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Sample records for 9-o-acetyl gd3 gangliosides

  1. Mice Lacking GD3 Synthase Display Morphological Abnormalities in the Sciatic Nerve and Neuronal Disturbances during Peripheral Nerve Regeneration

    PubMed Central

    Ribeiro-Resende, Victor Túlio; Gomes, Tiago Araújo; de Lima, Silmara; Nascimento-Lima, Maiara; Bargas-Rega, Michele; Santiago, Marcelo Felipe; Reis, Ricardo Augusto de Melo; de Mello, Fernando Garcia

    2014-01-01

    The ganglioside 9-O-acetyl GD3 is overexpressed in peripheral nerves after lesioning, and its expression is correlated with axonal degeneration and regeneration in adult rodents. However, the biological roles of this ganglioside during the regenerative process are unclear. We used mice lacking GD3 synthase (Siat3a KO), an enzyme that converts GM3 to GD3, which can be further converted to 9-O-acetyl GD3. Morphological analyses of longitudinal and transverse sections of the sciatic nerve revealed significant differences in the transverse area and nerve thickness. The number of axons and the levels of myelin basic protein were significantly reduced in adult KO mice compared to wild-type (WT) mice. The G-ratio was increased in KO mice compared to WT mice based on quantification of thin transverse sections stained with toluidine blue. We found that neurite outgrowth was significantly reduced in the absence of GD3. However, addition of exogenous GD3 led to neurite growth after 3 days, similar to that in WT mice. To evaluate fiber regeneration after nerve lesioning, we compared the regenerated distance from the lesion site and found that this distance was one-fourth the length in KO mice compared to WT mice. KO mice in which GD3 was administered showed markedly improved regeneration compared to the control KO mice. In summary, we suggest that 9-O-acetyl GD3 plays biological roles in neuron-glia interactions, facilitating axonal growth and myelination induced by Schwann cells. Moreover, exogenous GD3 can be converted to 9-O-acetyl GD3 in mice lacking GD3 synthase, improving regeneration. PMID:25330147

  2. Mice lacking GD3 synthase display morphological abnormalities in the sciatic nerve and neuronal disturbances during peripheral nerve regeneration.

    PubMed

    Ribeiro-Resende, Victor Túlio; Araújo Gomes, Tiago; de Lima, Silmara; Nascimento-Lima, Maiara; Bargas-Rega, Michele; Santiago, Marcelo Felipe; Reis, Ricardo Augusto de Melo; de Mello, Fernando Garcia

    2014-01-01

    The ganglioside 9-O-acetyl GD3 is overexpressed in peripheral nerves after lesioning, and its expression is correlated with axonal degeneration and regeneration in adult rodents. However, the biological roles of this ganglioside during the regenerative process are unclear. We used mice lacking GD3 synthase (Siat3a KO), an enzyme that converts GM3 to GD3, which can be further converted to 9-O-acetyl GD3. Morphological analyses of longitudinal and transverse sections of the sciatic nerve revealed significant differences in the transverse area and nerve thickness. The number of axons and the levels of myelin basic protein were significantly reduced in adult KO mice compared to wild-type (WT) mice. The G-ratio was increased in KO mice compared to WT mice based on quantification of thin transverse sections stained with toluidine blue. We found that neurite outgrowth was significantly reduced in the absence of GD3. However, addition of exogenous GD3 led to neurite growth after 3 days, similar to that in WT mice. To evaluate fiber regeneration after nerve lesioning, we compared the regenerated distance from the lesion site and found that this distance was one-fourth the length in KO mice compared to WT mice. KO mice in which GD3 was administered showed markedly improved regeneration compared to the control KO mice. In summary, we suggest that 9-O-acetyl GD3 plays biological roles in neuron-glia interactions, facilitating axonal growth and myelination induced by Schwann cells. Moreover, exogenous GD3 can be converted to 9-O-acetyl GD3 in mice lacking GD3 synthase, improving regeneration. PMID:25330147

  3. Targeted Delivery of Immunotoxin by Antibody to Ganglioside GD3: A Novel Drug Delivery Route for Tumor Cells

    PubMed Central

    Torres Demichelis, Vanina; Vilcaes, Aldo A.; Iglesias-Bartolomé, Ramiro; Ruggiero, Fernando M.; Daniotti, Jose L.

    2013-01-01

    Gangliosides are sialic acid-containing glycolipids expressed on plasma membranes from nearly all vertebrate cells. The expression of ganglioside GD3, which plays essential roles in normal brain development, decreases in adults but is up regulated in neuroectodermal and epithelial derived cancers. R24 antibody, directed against ganglioside GD3, is a validated tumor target which is specifically endocytosed and accumulated in endosomes. Here, we exploit the internalization feature of the R24 antibody for the selective delivery of saporin, a ribosome-inactivating protein, to GD3-expressing cells [human (SK-Mel-28) and mouse (B16) melanoma cells and Chinese hamster ovary (CHO)-K1 cells]. This immunotoxin showed a specific cytotoxicity on tumor cells grew on 2D monolayers, which was further evident by the lack of any effect on GD3-negative cells. To estimate the potential antitumor activity of R24-saporin complex, we also evaluated the effect of the immunotoxin on the clonogenic growth of SK-Mel-28 and CHO-K1GD3+ cells cultured in attachment-free conditions. A drastic growth inhibition (>80–90%) of the cell colonies was reached after 3 days of immunotoxin treatment. By the contrary, colonies continue to growth at the same concentration of the immuntoxin, but in the absence of R24 antibody, or in the absence of both immunotoxin and R24, undoubtedly indicating the specificity of the effect observed. Thus, the ganglioside GD3 emerge as a novel and attractive class of cell surface molecule for targeted delivery of cytotoxic agents and, therefore, provides a rationale for future therapeutic intervention in cancer. PMID:23383146

