carboxypeptidase inhibitor DL-2-mercaptomethyl-3-guanidino-ethylthiopropanoic acid. The results of this study suggest that CPM is a likely candidate for the regulation of biological processes relying on the CCL1-CCR8 system. PMID:22479563

  15. Mitogenic and Anti-apoptotic Effects of Insulin in En-dometrial Cancer Cells Are Phosphatidylinositol 3-ki-nase/Akt Dependent

    Institute of Scientific and Technical Information of China (English)

    Shaofang HUA; Fengxia XUE; Jing ZHAO

    2009-01-01

    Background and objective Endometrial carcinoma is the most common gynecologic malignancy in the world. Although the insulin-resistant state or hyperinsulinemia was recently suggested as a potent risk factor for endometrial carcinogenesis and progression, there is only limited supporting evidence and the mechanism is unclear. In this study, we explored the roles of phosphatidylinositol 3-k/nase (PI3K)/Akt signaling pathway in the response of a human endometrial cancer cell line, Ishikawa3-H-12 cells, to insulin.Methods The Ishikawa 3-H-12 cells were serum-starved and then stimulated by insulin at various concentrations and for different time periods. To identify the insnlin-mediated signal pathway in the cells, LY294002, a selective inhibitor of PI3K, was used. The proliferation and the apoptotic rates were determined with methyl thiazolyl tetrazolium (MTT) and flow cytometric assays, respectively.Results The insulin receptor positive Ishikawa 3-H-12 cells had enhanced proliferation upon insulin stimulation in a rinse-and time-dependent manner. The growth promoting effect of insulin was blocked when the cells were pre-incubated with LY294002 for 60 rains.Insulin was able to protect the cells from serum-starvation-induced apoptosis in a concentration-dependent manner, while the anti-apoptotic effects of insulin was reversed by adding LY294002. Treatment with insulin at 1 μM for 15 rain resulted in an increased level of activated Akt The insulin-induced Akt activation was inhibited by LY294002 in a dose-dependent manner.Conclusion Insulin activates PI3K/Akt signaling pathway and is a mitogenic and anti-apoptotic agent for Ishikewa 3-H-12 endometrial cancer cells.

  16. Kaurene diterpene induces apoptosis in U87 human malignant glioblastoma cells by suppression of anti-apoptotic signals and activation of cysteine proteases.

    Science.gov (United States)

    Lizarte Neto, F S; Tirapelli, D P C; Ambrosio, S R; Tirapelli, C R; Oliveira, F M; Novais, P C; Peria, F M; Oliveira, H F; Carlotti Junior, C G; Tirapelli, L F

    2013-01-01

    Gliomas are the most common and malignant primary brain tumors in humans. Studies have shown that classes of kaurene diterpene have anti-tumor activity related to their ability to induce apoptosis. We investigated the response of the human glioblastoma cell line U87 to treatment with ent-kaur-16-en-19-oic acid (kaurenoic acid, KA). We analyzed cell survival and the induction of apoptosis using flow cytometry and annexin V staining. Additionally, the expression of anti-apoptotic (c-FLIP and miR-21) and apoptotic (Fas, caspase-3 and caspase-8) genes was analyzed by relative quantification (real-time PCR) of mRNA levels in U87 cells that were either untreated or treated with KA (30, 50, or 70 µM) for 24, 48, and 72 h. U87 cells treated with KA demonstrated reduced viability, and an increase in annexin V- and annexin V/PI-positive cells was observed. The percentage of apoptotic cells was 9% for control cells, 26% for cells submitted to 48 h of treatment with 50 µM KA, and 31% for cells submitted to 48 h of treatment with 70 µM KA. Similarly, in U87 cells treated with KA for 48 h, we observed an increase in the expression of apoptotic genes (caspase-8, -3) and a decrease in the expression of anti-apoptotic genes (miR-21 and c-FLIP). KA possesses several interesting properties and induces apoptosis through a unique mechanism. Further experiments will be necessary to determine if KA may be used as a lead compound for the development of new chemotherapeutic drugs for the treatment of primary brain tumors.

  17. Kaurene diterpene induces apoptosis in U87 human malignant glioblastoma cells by suppression of anti-apoptotic signals and activation of cysteine proteases

    Directory of Open Access Journals (Sweden)

    F.S. Lizarte Neto

    2013-01-01

    Full Text Available Gliomas are the most common and malignant primary brain tumors in humans. Studies have shown that classes of kaurene diterpene have anti-tumor activity related to their ability to induce apoptosis. We investigated the response of the human glioblastoma cell line U87 to treatment with ent-kaur-16-en-19-oic acid (kaurenoic acid, KA. We analyzed cell survival and the induction of apoptosis using flow cytometry and annexin V staining. Additionally, the expression of anti-apoptotic (c-FLIP and miR-21 and apoptotic (Fas, caspase-3 and caspase-8 genes was analyzed by relative quantification (real-time PCR of mRNA levels in U87 cells that were either untreated or treated with KA (30, 50, or 70 µM for 24, 48, and 72 h. U87 cells treated with KA demonstrated reduced viability, and an increase in annexin V- and annexin V/PI-positive cells was observed. The percentage of apoptotic cells was 9% for control cells, 26% for cells submitted to 48 h of treatment with 50 µM KA, and 31% for cells submitted to 48 h of treatment with 70 µM KA. Similarly, in U87 cells treated with KA for 48 h, we observed an increase in the expression of apoptotic genes (caspase-8, -3 and a decrease in the expression of anti-apoptotic genes (miR-21 and c-FLIP. KA possesses several interesting properties and induces apoptosis through a unique mechanism. Further experiments will be necessary to determine if KA may be used as a lead compound for the development of new chemotherapeutic drugs for the treatment of primary brain tumors.

  18. Expression of Pokemon and Galectin-3 proteins in gastric carcinoma tissue%胃癌组织中Pokemon和半乳糖凝集素-3蛋白的表达

    Institute of Scientific and Technical Information of China (English)

    李志猛; 乔军波; 张谢夫; 赵春临

    2010-01-01

    目的:检测胃癌组织中Pokemon和半乳糖凝集素-3(Galectin-3)蛋白的表达情况.方法:采用免疫组织化学SP法检测76例胃癌组织和16例正常胃黏膜组织中Pokemon和Galectin-3的表达,并分析其与临床病理特征的关系.结果:胃癌组织中Pokemon蛋白阳性表达率为59.2%(45/76),Galectin-3蛋白阳性表达率为82.9%(63/76),均高于正常胃黏膜组织的18.8%(3/16)和12.5%(2/16)(χ2=8.671,P=0.003;χ2=28.284,P<0.001).胃癌组织中Pokemon与Galectin-3的阳性表达与淋巴结转移(χ2分别为10.787和11.626,P均=0.001)、pTNM分期(χ2=12.903,P<0.0010;χ2=6.435,P=0.011)和浸润深度(χ2分别为11.849和11.701,P均=0.003)有关,且Pokemon与Galectin-3表达有关联(χ2=5.253,rP=0.254,P=0.022).结论:Pokemon及Galectin-3与胃癌的侵袭、转移有关.

  19. c-Myc dependent expression of pro-apoptotic Bim renders HER2-overexpressing breast cancer cells dependent on anti-apoptotic Mcl-1

    Directory of Open Access Journals (Sweden)

    Jézéquel Pascal

    2011-09-01

    Full Text Available Abstract Background Anti-apoptotic signals induced downstream of HER2 are known to contribute to the resistance to current treatments of breast cancer cells that overexpress this member of the EGFR family. Whether or not some of these signals are also involved in tumor maintenance by counteracting constitutive death signals is much less understood. To address this, we investigated what role anti- and pro-apoptotic Bcl-2 family members, key regulators of cancer cell survival, might play in the viability of HER2 overexpressing breast cancer cells. Methods We used cell lines as an in vitro model of HER2-overexpressing cells in order to evaluate how anti-apoptotic Bcl-2, Bcl-xL and Mcl-1, and pro-apoptotic Puma and Bim impact on their survival, and to investigate how the constitutive expression of these proteins is regulated. Expression of the proteins of interest was confirmed using lysates from HER2-overexpressing tumors and through analysis of publicly available RNA expression data. Results We show that the depletion of Mcl-1 is sufficient to induce apoptosis in HER2-overexpressing breast cancer cells. This Mcl-1 dependence is due to Bim expression and it directly results from oncogenic signaling, as depletion of the oncoprotein c-Myc, which occupies regions of the Bim promoter as evaluated in ChIP assays, decreases Bim levels and mitigates Mcl-1 dependence. Consistently, a reduction of c-Myc expression by inhibition of mTORC1 activity abrogates occupancy of the Bim promoter by c-Myc, decreases Bim expression and promotes tolerance to Mcl-1 depletion. Western blot analysis confirms that naïve HER2-overexpressing tumors constitutively express detectable levels of Mcl-1 and Bim, while expression data hint on enrichment for Mcl-1 transcripts in these tumors. Conclusions This work establishes that, in HER2-overexpressing tumors, it is necessary, and maybe sufficient, to therapeutically impact on the Mcl-1/Bim balance for efficient induction of

  20. Increased ratio of anti-apoptotic to pro-apoptotic Bcl2 gene-family members in lithium-responders one month after treatment initiation

    Directory of Open Access Journals (Sweden)

    Lowthert Lori

    2012-09-01

    Full Text Available Abstract Background Lithium is considered by many as the gold standard medication in the management of bipolar disorder (BD. However, the clinical response to lithium is heterogeneous, and the molecular basis for this difference in response is unknown. In the present study, we sought to determine how the peripheral blood gene expression profiles of patients with bipolar disorder (BD changed over time following intitiation of treatment with lithium, and whether differences in those profiles over time were related to the clinical response. Methods Illumina Sentrix Beadchip (Human-6v2 microarrays containing > 48,000 transcript probes were used to measure levels of expression of gene-expression in peripheral blood from 20 depressed subjects with BD prior to and every two weeks during 8 weeks of open-label treatment with lithium. Changes in gene-expression were compared between treatment responders (defined as a decrease in the Hamilton Depression Rating Scale of 50% or more and non-responders. Pathway analysis was conducted using GeneGO Metacore software. Results 127 genes showed a differential response in responders vs. non-responders. Pathway analysis showed that regulation of apoptosis was the most significantly affected pathway among these genes. Closer examination of the time-course of changes among BCL2 related genes showed that in lithium-responders, one month after starting treatment with lithium, several anti-apoptotic genes including Bcl2 and insulin receptor substrate 2 (IRS2 were up-regulated, while pro-apoptotic genes, including BCL2-antagonist/killer 1 (BAK1 and BCL2-associated agonist of cell death (BAD, were down-regulated. In contrast, in lithium non-responders, BCL2 and IRS2 were down-regulated, while BAK1 and BAD up-regulated at the one-month time-point. Conclusions These results suggest that differential changes in the balance of pro- and anti- apoptotic gene-expression following treatment with lithium may explain some of

  1. Interaction of a putative BH3 domain of clusterin with anti-apoptotic Bcl-2 family proteins as revealed by NMR spectroscopy

    International Nuclear Information System (INIS)

    Highlights: → Identification of a conserved BH3 motif in C-terminal coiled coil region of nCLU. → The nCLU BH3 domain binds to BH3 peptide-binding grooves in both Bcl-XL and Bcl-2. → A conserved binding mechanism of nCLU BH3 and the other pro-apoptotic BH3 peptides with Bcl-XL. → The absolutely conserved Leu323 and Asp328 of nCLU BH3 domain are critical for binding to Bcl-XL. → Molecular understanding of the pro-apoptotic function of nCLU as a novel BH3-only protein. -- Abstract: Clusterin (CLU) is a multifunctional glycoprotein that is overexpressed in prostate and breast cancers. Although CLU is known to be involved in the regulation of apoptosis and cell survival, the precise molecular mechanism underlying the pro-apoptotic function of nuclear CLU (nCLU) remains unclear. In this study, we identified a conserved BH3 motif in C-terminal coiled coil (CC2) region of nCLU by sequence analysis and characterized the molecular interaction of the putative nCLU BH3 domain with anti-apoptotic Bcl-2 family proteins by nuclear magnetic resonance (NMR) spectroscopy. The chemical shift perturbation data demonstrated that the nCLU BH3 domain binds to pro-apoptotic BH3 peptide-binding grooves in both Bcl-XL and Bcl-2. A structural model of the Bcl-XL/nCLU BH3 peptide complex reveals that the binding mode is remarkably similar to those of other Bcl-XL/BH3 peptide complexes. In addition, mutational analysis confirmed that Leu323 and Asp328 of nCLU BH3 domain, absolutely conserved in the BH3 motifs of BH3-only protein family, are critical for binding to Bcl-XL. Taken altogether, our results suggest a molecular basis for the pro-apoptotic function of nCLU by elucidating the residue specific interactions of the BH3 motif in nCLU with anti-apoptotic Bcl-2 family proteins.

  2. Interaction of a putative BH3 domain of clusterin with anti-apoptotic Bcl-2 family proteins as revealed by NMR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong-Hwa; Ha, Ji-Hyang [Medical Proteomics Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Kim, Yul [Department of Bio and Brain Engineering, KAIST, Daejeon 305-701 (Korea, Republic of); Bae, Kwang-Hee [Medical Proteomics Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Park, Jae-Yong [Department of Physiology, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660-751 (Korea, Republic of); Choi, Wan Sung [Department of Anatomy and Neurobiology, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju, Gyeongnam 660-751 (Korea, Republic of); Yoon, Ho Sup [Division of Structural and Computational Biology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637511 (Singapore); Park, Sung Goo; Park, Byoung Chul [Medical Proteomics Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Yi, Gwan-Su, E-mail: gsyi@kaist.ac.kr [Department of Bio and Brain Engineering, KAIST, Daejeon 305-701 (Korea, Republic of); Chi, Seung-Wook, E-mail: swchi@kribb.re.kr [Medical Proteomics Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of)

    2011-05-20

    Highlights: {yields} Identification of a conserved BH3 motif in C-terminal coiled coil region of nCLU. {yields} The nCLU BH3 domain binds to BH3 peptide-binding grooves in both Bcl-X{sub L} and Bcl-2. {yields} A conserved binding mechanism of nCLU BH3 and the other pro-apoptotic BH3 peptides with Bcl-X{sub L}. {yields} The absolutely conserved Leu323 and Asp328 of nCLU BH3 domain are critical for binding to Bcl-X{sub L.} {yields} Molecular understanding of the pro-apoptotic function of nCLU as a novel BH3-only protein. -- Abstract: Clusterin (CLU) is a multifunctional glycoprotein that is overexpressed in prostate and breast cancers. Although CLU is known to be involved in the regulation of apoptosis and cell survival, the precise molecular mechanism underlying the pro-apoptotic function of nuclear CLU (nCLU) remains unclear. In this study, we identified a conserved BH3 motif in C-terminal coiled coil (CC2) region of nCLU by sequence analysis and characterized the molecular interaction of the putative nCLU BH3 domain with anti-apoptotic Bcl-2 family proteins by nuclear magnetic resonance (NMR) spectroscopy. The chemical shift perturbation data demonstrated that the nCLU BH3 domain binds to pro-apoptotic BH3 peptide-binding grooves in both Bcl-X{sub L} and Bcl-2. A structural model of the Bcl-X{sub L}/nCLU BH3 peptide complex reveals that the binding mode is remarkably similar to those of other Bcl-X{sub L}/BH3 peptide complexes. In addition, mutational analysis confirmed that Leu323 and Asp328 of nCLU BH3 domain, absolutely conserved in the BH3 motifs of BH3-only protein family, are critical for binding to Bcl-X{sub L}. Taken altogether, our results suggest a molecular basis for the pro-apoptotic function of nCLU by elucidating the residue specific interactions of the BH3 motif in nCLU with anti-apoptotic Bcl-2 family proteins.

  3. CK19、Galectin-3和HBME-1在甲状腺乳头状癌中的表达及意义%Expression and significance of detecting cytokeratin 19, galectin-3, HBME-1 in papillary thyroid carcinoma

    Institute of Scientific and Technical Information of China (English)

    顾春燕; 肖锋; 钱金锋; 孙艳; 刘宏斌

    2011-01-01

    Objective To investigate the expression and significance of detecting cytokeratin 19 (CK19), galectirr3, HBME-1 in the diagnosis of papillary thyroid carcinoma (PTC). Methods Immunohistochemical staining was performed in 44 PTC samples, 27 nodular goiter with papillary hyperplasia samples (NGWPH) and 40 follicular adenoma with papillary hyperplasia samples (FAWPH). Results The expressions of CK19, galectin-3 and HBME-1 were 100%,97.7% and 95. 5% in PTC,which were higher than 11.1%,7.4% and 3.7% in NGWPH and 12. 5%,2. 5% and 10. 0% in FAWPH, respectively(P<0. 01). The expression rate of one case with two or more positive markers in PTC was 97.7%,which was higher than 11.1% in NGWPH and 7.5% in FAWPH (P<0.01). Conclusion Detecting the expressions of CK19, galectin-3 and HBME-1, especially combined examinations, is valuable in differential diagnosis of thyroid lesions.%目的 探讨细胞角蛋白19(CK19)、Galectin-3和HBME-1在甲状腺乳头状癌(PTC)和乳头状增生性甲状腺疾病鉴别诊断中的作用.方法 应用免疫组织化学方法检测了44例PTC、27例结节性甲状腺肿伴乳头状增生(NGWPH)和40例甲状腺腺瘤伴乳头状增生(FAWPH)中单克隆抗体CK19、Galectin-3和HBME-1的表达.结果 CK19、Galectin-3和HBME-1在PTC中的阳性表达率分别为100%、97.7%和95.5%,均明显高于NGWPH中的11.1%、7.4%和3.7%,或FAWPH中的12.5%、2.5%和10.0%(P<0.01).同一病例有两种以上阳性表达在PTC为97.7%,明显高于NGWPH和FAWPH的11.1%和7.5%(P<0.01).结论 CK19、Galectin-3和HBME-1的检测,尤其是联合检测,对甲状腺良、恶性病变的诊断及鉴别诊断具有较高的临床使用价值.

  4. Plasma levels of galectin-3-binding protein reflect type I interferon activity and are increased in patients with systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Nielsen, Christoffer T; Lood, Christian; Østergaard, Ole;

    2014-01-01

    OBJECTIVE: Simple measures of type I interferon (IFN) activity constitute highly attractive biomarkers in systemic lupus erythematosus (SLE). We explore galectin-3-binding protein (G3BP) as a novel measure of type I IFN activity and serum/plasma biomarker in large independent cohorts of patients......-Denmark (DK) (n=70) and SLE-Sweden (SE) (n=68) cohorts were compared with the HC-DK (n=47) and HC-SE (n=50) cohorts and patients with systemic sclerosis (n=111). In 15 patients with SLE, serum G3BP in consecutive samples was correlated to disease activity. Correlation analysis between G3BP, clinical......-DK and SLE-SE cohorts compared with HCs and patients with systemic sclerosis (p

  5. Peptides derived from human galectin-3 N-terminal tail interact with its carbohydrate recognition domain in a phosphorylation-dependent manner

    International Nuclear Information System (INIS)

    Highlights: •Galectin-3 is composed of a carbohydrate recognition domain and an N-terminal tail. •Synthetic peptides derived from the tail are shown to interact with the CRD. •This interaction is modulated by Ser- and Tyr-phosphorylation of the peptides. -- Abstract: Galectin-3 (Gal-3) is a multi-functional effector protein that functions in the cytoplasm and the nucleus, as well as extracellularly following non-classical secretion. Structurally, Gal-3 is unique among galectins with its carbohydrate recognition domain (CRD) attached to a rather long N-terminal tail composed mostly of collagen-like repeats (nine in the human protein) and terminating in a short non-collagenous terminal peptide sequence unique in this lectin family and not yet fully explored. Although several Ser and Tyr sites within the N-terminal tail can be phosphorylated, the physiological significance of this post-translational modification remains unclear. Here, we used a series of synthetic (phospho)peptides derived from the tail to assess phosphorylation-mediated interactions with 15N-labeled Gal-3 CRD. HSQC-derived chemical shift perturbations revealed selective interactions at the backface of the CRD that were attenuated by phosphorylation of Tyr 107 and Tyr 118, while phosphorylation of Ser 6 and Ser 12 was essential. Controls with sequence scrambling underscored inherent specificity. Our studies shed light on how phosphorylation of the N-terminal tail may impact on Gal-3 function and prompt further studies using phosphorylated full-length protein

  6. Peptides derived from human galectin-3 N-terminal tail interact with its carbohydrate recognition domain in a phosphorylation-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Berbís, M. Álvaro [Chemical and Physical Biology Department, Centro de Investigaciones Biológicas, CSIC, 28040 Madrid (Spain); André, Sabine [Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians University, 80539 Munich (Germany); Cañada, F. Javier [Chemical and Physical Biology Department, Centro de Investigaciones Biológicas, CSIC, 28040 Madrid (Spain); Pipkorn, Rüdiger [Central Peptide Synthesis Unit, German Cancer Research Center, 69120 Heidelberg (Germany); Ippel, Hans [Department of Biochemistry, CARIM, University of Maastricht, Maastricht (Netherlands); Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455 (United States); Mayo, Kevin H. [Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455 (United States); Kübler, Dieter [Biomolecular Interactions, German Cancer Research Center, 69120 Heidelberg (Germany); Gabius, Hans-Joachim [Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians University, 80539 Munich (Germany); Jiménez-Barbero, Jesús, E-mail: jjbarbero@cib.csic.es [Chemical and Physical Biology Department, Centro de Investigaciones Biológicas, CSIC, 28040 Madrid (Spain)

    2014-01-03

    Highlights: •Galectin-3 is composed of a carbohydrate recognition domain and an N-terminal tail. •Synthetic peptides derived from the tail are shown to interact with the CRD. •This interaction is modulated by Ser- and Tyr-phosphorylation of the peptides. -- Abstract: Galectin-3 (Gal-3) is a multi-functional effector protein that functions in the cytoplasm and the nucleus, as well as extracellularly following non-classical secretion. Structurally, Gal-3 is unique among galectins with its carbohydrate recognition domain (CRD) attached to a rather long N-terminal tail composed mostly of collagen-like repeats (nine in the human protein) and terminating in a short non-collagenous terminal peptide sequence unique in this lectin family and not yet fully explored. Although several Ser and Tyr sites within the N-terminal tail can be phosphorylated, the physiological significance of this post-translational modification remains unclear. Here, we used a series of synthetic (phospho)peptides derived from the tail to assess phosphorylation-mediated interactions with {sup 15}N-labeled Gal-3 CRD. HSQC-derived chemical shift perturbations revealed selective interactions at the backface of the CRD that were attenuated by phosphorylation of Tyr 107 and Tyr 118, while phosphorylation of Ser 6 and Ser 12 was essential. Controls with sequence scrambling underscored inherent specificity. Our studies shed light on how phosphorylation of the N-terminal tail may impact on Gal-3 function and prompt further studies using phosphorylated full-length protein.

  7. Cribriform adenocarcinoma of minor salivary glands may express galectin-3, cytokeratin 19, and HBME-1 and contains polymorphisms of RET and H-RAS proto-oncogenes.

    Science.gov (United States)

    Laco, Jan; Kamarádová, Kateřina; Vítková, Pavla; Sehnálková, Eva; Dvořáková, Sárka; Václavíková, Eliška; Sýkorová, Vlasta; Kašpírková, Jana; Skálová, Alena; Ryška, Aleš

    2012-11-01

    The aim of the study was to further elucidate the immunohistochemical and genetic characteristics of cribriform adenocarcinoma of minor salivary glands (CAMSG). The study comprised five CAMSG from two males and three females, aged 21-72 years. Four tumors were localized at the base of tongue and one in the floor of mouth. At the time of diagnosis, four tumors had metastasised to regional lymph nodes. After tumor resection, two patients were treated by radiotherapy and one by chemoradiotherapy. During the follow-up (median 14 months), two patients developed lymph node metastasis. Microscopically, all tumors showed cribriform, papillary, follicular, and microcystic growth patterns. The tumor cells displayed vesicular nuclei with intranuclear grooves. Immunohistochemically, all tumors showed expression of cytokeratin (CK) 7, CK8, CK18, vimentin, smooth muscle actin, calponin, S-100 protein, and p16 protein. In addition, we observed expression of galectin-3, CK19, and HBME-1, but not of thyroglobulin and TTF-1. No mutations of RET, BRAF, K-RAS, H-RAS, and N-RAS proto-oncogenes were detected. However, in RET proto-oncogene, we found polymorphisms Gly691Ser (exon 11) and Ser904Ser (exon 15) in one case, p.Leu769Leu (exon 13) in one case, and variant p.IVS14-24 G/A of intron 14 in two cases, and in H-RAS proto-oncogene we found polymorphism 81 T-C (exon 1) in three cases. Thyroglobulin and TTF-1 are the only useful markers in the differential diagnosis between CAMSG and papillary thyroid carcinoma as both tumors may express galectin-3, CK19, and HBME-1. The RET, H-RAS, and N-RAS proto-oncoogenes are not mutated in CAMSG.

  8. Anti-apoptotic Activity of Ginsenoside Rb1 in Hydrogen Peroxide-treated Chondrocytes: Stabilization of Mitochondria and the Inhibition of Caspase-3.

    Science.gov (United States)

    Na, Ji-Young; Kim, Sokho; Song, Kibbeum; Lim, Kyu-Hee; Shin, Gee-Wook; Kim, Jong-Hoon; Kim, Bumseok; Kwon, Young-Bae; Kwon, Jungkee

    2012-07-01

    Chondrocyte apoptosis has been recognized as an important factor in the pathogenesis of osteoarthritis (OA). Hydrogen peroxide (H2O2), which produces reactive oxygen species, reportedly induces apoptosis in chondrocytes. The ginsenoside Rb1 (GRb1) is the principal component in ginseng and has been shown to have a variety of biological activities, such as anti-arthritis, anti-inflammation, and anti-tumor activities. In this study, we evaluated the effects of G-Rb1 on the mitochondrial permeability transition (MPT) and caspase-3 activity of chondrocyte apoptosis induced by H2O2. Cultured rat articular chondrocytes were exposed to H2O2 with or without G-Rb1 and assessed for viability, MPT, Bcl-xL/Bax expression, caspase-3 activity, and apoptosis. The co-treatment with G-Rb1 showed an inhibition of MPT, caspase-3 activity, and cell death. Additionally, the levels of the apoptotic protein Bax were significantly lower and the levels of the anti-apoptotic protein Bcl-xL were higher compared with H2O2 treatment alone. The results of this study demonstrate that G-Rb1 protects chondrocytes against H2O2-induced apoptosis, at least in part via the inhibition of MPT and caspase-3 activity. These results demonstrate that G-Rb1 is a potentially useful drug for the treatment of OA patients. PMID:23717124

  9. Biliverdin reductase/bilirubin mediates the anti-apoptotic effect of hypoxia in pulmonary arterial smooth muscle cells through ERK1/2 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Song, Shasha [Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical, University (Daqing), Daqing 163319 (China); Wang, Shuang [Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical, University (Daqing), Daqing 163319 (China); Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150081 (China); Ma, Jun; Yao, Lan; Xing, Hao; Zhang, Lei; Liao, Lin [Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical, University (Daqing), Daqing 163319 (China); Zhu, Daling, E-mail: dalingz@yahoo.com [Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical, University (Daqing), Daqing 163319 (China); Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150081 (China)

    2013-08-01

    Inhibition of pulmonary arterial smooth muscle cell (PASMC) apoptosis induced by hypoxia plays an important role in pulmonary arterial remodeling leading to aggravate hypoxic pulmonary arterial hypertension. However, the mechanisms of hypoxia acting on PASMC apoptosis remain exclusive. Biliverdin reductase (BVR) has many essential biologic roles in physiological and pathological processes. Nevertheless, it is unclear whether the hypoxia-induced inhibition on PASMC apoptosis is mediated by BVR. In the present work, we found BVR majorly localized in PASMCs and was up-regulated in levels of protein and mRNA by hypoxia. Then we studied the contribution of BVR to anti-apoptotic response of hypoxia in PASMCs. Our results showed that siBVR, blocking generation of bilirubin, reversed the effect of hypoxia on enhancing cell survival and apoptotic protein (Bcl-2, procasepase-9, procasepase-3) expression, preventing nuclear shrinkage, DNA fragmentation and mitochondrial depolarization in starved PASMCs, which were recovered by exogenous bilirubin. Moreover, the inhibitory effect of bilirubin on PASMC apoptosis under hypoxic condition was blocked by the inhibitor of ERK1/2 pathway. Taken together, our data indicate that BVR contributes to the inhibitory process of hypoxia on PASMC apoptosis, which is mediated by bilirubin through ERK1/2 pathway. Highlights: • BVR expresses in PASMC and is up-regulated by hypoxia in protein and mRNA levels. • BVR/bilirubin contribute to the inhibitive process of hypoxia on PASMC apoptosis. • Bilirubin protects PASMC from apoptosis under hypoxia via ERK1/2 pathway.

  10. Anti-apoptotic, anti-oxidant, and anti-inflammatory effects of thalidomide on cerebral ischemia/reperfusion injury in rats.

    Science.gov (United States)

    Palencia, Guadalupe; Medrano, Juan Ángel Núñez-; Ortiz-Plata, Alma; Farfán, Dolores Jiménez; Sotelo, Julio; Sánchez, Aurora; Trejo-Solís, Cristina

    2015-04-15

    Thalidomide has shown protective effects in different models of ischemia/reperfusion damage. To elucidate the mechanisms of such protection, this study assessed the effects of thalidomide on the oxidative stress and inflammatory response induced by ischemia/reperfusion episodes in rats. Rats underwent middle cerebral artery occlusion (MCAO) for 2hours. All animals were sacrificed after different reperfusion times. Rats were administered either DMSO or thalidomide (20mg/kg (i.p.)) at different times before or during reperfusion: 1) 1h before reperfusion; the infarct area was measured 2h after reperfusion. 2) 10min before reperfusion and 80min after reperfusion; the infarct area was measured 24h after reperfusion; and 3) 10min before reperfusion and 1h, 24h, 48h, and 68h after reperfusion; the infarct area was measured 72h after reperfusion. Thalidomide reduced the infarct area 24h and 72h after MCAO, and decreased the neurological deficit in all groups with respect to controls. Thalidomide also lowered significantly the number of TUNEL-positive cells, levels of Bax, caspase-3, lipoperoxidation, and pro-inflammatory cytokines, and increased the levels of SOD1, Bcl-2 and pAkt. These results show that thalidomide has neuroprotective effects, apparently due to its anti-apoptotic, anti-oxidant, and anti-inflammatory effects.

  11. Introduction of the anti-apoptotic baculovirus p35 gene in passion fruit induces herbicide tolerance, reduced bacterial lesions, but does not inhibits passion fruit woodiness disease progress induced by cowpea aphid-borne mosaic virus (CABMV).

    Science.gov (United States)

    de Freitas, Daniele Scandiucci; Coelho, Marly C Felipe; Souza, Manoel T; Marques, Abi; Ribeiro, E Bergmann Morais

    2007-01-01

    The introduction of anti-apoptotic genes into plants leads to resistance to environmental stress and broad-spectrum disease resistance. The anti-apoptotic gene (p35) from a baculovirus was introduced into the genome of passion fruit plants by biobalistics. Eleven regenerated plants showed the presence of the p35 gene by PCR and/or dot blot hybridization. Transcriptional analysis of regenerated plants showed the presence of specific p35 transcripts in 9 of them. Regenerated plants containing the p35 gene were inoculated with the cowpea aphid-borne mosaic virus (CABMV), the bacterium Xanthomonas axonopodis pv passiflorae, and the herbicide, glufosinate, (Syngenta). None of the plants showed resistance to CABMV. Regenerated plants (p35+) showed less than half of local lesions showed by non-transgenic plants when inoculated with X. axonopodis and some p35+ plants showed increased tolerance to the glufosinate herbicide when compared to non-transgenic plants. PMID:17016672

  12. 探讨抗体标记物MC联合应用CK19,TPO,Galectin-3,KI-67在甲状腺乳头状病变中应用%Discuss application of antibody marker MC combining with CK19, TPO, Galectin-3, KI-67 in thyroid papillary lesions

    Institute of Scientific and Technical Information of China (English)

    朱春良; 帅剑波; 邵庆庆; 胡广明

    2015-01-01

    ABSTRACT:Objective through application of antibody marker MC combining with CK19, TPO, Galectin-3, KI-67 in expression status of thyroid papillary lesions, to find out the best combination of thyroid papillary carcinoma antibodies. Method Review and analyze expression of MC CK19, TPO, KI-67, Galectin-3 and MC of 96 cases papillary thyroid lesion with immunohistochemistry during Feb, 2012 and Feb, 2015. Result expression of the combination antibodies in 96 cases papillary thyroid lesion is as follows:64 case papillary thyroid carcinoma, and positive expression is respectively 10%(7/64), 96.9%(62/64 cases), 7.8%(5 cases weak positive), 100%(64/64), 62.5%(40/64). Thyroid papillary hyperplasia expression is as follows:9.4%(3/32 cases weak positive), 6.5%(2 cases positive), 12.5%(4/32) 22.5%(7 cases positive), 31.2%(10/32). Expression of KI-67, CK19, TPO, Galectin-3 and MC in two groups shows statistical significance (P<0.01). MC is a new marker for thyroid papillary carcinoma in recent years, and its expression in papillary thyroid carcinoma does not diffuse, and has little and weak expression in papillary hyperplasia. Conclusion MC combined with CK19, TPO, Galectin-3 and KI-67 in diagnosis of benign and malignant thyroid papillary lesion further provides reliable evidence, which is one of the better referential antibodies for diagnosis of thyroid papillary carcinoma.%目的:通过联合应用MC、CK19、TPO、Galectin-3、KI-67在甲状腺乳头状病变中表达情况,寻求找到甲状腺乳头状癌的抗体的最佳组合。方法回顾分析我院2012年2月至2015年2月期间96例甲状腺乳头状病变行免疫组化对MC、CK19、TPO、Galectin-3、KI-67表达。结果该组联合抗体在96例甲状腺乳头状病变中表达如下:甲状腺乳头状癌64例,阳性表达分别为:10%(7/64),96.9%(62/64例)、7.8%(5例弱阳性),100%(64/64)、62.5%(40/64)。甲状腺乳头状增生表达如下:9.4%(3/32例弱阳性),6.5%

  13. Human Noxin is an anti-apoptotic protein in response to DNA damage of A549 non-small cell lung carcinoma.

    Science.gov (United States)

    Won, Kyoung-Jae; Im, Joo-Young; Yun, Chae-Ok; Chung, Kyung-Sook; Kim, Young Joo; Lee, Jung-Sun; Jung, Young-Jin; Kim, Bo-Kyung; Song, Kyung Bin; Kim, Young-Ho; Chun, Ho-Kyung; Jung, Kyeong Eun; Kim, Moon-Hee; Won, Misun

    2014-06-01

    Human Noxin (hNoxin, C11Orf82), a homolog of mouse noxin, is highly expressed in colorectal and lung cancer tissues. hNoxin contains a DNA-binding C-domain in RPA1, which mediates DNA metabolic processes, such as DNA replication and DNA repair. Expression of hNoxin is associated with S phase in cancer cells and in normal cells. Expression of hNoxin was induced by ultraviolet (UV) irradiation. Knockdown of hNoxin caused growth inhibition of colorectal and lung cancer cells. The comet assay and western blot analysis revealed that hNoxin knockdown induced apoptosis through activation of p38 mitogen-activated protein kinase (MAPK)/p53 in non-small cell lung carcinoma A549 cells. Furthermore, simultaneous hNoxin knockdown and treatment with DNA-damaging agents, such as camptothecin (CPT) and UV irradiation, enhanced apoptosis, whereas Trichostatin A (TSA) did not. However, transient overexpression of hNoxin rescued cells from DNA damage-induced apoptosis but did not block apoptosis in the absence of DNA damage. These results suggest that hNoxin may be associated with inhibition of apoptosis in response to DNA damage. An adenovirus expressing a short hairpin RNA against hNoxin transcripts significantly suppressed the growth of A549 tumor xenografts, indicating that hNoxin knockdown has in vivo anti-tumor efficacy. Thus, hNoxin is a DNA damage-induced anti-apoptotic protein and potential therapeutic target in cancer.

  14. Systems modeling of anti-apoptotic pathways in prostate cancer: psychological stress triggers a synergism pattern switch in drug combination therapy.

    Directory of Open Access Journals (Sweden)

    Xiaoqiang Sun

    Full Text Available Prostate cancer patients often have increased levels of psychological stress or anxiety, but the molecular mechanisms underlying the interaction between psychological stress and prostate cancer as well as therapy resistance have been rarely studied and remain poorly understood. Recent reports show that stress inhibits apoptosis in prostate cancer cells via epinephrine/beta2 adrenergic receptor/PKA/BAD pathway. In this study, we used experimental data on the signaling pathways that control BAD phosphorylation to build a dynamic network model of apoptosis regulation in prostate cancer cells. We then compared the predictive power of two different models with or without the role of Mcl-1, which justified the role of Mcl-1 stabilization in anti-apoptotic effects of emotional stress. Based on the selected model, we examined and quantitatively evaluated the induction of apoptosis by drug combination therapies. We predicted that the combination of PI3K inhibitor LY294002 and inhibition of BAD phosphorylation at S112 would produce the best synergistic effect among 8 interventions examined. Experimental validation confirmed the effectiveness of our predictive model. Moreover, we found that epinephrine signaling changes the synergism pattern and decreases efficacy of combination therapy. The molecular mechanisms responsible for therapeutic resistance and the switch in synergism were explored by analyzing a network model of signaling pathways affected by psychological stress. These results provide insights into the mechanisms of psychological stress signaling in therapy-resistant cancer, and indicate the potential benefit of reducing psychological stress in designing more effective therapies for prostate cancer patients.

  15. Anti-Apoptotic Effects of 3,3',5-Triiodo-L-Thyronine in the Liver of Brain-Dead Rats.

    Directory of Open Access Journals (Sweden)

    Rolando A Rebolledo

    Full Text Available Thyroid hormone treatment in brain-dead organ donors has been extensively studied and applied in the clinical setting. However, its clinical applicability remains controversial due to a varying degree of success and a lack of mechanistic understanding about the therapeutic effects of 3,3',5-Triiodo-L-thyronine (T3. T3 pre-conditioning leads to anti-apoptotic and pro-mitotic effects in liver tissue following ischemia/reperfusion injury. Therefore, we aimed to study the effects of T3 pre-conditioning in the liver of brain-dead rats.Brain death (BD was induced in mechanically ventilated rats by inflation of a Fogarty catheter in the epidural space. T3 (0.1 mg/kg or vehicle was administered intraperitoneally 2 h prior to BD induction. After 4 h of BD, serum and liver tissue were collected. RT-qPCR, routine biochemistry, and immunohistochemistry were performed.Brain-dead animals treated with T3 had lower plasma levels of AST and ALT, reduced Bax gene expression, and less hepatic cleaved Caspase-3 activation compared to brain-dead animals treated with vehicle. Interestingly, no differences in the expression of inflammatory genes (IL-6, MCP-1, IL-1β or the presence of pro-mitotic markers (Cyclin-D and Ki-67 were found in brain-dead animals treated with T3 compared to vehicle-treated animals.T3 pre-conditioning leads to beneficial effects in the liver of brain-dead rats as seen by lower cellular injury and reduced apoptosis, and supports the suggested role of T3 hormone therapy in the management of brain-dead donors.

  16. Anti-Apoptotic and Pro-Survival Effect of Alpinate Oxyphyllae Fructus (AOF in a d-Galactose-Induced Aging Heart

    Directory of Open Access Journals (Sweden)

    Yung-Ming Chang

    2016-03-01

    Full Text Available Aging, a natural biological/physiological phenomenon, is accelerated by reactive oxygen species (ROS accumulation and identified by a progressive decrease in physiological function. Several studies have shown a positive relationship between aging and chronic heart failure (HF. Cardiac apoptosis was found in age-related diseases. We used a traditional Chinese medicine, Alpinate Oxyphyllae Fructus (AOF, to evaluate its effect on cardiac anti-apoptosis and pro-survival. Male eight-week-old Sprague–Dawley (SD rats were segregated into five groups: normal control group (NC, d-Galactose-Induced aging group (Aging, and AOF of 50 (AL (AOF low, 100 (AM (AOF medium, 150 (AH (AOF high mg/kg/day. After eight weeks, hearts were measured by an Hematoxylin–Eosin (H&E stain, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL-assays and Western blotting. The experimental results show that the cardiomyocyte apoptotic pathway protein expression increased in the d-Galactose-Induced aging groups, with dose-dependent inhibition in the AOF treatment group (AL, AM, and AH. Moreover, the expression of the pro-survival p-Akt (protein kinase B (Akt, Bcl-2 (B-cell lymphoma 2, anti-apoptotic protein (Bcl-xL protein decreased significantly in the d-Galactose-induced aging group, with increased performance in the AOF treatment group with levels of p-IGFIR and p-PI3K (Phosphatidylinositol-3′ kinase (PI3K to increase by dosage and compensatory performance. On the other hand, the protein of the Sirtuin 1 (SIRT1 pathway expression decreased in the aging groups and showed improvement in the AOF treatment group. Our results suggest that AOF strongly works against ROS-induced aging heart problems.

  17. Galectin-3 immunostaining in thyroid neoplasms Imunomarcação por galectina-3 em neoplasias de tireóide

    Directory of Open Access Journals (Sweden)

    Marcos Emanuel de Alcântara Segura

    2005-10-01

    Full Text Available Although fine-needle aspiration biopsy (FNAB of the thyroid gland is the most important presurgical proceeding in defining the malignancy of a nodular lesion, it has limitations such as shared cytological morphology between malignant and benign lesions. Galectin-3, a b-galactoside-binding lectin is expressed mainly by malignant thyroid neoplasms. Fifty-seven specimens, including 14 papillary carcinomas, 22 follicular carcinomas and 21 follicular adenomas were tested for immunohistochemical staining against galectin-3. Normal thyroid adjacent to neoplastic tissue was also examined in 48 cases. All cases of papillary carcinoma were cytoplasmic stained, 18 cases of follicular carcinoma were cytoplasmic stained, and one case of follicular adenoma showed nuclear staining. No case of normal thyroid showed immunoreactivity. Sensitivity, specificity, positive predictive value and negative predictive value were respective 88%, 98%, 96%, and 94%. Galectin-3 expression is a valuable evidence of malignancy in cases where cytomorphological features are not conclusive. This immunomediated method could increase diagnosis accuracy for FNAB, thus making surgery indication more precise.A punção aspirativa por agulha fina de tireóide é o método pré-cirúrgico mais importante na definição da malignidade de uma lesão nodular. Entretanto esse procedimento apresenta limitações, como características morfológicas comuns entre neoplasias malignas e benignas. A expressão de uma lectina ligante de b-galactosídeos chamada galectina-3, aumentada em neoplasias malignas de tireóide, poderia ser utilizada como marcador de malignidade para neoplasias de tireóide. Cinqüenta e sete casos, entre eles 14 carcinomas papilares, 22 carcinomas foliculares e 21 adenomas foliculares, foram estudados quanto à expressão da galectina-3 por métodos imuno-histoquímicos. O tecido tireoidiano normal, adjacente ao tecido neoplásico, também foi avaliado em 48 casos. Todos

  18. Study on Galectin-3 Level in Patients with Rheumatoid Arthritis and Its Influential Factors%类风湿关节炎患者半乳糖凝集素-3水平及其影响因素的探讨

    Institute of Scientific and Technical Information of China (English)

    郝莉敏; 王笑夫; 张榕; 张洁文; 宋良月

    2013-01-01

    [目的]探讨类风湿关节炎(rheumatoid arthritis,RA)患者血清半乳糖凝集素-3(galectin-3)水平及其在RA疾病活动性、肺间质纤维化中的作用与相关影响因素.[方法]应用酶联免疫吸附法(ELISA)检测50例RA患者及30例正常健康对照者血清galectin-3水平,并分析其与临床相关症状及实验室有关指标的关系.[结果]RA患者血清galectin-3水平较正常对照明显升高(P<0.05),而且与红细胞沉降率(ESR)、IgA、DAS28呈正相关关系(r=0.288,r=0.314,r=0.499,P<0.05,P<0.05,P<0.05).RA患者低疾病活动组、中疾病活动组及高疾病活动组间血清galectin-3水平比较也存在统计学差异(P<0.05),此外,RA合并肺间质纤维化组患者血清galectin-3水平较非肺间质纤维化组显著升高(P<0.05).[结论]galectin-3参与了RA的发生发展,其水平的高低反映疾病的活动度,且与RA肺间质纤维化密切相关.%[Objective] To explore the serum level of galectin-3 in patients with rheumatoid arthritis(RA) and its role in the disease activity and pulmonary interstitial fibrosis of RA and the related influential factor. [Methods] Serum level of galectin-3 in 50 RA patients and 30 normal healthy controls were determined by enzyme-linked immunosorbent assay(ELISA). The relationship of galectin-3 level with clinical symptoms and laboratory indicators was analyzed. [Results] Compared with normal control group, serum level of galectin-3 in RA patients obviously increased( P<0. 05). There was positive correlation between serum galectin-3 level and ESR, IgA and DAS28(r= 0.288, r=0. 314, r=0. 499, P <0. 05, P <0. 05, P <0. 05). There were significant differences in serum galectin-3 level in RA patients among low disease activity group, moderate disease activity group and high disease activity group( P <0. 05). Moreover, serum galectin-3 level in RA patients with pulmonary interstitial fibrosis was significantly higher than that in RA patients without interstitial

  19. C linical Significance and Expression of Galectin-3 in Non-small-cell Carcinoma%半乳糖凝集素3在非小细胞肺癌中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    黄志伟

    2014-01-01

    Objective To investigate the clinical significance and expression of Galectin-3 in non-small-cell carcinoma. Method Non-small-cell carcinoma tissue, adjacent tissues and benign tumor tissue of lung were choosen, using immunohistochemical staining to detect. Results Compared to adjacent group and pulmonary benign tumor group, the expression of galectin-3 protein was in a larger extent, the diffe rence was statistically significant(P<0.01). There was a significant correlation in the expression of galectin-3 protein and histopathological types, TNM stage of non-small-cell carcinoma(P<0.01). Conclusion Over-expression of galectin-3 may be an important basis for occurrence, development, invasion and metastasis of non-small-cell carcinoma. Detecting the levels of galectin-3 can provide valuable information for in-vasion, metastasis and prognosis of non-small-cell carcinoma.%目的:探讨半乳糖凝集素3在非小细胞肺癌中的表达及临床意义。方法选择非小细胞肺癌组织、癌旁组织及肺良性肿瘤组织,采用免疫组化染色法进行检测。结果相比癌旁组和肺良性肿瘤组,非小细胞肺癌组的半乳糖凝集素3蛋白表达程度较大,差异有统计学意义(P<0.01);半乳糖凝集素3蛋白的表达同非小细胞肺癌组织的组织病理学类型、TNM分期、有无淋巴结转移之间存在显著相关性(P<0.01)。结论半乳糖凝集素3的过表达可能是非小细胞肺癌发生、发展、浸润、转移的重要基础,通过检测半乳糖凝集素3水平,可对非小细胞肺癌浸润、转移及预后提供有价值的信息。

  20. Galectin-3 cDNA Diversity in Oryctolagus cuniculus%兔半乳糖凝聚素-3 cDNA分子多样性分析

    Institute of Scientific and Technical Information of China (English)

    方恩浩; 张珊珊; 刘倩芸; 周建钟; 杨仙玉

    2015-01-01

    半乳糖凝聚素-3 (galectin-3, Gal-3)是一种多功能蛋白,参与细胞增殖、分化、凋亡、血管发生及肿瘤发生与转移等多种生命活动过程.前期工作表明一些两栖类动物存在个体水平的gal-3 cDNA分子多样性.鉴于哺乳动物尚缺乏这方面的研究,选择新西兰兔(Oryctolagus cuniculus)为实验材料,制备3只不同个体的肝脏第一链cDNA,通过DNA聚合酶链式反应扩增gal-3开放阅读框(open reading frame,ORF)并进行克隆测序.结果表明,兔gal-3 ORF中存在5个单核苷酸多态性(single nucleotide polymorphism,SNP)位点,导致11个不同的ORF,其中1个与GenBank注册的序列完全相同,另外10个均为本研究首次发现.从1~3号个体的肝脏分别获得6、6、2条不同的兔gal-3 ORF,揭示兔肝脏存在个体水平的gal-3 cDNA分子多样性.

  1. Usefulness of Combining Galectin-3 and BIVA Assessments in Predicting Short- and Long-Term Events in Patients Admitted for Acute Heart Failure

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    Benedetta De Berardinis

    2014-01-01

    Full Text Available Introduction. Acute heart failure (AHF is associated with a higher risk for the occurrence of rehospitalization and death. Galectin-3 (GAL3 is elevated in AHF patients and is an indicator in predicting short-term mortality. The total body water using bioimpedance vector analysis (BIVA is able to identify mortality within AHF patients. The aim of this study was to evaluate the short- and long-term predictive value of GAL3, BIVA, and the combination of both in AHF patients in Emergency Department (ED. Methods. 205 ED patients with AHF were evaluated by testing for B type natriuretic peptide (BNP and GAL3. The primary endpoint was death and rehospitalization at 30, 60, 90, and 180 days and 12 and 18 months. AHF patients were evaluated at the moment of ED arrival with clinical judgment and GAL3 and BIVA measurement. Results. GAL3 level was significantly higher in patients >71 years old, and with eGFR17.8 ng/mL shows significant survival difference. At multivariate Cox regression analysis GAL3 is an independent variable to predict death + rehospitalization with a value of 32.24 ng/mL at 30 days (P<0.005. Conclusion. In patients admitted for AHF an early assessment of GAL3 and BIVA seems to be useful in identifying patients at high risk for death and rehospitalization at short and long term. Combining the biomarker and the device could be of great utility since they monitor the severity of two pathophysiological different mechanisms: heart fibrosis and fluid overload.

  2. Expression of ck-19, galectin-3 and hbme-1 in the differentiation of thyroid lesions: systematic review and diagnostic meta-analysis

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    de Matos Leandro

    2012-08-01

    Full Text Available Abstract Background To distinguish between malignant and benign lesions of the thyroid gland histological demonstration is often required since the fine-needle aspiration biopsy method applied pre-operatively has some limitations. In an attempt to improve diagnostic accuracy, markers using immunocytochemistry and immunohistochemistry techniques have been studied, mainly cytokeratin-19 (CK-19, galectin-3 (Gal-3 and Hector Battifora mesothelial-1 (HBME-1. However, current results remain controversial. The aim of the present article was to establish the diagnostic accuracy of CK-19, Gal-3 and HBME-1 markers, as well as their associations, in the differentiation of malignant and benign thyroid lesions. Methods A systematic review of published articles on MEDLINE and The Cochrane Library was performed. After establishing inclusion and exclusion criteria, 66 articles were selected. The technique of meta-analysis of diagnostic accuracy was employed and global values of sensitivity, specificity, area under the summary ROC curve, and diagnostic odds ratio (dOR were calculated. Results For the immunohistochemistry technique, the positivity of CK-19 for the diagnosis of malignant thyroid lesions demonstrated global sensitivity of 81% and specificity of 73%; for Gal-3, sensitivity of 82% and specificity of 81%; and for HBME-1, sensitivity of 77% and specificity of 83%. The association of the three markers determined sensitivity of 85%, specificity of 97%, and diagnostic odds ratio of 95.1. Similar results were also found for the immunocytochemistry assay. Conclusion This meta-analysis demonstrated that the three immunomarkers studied are accurate in pre- and postoperative diagnosis of benign and malignant thyroid lesions. Nevertheless, the search for other molecular markers must continue in order to enhance this diagnostic accuracy since the results found still show a persistency of false-negative and false-positive tests. Virtual slides Http

  3. Expression changes of antioxidant, apoptotic, anti-apoptotic genes and miR-15b-34a-21-98 in over tissue by using erythromycin, quinacrine and tetracycline in non-surgical sterilization.

    Science.gov (United States)

    Kara, Murat; Yumrutas, Onder; Atilgan, Remzi; Baspinar, Melike; Sapmaz, Ekrem; Kuloglu, Tuncay

    2014-12-01

    In the present study, effects on expression of antioxidant, apoptotic and anti-apoptotic genes (GSR, GRX3, SOD1, RAI-NOS, HSP7, BAX, Bcl-2, CASP3 and MDH1) of substances being used in non-surgical sterilization such as quinacrine, erythromycin and tetracycline were evaluated in over tissue. Moreover, expression of some specific mi-RNA (miR-15b, miR-21, miR34a and miR-98) that playing a role in apoptosis was determined in same tissue. Prospective comparative experimental study. Genetics and Histology laboratory. Total number of 28 Wistar albino 12-14 week old female rats with regular cycles and 200-220 grams in weight. Total RNA was isolated from tissues by using a RNA isolation kit. Gene expression levels were evaluated by Real-Time PCR method. Tubal passage and fibrosis induction in tissues was observed in the histochemical analysis. In the statistical analysis of data Kruskal-Wallis variance analysis and Mann-Whitney U test were used and p tetracycline were significantly higher than control. Results of the present study suggest that the doses treated of quinacrine, erythromycin and tetracycline used in non-surgical sterilization effect poorly the expression of anti-oxidant, apoptotic and anti-apoptotic genes, but the expression of miR-34 playing the role in apoptosis increased after treatment of these substances. PMID:25195052

  4. Galectina-3 em tumores de próstata: imuno-histoquímica e análise digital de imagens Galectin-3 in prostatic tumours: immunohistochemistry and digital image analysis

    Directory of Open Access Journals (Sweden)

    Jorge Luiz Silva Araújo-Filho

    2006-12-01

    Full Text Available A imuno-histoquímica é uma técnica de grande ajuda no diagnóstico de doenças da próstata, incluindo os tumores. De igual importância, a análise digital de imagens vem sendo cada vez mais utilizada em estudos de alterações na próstata. O presente estudo teve como objetivo quantificar morfometricamente a expressão da galectina-3 através da imuno-histoquímica em tecidos de próstata normal (PN, hiperplasia benigna da próstata (HPB e adenocarcinoma prostático (AP. Fragmentos cirúrgicos de tecido prostático com AP (n = 10, HPB (n = 12 e PN (n = 10 foram fixados em formalina, submetidos à rotina histológica e embebidos em parafina. Foram feitos cortes histológicos (4µm montados em lâminas e corados com hematoxilina e eosina (HE para confirmar o diagnóstico. As amostras teciduais selecionadas foram incubadas com anticorpo monoclonal antigalectina-3 por uma hora em temperatura ambiente (37ºC e então incubadas com um anticorpo secundário. A revelação foi realizada após incubação com diaminobenzidina (DAB e peróxido de hidrogênio. A análise morfométrica foi realizada mediante uma estação de análise digital de imagens, que consiste num microscópio óptico acoplado a uma câmera digital ligada a um computador equipado com o software de análise OPTIMAS®. Nas células de adenocarcinoma foi observada diminuição significativa na marcação (p Immunohistochemistry helps pathologists in the diagnosis of prostatic diseases, mainly carcinomas. Equally important, digital image analysis is being increasingly used to study alterations in the prostate. The present work aims to morphometrically quantify the immunostain of galectin-3 expressed in normal prostate (NP, benign hyperplasia (BH and prostatic adenocarcinoma (PA in humans. Immunohistochemistry was developed using monoclonal anti-galectin-3 antibody. Surgical specimens from different patients with BH (n = 12, PA (n = 10 and NP (n = 10 were fixed in formalin, processed

  5. 半乳凝素-3和微小 RNA-21在非小细胞肺癌中的表达和临床意义∗%The expression level and clinical significance of Galectin-3 and miRNA-21 in non-small-cell lung carcinoma

    Institute of Scientific and Technical Information of China (English)

    易震南; 伍俊; 黄仁清; 黎东明; 张绪超

    2015-01-01

    Objective To study the expression level and clinical significance of Galectin-3 and miRNA-21 in non-small-cell lung carcinoma(NSCLC).Methods One hundred and fifty patients with NSCLC were chosen as cancer group,and 1 50 patients with benign pulmonary diseases were chosen as control group.The expression level of Galectin-3 and that of miRNA-21 between two groups were compared,and the relevance between expression level of Galectin-3 and that of miRNA-21 and clinical feature were analysed.Results In cancer group,the expression level of Galectin-3 was 6.75±2.38,and that of control group was 1.12 ±0.29;the expression level of miRNA-21 was 5.91 ± 1.59,and that of control group was 0.97 ± 0.1 7,and the difference between two groups had statistical significance(P 0.05 ).Conclusion The expression level of Galectin-3 and that of miRNA-21 can be applied in the diagnosis and prognosis of non-small-cell lung carcinoma.%目的:研究半乳凝素-3(Galectin-3)和微小 RNA-21(miRNA-21)在非小细胞肺癌(NSCLC)组织中的表达和临床意义。方法选取150例 NSCLC 患者作为肺癌组,同一时期来该院进行治疗的150例肺部良性病变患者作为对照组。比较两组患者的 Galectin-3和 miRNA-21的表达水平,分析它们与患者临床特征的相关性。结果肺癌组患者的 Galectin-3为6.75±2.38, miRNA-21为5.91±1.59;肺癌组患者的 Galectin-3为1.12±0.29,miRNA-21为0.97±0.17,差异具有统计学意义(P 0.05)。结论Ga-lectin-3和 miRNA-21的表达水平在 NSCLC 的诊断和预后判断中具有一定的应用价值。

  6. Galectin-3 Ablation Enhances Liver Steatosis, but Attenuates Inflammation and IL-33-Dependent Fibrosis in Obesogenic Mouse Model of Nonalcoholic Steatohepatitis.

    Science.gov (United States)

    Jeftic, Ilija; Jovicic, Nemanja; Pantic, Jelena; Arsenijevic, Nebojsa; Lukic, Miodrag L; Pejnovic, Nada

    2015-01-01

    The importance of Galectin-3 (Gal-3) in obesity-associated liver pathology is incompletely defined. To dissect the role of Gal-3 in fibrotic nonalcoholic steatohepatitis (NASH), Gal-3-deficient (LGALS3(-/-)) and wild-type (LGALS3(+/+)) C57Bl/6 mice were placed on an obesogenic high fat diet (HFD, 60% kcal fat) or standard chow diet for 12 and 24 wks. Compared to WT mice, HFD-fed LGALS3(-/-) mice developed, in addition to increased visceral adiposity and diabetes, marked liver steatosis, which was accompanied with higher expression of hepatic PPAR-γ, Cd36, Abca-1 and FAS. However, as opposed to LGALS3(-/-) mice, hepatocellular damage, inflammation and fibrosis were more extensive in WT mice which had an elevated number of mature myeloid dendritic cells, proinflammatory CD11b(+)Ly6C(hi) monocytes/macrophages in liver, peripheral blood and bone marrow, and increased hepatic CCL2, F4/80, CD11c, TLR4, CD14, NLRP3 inflammasome, IL-1β and NADPH-oxidase enzymes mRNA expression. Thus, obesity-driven greater steatosis was uncoupled with attenuated fibrotic NASH in Gal-3-deficient mice. HFD-fed WT mice had a higher number of hepatocytes that strongly expressed IL-33 and hepatic CD11b(+)IL-13(+) cells, increased levels of IL-33 and IL-13 and up-regulated IL-33, ST2 and IL-13 mRNA in liver compared with LGALS3(-/-) mice. IL-33 failed to induce ST2 upregulation and IL-13 production by LGALS3(-/-) peritoneal macrophages in vitro. Administration of IL-33 in vivo enhanced liver fibrosis in HFD-fed mice in both genotypes, albeit to a significantly lower extent in LGALS3(-/-) mice, which was associated with less numerous hepatic IL-13-expressing CD11b(+) cells. The present study provides evidence of a novel role for Gal-3 in regulating IL-33-dependent liver fibrosis. PMID:26018806

  7. MicroRNA-22 (miR-22 overexpression is neuroprotective via general anti-apoptotic effects and may also target specific Huntington's disease-related mechanisms.

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    Ana Jovicic

    Full Text Available BACKGROUND: Whereas many causes and mechanisms of neurodegenerative diseases have been identified, very few therapeutic strategies have emerged in parallel. One possible explanation is that successful treatment strategy may require simultaneous targeting of more than one molecule of pathway. A new therapeutic approach to have emerged recently is the engagement of microRNAs (miRNAs, which affords the opportunity to target multiple cellular pathways simultaneously using a single sequence. METHODOLOGY/PRINCIPAL FINDINGS: We identified miR-22 as a potentially neuroprotective miRNA based on its predicted regulation of several targets implicated in Huntington's disease (histone deacetylase 4 (HDAC4, REST corepresor 1 (Rcor1 and regulator of G-protein signaling 2 (Rgs2 and its diminished expression in Huntington's and Alzheimer's disease brains. We then tested the hypothesis that increasing cellular levels of miRNA-22 would achieve neuroprotection in in vitro models of neurodegeneration. As predicted, overexpression of miR-22 inhibited neurodegeneration in primary striatal and cortical cultures exposed to a mutated human huntingtin fragment (Htt171-82Q. Overexpression of miR-22 also decreased neurodegeneration in primary neuronal cultures exposed to 3-nitropropionic acid (3-NP, a mitochondrial complex II/III inhibitor. In addition, miR-22 improved neuronal viability in an in vitro model of brain aging. The mechanisms underlying the effects of miR-22 included a reduction in caspase activation, consistent with miR-22's targeting the pro-apoptotic activities of mitogen-activated protein kinase 14/p38 (MAPK14/p38 and tumor protein p53-inducible nuclear protein 1 (Tp53inp1. Moreover, HD-specific effects comprised not only targeting HDAC4, Rcor1 and Rgs2 mRNAs, but also decreasing focal accumulation of mutant Htt-positive foci, which occurred via an unknown mechanism. CONCLUSIONS: These data show that miR-22 has multipartite anti-neurodegenerative activities

  8. 半乳糖凝集素-3和细胞角蛋白19表达在甲状腺穿刺病理诊断中的应用%Application of Galectin-3 and CK19 expressions in pathological diagnosis of thyroid puncture biopsy

    Institute of Scientific and Technical Information of China (English)

    牛春波; 王丽萍; 王雪梅; 崔亚南; 贾飞勇; 张广

    2012-01-01

    目的:观察半乳糖凝集素-3 (Galectin-3)和细胞角蛋白19(CK19)在甲状腺穿刺标本中表达的特点,分析其在甲状腺良恶性病变鉴别诊断中的应用,探讨免疫组织化学方法标记CK19、Galectin-3表达在甲状腺穿刺小标本病理诊断中应用的可行性.方法:选择20例甲状腺乳头状癌( PTC)及16例甲状腺良性病变(BTL)穿刺组织,观察HE切片病理形态学特点,应用免疫组织化学EnVision法检测标本中Galectin-3、CK19和Ki67蛋白表达,对比3种蛋白在不同组间的表达,分析3种抗体在甲状腺术前穿刺病理诊断中的作用.结果:Galectin-3、CK19和Ki67在PTC组阳性率分别为90% (18/20)、95% (19/20)及60% (12/20),在BTL组阳性率分别为12.5%(2/16,均为弱阳性)、31.25%(5/16,均为弱阳性)及62.5% (10/16).Galectin-3和CK19在PTC与BTL组间表达率比较差异有统计学意义(均P<0.01),而Ki67在PTC与BTL组间表达率比较差异无统计学意义(P>0.05).结论:Galectin-3和CK19蛋白在PTC与BTL的表达存在显著差异,联合检测该2种蛋白在甲状腺乳头状癌穿刺标本的鉴别诊断中具有重要的应用价值,能有效提高甲状腺病变术前穿刺活检的确诊率.

  9. The N-terminus and alpha-5, alpha-6 helices of the pro-apoptotic protein Bax, modulate functional interactions with the anti-apoptotic protein Bcl-xL

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    Sowdhamini R

    2007-05-01

    Full Text Available Abstract Background Bcl-2 family proteins are key regulators of mitochondrial integrity and comprise both pro- and anti-apoptotic proteins. Bax a pro-apoptotic member localizes as monomers in the cytosol of healthy cells and accumulates as oligomers in mitochondria of apoptotic cells. The Bcl-2 homology-3 (BH3 domain regulates interactions within the family, but regions other than BH3 are also critical for Bax function. Thus, the N-terminus has been variously implicated in targeting to mitochondria, interactions with BH3-only proteins as well as conformational changes linked to Bax activation. The transmembrane (TM domains (α5-α6 helices in the core and α9 helix in the C-terminus in Bax are implicated in localization to mitochondria and triggering cytotoxicity. Here we have investigated N-terminus modulation of TM function in the context of regulation by the anti-apoptotic protein Bcl-xL. Results Deletion of 29 amino acids in the Bax N-terminus (Bax 30–192 caused constitutive accumulation at mitochondria and triggered high levels of cytotoxicity, not inhibited by Bcl-xL. Removal of the TM domains (Bax 30–105 abrogated mitochondrial localization but resulted in Bcl-xL regulated activation of endogenous Bax and Bax-Bak dependent apoptosis. Inclusion of the α5-α6 helices/TMI domain (Bax 30–146 phenocopied Bax 30–192 as it restored mitochondrial localization, Bcl-xL independent cytotoxicity and was not dependent on endogenous Bax-Bak. Inhibition of function and localization by Bcl-xL was restored in Bax 1–146, which included the TM1 domain. Regardless of regulation by Bcl-xL, all N-terminal deleted constructs immunoprecipitated Bcl-xLand converged on caspase-9 dependent apoptosis consistent with mitochondrial involvement in the apoptotic cascade. Sub-optimal sequence alignments of Bax and Bcl-xL indicated a sequence similarity between the α5–α6 helices of Bax and Bcl-xL. Alanine substitutions of three residues (T14A-S15A-S16A in

  10. Syntheses, Structures, and Characterization of Metal Carbonyl Complexes as Photoactive CO Releasing Molecules and their Biological Utility Towards Eradication of Cancer

    OpenAIRE

    Carrington, Samantha

    2016-01-01

    Carbon monoxide (CO) has recently been shown to elicit various salutary effects in mammalian physiology. This small molecule has shown to exert a multitude of actions, which includes, vasoregulation, inflammation reduction and anti-apoptotic actions in normal cells. Interestingly, in hyperproliferative cells, CO has shown to induce significant pro-apoptotic effects, which can be exploited therapeutically towards cancer eradication. However, the ability to deliver CO in a target-specific mann...

  11. IL-6 regulates Mcl-1L expression through the JAK/PI3K/Akt/CREB signaling pathway in hepatocytes: implication of an anti-apoptotic role during liver regeneration.

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    Chia-Hung Chou

    Full Text Available AIMS: To investigate the role and the regulation of the long variant of myeloid cell leukemia-1 protein (Mcl-1L during liver regeneration. BACKGROUND: Liver regeneration is an important phenomenon after liver injury. The rat partial hepatectomy (PH model was used to characterize liver regeneration and Mcl-1L expression after PH. METHODS: Male Wistar rats were subjected to 70% PH. The expression of mcl-1L mRNA was determined by quantitative RT-PCR, and protein levels were analyzed by Western blot analysis and immunohistochemistry during liver regeneration. Functional evaluations of Mcl-1L were tested using chemical inhibition (flavopiridol, genetic inhibition (siRNA of Mcl-1L production, and by assaying for annexin V levels and DNA ladder formation. Serum IL-6 levels were determined by enzyme immunoassays; signal transduction of IL-6-regulated Mcl-1L expression was verified by chemical inhibitors and decoy double-stranded oligodeoxynucleotides. RESULTS: High levels of Mcl-1L were observed in remnant tissue at 4 h after PH. Administration of flavopiridol decreased Mcl-1L accumulation and also inhibited liver regeneration. IL-6 administration promoted the accumulation of Mcl-1L in rat hepatocytes, an effect that was impaired by siRNA treatments that reduced Mcl-1L production. Chemical inhibition and decoy oligonucleotide competition demonstrated that IL-6-induced Mcl-1L production required signaling mediated by JAK kinase, phosphoinositide 3-kinase (PI3K, and cAMP response-element-binding (CREB proteins. CONCLUSION: Mcl-1L is an anti-apoptotic protein induced during liver regeneration after PH in rats. The expression of Mcl-1L is induced by IL-6 through the JAK/PI3K/Akt/CREB signaling pathway. Chemotherapy drugs that depend on Mcl-1L- or IL-6-related signaling should be considered carefully before use in patients undergoing hepatectomy for malignant tumor resection.

  12. Establishment and characterization of a transplantable tumor line (RMM) and cell line (RMM-C) from a malignant amelanotic melanoma in the F344 rat, with particular reference to galectin-3 expression in vivo and in vitro.

    Science.gov (United States)

    Bondoc, Alexandra; Katou-Ichikawa, Chisa; Golbar, Hossain M; Tanaka, Miyuu; Izawa, Takeshi; Kuwamura, Mitsuru; Yamate, Jyoji

    2016-11-01

    To investigate characteristics of malignant melanomas with various pathobiological features, a homotransplantable tumor line (RMM) was established from a spontaneous amelanotic melanoma found in the pinna of an aged F344 rat. RMM tumors were transplanted in syngeneic rats by serial subcutaneous implantation with 100% intake. The original and RMM tumors consisted of spindle-shaped cells arranged mainly in interlacing bundles. Immunohistochemically, the neoplastic cells were positive to PNL-2 (melanocytes), nestin (neuroectodermal stem cells), S-100 (neurogenic cells) and vimentin (mesenchymal cells). Electron microscopically, tumor cells possessed single membrane-bound pre-melanosomes. Further, a cell line (RMM-C) was induced from an RMM tumor. RMM-C cells and the induced tumors in syngeneic rats showed immunohistochemical reactions similar to the original and RMM tumors. Interestingly, serum level of galectin-3 expression was increased with growing RMM tumors, and the expression was influenced by TNF-α (increase) or TGF-β1 (decrease), indicating a possible biomarker of amelanotic melanomas. The RMM tumors and RMM-C cell line could become useful tools for studies on the pathobiology, including tumor immunity, and development of therapeutic strategies against this malignancy. These tools are the first tumor lines of amelanotic melanomas in the rat. PMID:26949998

  13. The anti-apoptotic and cardioprotective effects of salvianolic acid a on rat cardiomyocytes following ischemia/reperfusion by DUSP-mediated regulation of the ERK1/2/JNK pathway.

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    Tongda Xu

    +I/R group. SAA exerts an anti-apoptotic role against myocardial IRI by inhibiting DUSP2-mediated JNK dephosphorylation and activating DUSP4/16-mediated ERK1/2 phosphorylation.

  14. 半乳糖凝集素-3在邻苯二甲酸二丁酯致大鼠尿道下裂发生中的表达%Differential expression of galectin-3 in the hypospadiac male rats induced by Di-n-butyl phthalate

    Institute of Scientific and Technical Information of China (English)

    常俊锴; 魏云飞; 冯宁翰; 张炜

    2010-01-01

    目的 利用邻苯二甲酸二丁酯(DBP)胚胎期暴露导致SD大鼠尿道下裂发生的动物模型,观察半乳糖凝集素-3(galectin-3)在尿道下裂与正常大鼠生殖结节中的差异表达,探讨其在DBP致大鼠尿道下裂发生中的作用.方法 SD孕鼠20只,随机分为2组,妊娠14~18 d(GD14~18)实验组和对照组分别给予DBP 800 mg/(kg·d)和大豆油2 ml/d灌胃,GD19剖宫产后统计子鼠数、雄性子鼠出生体质量(BW)及肛门生殖器距离(AGD)、尿道下裂发生率,取两组雄性子鼠生殖结节,运用免疫印迹法和免疫组织化学方法分析galectin-3的表达.结果 尿道下裂仅实验组发生,发生率为40%,每窝子鼠数、雄性子鼠BW及AGD/BW在实验组分别为(8.90±1.25)只、(5.12±0.24)g、(0.57±0.03)mm/g,在对照组分别为(13.20±1.46)只、(6.72±0.42)g、(0.66±0.07)mm/g,差异有统计学意义(P<0.05);galectin-3在尿道下裂组的相对表达量为0.603±0.014(n=10),正常对照组为0.851±0.015(n=10),差异有统计学意义(P<0.05);galectin-3主要定位于生殖结节上皮细胞,尿道下裂组染色强度明显弱于对照组.结论 染毒期间DBP对雄性子鼠有明显毒性作用,改变了生殖结节中galectin-3的表达,影响了上皮细胞增殖、凋亡及尿生殖褶的融合.%Objective To verify the differential expression of galectin-3 in the genital tubercle (GT) of hypospadiac rats induced by maternal exposure to Di-n-butyl phthalate (DBP) and normal control rats in order to further explore the mechanism of hypospadias. Methods Twenty pregnant SD rats were randomly divided into two groups which were given DBP and soybean oil gavage at the dose of 800 mg/(kg·d) and 2 ml/d separately during the 14-18th day of pregnancy. Fetal rats per fossa, birth weight ( BW) , ano-genital distance (AGD), hapospadias incidence, and harvested GT of fetal rats at GD19.The expression of galectin-3 was analyzed by Western blotting and immunohistochemistry. Results The

  15. Small Molecule Inhibitors of Bcl-2 Family Proteins for Pancreatic Cancer Therapy

    International Nuclear Information System (INIS)

    Pancreatic cancer (PC) has a complex etiology and displays a wide range of cellular escape pathways that allow it to resist different treatment modalities. Crucial signaling molecules that function downstream of the survival pathways, particularly at points where several of these pathways crosstalk, provide valuable targets for the development of novel anti-cancer drugs. Bcl-2 family member proteins are anti-apoptotic molecules that are known to be overexpressed in most cancers including PC. The anti-apoptotic machinery has been linked to the observed resistance developed to chemotherapy and radiation and therefore is important from the targeted drug development point of view. Over the past ten years, our group has extensively studied a series of small molecule inhibitors of Bcl-2 against PC and provide solid preclinical platform for testing such novel drugs in the clinic. This review examines the efficacy, potency, and function of several small molecule inhibitor drugs targeted to the Bcl-2 family of proteins and their preclinical progress against PC. This article further focuses on compounds that have been studied the most and also discusses the anti-cancer potential of newer class of Bcl-2 drugs

  16. Single Nucleotide Polymorphisms at +191 and +292 of Galectin-3 Gene (LGALS3) Related to Lower GAL-3 Serum Levels Are Associated with Frequent Respiratory Tract Infection and Vaso-Occlusive Crisis in Children with Sickle Cell Anemia

    Science.gov (United States)

    de Mendonça Belmont, Taciana Furtado; do Ó, Kleyton Palmeira; Soares da Silva, Andreia; de Melo Vilar, Kamila; Silva Medeiros, Fernanda; Silva Vasconcelos, Luydson Richardson; Mendonça dos Anjos, Ana Claudia; Domingues Hatzlhofer, Betânia Lucena; Pitta, Maíra Galdino da Rocha; Bezerra, Marcos André Cavalcanti; Araújo, Aderson da Silva; de Melo Rego, Moacyr Jesus Barreto; Moura, Patrícia; Cavalcanti, Maria do Socorro Mendonça

    2016-01-01

    Introduction Patients with sickle cell anemia (SCA) may present chronic hemolytic anemia, vaso-occlusion and respiratory tract infection (RTI) episodes. Galectin-3 (GAL-3) is a multifunctional protein involved in inflammation, apoptosis, adhesion and resistance to reactive oxygen species. Studies point to a dual role for GAL-3 as both a circulation damage-associated molecular pattern and a cell membrane associated pattern recognition receptor. Objective To investigate associations between the SNPs of GAL-3 gene (LGALS3) and serum levels with RTI and vaso-occlusive crisis (VOC) in children with SCA. Materials and Methods SNPs +191 and +292 in LGALS3 were studied using the TaqMan real-time PCR system; GAL-3 serum levels were measured by ELISA. The study included 79 children with SCA ranging from 2 to 12 years old. Results GAL-3 serum levels were associated with LGALS3 +191 and +292 genotypes (p <0.0001; p = 0.0169, respectively). LGALS3 +191, AA genotype was associated with low and CC with higher levels of GAL-3. For LGALS3 +292, the CC genotype was associated with lower GAL-3 and AA with higher levels. Patients with Frequency of RTI (FRTI) ≥1 presented higher frequency of +191AA (p = 0.0263) and +292AC/CC genotypes (p = 0.0320). SNP +292 was associated with Frequency of VOC (FVOC) (p = 0.0347), whereas no association was shown with SNP +191 and FVOC. However, CA/AC and AA/CC genotypes with lower GAL-3 levels showed a higher frequency in patients with FRTI ≥1 (p = 0.0170; p = 0.0138, respectively). Also, patients with FVOC ≥1 presented association with CA/AC (p = 0.0228). LGALS3 +191 and +292 combined genotypes related to low (p = 0.0263) and intermediate expression (p = 0.0245) were associated with FRTI ≥1. Lower GAL-3 serum levels were associated with FRTI ≥1 (p = 0.0426) and FVOC ≥1 (p = 0.0012). Conclusion Variation of GAL-3 serum levels related to SNPs at +191 and +292 may constitute a susceptibility factor for RTI and VOC frequency. PMID:27603703

  17. Expressão de galectina-3 e beta-catenina em lesões pré-malignas e carcinomatosas de língua de camundongos Galectin-3 and beta-catenin expression in premalignant and carcinomatous lesions in tongue of mice

    Directory of Open Access Journals (Sweden)

    Juliana Moreira de Almeida Sant'ana

    2011-02-01

    Full Text Available INTRODUÇÃO: A galectina-3 (GAL3 apresenta importantes papéis na biologia tumoral e recentemente foi mostrada a sua participação na via de sinalização Wnt, translocando a beta-catenina para o núcleo. Expressão alterada de GAL3 e beta-catenina tem sido descrita em cânceres, mas não há estudos avaliando a expressão de ambas em displasias e carcinomas desenvolvidos em modelos de carcinogênese de língua. OBJETIVOS: Estudar a expressão de GAL3 e beta-catenina em lesões displásicas e carcinomas induzidos experimentalmente em língua de camundongos. MATERIAL E MÉTODOS: Vinte camundongos C57BL/6 machos foram desafiados com 4NQO na água de beber por 16 semanas e sacrificados na semana 16 e 32. Após o sacrifício, as línguas foram removidas, processadas, coradas por hematoxilina e eosina (HE para detecção de displasias e carcinomas. Ensaio imuno-histoquímico foi realizado para determinar o índice de positividade para GAL3 e beta-catenina nessas lesões, bem como uma correlação entre elas em carcinomas. RESULTADOS: O número de camundongos afetados por carcinoma aumentou entre as semanas 16 e 32 (22,2% vs. 88,9% e o de displasia diminuiu (66,7% vs. 11,1%. Um aumento de células positivas para beta-catenina não membranosa e GAL3 citoplasmática foi observado nas displasias e nos carcinomas, mas essa diferença não foi estatisticamente significativa. No entanto, um aumento estatisticamente significativo de GAL3 nuclear foi observado na evolução de displasia para carcinoma (p = 0,04. Nenhuma correlação foi encontrada entre beta-catenina e GAL3. CONCLUSÃO: Tanto nas displasias quanto nos carcinomas a via de sinalização Wnt está ativa, e o aumento de GAL3 nuclear nos carcinomas sugere um papel na transformação maligna do epitélio lingual.INTRODUCTION: Galectin-3 plays pivotal role in tumor biology and its participation in Wnt signaling pathway translocating beta-catenin into the nucleus has been recently demonstrated

  18. Carbon Monoxide: An Essential Signalling Molecule

    Science.gov (United States)

    Mann, Brian E.

    Carbon monoxide (CO), like nitric oxide (NO), is an essential signalling molecule in humans. It is active in the cardiovascular system as a vasodilator. In addition, CO possesses anti-inflammatory, anti-apoptotic and anti-proliferative properties and protects tissues from hypoxia and reperfusion injury. Some of its applications in animal models include suppression of organ graft rejection and safeguarding the heart during reperfusion after cardiopulmonary bypass surgery. CO also suppresses arteriosclerotic lesions following angioplasty, reverses established pulmonary hypertension and mitigates the development of post-operative ileus in the murine small intestine and the development of cerebral malaria in mice as well as graft-induced intimal hyperplasia in pigs. There have been several clinical trials using air-CO mixtures for the treatment of lung-, heart-, kidney- and abdominal-related diseases. This review examines the research involving the development of classes of compounds (with particular emphasis on metal carbonyls) that release CO, which could be used in clinically relevant conditions. The review is drawn not only from published papers in the chemical literature but also from the extensive biological literature and patents on CO-releasing molecules (CO-RMs).

  19. Effect of ionizing radiation on hematopoietic stem cells and progenitor cells: Role of apoptosis and potential therapeutic significance of anti-apoptotic treatments; Effet des rayonnements ionisants sur les cellules souches et progeniteurs hematopoietiques : place de l'apoptose et interet therapeutique potentiel des traitements antiapoptotiques

    Energy Technology Data Exchange (ETDEWEB)

    Drouet, M.; Mourcin, F.; Grenier, N.; Mayol, J.F.; Leroux, V. [Unite de Radiohematologie experimentale, Centre de Recherches du Service de Sante des Armees, La Tronche CEDEX (France); Sotto, J.J. [Inst. Albert Bonniot, La Tronche (France); Herodin, F. [Unite de Radiohematologie experimentale, Centre de Recherches du Service de Sante des Armees, La Tronche CEDEX (France)

    2002-07-01

    Bone marrow aplasia observed following ionizing radiation exposure (Total Body Irradiation; gamma dose range: 2-10 Gy) is a result, in particular, of the radiation-induced (RI) apoptosis in hematopoietic stem and progenitor cells (HSPC). We have previously shown in a baboon model of mobilized peripheral blood CD34{sup +} cell irradiation in vitro that RI apoptosis in HSPC was an early event, mostly occurring within the first 24 hours, which involves the CD95 Fas pathway. Apoptosis may be significantly reduced with a combination of 4 cytokines (4F): Stem Cell Factor (SCF), FLT-3 Ligand (FL), thrombopoietin (TPO), and interleukin-3 (IL-3), each at 50 ng{center_dot}mL{sup -1} (15% survival versus <3% untreated cells, 24 h post-irradiation at 2.5 Gy). In this study we show that addition of TNF-{alpha}(800 IU/ml) induces an increase in 4F efficacy in terms of cell survival 24 h after incubation (26% survival after 24 h irradiation exposure at 2.5 Gy) and amplification (k) of CD34{sup +} cells after 6 days in a serum free culture medium (SFM) (k{sub CD34{sup +}} = 4.3 and 6.3 respectively for 4F and successive 4F + TNF-{alpha}/4F treatments). In addition, the 4F combination allows culture on pre-established allogenic irradiated stromal cells in vitro at 4 Gy (k{sub CD34{sup +}} = 4.5). Overall this study suggests (i) the potential therapeutic interest for an early administration of anti-apoptotic cytokines with or without hematopoiesis inhibitors (emergency cytokine therapy) and (ii) the feasibility in the accidentally irradiated individual, of autologous cell therapy based on ex vivo expansion in order to perform autograft of residual HSPC collected after the accident. (author)

  20. Small molecules reveal an alternative mechanism of Bax activation.

    Science.gov (United States)

    Brahmbhatt, Hetal; Uehling, David; Al-Awar, Rima; Leber, Brian; Andrews, David

    2016-04-15

    The pro-apoptotic protein Bax commits a cell to death by permeabilizing the mitochondrial outer membrane (MOM). To obtain small-molecule probes for elucidating the molecular mechanism(s) of Bax activation, we screened for compounds that induced Bax-mediated liposome permeabilization. We identified five structurally different small molecules that promoted both Bax targeting to and oligomerization at membranes. All five compounds initiated Bax oligomerization in the absence of membranes by a mechanism unlike Bax activation by Bcl-2 homology 3 domain (BH3) proteins. Some of the compounds induced Bax/Bak-dependent apoptosis in cells. Activation of Bax by the most active compound was poorly inhibited by the anti-apoptotic protein Bcl-XL and requires a cysteine residue at position 126 of Bax that is not required for activation by BH3 proteins. Our results reveal a novel pathway for Bax activation independent of pro-apoptotic BH3 proteins that may have important implications for the regulation of Bax activity in cells. PMID:26916338

  1. Oncostatic-Cytoprotective Effect of Melatonin and Other Bioactive Molecules: A Common Target in Mitochondrial Respiration

    Directory of Open Access Journals (Sweden)

    Nicola Pacini

    2016-03-01

    Full Text Available For several years, oncostatic and antiproliferative properties, as well as thoses of cell death induction through 5-methoxy-N-acetiltryptamine or melatonin treatment, have been known. Paradoxically, its remarkable scavenger, cytoprotective and anti-apoptotic characteristics in neurodegeneration models, such as Alzheimer’s disease and Parkinson’s disease are known too. Analogous results have been confirmed by a large literature to be associated to the use of many other bioactive molecules such as resveratrol, tocopherol derivatives or vitamin E and others. It is interesting to note that the two opposite situations, namely the neoplastic pathology and the neurodegeneration, are characterized by deep alterations of the metabolome, of mitochondrial function and of oxygen consumption, so that the oncostatic and cytoprotective action can find a potential rationalization because of the different metabolic and mitochondrial situations, and in the effect that these molecules exercise on the mitochondrial function. In this review we discuss historical and general aspects of melatonin, relations between cancers and the metabolome and between neurodegeneration and the metabolome, and the possible effects of melatonin and of other bioactive molecules on metabolic and mitochondrial dynamics. Finally, we suggest a common general mechanism as responsible for the oncostatic/cytoprotective effect of melatonin and of other molecules examined.

  2. 乙醛脱氢酶2在糖尿病大鼠心肌缺血/再灌注损伤中的抗凋亡作用%Anti-apoptotic role of mitochondrial aldehyde dehydrogenase 2 in myocardial ischemia/reperfusion injury in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    王洪巨; 康品方; 叶红伟; 于影; 王晓梅; 高琴

    2012-01-01

    目的 观察乙醛脱氢酶2(ALDH2)在糖尿病大鼠心肌缺血/再灌注凋亡发生中的作用.方法 大鼠分为正常组、糖尿病组和ALDH2激动剂乙醇+糖尿病组.4周后行离体心肌缺血/再灌注(I/R).测定复灌期间冠脉流出液中乳酸脱氢酶(LDH)含量.检测心肌组织细胞ALDH2、caspase-3的活性;RT-PCR测定左心室前壁心尖组织Bcl-2、Bax mRNA的表达.结果 与正常大鼠I/R相比,糖尿病大鼠复灌期冠脉流出液中LDH释放增加,心肌组织caspase-3活性增加,ALDH2活性降低,Bcl-2/Bax mRNA比值降低;与糖尿病大鼠心肌I/R相比,ALDH2激动剂乙醇使得心肌复灌期间冠脉流出液中LDH释放减少,心肌caspase,-3活性降低,ALDH2活性增高,Bcl-2/Bax mRNA比值增高.结论 增强ALDH2在糖尿病大鼠心肌中的表达对缺血/再灌注损伤有明显的保护作用;其机制可能与抑制细胞凋亡的发生有关.%Objective To evaluate the anti-apoptotic effect of aldehyde dehydrogenase 2 (ALDH2) on myocardial ischemia/ reperfusion (I/R) injury in diabetic rats. Methods Normal male SD rats were divided into normal, diabetes and ethanol (the agonist of ALDH2) + diabetes groups. In the latter two groups, diabetes was induced by an intraperitoneal injection of 55 mg/kg STZ. Four weeks after the modeling, myocardial I/R was mimicked ex vivo, and lactate dehydrogenase (LDH) content in the coronary flow was determined. The activities of caspase-3 and ALDH2 were evaluated, and the expressions of Bd-2 and Bax mRNA in the left anterior myocardium were detected using RT-PCR. Results In diabetic group, LDH release and caspase-3 activity were increased, while ALDH2 activity and Bd-2/Bax mRNA expression were decreased as compared to those in normal control group. Compared with the diabetic group, ALDH2 agonist ethanol significantly reduced LDH release and caspase-3 activity, increased ALDH2 activity and Bd-2/Bax mRNA expression. Condusion In diabetic rats, enhanced ALDH2 expression

  3. Molecule nanoweaver

    Science.gov (United States)

    Gerald, II; Rex E.; Klingler, Robert J.; Rathke, Jerome W.; Diaz, Rocio; Vukovic, Lela

    2009-03-10

    A method, apparatus, and system for constructing uniform macroscopic films with tailored geometric assemblies of molecules on the nanometer scale. The method, apparatus, and system include providing starting molecules of selected character, applying one or more force fields to the molecules to cause them to order and condense with NMR spectra and images being used to monitor progress in creating the desired geometrical assembly and functionality of molecules that comprise the films.

  4. The conveyor belt hypothesis for thymocyte migration: participation of adhesion and de-adhesion molecules

    Directory of Open Access Journals (Sweden)

    Villa-Verde D.M.S.

    1999-01-01

    Full Text Available Thymocyte differentiation is the process by which bone marrow-derived precursors enter the thymus, proliferate, rearrange the genes and express the corresponding T cell receptors, and undergo positive and/or negative selection, ultimately yielding mature T cells that will represent the so-called T cell repertoire. This process occurs in the context of cell migration, whose cellular and molecular basis is still poorly understood. Kinetic studies favor the idea that these cells leave the organ in an ordered pattern, as if they were moving on a conveyor belt. We have recently proposed that extracellular matrix glycoproteins, such as fibronectin, laminin and type IV collagen, among others, produced by non-lymphoid cells both in the cortex and in the medulla, would constitute a macromolecular arrangement allowing differentiating thymocytes to migrate. Here we discuss the participation of both molecules with adhesive and de-adhesive properties in the intrathymic T cell migration. Functional experiments demonstrated that galectin-3, a soluble ß-galactoside-binding lectin secreted by thymic microenvironmental cells, is a likely candidate for de-adhesion proteins by decreasing thymocyte interaction with the thymic microenvironment.

  5. Small molecules and targeted therapies in distant metastatic disease

    DEFF Research Database (Denmark)

    Hersey, P; Bastholt, L; Chiarion-Sileni, V;

    2009-01-01

    up-regulated in signal cell pathways or inhibit anti-apoptotic proteins. Sorafenib, a multikinase inhibitor of the RAF/RAS/MEK pathway, elesclomol (STA-4783) and oblimersen (G3139), an antisense oligonucleotide targeting anti-apoptotic BCl-2, are in phase III clinical studies in combination...... with chemotherapy. Agents targeting mutant B-Raf (RAF265 and PLX4032), MEK (PD0325901, AZD6244), heat-shock protein 90 (tanespimycin), mTOR (everolimus, deforolimus, temsirolimus) and VEGFR (axitinib) showed some promise in earlier stages of clinical development. Receptor tyrosine-kinase inhibitors (imatinib...

  6. Enumerating molecules.

    Energy Technology Data Exchange (ETDEWEB)

    Visco, Donald Patrick, Jr. (, . Tennessee Technological University, Cookeville, TN); Faulon, Jean-Loup Michel; Roe, Diana C.

    2004-04-01

    This report is a comprehensive review of the field of molecular enumeration from early isomer counting theories to evolutionary algorithms that design molecules in silico. The core of the review is a detail account on how molecules are counted, enumerated, and sampled. The practical applications of molecular enumeration are also reviewed for chemical information, structure elucidation, molecular design, and combinatorial library design purposes. This review is to appear as a chapter in Reviews in Computational Chemistry volume 21 edited by Kenny B. Lipkowitz.

  7. Hadron Molecules

    CERN Document Server

    Gutsche, Thomas; Faessler, Amand; Lee, Ian Woo; Lyubovitskij, Valery E

    2010-01-01

    We discuss a possible interpretation of the open charm mesons $D_{s0}^*(2317)$, $D_{s1}(2460)$ and the hidden charm mesons X(3872), Y(3940) and Y(4140) as hadron molecules. Using a phenomenological Lagrangian approach we review the strong and radiative decays of the $D_{s0}^* (2317)$ and $D_{s1}(2460)$ states. The X(3872) is assumed to consist dominantly of molecular hadronic components with an additional small admixture of a charmonium configuration. Determing the radiative ($\\gamma J/\\psi$ and $\\gamma \\psi(2s)$) and strong ($J/\\psi 2\\pi $ and $ J/\\psi 3\\pi$) decay modes we show that present experimental observation is consistent with the molecular structure assumption of the X(3872). Finally we give evidence for molecular interpretations of the Y(3940) and Y(4140) related to the observed strong decay modes $J/\\psi + \\omega$ or $J/\\psi + \\phi$, respectively.

  8. Activated peripheral lymphocytes with increased expression of cell adhesion molecules and cytotoxic markers are associated with dengue fever disease.

    Science.gov (United States)

    Azeredo, Elzinandes L; Zagne, Sonia M O; Alvarenga, Allan R; Nogueira, Rita M R; Kubelka, Claire F; de Oliveira-Pinto, Luzia M

    2006-06-01

    The immune mechanisms involved in dengue fever and dengue hemorrhagic/dengue shock syndrome are not well understood. The ex vivo activation status of immune cells during the dengue disease in patients was examined. CD4 and CD8 T cells were reduced during the acute phase. Interestingly, CD8 T cells co-expressing activation marker HLA-DR, Q, P, and cytolytic granule protein-Tia-1 were significantly higher in dengue patients than in controls. Detection of adhesion molecules indicated that in dengue patients the majority of T cells (CD4 and CD8) express the activation/memory phenotype, characterized as CD44HIGH and lack the expression of the naïve cell marker, CD62L LOW. Also, the levels of T cells co-expressing ICAM-1 (CD54), VLA-4, and LFA-1 (CD11a) were significantly increased. CD8 T lymphocytes expressed predominantly low levels of anti-apoptotic molecule Bcl-2 in the acute phase, possibly leading to the exhibition of a phenotype of activated/effector cells. Circulating levels of IL-18, TGF-b1 and sICAM-1 were significantly elevated in dengue patients. Early activation events occur during acute dengue infection which might contribute to viral clearance. Differences in expression of adhesion molecules among CD4 and CD8 T cells might underlie the selective extravasation of these subsets from blood circulation into lymphoid organs and/or tissues. In addition, activated CD8 T cells would be more susceptible to apoptosis as shown by the alteration in Bcl-2 expression. Cytokines such as IL-18, TGF-b1, and sICAM-1 may be contributing by either stimulating or suppressing the adaptative immune response, during dengue infection, thereby perhaps establishing a relationship with disease severity.

  9. Activated peripheral lymphocytes with increased expression of cell adhesion molecules and cytotoxic markers are associated with dengue fever disease

    Directory of Open Access Journals (Sweden)

    Elzinandes L Azeredo

    2006-06-01

    Full Text Available The immune mechanisms involved in dengue fever and dengue hemorrhagic/dengue shock syndrome are not well understood. The ex vivo activation status of immune cells during the dengue disease in patients was examined. CD4and CD8 T cells were reduced during the acute phase. Interestingly, CD8 T cells co-expressing activation marker HLA-DR, Q, P, and cytolytic granule protein-Tia-1 were significantly higher in dengue patients than in controls. Detection of adhesion molecules indicated that in dengue patients the majority of T cells (CD4 and CD8 express the activation/memory phenotype, characterized as CD44HIGH and lack the expression of the naïve cell marker, CD62L LOW. Also, the levels of T cells co-expressing ICAM-1 (CD54, VLA-4, and LFA-1 (CD11a were significantly increased. CD8 T lymphocytes expressed predominantly low levels of anti-apoptotic molecule Bcl-2 in the acute phase, possibly leading to the exhibition of a phenotype of activated/effector cells. Circulating levels of IL-18, TGF-b1 and sICAM-1 were significantly elevated in dengue patients. Early activation events occur during acute dengue infection which might contribute to viral clearance. Differences in expression of adhesion molecules among CD4 and CD8 T cells might underlie the selective extravasation of these subsets from blood circulation into lymphoid organs and/or tissues. In addition, activated CD8 T cells would be more susceptible to apoptosis as shown by the alteration in Bcl-2 expression. Cytokines such as IL-18, TGF-b1, and sICAM-1 may be contributing by either stimulating or suppressing the adaptative immune response, during dengue infection, thereby perhaps establishing a relationship with disease severity.

  10. IL-17 attenuates the anti-apoptotic effects of GM-CSF in human neutrophils.

    Science.gov (United States)

    Dragon, Stéphane; Saffar, Arash Shoja; Shan, Lianyu; Gounni, Abdelilah Soussi

    2008-01-01

    Interleukin (IL)-17A is a pleiotropic, pro-inflammatory cytokine that is implicated in chronic inflammatory and degenerative disorders. IL-17 has been demonstrated to link activated T-lymphocyte with the recruitment of neutrophils at sites of inflammation, however whether IL-17 can mediate neutrophil survival and subsequently affect inflammatory responses has not fully been elucidated. In our study, we demonstrate that human peripheral blood and HL-60 differentiated neutrophils express mRNA and cell surface IL-17A receptor. IL-17A does not affect the rate of spontaneous neutrophil apoptosis, however significantly decreased granulocyte macrophage-colony stimulating factor (GM-CSF)-mediated survival by antagonizing the signal transduction pathways of p38, Erk1/2 and signal transducer and activator of transcription (STAT) 5B. These events were associated with reduced myeloid cell lymphoma-1 (Mcl-1) protein levels, increased translocation and aggregation of Bax to mitochondria, decreased mitochondrial transmembrane potential and in an increase in caspase-3/7 activity. These events were independent of increased Fas or soluble Fas ligand expression levels. Taken together, our findings suggest that IL-17 may regulate neutrophil homeostasis and favor the resolution of inflamed tissues by attenuating the delay in neutrophil apoptosis induced by inflammatory cytokines.

  11. Simultaneous gene silencing of KRAS and anti-apoptotic genes as a multitarget therapy

    Science.gov (United States)

    Werner, Kristin; Lademann, Franziska; Thepkaysone, May-Linn; Jahnke, Beatrix; Aust, Daniela E.; Kahlert, Christoph; Weber, Georg; Weitz, Jürgen; Grützmann, Robert; Pilarsky, Christian

    2016-01-01

    Pancreatic cancer is one of the most lethal tumor types worldwide and an effective therapy is still elusive. Targeted therapy focused against a specific alteration is by definition unable to attack broad pathway signaling modification. Tumor heterogeneity will render targeted therapies ineffective based on the regrowth of cancer cell sub-clones. Therefore multimodal therapy strategies, targeting signaling pathways simultaneously should improve treatment. SiRNAs against KRAS and the apoptosis associated genes BCLXL, FLIP, MCL1L, SURVIVIN and XIAP were transfected into human and murine pancreatic cancer cell lines. Induction of apoptosis was measured by Caspase 3/7 activation, subG1 FACS analysis and PARP cleavage. The therapeutic approach was tested in a subcutaneous allograft model with a murine cancer cell line. By using siRNAs as a systematic approach to remodel signal transduction in pancreatic cancer the results showed increasing inhibition of proliferation and apoptosis induction in vitro and in vivo. Thus, siRNAs are suitable to model multimodal therapy against signaling pathways in pancreatic cancer. Improvements in in vivo delivery of siRNAs against a multitude of targets might therefore be a potential therapeutic approach. PMID:26716649

  12. Homologous recombination control by the anti-apoptotic onco-protein Bcl-2

    International Nuclear Information System (INIS)

    This research thesis deals with the different biological mechanisms, notably the repair and apoptosis mechanisms induced by irradiation in cells. After a presentation of the genotoxic stress and DNA repair mechanisms, the author discusses the cellular response to a DNA double-strand break, and the regulation of these response mechanisms (how a cellular response emerges: life or death). The next part deals with the apoptosis (cell death by necrosis or apoptosis), and presents the BCL-2 protein family. Results are then reported on laboratory studies of the effect of this protein family

  13. The Anti-apoptotic Effect of Ghrelin on Restraint Stress-Induced Thymus Atrophy in Mice.

    Science.gov (United States)

    Lee, Jun Ho; Kim, Tae-Jin; Kim, Jie Wan; Yoon, Jeong Seon; Kim, Hyuk Soon; Lee, Kyung-Mi

    2016-08-01

    Thymic atrophy is a complication that results from exposure to many environmental stressors, disease treatments, and microbial challenges. Such acute stress-associated thymic loss can have a dramatic impact on the host's ability to replenish the necessary naïve T cell output to reconstitute the peripheral T cell numbers and repertoire to respond to new antigenic challenges. We have previously reported that treatment with the orexigenic hormone ghrelin results in an increase in the number and proliferation of thymocytes after dexamethasone challenge, suggesting a role for ghrelin in restraint stress-induced thymic involution and cell apoptosis and its potential use as a thymostimulatory agent. In an effort to understand how ghrelin suppresses thymic T cell apoptosis, we have examined the various signaling pathways induced by receptor-specific ghrelin stimulation using a restraint stress mouse model. In this model, stress-induced apoptosis in thymocytes was effectively blocked by ghrelin. Western blot analysis demonstrated that ghrelin prevents the cleavage of pro-apoptotic proteins such as Bim, Caspase-3, and PARP. In addition, ghrelin stimulation activates the Akt and Mitogen-activated protein kinases (MAPK) signaling pathways in a time/dose-dependent manner. Moreover, we also revealed the involvement of the FoxO3a pathway in the phosphorylation of Akt and ERK1/2. Together, these findings suggest that ghrelin inhibits apoptosis by modulating the stress-induced apoptotic signal pathway in the restraint-induced thymic apoptosis. PMID:27574503

  14. Formation of Ultracold Molecules

    Energy Technology Data Exchange (ETDEWEB)

    Cote, Robin [Univ. of Connecticut, Storrs, CT (United States)

    2016-01-28

    Advances in our ability to slow down and cool atoms and molecules to ultracold temperatures have paved the way to a revolution in basic research on molecules. Ultracold molecules are sensitive of very weak interactions, even when separated by large distances, which allow studies of the effect of those interactions on the behavior of molecules. In this program, we have explored ways to form ultracold molecules starting from pairs of atoms that have already reached the ultracold regime. We devised methods that enhance the efficiency of ultracold molecule production, for example by tuning external magnetic fields and using appropriate laser excitations. We also investigates the properties of those ultracold molecules, especially their de-excitation into stable molecules. We studied the possibility of creating new classes of ultra-long range molecules, named macrodimers, thousand times more extended than regular molecules. Again, such objects are possible because ultra low temperatures prevent their breakup by collision. Finally, we carried out calculations on how chemical reactions are affected and modified at ultracold temperatures. Normally, reactions become less effective as the temperature decreases, but at ultracold temperatures, they can become very effective. We studied this counter-intuitive behavior for benchmark chemical reactions involving molecular hydrogen.

  15. Trapping molecules on chips

    CERN Document Server

    Santambrogio, Gabriele

    2015-01-01

    In the last years, it was demonstrated that neutral molecules can be loaded on a microchip directly from a supersonic beam. The molecules are confined in microscopic traps that can be moved smoothly over the surface of the chip. Once the molecules are trapped, they can be decelerated to a standstill, for instance, or pumped into selected quantum states by laser light or microwaves. Molecules are detected on the chip by time-resolved spatial imaging, which allows for the study of the distribution in the phase space of the molecular ensemble.

  16. [Endothelial cell adhesion molecules].

    Science.gov (United States)

    Ivanov, A N; Norkin, I A; Puchin'ian, D M; Shirokov, V Iu; Zhdanova, O Iu

    2014-01-01

    The review presents current data concerning the functional role of endothelial cell adhesion molecules belonging to different structural families: integrins, selectins, cadherins, and the immunoglobulin super-family. In this manuscript the regulatory mechanisms and factors of adhesion molecules expression and distribution on the surface of endothelial cells are discussed. The data presented reveal the importance of adhesion molecules in the regulation of structural and functional state of endothelial cells in normal conditions and in pathology. Particular attention is paid to the importance of these molecules in the processes of physiological and pathological angiogenesis, regulation of permeability of the endothelial barrier and cell transmigration.

  17. Molecules in galaxies

    CERN Document Server

    Omont, Alain

    2007-01-01

    The main achievements, current developments and prospects of molecular studies in external galaxies are reviewed. They are put in the context of the results of several decades of studies of molecules in local interstellar medium, their chemistry and their importance for star formation. CO observations have revealed the gross structure of molecular gas in galaxies. Together with other molecules, they are among the best tracers of star formation at galactic scales. Our knowledge about molecular abundances in various local galactic environments is progressing. They trace physical conditions and metallicity, and they are closely related to dust processes and large aromatic molecules. Major recent developments include mega-masers, and molecules in Active Galactic Nuclei; millimetre emission of molecules at very high redshift; and infrared H2 emission as tracer of warm molecular gas, shocks and photodissociation regions. The advent of sensitive giant interferometers from the centimetre to sub-millimetre range, espe...

  18. Galectin-3 is a new MerTK-specific eat-me signal

    OpenAIRE

    Caberoy, Nora B.; Alvarado, Gabriela; Bigcas, Jo-Lawrence; Li, Wei

    2012-01-01

    Phagocytosis of apoptotic cells and cellular debris is a critical process of maintaining tissue and immune homeostasis. Defects in the phagocytosis process cause autoimmunity and degenerative diseases. Phagocytosis ligands or “eat-me” signals control the initiation of the process by linking apoptotic cells to receptors on phagocyte surface and triggering signaling cascades for cargo engulfment. Eat-me signals are traditionally identified on a case-by-case basis with challenges, and the identi...

  19. Heavy Exotic Molecules

    CERN Document Server

    Liu, Yizhuang

    2016-01-01

    We briefly review the formation of pion-mediated heavy-light exotic molecules with both charm and bottom, under the general strictures of chiral and heavy quark symmetries. The charm isosinglet exotic molecules with $J^{PC}=1^{++}$ binds, which we identify as the reported neutral $X(3872)$. The bottom isotriplet exotic with $J^{PC}=1^{+-}$ binds, and is identified as a mixed state of the reported charged exotics $Z^+_b(10610)$ and $Z^+_b(10650)$. The bound bottom isosinglet molecule with $J^{PC}=1^{++}$ is a possible neutral $X_b(10532)$ to be observed.

  20. Electron correlation in molecules

    CERN Document Server

    Wilson, S

    2007-01-01

    Electron correlation effects are of vital significance to the calculation of potential energy curves and surfaces, the study of molecular excitation processes, and in the theory of electron-molecule scattering. This text describes methods for addressing one of theoretical chemistry's central problems, the study of electron correlation effects in molecules.Although the energy associated with electron correlation is a small fraction of the total energy of an atom or molecule, it is of the same order of magnitude as most energies of chemical interest. If the solution of quantum mechanical equatio

  1. Single molecules and nanotechnology

    CERN Document Server

    Vogel, Horst

    2007-01-01

    This book focuses on recent advances in the rapidly evolving field of single molecule research. These advances are of importance for the investigation of biopolymers and cellular biochemical reactions, and are essential to the development of quantitative biology. Written by leading experts in the field, the articles cover a broad range of topics, including: quantum photonics of organic dyes and inorganic nanoparticles their use in detecting properties of single molecules the monitoring of single molecule (enzymatic) reactions single protein (un)folding in nanometer-sized confined volumes the dynamics of molecular interactions in biological cells The book is written for advanced students and scientists who wish to survey the concepts, techniques and results of single molecule research and assess them for their own scientific activities.

  2. Electron-molecule collisions

    CERN Document Server

    Takayanagi, Kazuo

    1984-01-01

    Scattering phenomena play an important role in modern physics. Many significant discoveries have been made through collision experiments. Amongst diverse kinds of collision systems, this book sheds light on the collision of an electron with a molecule. The electron-molecule collision provides a basic scattering problem. It is scattering by a nonspherical, multicentered composite particle with its centers having degrees of freedom of motion. The molecule can even disintegrate, Le., dissociate or ionize into fragments, some or all of which may also be molecules. Although it is a difficult problem, the recent theoretical, experimental, and computational progress has been so significant as to warrant publication of a book that specializes in this field. The progress owes partly to technical develop­ ments in measurements and computations. No less important has been the great and continuing stimulus from such fields of application as astrophysics, the physics of the earth's upper atmosphere, laser physics, radiat...

  3. Optothermal Molecule Trap

    OpenAIRE

    Duhr, Stefan; Braun, Dieter

    2006-01-01

    Thermophoresis moves molecules along temperature gradients, typically from hot to cold. We superpose fluid flow with thermophoretic molecule flow under well defined microfluidic conditions, imaged by fluorescence microscopy. DNA is trapped and accumulated 16-fold in regions where both flows move in opposite directions. Strong 800-fold accumulation is expected, however with slow trapping kinetics. The experiment is equally described by a three-dimensional and one-dimensional analytical model. ...

  4. Expression of human carcinoembryonic antigen-related cell adhesion molecule 6 and alveolar progenitor cells in normal and injured lungs of transgenic mice.

    Science.gov (United States)

    Lin, Shin-E; Barrette, Anne Marie; Chapin, Cheryl; Gonzales, Linda W; Gonzalez, Robert F; Dobbs, Leland G; Ballard, Philip L

    2015-12-01

    Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is expressed in the epithelium of various primate tissues, including lung airway and alveoli. In human lung, CEACAM6 is developmentally and hormonally regulated, protects surfactant function, has anti-apoptotic activity and is dysregulated in cancers. We hypothesized that alveolar CEACAM6 expression increases in lung injury and promotes cell proliferation during repair. Studies were performed in CEABAC transgenic mice-containing human CEACAM genes. The level of CEACAM6 in adult CEABAC lung was comparable to that in human infants; expression occurred in epithelium of airways and of some alveoli but rarely co-localized with markers of type I or type II cells. Ten days after bleomycin instillation, both the number of CEACAM6(+) cells and immunostaining intensity were elevated in injured lung areas, and there was increased co-localization with type I and II cell markers. To specifically address type II cells, we crossed CEABAC mice with animals expressing EGFP driven by the SP-C promoter. After bleomycin injury, partially flattened, elongated epithelial cells were observed that expressed type I cell markers and were primarily either EGFP(+) or CEACAM6(+). In cell cycle studies, mitosis was greater in CEACAM6(+) non-type II cells versus CEACAM6(+)/EGFP(+) cells. CEACAM6 epithelial expression was also increased after hyperoxic exposure and LPS instillation, suggesting a generalized response to acute lung injuries. We conclude that CEACAM6 expression is comparable in human lung and the CEABAC mouse. CEACAM6 in this model appears to be a marker of a progenitor cell population that contributes to alveolar epithelial cell replenishment after lung injury. PMID:26702074

  5. Towards single molecule switches.

    Science.gov (United States)

    Zhang, Jia Lin; Zhong, Jian Qiang; Lin, Jia Dan; Hu, Wen Ping; Wu, Kai; Xu, Guo Qin; Wee, Andrew T S; Chen, Wei

    2015-05-21

    The concept of using single molecules as key building blocks for logic gates, diodes and transistors to perform basic functions of digital electronic devices at the molecular scale has been explored over the past decades. However, in addition to mimicking the basic functions of current silicon devices, molecules often possess unique properties that have no parallel in conventional materials and promise new hybrid devices with novel functions that cannot be achieved with equivalent solid-state devices. The most appealing example is the molecular switch. Over the past decade, molecular switches on surfaces have been intensely investigated. A variety of external stimuli such as light, electric field, temperature, tunneling electrons and even chemical stimulus have been used to activate these molecular switches between bistable or even multiple states by manipulating molecular conformations, dipole orientations, spin states, charge states and even chemical bond formation. The switching event can occur either on surfaces or in break junctions. The aim of this review is to highlight recent advances in molecular switches triggered by various external stimuli, as investigated by low-temperature scanning tunneling microscopy (LT-STM) and the break junction technique. We begin by presenting the molecular switches triggered by various external stimuli that do not provide single molecule selectivity, referred to as non-selective switching. Special focus is then given to selective single molecule switching realized using the LT-STM tip on surfaces. Single molecule switches operated by different mechanisms are reviewed and discussed. Finally, molecular switches embedded in self-assembled monolayers (SAMs) and single molecule junctions are addressed. PMID:25757483

  6. Multicolor Bound Soliton Molecule

    CERN Document Server

    Luo, Rui; Lin, Qiang

    2015-01-01

    We show a new class of bound soliton molecule that exists in a parametrically driven nonlinear optical cavity with appropriate dispersion characteristics. The composed solitons exhibit distinctive colors but coincide in time and share a common phase, bound together via strong inter-soliton four-wave mixing and Cherenkov radiation. The multicolor bound soliton molecule shows intriguing spectral locking characteristics and remarkable capability of spectrum management to tailor soliton frequencies, which may open up a great avenue towards versatile generation and manipulation of multi-octave spanning phase-locked Kerr frequency combs, with great potential for applications in frequency metrology, optical frequency synthesis, and spectroscopy.

  7. Proliferation and survival molecules implicated in the inhibition of BRAF pathway in thyroid cancer cells harbouring different genetic mutations

    Directory of Open Access Journals (Sweden)

    Seca Hugo

    2009-10-01

    Full Text Available Abstract Background Thyroid carcinomas show a high prevalence of mutations in the oncogene BRAF which are inversely associated with RAS or RET/PTC oncogenic activation. The possibility of using inhibitors on the BRAF pathway as became an interesting therapeutic approach. In thyroid cancer cells the target molecules, implicated on the cellular effects, mediated by inhibition of BRAF are not well established. In order to fill this lack of knowledge we studied the proliferation and survival pathways and associated molecules induced by BRAF inhibition in thyroid carcinoma cell lines harbouring distinct genetic backgrounds. Methods Suppression of BRAF pathway in thyroid cancer cell lines (8505C, TPC1 and C643 was achieved using RNA interference (RNAi for BRAF and the kinase inhibitor, sorafenib. Proliferation analysis was performed by BrdU incorporation and apoptosis was accessed by TUNEL assay. Levels of protein expression were analysed by western-blot. Results Both BRAF RNAi and sorafenib inhibited proliferation in all the cell lines independently of the genetic background, mostly in cells with BRAFV600E mutation. In BRAFV600E mutated cells inhibition of BRAF pathway lead to a decrease in ERK1/2 phosphorylation and cyclin D1 levels and an increase in p27Kip1. Specific inhibition of BRAF by RNAi in cells with BRAFV600E mutation had no effect on apoptosis. In the case of sorafenib treatment, cells harbouring BRAFV600E mutation showed increase levels of apoptosis due to a balance of the anti-apoptotic proteins Mcl-1 and Bcl-2. Conclusion Our results in thyroid cancer cells, namely those harbouring BRAFV600Emutation showed that BRAF signalling pathway provides important proliferation signals. We have shown that in thyroid cancer cells sorafenib induces apoptosis by affecting Mcl-1 and Bcl-2 in BRAFV600E mutated cells which was independent of BRAF. These results suggest that sorafenib may prove useful in the treatment of thyroid carcinomas, particularly

  8. Mighty Molecule Models

    Science.gov (United States)

    Brown, Tom; Rushton, Greg; Bencomo, Marie

    2008-01-01

    As part of the SMATHematics Project: The Wonder of Science, The Power of Mathematics--a collaborative partnership between Kennesaw State University and two local school districts, fifth graders had the opportunity to puzzle out chemical formulas of propane, methanol, and other important molecules. In addition, they explored properties that…

  9. Synthesis beyond the molecule

    NARCIS (Netherlands)

    Reinhoudt, D.N.; Crego-Calama, M.

    2002-01-01

    Weak, noncovalent interactions between molecules control many biological functions. In chemistry, noncovalent interactions are now exploited for the synthesis in solution of large supramolecular aggregates. The aim of these syntheses is not only the creation of a particular structure, but also the i

  10. Atoms, Molecules, and Compounds

    CERN Document Server

    Manning, Phillip

    2007-01-01

    Explores the atoms that govern chemical processes. This book shows how the interactions between simple substances such as salt and water are crucial to life on Earth and how those interactions are predestined by the atoms that make up the molecules.

  11. OMG: Open Molecule Generator

    Directory of Open Access Journals (Sweden)

    Peironcely Julio E

    2012-09-01

    Full Text Available Abstract Computer Assisted Structure Elucidation has been used for decades to discover the chemical structure of unknown compounds. In this work we introduce the first open source structure generator, Open Molecule Generator (OMG, which for a given elemental composition produces all non-isomorphic chemical structures that match that elemental composition. Furthermore, this structure generator can accept as additional input one or multiple non-overlapping prescribed substructures to drastically reduce the number of possible chemical structures. Being open source allows for customization and future extension of its functionality. OMG relies on a modified version of the Canonical Augmentation Path, which grows intermediate chemical structures by adding bonds and checks that at each step only unique molecules are produced. In order to benchmark the tool, we generated chemical structures for the elemental formulas and substructures of different metabolites and compared the results with a commercially available structure generator. The results obtained, i.e. the number of molecules generated, were identical for elemental compositions having only C, O and H. For elemental compositions containing C, O, H, N, P and S, OMG produces all the chemically valid molecules while the other generator produces more, yet chemically impossible, molecules. The chemical completeness of the OMG results comes at the expense of being slower than the commercial generator. In addition to being open source, OMG clearly showed the added value of constraining the solution space by using multiple prescribed substructures as input. We expect this structure generator to be useful in many fields, but to be especially of great importance for metabolomics, where identifying unknown metabolites is still a major bottleneck.

  12. OMG: Open Molecule Generator.

    Science.gov (United States)

    Peironcely, Julio E; Rojas-Chertó, Miguel; Fichera, Davide; Reijmers, Theo; Coulier, Leon; Faulon, Jean-Loup; Hankemeier, Thomas

    2012-01-01

    Computer Assisted Structure Elucidation has been used for decades to discover the chemical structure of unknown compounds. In this work we introduce the first open source structure generator, Open Molecule Generator (OMG), which for a given elemental composition produces all non-isomorphic chemical structures that match that elemental composition. Furthermore, this structure generator can accept as additional input one or multiple non-overlapping prescribed substructures to drastically reduce the number of possible chemical structures. Being open source allows for customization and future extension of its functionality. OMG relies on a modified version of the Canonical Augmentation Path, which grows intermediate chemical structures by adding bonds and checks that at each step only unique molecules are produced. In order to benchmark the tool, we generated chemical structures for the elemental formulas and substructures of different metabolites and compared the results with a commercially available structure generator. The results obtained, i.e. the number of molecules generated, were identical for elemental compositions having only C, O and H. For elemental compositions containing C, O, H, N, P and S, OMG produces all the chemically valid molecules while the other generator produces more, yet chemically impossible, molecules. The chemical completeness of the OMG results comes at the expense of being slower than the commercial generator. In addition to being open source, OMG clearly showed the added value of constraining the solution space by using multiple prescribed substructures as input. We expect this structure generator to be useful in many fields, but to be especially of great importance for metabolomics, where identifying unknown metabolites is still a major bottleneck. PMID:22985496

  13. Exotic helium molecules

    International Nuclear Information System (INIS)

    We study the photo-association of an ultracold cloud of magnetically trapped helium atoms: pairs of colliding atoms interact with one or two laser fields to produce a purely long range 4He2(23S1-23P0) molecule, or a 4He2(23S1-23S1) long range molecule. Light shifts in one photon photo-association spectra are measured and studied as a function of the laser polarization and intensity, and the vibrational state of the excited molecule. They result from the light-induced coupling between the excited molecule, and bound and scattering states of the interaction between two metastable atoms. Their analysis leads to the determination of the scattering length a = (7.2 ± 0.6) ruling collisions between spin polarized atoms. The two photon photo-association spectra show evidence of the production of polarized, long-range 4He2(23S1-23S1) molecules. They are said to be exotic as they are made of two metastable atoms, each one carrying a enough energy to ionize the other. The corresponding lineshapes are calculated and decomposed in sums and products of Breit-Wigner and Fano profiles associated to one and two photon processes. The experimental spectra are fit, and an intrinsic lifetime τ = (1.4 ± 0.3) μs is deduced. It is checked whether this lifetime could be limited by spin-dipole induced Penning autoionization. This interpretation requires that there is a quasi-bound state close to the dissociation threshold in the singlet interaction potential between metastable helium atoms for the theory to match the experiment. (author)

  14. Bacterial invasion reconstructed molecule by molecule

    Energy Technology Data Exchange (ETDEWEB)

    Werner, James H [Los Alamos National Laboratory

    2009-01-01

    We propose to visualize the initial stages of bacterial infection of a human host cell with unmatched spatial and temporal resolution. This work will develop a new capability for the laboratory (super-resolution optical imaging), will test unresolved scientific hypotheses regarding host-pathogen interaction dynamics, and leverages state of the art 3D molecular tracking instrumentation developed recently by our group. There is much to be gained by applying new single molecule tools to the important and familiar problem of pathogen entry into a host cell. For example, conventional fluorescence microscopy has identified key host receptors, such as CD44 and {alpha}5{beta}1 integrin, that aggregate near the site of Salmonella typhimurium infection of human cells. However, due to the small size of the bacteria ({approx} 2 {micro}m) and the diffraction of the emitted light, one just sees a fluorescent 'blob' of host receptors that aggregate at the site of attachment, making it difficult to determine the exact number of receptors present or whether there is any particular spatial arrangement of the receptors that facilitates bacterial adhesion/entry. Using newly developed single molecule based super-resolution imaging methods, we will visualize how host receptors are directed to the site of pathogen adhesion and whether host receptors adopt a specific spatial arrangement for successful infection. Furthermore, we will employ our 3D molecular tracking methods to follow the injection of virulence proteins, or effectors, into the host cell by the pathogen Type III secretion system (TTSS). We expect these studies to provide mechanistic insights into the early events of pathogen infection that have here-to-fore been technically beyond our reach. Our Research Goals are: Goal 1--Construct a super-resolution fluorescence microscope and use this new capability to image the spatial distribution of different host receptors (e.g. CD44, as {alpha}5{beta}1 integrin) at the

  15. Atoms, molecules & elements

    CERN Document Server

    Graybill, George

    2007-01-01

    Young scientists will be thrilled to explore the invisible world of atoms, molecules and elements. Our resource provides ready-to-use information and activities for remedial students using simplified language and vocabulary. Students will label each part of the atom, learn what compounds are, and explore the patterns in the periodic table of elements to find calcium (Ca), chlorine (Cl), and helium (He) through hands-on activities.

  16. Single Molecule Mechanochemistry

    Science.gov (United States)

    Li, Shaowei; Zhang, Yanxing; Ho, Wilson; Wu, Ruqian; Ruqian Wu, Yanxing Zhang Team; Wilson Ho, Shaowei Li Team

    Mechanical forces can be used to trigger chemical reactions through bending and stretching of chemical bonds. Using the reciprocating movement of the tip of a scanning tunneling microscope (STM), mechanical energy can be provided to a single molecule sandwiched between the tip and substrate. When the mechanical pulse center was moved to the outer ring feature of a CO molecule, the reaction rate was significantly increased compared with bare Cu surface and over Au atoms. First, DFT calculations show that the presence of CO makes the Cu cavity more attractive toward H2 Second, H2 prefers the horizontal adsorption geometry in the Cu-Cu and Au-Cu cavities and no hybridization occurs between the antibonding states of H2 and states of Cu atoms. While H2 loses electrons from its bonding state in all three cavities, the filling of its anti-bonding state only occurs in the CO-Cu cavity. Both make the CO-Cu cavity much more effectively to chop the H2 molecule. Work was supported by the National Science Foundation Center for Chemical Innovation on Chemistry at the Space-Time Limit (CaSTL) under Grant No. CHE-1414466.

  17. Photonic Molecule Lasers Revisited

    Science.gov (United States)

    Gagnon, Denis; Dumont, Joey; Déziel, Jean-Luc; Dubé, Louis J.

    2014-05-01

    Photonic molecules (PMs) formed by coupling two or more optical resonators are ideal candidates for the fabrication of integrated microlasers, photonic molecule lasers. Whereas most calculations on PM lasers have been based on cold-cavity (passive) modes, i.e. quasi-bound states, a recently formulated steady-state ab initio laser theory (SALT) offers the possibility to take into account the spectral properties of the underlying gain transition, its position and linewidth, as well as incorporating an arbitrary pump profile. We will combine two theoretical approaches to characterize the lasing properties of PM lasers: for two-dimensional systems, the generalized Lorenz-Mie theory will obtain the resonant modes of the coupled molecules in an active medium described by SALT. Not only is then the theoretical description more complete, the use of an active medium provides additional parameters to control, engineer and harness the lasing properties of PM lasers for ultra-low threshold and directional single-mode emission. We will extend our recent study and present new results for a number of promising geometries. The authors acknowledge financial support from NSERC (Canada) and the CERC in Photonic Innovations of Y. Messaddeq.

  18. Mmu-miR-702 functions as an anti-apoptotic mirtron by mediating ATF6 inhibition in mice.

    Science.gov (United States)

    Zhang, Wei-Guang; Chen, Lin; Dong, Qin; He, Juan; Zhao, Han-Dong; Li, Feng-Lan; Li, Hui

    2013-12-01

    MicroRNAs (miRNAs) are a group of endogenous, small, noncoding RNAs that function as key post-transcriptional regulators. miRNAs are involved in many biological processes including apoptosis. In this study, mouse miR-702 (mmu-miR-702), a mirtron derived from the 13th intron of the Plod3 gene, was identified as a regulator of anti-apoptosis. mmu-miR-702 was down-regulated after treatment with the apoptosis-inducer isoproterenol both in vivo and in vitro. According to over-expression experiments, mmu-miR-702 inhibited apoptosis as well as the expression levels of a subset of apoptosis-related genes including activating transcription factor 6 (ATF6). An interaction between mmu-miR-702 and the ATF6 3'-UTR binding site was confirmed using luciferase reporter and western blot assays. This is the first report of ATF6 interaction with miRNA. Although the possible existence of miR-702 in the human genome is low, our results indicate that mirtrons also participate in the process of apoptosis and may provide a novel study strategy for apoptosis. PMID:24035931

  19. A Single Amino Acid Change (Asp 53→ Ala53) Converts Survivin from Anti-apoptotic to Pro-apoptotic

    Science.gov (United States)

    Song, Zhiyin; Liu, Shixin; He, He; Hoti, Naser; Wang, Yi; Feng, Shanshan; Wu, Mian

    2004-01-01

    Survivin is a member of the inhibitor of apoptosis protein (IAP) family that has been implicated in both apoptosis inhibition and cell cycle control. Recently, Survivin has attracted growing attention because of its tumor-specific expression and potential applications in tumor therapy. However, its inhibitory mechanism and subcellular localization remain controversial. Here, we report a novel Survivin mutant Surv-D53A, which displays a function opposite to Survivin and a distinctive subcellular distribution compared with its wild-type counterpart. Surv-D53A was shown to induce apoptosis in a p53-independent manner, indicating that tumor suppressor p53 is not involved in its apoptosis pathway. Surv-D53A was shown to markedly sensitize apoptosis induced by TRAIL, doxorubicin, and RIP3. We also demonstrated that similar to wild-type Survivin, Surv-D53A was localized in cytoplasm in interphase and to midbody at telophase. However, it fails to colocalize in chromosomes with Aurora-B in metaphase as wt-Survivin. Surv-D53A mutant is less stable than wt-Survivin and is degraded more rapidly by ubiquitin-proteasome pathway. Additionally, we found that Surv-D53A interacts with wt-Survivin to form heterodimer or with itself to form mutant homodimer, which may account for the loss of its antiapoptotic function. Finally, unlike Survivin*Survivin, neither Surv-D53A*Survivin nor Surv-D53A*Surv-D53A is able to bind to Smac/DIABLO, which may explain the underlying mechanism for its abolishment of antiapoptotic activity of Survivin. PMID:14699067

  20. A Single Amino Acid Change (Asp 53→ Ala53) Converts Survivin from Anti-apoptotic to Pro-apoptotic

    OpenAIRE

    Song, Zhiyin; Liu, Shixin; He, He; Hoti, Naser; Wang, Yi; Feng, Shanshan; Wu, Mian

    2004-01-01

    Survivin is a member of the inhibitor of apoptosis protein (IAP) family that has been implicated in both apoptosis inhibition and cell cycle control. Recently, Survivin has attracted growing attention because of its tumor-specific expression and potential applications in tumor therapy. However, its inhibitory mechanism and subcellular localization remain controversial. Here, we report a novel Survivin mutant Surv-D53A, which displays a function opposite to Survivin and a distinctive subcellul...

  1. Candida albicans induces pro-inflammatory and anti-apoptotic signals in macrophages as revealed by quantitative proteomics and phosphoproteomics

    DEFF Research Database (Denmark)

    Reales-Calderón, Jose Antonio; Sylvester, Marc; Strijbis, Karin;

    2013-01-01

    Macrophages play a pivotal role in the prevention of Candida albicans infections. Yeast recognition and phagocytosis by macrophages is mediated by Pattern Recognition Receptors (PRRs) that initiate downstream signal transduction cascades by protein phosphorylation and dephosphorylation. We expose...

  2. CREB mediates the insulinotropic and anti-apoptotic effects of GLP-1 signaling in adult mouse β-cells

    Directory of Open Access Journals (Sweden)

    Soona Shin

    2014-11-01

    Conclusions: In sum, our studies using conditional gene deletion put into question current notions about the importance of CREB in regulating β-cell function and mass. However, we reveal an important role for CREB in the β-cell response to GLP-1 receptor signaling, further validating CREB as a therapeutic target for diabetes.

  3. Arctigenin Treatment Protects Against Brain Damage Through an Anti-inflammatory and Anti-apoptotic Mechanism After Needle Insertion

    OpenAIRE

    Jie Song; Na Li; Xia Yang; Zhong Gao; Liang Kong; Yingjia Yao; Yanan Jiao; Yuhui Yan; Shaoheng Li; Zhenyu Tao; Guan Lian; Jingxian Yang; Tingguo Kang

    2016-01-01

    Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in a stab wound injury (SWI). Subsequent secondary injury involves the release of inflammatory and apoptotic cytokines, which have dramatic consequences on the integrity of damaged tissue, leading to the evolution of a pericontusional-damaged area minutes to days after in the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary ...

  4. Dynamical Binding of Hydrogen Bond Surrogate-Derived Bak Helices to Anti-apoptotic Protein Bcl-xL

    OpenAIRE

    Bao, Ju; Dong, Xiao Y.; John Z. H. Zhang; Arora, Paramjit S.

    2009-01-01

    A new peptide modification strategy was recently developed to replace the i to i+4 hydrogen bond of the main chain of an a-helix with a carbon-carbon covalent bond to afford highly stable constrained α-helices, termed Hydrogen Bond Surrogate (HBS) helices. HBS helices that mimic the Bak BH3 domains were experimentally demonstrated to target protein Bcl-xL with high affinity. In this study, molecular dynamics (MD) simulation is used to understand how the covalent modification of the natural Ba...

  5. Arctigenin Treatment Protects against Brain Damage through an Anti-Inflammatory and Anti-Apoptotic Mechanism after Needle Insertion

    OpenAIRE

    Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-feng; Kong, Liang; Yao, Ying-Jia; Jiao, Ya-Nan; Yan, Yu-Hui; Li, Shao-Heng; Tao, Zhen-Yu; Lian, Guan; Yang, Jing-xian; Kang, Ting-Guo

    2016-01-01

    Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in a stab wound injury (SWI). Subsequent secondary injury involves the release of inflammatory and apoptotic cytokines, which have dramatic consequences on the integrity of damaged tissue, leading to the evolution of a pericontusional-damaged area minutes to days after in the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary ...

  6. Regulation of dental pulp stem cell's anti-apoptotic ability and proliferation through over-expression of Bcl-2

    OpenAIRE

    Liu, Yuan; 刘源

    2014-01-01

    The pulp organ is retained in the pulp chamber of teeth and maintains the biological and physiological vitality of the surrounding dentin. It works as a biosensor and generates secondary dentine and tertiary dentine to resist tooth abrasion and pathogenic stimuli (Zhang and Yelick, 2010). However, dental pulp is vulnerable to injury (Smulson and Sieraski, 1989). Most people experience some irreversible pulpal diseases during their lifetime. Hence, pulp regeneration is one of the research task...

  7. Anti-apoptotic effect of San Huang Shel Shin Tang cyclodextrin complex (SHSSTc) on CCl4 -induced hepatotoxicity in rats.

    Science.gov (United States)

    Yang, Cheng-Hsun; Ting, Wei-Jen; Shen, Chia-Yao; Hsu, Hsi-Hsien; Lin, Yueh-Min; Kuo, Chia-Hua; Tsai, Fuu-Jen; Tsai, Chang-Hai; Tsai, Yuhsin; Huang, Chih-Yang

    2016-06-01

    The metabolic loading is heavier in liver especially when injured or inflammation. San Huang Shel Shin Tang (SHSST) was an old traditional herbal decoction, which composed with Rheum officinale Baill, Scutellaria baicalnsis Geprgi and Coptis chinensis Franch (1:1:2 in weight), can provide a liver protection effects. We used a beta-cyclodextrin (β-CD) drug modification method in reduce of the necessary dose of the SHSST. As the results, the FAS-FADD expressions leaded apoptosis in CCl4 intraperitoneal (IP) injection induced acute liver injury in rats. Silymarin, baicalein, SHSST, and SHSST β-CD complex (SHSSTc) pretreatments protected liver through the decreasing of the expressions of FAS-FADD and downstream caspase-3 and caspase-8. Particularly, SHSSTc (30 mg/kg day) treatment enhanced cell survival pathway activation through the PI3K, Akt and Bad phosphorylation. Compared with SHSST as well as silymarin and baicalein, SHSSTc provided a magnificent liver protection effect, especially in survival pathway activation/TUNEL-apoptotic cell reduction/serum cholesterol level suppression. All these data suggested that β-CD complex modified the SHSST and promoted the bioavailability and liver protection effects. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 663-670, 2016.

  8. Tobacco use induces anti-apoptotic, proliferative patterns of gene expression in circulating leukocytes of Caucasian males

    Directory of Open Access Journals (Sweden)

    Wu Samuel S

    2008-08-01

    Full Text Available Abstract Background Strong epidemiologic evidence correlates tobacco use with a variety of serious adverse health effects, but the biological mechanisms that produce these effects remain elusive. Results We analyzed gene transcription data to identify expression spectra related to tobacco use in circulating leukocytes of 67 Caucasian male subjects. Levels of cotinine, a nicotine metabolite, were used as a surrogate marker for tobacco exposure. Significance Analysis of Microarray and Gene Set Analysis identified 109 genes in 16 gene sets whose transcription levels were differentially regulated by nicotine exposure. We subsequently analyzed this gene set by hyperclustering, a technique that allows the data to be clustered by both expression ratio and gene annotation (e.g. Gene Ontologies. Conclusion Our results demonstrate that tobacco use affects transcription of groups of genes that are involved in proliferation and apoptosis in circulating leukocytes. These transcriptional effects include a repertoire of transcriptional changes likely to increase the incidence of neoplasia through an altered expression of genes associated with transcription and signaling, interferon responses and repression of apoptotic pathways.

  9. Lens gene expression analysis reveals downregulation of the anti-apoptotic chaperone alphaA-crystallin during cavefish eye degeneration.

    Science.gov (United States)

    Strickler, Allen G; Byerly, Mardi S; Jeffery, William R

    2007-12-01

    We have conducted a survey of the expression patterns of five genes encoding three different classes of major lens proteins during eye degeneration in the blind cavefish Astyanax mexicanus. This species consists of two forms, an eyed surface-dwelling form (surface fish) and a blind cave-dwelling (cavefish) form. Cavefish form an optic primordium with a lens vesicle and optic cup. In contrast to surface fish, however, the cavefish lens does not differentiate fiber cells and undergoes massive apoptosis. The genes encoding the lens intrinsic membrane proteins MIP and MP19 and the divergent betaB1- and gammaM2-crystallins are expressed during cavefish lens development, although their levels are reduced because of a smaller lens, and the spatial distribution of their transcripts is modified because of the lack of differentiated fiber cells. In contrast, the alphaA-crystallin gene, which encodes a heat shock protein-related chaperone with antiapoptotic activity, is substantially downregulated in the developing cavefish lens. The results suggest that suppression of alphaA-crystallin antiapoptotic activity may be involved in cavefish eye degeneration.

  10. Role of connexin 43 in the mechanism of action of alendronate: dissociation of anti-apoptotic and proliferative signaling pathways

    OpenAIRE

    Lezcano, V; Bellido, T; LI, Plotkin; Boland, R; Morelli, S.

    2012-01-01

    Bisphosphonates (BPs) inhibit osteocyte and osteoblast apoptosis via opening of connexin (Cx) 43 hemichannels and activating the extracellular signal regulated kinases ERKs. Previously, we hypothesized that intracellular survival signaling is initiated by interaction of BPs with Cx43. However, using whole cell binding assays with [3H]-alendronate, herein we demonstrated the presence of saturable, specific and high affinity binding sites in the Cx43-expressing ROS 17/2.8 osteoblastic cells, au...

  11. Role of connexin 43 in the mechanism of action of alendronate: dissociation of anti-apoptotic and proliferative signaling pathways.

    Science.gov (United States)

    Lezcano, V; Bellido, T; Plotkin, L I; Boland, R; Morelli, S

    2012-02-15

    Bisphosphonates (BPs) inhibit osteocyte and osteoblast apoptosis via opening of connexin (Cx) 43 hemichannels and activating the extracellular signal regulated kinases ERKs. Previously, we hypothesized that intracellular survival signaling is initiated by interaction of BPs with Cx43. However, using whole cell binding assays with [(3)H]-alendronate, herein we demonstrated the presence of saturable, specific and high affinity binding sites in the Cx43-expressing ROS 17/2.8 osteoblastic cells, authentic osteoblasts and MLO-Y4 cells expressing Cx43 or not, as well as in HeLa cells lacking Cx43 expression and ROS 17/2.8 cells pretreated with agents that disassemble Cx channels. In addition, both BPs and the PTP inhibitor Na(3)VO(4) increased proliferation of cells expressing Cx43 or not. Furthermore, although BPs are internalized and inhibit intracellular enzymes in osteoclasts, whether the drugs penetrate non-resorptive bone cells is not known. To clarify this, we evaluated the osteoblastic uptake of AF-ALN, a fluorescently labeled analog of alendronate. AF-ALN was rapidly internalized in cells expressing Cx43 or not indicating that this process is not mediated via Cx43 hemichannels. Altogether, these findings suggest that although required for triggering intracellular survival signaling by BPs, Cx43 is dispensable for cellular BP binding, its uptake, as well as the proliferative effects of these agents. PMID:22230328

  12. Anti-apoptotic and anti-inflammatory effects of naringin on cisplatin-induced renal injury in the rat.

    Science.gov (United States)

    Chtourou, Yassine; Aouey, Baktha; Aroui, Sonia; Kebieche, Mohammed; Fetoui, Hamadi

    2016-01-01

    Nephrotoxicity is a common complication of cisplatin chemotherapy and thus limits the use of cisplatin in clinic. Naringin, a natural flavonoid, plays important roles in inflammation and apoptosis in some inflammatory diseases; however, its roles in cisplatin-induced nephrotoxicity remain unclear. In this study, we first assessed the involvement of ROS overproduction and inflammation in cisplatin-induced nephrotoxicity in aged rats, and then we investigated the changes of renal function, histological injury, inflammatory response, and apoptosis in renal tissues after treatment with naringin (20, 50 or 100 mg/kg body weight). Cisplatin resulted in an increase of renal markers, lipid peroxidation, protein and DNA oxidation, and ROS formation. Renal tumor necrosis factor-α (TNF-α) and nitrite levels were also elevated. Expressions of nuclear factor-kappa B (NF-κB), inductible nitric oxide synthase (iNOS), caspase-3 and p53 were up-regulated in renal tissues of Cis-treated rats compared with the normal control group. Histopathological changes were also observed in cisplatin group. Adminstration of naringin at different doses (25, 50 and 100 mg/kg) was able to protect against the deterioration in kidney function, abrogate the decline in antioxidant enzyme activities and suppressed the increase in TBARS, nitrite and TNF-α concentrations. Moreover, naringin inhibited NF-κB and iNOS pathways, caspase-3 and p53 activation and improved the histological changes induced by cisplatin. In conclusion, our studies suggest that oxidative stress and inflammation might play important roles in the development of cisplatin-induced nephrotoxicity and naringin might become an effective therapeutic strategy for this disease. PMID:26612654

  13. Effect of preoperative radio-frequency thermotherapy combined with FOLFOX adjuvant treatment on microvessel density and expression apoptosis-related molecules in colon carcinoma%术前射频热疗联合FOLFOX辅助治疗对结肠癌组织中 MVD以及凋亡相关分子表达的影响

    Institute of Scientific and Technical Information of China (English)

    付全航

    2016-01-01

    mRNA and protein expression of anti- apoptotic molecules p53, CDC25A and Bcl- 2 in tumor tissue of study group were lower than those of control group (P<0.05). Conclusion Preoperative radio- frequency thermotherapy combined with FOLFOX adjuvant treatment may reduce microvessel density, up- regulate pro- apoptotic molecules expression, and down- regulate anti- apoptotic molecules expression in colon cancer.

  14. Molecules in crystals

    Science.gov (United States)

    Spackman, Mark A.

    2013-04-01

    Hirshfeld surface analysis has developed from the serendipitous discovery of a novel partitioning of the crystal electron density into discrete molecular fragments, to a suite of computational tools used widely for the identification, analysis and discussion of intermolecular interactions in molecular crystals. The relationship between the Hirshfeld surface and very early ideas on the internal structure of crystals is outlined, and applications of Hirshfeld surface analysis are presented for three molecules of historical importance in the development of modern x-ray crystallography: hexamethylbenzene, hexamethylenetetramine and diketopiperazine.

  15. Carbon Monoxide Releasing Molecule-A1 (CORM-A1 Improves Neurogenesis: Increase of Neuronal Differentiation Yield by Preventing Cell Death.

    Directory of Open Access Journals (Sweden)

    Ana S Almeida

    Full Text Available Cerebral ischemia and neurodegenerative diseases lead to impairment or death of neurons in the central nervous system. Stem cell based therapies are promising strategies currently under investigation. Carbon monoxide (CO is an endogenous product of heme degradation by heme oxygenase (HO activity. Administration of CO at low concentrations produces several beneficial effects in distinct tissues, namely anti-apoptotic and anti-inflammatory. Herein the CO role on modulation of neuronal differentiation was assessed. Three different models with increasing complexity were used: human neuroblastoma SH-S5Y5 cell line, human teratocarcinoma NT2 cell line and organotypic hippocampal slice cultures (OHSC. Cell lines were differentiated into post-mitotic neurons by treatment with retinoic acid (RA supplemented with CO-releasing molecule A1 (CORM-A1. CORM-A1 positively modulated neuronal differentiation, since it increased final neuronal production and enhanced the expression of specific neuronal genes: Nestin, Tuj1 and MAP2. Furthermore, during neuronal differentiation process, there was an increase in proliferative cell number (ki67 mRNA expressing cells and a decrease in cell death (lower propidium iodide (PI uptake, limitation of caspase-3 activation and higher Bcl-2 expressing cells. CO supplementation did not increase the expression of RA receptors. In the case of SH-S5Y5 model, small amounts of reactive oxygen species (ROS generation emerges as important signaling molecules during CO-promoted neuronal differentiation. CO's improvement of neuronal differentiation yield was validated using OHSC as ex vivo model. CORM-A1 treatment of OHSC promoted higher levels of cells expressing the neuronal marker Tuj1. Still, CORM-A1 increased cell proliferation assessed by ki67 expression and also prevented cell death, which was followed by increased Bcl-2 expression, decreased levels of active caspase-3 and PI uptake. Likewise, ROS signaling emerged as key factors

  16. Carbon Monoxide Releasing Molecule-A1 (CORM-A1) Improves Neurogenesis: Increase of Neuronal Differentiation Yield by Preventing Cell Death.

    Science.gov (United States)

    Almeida, Ana S; Soares, Nuno L; Vieira, Melissa; Gramsbergen, Jan Bert; Vieira, Helena L A

    2016-01-01

    Cerebral ischemia and neurodegenerative diseases lead to impairment or death of neurons in the central nervous system. Stem cell based therapies are promising strategies currently under investigation. Carbon monoxide (CO) is an endogenous product of heme degradation by heme oxygenase (HO) activity. Administration of CO at low concentrations produces several beneficial effects in distinct tissues, namely anti-apoptotic and anti-inflammatory. Herein the CO role on modulation of neuronal differentiation was assessed. Three different models with increasing complexity were used: human neuroblastoma SH-S5Y5 cell line, human teratocarcinoma NT2 cell line and organotypic hippocampal slice cultures (OHSC). Cell lines were differentiated into post-mitotic neurons by treatment with retinoic acid (RA) supplemented with CO-releasing molecule A1 (CORM-A1). CORM-A1 positively modulated neuronal differentiation, since it increased final neuronal production and enhanced the expression of specific neuronal genes: Nestin, Tuj1 and MAP2. Furthermore, during neuronal differentiation process, there was an increase in proliferative cell number (ki67 mRNA expressing cells) and a decrease in cell death (lower propidium iodide (PI) uptake, limitation of caspase-3 activation and higher Bcl-2 expressing cells). CO supplementation did not increase the expression of RA receptors. In the case of SH-S5Y5 model, small amounts of reactive oxygen species (ROS) generation emerges as important signaling molecules during CO-promoted neuronal differentiation. CO's improvement of neuronal differentiation yield was validated using OHSC as ex vivo model. CORM-A1 treatment of OHSC promoted higher levels of cells expressing the neuronal marker Tuj1. Still, CORM-A1 increased cell proliferation assessed by ki67 expression and also prevented cell death, which was followed by increased Bcl-2 expression, decreased levels of active caspase-3 and PI uptake. Likewise, ROS signaling emerged as key factors in CO

  17. Ultra-cold molecule production.

    Energy Technology Data Exchange (ETDEWEB)

    Ramirez-Serrano, Jamie; Chandler, David W.; Strecker, Kevin; Rahn, Larry A.

    2005-12-01

    The production of Ultra-cold molecules is a goal of many laboratories through out the world. Here we are pursuing a unique technique that utilizes the kinematics of atomic and molecular collisions to achieve the goal of producing substantial numbers of sub Kelvin molecules confined in a trap. Here a trap is defined as an apparatus that spatially localizes, in a known location in the laboratory, a sample of molecules whose temperature is below one degree absolute Kelvin. Further, the storage time for the molecules must be sufficient to measure and possibly further cool the molecules. We utilize a technique unique to Sandia to form cold molecules from near mass degenerate collisions between atoms and molecules. This report describes the progress we have made using this novel technique and the further progress towards trapping molecules we have cooled.

  18. Immunohistochemical expression of the oncogenic molecules active Stat3 and survivin in benign and malignant salivary gland tumors

    Science.gov (United States)

    Nikitakis, Nikolaos G.; Scheper, Mark A.; Papanicolaou, Vasileios S.; Sklavounou, Alexandra; Sauk, John J.

    2009-01-01

    Objective Signal transducer and activator of transcription 3 (Stat3) and survivin have been shown to exert oncogenic effects in various human neoplasms. The purpose of this study was to evaluate the expression of the tyrosine phosphorylated (active) Stat3 and survivin in various benign and malignant salivary gland tumors (SGTs). Study design Eighty-six SGTs (65 malignant and 21 benign tumors of various histopathologic subtypes) were immunohistochemically stained with anti-survivin or anti-phosphorylated tyrosine-705 (p-tyr) Stat3 antibodies. Immunohistochemical reactivity was graded in a semi-quantitative manner; a combined score of immunohistochemical positivity (0–6) was calculated for each tumor by adding the individual scores for percentage of tumor cells (0–3) and intensity of staining (0–3). Results Survivin was immunohistochemically detected in all studied benign and malignant SGTs; p-tyr Stat3 was also detected in the majority (91%) of SGTs. The average combined scores for survivin and p-tyr Stat3 immunohistochemical expression in the studied malignant SGTs was 4.40 and 3.35, respectively; the corresponding combined scores for survivin and p-tyr Stat3 in the studied benign SGTs were 4.37 and 3.22, respectively. No statistically significant differences (p>0.05) in p-tyr Stat3 or survivin expression were detected between the benign and malignant groups, or among the various examined histopathological subtypes of SGTs. In contrast, normal salivary gland elements in the vicinity of the studied tumors revealed only weak and focal survivin or p-tyr Stat3 immunoreactivity, mainly localized to ductal and mucous cells. Conclusions Our data indicate an almost universal expression of activated Stat3 and survivin in benign and malignant SGTs. Considering the well-established proliferative and anti-apoptotic properties of these molecules and their functional interrelationship, selective targeting techniques against Stat3 and/or survivin may represent promising

  19. Magnetic field modification of ultracold molecule-molecule collisions

    OpenAIRE

    Tscherbul, T. V.; Suleimanov, Yu. V.; Aquilanti, V.; Krems, R.V.

    2008-01-01

    We present an accurate quantum mechanical study of molecule-molecule collisions in the presence of a magnetic field. The work focusses on the analysis of elastic scattering and spin relaxation in collisions of O2(3Sigma_g) molecules at cold (~0.1 K) and ultracold (~10^{-6} K) temperatures. Our calculations show that magnetic spin relaxation in molecule-molecule collisions is extremely efficient except at magnetic fields below 1 mT. The rate constant for spin relaxation at T=0.1 K and a magnet...

  20. Passing Current through Touching Molecules

    DEFF Research Database (Denmark)

    Schull, G.; Frederiksen, Thomas; Brandbyge, Mads;

    2009-01-01

    The charge flow from a single C-60 molecule to another one has been probed. The conformation and electronic states of both molecules on the contacting electrodes have been characterized using a cryogenic scanning tunneling microscope. While the contact conductance of a single molecule between two...

  1. Forces in molecules.

    Science.gov (United States)

    Hernández-Trujillo, Jesús; Cortés-Guzmán, Fernando; Fang, De-Chai; Bader, Richard F W

    2007-01-01

    Chemistry is determined by the electrostatic forces acting within a collection of nuclei and electrons. The attraction of the nuclei for the electrons is the only attractive force in a molecule and is the force responsible for the bonding between atoms. This is the attractive force acting on the electrons in the Ehrenfest force and on the nuclei in the Feynman force, one that is countered by the repulsion between the electrons in the former and by the repulsion between the nuclei in the latter. The virial theorem relates these forces to the energy changes resulting from interactions between atoms. All bonding, as signified by the presence of a bond path, has a common origin in terms of the mechanics determined by the Ehrenfest, Feynman and virial theorems. This paper is concerned in particular with the mechanics of interaction encountered in what are classically described as 'nonbonded interactions'--are atoms that 'touch' bonded or repelling one another? PMID:17328425

  2. Forces in molecules.

    Science.gov (United States)

    Hernández-Trujillo, Jesús; Cortés-Guzmán, Fernando; Fang, De-Chai; Bader, Richard F W

    2007-01-01

    Chemistry is determined by the electrostatic forces acting within a collection of nuclei and electrons. The attraction of the nuclei for the electrons is the only attractive force in a molecule and is the force responsible for the bonding between atoms. This is the attractive force acting on the electrons in the Ehrenfest force and on the nuclei in the Feynman force, one that is countered by the repulsion between the electrons in the former and by the repulsion between the nuclei in the latter. The virial theorem relates these forces to the energy changes resulting from interactions between atoms. All bonding, as signified by the presence of a bond path, has a common origin in terms of the mechanics determined by the Ehrenfest, Feynman and virial theorems. This paper is concerned in particular with the mechanics of interaction encountered in what are classically described as 'nonbonded interactions'--are atoms that 'touch' bonded or repelling one another?

  3. Lanthanide single molecule magnets

    CERN Document Server

    Tang, Jinkui

    2015-01-01

    This book begins by providing basic information on single-molecule magnets (SMMs), covering the magnetism of lanthanide, the characterization and relaxation dynamics of SMMs, and advanced means of studying lanthanide SMMs. It then systematically introduces lanthanide SMMs ranging from mononuclear and dinuclear to polynuclear complexes, classifying them and highlighting those SMMs with high barrier and blocking temperatures – an approach that provides some very valuable indicators for the structural features needed to optimize the contribution of an Ising type spin to a molecular magnet. The final chapter presents some of the newest developments in the lanthanide SMM field, such as the design of multifunctional and stimuli-responsive magnetic materials as well as the anchoring and organization of the SMMs on surfaces. In addition, the crystal structure and magnetic data are clearly presented with a wealth of illustrations in each chapter, helping newcomers and experts alike to better grasp ongoing trends and...

  4. Lanthanide single molecule magnets

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Jinkui; Zhang, Peng [Chinese Academy of Sciences, Changchun (China). Changchun Inst. of Applied Chemistry

    2015-10-01

    This book begins by providing basic information on single-molecule magnets (SMMs), covering the magnetism of lanthanide, the characterization and relaxation dynamics of SMMs and advanced means of studying lanthanide SMMs. It then systematically introduces lanthanide SMMs ranging from mononuclear and dinuclear to polynuclear complexes, classifying them and highlighting those SMMs with high barrier and blocking temperatures - an approach that provides some very valuable indicators for the structural features needed to optimize the contribution of an Ising type spin to a molecular magnet. The final chapter presents some of the newest developments in the lanthanide SMM field, such as the design of multifunctional and stimuli-responsive magnetic materials as well as the anchoring and organization of the SMMs on surfaces. In addition, the crystal structure and magnetic data are clearly presented with a wealth of illustrations in each chapter, helping newcomers and experts alike to better grasp ongoing trends and explore new directions.

  5. Carbon monoxide-Releasing Molecule-2 (CORM-2 attenuates acute hepatic ischemia reperfusion injury in rats

    Directory of Open Access Journals (Sweden)

    Zhang Weihui

    2010-05-01

    Full Text Available Abstract Background Hepatic ischemia-reperfusion injury (I/Ri is a serious complication occurring during liver surgery that may lead to liver failure. Hepatic I/Ri induces formation of reactive oxygen species, hepatocyte apoptosis, and release of pro-inflammatory cytokines, which together causes liver damage and organ dysfunction. A potential strategy to alleviate hepatic I/Ri is to exploit the potent anti-inflammatory and cytoprotective effects of carbon monoxide (CO by application of so-called CO-releasing molecules (CORMs. Here, we assessed whether CO released from CORM-2 protects against hepatic I/Ri in a rat model. Methods Forty male Wistar rats were randomly assigned into four groups (n = 10. Sham group underwent a sham operation and received saline. I/R group underwent hepatic I/R procedure by partial clamping of portal structures to the left and median lobes with a microvascular clip for 60 minutes, yielding ~70% hepatic ischemia and subsequently received saline. CORM-2 group underwent the same procedure and received 8 mg/kg of CORM-2 at time of reperfusion. iCORM-2 group underwent the same procedure and received iCORM-2 (8 mg/kg, which does not release CO. Therapeutic effects of CORM-2 on hepatic I/Ri was assessed by measuring serum damage markers AST and ALT, liver histology score, TUNEL-scoring of apoptotic cells, NFkB-activity in nuclear liver extracts, serum levels of pro-inflammatory cytokines TNF-α and IL-6, and hepatic neutrophil infiltration. Results A single systemic infusion with CORM-2 protected the liver from I/Ri as evidenced by a reduction in serum AST/ALT levels and an improved liver histology score. Treatment with CORM-2 also up-regulated expression of the anti-apoptotic protein Bcl-2, down-regulated caspase-3 activation, and significantly reduced the levels of apoptosis after I/Ri. Furthermore, treatment with CORM-2 significantly inhibited the activity of the pro-inflammatory transcription factor NF-κB as measured in

  6. Thread bonds in molecules

    CERN Document Server

    Ivlev, B

    2015-01-01

    Unusual chemical bonds are proposed. Each bond is almost covalent but is characterized by the thread of a small radius $\\sim 0.6\\times 10^{-11}$cm, between two nuclei in a molecule. The main electron density is concentrated outside the thread as in a covalent bond. The thread is formed by the electron wave function which has a tendency to be singular on it. The singularity along the thread is cut off by electron "vibrations" due to the interaction with zero point electromagnetic oscillations. The electron energy has its typical value of (1-10)eV. Due to the small tread radius the uncertainty of the electron momentum inside the thread is large resulting in a large electron kinetic energy $\\sim 1 MeV$. This energy is compensated by formation of a potential well due to the reduction of the energy of electromagnetic zero point oscillations. This is similar to formation of a negative van der Waals potential. Thread bonds are stable and cannot be created or destructed in chemical or optical processes.

  7. Tunnelling of a molecule

    International Nuclear Information System (INIS)

    A quantum-mechanical description of tunnelling is presented for a one-dimensional system with internal oscillator degrees of freedom. The 'charged diatomic molecule' is frustrated on encountering a barrier potential by its centre of charge not being coincident with its centre of mass, resulting in transitions amongst internal states. In an adiabatic limit, the tunnelling of semiclassical coherent-like oscillator states is shown to exhibit the Hartman and Bueuttiker-Landauer times tH and tBL, with the time dependence of the coherent state parameter for the tunnelled state given by α(t) = α e-iω(t+Δt) , Δt = tH - itBL. A perturbation formalism is developed, whereby the exact transfer matrix can be expanded to any desired accuracy in a suitable limit. An 'intrinsic' time, based on the oscillator transition rate during tunnelling, transmission or reflection, is introduced. In simple situations the resulting intrinsic tunnelling time is shown to vanish to lowest order. In the general case a particular (nonzero) parametrisation is inferred, and its properties discussed in comparison with the literature on tunnelling times for both wavepackets and internal clocks. Copyright (1998) CSIRO Australia

  8. Molecule-based magnets

    Indian Academy of Sciences (India)

    J V Yakhmi

    2009-06-01

    The conventional magnetic materials used in current technology, such as, Fe, Fe2O3, Cr2O3, SmCo5, Nd2Fe14B etc are all atom-based, and their preparation/processing require high temperature routes. Employing self-assembly methods, it is possible to engineer a bulk molecular material with long-range magnetic order, mainly because one can play with the weak intermolecular interactions. Since the first successful synthesis of molecular magnets in 1986, a large variety of them have been synthesized, which can be categorized on the basis of the chemical nature of the magnetic units involved: organic-, metal-based systems, heterobimetallic assemblies, or mixed organic–inorganic systems. The design of molecule-based magnets has also been extended to the design of poly-functional molecular magnets, such as those exhibiting second-order optical nonlinearity, liquid crystallinity, or chirality simultaneously with long-range magnetic order. Solubility, low density and biocompatibility are attractive features of molecular magnets. Being weakly coloured, unlike their opaque classical magnet ‘cousins’ listed above, possibilities of photomagnetic switching exist. Persistent efforts also continue to design the ever-elusive polymer magnets towards applications in industry. While providing a brief overview of the field of molecular magnetism, this article highlights some recent developments in it, with emphasis on a few studies from the author’s own lab.

  9. Strongly interacting ultracold polar molecules

    Science.gov (United States)

    Gadway, Bryce; Yan, Bo

    2016-08-01

    This paper reviews recent advances in the study of strongly interacting systems of dipolar molecules. Heteronuclear molecules feature large and tunable electric dipole moments, which give rise to long-range and anisotropic dipole–dipole interactions. Ultracold samples of dipolar molecules with long-range interactions offer a unique platform for quantum simulations and the study of correlated many-body physics. We provide an introduction to the physics of dipolar quantum gases, both electric and magnetic, and summarize the multipronged efforts to bring dipolar molecules into the quantum regime. We discuss in detail the recent experimental progress in realizing and studying strongly interacting systems of polar molecules trapped in optical lattices, with particular emphasis on the study of interacting spin systems and non-equilibrium quantum magnetism. Finally, we conclude with a brief discussion of the future prospects for studies of strongly interacting dipolar molecules.

  10. Strongly interacting ultracold polar molecules

    CERN Document Server

    Gadway, Bryce

    2016-01-01

    This paper reviews recent advances in the study of strongly interacting systems of dipolar molecules. Heteronuclear molecules feature large and tunable electric dipole moments, which give rise to long-range and anisotropic dipole-dipole interactions. Ultracold samples of dipolar molecules with long-range interactions offer a unique platform for quantum simulations and the study of correlated many-body physics. We provide an introduction to the physics of dipolar quantum gases, both electric and magnetic, and summarize the multipronged efforts to bring dipolar molecules into the quantum regime. We discuss in detail the recent experimental progress in realizing and studying strongly interacting systems of polar molecules trapped in optical lattices, with particular emphasis on the study of interacting spin systems and non-equilibrium quantum magnetism. Finally, we conclude with a brief discussion of the future prospects for studies of strongly interacting dipolar molecules.

  11. Molecules Best Paper Award 2012

    Directory of Open Access Journals (Sweden)

    Derek J. McPhee

    2012-02-01

    Full Text Available Molecules starts to institute the “Best Paper” award to recognize these outstanding papers in the area of natural products, medicinal chemistry and molecular diversity published in Molecules. We are pleased to announce the first “Molecules Best Paper Award” for 2012. Nominations were selected by the editor-in-chief and selected editorial board members from all the papers published in 2008. [...

  12. Molecules Best Paper Award 2014

    Directory of Open Access Journals (Sweden)

    Derek J. McPhee

    2014-01-01

    Full Text Available Molecules instituted some years ago a “Best Paper” award to recognize the most outstanding papers in the area of natural products, medicinal chemistry and molecular diversity published each year in Molecules. We are pleased to announce the third “Molecules Best Paper Award” for 2014. The winners were chosen by the Editor-in-Chief and selected editorial board members from among all the papers published in 2010. Reviews and research papers were evaluated separately.

  13. Molecules Best Paper Award 2013

    Directory of Open Access Journals (Sweden)

    Derek J. McPhee

    2013-02-01

    Full Text Available Molecules has started to institute a "Best Paper" award to recognize the most outstanding papers in the area of natural products, medicinal chemistry and molecular diversity published in Molecules. We are pleased to announce the second "Molecules Best Paper Award" for 2013. Candidates were chosen by the Editor-in-Chief and selected editorial board members from among all the papers published in 2009.

  14. Recoiling DNA Molecule: Simulation & Experiment

    OpenAIRE

    Neto, Jose Coelho; Dickman, Ronald; Mesquita, O. N.

    2002-01-01

    Single molecule DNA experiments often generate data from force versus extension measurements involving the tethering of a microsphere to one end of a single DNA molecule while the other is attached to a substrate. We show that the persistence length of single DNA molecules can also be measured based on the recoil dynamics of these DNA-microsphere complexes if appropriate corrections are made to the friction coefficient of the microsphere in the vicinity of the substrate. Comparison between co...

  15. Molecules Best Paper Award 2015

    Directory of Open Access Journals (Sweden)

    Derek J. McPhee

    2015-01-01

    Full Text Available Molecules instituted some years ago a “Best Paper” award to recognize the most outstanding papers in the area of organic synthesis, natural products, medicinal chemistry and molecular diversity published each year in Molecules. We are pleased to announce the third “Molecules Best Paper Award” for 2015. The winners were chosen by the Editor-in-Chief and selected editorial board members from among all the papers published in 2011. Reviews and research papers were evaluated separately. We are pleased to announce that the following eight papers have won the Molecules Best Paper Award for 2015:[...

  16. STM investigation of surfactant molecules

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Adsorption and self-organization of sodium alkyl sulfonates (STS and SHS) have been studied on HOPG by using the in situ scanning tunneling microscopy (STM). Both SHS and STS molecules adsorb on the HOPG surface and form long-range well-ordered monolayers. The neighboring molecules in different rows form a "head to head" configuration. In the high-resolution images of STS and SHS molecules, one end of the molecules shows bright spots which are attributed to the SO3- groups.

  17. Micro-Kelvin cold molecules.

    Energy Technology Data Exchange (ETDEWEB)

    Strecker, Kevin E.; Chandler, David W.

    2009-10-01

    We have developed a novel experimental technique for direct production of cold molecules using a combination of techniques from atomic optical and molecular physics and physical chemistry. The ability to produce samples of cold molecules has application in a broad spectrum of technical fields high-resolution spectroscopy, remote sensing, quantum computing, materials simulation, and understanding fundamental chemical dynamics. Researchers around the world are currently exploring many techniques for producing samples of cold molecules, but to-date these attempts have offered only limited success achieving milli-Kelvin temperatures with low densities. This Laboratory Directed Research and Development project is to develops a new experimental technique for producing micro-Kelvin temperature molecules via collisions with laser cooled samples of trapped atoms. The technique relies on near mass degenerate collisions between the molecule of interest and a laser cooled (micro-Kelvin) atom. A subset of collisions will transfer all (nearly all) of the kinetic energy from the 'hot' molecule, cooling the molecule at the expense of heating the atom. Further collisions with the remaining laser cooled atoms will thermally equilibrate the molecules to the micro-Kelvin temperature of the laser-cooled atoms.

  18. Organic heterocyclic molecules become superalkalis.

    Science.gov (United States)

    Reddy, G Naaresh; Giri, Santanab

    2016-09-21

    An organic molecule which behaves like a superalkali has been designed from an aromatic heterocyclic molecule, pyrrole. Using first-principles calculation and a systematic two-step approach, we can have superalkali molecules with a low ionization energy, even lower than that of Cs. Couple cluster (CCSD) calculation reveals that a new heterocycle, C3N2(CH3)5 derived from a well-known aromatic heterocycle, pyrrole (C4H5N) has an ionization energy close to 3.0 eV. A molecular dynamics calculation on C3N2(CH3)5 reveals that the structure is dynamically stable. PMID:27530344

  19. Polar molecule dominated electrorheological effect

    Institute of Scientific and Technical Information of China (English)

    Lu Kun-Quan; Shen Rong; Wang Xue-Zhao; Sun Gang; Wen Wei-Jia; Liu Ji-Xing

    2006-01-01

    The yield stress of our newly developed electrorheological (ER) fluids consisting of dielectric nano-particles suspended in silicone oil reaches hundreds of kPa, which is orders of magnitude higher than that of conventional ones. We found that the polar molecules adsorbed on the particles play a decisive role in such new ER fluids. To explain this polar molecule dominated ER (PM-ER) effect a model is proposed based on the interaction of polar molecule-charge between the particles, where the local electric field is significantly enhanced and results in the polar molecules aligning in the direction of the electric field. The model can well explain the giant ER effect and a near-linear dependence of the yield stress on the electric field. The main effective factors for achieving high-performance PM-ER fluids are discussed. The PM-ER fluids with the yield stress higher than one MPa can be expected.

  20. Special Issue: Single Molecule Techniques

    Directory of Open Access Journals (Sweden)

    Hans H. Gorris

    2015-04-01

    Full Text Available Technological advances in the detection and manipulation of single molecules have enabled new insights into the function, structure and interactions of biomolecules. This Special Issue was launched to account for the rapid progress in the field of “Single Molecule Techniques”. Four original research articles and seven review articles provide an introduction, as well as an in-depth discussion, of technical developments that are indispensable for the characterization of individual biomolecules. Fluorescence microscopy takes center stage in this Special Issue because it is one of the most sensitive and flexible techniques, which has been adapted in many variations to the specific demands of single molecule analysis. Two additional articles are dedicated to single molecule detection based on atomic force microscopy.

  1. Absorption characteristics of bacteriorhodopsin molecules

    Indian Academy of Sciences (India)

    H K T Kumar; K Appaji Gowda

    2000-03-01

    The bacteriorhodopsin molecule absorbs light and undergoes a series of structural transformation following a well-defined photocycle. The complex photocycle is transformed to an equivalent level diagram by considering the lifetime of the intermediate states. Assuming that only and states are appreciably populated at any instant of time, the level diagram is further simplified to two-level system. Based on the rate equations for two-level system, an analytic expression for the absorption coefficient of bacteriorhodopsin molecule is derived. It is applied to study the behaviour of absorption coefficient of bacteriorhodopsin film in the visible wavelength region of 514 nm. The dependence of absorption coefficient of bacteriorhodopsin film on the thickness of the film, total number density of active molecules and initial number density of molecules in -state is presented in the graphical form.

  2. Theoretical Investigations Regarding Single Molecules

    DEFF Research Database (Denmark)

    Pedersen, Kim Georg Lind

    interfere destructively or constructively. Destructive interference effects in electron transport could potentially improve thermo-electrics, organic logic circuits and energy harvesting. We have investigated destructive interference in off-resonant transport through organic molecules, and have found a set...

  3. Ultracold molecules and ultracold chemistry

    OpenAIRE

    Softley, Tim; Bell, Martin

    2009-01-01

    Abstract The recent development of a range of new methods for producing samples of gas phase molecules that are translationally cold (T < 1 K) or ultracold (T < 1 mK) is driving efforts to study reactive and inelastic collisional processes in these temperature regimes. In this review article the new methods for cold/ultracold molecule production are reviewed in the context of their potential or current use in collisional studies and progress in the application of these methods i...

  4. Galectin-3 augments tumor initiating property and tumorigenicity of lung cancer through interaction with β-catenin

    OpenAIRE

    Chung, Ling-Yen; Tang, Shye-Jye; Wu, Yi-Ching; Sun, Guang-Huan; Liu, Huan-Yun; Sun, Kuang-Hui

    2014-01-01

    Cancer stem cells (CSCs) are comprised of a rare sub-population of cells in tumors that have been proposed to be responsible for high recurrence rates and resistance to chemotherapy. Galectins are highly expressed in cancers that correlate with the aggressiveness of tumors. Galectins may also promote the resistance of cancer cells to chemotherapy. However, the role of galectins in CSCs remains unknown. In this study, sphere formation was used to enrich H1299 human lung CSCs that had self-rene...

  5. Placental Expression Patterns of Galectin-1, Galectin-2, Galectin-3 and Galectin-13 in Cases of Intrauterine Growth Restriction (IUGR

    Directory of Open Access Journals (Sweden)

    Stefan Hutter

    2016-04-01

    Full Text Available Galectins (gal are members of the mammalian β-galactoside-binding proteins and recognize Galβ1-4GlcNAc and Galβ1-4GalNac (Thomsen-Friedenreich antigen (TF sequences of several cell surface oligosaccharides. In this study, gal-1, -2, -3 and -13 were investigated systematically in the trophoblast and decidua compartment of intrauterine growth restriction (IUGR placentas and normal third trimester control placentas and stratified by fetal gender and gestational age. Within this study, 29 third trimester placentas after delivery were analyzed. Fetal gender was equally divided within both groups, and immunohistochemical staining was analyzed according to fetal gender and gestational age. Double immune-fluorescence with trophoblast-specific markers was used to identify galectin-expressing cells at the feto-maternal interface in the decidua. Gal-3 was significantly downregulated only in the extravillous trophoblast of IUGR placentas. In contrast, expressions of gal-2 and gal-13 were downregulated in both villous and extravillous trophoblast cells of IUGR placentas. In addition, gal-2 and gal-13 showed a highly correlated expression scheme in the placenta. There are significant gender-specific expression patterns for single prototype galectins with downregulation of gal-2 and gal-13 of male gender placentas in cases of IUGR. Gal-3 as the chimera type galectin shows only little gender-specific differences in expression, which disappear in IUGR cases.

  6. The Molecule Cloud - compact visualization of large collections of molecules

    Directory of Open Access Journals (Sweden)

    Ertl Peter

    2012-07-01

    Full Text Available Abstract Background Analysis and visualization of large collections of molecules is one of the most frequent challenges cheminformatics experts in pharmaceutical industry are facing. Various sophisticated methods are available to perform this task, including clustering, dimensionality reduction or scaffold frequency analysis. In any case, however, viewing and analyzing large tables with molecular structures is necessary. We present a new visualization technique, providing basic information about the composition of molecular data sets at a single glance. Summary A method is presented here allowing visual representation of the most common structural features of chemical databases in a form of a cloud diagram. The frequency of molecules containing particular substructure is indicated by the size of respective structural image. The method is useful to quickly perceive the most prominent structural features present in the data set. This approach was inspired by popular word cloud diagrams that are used to visualize textual information in a compact form. Therefore we call this approach “Molecule Cloud”. The method also supports visualization of additional information, for example biological activity of molecules containing this scaffold or the protein target class typical for particular scaffolds, by color coding. Detailed description of the algorithm is provided, allowing easy implementation of the method by any cheminformatics toolkit. The layout algorithm is available as open source Java code. Conclusions Visualization of large molecular data sets using the Molecule Cloud approach allows scientists to get information about the composition of molecular databases and their most frequent structural features easily. The method may be used in the areas where analysis of large molecular collections is needed, for example processing of high throughput screening results, virtual screening or compound purchasing. Several example visualizations of large

  7. Molecule-by-Molecule Writing Using a Focused Electron Beam

    DEFF Research Database (Denmark)

    Van Dorp, Willem F.; Zhang, Xiaoyan; Feringa, Ben L.;

    2012-01-01

    on graphene can be followed molecule-by-molecule with FEBID. The results show that mechanisms that are inherent to the process inhibit a further increase in control over the process. Hence, our results present the resolution limit of (electron) optical lithography techniques. The writing of isolated...... atoms also be written with an electron beam? We verify this with focused electron-beam-induced deposition (FEBID), a direct-write technique that has the current record for the smallest feature written by (electron) optical lithography. We show that the deposition of an organometallic precursor...

  8. Measuring an antibody affinity distribution molecule by molecule

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M [Los Alamos National Laboratory; Werner, James H [Los Alamos National Laboratory; Temirov, Jamshid [INVITROGEN

    2008-01-01

    Single molecule fluorescence mIcroscopy was used to observe the binding and unbinding of hapten decorated quantum dots with individual surface immobilized antibodies. The fluorescence time history from an individual antibody site can be used to calculate its binding affinity. While quantum dot blinking occurs during these measurements, we describe a simple empirical method to correct the apparent/observed affinity to account for the blinking contribution. The combination of many single molecule affinity measurements from different antibodies yields not only the average affinity, it directly measures the full shape and character of the surface affinity distribution function.

  9. Laser spectroscopy of cold molecules

    CERN Document Server

    Borri, Simone

    2016-01-01

    This paper reviews the recent results in high-resolution spectroscopy on cold molecules. Laser spectroscopy of cold molecules addresses issues of symmetry violation, like in the search for the electric dipole moment of the electron and the studies on energy differences in enantiomers of chiral species; tries to improve the precision to which fundamental physical constants are known and tests for their possible variation in time and space; tests quantum electrodynamics, and searches for a fifth force. Further, we briefly review the recent technological progresses in the fields of cold molecules and mid-infrared lasers, which are the tools that mainly set the limits for the resolution that is currently attainable in the measurements.

  10. Phase structure of soliton molecules

    International Nuclear Information System (INIS)

    Temporal optical soliton molecules were recently demonstrated; they potentially allow further increase of data rates in optical telecommunication. Their binding mechanism relies on the internal phases, but these have not been experimentally accessible so far. Conventional frequency-resolved optical gating techniques are not suited for measurement of their phase profile: Their algorithms fail to converge due to zeros both in their temporal and their spectral profile. We show that the VAMPIRE (very advanced method of phase and intensity retrieval of E-fields) method performs reliably. With VAMPIRE the phase profile of soliton molecules has been measured, and further insight into the mechanism is obtained

  11. Phase structure of soliton molecules

    Science.gov (United States)

    Hause, A.; Hartwig, H.; Seifert, B.; Stolz, H.; Böhm, M.; Mitschke, F.

    2007-06-01

    Temporal optical soliton molecules were recently demonstrated; they potentially allow further increase of data rates in optical telecommunication. Their binding mechanism relies on the internal phases, but these have not been experimentally accessible so far. Conventional frequency-resolved optical gating techniques are not suited for measurement of their phase profile: Their algorithms fail to converge due to zeros both in their temporal and their spectral profile. We show that the VAMPIRE (very advanced method of phase and intensity retrieval of E -fields) method performs reliably. With VAMPIRE the phase profile of soliton molecules has been measured, and further insight into the mechanism is obtained.

  12. Recoiling DNA Molecule Simulation & Experiment

    CERN Document Server

    Neto, J C; Mesquita, O N; Neto, Jose Coelho; Dickman, Ronald

    2002-01-01

    Many recent experiments with single DNA molecules are based on force versus extension measurements and involve tethering a microsphere to one of its extremities and the other to a microscope coverglass. In this work we show that similar results can also be obtained by studying the recoil dynamics of the tethered microspheres. Computer simulations of the corresponding Langevin equation indicate which assumptions are required for a reliable analysis of the experimental recoil curves. We have measured the persistence length A of single naked DNA molecules and DNA-Ethidium Bromide complexes using this approach.

  13. Technetium-aspirin molecule complexes

    Energy Technology Data Exchange (ETDEWEB)

    El-Shahawy, A.S.; Mahfouz, R.M.; Aly, A.A.M.; El-Zohry, M. (Assiut Univ. (Egypt))

    1993-01-01

    Technetium-aspirin and technetium-aspirin-like molecule complexes were prepared. The structure of N-acetylanthranilic acid (NAA) has been decided through CNDO calculations. The ionization potential and electron affinity of the NAA molecule as well as the charge densities were calculated. The electronic absorption spectra of Tc(V)-Asp and Tc(V)-ATS complexes have two characteristic absorption bands at 450 and 600 nm, but the Tc(V)-NAA spectrum has one characteristic band at 450 nm. As a comparative study, Mo-ATS complex was prepared and its electronic absorption spectrum is comparable with the Tc-ATS complex spectrum. (author).

  14. Tunneling Ionization of Diatomic Molecules

    DEFF Research Database (Denmark)

    Svensmark, Jens Søren Sieg

    2016-01-01

    When a molecule is subject to a strong laser field, there is a probability that an electron can escape, even though the electrons are bound by a large potential barrier. This is possible because electrons are quantum mechanical in nature, and they are therefore able to tunnel through potential...... of tunneling ionizaion of molecules is presented and the results of numerical calculations are shown. One perhaps surprising result is, that the frequently used Born-Oppenheimer approximation breaks down for weak fields when describing tunneling ionization. An analytic theory applicable in the weak-field limit...

  15. Exotic helium molecules; Molecules exotiques d'helium

    Energy Technology Data Exchange (ETDEWEB)

    Portier, M

    2007-12-15

    We study the photo-association of an ultracold cloud of magnetically trapped helium atoms: pairs of colliding atoms interact with one or two laser fields to produce a purely long range {sup 4}He{sub 2}(2{sup 3}S{sub 1}-2{sup 3}P{sub 0}) molecule, or a {sup 4}He{sub 2}(2{sup 3}S{sub 1}-2{sup 3}S{sub 1}) long range molecule. Light shifts in one photon photo-association spectra are measured and studied as a function of the laser polarization and intensity, and the vibrational state of the excited molecule. They result from the light-induced coupling between the excited molecule, and bound and scattering states of the interaction between two metastable atoms. Their analysis leads to the determination of the scattering length a = (7.2 {+-} 0.6) ruling collisions between spin polarized atoms. The two photon photo-association spectra show evidence of the production of polarized, long-range {sup 4}He{sub 2}(2{sup 3}S{sub 1}-2{sup 3}S{sub 1}) molecules. They are said to be exotic as they are made of two metastable atoms, each one carrying a enough energy to ionize the other. The corresponding lineshapes are calculated and decomposed in sums and products of Breit-Wigner and Fano profiles associated to one and two photon processes. The experimental spectra are fit, and an intrinsic lifetime {tau} = (1.4 {+-} 0.3) {mu}s is deduced. It is checked whether this lifetime could be limited by spin-dipole induced Penning autoionization. This interpretation requires that there is a quasi-bound state close to the dissociation threshold in the singlet interaction potential between metastable helium atoms for the theory to match the experiment. (author)

  16. Engineering crystals of dendritic molecules.

    Science.gov (United States)

    Lukin, Oleg; Schubert, Dirk; Müller, Claudia M; Schweizer, W Bernd; Gramlich, Volker; Schneider, Julian; Dolgonos, Grygoriy; Shivanyuk, Alexander

    2009-07-01

    A detailed single-crystal X-ray study of conformationally flexible sulfonimide-based dendritic molecules with systematically varied molecular architectures was undertaken. Thirteen crystal structures reported in this work include 9 structures of the second-generation dendritic sulfonimides decorated with different aryl groups, 2 compounds bearing branches of both second and first generation, and 2 representatives of the first generation. Analysis of the packing patterns of 9 compounds bearing second-generation branches shows that despite their lack of strong directive functional groups there is a repeatedly reproduced intermolecular interaction mode consisting in an anchor-type packing of complementary second-generation branches of neighbouring molecules. The observed interaction tolerates a wide range of substituents in meta- and para-positions of the peripheral arylsulfonyl rings. Quantum chemical calculations of the molecule-molecule interaction energies agree at the qualitative level with the packing preferences found in the crystalline state. The calculations can therefore be used as a tool to rationalize and predict molecular structures with commensurate and non-commensurate branches for programming of different packing modes in crystal. PMID:19549870

  17. Small Molecules Target Carcinogenic Proteins

    Science.gov (United States)

    Gradinaru, Claudiu

    2009-03-01

    An ingenious cellular mechanism of effecting protein localization is prenylation: the covalent attachment of a hydrophobic prenyl group to a protein that facilitates protein association with cell membranes. Fluorescence microscopy was used to investigate whether the oncogenic Stat3 protein can undergo artificial prenylation via high-affinity prenylated small-molecule binding agents and thus be rendered inactive by localization at the plasma membrane instead of nucleus. The measurements were performed on a home-built instrument capable of recording simultaneously several optical parameters (lifetime, polarization, color, etc) and with single-molecule sensitivity. A pH-invariant fluorescein derivative with double moiety was designed to bridge a prenyl group and a small peptide that binds Stat3 with high affinity. Confocal fluorescence images show effective localization of the ligand to the membrane of liposomes. Stat3 predominantly localizes at the membrane only in the presence of the prenylated ligand. Single-molecule FRET (fluorescence resonance energy transfer) between donor-labeled prenylated agents and acceptor-labeled, surface tethered Stat3 protein is used to determine the dynamic heterogeneity of the protein-ligand interaction and follow individual binding-unbinding events in real time. The data indicates that molecules can effect protein localization, validating a therapeutic design that influences protein activity via induced localization.

  18. Quantum interferometry with complex molecules

    OpenAIRE

    Arndt, Markus; Hornberger, Klaus

    2009-01-01

    This chapter reviews recent experiments on matter wave interferometry with large molecules. Starting from an elementary introduction to matter wave physics we discuss far-field diffraction and near-field interferometry with thermally excited many-body systems. We describe the constraints imposed by decoherence and dephasing effects, and present an outlook to the future challenges in macromolecule and cluster interferometry.

  19. Azobenzene-functionalized cascade molecules

    DEFF Research Database (Denmark)

    Archut, A.; Vogtle, F.; De Cola, L.;

    1998-01-01

    Cascade molecules bearing up to 32 azobenzene groups in the periphery have been prepared from poly(propylene imine) dendrimers and N-hydroxysuccinimide esters. The dendritic azobenzene species show similar isomerization properties as the corresponding azobenzene monomers. The all-E azobenzene...

  20. Pair Tunneling through Single Molecules

    Science.gov (United States)

    Raikh, Mikhail

    2007-03-01

    Coupling to molecular vibrations induces a polaronic shift, and can lead to a negative charging energy, U. For negative U, the occupation of the ground state of the molecule is even. In this situation, virtual pair transitions between the molecule and the leads can dominate electron transport. At low temperature, T, these transitions give rise to the charge-Kondo effect [1]. We developed the electron transport theory through the negative-U molecule [2] at relatively high T, when the Kondo correlations are suppressed. Two physical ingredients distinguish our theory from the transport through a superconducting grain coupled to the normal leads [3]: (i) in parallel with sequential pair-tunneling processes, single-particle cotunneling processes take place; (ii) the electron pair on the molecule can be created (or annihilated) by two electrons tunneling in from (or out to) opposite leads. We found that, even within the rate-equation description, the behavior of differential conductance through the negative-U molecule as function of the gate voltage is quite peculiar: the height of the peak near the degeneracy point is independent of temperature, while its width is proportional to T. This is in contrast to the ordinary Coulomb-blockade conductance peak, whose integral strength is T-independent. At finite source-drain bias, V>>T, the width of the conductance peak is ˜V, whereas the conventional Coulomb-blockade peak at finite V splits into two sharp peaks at detunings V/2, and -V/2. Possible applications to the gate-controlled current rectification and switching will be discussed. [1] A. Taraphder and P. Coleman, Phys. Rev. Lett. 66, 2814 (1991). [2] J. Koch, M. E. Raikh, and F. von Oppen, Phys. Rev. Lett. 96, 056803 (2006). [3] F. W. J. Hekking, L. I. Glazman, K. A. Matveev, and R. I. Shekhter, Phys. Rev. Lett. 70, 4138 (1993).

  1. Electrochemical detection of single molecules.

    Science.gov (United States)

    Fan, F R; Bard, A J

    1995-02-10

    The electrochemical behavior of a single molecule can be observed by trapping a small volume of a dilute solution of the electroactive species between an ultramicroelectrode tip with a diameter of approximately 15 nanometers and a conductive substrate. A scanning electrochemical microscope was used to adjust the tip-substrate distance ( approximately 10 nanometers), and the oxidation of [(trimethylammonio)methyl] ferrocene (Cp(2)FeTMA(+)) to Cp(2)FeTMA(2+) was carried out. The response was stochastic, and anodic current peaks were observed as the molecule moved into and out of the electrode-substrate gap. Similar experiments were performed with a solution containing two redox species, ferrocene carboxylate (Cp(2)FeCOO(-)) and Os(bpy)(3)(2+) (bpy is 2,2'-bipyridyl). PMID:17813918

  2. Metagenomic small molecule discovery methods

    OpenAIRE

    Charlop-Powers, Zachary; Milshteyn, Aleksandr; Brady, Sean F

    2014-01-01

    Metagenomic approaches to natural product discovery provide the means of harvesting bioactive small molecules synthesized by environmental bacteria without the requirement of first culturing these organisms. Advances in sequencing technologies and general metagenomic methods are beginning to provide the tools necessary to unlock the unexplored biosynthetic potential encoded by the genomes of uncultured environmental bacteria. Here, we highlight recent advances in sequence- and functional- bas...

  3. Laser tunneling from aligned molecules

    CERN Document Server

    Smeenk, C T L; Sokolov, A V; Spanner, M; Lee, K F; Staudte, A; Villeneuve, D M; Corkum, P B

    2013-01-01

    We study multi-photon ionization from N_2, O_2 and benzene using circularly polarized light. By examining molecular frame photo-electron angular distributions, we illustrate how multi-photon ionization acts a momentum-selective probe of the local electron density in the Dyson orbitals for these molecules. We find good agreement with calculations based on a tunneling model and including saturation effects.

  4. Bioactive molecules from sea hares.

    Science.gov (United States)

    Kamiya, H; Sakai, R; Jimbo, M

    2006-01-01

    Sea hares, belonging to the order Opisthobranchia, subclass Gastropoda, are mollusks that have attracted many researchers who are interested in the chemical defense mechanisms of these soft and "shell-less" snails. Numbers of small molecules of dietary origin have been isolated from sea hares and some have ecologically relevant activities, such as fish deterrent activity or toxicity. Recently, however, greater attention has been paid to biomedically interesting sea hare isolates such as dolastatins, a series of antitumor peptide/macrolides isolated from Dolabella auricularia. Another series of bioactive peptide/macrolides, as represented by aplyronines, have been isolated from sea hares in Japanese waters. Although earlier studies indicated the potent antitumor activity of aplyronines, their clinical development has never been conducted because of the minute amount of compound available from the natural source. Recent synthetic studies, however, have made it possible to prepare these compounds and analogs for a structure-activity relationship study, and started to uncover their unique action mechanism towards their putative targets, microfilaments. Here, recent findings of small antitumor molecules isolated from Japanese sea hares are reviewed. Sea hares are also known to produce cytotoxic and antimicrobial proteins. In contrast to the small molecules of dietary origin, proteins are the genetic products of sea hares and they are likely to have some primary physiological functions in addition to ecological roles in the sea hare. Based on the biochemical properties and phylogenetic analysis of these proteins, we propose that they belong to one family of molecule, the "Aplysianin A family," although their molecular weights are apparently divided into two groups. Interestingly, the active principles in Aplysia species and Dolabella auricularia were shown to be L-amino acid oxidase (LAAO), a flavin enzyme that oxidizes an alpha-amino group of the substrate with

  5. Optical highlighter molecules in neurobiology.

    Science.gov (United States)

    Datta, Sandeep Robert; Patterson, George H

    2012-02-01

    The development of advanced optical methods has played a key role in propelling progress in neurobiology. Genetically-encoded fluorescent molecules found in nature have enabled labeling of individual neurons to study their physiology and anatomy. Here we discuss the recent use of both native and synthetic optical highlighter proteins to address key problems in neurobiology, including questions relevant to synaptic function, neuroanatomy, and the organization of neural circuits.

  6. Physics of Atoms and Molecules

    CERN Document Server

    Bransden, B H

    2003-01-01

    New edition of a well-established second and third year textbook for Physics degree students, covering the physical structure and behaviour of atoms and molecules. The aim of this new edition is to provide a unified account of the subject within an undergraduate framework, taking the opportunity to make improvements based on the teaching experience of users of the first edition, and cover important new developments in the subject.

  7. Functional molecules in electronic circuits.

    Science.gov (United States)

    Weibel, Nicolas; Grunder, Sergio; Mayor, Marcel

    2007-08-01

    Molecular electronics is a fascinating field of research contributing to both fundamental science and future technological achievements. A promising starting point for molecular devices is to mimic existing electronic functions to investigate the potential of molecules to enrich and complement existing electronic strategies. Molecules designed and synthesized to be integrated into electronic circuits and to perform an electronic function are presented in this article. The focus is set in particular on rectification and switching based on molecular devices, since the control over these two parameters enables the assembly of memory units, likely the most interesting and economic application of molecular based electronics. Both historical and contemporary solutions to molecular rectification are discussed, although not exhaustively. Several examples of integrated molecular switches that respond to light are presented. Molecular switches responding to an electrochemical signal are also discussed. Finally, supramolecular and molecular systems with intuitive application potential as memory units due to their hysteretic switching are highlighted. Although a particularly attractive feature of molecular electronics is its close cooperation with neighbouring disciplines, this article is written from the point of view of a chemist. Although the focus here is largely on molecular considerations, innovative contributions from physics, electro engineering, nanotechnology and other scientific disciplines are equally important. However, the ability of the chemist to correlate function with structure, to design and to provide tailor-made functional molecules is central to molecular electronics. PMID:17637951

  8. Simultaneous gene silencing of Bcl-2, XIAP and Survivin re-sensitizes pancreatic cancer cells towards apoptosis

    International Nuclear Information System (INIS)

    Pancreatic ductal adenocarcinoma shows a distinct apoptosis resistance, which contributes significantly to the aggressive nature of this tumor and constrains the effectiveness of new therapeutic strategies. Apoptosis resistance is determined by the net balance of the cells pro-and anti-apoptotic 'control mechanisms'. Numerous dysregulated anti-apoptotic genes have been identified in pancreatic cancer and seem to contribute to the high anti-apoptotic buffering capacity. We aimed to compare the benefit of simultaneous gene silencing (SGS) of several candidate genes with conventional gene silencing of single genes. From literature search we identified the anti-apoptotic genes XIAP, Survivin and Bcl-2 as commonly upregulated in pancreatic cancer. We performed SGS and silencing of single candidate genes using siRNA molecules in two pancreatic cancer cell lines. Effectiveness of SGS was assessed by qRT-PCR and western blotting. Apoptosis induction was measured by flow cytometry and caspase activation. Simultaneous gene silencing reduced expression of the three target genes effectively. Compared to silencing of a single target or control, SGS of these genes resulted in a significant higher induction of apoptosis in pancreatic cancer cells. In the present study we performed a subliminal silencing of different anti-apoptotic target genes simultaneously. Compared to silencing of single target genes, SGS had a significant higher impact on apoptosis induction in pancreatic cancer cells. Thereby, we give further evidence for the concept of an anti-apoptotic buffering capacity of pancreatic cancer cells

  9. Water molecules orientation in surface layer

    Science.gov (United States)

    Klingo, V. V.

    2000-08-01

    The water molecules orientation has been investigated theoretically in the water surface layer. The surface molecule orientation is determined by the direction of a molecule dipole moment in relation to outward normal to the water surface. Entropy expressions of the superficial molecules in statistical meaning and from thermodynamical approach to a liquid surface tension have been found. The molecules share directed opposite to the outward normal that is hydrogen protons inside is equal 51.6%. 48.4% water molecules are directed along to surface outward normal that is by oxygen inside. A potential jump at the water surface layer amounts about 0.2 volts.

  10. XUV ionization of aligned molecules

    Energy Technology Data Exchange (ETDEWEB)

    Kelkensberg, F.; Siu, W.; Gademann, G. [FOM Institute AMOLF, Science Park 104, NL-1098 XG Amsterdam (Netherlands); Rouzee, A.; Vrakking, M. J. J. [FOM Institute AMOLF, Science Park 104, NL-1098 XG Amsterdam (Netherlands); Max-Born-Institut, Max-Born Strasse 2A, D-12489 Berlin (Germany); Johnsson, P. [FOM Institute AMOLF, Science Park 104, NL-1098 XG Amsterdam (Netherlands); Department of Physics, Lund University, Post Office Box 118, SE-221 00 Lund (Sweden); Lucchini, M. [Department of Physics, Politecnico di Milano, Istituto di Fotonica e Nanotecnologie CNR-IFN, Piazza Leonardo da Vinci 32, 20133 Milano (Italy); Lucchese, R. R. [Department of Chemistry, Texas A and M University, College Station, Texas 77843-3255 (United States)

    2011-11-15

    New extreme-ultraviolet (XUV) light sources such as high-order-harmonic generation (HHG) and free-electron lasers (FELs), combined with laser-induced alignment techniques, enable novel methods for making molecular movies based on measuring molecular frame photoelectron angular distributions. Experiments are presented where CO{sub 2} molecules were impulsively aligned using a near-infrared laser and ionized using femtosecond XUV pulses obtained by HHG. Measured electron angular distributions reveal contributions from four orbitals and the onset of the influence of the molecular structure.

  11. The neural cell adhesion molecule

    DEFF Research Database (Denmark)

    Berezin, V; Bock, E; Poulsen, F M

    2000-01-01

    During the past year, the understanding of the structure and function of neural cell adhesion has advanced considerably. The three-dimensional structures of several of the individual modules of the neural cell adhesion molecule (NCAM) have been determined, as well as the structure of the complex...... between two identical fragments of the NCAM. Also during the past year, a link between homophilic cell adhesion and several signal transduction pathways has been proposed, connecting the event of cell surface adhesion to cellular responses such as neurite outgrowth. Finally, the stimulation of neurite...

  12. Small molecules for big tasks

    Institute of Scientific and Technical Information of China (English)

    Jiarui Wu

    2011-01-01

    @@ One of the most important achievements in the post-genome era is discovery of microRNAs (miRNAs), which widely exist from simple-genome organisms such as viruses and bacteria to complexgenome organisms such as plants and animals.miRNAs are single-stranded non-coding RNAs of 18-25 nucleotides in length, which are generated from larger precursors that are transcribed from noncoding genes.As a new type of regulatory molecules, miRNAs present unique features in regulating gene and its products, including rapidly turning off protein production, reversibly, and compartmentalized regulating gene expression.

  13. Dissociation Energies of Diatomic Molecules

    Institute of Scientific and Technical Information of China (English)

    FAN Qun-Chao; SUN Wei-Guo

    2008-01-01

    Molecular dissociation energies of 10 electronic states of alkali molecules of KH, 7LID, 7LiH, 6LiH, NaK, NaLi and NaRb are studied using the highest three accurate vibrational energies of each electronic state, and an improved parameter-free analytical formula which is obtained starting from the LeRoy-Bernstein vibrational energy expression near the dissociation limit. The results show that as long as the highest three vibrational energies are accurate, the current analytical formula will give accurate theoretical dissociation energies Detheory, which are in excellent agreement with the experimental dissociation energies Dexpte.

  14. The molecule-metal interface

    CERN Document Server

    Koch, Norbert; Wee, Andrew Thye Shen

    2013-01-01

    Reviewing recent progress in the fundamental understanding of the molecule-metal interface, this useful addition to the literature focuses on experimental studies and introduces the latest analytical techniques as applied to this interface.The first part covers basic theory and initial principle studies, while the second part introduces readers to photoemission, STM, and synchrotron techniques to examine the atomic structure of the interfaces. The third part presents photoelectron spectroscopy, high-resolution UV photoelectron spectroscopy and electron spin resonance to study the electroni

  15. Molecules in Studio v. 1.0

    Energy Technology Data Exchange (ETDEWEB)

    2016-04-22

    A Powersim Studio implementation of the system dynamics’ ‘Molecules of Structure’. The original implementation was in Ventana’s Vensim language by James Hines. The molecules are fundamental constructs of the system dynamics simulation methodology.

  16. Hydrophobic Porous Material Adsorbs Small Organic Molecules

    Science.gov (United States)

    Sharma, Pramod K.; Hickey, Gregory S.

    1994-01-01

    Composite molecular-sieve material has pore structure designed specifically for preferential adsorption of organic molecules for sizes ranging from 3 to 6 angstrom. Design based on principle that contaminant molecules become strongly bound to surface of adsorbent when size of contaminant molecules is nearly same as that of pores in adsorbent. Material used to remove small organic contaminant molecules from vacuum systems or from enclosed gaseous environments like closed-loop life-support systems.

  17. How Is a Protein Molecule Nearsighted?

    Institute of Scientific and Technical Information of China (English)

    GAO De; JI Qing; L(U) Gang

    2005-01-01

    @@ The effect range of a local change of a protein molecule is calculated using a cluster method developed in this work based on the Gaussian software. This range is found to be about 8 A, which gives a concrete estimation on the "nearsightedness" by Kohn for protein molecules. The cluster method can be applied to calculation of the electronic density of a large molecule such as a motor protein and can provide a basis for the dynamical analysis of a single protein molecule.

  18. Analytical design of soliton molecules in fibers

    Science.gov (United States)

    Moubissi, A.-B.; Nse Biyoghe, S.; Mback, C. B. L.; Ekogo, T. B.; Ben-Bolie, G. H.; Kofane, T. C.; Tchofo Dinda, P.

    2016-09-01

    We present an analytical method for designing fiber systems for a highly stable propagation of soliton molecules. This analytical design uses the variational equations of the soliton molecule to determine the parameters of the most suitable fiber system for any desired soliton, thus reducing dramatically the cost of the whole procedure of design, for both the appropriate fiber system and the desired soliton molecule.

  19. Electric dipole moment of diatomic molecules

    International Nuclear Information System (INIS)

    The calculation of the electric dipole moment of diatomic molecules by the Variational Cellular Method is presented, discussed and compared with the semiempirical CNDO/2 method. The molecule HF is taken as example. It is also shown that the value of the electric dipole moment by the VCM improves considerably when the electronegativity of the atoms of the molecule is taken into account. (Author)

  20. Ultrafast electron diffraction from aligned molecules

    Energy Technology Data Exchange (ETDEWEB)

    Centurion, Martin [Univ. of Nebraska, Lincoln, NE (United States)

    2015-08-17

    The aim of this project was to record time-resolved electron diffraction patterns of aligned molecules and to reconstruct the 3D molecular structure. The molecules are aligned non-adiabatically using a femtosecond laser pulse. A femtosecond electron pulse then records a diffraction pattern while the molecules are aligned. The diffraction patterns are then be processed to obtain the molecular structure.

  1. Optoelectronics of Molecules and Polymers

    CERN Document Server

    Moliton, André

    2006-01-01

    Optoelectronic devices are being developed at an extraordinary rate. Organic light emitting diodes, photovoltaic devices and electro-optical modulators are pivotal to the future of displays, photosensors and solar cells, and communication technologies. This book details the theories underlying the relevant mechanisms in organic materials and covers, at a basic level, how the organic components are made. The first part of this book introduces the fundamental theories used to detail ordered solids and localised energy levels. The methods used to determine energy levels in perfectly ordered molecular and macromolecular systems are discussed, making sure that the effects of quasi-particles are not missed. The function of excitons and their transfer between two molecules are studied, and the problems associated with interfaces and charge injection into resistive media are presented. The second part details technological aspects such as the fabrication of devices based on organic materials by dry etching. The princ...

  2. Anti-cancer Lead Molecule

    KAUST Repository

    Sagar, Sunil

    2014-04-17

    Derivatives of plumbagin can be selectively cytotoxic to breast cancer cells. Derivative `A` (Acetyl Plumbagin) has emerged as a lead molecule for testing against estrogen positive breast cancer and has shown low hepatotoxicity as well as overall lower toxicity in nude mice model. The toxicity of derivative `A` was determined to be even lower than vehicle control (ALT and AST markers). The possible mechanism of action identified based on the microarray experiments and pathway mapping shows that derivative `A` could be acting by altering the cholesterol-related mechanisms. The low toxicity profile of derivative `A` highlights its possible role\\'as future anti-cancer drug and/or as an adjuvant drug to reduce the toxicity of highly toxic chemotherapeutic\\'drugs

  3. Photonic molecules and spectral engineering

    CERN Document Server

    Boriskina, Svetlana V

    2012-01-01

    This chapter reviews the fundamental optical properties and applications of pho-tonic molecules (PMs) - photonic structures formed by electromagnetic coupling of two or more optical microcavities (photonic atoms). Controllable interaction between light and matter in photonic atoms can be further modified and en-hanced by the manipulation of their mutual coupling. Mechanical and optical tunability of PMs not only adds new functionalities to microcavity-based optical components but also paves the way for their use as testbeds for the exploration of novel physical regimes in atomic physics and quantum optics. Theoretical studies carried on for over a decade yielded novel PM designs that make possible lowering thresholds of semiconductor microlasers, producing directional light emission, achieving optically-induced transparency, and enhancing sensitivity of microcavity-based bio-, stress- and rotation-sensors. Recent advances in material science and nano-fabrication techniques make possible the realization of opt...

  4. Photoluminescence of a Plasmonic Molecule.

    Science.gov (United States)

    Huang, Da; Byers, Chad P; Wang, Lin-Yung; Hoggard, Anneli; Hoener, Ben; Dominguez-Medina, Sergio; Chen, Sishan; Chang, Wei-Shun; Landes, Christy F; Link, Stephan

    2015-07-28

    Photoluminescent Au nanoparticles are appealing for biosensing and bioimaging applications because of their non-photobleaching and non-photoblinking emission. The mechanism of one-photon photoluminescence from plasmonic nanostructures is still heavily debated though. Here, we report on the one-photon photoluminescence of strongly coupled 50 nm Au nanosphere dimers, the simplest plasmonic molecule. We observe emission from coupled plasmonic modes as revealed by single-particle photoluminescence spectra in comparison to correlated dark-field scattering spectroscopy. The photoluminescence quantum yield of the dimers is found to be surprisingly similar to the constituent monomers, suggesting that the increased local electric field of the dimer plays a minor role, in contradiction to several proposed mechanisms. Aided by electromagnetic simulations of scattering and absorption spectra, we conclude that our data are instead consistent with a multistep mechanism that involves the emission due to radiative decay of surface plasmons generated from excited electron-hole pairs following interband absorption. PMID:26165983

  5. Single-molecule dynamics in nanofabricated traps

    Science.gov (United States)

    Cohen, Adam

    2009-03-01

    The Anti-Brownian Electrokinetic trap (ABEL trap) provides a means to immobilize a single fluorescent molecule in solution, without surface attachment chemistry. The ABEL trap works by tracking the Brownian motion of a single molecule, and applying feedback electric fields to induce an electrokinetic motion that approximately cancels the Brownian motion. We present a new design for the ABEL trap that allows smaller molecules to be trapped and more information to be extracted from the dynamics of a single molecule than was previously possible. In particular, we present strategies for extracting dynamically fluctuating mobilities and diffusion coefficients, as a means to probe dynamic changes in molecular charge and shape. If one trapped molecule is good, many trapped molecules are better. An array of single molecules in solution, each immobilized without surface attachment chemistry, provides an ideal test-bed for single-molecule analyses of intramolecular dynamics and intermolecular interactions. We present a technology for creating such an array, using a fused silica plate with nanofabricated dimples and a removable cover for sealing single molecules within the dimples. With this device one can watch the shape fluctuations of single molecules of DNA or study cooperative interactions in weakly associating protein complexes.

  6. Spin polarization effect of Ni2 molecule

    Institute of Scientific and Technical Information of China (English)

    Yan Shi-Ying; Zhu Zheng-He

    2008-01-01

    The density functional theory (DFT) method (b3p86) of Gaussian 03 is used to optimize the structure of the Ni2 molecule. The result shows that the ground state for the Ni2 molecule is a 5-multiple state, symbolizing a spin polarization effect existing in the Ni2 molecule, a transition metal molecule, but no spin pollution is found because the wavefunction of the ground state does not mingle with wavefunctions of higher-energy states. So the ground state for Ni2 molecule, which is a 5-multiple state, is indicative of spin polarization effect of the Ni2 molecule, that is, there exist 4 parallel spin electrons in Ni2 molecule. The number of non-conjugated electrons is greatest. These electrons occupy different spatial orbitals so that the energy of the Ni2 molecule is minimized. It can be concluded that the effect of parallel spin in the Ni2 molecule is larger than that of the conjugated molecule, which is obviously related to the effect of electron d delocalization. In addition, the Murrell-Sorbie potential functions with the parameters of the ground state and other states of the Ni2 molecule are derived. The dissociation energy De for the ground state of the Ni2 molecule is 1.835 eV, equilibrium bond length Re is 0.2243 nm, vibration frequency ωe is 262.35 cm-1. Its force constants f2, f3 and f4 are 1.1901 aJ.nm-2, 5.8723 aJ.nm-3, and 21.2505 aJ.nm-4 respectively. The other spectroscopic data for the ground state of the Ni2 molecule ωexe, Be and αe are 1.6315cm-1, 0.1141 cm-1, and 8.0145×10-4 cm-1 respectively.

  7. Spin polarization effect for Cr2 molecule

    Institute of Scientific and Technical Information of China (English)

    Yan Shi-Ying

    2008-01-01

    Density functional theory (DFT) (B3P86) of Ganssian 03 has been used to optimize the structure of the Cr2 molecule, a transition metal element molecule. The result shows that the ground state for the Cr2 molecule is a 13-multiple state, indicating that there exists a spin polarization effect in the Cr2 molecule. Meanwhile, we have not found any spin pollution because the wave function of the ground state does not mingle with wave functions of higher-energy states. So the ground state for Cr2 molecule being a 13-multiple state is indicative of spin polarization effect of the Cr2 molecule among transition metal elements, that is, there are 12 parallel spin electrons in the Cr2 molecule. The number of non-conjugated electrons is greatest. These electrons occupy different spatial orbitals so that the energy of the Cr2 molecule is minimized. It can be concluded that the effect of parallel spin in the Cr2 molecule is larger than the effect of the conjugated molecule, which is obviously related to the effect of electron d delocalization. In addition,the Murrell-Sorbie potential functions with the parameters for the ground state and other states of the Cr2 molecule are derived. The dissociation energy De for the ground state of the Cr2 molecule is 0.1034eV, equilibrium bond length Re is 0.3396nm, and vibration frequency ωe is 73.81cm-1. Its force constants f2, f3 and f4 are 0.0835, -0.2831 and 0.3535 aJ·nm-4 respectively. The other spectroscopic data for the ground state of the Cr2 molecule ωeχe, Be and αe are 1.2105, 0.0562 and 7.2938 × 10-4cm-1 respectively.

  8. Anti-apoptotic ARC protein confers chemoresistance by controlling leukemia-microenvironment interactions through a NFκB/IL1β signaling network

    KAUST Repository

    Carter, Bing Z.

    2016-04-11

    To better understand how the apoptosis repressor with caspase recruitment domain (ARC) protein confers drug resistance in acute myeloid leukemia (AML), we investigated the role of ARC in regulating leukemia-mesenchymal stromal cell (MSC) interactions. In addition to the previously reported effect on AML apoptosis, we have demonstrated that ARC enhances migration and adhesion of leukemia cells to MSCs both in vitro and in a novel human extramedullary bone/bone marrow mouse model. Mechanistic studies revealed that ARC induces IL1β expression in AML cells and increases CCL2, CCL4, and CXCL12 expression in MSCs, both through ARC-mediated activation of NFκB. Expression of these chemokines in MSCs increased by AML cells in an ARC/IL1β-dependent manner; likewise, IL1β expression was elevated when leukemia cells were co-cultured with MSCs. Further, cells from AML patients expressed the receptors for and migrated toward CCL2, CCL4, and CXCL12. Inhibition of IL1β suppressed AML cell migration and sensitized the cells co-cultured with MSCs to chemotherapy. Our results suggest the existence of a complex ARC-regulated circuit that maintains intimate connection of AML with the tumor microenvironment through NFκB/IL1β-regulated chemokine receptor/ligand axes and reciprocal crosstalk resulting in cytoprotection. The data implicate ARC as a promising drug target to potentially sensitize AML cells to chemotherapy.

  9. Review of the apoptosis pathways in pancreatic cancer and the anti-apoptotic effects of the novel sea cucumber compound, Frondoside A.

    Science.gov (United States)

    Li, X; Roginsky, A B; Ding, X-Z; Woodward, C; Collin, P; Newman, R A; Bell, R H; Adrian, T E

    2008-09-01

    Pancreatic cancer cells are resistant to the growth-inhibitory and apoptosis-inducing effects of conventional chemotherapeutic agents. There are multiple genetic and epigenetic events during the process of carcinogenesis that enable the cancer cells to avoid normal growth constraints and apoptosis. Investigation of the mechanisms involved has led to multiple strategies that encourage cell death and apoptosis to occur. The pathways involved are summarized in this review, together with some recently developed strategies to promote cell death in this cancer and with a particular focus on the frondoside A, a novel triterpenoid glycoside isolated from the Atlantic sea cucumber, Cucumaria frondosa. Frondoside A inhibited proliferation of AsPC-1 human pancreatic cancer cells in a concentration- and time-dependent manner, as measured by (3)H-thymidine incorporation and cell counting. In concert with inhibition of cell growth, frondoside A induced significant morphological changes consistent with apoptosis. Propidium iodide DNA staining showed an increase of sub-G0/G1 cell population of apoptotic cells induced by frondoside A. Frondoside A-induced apoptosis was confirmed by annexin V binding and TUNEL assay. Furthermore, western blotting showed a decrease in expression of Bcl-2 and Mcl-1, an increase in Bax expression, activation of caspases 3, 7, and 9, and an increase in the expression of the cyclin-dependent kinase inhibitor, p21. These findings show that frondoside A induced apoptosis in human pancreatic cancer cells through the mitochondrial pathway and activation of the caspase cascade. Finally, a very low concentration of frondoside A (10 mug/kg/day) inhibited growth of AsPC-1 xenografts in athymic mice. In conclusion, new chemotherapeutic agents are desperately needed for pancreatic cancer because of the poor responsiveness to currently available treatment options. Frondoside A has potent growth inhibitory effects on human pancreatic cancer cells, and the inhibition of proliferation is accompanied by marked apoptosis. Frondoside A may be valuable for the treatment or chemoprevention of this devastating disease. PMID:18837899

  10. Turmeric toxicity in A431 epidermoid cancer cells associates with autophagy degradation of anti-apoptotic and anti-autophagic p53 mutant.

    Science.gov (United States)

    Thongrakard, Visa; Titone, Rossella; Follo, Carlo; Morani, Federica; Suksamrarn, Apichart; Tencomnao, Tewin; Isidoro, Ciro

    2014-12-01

    The keratinocyte-derived A431 Squamous Cell Carcinoma cells express the p53R273H mutant, which has been reported to inhibit apoptosis and autophagy. Here, we show that the crude extract of turmeric (Curcuma longa), similarly to its bioactive component Curcumin, could induce both apoptosis and autophagy in A431 cells, and these effects were concomitant with degradation of p53. Turmeric and curcumin also stimulated the activity of mTOR, which notoriously promotes cell growth and acts negatively on basal autophagy. Rapamycin-mediated inhibition of mTOR synergized with turmeric and curcumin in causing p53 degradation, increased the production of autophagosomes and exacerbated cell toxicity leading to cell necrosis. Small-interference mediated silencing of the autophagy proteins BECLIN 1 or ATG7 abrogated the induction of autophagy and largely rescued p53 stability in Turmeric-treated or Curcumin-treated cells, indicating that macroautophagy was mainly responsible for mutant p53 degradation. These data uncover a novel mechanism of turmeric and curcumin toxicity in chemoresistant cancer cells bearing mutant p53.

  11. Irinotecan treatment and senescence failure promote the emergence of more transformed and invasive cells that depend on anti-apoptotic Mcl-1

    OpenAIRE

    Jonchère, Barbara; Vétillard, Alexandra; Toutain, Bertrand; Lam, David; Bernard, Anne Charlotte; Henry, Cécile; Trécesson, Sophie De Carné; Gamelin, Erick; Juin, Philippe; Guette, Catherine; Coqueret, Olivier

    2014-01-01

    Induction of senescence by chemotherapy was initially characterized as a suppressive response that prevents tumor cell proliferation. However, in response to treatment, it is not really known how cells can survive senescence and how irreversible this pathway is. In this study, we analyzed cell escape in response to irinotecan, a first line treatment used in colorectal cancer that induced senescence. We detected subpopulations of cells that adapted to chemotherapy and resumed proliferation. Su...

  12. Antioxidant, anti-inflammatory, anti-apoptotic, and skin regenerative properties of an Aloe vera-based extract of Nerium oleander leaves (NAE-8®

    Directory of Open Access Journals (Sweden)

    Benson KF

    2015-05-01

    Full Text Available Kathleen F Benson,1 Robert A Newman,2,3 Gitte S Jensen1 1NIS Labs, Klamath Falls, Oregon, USA; 2University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Nerium Biotechnology, Inc, San Antonio, TX, USA Objective: The goal for this study was to evaluate the effects of an Aloe vera-based Nerium oleander extract (NAE-8®, compared to an extract of A. vera gel alone (ALOE, and to an aqueous extract of N. oleander (AQ-NOE in bioassays pertaining to dermatologic potential with respect to antioxidant protection, anti-inflammatory effects, and cytokine profiles in vitro. Methods: Cellular antioxidant protection was evaluated in three separate bioassays: The cellular antioxidant protection of erythrocytes (CAP-e assay, protection of cellular viability and prevention of apoptosis, and protection of intracellular reduced glutathione levels, where the last two assays were performed using human primary dermal fibroblasts. Reduction of intracellular formation of reactive oxygen species (ROS was tested using polymorphonuclear cells in the absence and presence of oxidative stress. Changes to cytokine and chemokine profiles when whole blood cells and human primary dermal fibroblasts were exposed to test products were determined using a 40-plex Luminex array as a method for exploring the potential cross-talk between circulating and skin-resident cells. Results: The NAE-8® provided significantly better antioxidant protection in the CAP-e bioassay than AQ-NOE. NAE-8® and AQ-NOE both protected cellular viability and intracellular reduced glutathione, and reduced the ROS formation significantly when compared to control cells, both under inflamed and neutral culture conditions. ALOE showed minimal effect in these bioassays. In contrast to the NAE-8®, the AQ-NOE showed induction of inflammation in the whole blood cultures, as evidenced by the high induction of CD69 expression and secretion of a number of inflammatory cytokines. The treatment of dermal fibroblasts with NAE-8® resulted in selective secretion of cytokines involved in collagen and hyaluronan production as well as re-epithelialization during wound healing. Conclusion: NAE-8®, a novel component of a commercial cosmetic product, showed beneficial antioxidant protection in several cellular models, without the induction of leukocyte activation and secretion of inflammatory cytokines. The biological efficacy of NAE-8® was unique from both ALOE and AQ-NOE. Keywords: CAP-e bioassay, dermal fibroblasts, oxidative damage, ROS formation, safety

  13. Expression of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax after delayed paraplegia induced by ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Bibo Liu; Miao Liu; Duoning Wang; Wei Ma; Shengli Dang

    2006-01-01

    BACKGROUND:Operation of spine does not involve in spinal cord;however,spinal cord injury occurs at post-operation induced by unclear factors.Meanwhile,after decompression of lumbar spinal canal,symptoms are severer and severer.In addition,during extirpation of oervical and lumbar intervertabral disc,spinal cord and its vessels are not damaged,but spinal cord injury is also suffered from patients with partial improvement.All statuses mentioned above are related to expressed changes of bc/-2 gene inhibiting apoptosis and bax gene accelerating apoptosis.OBJECTIVE:To observe motor function of hindlimbs of ischemia/reperfusion model in rabbits at various time points after reperfusion and expressions of apoptosis correlated protein Bcl-2 and Bax.DESIGN:Completely randomized grouping design and contrast study.SEITING:Department of Orthopedics,the First Affiliated Hospital of Medical School,Xi'an Jiao Tong University.MATERIALS:Forty-eight New Zealand white rabbits of both genders were randomly divided into sham operation group(n=24) and model group(n=24),and then,rabbits in each group were observed at four time points:8,24,72 and 168 hours after reperfusion,with 6 in each time point.Rabbit-anti-rabbit Bcl-2 antibody and rabbit-anti-rabbit Bax antibody were provided by Boster Company.The procedures were accordant to the METHODS:The experiment was carried out at Laboratory of Orthopaedics of First Affiliated Hospital of Medical School,Xi'an Jiao Tong University from April to August 2005.①Delayed paralysis models of spinal cord after ischemia/reperfusion were established based on method of Zivin et al.Animals in sham operation group underwent an exposure of abdominal aorta but the aorta was not occluded.②Motor function of hindlimb was observed 8,24,72 and 168 hours after reperfusion.A grade of 0-5 was assigned to each animal (grade 0:no voluntary hind limb function;grade 5:normal hop;grades 0-3:paraplegia).③The lumbar segment of the spinal cord(L3 to L5)was used for morphological studies at 168 hours after reperfusion and cut into sections with the thickness of 4μm:and then,the sections were stained with hematoxylin and eosin and observed under optic microscope.④After dewaxing,paraffin sections were used to detect expression of Bcl-2 and Bax proteins With Strept-Avidin-Biotin Complex,(SABC)kit(Wuhan Boster Company).The detailed operation was accordant to kit instruction.⑤Sections under the same staining condition but at various time points were measured with Image-Pro Plus Version 5.1 for Window TM (Median Cybemetics,Inc.USA.)to detect average integrated absorbency of positive cells of Bcl-2 and Bax protein.⑥Measurament data were compared with one-way analysis of variance and ttest. MAIN OUTCOME MEASURES:①Hind limb motor function deficit;②Histopathological examination;③Expression of Bcl-2 and Bax proteins at different reperfusion time points in spinal cord.RESULTS:All the 48 rabbits were involved in the analysis of results.①Motor function of hindlimb:Rabbits did not have paralysis in sham operation group.Rabbits in model group did not have paralysis at 8 hours after repertusion,but had delayed paralysis at 24,72 and 168 hours after reperfusion.Grade of motor function was lower than that in sham operation group(t=15.65,20.55.29.00,P.<0.01),similar to that in sham operation group at 8 hours after reperfusion and decreased obviously at 24 hours after reperfusion.②Pathological changes of spinal cord tissue:Spinal cord tissue was normal in sham operation group.With the reperfusion time passing by.necrosis of neurons in spinal cord tissue in model group was increased,inflammatory reaction was strengthened gradually and pathological changes were obvious at 72 hours after reperfusion.③Exprasslons of Bcl-2 and Bax protein:At 8 hours after reperfusion,expressions were similar in both sham operation group and model group(Bcl-2:20.42±4.22,19.63±2.72;Bax:5.22±1.24,4.82±1.52,P>0.05);expression of Bcl-2 was decreased obviously at 24 hours after reperfusion(8.09±0.96,t=9.78,P<0.05)and reached the lowest value at 72 hours after reperfusion(6.08±1.51,t=11.06,P<0.05).However,expression of Bax was increased obviously at 24 hours after reperfusion(12.84±1.77,f=7.88,P<0.05)and reached peak at 72 hours after reperfusion(15.84±5.19,t=4.42,P<0.05).At 168 hours after reperfusion,structure of gray matter was damaged severely and only a few of neurons survived.However,numbers of positive glial cells in white matter were increased,and expression of Bax was higher than that in sham operation group(9.41±1.53,t=6.44,P<0.05).CONCLUSION:Ischemia/reperfusion injury of spinal cord can induce decrease of motor function of experimental animals and cause apoptosis.Changes of both of them are general coincidence with changes of Bcl-2 and Bax expressions with the reperfusion time passing by.

  14. ANTI-APOPTOTIC EFFECT OF CD95 RECEPTOR IN NA VE CD8+ T-LYMPHOCYTES IN CHILDREN WITH ACUTE INFECTIOUS MONONUCLEOSIS

    Directory of Open Access Journals (Sweden)

    E. N. Filatova

    2016-01-01

    Full Text Available Acute infectious mononucleosis is a widespread viral disease, which most often manifests in childhood. The development of acute infectious mononucleosis is accompanied by the change of the CD4+/CD8+ T-lymphocytes ratio and the increase of the virus-specific CD8+ cytotoxic T-lymphocytes number. One of the T-lymphocytes number regulation mechanisms is the modulation of their progenitor cells apoptosis. The death receptor CD95 takes part in the regulation of T-lymphocytes apoptosis, including naïve T-cells. We studied the effect of CD95 receptor activation on apoptosis of naïve CD4+ and naïve cytotoxic CD8+ T-lymphocytes in healthy children and children with acute infectious mononucleosis. In this study children with acute infectious mononucleosis at the age of 9 to 16 years were included. For comparison healthy children of the same age with no clinical and laboratory signs of the disease were used. Naïve CD4+ and naïve cytotoxic CD8+ T-lymphocytes were isolated by negative magnetic immunoseparation. The analysis of naïve T-cells apoptosis and the CD95 receptor surface expression density was performed by using the flow cytometry analysis. The analysis of T-cells was performed in three variants: freshly isolated naïve CD4+ T-lymphocytes and naïve cytotoxic CD8+ T-lymphocytes, and also cells after 24 hours of the cultivation with anti-CD95 monoclonal antibodies or without them. In healthy children both CD95– and CD95+ naïve CD4+ T-lymphocytes underwent apoptosis. In children with acute infectious mononucleosis CD95– naïve CD4+ T-lymphocytes lost their susceptibility to apoptosis induction. In healthy children and children with acute infectious mononucleosis CD95– naïve cytotoxic CD8+ T-lymphocytes were resistant to apoptosis in contrast to CD95+ naïve CD4+ T-lymphocytes. In healthy children CD95 receptor did not induce apoptosis of isolated naïve CD4+ T-lymphocytes and naïve cytotoxic CD8+ T-lymphocytes. In children with acute infectious mononucleosis CD95 receptor was involved in inhibition of apoptosis of naïve cytotoxic CD8+ T-lymphocytes and did not effect on the level of apoptosis of naïve CD4+ T-lymphocytes. We suggest that CD95-dependent suppression of naïve cytotoxic CD8+ T-lymphocytes apoptosis is a protective mechanism for the maintenance of a sufficient number of cytotoxic T-lymphocytes in the blood for the realization of effective antiviral immune response.

  15. Pro- and anti-apoptotic effects of p53 in cisplatin-treated human testicular cancer are cell context-dependent

    NARCIS (Netherlands)

    di Pietro, Alessandra; Koster, Roelof; Boersma-van Eck, Wytske; Dam, Wendy A.; Mulder, Nanno H.; Gietema, Jourik A.; de Vries, Elisabeth G. E.; de Jong, Steven

    2012-01-01

    In murine testicular cancer (TC) cells wild-type p53 contributes to sensitivity to DNA-damaging drugs in a dose-dependent way. In human TC, however, the role of wild-type p53 functionality in chemotherapeutic response remains elusive. We analyzed functionality of wild-type p53 in cisplatin sensitivi

  16. Elevated Levels of Uterine Anti-Apoptotic Signaling May Activate NFKB and Potentially Confer Resistance to Caspase 3-Mediated Apoptotic Cell Death During Pregnancy in Mice1

    OpenAIRE

    Jeyasuria, Pancharatnam; Subedi, Kalpana; Suresh, Arvind; Condon, Jennifer C.

    2011-01-01

    Preserving the uterus in a state of relative quiescence is vital to the maintenance of a successful pregnancy. Elevated cytoplasmic levels of uterine caspase 3 during pregnancy have been proposed as a potential regulator of uterine quiescence through direct targeting and disabling of the uterine contractile architecture. However, despite highly elevated levels of uterine caspase 3 during pregnancy, there is minimal evidence of apoptosis. This current study defines the mechanism whereby the pr...

  17. Elevated Levels of Uterine Anti-Apoptotic Signaling May Activate NFKB and Potentially Confer Resistance to Caspase 3-Mediated Apoptotic Cell Death During Pregnancy in Mice1

    Science.gov (United States)

    Jeyasuria, Pancharatnam; Subedi, Kalpana; Suresh, Arvind; Condon, Jennifer C.

    2011-01-01

    Preserving the uterus in a state of relative quiescence is vital to the maintenance of a successful pregnancy. Elevated cytoplasmic levels of uterine caspase 3 during pregnancy have been proposed as a potential regulator of uterine quiescence through direct targeting and disabling of the uterine contractile architecture. However, despite highly elevated levels of uterine caspase 3 during pregnancy, there is minimal evidence of apoptosis. This current study defines the mechanism whereby the pregnant uterine myocyte may harness the tocolytic activity of active caspases while avoiding apoptotic cell death. Using the pregnant mouse model, we have analyzed the uterus for changes in pro- and antiapoptotic signaling patterns associated with the advancing stages of pregnancy. Briefly, we have found that members of the IAP family, such as SURVIVIN and XIAP, and the Bcl2 family members, such as MCL1, are elevated in the uterine myocyte during late gestation. The IAP family members are the only endogenous inhibitors of active caspase 3, and MCL1 limits activation of caspase 3 by suppressing proapoptotic signaling. Elevated XIAP levels partner with SURVIVIN, resulting in increased levels of the antiapoptotic MCL1 via NFKB activation; these together have the potential to limit both the activity and level of active caspase 3 in the pregnant uterus as term approaches. We propose that modification of these antiapoptotic signaling partners allows the pregnant uterus to escape the apoptotic action of elevated active caspase 3 levels but also functions to limit the levels of active uterine caspase 3 near term. PMID:21566000

  18. Anti-apoptotic effects of novel phenolic antioxidant isolated from the Pacific oyster (Crassostrea gigas) on cultured human hepatocytes under oxidative stress.

    Science.gov (United States)

    Fuda, Hirotoshi; Watanabe, Mitsugu; Hui, Shu-Ping; Joko, Sae; Okabe, Hiroaki; Jin, Shigeki; Takeda, Seiji; Miki, Emiko; Watanabe, Takayuki; Chiba, Hitoshi

    2015-06-01

    The antioxidant, and hepatoprotective properties of 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), a natural phenolic antioxidant isolated from the Pacific oyster, were defined using cultured human hepatocyte-derived cells (C3A). DHMBA showed no cytotoxicity at 62.5-500μM, as well as chlorogenic acid (CGA), vitamin C, and vitamin E. However, butylated hydroxytoluene, eicosapentaenoic acid, docosahexaenoic acid and catechin reduced cell viability. In the presence of the prooxidant 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH), DHMBA at 125-500μM improved cell viability, whereas CGA had no effect. DNA ladder formation and flow-cytometric studies indicated that DHMBA inhibited AAPH-induced apoptosis and necrosis. CGA was ineffective. Thus, DHMBA is a novel, potent antioxidant, effectively protecting cultured hepatocytes from apoptosis and necrosis caused by oxidative stress. Additionally, the concentration of DHMBA was determined by mass spectrometry to be 24.4μmol/kg wet oyster meat, and three polyphenols (gentisic acid, daidzein, and matairesinol) were newly identified in the oyster extracts. PMID:25624228

  19. The effect of marathon on mRNA expression of anti-apoptotic and pro-apoptotic proteins and sirtuins family in male recreational long-distance runners

    Directory of Open Access Journals (Sweden)

    Russo Matteo

    2010-05-01

    Full Text Available Abstract Background A large body of evidence shows that a single bout of strenuous exercise induces oxidative stress in circulating human lymphocytes leading to lipid peroxidation, DNA damage, mitochondrial perturbations, and protein oxidation. In our research, we investigated the effect of physical load on the extent of apoptosis in primary cells derived from blood samples of sixteen healthy amateur runners after marathon (a.m.. Results Blood samples were collected from ten healthy amateur runners peripheral blood mononuclear cells (PBMCs were isolated from whole blood and bcl-2, bax, heat shock protein (HSP70, Cu-Zn superoxide dismutase (SOD, Mn-SOD, inducible nitric oxide synthase (i-NOS, SIRT1, SIRT3 and SIRT4 (Sirtuins RNA levels were determined by Northern Blot analysis. Strenuous physical load significantly increased HSP70, HSP32, Mn-SOD, Cu-Zn SOD, iNOS, GADD45, bcl-2, forkhead box O (FOXO3A and SIRT1 expression after the marathon, while decreasing bax, SIRT3 and SIRT4 expression (P Conclusion These data suggest that the physiological load imposed in amateur runners during marathon attenuates the extent of apoptosis and may interfere with sirtuin expression.

  20. Anti-Apoptotic Effects of 3,3 ',5-Triiodo-L-Thyronine in the Liver of Brain-Dead Rats

    NARCIS (Netherlands)

    Rebolledo Acevedo, Rolando; Van Erp, Anne C.; Ottens, Petra J.; Wiersema-Buist, Jantje; Leuvenink, Henri G. D.; Romanque, Pamela

    2015-01-01

    Background Thyroid hormone treatment in brain-dead organ donors has been extensively studied and applied in the clinical setting. However, its clinical applicability remains controversial due to a varying degree of success and a lack of mechanistic understanding about the therapeutic effects of 3,3'

  1. Expression of baculovirus anti-apoptotic genes p35 and op-iap in cotton (Gossypium hirsutum L. enhances tolerance to verticillium wilt.

    Directory of Open Access Journals (Sweden)

    Juan Tian

    Full Text Available BACKGROUND: Programmed cell death plays an important role in mediating plant adaptive responses to the environment such as the invasion of pathogens. Verticillium wilt, caused by the necrotrophic pathogen Verticillium dahliae, is a serious vascular disease responsible for great economic losses to cotton, but the molecular mechanisms of verticillium disease and effective, safe methods of resistance to verticillium wilt remain unexplored. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we introduced baculovirus apoptosis inhibitor genes p35 and op-iap into the genome of cotton via Agrobacterium-mediated transformation and analyzed the response of transgenic plants to verticillium wilt. Results showed that p35 and op-iap constructs were stably integrated into the cotton genome, expressed in the transgenic lines, and inherited through the T(3 generation. The transgenic lines had significantly increased tolerance to verticillium wilt throughout the developmental stages. The disease index of T(1-T(3 generation was lower than 19, significantly (P<0.05 better than the negative control line z99668. After treatment with 250 mg/L VD-toxins for 36 hours, DNA from negative control leaves was fragmented, whereas fragmentation in the transgenic leaf DNA did not occur. The percentage of cell death in transgenic lines increased by 7.11% after 60 mg/L VD-toxin treatment, which was less than that of the negative control lines's 21.27%. This indicates that p35 and op-iap gene expression partially protects cells from VD-toxin induced programmed cell death (PCD. CONCLUSION/SIGNIFICANCE: Verticillium dahliae can trigger plant cells to die through induction of a PCD mechanism involved in pathogenesis. This paper provides a potential strategy for engineering broad-spectrum necrotrophic disease resistance in plants.

  2. The anti-apoptotic MAP kinase pathway is inhibited in NIH3T3 fibroblasts with increased expression of phosphatidylinositol transfer protein β

    NARCIS (Netherlands)

    Schenning, M.; van Tiel, C.M.; Wirtz, K.W.A.; Snoek, G.T.

    2007-01-01

    Mouse NIH3T3 fibroblast cells overexpressing phosphatidylinositol transfer protein ß (PI-TPß, SPIß cells) demonstrate a low rate of proliferation and a high sensitivity towards UV-induced apoptosis when compared with wtNIH3T3 cells. In contrast, SPIßS262A cells overexpressing a mutant PI-TPß that la

  3. The anti-inflammatory and anti-apoptotic effects of gallic acid against mucosal inflammation- and erosions-induced by gastric ischemia-reperfusion in rats

    OpenAIRE

    Mard, Seyyed Ali; Mojadami, Shahnaz; Farbood, Yaghoob; Gharib Naseri, Mohammad Kazem

    2015-01-01

    The present study aimed to evaluate the protective effect of gallic acid on gastric mucosal lesions caused by ischemia-reperfusion (I/R) injury in rat. Forty male rats were randomly divided into sham, control (I/R injury) and three gallic acid-pretreated groups. To induce I/R lesions, the celiac artery was clamped for 30 min and then the clamp was removed to allow reperfusion for 6 hr. Pretreated rats received gallic acid (15, 30 or 60 mg kg-1, intraperitoneally) 30 min prior to the induction...

  4. Expression of animal anti-apoptotic gene Ced-9 enhances tolerance during Glycine max L.-Bradyrhizobium japonicum interaction under saline stress but reduces nodule formation.

    Directory of Open Access Journals (Sweden)

    Germán Robert

    Full Text Available The mechanisms by which the expression of animal cell death suppressors in economically important plants conferred enhanced stress tolerance are not fully understood. In the present work, the effect of expression of animal antiapoptotic gene Ced-9 in soybean hairy roots was evaluated under root hairs and hairy roots death-inducing stress conditions given by i Bradyrhizobium japonicum inoculation in presence of 50 mM NaCl, and ii severe salt stress (150 mM NaCl, for 30 min and 3 h, respectively. We have determined that root hairs death induced by inoculation in presence of 50 mM NaCl showed characteristics of ordered process, with increased ROS generation, MDA and ATP levels, whereas the cell death induced by 150 mM NaCl treatment showed non-ordered or necrotic-like characteristics. The expression of Ced-9 inhibited or at least delayed root hairs death under these treatments. Hairy roots expressing Ced-9 had better homeostasis maintenance, preventing potassium release; increasing the ATP levels and controlling the oxidative damage avoiding the increase of reactive oxygen species production. Even when our results demonstrate a positive effect of animal cell death suppressors in plant cell ionic and redox homeostasis under cell death-inducing conditions, its expression, contrary to expectations, drastically inhibited nodule formation even under control conditions.

  5. Single-molecule stochastic resonance

    CERN Document Server

    Hayashi, K; Manosas, M; Huguet, J M; Ritort, F; 10.1103/PhysRevX.2.031012

    2012-01-01

    Stochastic resonance (SR) is a well known phenomenon in dynamical systems. It consists of the amplification and optimization of the response of a system assisted by stochastic noise. Here we carry out the first experimental study of SR in single DNA hairpins which exhibit cooperatively folding/unfolding transitions under the action of an applied oscillating mechanical force with optical tweezers. By varying the frequency of the force oscillation, we investigated the folding/unfolding kinetics of DNA hairpins in a periodically driven bistable free-energy potential. We measured several SR quantifiers under varied conditions of the experimental setup such as trap stiffness and length of the molecular handles used for single-molecule manipulation. We find that the signal-to-noise ratio (SNR) of the spectral density of measured fluctuations in molecular extension of the DNA hairpins is a good quantifier of the SR. The frequency dependence of the SNR exhibits a peak at a frequency value given by the resonance match...

  6. Spin squeezing an ultracold molecule

    CERN Document Server

    Bhattacharya, M

    2015-01-01

    Most research on spin squeezing thus far has focused on realizations involving either atomic or nuclear degrees of freedom. In this article we discuss a concrete proposal for spin squeezing the ultracold ground state polar paramagnetic molecule OH, a system currently under fine control in the laboratory. Starting from an experimentally relevant effective Hamiltonian, we identify a parameter regime where different combinations of static electric and magnetic fields can be used to realize the single-axis twisting Hamiltonian of Kitagawa and Ueda [M. Kitagawa and M. Ueda, Phys. Rev. A 47, 5138 (1993)], the uniform field Hamiltonian proposed by Law et al. [C. K. Law, H. T Ng and P. T. Leung, Phys. Rev. A 63, 055601 (2001)], and a model of field propagation in a Kerr medium considered by Agarwal and Puri [G. S. Agarwal and R. R. Puri, Phys. Rev. A 39, 2969 (1989)]. To support our conclusions, we provide analytical expressions as well as numerical calculations, including optimization of field strengths and accounti...

  7. Coordination programming of photofunctional molecules.

    Science.gov (United States)

    Sakamoto, Ryota; Kusaka, Shinpei; Hayashi, Mikihiro; Nishikawa, Michihiro; Nishihara, Hiroshi

    2013-01-01

    Our recent achievements relating to photofunctional molecules are addressed. Section 1 discloses a new concept of photoisomerization. Pyridylpyrimidine-copper complexes undergo a ring inversion that can be modulated by the redox state of the copper center. In combination with an intermolecular photoelectron transfer (PET) initiated by the metal-to-ligand charge transfer (MLCT) transition of the Cu(I) state, we realize photonic regulation of the ring inversion. Section 2 reports on the first examples of heteroleptic bis(dipyrrinato)zinc(II) complexes. Conventional homoleptic bis(dipyrrinato)zinc(II) complexes suffered from low fluorescence quantum yields, whereas the heteroleptic ones feature bright fluorescence even in polar solvents. Section 3 describes our new findings on Pechmann dye, which was first synthesized in 1882. New synthetic procedures for Pechmann dye using dimethyl bis(arylethynyl)fumarate as a starting material gives rise to its new structural isomer. We also demonstrate potentiality of a donor-acceptor-donor type of Pechmann dye in organic electronics. PMID:23563859

  8. Coordination Programming of Photofunctional Molecules

    Directory of Open Access Journals (Sweden)

    Hiroshi Nishihara

    2013-04-01

    Full Text Available Our recent achievements relating to photofunctional molecules are addressed. Section 1 discloses a new concept of photoisomerization. Pyridylpyrimidine-copper complexes undergo a ring inversion that can be modulated by the redox state of the copper center. In combination with an intermolecular photoelectron transfer (PET initiated by the metal-to-ligand charge transfer (MLCT transition of the Cu(I state, we realize photonic regulation of the ring inversion. Section 2 reports on the first examples of heteroleptic bis(dipyrrinatozinc(II complexes. Conventional homoleptic bis(dipyrrinatozinc(II complexes suffered from low fluorescence quantum yields, whereas the heteroleptic ones feature bright fluorescence even in polar solvents. Section 3 describes our new findings on Pechmann dye, which was first synthesized in 1882. New synthetic procedures for Pechmann dye using dimethyl bis(arylethynylfumarate as a starting material gives rise to its new structural isomer. We also demonstrate potentiality of a donor-acceptor-donor type of Pechmann dye in organic electronics.

  9. Coordination programming of photofunctional molecules.

    Science.gov (United States)

    Sakamoto, Ryota; Kusaka, Shinpei; Hayashi, Mikihiro; Nishikawa, Michihiro; Nishihara, Hiroshi

    2013-04-05

    Our recent achievements relating to photofunctional molecules are addressed. Section 1 discloses a new concept of photoisomerization. Pyridylpyrimidine-copper complexes undergo a ring inversion that can be modulated by the redox state of the copper center. In combination with an intermolecular photoelectron transfer (PET) initiated by the metal-to-ligand charge transfer (MLCT) transition of the Cu(I) state, we realize photonic regulation of the ring inversion. Section 2 reports on the first examples of heteroleptic bis(dipyrrinato)zinc(II) complexes. Conventional homoleptic bis(dipyrrinato)zinc(II) complexes suffered from low fluorescence quantum yields, whereas the heteroleptic ones feature bright fluorescence even in polar solvents. Section 3 describes our new findings on Pechmann dye, which was first synthesized in 1882. New synthetic procedures for Pechmann dye using dimethyl bis(arylethynyl)fumarate as a starting material gives rise to its new structural isomer. We also demonstrate potentiality of a donor-acceptor-donor type of Pechmann dye in organic electronics.

  10. Single Molecule Studies of Chromatin

    Energy Technology Data Exchange (ETDEWEB)

    Jeans, C; Thelen, M P; Noy, A

    2006-02-06

    In eukaryotic cells, DNA is packaged as chromatin, a highly ordered structure formed through the wrapping of the DNA around histone proteins, and further packed through interactions with a number of other proteins. In order for processes such as DNA replication, DNA repair, and transcription to occur, the structure of chromatin must be remodeled such that the necessary enzymes can access the DNA. A number of remodeling enzymes have been described, but our understanding of the remodeling process is hindered by a lack of knowledge of the fine structure of chromatin, and how this structure is modulated in the living cell. We have carried out single molecule experiments using atomic force microscopy (AFM) to study the packaging arrangements in chromatin from a variety of cell types. Comparison of the structures observed reveals differences which can be explained in terms of the cell type and its transcriptional activity. During the course of this project, sample preparation and AFM techniques were developed and optimized. Several opportunities for follow-up work are outlined which could provide further insight into the dynamic structural rearrangements of chromatin.

  11. Geochemical Origin of Biological Molecules

    Science.gov (United States)

    Bassez, Marie-Paule

    2013-04-01

    A model for the geochemical origin of biological molecules is presented. Rocks such as peridotites and basalts, which contain ferromagnesian minerals, evolve in the presence of water. Their hydrolysis is an exothermic reaction which generates heat and a release of H2 and of minerals with modified structures. The hydrogen reacts with the CO2 embedded inside the rock or with the CO2 of the environment to form CO in an hydrothermal process. With the N2 of the environment, and with an activation source arising from cosmic radiation, ferromagnesian rocks might evolve towards the abiotic formation of biological molecules, such as peptide like macromolecules which produce amino acids after acid hydrolysis. The reactions concerned are described. The production of hydrothermal CO is discussed in geological sites containing ferromagnesian silicate minerals and the low intensity of the Earth's magnetic field during Paleoarchaean Era is also discussed. It is concluded that excitation sources arising from cosmic radiation were much more abundant during Paleoarchaean Era and that macromolecular structures of biological relevance might consequently form during Archaean Eon, as a product of the chemical evolution of the rocks and of their mineral contents. This synthesis of abiotically formed biological molecules is consecutively discussed for meteorites and other planets such as Mars. This model for the geochemical origin of biological molecules has first been proposed in 2008 in the context of reactions involving catalysers such as kaolinite [Bassez 2008a] and then presented in conferences and articles [Bassez 2008b, 2009, 2012; Bassez et al. 2009a to 2012b]. BASSEZ M.P. 2008a Synthèse prébiotique dans les conditions hydrothermales, CNRIUT'08, Lyon 29-30/05/2008, Conf. and open access article:http://liris.cnrs.fr/~cnriut08/actes/ 29 mai 11h-12h40. BASSEZ M.P. 2008b Prebiotic synthesis under hydrothermal conditions, ISSOL'08, P2-6, Firenze-Italy, 24-29/08/2008. Poster at the

  12. Rotational cooling of trapped polyatomic molecules

    CERN Document Server

    Glöckner, Rosa; Englert, Barbara G U; Rempe, Gerhard; Zeppenfeld, Martin

    2015-01-01

    Controlling the internal degrees of freedom is a key challenge for applications of cold and ultracold molecules. Here, we demonstrate rotational-state cooling of trapped methyl fluoride molecules (CH3F) by optically pumping the population of 16 M-sublevels in the rotational states J=3,4,5, and 6 into a single level. By combining rotational-state cooling with motional cooling, we increase the relative number of molecules in the state J=4, K=3, M=4 from a few percent to over 70%, thereby generating a translationally cold (~30mK) and nearly pure state ensemble of about 10^6 molecules. Our scheme is extendable to larger sets of initial states, other final states and a variety of molecule species, thus paving the way for internal-state control of ever larger molecules.

  13. Laser cooling of a diatomic molecule

    CERN Document Server

    Shuman, E S; DeMille, D

    2011-01-01

    It has been roughly three decades since laser cooling techniques produced ultracold atoms, leading to rapid advances in a vast array of fields. Unfortunately laser cooling has not yet been extended to molecules because of their complex internal structure. However, this complexity makes molecules potentially useful for many applications. For example, heteronuclear molecules possess permanent electric dipole moments which lead to long-range, tunable, anisotropic dipole-dipole interactions. The combination of the dipole-dipole interaction and the precise control over molecular degrees of freedom possible at ultracold temperatures make ultracold molecules attractive candidates for use in quantum simulation of condensed matter systems and quantum computation. Also ultracold molecules may provide unique opportunities for studying chemical dynamics and for tests of fundamental symmetries. Here we experimentally demonstrate laser cooling of the molecule strontium monofluoride (SrF). Using an optical cycling scheme re...

  14. Rotational Cooling of Trapped Polyatomic Molecules.

    Science.gov (United States)

    Glöckner, Rosa; Prehn, Alexander; Englert, Barbara G U; Rempe, Gerhard; Zeppenfeld, Martin

    2015-12-01

    Controlling the internal degrees of freedom is a key challenge for applications of cold and ultracold molecules. Here, we demonstrate rotational-state cooling of trapped methyl fluoride molecules (CH_{3}F) by optically pumping the population of 16 M sublevels in the rotational states J=3, 4, 5 and 6 into a single level. By combining rotational-state cooling with motional cooling, we increase the relative number of molecules in the state J=4, K=3, M=4 from a few percent to over 70%, thereby generating a translationally cold (≈30  mK) and nearly pure state ensemble of about 10^{6} molecules. Our scheme is extendable to larger sets of initial states, other final states, and a variety of molecule species, thus paving the way for internal-state control of ever-larger molecules. PMID:26684114

  15. Observation of pendular butterfly Rydberg molecules

    CERN Document Server

    Niederprüm, Thomas; Eichert, Tanita; Lippe, Carsten; Pérez-Ríos, Jesús; Greene, Chris H; Ott, Herwig

    2016-01-01

    Obtaining full control over the internal and external quantum states of molecules is the central goal of ultracold chemistry and allows for the study of coherent molecular dynamics, collisions and tests of fundamental laws of physics. When the molecules additionally have a permanent electric dipole moment, the study of dipolar quantum gases and spin-systems with long-range interactions as well as applications in quantum information processing are possible. Rydberg molecules constitute a class of exotic molecules, which are bound by the interaction between the Rydberg electron and the ground state atom. They exhibit extreme bond lengths of hundreds of Bohr radii and giant permanent dipole moments in the kilo-Debye range. A special type with exceptional properties are the so-called butterfly molecules, whose electron density resembles the shape of a butterfly. Here, we report on the photoassociation of butterfly Rydberg molecules and their orientation in a weak electric field. Starting from a Bose-Einstein cond...

  16. Charge correlations in polaron hopping through molecules

    OpenAIRE

    Schmidt, Benjamin B.; Hettler, Matthias H.; Schön, Gerd

    2009-01-01

    In many organic molecules the strong coupling of excess charges to vibrational modes leads to the formation of polarons, i.e., a localized state of a charge carrier and a molecular deformation. Incoherent hopping of polarons along the molecule is the dominant mechanism of transport at room temperature. We study the far-from-equilibrium situation where, due to the applied bias, the induced number of charge carriers on the molecule is high enough such that charge correlations become relevant. W...

  17. Scanning tunneling microscopy of biological molecules

    International Nuclear Information System (INIS)

    Scanning Tunnelling Microscopy (STM) has been used to image a number of biological molecules including thrombospondin and glycoprotein 88 (GP88). In this paper, STM images which clearly resolve the morphology of these molecules are presented. Ultimately, it is hoped that STM will provide information about the interaction between these molecules after overcoming problems associated with sample preparation and reproducibility of results which are discussed. 4 refs., 2 figs

  18. RNA Reactions One Molecule at a Time

    OpenAIRE

    Tinoco, Ignacio; Chen, Gang; Qu, Xiaohui

    2010-01-01

    Much of the dynamics information is lost in bulk measurements because of the population averaging. Single-molecule methods measure one molecule at a time; they provide knowledge not obtainable by other means. In this article, we review the application of the two most widely used single-molecule methods—fluorescence resonance energy transfer (FRET) and force versus extension measurements—to several RNA reactions. First, we discuss folding/unfolding studies on a hairpin ribozyme that revealed m...

  19. Dynamics of a linear magnetic "microswimmer molecule"

    OpenAIRE

    Babel, Sonja; Löwen, Hartmut; Menzel, Andreas M.

    2015-01-01

    In analogy to nanoscopic molecules that are composed of individual atoms, we consider an active "microswimmer molecule". It is built up from three individual magnetic colloidal microswimmers that are connected by harmonic springs and hydrodynamically interact with each other. In the ground state, they form a linear straight molecule. We analyze the relaxation dynamics for perturbations of this straight configuration. As a central result, with increasing self-propulsion, we observe an oscillat...

  20. Making "Operations" inside a Single Molecule

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ Free and delicate manipulation of single molecules has long been expected by scientists so as to realize specific functions. In the 1990s, the laboratory led by Prof. Wison Ho from the University of California was successful in inducing chemical reactions at the single molecule level with scanning tunneling microscopy (STM), revealing the extensive potentials of "single molecule operation." However, until recently, researchers have failed to utilize the reaction to give rise to special physical properties.

  1. Ultracold polar molecules near quantum degeneracy

    OpenAIRE

    Ospelkaus, S.; Ni, K.-K.; de Miranda, M. H. G.; Neyenhuis, B.; Wang, D; Kotochigova, S.; Julienne, P. S.; Jin, D. S.; J. Ye

    2008-01-01

    We report the creation and characterization of a near quantum-degenerate gas of polar $^{40}$K-$^{87}$Rb molecules in their absolute rovibrational ground state. Starting from weakly bound heteronuclear KRb Feshbach molecules, we implement precise control of the molecular electronic, vibrational, and rotational degrees of freedom with phase-coherent laser fields. In particular, we coherently transfer these weakly bound molecules across a 125 THz frequency gap in a single step into the absolute...

  2. Electron-molecule interactions and their applications

    CERN Document Server

    Christophorou, L G

    1984-01-01

    Electron-Molecule Interactions and Their Applications, Volume 2 provides a balanced and comprehensive account of electron-molecule interactions in dilute and dense gases and liquid media. This book consists of six chapters. Chapter 1 deals with electron transfer reactions, while Chapter 2 discusses electron-molecular positive-ion recombination. The electron motion in high-pressure gases and electron-molecule interactions from single- to multiple-collision conditions is deliberated in Chapter 3. In Chapter 4, knowledge on electron-molecule interactions in gases is linked to that on similar proc

  3. Single-molecule pulling: phenomenology and interpretation

    CERN Document Server

    Franco, Ignacio; Schatz, George C

    2012-01-01

    Single-molecule pulling techniques have emerged as versatile tools for probing the noncovalent forces holding together the secondary and tertiary structure of macromolecules. They also constitute a way to study at the single-molecule level processes that are familiar from our macroscopic thermodynamic experience. In this Chapter, we summarize the essential phenomenology that is typically observed during single-molecule pulling, provide a general statistical mechanical framework for the interpretation of the equilibrium force spectroscopy and illustrate how to simulate single-molecule pulling experiments using molecular dynamics.

  4. Submillimeter Spectroscopy of Hydride Molecules

    Science.gov (United States)

    Phillips, T. G.

    1998-05-01

    Simple hydride molecules are of great importance in astrophysics and astrochemistry. Physically they dominate the cooling of dense, warm phases of the ISM, such as the cores and disks of YSOs. Chemically they are often stable end points of chemical reactions, or may represent important intermediate stages of the reaction chains, which can be used to test the validity of the process. Through the efforts of astronomers, physicists, chemists, and laboratory spectroscopists we have an approximate knowledge of the abundance of some of the important species, but a great deal of new effort will be required to achieve the comprehensive and accurate data set needed to determine the energy balance and firmly establish the chemical pathways. Due to the low moment of inertia, the hydrides rotate rapidly and so have their fundamental spectral lines in the submillimeter. Depending on the cloud geometry and temperature profile they may be observed in emission or absorption. Species such as HCl, HF, OH, CH, CH(+) , NH_2, NH_3, H_2O, H_2S, H_3O(+) and even H_3(+) have been detected, but this is just a fraction of the available set. Also, most deduced abundances are not nearly sufficiently well known to draw definitive conclusions about the chemical processes. For example, the most important coolant for many regions, H_2O, has a possible range of deduced abundance of a factor of 1000. The very low submillimeter opacity at the South Pole site will be a significant factor in providing a new capabilty for interstellar hydride spectroscopy. The new species and lines made available in this way will be discussed.

  5. Theoretical spectra of floppy molecules

    Science.gov (United States)

    Chen, Hua

    2000-09-01

    Detailed studies of the vibrational dynamics of floppy molecules are presented. Six-D bound-state calculations of the vibrations of rigid water dimer based on several anisotropic site potentials (ASP) are presented. A new sequential diagonalization truncation approach was used to diagonalize the angular part of the Hamiltonian. Symmetrized angular basis and a potential optimized discrete variable representation for intermonomer distance coordinate were used in the calculations. The converged results differ significantly from the results presented by Leforestier et al. [J. Chem. Phys. 106 , 8527 (1997)]. It was demonstrated that ASP-S potential yields more accurate tunneling splittings than other ASP potentials used. Fully coupled 4D quantum mechanical calculations were performed for carbon dioxide dimer using the potential energy surface given by Bukowski et al [J. Chem. Phys., 110, 3785 (1999)]. The intermolecular vibrational frequencies and symmetry adapted force constants were estimated and compared with experiments. The inter-conversion tunneling dynamics was studied using the calculated virtual tunneling splittings. Symmetrized Radau coordinates and the sequential diagonalization truncation approach were formulated for acetylene. A 6D calculation was performed with 5 DVR points for each stretch coordinate, and an angular basis that is capable of converging the angular part of the Hamiltonian to 30 cm-1 for internal energies up to 14000 cm-1. The probability at vinylidene configuration were evaluated. It was found that the eigenstates begin to extend to vinylidene configuration from about 10000 cm-1, and the ra, coordinate is closely related to the vibrational dynamics at high energy. Finally, a direct product DVR was defined for coupled angular momentum operators, and the SDT approach were formulated. They were applied in solving the angular part of the Hamiltonian for carbon dioxide dimer problem. The results show the method is capable of giving very accurate

  6. Spin polarization effect for Fe2 molecule

    Institute of Scientific and Technical Information of China (English)

    Yan Shi-Ying; Zhu Zheng-He

    2006-01-01

    This paper uses the density functional theory (DFT)(B3p86) of Gaussian03 to optimize the structure of Fe2 molecule. The result shows that the ground state for Fe2 molecule is a 9-multiple state, which shows spin polarization effect of Fe2 molecule of transition metal elements for the first time. Meanwhile, we have not found any spin pollution because the wavefunction of the ground state does not mingle with wavefunctions with higher energy states. So, that the ground state for Fe2 molecule is a 9-multiple state is indicative of the spin polarization effect of Fe2 molecule of transition metal elements. That is, there exist 8 parallel spin electrons. The non-conjugated electron is greatest in number. These electrons occupy different spacious tracks, so that the energy of the Fe2 molecule is minimized. It can be concluded that the effect of parallel spin of the Fe2 molecule is larger than the effect of the conjugated molecule, which is obviously related to the effect of electron d delocalization. In addition, the Murrell-Sorbie potential functions with the parameters for the ground state and other states of Fe2 molecule are derived. Dissociation energy De for the ground state of Fe2 molecule is 2.8586ev, equilibrium bond length Re is 0.2124nm, vibration frequency ωe is 336.38 cm-1. Its force constants f2, f3, and f4 are 1.8615aJ·nm-2, -8.6704a J·nm-3, 29.1676aJ·nm-4 respectively. The other spectroscopic data for the ground state of Fe2 moleculeωeχe, Be, αe are 1.5461 cm-1, 0.1339 cm-1, 7.3428×10-4 cm-1 respectively.

  7. Spin polarization effect for Tc2 molecule

    Institute of Scientific and Technical Information of China (English)

    Yan Shi-Ying; Zhu Zheng-He

    2004-01-01

    Density functional method (DFT) (B3p86) of Gaussian98 has been used to optimize the structure of the Tc2 molecule. The result shows that the ground state for Tc2 molecule is an 11-multiple state and its electronic configuration is 11∑- g, which shows the spin polarization effect of Tc2 molecule of a transition metal element for the first time.Meanwhile, we have not found any spin pollution because the wavefunction of the ground state does not mingle with wavefunctions of higher energy states. So, that the ground state for Tc2 molecule is an 11-multiple state is indicative of the spin polarization effect of Tc2 molecule of a transition metal element: that is, there exist 10 parallel spin electrons. The non-conjugated electron is greatest in number. These electrons occupy different spacious tracks, so that the energy of Tc2 molecule is minimized. It can be concluded that the effect of parallel spin of the Tc2 molecule is larger than the effect of the conjugated molecule, which is obviously related to the effect of electron d delocalization.In addition, the Murrell-Sorbie potential functions with the parameters for the ground state 11∑- g and other states of Tc2 molecule are derived. Dissociation energy De for the ground state of Tc2 molecule is 2.266eV, equilibrium bond length Re is 0.2841nm, vibration frequency ωe is 178.52cm-1. Its force constants f2, f3, and f4 are 0.9200aJ.nm-2,-3.5700aJ.nm-3, 11.2748aJ.nm-4 respectively. The other spectroscopic data for the ground state of Tc2 molecule ωexe,Be, αe are 0.5523cm- 1, 0.0426cm- 1, 1.6331 × 10-4cm- 1 respectively.

  8. Infrared emission from electronically excited biacetyl molecules

    NARCIS (Netherlands)

    Drent, E.; Kommandeur, J.

    1971-01-01

    The infrared emission of electronically excited biacetyl molecules in the gas phase at low pressure was observed. Some experimental details are given, and it is shown that the emission derives from biacetyl molecules in their triplet state. The emission is dependent on the wavelength of excitation.

  9. Molecular Wring Resonances in Chain Molecules

    DEFF Research Database (Denmark)

    Bohr, Henrik; Brunak, Søren; Bohr, Jakob

    1997-01-01

    It is shown that the eigenfrequency of collective twist excitations in chain molecules can be in the megahertz and gigahertz range. Accordingly, resonance states can be obtained at specific frequencies, and phenomena that involve structural properties can take place. Chain molecules can alter the...

  10. Molecule-oriented programming in Java

    NARCIS (Netherlands)

    Bergstra, J.A.

    2002-01-01

    Molecule-oriented programming is introduced as a programming style carrying some perspective for Java. A sequence of examples is provided. Supporting the development of the molecule-oriented programming style several matters are introduced and developed: profile classes allowing the representation o

  11. Spectrum Generating Algebra for X$_{3}$ Molecules

    CERN Document Server

    Bijker, R; Leviatan, A

    1995-01-01

    A new spectrum generating algebra for a unified description of rotations and vibrations in polyatomic molecules is introduced. An application to nonlinear X$_3$ molecules shows that this model (i) incorporates exactly the relevant point group, (ii) provides a complete classification of oblate top states, and (iii) treats properly both degenerate and nondegenerate vibrations.

  12. Allosteric small-molecule kinase inhibitors

    DEFF Research Database (Denmark)

    Wu, Peng; Clausen, Mads Hartvig; Nielsen, Thomas E.

    2015-01-01

    -molecule allosteric inhibitor trametinib in 2013, the progress of more than 10 other allosteric inhibitors in clinical trials, and the emergence of a pipeline of highly selective and potent preclinical molecules, have been reported in the past decade. In this article, we present the current knowledge on allosteric...

  13. Controlled contact to a C-60 molecule

    DEFF Research Database (Denmark)

    Neel, N.; Kröger, J.; Limot, L.;

    2007-01-01

    The tip of a low-temperature scanning tunneling microscope is approached towards a C-60 molecule adsorbed at a pentagon-hexagon bond on Cu(100) to form a tip-molecule contact. The conductance rapidly increases to approximate to 0.25 conductance quanta in the transition region from tunneling...

  14. Spin polarization effect for Co2 molecule

    Institute of Scientific and Technical Information of China (English)

    Yan Shi-Ying; Bao Wen-Sheng

    2007-01-01

    The density functional theory (DFT)(b3p86) of Gaussian 03 has been used to optimize the structure of the Co2molecule, a transition metal element molecule. The result shows that the ground state for the Co2 molecule is a 7-multiple state, indicating a spin polarization effect in the Co2 molecule. Meanwhile, we have not found any spin pollution because the wavefunction of the ground state is not mingled with wavefunctions of higher-energy states. So for the ground state of Co2 molecule to be a 7-multiple state is the indicative of spin polarization effect of the Co2molecule, that is, there exist 6 parallel spin electrons in a Co2 molecule. The number of non-conjugated electrons is the greatest. These electrons occupy different spacial orbitals so that the energy of the Co2 molecule is minimized. It can be concluded that the effect of parallel spin in the Co2 molecule is larger than the effect of the conjugated molecule,which is obviously related to the effect of electron d delocalization. In addition, the Murrell-Sorbie potential functions with the parameters for the ground state and the other states of the Co2 molecule are derived. The dissociation energy De for the ground state of Co2 molecule is 4.0489eV, equilibrium bond length Re is 0.2061 nm, and vibration frequency 11.2222 aJ.nm-4respectively(1 a.J=10-18 J). The other spectroscopic data for the ground state of Co2 molecule ωexe,Be, and αe are 0.7202 cm-1, 0.1347 cm-1, and 2.9120× 10-1 cm-1 respectively. And ωexe is the non-syntonic part of frequency, Be is the rotational constant, αe is revised constant of rotational constant for non-rigid part of Co2 molecule.

  15. Small azomethine molecules and their use in photovoltaic devices

    NARCIS (Netherlands)

    Dingemans, T.J.; Petrus, M.L.

    2015-01-01

    The present invention is in the field of a small azomethine molecule having photovoltaic characteristics, a method of synthesizing said molecule, use of said molecule in a photovoltaic device, a solar cell comprising said molecule, and a film comprising said molecule. The present molecules may find

  16. The symmetry of single-molecule conduction.

    Science.gov (United States)

    Solomon, Gemma C; Gagliardi, Alessio; Pecchia, Alessandro; Frauenheim, Thomas; Di Carlo, Aldo; Reimers, Jeffrey R; Hush, Noel S

    2006-11-14

    We introduce the conductance point group which defines the symmetry of single-molecule conduction within the nonequilibrium Green's function formalism. It is shown, either rigorously or to within a very good approximation, to correspond to a molecular-conductance point group defined purely in terms of the properties of the conducting molecule. This enables single-molecule conductivity to be described in terms of key qualitative chemical descriptors that are independent of the nature of the molecule-conductor interfaces. We apply this to demonstrate how symmetry controls the conduction through 1,4-benzenedithiol chemisorbed to gold electrodes as an example system, listing also the molecular-conductance point groups for a range of molecules commonly used in molecular electronics research.

  17. The symmetry of single-molecule conduction.

    Science.gov (United States)

    Solomon, Gemma C; Gagliardi, Alessio; Pecchia, Alessandro; Frauenheim, Thomas; Di Carlo, Aldo; Reimers, Jeffrey R; Hush, Noel S

    2006-11-14

    We introduce the conductance point group which defines the symmetry of single-molecule conduction within the nonequilibrium Green's function formalism. It is shown, either rigorously or to within a very good approximation, to correspond to a molecular-conductance point group defined purely in terms of the properties of the conducting molecule. This enables single-molecule conductivity to be described in terms of key qualitative chemical descriptors that are independent of the nature of the molecule-conductor interfaces. We apply this to demonstrate how symmetry controls the conduction through 1,4-benzenedithiol chemisorbed to gold electrodes as an example system, listing also the molecular-conductance point groups for a range of molecules commonly used in molecular electronics research. PMID:17115774

  18. Quantum transport of the single metallocene molecule

    Science.gov (United States)

    Yu, Jing-Xin; Chang, Jing; Wei, Rong-Kai; Liu, Xiu-Ying; Li, Xiao-Dong

    2016-10-01

    The Quantum transport of three single metallocene molecule is investigated by performing theoretical calculations using the non-equilibrium Green's function method combined with density functional theory. We find that the three metallocen molecules structure become stretched along the transport direction, the distance between two Cp rings longer than the other theory and experiment results. The lager conductance is found in nickelocene molecule, the main transmission channel is the electron coupling between molecule and the electrodes is through the Ni dxz and dyz orbitals and the s, dxz, dyz of gold. This is also confirmed by the highest occupied molecular orbital resonance at Fermi level. In addition, negative differential resistance effect is found in the ferrocene, cobaltocene molecules, this is also closely related with the evolution of the transmission spectrum under applied bias.

  19. Chemical principles of single-molecule electronics

    Science.gov (United States)

    Su, Timothy A.; Neupane, Madhav; Steigerwald, Michael L.; Venkataraman, Latha; Nuckolls, Colin

    2016-03-01

    The field of single-molecule electronics harnesses expertise from engineering, physics and chemistry to realize circuit elements at the limit of miniaturization; it is a subfield of nanoelectronics in which the electronic components are single molecules. In this Review, we survey the field from a chemical perspective and discuss the structure-property relationships of the three components that form a single-molecule junction: the anchor, the electrode and the molecular bridge. The spatial orientation and electronic coupling between each component profoundly affect the conductance properties and functions of the single-molecule device. We describe the design principles of the anchor group, the influence of the electronic configuration of the electrode and the effect of manipulating the structure of the molecular backbone and of its substituent groups. We discuss single-molecule conductance switches as well as the phenomenon of quantum interference and then trace their fundamental roots back to chemical principles.

  20. Collecting single molecules with conventional optical tweezers

    CERN Document Server

    Singer, W; Heckenberg, N R; Rubinsztein-Dunlop, H; Singer, Wolfgang; Nieminen, Timo A.; Heckenberg, Norman R.; Rubinsztein-Dunlop, Halina

    2007-01-01

    The size of particles which can be trapped in optical tweezers ranges from tens of nanometres to tens of micrometres. This size regime also includes large single molecules. Here we present experiments demonstrating that optical tweezers can be used to collect polyethylene oxide (PEO) molecules suspended in water. The molecules that accumulate in the focal volume do not aggregate and therefore represent a region of increased molecule concentration, which can be controlled by the trapping potential. We also present a model which relates the change in concentration to the trapping potential. Since many protein molecules have molecular weights for which this method is applicable the effect may be useful in assisting nucleation of protein crystals.

  1. High Harmonic Generation from Rotationally Excited Molecules

    Science.gov (United States)

    Lock, Robynne M.

    2011-12-01

    High harmonic generation (HHG) is understood through a three-step model. A strong laser field ionizes an atom or molecule. The free electron propagates in the laser field and may recombine with the atom or molecule leading to the generation of extreme ultraviolet or soft x-ray light at odd harmonics of the fundamental. Since the wavelength of the recombining electron is on the order of internuclear distances in molecules, HHG acts as a probe of molecular structure and dynamics. Conversely, control of the molecules leads to control of the properties (intensity, phase, and polarization) of the harmonic emission. Rotationally exciting molecules provides field-free molecular alignment at time intervals corresponding to fractions of the rotational period of the molecule. Alignment is necessary for understanding how the harmonic emission depends on molecular structure and alignment. Additionally, HHG acts as a probe of the rotational wavepackets. This thesis reports three experiments on HHG from rotationally excited molecules. Before we can use HHG as a probe of complex molecular dynamics or control harmonic properties through molecules, the harmonic emission from aligned, linear molecules must first be understood. To that end, the first experiment measures the intensity and phase of harmonics generated from N 2O and N2 near times of strong alignment revealing interferences during recombination. The second experiment demonstrates HHG as a sensitive probe of rotational wavepacket dynamics in CO2 and N2O, revealing new revival features not detected by any other probe. The final experiment focuses on understanding and controlling the polarization state of the harmonic emission. Generating elliptically polarized harmonics would be very useful for probing molecular and materials systems. We observe an elliptical dichroism in polarization-resolved measurements of the harmonic emission from aligned N2 and CO2 molecules, revealing evidence for electron-hole dynamics between the

  2. Search for complex organic molecules in space

    Science.gov (United States)

    Ohishi, Masatoshi

    2016-07-01

    It was 1969 when the first organic molecule in space, H2CO, was discovered. Since then many organic molecules were discovered by using the NRAO 11 m (upgraded later to 12 m), Nobeyama 45 m, IRAM 30 m, and other highly sensitive radio telescopes as a result of close collaboration between radio astronomers and microwave spectroscopists. It is noteworthy that many famous organic molecules such as CH3OH, C2H5OH, (CH3)2O and CH3NH2 were detected by 1975. Organic molecules were found in so-called hot cores where molecules were thought to form on cold dust surfaces and then to evaporate by the UV photons emitted from the central star. These days organic molecules are known to exist not only in hot cores but in hot corinos (a warm, compact molecular clump found in the inner envelope of a class 0 protostar) and even protoplanetary disks. As was described above, major organic molecules were known since 1970s. It was very natural that astronomers considered a relationship between organic molecules in space and the origin of life. Several astronomers challenged to detect glycine and other prebiotic molecules without success. ALMA is expected to detect such important materials to further consider the gexogenous deliveryh hypothesis. In this paper I summarize the history in searching for complex organic molecules together with difficulties in observing very weak signals from larger species. The awfully long list of references at the end of this article may be the most useful part for readers who want to feel the exciting discovery stories.

  3. Spin polarization effect for Mn2 molecule

    Institute of Scientific and Technical Information of China (English)

    Yan Shi-Ying; Xu Guo-Liang

    2007-01-01

    The density functional theory method (DFT) (b3p86) of Gaussian 03 has been used to optimize the structure of the Mn2 molecule.The result shows that the ground state of the Mn2 molecule is an 11-multiple state,indicating a spin polarization effect in the Mn2 molecule,a transition metal element molecule.Meanwhile,we have not found any spin pollution because the wavefunction of the ground state does not mingle with wavefunctions of higher-energy states.So the ground state for Mn2 molecule being of an 11-multiple state is the indicative of spin polarization effect of the Mn2 molecule among those in the transition metal elements:that is,there are 10 parallel spin electrons in a Mn2 molecule.The number of non-conjugated electrons is the greatest.These electrons occupy different spacious orbitals so that the energy of the Mn2 molecule is minimized.It can be concluded that the effect of parallel spin in the Mn2 molecule is larger than the effect of the conjugated molecule,which is obviously related to the effect of electron d delocalization.In addition,the Murrell-Sorbie potential functions with the parameters for the ground state and other states of the Mn2 molecule are derived.The dissociation energy De for the ground state of the Mn2 molecule is 1.4477eV,equilibrium bond length Re is 0.2506 nm,vibration frequency ωe is 211.51 cm-1.Its force constants,f2,f3,and f4 are 0.7240 aJ·nm-2,-3.35574 aJ·nm-3,11.4813 aJ·nm-4 respectively. The other spectroscopic data for the ground state of the Mn2 molecule ωeχe,Be,αe are 1.5301 cm-1,0.0978 cm-1,7.7825×10-4 cm-1 respectively.

  4. Molecules-in-Molecules: An Extrapolated Fragment-Based Approach for Accurate Calculations on Large Molecules and Materials.

    Science.gov (United States)

    Mayhall, Nicholas J; Raghavachari, Krishnan

    2011-05-10

    We present a new extrapolated fragment-based approach, termed molecules-in-molecules (MIM), for accurate energy calculations on large molecules. In this method, we use a multilevel partitioning approach coupled with electronic structure studies at multiple levels of theory to provide a hierarchical strategy for systematically improving the computed results. In particular, we use a generalized hybrid energy expression, similar in spirit to that in the popular ONIOM methodology, that can be combined easily with any fragmentation procedure. In the current work, we explore a MIM scheme which first partitions a molecule into nonoverlapping fragments and then recombines the interacting fragments to form overlapping subsystems. By including all interactions with a cheaper level of theory, the MIM approach is shown to significantly reduce the errors arising from a single level fragmentation procedure. We report the implementation of energies and gradients and the initial assessment of the MIM method using both biological and materials systems as test cases. PMID:26610128

  5. Understanding Polymer Properties through Imaging of Molecules.

    Science.gov (United States)

    Sheiko, Sergei

    2008-03-01

    The unique advantage of Scanning Probe Microscopy (SPM) is that it allows imaging of flexible polymer molecules, whose overall size and local curvature are below the optical resolution limit. The role of molecular visualization has grown to be especially profound with the synthesis of complex macromolecules whose structure is difficult to confirm using conventional techniques such as NMR and light scattering. This is especially true for molecules that are branched, heterogeneous, and polydisperse. Here, SPM images provide unambiguous proof of the molecular architecture along with accurate analysis of size, conformation, and ordering of molecules on surfaces. The unique advantage of SPM is that one obtains molecular dimensions in direct space. This offers more opportunities for statistical analysis including fractionation of molecules by size, branching topology, and chemical composition as well as sorting out the irrelevant species. Unlike molecular characterization of static molecules, it remains challenging to study molecules as they move and react on surfaces. We will discuss pioneering AFM studies of flowing monolayers one molecule at a time. Through use of AFM, the flow process was monitored over a broad range of length scales from the millimeter long precursor film all the way down to the movements of individual molecules within the film. Molecular imaging enabled independent measurements both the driving and frictional forces that control spreading rate. In these studies, one also discovered a new type of flow instability in polymer monolayers caused by flow-induced conformational transitions. Recently, molecular imaging has been successfully used to monitor adsorption-induced degradation of branched molecules. These experiments open an entirely new perspective in chemistry wherein the chemical bonds can be mechanically activated upon the physical contact of a macromolecule with a substrate. This research directly impacts coatings, lubrication, heterogeneous

  6. Aligning molecules with intense nonresonant laser fields

    DEFF Research Database (Denmark)

    Larsen, J.J.; Safvan, C.P.; Sakai, H.;

    1999-01-01

    Molecules in a seeded supersonic beam are aligned by the interaction between an intense nonresonant linearly polarized laser field and the molecular polarizability. We demonstrate the general applicability of the scheme by aligning I2, ICl, CS2, CH3I, and C6H5I molecules. The alignment is probed...... by mass selective two dimensional imaging of the photofragment ions produced by femtosecond laser pulses. Calculations on the degree of alignment of I2 are in good agreement with the experiments. We discuss some future applications of laser aligned molecules....

  7. Imaging Cold Molecules on a Chip

    CERN Document Server

    Marx, S; Abel, M J; Zehentbauer, T; Meijer, G; Santambrogio, G

    2013-01-01

    We present the integrated imaging of cold molecules in a microchip environment. The on-chip de- tection is based on REMPI, which is quantum-state-selective and generally applicable. We demon- strate and characterize time-resolved spatial imaging and subsequently use it to analyze the effect of a phase-space manipulation sequence aimed at compressing the velocity distribution of a molec- ular ensemble with a view to future high-resolution spectroscopic studies. The realization of such on-chip measurements adds the final fundamental component to the molecule chip, offering a new and promising route for investigating cold molecules.

  8. Tunable optical absorption in silicene molecules

    KAUST Repository

    Mokkath, Junais Habeeb

    2016-07-13

    Two-dimensional materials with a tunable band gap that covers a wide range of the solar spectrum hold great promise for sunlight harvesting. For this reason, we investigate the structural, electronic, and optical properties of silicene molecules using time dependent density functional theory. We address the influence of the molecular size, buckling, and charge state as well as that of a dielectric environment. Unlike planar graphene molecules, silicene molecules prefer to form low-buckled structures with strong visible to ultraviolet optical response. We also identify molecular plasmons.

  9. Rotational cooling of trapped polyatomic molecules

    OpenAIRE

    Glöckner, Rosa; Prehn, Alexander; Englert, Barbara G. U.; Rempe, Gerhard; Zeppenfeld, Martin

    2015-01-01

    Controlling the internal degrees of freedom is a key challenge for applications of cold and ultracold molecules. Here, we demonstrate rotational-state cooling of trapped methyl fluoride molecules (CH3F) by optically pumping the population of 16 M-sublevels in the rotational states J=3,4,5, and 6 into a single level. By combining rotational-state cooling with motional cooling, we increase the relative number of molecules in the state J=4, K=3, M=4 from a few percent to over 70%, thereby genera...

  10. Kondo effect in molecules with strong correlations

    Energy Technology Data Exchange (ETDEWEB)

    Kuzmenko, Tetyana [Department of Physics, Ben-Gurion University, P.O. Box 653, Beer-Sheva 84105 (Israel)]. E-mail: tetyana@bgumail.bgu.ac.il; Kikoin, Konstantin [Department of Physics, Ben-Gurion University, P.O. Box 653, Beer-Sheva 84105 (Israel); Avishai, Yshai [Department of Physics, Ben-Gurion University, P.O. Box 653, Beer-Sheva 84105 (Israel)

    2005-04-30

    A theory of Kondo tunneling through molecules adsorbed on metallic substrate is constructed and the underlying physics is exposed. It is shown that in the case of weak chemisorption the sandwich-type molecules manifest a novel type of Kondo effect that has not been observed in magnetically doped bulk metals. The exchange Hamiltonian of these molecules unveils unusual dynamical SO(n) symmetries instead of conventional SU(2) symmetry. These symmetries can be experimentally realized and the specific value of n can be controlled by gate voltage.

  11. Nano-manipulation of single DNA molecules

    Institute of Scientific and Technical Information of China (English)

    HU Jun; L(U) Jun-Hong; LI Hai-Kuo; AN Hong-Jie; WANG Guo-Hua; WANG Ying; LI Min-Qian; ZHANG Yi; LI Bin

    2004-01-01

    Nano-manipulation of single atoms and molecules is a critical technique in nanoscience and nanotechnology. This review paper will focus on the recent development of the manipulation of single DNA molecules based on atomic force microscopy (AFM). Precise manipulation has been realized including varied manipulating modes such as "cutting", "pushing", "folding", "kneading", "picking up", "dipping", etc. The cutting accuracy is dominated by the size of the AFM tip, which is usually 10nm or less. Single DNA fragments can be cut and picked up and then amplified by single molecule PCR. Thus positioning isolation and sequencing can be performed.

  12. Multichannel long-range Rydberg molecules

    CERN Document Server

    Eiles, Matthew T

    2015-01-01

    A generalized class of ultra-long-range Rydberg molecules is proposed which consist of a multichannel Rydberg atom whose outermost electron creates a chemical bond with a distant ground state atom. Such multichannel Rydberg molecules exhibit favorable properties for laser excitation, because states exist where the quantum defect varies strongly with the principal quantum number. The resulting occurrence of near degeneracies with states of high orbital angular momentum promotes the admixture of low $l$ into the high $l$ deeply bound `trilobite' molecule states, thereby circumventing the usual difficulty posed by electric dipole selection rules. Such states also can exhibit multi-scale binding possibilities that could present novel options for quantum manipulation.

  13. Single Molecule Biophysics Experiments and Theory

    CERN Document Server

    Komatsuzaki, Tamiki; Takahashi, Satoshi; Yang, Haw; Silbey, Robert J; Rice, Stuart A; Dinner, Aaron R

    2011-01-01

    Discover the experimental and theoretical developments in optical single-molecule spectroscopy that are changing the ways we think about molecules and atoms The Advances in Chemical Physics series provides the chemical physics field with a forum for critical, authoritative evaluations of advances in every area of the discipline. This latest volume explores the advent of optical single-molecule spectroscopy, and how atomic force microscopy has empowered novel experiments on individual biomolecules, opening up new frontiers in molecular and cell biology and leading to new theoretical approaches

  14. Non-sequential double ionization of molecules

    CERN Document Server

    Prauzner-Bechcicki, J S; Eckhardt, B; Zakrzewski, J; Prauzner-Bechcicki, Jakub S.; Sacha, Krzysztof; Eckhardt, Bruno; Zakrzewski, Jakub

    2004-01-01

    Double ionization of diatomic molecules by short linearly polarized laser pulses is analyzed. We consider the final stage of the ionization process, that is the decay of a highly excited two electron molecule, which is formed after re-scattering. The saddles of the effective adiabatic potential energy close to which simultaneous escape of electrons takes place are identified. Numerical simulations of the ionization of molecules show that the process can be dominated by either sequential or non-sequential events. In order to increase the ratio of non-sequential to sequential ionizations very short laser pulses should be applied.

  15. A Classification Scheme For Toroidal Molecules

    CERN Document Server

    Berger, J; Berger, Jorge; Avron, Joseph E.

    1995-01-01

    We construct a class of periodic tilings of the plane, which corresponds to toroidal arrangements of trivalent atoms, with pentagonal, hexagonal and heptagonal rings. Each tiling is characterized by a set of four integers and determines a toroidal molecule. The tiling rules are motivated by geometric considerations and the tiling patterns are rich enough to describe a wide class of toroidal carbon molecules, with a broad range of shapes and numbers of atoms. The molecular dimensions are simply related to the integers that determine the tiling. The configurational energy and the delocalisation energy of several molecules obtained in this way were computed for Tersoff and H\\"uckel models. The results indicate that many of these molecules are not strained, and may be expected to be stable. We studied the influence of size on the H\\"{u}ckel spectrum: it bears both similarities and differences as compared with the case of tubules.

  16. Novel electrostatic trap for cold polar molecules

    Institute of Scientific and Technical Information of China (English)

    Xu Xue-Yan; Ma Hui; Yin Jian-Ping

    2007-01-01

    We propose a novel scheme in which cold polar molecules are trapped by an electrostatic field generated by the combination of a pair of parallel transparent electrodes (i.e., two infinite transparent plates) and a ring electrode (i.e., a ring wire). The spatial distributions of the electrostatic fields from the above charged wire and the charged plates and the corresponding Stark potentials for cold CO molecules are calculated; the dependences of the trap centre position on the geometric parameters of the electrode are analysed. We also discuss the loading process of cold molecules from a cold molecular beam into our trap. This study shows that the proposed scheme is not only simple and convenient to trap, manipulate and control cold polar molecules in weak-field-seeking states, but also provides an opportunity to study cold collisions and collective quantum effects in a variety of cold molecular systems, etc.

  17. Models, mysteries, and magic of molecules

    CERN Document Server

    Boeyens, Jan CA

    2007-01-01

    Molecules have for a long time been of central importance in chemistry as the basis on which all new products and materials have been designed, developed and interpreted. Since the discovery and characterization of active biomolecules, biology has also been transformed into a molecular science. With the new developments of molecular devices, single-molecule spectroscopy, time-resolved x-ray diffraction and the study of mass-selected clusters in molecular beams, materials science and electronics may move in the same direction. The understanding of molecules and the dynamics of their transition between isolated and assembled states rests on three pillars: structure, activity and function. Enormous progress has been made in the experimental study of molecules by diffraction and spectroscopic analysis, directed at all three of the basic aspects. In the process molecular scientists have developed efficient working models in terms of which to design and interpret their experiments. A vital feature of such models is...

  18. Global warming and SF6 molecule

    Directory of Open Access Journals (Sweden)

    Gajević Jelena

    2006-01-01

    Full Text Available In this paper the basic SF6 molecule physical characteristics are given concerning its influence on global warming and green house effect. Absorption and relaxation characteristics of this molecule have been investigated within the frame of nonlinear molecule – strong laser field interaction in different gas mixtures. All experiments have been performed on a different gas mixture pressures to analyze and investigate relaxation and energy transfer characteristics of absorbing molecules and non-absorbing collision partners. To show the SF6 absorption and relaxation and energy transfer capability comparison between SF6 and C2H4 was given using the same experimental conditions and argon as a buffer gas. All measurement points and their calculated values presented in this paper have been obtained using the infrared-pulsed photoacoustics technique adopted for atmospheric and subatmospheric pressures.

  19. The evolution of polymorphic compatibility molecules

    NARCIS (Netherlands)

    Boer, R.J. de

    1995-01-01

    Several primitive colonial organisms distinguish self from nonself by means of polymorphic compatibility molecules bearing similarity to the major histocompatibility complex (MHC). The evolution of such polymorphisms is generally explained in terms of resistance to parasites. Ignoring parasites, I d

  20. Single-Molecule Studies in Live Cells

    Science.gov (United States)

    Yu, Ji

    2016-05-01

    Live-cell single-molecule experiments are now widely used to study complex biological processes such as signal transduction, self-assembly, active trafficking, and gene regulation. These experiments' increased popularity results in part from rapid methodological developments that have significantly lowered the technical barriers to performing them. Another important advance is the development of novel statistical algorithms, which, by modeling the stochastic behaviors of single molecules, can be used to extract systemic parameters describing the in vivo biochemistry or super-resolution localization of biological molecules within their physiological environment. This review discusses recent advances in experimental and computational strategies for live-cell single-molecule studies, as well as a selected subset of biological studies that have utilized these new technologies.

  1. Sisyphus Cooling of Electrically Trapped Polyatomic Molecules

    CERN Document Server

    Zeppenfeld, M; Glöckner, R; Prehn, A; Mielenz, M; Sommer, C; van Buuren, L D; Motsch, M; Rempe, G

    2012-01-01

    The rich internal structure and long-range dipole-dipole interactions establish polar molecules as unique instruments for quantum-controlled applications and fundamental investigations. Their potential fully unfolds at ultracold temperatures, where a plethora of effects is predicted in many-body physics, quantum information science, ultracold chemistry, and physics beyond the standard model. These objectives have inspired the development of a wide range of methods to produce cold molecular ensembles. However, cooling polyatomic molecules to ultracold temperatures has until now seemed intractable. Here we report on the experimental realization of opto-electrical cooling, a paradigm-changing cooling and accumulation method for polar molecules. Its key attribute is the removal of a large fraction of a molecule's kinetic energy in each step of the cooling cycle via a Sisyphus effect, allowing cooling with only few dissipative decay processes. We demonstrate its potential by reducing the temperature of about 10^6 ...

  2. Polyatomic molecules under intense femtosecond laser irradiation.

    Science.gov (United States)

    Konar, Arkaprabha; Shu, Yinan; Lozovoy, Vadim V; Jackson, James E; Levine, Benjamin G; Dantus, Marcos

    2014-12-11

    Interaction of intense laser pulses with atoms and molecules is at the forefront of atomic, molecular, and optical physics. It is the gateway to powerful new tools that include above threshold ionization, high harmonic generation, electron diffraction, molecular tomography, and attosecond pulse generation. Intense laser pulses are ideal for probing and manipulating chemical bonding. Though the behavior of atoms in strong fields has been well studied, molecules under intense fields are not as well understood and current models have failed in certain important aspects. Molecules, as opposed to atoms, present confounding possibilities of nuclear and electronic motion upon excitation. The dynamics and fragmentation patterns in response to the laser field are structure sensitive; therefore, a molecule cannot simply be treated as a "bag of atoms" during field induced ionization. In this article we present a set of experiments and theoretical calculations exploring the behavior of a large collection of aryl alkyl ketones when irradiated with intense femtosecond pulses. Specifically, we consider to what extent molecules retain their molecular identity and properties under strong laser fields. Using time-of-flight mass spectrometry in conjunction with pump-probe techniques we study the dynamical behavior of these molecules, monitoring ion yield modulation caused by intramolecular motions post ionization. The set of molecules studied is further divided into smaller sets, sorted by type and position of functional groups. The pump-probe time-delay scans show that among positional isomers the variations in relative energies, which amount to only a few hundred millielectronvolts, influence the dynamical behavior of the molecules despite their having experienced such high fields (V/Å). High level ab initio quantum chemical calculations were performed to predict molecular dynamics along with single and multiphoton resonances in the neutral and ionic states. We propose the

  3. Spin polarization effect for Os2 molecule

    Institute of Scientific and Technical Information of China (English)

    Xie An-Dong; Yan Shi-Ying; Zhu Zheng-He; Fu Yi-Bei

    2005-01-01

    Density functional Theory (DFT) (B3p86) of Gaussian03 has been used to optimize the structure of Os2 molecule.The result shows that the ground state for Os2 molecule is 9-multiple state and its electronic configuration is 9∑+g,which shows spin polarization effect of Os2 molecule of transition metal elements for the first time. Meanwhile, we have not found any spin pollution because the wavefunction of the ground state does not mingle with wavefunctions with higher energy states. So, the fact that the ground state for Os2 molecule is a 9-multiple state is indicative of spin polarization effect of Os2 molecule of transition metal elements. That is, there exist 8 parallel spin electrons.The non-conjugated electron is greatest in number. These electrons occupy different spacious tracks, so that the energy of Os2 molecule is minimized. It can be concluded that the effect of parallel spin of Os2 molecule is larger than the effect of the conjugated molecule, which is obviously related to the effect of electron d delocalization. In addition, the Murrell-Sorbie potential functions with the parameters for the ground state 9∑+g and other states of Os2 molecule are derived. Dissociation energy De for the ground state of Os2 molecule is 3.3971eV, equilibrium bond length Re is 0.2403nm, vibration frequency ωe is 235.32cm-1. Its force constants f2, f3, and f4 are 3.1032×102aJ.nm-2,-14.3425×103aJ.nm-3 and 50.5792×104aJ.nm-4 respectively. The other spectroscopic data for the ground state of Os2 molecule ωeχe, Be and αe are 0.4277cm-1, 0.0307cm-1 and 0.6491× 10-4cm-1 respectively.

  4. The coordination chemistry of saturated molecules

    OpenAIRE

    Bercaw, John E.; Labinger, Jay A.

    2007-01-01

    Our understanding of bonding in transition metal complexes, as well as our ability to use that understanding in the synthesis and application of new species, has evolved over the last 100 years; and in some sense this special feature on the coordination chemistry of saturated molecules may be considered to represent its culmination. The nature of complexes between transition metal ions and neutral molecules such as ammonia was first correctly described by Werner around the beginning of the 20...

  5. Probing halo molecules with nonresonant light

    CERN Document Server

    Lemeshko, Mikhail

    2009-01-01

    We show that halo molecules can be probed by "shaking" in a pulsed nonresonant laser field. The field introduces a centrifugal term which expels the highest vibrational level from the potential that binds it. Our numerical simulations as well as an analytic model applied to the Rb$_2$ and KRb Feshbach molecules indicate that shaking by feasible laser pulses can be used to accurately recover the square of the vibrational wavefunction and, by inversion, also the molecular potential.

  6. Biological mechanisms, one molecule at a time

    OpenAIRE

    Tinoco, Ignacio; Gonzalez, Ruben L.

    2011-01-01

    The last 15 years have witnessed the development of tools that allow the observation and manipulation of single molecules. The rapidly expanding application of these technologies for investigating biological systems of ever-increasing complexity is revolutionizing our ability to probe the mechanisms of biological reactions. Here, we compare the mechanistic information available from single-molecule experiments with the information typically obtained from ensemble studies and show how these tw...

  7. Single-molecule dynamics at variable temperatures

    OpenAIRE

    Zondervan, Rob

    2006-01-01

    Single-molecule optics has evolved from a specialized variety of optical spectroscopy at low temperatures into a versatile tool to address questions in physics, chemistry, biology, and materials science. In this thesis, the potential of single-molecule (and ensemble) optical microscopy at variable temperatures is demonstrated: Electron transfer has been identified as a crucial step in the photodynamics of organic fluorophores, and long-term memory effects have been discovered in the relaxatio...

  8. Modelling water molecules inside cyclic peptide nanotubes

    Science.gov (United States)

    Tiangtrong, Prangsai; Thamwattana, Ngamta; Baowan, Duangkamon

    2016-03-01

    Cyclic peptide nanotubes occur during the self-assembly process of cyclic peptides. Due to the ease of synthesis and ability to control the properties of outer surface and inner diameter by manipulating the functional side chains and the number of amino acids, cyclic peptide nanotubes have attracted much interest from many research areas. A potential application of peptide nanotubes is their use as artificial transmembrane channels for transporting ions, biomolecules and waters into cells. Here, we use the Lennard-Jones potential and a continuum approach to study the interaction of a water molecule in a cyclo[(- D-Ala- L-Ala)_4-] peptide nanotube. Assuming that each unit of a nanotube comprises an inner and an outer tube and that a water molecule is made up of a sphere of two hydrogen atoms uniformly distributed over its surface and a single oxygen atom at the centre, we determine analytically the interaction energy of the water molecule and the peptide nanotube. Using this energy, we find that, independent of the number of peptide units, the water molecule will be accepted inside the nanotube. Once inside the nanotube, we show that a water molecule prefers to be off-axis, closer to the surface of the inner nanotube. Furthermore, our study of two water molecules inside the peptide nanotube supports the finding that water molecules form an array of a 1-2-1-2 file inside peptide nanotubes. The theoretical study presented here can facilitate thorough understanding of the behaviour of water molecules inside peptide nanotubes for applications, such as artificial transmembrane channels.

  9. Vibrational spectroscopy of polar molecules with superradiance

    Science.gov (United States)

    Lin, Guin-Dar; Yelin, Susanne F.

    2013-07-01

    We investigate cooperative phenomena and superradiance for vibrational transitions in polar molecule spectroscopy of high optical-depth samples. Such cooperativity comes from the build-up of inter-particle coherence through dipole-dipole interactions and leads to speed-up of decay processes. We compare our calculation to recent work and find very good agreement, suggesting that superradiant effects need to be taken into account in a wide variety of ultracold molecule experiments, including vibrational and rotational states.

  10. Electron affinities of atoms, molecules, and radicals

    International Nuclear Information System (INIS)

    We review briefly but comprehensively the theoretical, semiempirical and experimental methods employed to determine electron affinities (EAs) of atoms, molecules and radicals, and summarize the EA data obtained by these methods. The detailed processes underlying the principles of the experimental methods are discussed very briefly. It is, nonetheless, instructive to recapitulate the definition of EA and those of the related quantities, namely, the vertical detachment energy, VDE, and the vertical attachment energy, VAE. The EA of an atom is defined as the difference in total energy between the ground state of the neutral atom (plus the electron at rest at infinity) and its negative ion. The EA of a molecule is defined as the difference in energy between the neutral molecule plus an electron at rest at infinity and the molecular negative ion when both, the neutral molecules and the negative ion, are in their ground electronic, vibrational and rotational states. The VDE is defined as the minimum energy required to eject the electron from the negative ion (in its ground electronic and nuclear state) without changing the internuclear separation; since the vertical transition may leave the neutral molecule in an excited vibrational/rotational state, the VDE, although the same as the EA for atoms is, in general, different (larger than), from the EA for molecules. Similarly, the VAE is defined as the difference in energy between the neutral molecule in its ground electronic, vibrational and rotational states plus an electron at rest at infinity and the molecular negative ion formed by addition of an electron to the neutral molecule without allowing a change in the intermolecular separation of the constituent nuclei; it is a quantity appropriate to those cases where the lowest negative ion state lies above the ground states of the neutral species and is less or equal to EA

  11. Hadronic molecules in the heavy baryon spectrum

    Science.gov (United States)

    Entem, D. R.; Ortega, P. G.; Fernández, F.

    2016-01-01

    We study possible baryon molecules in the non-strange heavy baryon spectrum. We include configurations with a heavy-meson and a light baryon. We find several structures, in particular we can understand the Λc(2940) as a D*N molecule with JP = 3/2- quantum numbers. We also find D(*)Δ candidates for the recently discovered Xc(3250) resonance.

  12. On Chiral Space Groups and Chiral Molecules

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    This note explains the relationship (as well as the absence of a relationship) between chiral space groups and chiral molecules (which have absolute configurations). For a chiral molecule, which must crystallize in a chiral space group, the outcome of the absolute configuration determination must be linked to some other properties of the chiral crystal such as its optical activity for the observation to the relevant.

  13. Self-Assemblies of novel molecules, VECAR

    Science.gov (United States)

    Shrestha, Bijay; Kim, Hye-Young; Lee, Soojin; Novak, Brian; Moldovan, Dorel

    2015-03-01

    VECAR is a newly synthesized molecule, which is an amphiphilic antioxidant molecule that consists of two molecular groups, vitamin-E and Carnosine, linked by a hydrocarbon chain. The hydrocarbon chain is hydrophobic and both vitamin-E and Carnosine ends are hydrophilic. In the synthesis process, the length of the hydrophobic chain of VECAR molecules can vary from the shortest (n =0) to the longest (n =18), where n indicates the number of carbon atoms in the chain. We conducted MD simulation studies of self-assembly of VECAR molecules in water using GROMACS on LONI HPC resources. Our study shows that there is a strong correlation between the shape and atomistic structure of the self-assembled nano-structures (SANs) and the chain-length (n) of VECAR molecules. We will report the results of data analyses including the atomistic structure of each SANs and the dynamic and energetic mechanisms of their formation as function of time. In summary, both VECAR molecules of chain-length n =18 and 9 form worm-like micelles, which may be used as a drug delivery system. This research is supported by the Louisiana Board of Regents-RCS Grant (LEQSF(2012-15)-RD-A-19).

  14. Auxin biology revealed by small molecules.

    Science.gov (United States)

    Ma, Qian; Robert, Stéphanie

    2014-05-01

    The plant hormone auxin regulates virtually every aspect of plant growth and development and unraveling its molecular and cellular modes of action is fundamental for plant biology research. Chemical genomics is the use of small molecules to modify protein functions. This approach currently rises as a powerful technology for basic research. Small compounds with auxin-like activities or affecting auxin-mediated biological processes have been widely used in auxin research. They can serve as a tool complementary to genetic and genomic methods, facilitating the identification of an array of components modulating auxin metabolism, transport and signaling. The employment of high-throughput screening technologies combined with informatics-based chemical design and organic chemical synthesis has since yielded many novel small molecules with more instantaneous, precise and specific functionalities. By applying those small molecules, novel molecular targets can be isolated to further understand and dissect auxin-related pathways and networks that otherwise are too complex to be elucidated only by gene-based methods. Here, we will review examples of recently characterized molecules used in auxin research, highlight the strategies of unraveling the mechanisms of these small molecules and discuss future perspectives of small molecule applications in auxin biology. PMID:24252105

  15. Scanning tunneling spectroscopy on organic molecules

    Science.gov (United States)

    Labonte, Andre Paul

    2002-08-01

    Scanning Tunneling Spectroscopy was performed on a number of organic molecules. Current-Voltage response, I(V), and dynamic conductance, dI/dV, data were collected using new systematic techniques. The new techniques are understood in terms of known theories and provide a means by which a scanning tunneling microscope (STM) can perform reproducible two-terminal electrical measurements on an organic film. In particular, STS clearly discerns the relative conductivity (resistivity) of organic films. The I(V) and dI/dV data collected demonstrate that the conductivity of organic molecules may be changed in a variety of ways, including: altering molecular endgroups, altering morphology, a chemical doping event, altering the orientation of an internal component of the molecule. It has also been demonstrated that organic molecules can exhibit conducting, semiconducting and insulating behaviors. Through measurements performed on the dI/dV data, a table of conduction gaps and Ef-HOMO has been tabulated for the molecules studied. In certain instances (see Chapter 7), molecular resistances have been estimated from the I(V) data. In summary, this body of work firmly establishes that STS provides a useful tool in the study of the electrical properties of molecular films. Additionally, it has been shown that organic molecules exhibit a broad range of electrical behaviors and that these behaviors can be controllably altered.

  16. Chapter 3: Small molecules and disease.

    Directory of Open Access Journals (Sweden)

    David S Wishart

    Full Text Available "Big" molecules such as proteins and genes still continue to capture the imagination of most biologists, biochemists and bioinformaticians. "Small" molecules, on the other hand, are the molecules that most biologists, biochemists and bioinformaticians prefer to ignore. However, it is becoming increasingly apparent that small molecules such as amino acids, lipids and sugars play a far more important role in all aspects of disease etiology and disease treatment than we realized. This particular chapter focuses on an emerging field of bioinformatics called "chemical bioinformatics"--a discipline that has evolved to help address the blended chemical and molecular biological needs of toxicogenomics, pharmacogenomics, metabolomics and systems biology. In the following pages we will cover several topics related to chemical bioinformatics. First, a brief overview of some of the most important or useful chemical bioinformatic resources will be given. Second, a more detailed overview will be given on those particular resources that allow researchers to connect small molecules to diseases. This section will focus on describing a number of recently developed databases or knowledgebases that explicitly relate small molecules--either as the treatment, symptom or cause--to disease. Finally a short discussion will be provided on newly emerging software tools that exploit these databases as a means to discover new biomarkers or even new treatments for disease.

  17. Dissociation and Decay of Ultra-cold Sodium Molecules

    OpenAIRE

    Mukaiyama, T.; Abo-Shaeer, J. R.; Xu, K.; Chin, J. K.; Ketterle, W.

    2003-01-01

    The dissociation of ultracold molecules is studied by ramping an external magnetic field through a Feshbach resonance. The observed dissociation energy shows non-linear dependence on the ramp speed and directly yields the strength of the atom-molecule coupling. In addition, inelastic molecule-molecule and molecule-atom collisions are characterized.

  18. Spin polarization effect for molecule Ta2

    Institute of Scientific and Technical Information of China (English)

    Xie An-Dong

    2006-01-01

    Density functional theory (DFT) (B3p86) has been used to optimize the structure of the molecule Taa- The result shows that the ground state of molecule Ta,2 is a 7- multiple state and its electronic configuration is 7∑+u which shows the spin polarization effect for molecule Ta2 of transition metal elements for the first time. Meanwhile, spin pollution has not been found because the wavefunction of the ground state does not mix with those of higher states. So, the fact that the ground state of molecule Ta2 is a 7-multiple state indicates a spin polarization effect of molecule Ta2 of the transition metal elements, i.e. there exist 6 parallel spin electrons and the non-conjugated electrons are greatest in number. These electrons occupy different space orbitals so that the energy of molecule Ta2 is minimized. It can be concluded that the effect of parallel spin of the molecule Ta2 is larger than the effect of the conjugated molecule, which is obviously related to the effect of d-electron delocalization. In addition, the Murrell-Sorbie potential functions with parameters for the ground state 7∑+u and other states of the molecule Ta2 are derived. The dissociation energy De, equilibrium bond length Re and vibration frequency ωe for the ground state of molecule Ta2 are 4.5513eV, 0.2433nm and 173.06cm-1, respectively. Its force constants f2,f3 and f4 are 1.5965×l02aJ·nm-2,-6.4722×l03aJ·nm-3 and 29.4851×04aJ·nm-4, respectively. Other spectroscopic data ωe χe, Be and αe for the ground state of Ta2 are 0.2078cm-1, 0.0315cm-1 and 0.7858×104 cm-1, respectively.

  19. Quantifying molecule-surface interactions using AFM-based single-molecule manipulation

    Science.gov (United States)

    Tautz, F. S.; Wagner, C.; Temirov, R.; Fournier, N.; Green, M.; Esat, T.; Leinen, P.; Groetsch, A.; Ruiz, V. G.; Tkatchenko, A.; Li, C.; Muellen, K.; Rohlfing, M.

    2015-03-01

    Scanning probe microscopy plays an important role in the investigation of molecular adsorption. Promising, is the possibility to probe the molecule-surface interaction while tuning its strength through AFM tip-induced single-molecule manipulation. Here, we outline a strategy to achieve quantitative understanding of such manipulation experiments. The example of qPlus sensor based PTCDA molecule lifting experiments is used to demonstrate how different aspects of the molecule-surface interaction, namely the short-range adsorption potential, the asymptotic van der Waals potential, local chemical bonds which are the source of the surface corrugation, and molecule-molecule interactions can be measured with SPM and interpreted by the help of force-field simulations.

  20. Electromechanical Properties of Single Molecule Devices

    Science.gov (United States)

    Bruot, Christopher

    Understanding the interplay between the electrical and mechanical properties of single molecules is of fundamental importance for molecular electronics. The sensitivity of charge transport to mechanical fluctuations is a key problem in developing long lasting molecular devices. Furthermore, harnessing this response to mechanical perturbation, molecular devices which can be mechanically gated can be developed. This thesis demonstrates three examples of the unique electromechanical properties of single molecules. First, the electromechanical properties of 1,4-benzenedithiol molecular junctions are investigate. Counterintuitively, the conductance of this molecule is found to increase by more than an order of magnitude when stretched. This conductance increase is found to be reversible when the molecular junction is compressed. The current-voltage, conductance-voltage and inelastic electron tunneling spectroscopy characteristics are used to attribute the conductance increase to a strain-induced shift in the frontier molecular orbital relative to the electrode Fermi level, leading to resonant enhancement in the conductance. Next, the effect of stretching-induced structural changes on charge transport in DNA molecules is studied. The conductance of single DNA molecules with lengths varying from 6 to 26 base pairs is measured and found to follow a hopping transport mechanism. The conductance of DNA molecules is highly sensitive to mechanical stretching, showing an abrupt decrease in conductance at surprisingly short stretching distances, with weak dependence on DNA length. This abrupt conductance decrease is attributed to force-induced breaking of hydrogen bonds in the base pairs at the end of the DNA sequence. Finally, the effect of small mechanical modulation of the base separation on DNA conductance is investigated. The sensitivity of conductance to mechanical modulation is studied for molecules of different sequence and length. Sequences with purine-purine stacking

  1. Image Analysis of Defocused Single-molecule Images for Three-dimensional Molecule Orientation Studies

    OpenAIRE

    Patra, D; Gregor, I.; Enderlein, J.

    2004-01-01

    An efficient algorithm for pattern matching has been developed based on least-squares analysis of fitting a discrete set of master patterns against measured images. This algorithm has been applied to determine three-dimensional molecule orientations in defocused single-molecule images. The developed algorithm exploits the excellent agreement between electrodynamic calculations of single-molecule emission and experimentally measured images. The procedure is found to be reliable and simple and ...

  2. Mining for Molecules in the Milky Way

    Science.gov (United States)

    2008-06-01

    Scientists are using the giant Robert C. Byrd Green Bank Telescope (GBT) to go prospecting in a rich molecular cloud in our Milky Way Galaxy. They seek to discover new, complex molecules in interstellar space that may be precursors to life. The GBT and Molecules The Robert C. Byrd Green Bank Telescope and some molecules it has discovered. CREDIT: Bill Saxton, NRAO/AUI/NSF "Clouds like this one are the raw material for new stars and planets. We know that complex chemistry builds prebiotic molecules in such clouds long before the stars and planets are formed. There is a good chance that some of these interstellar molecules may find their way to the surface of young planets such as the early Earth, and provide a head start for the chemistry of life. For the first time, we now have the capability to make a very thorough and methodical search to find all the chemicals in the clouds," said Anthony Remijan, of the National Radio Astronomy Observatory (NRAO). In the past three years, Remijan and his colleagues have used the GBT to discover ten new interstellar molecules, a feat unequalled in such a short time by any other team or telescope. The scientists discovered those molecules by looking specifically for them. However, they now are changing their strategy and casting a wide net designed to find whatever molecules are present, without knowing in advance what they'll find. In addition, they are making their data available freely to other scientists, in hopes of speeding the discovery process. The research team presented its plan to the American Astronomical Society's meeting in St. Louis, MO. As molecules rotate and vibrate, they emit radio waves at specific frequencies. Each molecule has a unique pattern of such frequencies, called spectral lines, that constitutes a "fingerprint" identifying that molecule. Laboratory tests can determine the pattern of spectral lines that identifies a specific molecule. Most past discoveries came from identifying a molecule's pattern in

  3. The reaction dynamics of alkali dimer molecules and electronically excited alkali atoms with simple molecules

    Energy Technology Data Exchange (ETDEWEB)

    Hou, H [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry

    1995-12-01

    This dissertation presents the results from the crossed molecular beam studies on the dynamics of bimolecular collisions in the gas phase. The primary subjects include the interactions of alkali dimer molecules with simple molecules, and the inelastic scattering of electronically excited alkali atoms with O2. The reaction of the sodium dimers with oxygen molecules is described in Chapter 2. Two reaction pathways were observed for this four-center molecule-molecule reaction, i.e. the formations of NaO2 + Na and NaO + NaO. NaO2 products exhibit a very anisotropic angular distribution, indicating a direct spectator stripping mechanism for this reaction channel. The NaO formation follows the bond breaking of O2, which is likely a result of a charge transfer from Na2 to the excited state orbital of O2-. The scattering of sodium dimers from ammonium and methanol produced novel molecules, NaNH3 and Na(CH3OH), respectively. These experimental observations, as well as the discussions on the reaction dynamics and the chemical bonding within these molecules, will be presented in Chapter 3. The lower limits for the bond dissociation energies of these molecules are also obtained. Finally, Chapter 4 describes the energy transfer between oxygen molecules and electronically excited sodium atoms.

  4. Single-Molecule Electronics with Cross- Conjugated Molecules: Quantum Interference, IETS and Non-Equilibrium "Temperatures"

    DEFF Research Database (Denmark)

    Jørgensen, Jacob Lykkebo

    , which is characterised by destructive quantum interference. The molecules are cross-conjugated, which means that the two parts of the molecules are conjugated to a third part, but not to each other. This gives rise to an anti-resonance in the trans- mission. In the low bias and low temperature regime......, the electrons can tunnel in- elastically from the left to the right electrode. This is the process behind inelastic electron tunnelling spectroscopy (IETS), which is a single-molecule spectroscopic method, where the vibrational ngerprint of a molecule is di- rectly observed by the tunnelling current...

  5. Preparation and manipulation of molecules for fundamental physics tests

    OpenAIRE

    Tarbutt, M. R.; Hudson, J. J.; Sauer, B. E.; Hinds, E. A.

    2008-01-01

    This paper is a chapter from an upcoming book on cold molecule physics. In it we describe techniques for the preparation and manipulation of cold molecules. We further describe techniques for applying said cold molecules to tests of fundamental physics.

  6. Quantum Computer Using Coupled Quantum Dot Molecules

    CERN Document Server

    Wu, N J; Natori, A; Yasunaga, H; Wu*, Nan-Jian

    1999-01-01

    We propose a method for implementation of a quantum computer using artificial molecules. The artificial molecule consists of two coupled quantum dots stacked along z direction and one single electron. One-qubit and two-qubit gates are constructed by one molecule and two coupled molecules, respectively.The ground state and the first excited state of the molecule are used to encode the |0> and |1> states of a qubit. The qubit is manipulated by a resonant electromagnetic wave that is applied directly to the qubit through a microstrip line. The coupling between two qubits in a quantum controlled NOT gate is switched on (off) by floating (grounding) the metal film electrodes. We study the operations of the gates by using a box-shaped quantum dot model and numerically solving a time-dependent Schridinger equation, and demonstrate that the quantum gates can perform the quantum computation. The operating speed of the gates is about one operation per 4ps. The reading operation of the output of the quantum computer can...

  7. Ultracold polar molecules near quantum degeneracy.

    Science.gov (United States)

    Ospelkaus, S; Ni, K K; de Miranda, M H G; Neyenhuis, B; Wang, D; Kotochigova, S; Julienne, P S; Jin, D S; Ye, J

    2009-01-01

    We report the creation and characterization of a near quantum-degenerate gas of polar 40K-87Rb molecules in their absolute rovibrational ground state. Starting from weakly bound heteronuclear KRb Feshbach molecules, we implement precise control of the molecular electronic, vibrational, and rotational degrees of freedom with phase-coherent laser fields. In particular, we coherently transfer these weakly bound molecules across a 125 THz frequency gap in a single step into the absolute rovibrational ground state of the electronic ground potential. Phase coherence between lasers involved in the transfer process is ensured by referencing the lasers to two single components of a phase-stabilized optical frequency comb. Using these methods, we prepare a dense gas of 4 x 10(4) polar molecules at a temperature below 400 nK. This fermionic molecular ensemble is close to quantum degeneracy and can be characterized by a degeneracy parameter of T/T(F) = 3. We have measured the molecular polarizability in an optical dipole trap where the trap lifetime gives clues to interesting decay mechanisms. Given the large measured dipole moment of the KRb molecules of 0.5 Debye, the study of quantum degenerate molecular gases interacting via strong dipolar interactions is now within experimental reach. PACS numbers: 37.10.Mn, 37.10.Pq. PMID:20151553

  8. Collision data involving hydro-carbon molecules

    International Nuclear Information System (INIS)

    Hydro-carbon molecules are abundantly produced when graphites are used as internal wall materials of hydrogen plasmas and strongly influence properties of low temperature plasmas near the edges as well as those of high temperature plasmas at the center. In this report, following simple description of the production mechanisms of hydro-carbon molecules under the interactions between graphite and hydrogen plasma, the present status of collision data for hydro-carbon molecules by electron impact is discussed and the relevant data are summarized in a series of figures and tables. It should also be noted that, in addition to fusion plasmas, these hydrocarbon data compiled here are quite useful in other applications such as plasma chemistry and material processing. (author)

  9. Single Molecule Sensitive FRET in Attoliter Droplets

    CERN Document Server

    Milas, Peker; Gamari, Ben D; Goldner, Lori S

    2013-01-01

    Single molecular-pair fluorescence resonance energy transfer (spFRET) has become an cross-disciplinary tool for understanding molecular folding and interactions. While providing detailed information about the individual members of a molecular ensemble, this technique is always limited by fluorophore brightness and stability. In the case of diffusing molecules, the experiment is further limited by the number of photons that can be collected during the time it takes for a molecule to diffuse across the detection volume. To maximize the number of photons it is common to either increase the detection volume at the expense of increased background, or increase the diffusion time by adding glycerol or sucrose to increase viscosity. Here we demonstrate that FRET from attoliter volume (100 nm radius) aqueous droplets in perfluorinated oil has significantly higher signal-to-noise and a much wider dynamic range than FRET from molecules diffusing in solution. However, our measurements also reveal a droplet environment th...

  10. Photodissociation and excitation of interstellar molecules

    International Nuclear Information System (INIS)

    Apart from a rather long introduction containing some elementary astrophysics, quantum chemistry and spectroscopy and an incomplete, historical review of molecular observations, this thesis is divided into three sections. In part A, a rigorous quantum chemical and dynamical study is made of the photodissociation processes in the OH and HCl molecules. In part B, the cross sections obtained in part A are used in various astrophysical problems such as the study of the abundances of the OH and HCl molecules in interstellar clouds, the use of the OH abundance as a measure of the cosmic ray ionization rate, the lifetime of the OH radical in comets and the abundance of OH in the solar photosphere. Part C discusses the excitation of the C2 molecule under interstellar conditions, its use as a diagnostic probe of the temperature, density and strength of the radiation field in interstellar clouds. Quadrupole moments and oscillator strengths are analyzed. (Auth.)

  11. Theoretical study on single-molecule spectroscopy

    Institute of Scientific and Technical Information of China (English)

    SHAN Guang-cun; HUANG Wei

    2006-01-01

    The photon-by-photon approach for single molecule spectroscopy experiments utilizes the information carried by each detected photon and allows the measurements of conformational fluctuation with time resolution on a vast range of time scales,where each photon represents a data point.Here,we theoretically simulate the photon emission dynamics of a single molecule spectroscopy using the kinetic Monte Carlo algorithm to understand the underlying complex photon dynamic process of a single molecule.In addition,by following the molecular process in real time,the mechanism of complex biochemical reactions can be revealed.We hope that this theoretical study will serve as an introduction and a guideline into this exciting new field.

  12. Protein Scaffolding for Small Molecule Catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Baker, David [Univ. of Washington, Seattle, WA (United States)

    2014-09-14

    We aim to design hybrid catalysts for energy production and storage that combine the high specificity, affinity, and tunability of proteins with the potent chemical reactivities of small organometallic molecules. The widely used Rosetta and RosettaDesign methodologies will be extended to model novel protein / small molecule catalysts in which one or many small molecule active centers are supported and coordinated by protein scaffolding. The promise of such hybrid molecular systems will be demonstrated with the nickel-phosphine hydrogenase of DuBois et. al.We will enhance the hydrogenase activity of the catalyst by designing protein scaffolds that incorporate proton relays and systematically modulate the local environment of the catalyticcenter. In collaboration with DuBois and Shaw, the designs will be experimentally synthesized and characterized.

  13. Difference Raman spectroscopy of DNA molecules

    International Nuclear Information System (INIS)

    In this paper the micro-Raman spectra of calf DNA for different points of DNA sample have been recorded. The Raman spectra were made with help of difference Raman spectroscopy technique. Raman spectra were recorded with high spatial resolution from different points of the wet and dry samples in different spectral range (100÷4000cm−1) using two lasers: argon (514.5 nm) and helium -neon (632.8 nm). The significant differences in the Raman spectra for dry and wet DNA and for different points of DNA molecules were observed. The obtained data on difference Raman scattering spectra of DNA molecules may be used for identification of DNA types and for analysis of genetic information associated with the molecular structure of this molecule

  14. Multiphoton processes in isolated atoms and molecules

    International Nuclear Information System (INIS)

    The theory of coherent excitation of a multilevel quantum mechanical system is developed. Damping of the system is taken into account by the use of a density matrix formalism. General properties of the wave function and/or the density matrix are discussed. The physical implications for the behavior of the system are described, together with possible applications of the formalism, including the infrared multiphoton excitation of molecules, and optical pumping in alkali atoms. Experimental results are presented on the infrared multiphoton dissociation of molecules, followed by a discussion of the general features of this process. The experimental results were obtained using a crossed laser and molecular beam method, and the emphasis is on determining the properties of the dissociating molecule and the dissociation products. The dissociation process is shown to be described very well by the standard statistical theory (RRKM theory) of unimolecular reactions, a brief presentation of which is also included

  15. A toy model for a diatomic molecule

    Science.gov (United States)

    Hecker Denschlag, Johannes

    2016-08-01

    We introduce a toy model for a diatomic molecule which is based on coupling electronic and nuclear spins to a rigid rotor. Despite its simplicity, the model can be used scientifically to analyze and understand complex molecular hyperfine spectra. In addition, the model has educational value as a number of fundamental symmetries and conservation laws of the molecule can be studied. Because of its simple structure, the model can be readily implemented as a computer program with comparatively short computing times on the order of a few seconds.

  16. Molecules and Clusters in Intense Laser Fields

    Science.gov (United States)

    Posthumus, Jan

    2009-09-01

    Preface; 1. Ultra-high intensity based on Ti:Sapphire Philip F. Taday and Andrew J. Langley; 2. Diatomic molecules in intense laser fields Jan H. Posthumus and James F. McCann; 3. Small polyatomic molecules in intense laser fields C. Cornaggia; 4. Coherent control in intense laser fields Eric Charron and Brian Sheehy; 5. Experimental studies of laser-heated rare gas clusters M. Lezius and M. Schmidt; 6. Single cluster explosions and high harmonic generation John W. G. Tisch and Emma Springate; 7. Intense laser interaction with extended cluster media Roland A. Smith and Todd Ditmire.

  17. Anderson localisation in laser kicked molecules

    CERN Document Server

    Floß, Johannes; Averbukh, Ilya Sh

    2013-01-01

    The paper explores the prospects of observing the phenomenon of dynamical Anderson localisation via non-resonant Raman-type rotational excitation of molecules by periodic trains of short laser pulses. We define conditions for such an experiment, and show that current femtosecond technology used for non-adiabatic laser alignment of linear molecules is sufficient for this task. Several observables which can serve as indicator for Anderson localisation are suggested for measurement, and the influence of experimental limitations imposed by laser intensity noise, finite pulse duration, limited number of pulses in a train, and thermal effects is analysed.

  18. Photoassociative production of ultracold heteronuclear ytterbium molecules

    Energy Technology Data Exchange (ETDEWEB)

    Borkowski, Mateusz; Ciurylo, Roman [Instytut Fizyki, Uniwersytet Mikolaja Kopernika, ul. Grudziadzka 5/7, PL-87-100 Torun (Poland); Julienne, Paul S. [Joint Quantum Institute, National Institute of Standards and Technology and the University of Maryland, 100 Bureau Drive, Stop 8423, Gaithersburg, Maryland 20899-8423 (United States); Yamazaki, Rekishu; Takahashi, Yoshiro [Department of Physics, Graduate School of Science, Kyoto University, Kyoto 606-8502 (Japan); CREST, JST, 4-1-8 Honcho Kawaguchi, Saitama 332-0012 (Japan); Hara, Hideaki; Taie, Shintaro; Sugawa, Seiji; Takasu, Yosuke [Department of Physics, Graduate School of Science, Kyoto University, Kyoto 606-8502 (Japan); Enomoto, Katsunari [Department of Physics, University of Toyama, Toyama 930-8555 (Japan)

    2011-09-15

    We report observations of photoassociation (PA) spectra near the intercombination line in isotopic mixtures of ultracold ytterbium gases. Several heteronuclear bound states have been found for the excited {sup 170}Yb{sup 174}Yb and {sup 174}Yb{sup 176}Yb molecules. We develop a single-channel mass-scaled interaction model for the excited state molecule which well reproduces the measured bound state energies. This is an important step toward optical control of interactions in mixtures of ultracold ytterbium gases using heteronuclear optical Feshbach resonances. The model developed is applicable in collisions of other similar systems, such as cadmium and mercury.

  19. Matter-wave interferometer for large molecules

    CERN Document Server

    Brezger, B; Uttenthaler, S; Petschinka, J; Arndt, M; Zeilinger, Anton

    2002-01-01

    We demonstrate a near-field Talbot-Lau interferometer for C-70 fullerene molecules. Such interferometers are particularly suitable for larger masses. Using three free-standing gold gratings of one micrometer period and a transversally incoherent but velocity-selected molecular beam, we achieve an interference fringe visibility of 40 % with high count rate. Both the high visibility and its velocity dependence are in good agreement with a quantum simulation that takes into account the van der Waals interaction of the molecules with the gratings and are in striking contrast to a classical moire model.

  20. Extracellular Molecules Involved in Cancer Cell Invasion

    Directory of Open Access Journals (Sweden)

    Theodora Stivarou

    2015-01-01

    Full Text Available Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion.

  1. Extracellular Molecules Involved in Cancer Cell Invasion

    Energy Technology Data Exchange (ETDEWEB)

    Stivarou, Theodora; Patsavoudi, Evangelia, E-mail: epatsavoudi@pasteur.gr [Department of Biochemistry, Hellenic Pasteur Institute, Athens 11521 (Greece); Technological Educational Institute of Athens, Egaleo, Athens 12210 (Greece)

    2015-01-26

    Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion.

  2. Organic- and molecule-based magnets

    Indian Academy of Sciences (India)

    Joel S Miller

    2006-07-01

    The discovery of organic- and molecule-based magnets has led to design and synthesis of several families with magnetic ordering temperatures as high as ∼ 125° C. Examples of soft and hard magnets with coercivities as high as 27 kOe have also been reported. Examples from our laboratory of organic-based magnets using the tetracya- noethylene radical anion, [TCNE]$^{\\bullet -}$, are discussed. In addition, several molecule-based magnets based on Prussian Blue structured materials as well as dicyanamide are discussed.

  3. Single-molecule electrophoresis. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Castro, A.; Shera, E.B.

    1996-05-22

    A novel method for the detection and identification of single molecules in solution has been devised, computer-simulated, and experimentally achieved. The technique involves the determination of electrophoretic velocities by measuring the time required by individual molecules to travel a fixed distance between two laser beams. Computer simulations of the process were performed beforehand in order to estimate the experimental feasibility of the method, and to determine the optimum values for the various experimental parameters. Examples of the use of the technique for the ultrasensitive detection and identification of rhodamine-6G, a mixture of DNA restriction fragments, and a mixture of proteins in aqueous solution are presented.

  4. Vibrational spectroscopy of polar molecules with superradiance

    CERN Document Server

    Lin, Guin-Dar

    2013-01-01

    We investigate cooperative phenomena and superradiance for vibrational transitions in polar molecule spectroscopy when a high optical-depth (OD) sample is studied. Such cooperativity comes from the build-up of inter-particle coherence through dipole-dipole interactions and leads to the speed-up of decay process. We compare our calculation to recent work [Deiglmayr et al., Eur. Phys. J. D 65, 99 (2011)] and find very good agreement, suggesting that superradiant effects need to be included in a wide variety of ultracold molecule setups including vibrational and rotational states.

  5. Scanning probe microscopy characterisation of immobilised enzyme molecules on a biosensor surface: visualisation of individual molecules

    Directory of Open Access Journals (Sweden)

    JOE G. SHAPTER

    2004-02-01

    Full Text Available Scanning probe microscopy techniques were used to study immobilised enzyme molecules of glucose oxidase (GOD on a biosensor surface. The study was carried out in order to optimise atomic force microscopy (AFM imaging and reveal the molecular resolution of individual GOD molecules. Chemically modified AFM tips and the light tapping mode were found to be the optimal conditions for imaging soft biomolecules such as GOD. The information obtained from the AFM images included spatial distribution and organization of the enzyme molecules on the surface, surface coverage and shape, size and orientation of individual molecules. Two typical shapes of GOD molecules were found, spherical and butterfly, which are in accordance with the shapes obtained from scanning tunnelling microscopy (STM images. Using a model of the orientation of the GOD molecules on the surface, these shapes are assigned to the enzyme standing and lying on the surface. After AFM tip deconvolution, the size of the spherical shaped GOD molecules was found to be 12 ± 2.1 nm in diameter, whereas the butterfly shapes were 16.5 ± 3.3 nm ´10.2 ± 2.5 nm. Corresponding STM images showed smaller lateral dimensions of 10 ± 1 nm ´ 6 ± 1 nm and 6.5 ± 1 nm ´ 5 ± 1 nm. The disagreement between these two techniques is attributed to the deformation of the GOD molecules caused by the tapping process.

  6. Single Molecule Analysis Research Tool (SMART: an integrated approach for analyzing single molecule data.

    Directory of Open Access Journals (Sweden)

    Max Greenfeld

    Full Text Available Single molecule studies have expanded rapidly over the past decade and have the ability to provide an unprecedented level of understanding of biological systems. A common challenge upon introduction of novel, data-rich approaches is the management, processing, and analysis of the complex data sets that are generated. We provide a standardized approach for analyzing these data in the freely available software package SMART: Single Molecule Analysis Research Tool. SMART provides a format for organizing and easily accessing single molecule data, a general hidden Markov modeling algorithm for fitting an array of possible models specified by the user, a standardized data structure and graphical user interfaces to streamline the analysis and visualization of data. This approach guides experimental design, facilitating acquisition of the maximal information from single molecule experiments. SMART also provides a standardized format to allow dissemination of single molecule data and transparency in the analysis of reported data.

  7. Making More-Complex Molecules Using Superthermal Atom/Molecule Collisions

    Science.gov (United States)

    Shortt, Brian; Chutjian, Ara; Orient, Otto

    2008-01-01

    A method of making more-complex molecules from simpler ones has emerged as a by-product of an experimental study in outer-space atom/surface collision physics. The subject of the study was the formation of CO2 molecules as a result of impingement of O atoms at controlled kinetic energies upon cold surfaces onto which CO molecules had been adsorbed. In this study, the O/CO system served as a laboratory model, not only for the formation of CO2 but also for the formation of other compounds through impingement of rapidly moving atoms upon molecules adsorbed on such cold interstellar surfaces as those of dust grains or comets. By contributing to the formation of increasingly complex molecules, including organic ones, this study and related other studies may eventually contribute to understanding of the origins of life.

  8. Long-lived dipolar molecules and Feshbach molecules in a 3D optical lattice

    CERN Document Server

    Chotia, Amodsen; Moses, Steven A; Yan, Bo; Covey, Jacob P; Foss-Feig, Michael; Rey, Ana Maria; Jin, Deborah S; Ye, Jun

    2011-01-01

    We have realized long-lived ground-state polar molecules in a 3D optical lattice, with a lifetime of up to 25 s, which is limited only by off-resonant scattering of the trapping light. Starting from a 2D optical lattice, we observe that the lifetime increases dramatically as a small lattice potential is added along the tube-shaped lattice traps. The 3D optical lattice also dramatically increases the lifetime for weakly bound Feshbach molecules. For a pure gas of Feshbach molecules, we observe a lifetime of >20 s in a 3D optical lattice; this represents a 100-fold improvement over previous results. This lifetime is also limited by off-resonant scattering, the rate of which is related to the size of the Feshbach molecule. Individually trapped Feshbach molecules in the 3D lattice can be converted to pairs of K and Rb atoms and back with nearly 100% efficiency.

  9. Evidence of disorder in biological molecules from single molecule pulling experiments

    CERN Document Server

    Hyeon, Changbong; Thirumalai, D

    2014-01-01

    Heterogeneity in biological molecules, resulting in molecule-to-molecule variations in their dynamics and function, is an emerging theme. To elucidate the consequences of heterogeneous behavior at the single molecule level, we propose an exactly solvable model in which the unfolding rate due to mechanical force depends parametrically on an auxiliary variable representing an entropy barrier arising from fluctuations in internal dynamics. When the rate of fluctuations, a measure of dynamical disorder, is comparable to or smaller than the rate of force-induced unbinding, we show that there are two experimentally observable consequences: non-exponential survival probability at constant force, and a heavy-tailed rupture force distribution at constant loading rate. By fitting our analytical expressions to data from single molecule pulling experiments on proteins and DNA, we quantify the extent of disorder. We show that only by analyzing data over a wide range of forces and loading rates can the role of disorder due...

  10. Papillary microcarcinoma of the thyroid gland: is the immunohistochemical expression of cyclin D1 or galectin-3 in primary tumour an indicator of metastatic disease?

    DEFF Research Database (Denmark)

    Londero, Stefano Christian; Godballe, Christian; Krogdahl, Annelise;

    2007-01-01

    INTRODUCTION: Papillary microcarcinomas (PMC) of the thyroid gland are defined according to The WHO Committee as papillary carcinomas measuring 10 mm or less in diameter. A large proportion of these tumours are found coincidentally in the treatment of symptomatic goitre and most cases follow...... at the time of diagnosis. MATERIAL AND METHODS: From the 1(st) of January 1996 to 31(st) of December 2002 a total of 169 PMC patients were diagnosed and registered in the national Danish thyroid cancer database DATHYRCA and 131 of these were eligible for the study. Forty-three (33%) had histologically...

  11. Intercellular adhesion molecule-1 clusters during osteoclastogenesis

    NARCIS (Netherlands)

    V. Bloemen; T.J. de Vries; T. Schoenmaker; V. Everts

    2009-01-01

    Adhesion between osteoblasts and osteoclast precursors is established via an interaction involving intercellular adhesion molecule-1 (ICAM-1) on osteoblasts and leukocyte function-associated antigen-1 (LFA-1) on osteoclast precursors. The latter cells also express ICAM-1, but little is known about t

  12. Orbits in the H2O molecule

    NARCIS (Netherlands)

    Efstathiou, K; Contopoulos, G

    2001-01-01

    We study the forms of the orbits in a symmetric configuration of a realistic model of the H2O molecule with particular emphasis on the periodic orbits. We use an appropriate Poincare surface of section (PSS) and study the distribution of the orbits on this PSS for various energies. We find both orde

  13. Relativistic Scott correction for atoms and molecules

    DEFF Research Database (Denmark)

    Solovej, Jan Philip; Sørensen, Thomas Østergaard; Spitzer, Wolfgang Ludwig

    2010-01-01

    We prove the first correction to the leading Thomas-Fermi energy for the ground state energy of atoms and molecules in a model where the kinetic energy of the electrons is treated relativistically. The leading Thomas-Fermi energy, established in [25], as well as the correction given here, are of ...

  14. Cluster ions and van der Waals molecules

    CERN Document Server

    Smirnov, Boris M

    1992-01-01

    This review discusses current ideas in the physics and chemistry of cluster ions and Van der Waals molecules as well as presenting numerical data on their parameters and the processes involving them. It is also a detailed reference on basic data relating to many species.

  15. Hierarchical organization in aggregates of protein molecules

    DEFF Research Database (Denmark)

    Bohr, Henrik; Kyhle, Anders; Sørensen, Alexis Hammer;

    1997-01-01

    of the solution and the density of protein are varied shows the existence of specific growth processes resulting in different branch-like structures. The resulting structures are strongly influenced by the shape of each protein molecule. Lysozyme and ribonuclease are found to form spherical structures...

  16. Modified "DMC" technique for stretching DNA molecules

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    A modified "dynamic molecular combing"(DMC)technique used for stretching double-strandedDNA is reported. DNA molecules were stretched on the silanized mica surface by thistechnique, its speed being precisely controlled with a computer. This approachcombinedthe precise DNA stretching method with high resolution AFM imaging at nanometer scale,thusmaking it useful for DNA alignment manipulation and subsequent gene research.

  17. Organic chemistry: Precision pruning of molecules

    Science.gov (United States)

    Yang, Kin S.; Engle, Keary M.

    2016-05-01

    If organic molecules were trees, then the numerous carbon-hydrogen bonds within them would be leaves. A catalyst that targets one 'leaf' out of many similar other ones looks set to be a huge leap for synthetic chemistry. See Letter p.230

  18. Comprehensive Map of Molecules Implicated in Obesity.

    Science.gov (United States)

    Jagannadham, Jaisri; Jaiswal, Hitesh Kumar; Agrawal, Stuti; Rawal, Kamal

    2016-01-01

    Obesity is a global epidemic affecting over 1.5 billion people and is one of the risk factors for several diseases such as type 2 diabetes mellitus and hypertension. We have constructed a comprehensive map of the molecules reported to be implicated in obesity. A deep curation strategy was complemented by a novel semi-automated text mining system in order to screen 1,000 full-length research articles and over 90,000 abstracts that are relevant to obesity. We obtain a scale free network of 804 nodes and 971 edges, composed of 510 proteins, 115 genes, 62 complexes, 23 RNA molecules, 83 simple molecules, 3 phenotype and 3 drugs in "bow-tie" architecture. We classify this network into 5 modules and identify new links between the recently discovered fat mass and obesity associated FTO gene with well studied examples such as insulin and leptin. We further built an automated docking pipeline to dock orlistat as well as other drugs against the 24,000 proteins in the human structural proteome to explain the therapeutics and side effects at a network level. Based upon our experiments, we propose that therapeutic effect comes through the binding of one drug with several molecules in target network, and the binding propensity is both statistically significant and different in comparison with any other part of human structural proteome. PMID:26886906

  19. Large molecules in diffuse interstellar clouds

    NARCIS (Netherlands)

    Lepp, S.; Dalgarno, A.; Dishoeck, van E.F.; Black, J.H.

    1988-01-01

    The effects of the presence of a substantial component of large molecules on the chemistry of diffuse molecular clouds are explored, and detailed models of the zeta Persei and zeta Ophiuchi clouds are constructed. The major consequence is a reduction in the abundances of singly charged atomic specie

  20. Small molecule control of bacterial biofilms.

    Science.gov (United States)

    Worthington, Roberta J; Richards, Justin J; Melander, Christian

    2012-10-01

    Bacterial biofilms are defined as a surface attached community of bacteria embedded in a matrix of extracellular polymeric substances that they have produced. When in the biofilm state, bacteria are more resistant to antibiotics and the host immune response than are their planktonic counterparts. Biofilms are increasingly recognized as being significant in human disease, accounting for 80% of bacterial infections in the body and diseases associated with bacterial biofilms include: lung infections of cystic fibrosis patients, colitis, urethritis, conjunctivitis, otitis, endocarditis and periodontitis. Additionally, biofilm infections of indwelling medical devices are of particular concern, as once the device is colonized infection is virtually impossible to eradicate. Given the prominence of biofilms in infectious diseases, there has been an increased effort toward the development of small molecules that will modulate bacterial biofilm development and maintenance. In this review, we highlight the development of small molecules that inhibit and/or disperse bacterial biofilms through non-microbicidal mechanisms. The review discuses the numerous approaches that have been applied to the discovery of lead small molecules that mediate biofilm development. These approaches are grouped into: (1) the identification and development of small molecules that target one of the bacterial signaling pathways involved in biofilm regulation, (2) chemical library screening for compounds with anti-biofilm activity, and (3) the identification of natural products that possess anti-biofilm activity, and the chemical manipulation of these natural products to obtain analogues with increased activity. PMID:22733439

  1. Self and directed assembly: people and molecules.

    Science.gov (United States)

    James, Tony D

    2016-01-01

    Self-assembly and directed-assembly are two very important aspects of supramolecular chemistry. As a young postgraduate student working in Canada with Tom Fyles my introduction to Supramolecular Chemistry was through the self-assembly of phospholipid membranes to form vesicles for which we were developing unimolecular and self-assembling transporter molecules. The next stage of my development as a scientist was in Japan with Seiji Shinkai where in a "Eureka" moment, the boronic acid templating unit (directed-assembly) of Wulff was combined with photoinduced electron transfer systems pioneered by De Silva. The result was a turn-on fluorescence sensor for saccharides; this simple result has continued to fuel my research to the present day. Throughout my career as well as assembling molecules, I have enjoyed bringing together researchers in order to develop collaborative networks. This is where molecules meet people resulting in assemblies worth more than the individual "molecule" or "researcher". My role in developing networks with Japan was rewarded by the award of a Daiwa-Adrian Prize in 2013 and I was recently rewarded for developing networks with China with an Inaugural CASE Prize in 2015. PMID:27340435

  2. Comprehensive Map of Molecules Implicated in Obesity.

    Directory of Open Access Journals (Sweden)

    Jaisri Jagannadham

    Full Text Available Obesity is a global epidemic affecting over 1.5 billion people and is one of the risk factors for several diseases such as type 2 diabetes mellitus and hypertension. We have constructed a comprehensive map of the molecules reported to be implicated in obesity. A deep curation strategy was complemented by a novel semi-automated text mining system in order to screen 1,000 full-length research articles and over 90,000 abstracts that are relevant to obesity. We obtain a scale free network of 804 nodes and 971 edges, composed of 510 proteins, 115 genes, 62 complexes, 23 RNA molecules, 83 simple molecules, 3 phenotype and 3 drugs in "bow-tie" architecture. We classify this network into 5 modules and identify new links between the recently discovered fat mass and obesity associated FTO gene with well studied examples such as insulin and leptin. We further built an automated docking pipeline to dock orlistat as well as other drugs against the 24,000 proteins in the human structural proteome to explain the therapeutics and side effects at a network level. Based upon our experiments, we propose that therapeutic effect comes through the binding of one drug with several molecules in target network, and the binding propensity is both statistically significant and different in comparison with any other part of human structural proteome.

  3. Photoelectron spectroscopy of heavy atoms and molecules

    International Nuclear Information System (INIS)

    The importance of relativistic interactions in the photoionization of heavy atoms and molecules has been investigated by the technique of photoelectron spectroscopy. In particular, experiments are reported which illustrate the effects of the spin-orbit interaction in the neutral ground state, final ionic states and continuum states of the photoionization target

  4. Complex organic molecules and star formation

    Science.gov (United States)

    Bacmann, A.; Faure, A.

    2014-12-01

    Star forming regions are characterised by the presence of a wealth of chemical species. For the past two to three decades, ever more complex organic species have been detected in the hot cores of protostars. The evolution of these molecules in the course of the star forming process is still uncertain, but it is likely that they are partially incorporated into protoplanetary disks and then into planetesimals and the small bodies of planetary systems. The complex organic molecules seen in star forming regions are particularly interesting since they probably make up building blocks for prebiotic chemistry. Recently we showed that these species were also present in the cold gas in prestellar cores, which represent the very first stages of star formation. These detections question the models which were until now accepted to account for the presence of complex organic molecules in star forming regions. In this article, we shortly review our current understanding of complex organic molecule formation in the early stages of star formation, in hot and cold cores alike and present new results on the formation of their likely precursor radicals.

  5. Molecules for Fluorescence Detection of Specific Chemicals

    Science.gov (United States)

    Fedor, Steve

    2008-01-01

    A family of fluorescent dye molecules has been developed for use in on-off fluorescence detection of specific chemicals. By themselves, these molecules do not fluoresce. However, when exposed to certain chemical analytes in liquid or vapor forms, they do fluoresce (see figure). These compounds are amenable to fixation on or in a variety of substrates for use in fluorescence-based detection devices: they can be chemically modified to anchor them to porous or non-porous solid supports or can be incorporated into polymer films. Potential applications for these compounds include detection of chemical warfare agents, sensing of acidity or alkalinity, and fluorescent tagging of proteins in pharmaceutical research and development. These molecules could also be exploited for use as two-photon materials for photodynamic therapy in the treatment of certain cancers and other diseases. A molecule in this family consists of a fluorescent core (such as an anthracene or pyrene) attached to two end groups that, when the dye is excited by absorption of light, transfer an electron to the core, thereby quenching the fluorescence. The end groups can be engineered so that they react chemically with certain analytes. Upon reaction, electrons on the end groups are no longer available for transfer to the core and, consequently, the fluorescence from the core is no longer quenched. The chemoselectivity of these molecules can be changed by changing the end groups. For example, aniline end groups afford a capability for sensing acids or acid halides (including those contained in chemical warfare agents). Pyridine or bipyridyl end groups would enable sensing of metal ions. Other chemicals that can be selectively detected through suitable choice of end groups include glucose and proteins. Moreover, the fluorescent cores can be changed to alter light-absorption and -emission characteristics: anthracene cores fluoresce at wavelengths around 500 nm, whereas perylene cores absorb and emit at

  6. Prebiotic molecules and interstellar grain clumps

    International Nuclear Information System (INIS)

    It is stated that interstellar molecules detected by radioastronomical techniques in galactic clouds cover a wide range of types and complexities. Amongst the heaviest recently discovered is cyanodiacetylene. There have also been earlier detections of precursors to the simplest amino-acid, glycine and probably detections of polyoxymethylene polymers and co-polymers. A possible identification of organic molecules of even greater complexity is here discussed, together with implications for the commencement of biological activity. The large departures from thermodynamic equilibrium in the interstellar medium and the co-existence of solid grains, molecules, radicals, ions, and uv photons provide conditions that are ideal for production of 'exotic' molecular species. The effect of clumping of dust grains is discussed. The possible spectral identification of highly complex organic species in the interstellar medium is also discussed and reference is made to a property common to a wide class of such molecules, that is, an absorption band centered at 2,200 A. It is tempting to identify this feature with the well-known 2,200 A band of the interstellar extinction curve. It is thought that it may be tentatively concluded that the data so far obtained could be interpreted as independent new chemical evidence of the existence of composite grain clumps in the interstellar medium and in carbonaceous chondrites, and that these grain clumps probably include a significant mass fraction of highly complex organic pre-biotic molecules that could have led to the start and dispersal of biological activity on the Earth and elsewhere in the Galaxy. Processes of natural selection probably also played an important part, particularly in the production of self-replicable peptide chains. The problem of protection of pre-biotic material against external disruptive agencies, such as u/v light, is also discussed. (U.K.)

  7. Identifying immunogenic CD4+ T-cell epitopes of Myeloid cell leukemia 1 using overlapping 20-mer peptides spanning the whole protein

    DEFF Research Database (Denmark)

    Woodworth, Joshua S.; Agger, Else Marie; Hansen, Paul Robert

    2015-01-01

    ) small-molecule inhibitors [6] and (iii) peptide inhibitors [7]. In recent years, therapeutic vaccination with synthetic peptides derived from anti-apoptotic proteins such as Mcl-1 has emerged as a promising strategy against hematological cancers. In this study, 34 overlapping 20-mer peptides, spanning...

  8. Multiorbital tunneling ionization of the CO molecule

    CERN Document Server

    Wu, J; Kunitski, M; Meckel, M; Voss, S; Sann, H; Kim, H; Jahnke, T; Czasch, A; Dörner, R

    2012-01-01

    We coincidently measure the molecular frame photoelectron angular distribution and the ion sum-momentum distribution of single and double ionization of CO molecules by using circularly and elliptically polarized femtosecond laser pulses, respectively. The orientation dependent ionization rates for various kinetic energy releases allow us to individually identify the ionizations of multiple orbitals, ranging from the highest occupied to the next two lower-lying molecular orbitals for various channels observed in our experiments. Not only the emission of a single electron, but also the sequential tunneling dynamics of two electrons from multiple orbitals are traced step by step. Our results confirm that the shape of the ionizing orbitals determine the strong laser field tunneling ionization in the CO molecule, whereas the linear Stark effect plays a minor role.

  9. Watching single protein molecules in action

    DEFF Research Database (Denmark)

    Heiðarsson, Pétur Orri

    . This knowledge-gap is partly due to our inability to unveil the details of folding mechanisms that can be buried in the ensemble-averaged output of traditional bulk methods. Single-molecule techniques have provided a perspective beyond the ensemble average and enable studying the folding trajectories of protein......, with transition states located almost halfway between the native and unfolded states. When pulled from the N- and C-termini, both experiments and simulations suggested that the molecule populates a transition state that resembles that observed during chemical denaturation, with respect to structure and position...... along the reaction coordinate. The results call for a modified view of the mechanical response of native states which may be relevant in an evolutionary sense for functionality and for biomolecular design. A vastly more complex folding behavior was observed for the two-domain neuronal calcium sensor 1...

  10. Is the focus on "molecules" obsolete?

    Science.gov (United States)

    Whitesides, George M

    2013-01-01

    The technologies developed in analytical chemistry have defined in spectacular detail the properties of molecules. The field now faces enormously important and interesting problems of which molecules are only a part: for example, understanding the nature of life; helping to manage megacities, oceans, and atmospheres; and making health care (especially diagnostics) affordable and relevant. The emergence of these problems involving molecular systems raises the issue of how (and what) analytical chemistry should teach. Historically, it has been essential to chemistry in teaching the science of measurement. As complicated analytical techniques proliferate, it must consider how to balance teaching the uses of sophisticated devices and the fundamentals of analysis and measurement. This review (by an admiring but nonanalytical chemist) sketches the essential role of analytical methods--especially simple ones made up on the spot--in guiding research in new fields, with examples from self-assembled monolayers, soft lithography, paper diagnostics, and self-assembly; and suggests issues in teaching. PMID:23772657

  11. Is the Focus on ``Molecules'' Obsolete?

    Science.gov (United States)

    Whitesides, George M.

    2013-06-01

    The technologies developed in analytical chemistry have defined in spectacular detail the properties of molecules. The field now faces enormously important and interesting problems of which molecules are only a part: for example, understanding the nature of life; helping to manage megacities, oceans, and atmospheres; and making health care (especially diagnostics) affordable and relevant. The emergence of these problems involving molecular systems raises the issue of how (and what) analytical chemistry should teach. Historically, it has been essential to chemistry in teaching the science of measurement. As complicated analytical techniques proliferate, it must consider how to balance teaching the uses of sophisticated devices and the fundamentals of analysis and measurement. This review (by an admiring but nonanalytical chemist) sketches the essential role of analytical methods—especially simple ones made up on the spot—in guiding research in new fields, with examples from self-assembled monolayers, soft lithography, paper diagnostics, and self-assembly; and suggests issues in teaching.

  12. Imaging Genetic Molecules At Atomic Resolution

    Science.gov (United States)

    Coles, L. Stephen

    1993-01-01

    Proposed method of imaging informational polymeric biological molecules at atomic resolution enables determination of sequences of component monomers about 10 to the 3rd power to 10 to the 4th power times as fast as conventional methods do. Accelerates research on genetic structures of animals and plants. Also contributes significantly to imaging processes like scanning electron microscopy (SEM), atomic-force microscopy (AFM), and scanning tunneling microscopy (STM) in cases in which necessary to locate or identify small specimens on relatively large backgrounds and subtract background images to obtain images of specimens in isolation. V-grooves on silicon wafer laid out in square pattern, intersections of which marked to identify coordinates. Specimen molecules held in grooves for reproducible positioning and scanning by AFM or STM.

  13. Field-free orientation of molecules

    DEFF Research Database (Denmark)

    Machholm, Mette; Henriksen, Niels Engholm

    2001-01-01

    The excitation of angular motion, in particular, the creation of a wave packet in the angular degrees of freedom via short-pulse, off-resonant excitation with respect to rotational transitions, was examined. The key result was that field-free time-dependent orientation for a molecule like LiH can...... be generated after the turn-off of a state-of-the-art electromagnetic half-cycle pulse.......The excitation of angular motion, in particular, the creation of a wave packet in the angular degrees of freedom via short-pulse, off-resonant excitation with respect to rotational transitions, was examined. The key result was that field-free time-dependent orientation for a molecule like LiH can...

  14. Effective interaction between helical bio-molecules

    CERN Document Server

    Allahyarov, E

    1999-01-01

    The effective interaction between two parallel strands of helicalbio-molecules, such as deoxyribose nucleic acids (DNA), is calculated usingcomputer simulations of the "primitive" model of electrolytes. In particular westudy a simple model for B-DNA incorporating explicitly its charge pattern as adouble-helix structure. The effective force and the effective torque exertedonto the molecules depend on the central distance and on the relativeorientation. The contributions of nonlinear screening by monovalent counterionsto these forces and torques are analyzed and calculated for different saltconcentrations. As a result, we find that the sign of the force dependssensitively on the relative orientation. For intermolecular distances smallerthan $6\\AA$ it can be both attractive and repulsive. Furthermore we report anonmonotonic behaviour of the effective force for increasing saltconcentration. Both features cannot be described within linear screeningtheories. For large distances, on the other hand, the results agree...

  15. Photochemical dynamics of surface oriented molecules

    International Nuclear Information System (INIS)

    The period 8/01/91-7/31/92 is the first year of a new project titled ''Photochemical Dynamics of Surface Oriented Molecules'', initiated with DOE Support. The main objective of this project is to understand the dynamics of elementary chemical reactions by studying photochemical dynamics of surface-oriented molecules. In addition, the mechanisms of photon-surface interactions need to be elucidated. The strategy is to carry out experiments to measure the translational energy distribution, as a function of the angle from the surface normal, of the photoproducts by time-of-flight (TOF) technique by varying the photon wavelength, intensity, polarization, and pulse duration. By choosing adsorbates with different bonding configuration, the effects of adsorbate orientation on surface photochemical dynamics can be studied

  16. Atomic Rydberg Reservoirs for Polar Molecules

    CERN Document Server

    Zhao, Bo; Pupillo, Guido; Zoller, Peter

    2011-01-01

    We discuss laser dressed dipolar and Van der Waals interactions between atoms and polar molecules, so that a cold atomic gas with laser admixed Rydberg levels acts as a designed reservoir for both elastic and inelastic collisional processes. The elastic scattering channel is characterized by large elastic scattering cross sections and repulsive shields to protect from close encounter collisions. In addition, we discuss a dissipative (inelastic) collision where a spontaneously emitted photon carries away (kinetic) energy of the collision partners, thus providing a significant energy loss in a single collision. This leads to the scenario of rapid thermalization and cooling of a molecule in the mK down to the \\mu K regime by cold atoms.

  17. Atomic Rydberg Reservoirs for Polar Molecules

    Science.gov (United States)

    Zhao, B.; Glaetzle, A. W.; Pupillo, G.; Zoller, P.

    2012-05-01

    We discuss laser-dressed dipolar and van der Waals interactions between atoms and polar molecules, so that a cold atomic gas with laser admixed Rydberg levels acts as a designed reservoir for both elastic and inelastic collisional processes. The elastic scattering channel is characterized by large elastic scattering cross sections and repulsive shields to protect from close encounter collisions. In addition, we discuss a dissipative (inelastic) collision where a spontaneously emitted photon carries away (kinetic) energy of the collision partners, thus providing a significant energy loss in a single collision. This leads to the scenario of rapid thermalization and cooling of a molecule in the mK down to the μK regime by cold atoms.

  18. Modelling proton transfer in water molecule chains

    CERN Document Server

    Korzhimanov, Artem; Shutova, Tatiana; Samuelsson, Goran

    2011-01-01

    The process of protons transport in molecular water chains is of fundamental interest for many biological systems. Although many features of such systems can be analyzed using large-scale computational modeling, other features are better understood in terms of simplified model problems. Here we have tested, analytically and numerically, a model describing the classical proton hopping process in molecular water chains. In order to capture the main features of the proton hopping process in such molecular chains, we use a simplified model for our analysis. In particular, our discrete model describes a 1D chain of water molecules situated in an external protein channel structure, and each water molecule is allowed to oscillate around its equilibrium point in this system, while the protons are allowed to move along the line of neighboring oxygen atoms. The occurrence and properties of nonlinear solitary transport structures, allowing for much faster proton transport, are discussed, and the possible implications of...

  19. Multichannel quantum defect theory for ro-vibrational transitions in ultracold molecule-molecule collisions

    OpenAIRE

    Hazra, Jisha; Ruzic, Brandon P.; Balakrishnan, N.; Bohn, John L.

    2014-01-01

    Multichannel quantum defect theory (MQDT) has been widely applied to resonant and non-resonant scattering in a variety of atomic collision processes. In recent years, the method has been applied to cold collisions with considerable success, and it has proven to be a computationally viable alternative to full-close coupling (CC) calculations when spin, hyperfine and external field effects are included. In this paper, we describe a hybrid approach for molecule-molecule scattering that includes ...

  20. Stepwise oscillatory circuits of a DNA molecule

    OpenAIRE

    Xu, Kunming

    2009-01-01

    A DNA molecule is characterized by a stepwise oscillatory circuit where every base pair is a capacitor, every phosphate bridge is an inductance, and every deoxyribose is a charge router. The circuitry accounts for DNA conductivity through both short and long distances in good agreement with experimental evidence that has led to the identification of the so-called super-exchange and multiple-step hopping mechanisms. However, in contrast to the haphazard hopping and super-exchanging events, the...

  1. Spontaneous emission of molecules in open resonators

    CERN Document Server

    Datsyuk, V V

    2002-01-01

    The formulas for the molecule and atoms spontaneous emission rate in the arbitrary open resonator in the weak bond approximation with an account of the emission absorption or increase through the resonator substance is obtained within the frames of the classical electrodynamics. The proposed formulas agrees well with the data on the microdrops luminescence. The effect of the spontaneous resonance emission rate suppression through the laser active medium is forecasted

  2. Electron correlation in molecules and condensed phases

    CERN Document Server

    March, N H

    1996-01-01

    This reference describes the latest research on correlation effects in the multicenter problems of atoms, molecules, and solids The author utilizes first- and second-order matrices, including the important observable electron density rho(r), and the Green function for discussing quantum computer simulations With its focus on concepts and theories, this volume will benefit experimental physicists, materials scientists, and physical and inorganic chemists as well as graduate students

  3. Circular Intensity Differential Scattering of chiral molecules

    Energy Technology Data Exchange (ETDEWEB)

    Bustamante, C.J.

    1980-12-01

    In this thesis a theory of the Circular Intensity Differential Scattering (CIDS) of chiral molecules as modelled by a helix oriented with respect to the direction of incidence of light is presented. It is shown that a necessary condition for the existence of CIDS is the presence of an asymmetric polarizability in the scatterer. The polarizability of the scatterer is assumed generally complex, so that both refractive and absorptive phenomena are taken into account.

  4. Small Talk: Children's Everyday `Molecule' Ideas

    Science.gov (United States)

    Jakab, Cheryl

    2013-08-01

    This paper reports on 6-11-year-old children's `sayings and doings' (Harré 2002) as they explore molecule artefacts in dialectical-interactive teaching interviews (Fleer, Cultural Studies of Science Education 3:781-786, 2008; Hedegaard et al. 2008). This sociocultural study was designed to explore children's everyday awareness of and meaning-making with cultural molecular artefacts. Our everyday world is populated with an ever increasing range of molecular or nanoworld words, symbols, images, and games. What do children today say about these artefacts that are used to represent molecular world entities? What are the material and social resources that can influence a child's everyday and developing scientific ideas about `molecules'? How do children interact with these cognitive tools when given expert assistance? What meaning-making is afforded when children are socially and materially assisted in using molecular tools in early chemical and nanoworld thinking? Tool-dependent discursive studies show that provision of cultural artefacts can assist and direct developmental thinking across many domains of science (Schoultz et al., Human Development 44:103-118, 2001; Siegal 2008). Young children's use of molecular artefacts as cognitive tools has not received much attention to date (Jakab 2009a, b). This study shows 6-11-year-old children expressing everyday ideas of molecular artefacts and raising their own questions about the artefacts. They are seen beginning to domesticate (Erneling 2010) the words, symbols, and images to their own purposes when given the opportunity to interact with such artefacts in supported activity. Discursive analysis supports the notion that using `molecules' as cultural tools can help young children to begin `putting on molecular spectacles' (Kind 2004). Playing with an interactive game (ICT) is shown to be particularly helpful in assisting children's early meaning-making with representations of molecules, atoms, and their chemical symbols.

  5. Imaging Cold Molecules on a Chip

    OpenAIRE

    Marx, S.; Adu Smith, D.; Abel, M.; Zehentbauer, T.; Meijer, G.J.M.; Santambrogio, G.

    2013-01-01

    We present the integrated imaging of cold molecules in a microchip environment. The on-chip detection is based on resonance-enhanced multiphoton ionization, which is quantum state selective and generally applicable. We demonstrate and characterize time-resolved spatial imaging and subsequently use it to analyze the effect of a phase-space manipulation sequence aimed at compressing the velocity distribution of a molecular ensemble with a view to future high-resolution spectroscopic studies. Th...

  6. Single molecules as whispering galleries for electrons

    Science.gov (United States)

    Reecht, G.; Bulou, H.; Schull, G.; Scheurer, F.

    2016-04-01

    Whispering gallery modes, well-known for acoustic and optical waves, have been shown recently for electrons in molecules on surfaces. The existence of such waves opens new possibilities for nanoelectronic devices. Here we propose a simple analytical textbook model which allows the main characteristic features of such electronic waves to be understood. The model is illustrated by two- and three-dimensional experimental situations.

  7. Rotations and Vibrations of trinuclear molecules

    International Nuclear Information System (INIS)

    A model describing the rotations and vibrations of trinuclear molecules is presented. The treatment is made in the spirit of Bohr-Mottelson collective model of nucleus. The two-body interactions between the composing clusters are calculated assuming the density independent M3Y forces, supplemented by a phenomenological repulsive component. Under simplifying assumptions, such as linear chain quasi-equilibrium configuration and freezing of the contact point between the light cluster and the heavy clusters, analytical solutions are available. (authors)

  8. Development of proneurogenic, neuroprotective small molecules

    OpenAIRE

    MacMillan, Karen S.; Naidoo, Jacinth; Liang, Jue; Melito, Lisa; Williams, Noelle S.; Morlock, Lorraine; Huntington, Paula J.; Estill, Sandi Jo; Longgood, Jamie; Becker, Ginger L.; McKnight, Steven L.; Pieper, Andrew A.; De Brabander, Jef K.; Ready, Joseph M.

    2011-01-01

    Degeneration of the hippocampus is associated with Alzheimer’s disease, and occurs very early in the progression of the disease. Current options for treating the cognitive symptoms associated with Alzheimer’s are inadequate, giving urgency to the search for novel therapeutic strategies. Pharmacologic agents that safely enhance hippocampal neurogenesis may provide new therapeutic approaches. We discovered the first synthetic molecule, named P7C3, which protects newborn neurons from apopotic ce...

  9. Femtosecond Photodissociation of Molecules Facilitated by Noise

    OpenAIRE

    Singh, Kamal P.; Kenfack, Anatole; Rost, Jan M

    2007-01-01

    We investigate the dynamics of diatomic molecules subjected to both a femtosecond mid-infrared laser pulse and Gaussian white noise. The stochastic Schr\\"odinger equation with a Morse potential is used to describe the molecular vibrations under noise and the laser pulse. For weak laser intensity, well below the dissociation threshold, it is shown that one can find an optimum amount of noise that leads to a dramatic enhancement of the dissociation probability. The enhancement landscape which i...

  10. Small Molecule Library Synthesis Using Segmented Flow

    OpenAIRE

    Thompson, Christina M.; Djuric, Stevan W.; Cross, Jeffrey L.; Irini Akritopoulou-Zanze; Poole, Jennifer L.

    2011-01-01

    Flow chemistry has gained considerable recognition as a simple, efficient, and safe technology for the synthesis of many types of organic and inorganic molecules ranging in scope from large complex natural products to silicon nanoparticles. In this paper we describe a method that adapts flow chemistry to the synthesis of libraries of compounds using a fluorous immiscible solvent as a spacer between reactions. The methodology was validated in the synthesis of two small heterocycle containing l...

  11. Colloquium: Quantum interference of clusters and molecules

    OpenAIRE

    Hornberger, Klaus; Gerlich, Stefan; Haslinger, Philipp; Nimmrichter, Stefan; Arndt, Markus

    2011-01-01

    We review recent progress and future prospects of matter wave interferometry with complex organic molecules and inorganic clusters. Three variants of a near-field interference effect, based on diffraction by material nanostructures, at optical phase gratings, and at ionizing laser fields are considered. We discuss the theoretical concepts underlying these experiments and the experimental challenges. This includes optimizing interferometer designs as well as understanding the role of decoheren...

  12. 'Single molecule': theory and experiments, an introduction.

    Science.gov (United States)

    Riveline, Daniel

    2013-01-01

    At scales below micrometers, Brownian motion dictates most of the behaviors. The simple observation of a colloid is striking: a permanent and random motion is seen, whereas inertial forces play a negligible role. This Physics, where velocity is proportional to force, has opened new horizons in biology. The random feature is challenged in living systems where some proteins--molecular motors--have a directed motion whereas their passive behaviors of colloid should lead to a Brownian motion. Individual proteins, polymers of living matter such as DNA, RNA, actin or microtubules, molecular motors, all these objects can be viewed as chains of colloids. They are submitted to shocks from molecules of the solvent. Shapes taken by these biopolymers or dynamics imposed by motors can be measured and modeled from single molecules to their collective effects. Thanks to the development of experimental methods such as optical tweezers, Atomic Force Microscope (AFM), micropipettes, and quantitative fluorescence (such as Förster Resonance Energy Transfer, FRET), it is possible to manipulate these individual biomolecules in an unprecedented manner: experiments allow to probe the validity of models; and a new Physics has thereby emerged with original biological insights. Theories based on statistical mechanics are needed to explain behaviors of these systems. When force-extension curves of these molecules are extracted, the curves need to be fitted with models that predict the deformation of free objects or submitted to a force. When velocity of motors is altered, a quantitative analysis is required to explain the motions of individual molecules under external forces. This lecture will give some elements of introduction to the lectures of the session 'Nanophysics for Molecular Biology'. PMID:24565227

  13. Matter-wave interferometer for large molecules

    OpenAIRE

    Brezger, B.; Hackermüller, L.; Uttenthaler, S.; Petschinka, J.; Arndt, M.; Zeilinger, A.

    2002-01-01

    We demonstrate a near-field Talbot-Lau interferometer for C-70 fullerene molecules. Such interferometers are particularly suitable for larger masses. Using three free-standing gold gratings of one micrometer period and a transversally incoherent but velocity-selected molecular beam, we achieve an interference fringe visibility of 40 % with high count rate. Both the high visibility and its velocity dependence are in good agreement with a quantum simulation that takes into account the van der W...

  14. Dipole-Dipole coupled double Rydberg molecules

    OpenAIRE

    Kiffner, Martin; Park, Hyunwook; Li, Wenhui; Gallagher, Tom F.

    2012-01-01

    We show that the dipole-dipole interaction between two Rydberg atoms can give rise to long range molecules. The binding potential arises from two states that converge to different separated atom asymptotes. These states interact weakly at large distances, but start to repel each other strongly as the van der Waals interaction turns into a resonant dipole-dipole interaction with decreasing separation between the atoms. This mechanism leads to the formation of an attractive well for one of the ...

  15. Single Molecule Data Analysis: An Introduction

    CERN Document Server

    Tavakoli, Meysam; Li, Chun-Biu; Komatsuzaki, Tamiki; Pressé, Steve

    2016-01-01

    We review methods of data analysis for biophysical data with a special emphasis on single molecule applications. Our review is intended for anyone, from student to established researcher. For someone just getting started, we focus on exposing the logic, strength and limitations of each method and cite, as appropriate, the relevant literature for implementation details. We review traditional frequentist and Bayesian parametric approaches to data analysis and subsequently extend our discussion to recent non-parametric and information theoretic methods.

  16. Isatin, a versatile molecule: studies in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Barbara, E-mail: barbara.iq@gmail.com [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil)

    2013-05-15

    Isatin is a small, versatile and widely applicable pharmacological molecule. These characteristics make isatin and its derivatives attractive to many research groups as resources for chemical and pharmacological studies. Although it has a relatively simple structure, isatin is a useful chemical scaffold for a variety of chemical transformations. This article discusses several studies performed by Brazilian groups, including investigations of its structural changes, biological assay designs and new methods for the synthesis of isatin. (author)

  17. Vibrational spectroscopy of polar molecules with superradiance

    OpenAIRE

    Lin, Guin-Dar; Yelin, Susanne F.

    2013-01-01

    We investigate cooperative phenomena and superradiance for vibrational transitions in polar molecule spectroscopy when a high optical-depth (OD) sample is studied. Such cooperativity comes from the build-up of inter-particle coherence through dipole-dipole interactions and leads to the speed-up of decay process. We compare our calculation to recent work [Deiglmayr et al., Eur. Phys. J. D 65, 99 (2011)] and find very good agreement, suggesting that superradiant effects need to be included in a...

  18. Electrical transport through individual DNA molecules

    OpenAIRE

    Li, Xin-Qi; Yan, YiJing

    2001-01-01

    A theoretical study is presented to quantitatively analyze the transport experiment through individual DNA molecules reported recently by Porath {\\it et al.} [Nature {\\bf 403}, 635 (2000)]. A variety of valuable quantities are identified by contacting the theoretical model with the measured data. The partially decoherent nature on the GC pairs of DNA is elaborated in contrast to the completely incoherent hopping mechanism discussed in the context of charge transfer experiments.

  19. Sisyphus Cooling of Electrically Trapped Polyatomic Molecules

    OpenAIRE

    Zeppenfeld, M.; Englert, B. G. U.; Glöckner, R.; Prehn, A; Mielenz, M; Sommer, C.; van Buuren, L. D.; Motsch, M.; Rempe, G.

    2012-01-01

    The rich internal structure and long-range dipole-dipole interactions establish polar molecules as unique instruments for quantum-controlled applications and fundamental investigations. Their potential fully unfolds at ultracold temperatures, where a plethora of effects is predicted in many-body physics, quantum information science, ultracold chemistry, and physics beyond the standard model. These objectives have inspired the development of a wide range of methods to produce cold molecular en...

  20. DNA, the central molecule of aging.

    Science.gov (United States)

    Lenart, Peter; Krejci, Lumir

    2016-04-01

    Understanding the molecular mechanism of aging could have enormous medical implications. Despite a century of research, however, there is no universally accepted theory regarding the molecular basis of aging. On the other hand, there is plentiful evidence suggesting that DNA constitutes the central molecule in this process. Here, we review the roles of chromatin structure, DNA damage, and shortening of telomeres in aging and propose a hypothesis for how their interplay leads to aging phenotypes.