  4. Ganglioside GD3 Is Required for Neurogenesis and Long-Term Maintenance of Neural Stem Cells in the Postnatal Mouse Brain

    PubMed Central

    Wang, Jing; Cheng, Allison; Wakade, Chandramohan

    2014-01-01

    The maintenance of a neural stem cell (NSC) population in mammalian postnatal and adult life is crucial for continuous neurogenesis and neural repair. However, the molecular mechanism of how NSC populations are maintained remains unclear. Gangliosides are important cellular membrane components in the nervous system. We previously showed that ganglioside GD3 plays a crucial role in the maintenance of the self-renewal capacity of NSCs in vitro. Here, we investigated its role in postnatal and adult neurogenesis in GD3-synthase knock-out (GD3S-KO) and wild-type mice. GD3S-KO mice with deficiency in GD3 and the downstream b-series gangliosides showed a progressive loss of NSCs both at the SVZ and the DG of the hippocampus. The decrease of NSC populations in the GD3S-KO mice resulted in impaired neurogenesis at the granular cell layer of the olfactory bulb and the DG in the adult. In addition, defects of the self-renewal capacity and radial glia-like stem cell outgrowth of postnatal GD3S-KO NSCs could be rescued by restoration of GD3 expression in these cells. Our study demonstrates that the b-series gangliosides, especially GD3, play a crucial role in the long-term maintenance NSC populations in postnatal mouse brain. Moreover, the impaired neurogenesis in the adult GD3S-KO mice led to depression-like behaviors. Thus, our results provide convincing evidence linking b-series gangliosides deficiency and neurogenesis defects to behavioral deficits, and support a crucial role of gangliosides in the long-term maintenance of NSCs in adult mice. PMID:25297105

  5. 9-O-Acetylation of sialomucins: a novel marker of murine CD4 T cells that is regulated during maturation and activation.

    PubMed

    Krishna, M; Varki, A

    1997-06-01

    Terminal sialic acids on cell surface glycoconjugates can carry 9-O-acetyl esters. For technical reasons, it has previously been difficult to determine their precise distribution on different cell types. Using a recombinant soluble form of the Influenza C virus hemagglutinin-esterase as a probe for 9-O-acetylated sialic acids, we demonstrate here their preferential expression on the CD4 T cell lineage in normal B10.A mouse lymphoid organs. Of total thymocytes, 8-10% carry 9-O-acetylation; the great majority of these are the more mature PNA-, HSA-, and TCRhi medullary cells. While low levels of 9-O-acetylation are seen on some CD4/CD8 double positive (DP) and CD8 single positive (SP) cells, high levels are present primarily on 80- 85% of CD4 SP cells. Correlation with CD4 and CD8 levels suggests that 9-O-acetylation appears as an early differentiation marker as cells mature from the DP to the CD4 SP phenotype. This high degree of 9-O-acetylation is also present on 90-95% of peripheral spleen and lymph node CD4 T cells. In contrast, only a small minority of CD8 T cells and B cells show such levels of 9-O-acetylation. Among mature peripheral CD4 T lymphocytes, the highly O-acetylated cells are Mel 14(hi), CD44(lo), and CD45R(exon B)hi, features typical of naive cells. Digestions with trypsin and O-sialoglycoprotease (OSGPase) and ELISA studies of lipid extracts indicate that the 9-O-acetylated sialic acids on peripheral CD4 T cells are predominantly on O-linked mucintype glycoproteins and to a lesser degree, on sialylated glycolipids (gangliosides). In contrast, sialic acids on mucin type molecules of CD8 T cells are not O-acetylated; instead these molecules mask the recognition of O-acetylated gangliosides that seem to be present at similar levels as on CD4 cells. The 9-O-acetylated gangliosides on mouse T cells are not bound by CD60 antibodies, which recognize O-acetylated gangliosides in human T cells. Tethering 9-O-acetylated mucins with the Influenza C probe with

  6. UVB-irradiated keratinocytes induce melanoma-associated ganglioside GD3 synthase gene in melanocytes via secretion of tumor necrosis factor α and interleukin 6.

    PubMed

    Miyata, Maiko; Ichihara, Masatoshi; Tajima, Orie; Sobue, Sayaka; Kambe, Mariko; Sugiura, Kazumitsu; Furukawa, Koichi; Furukawa, Keiko

    2014-03-01

    Although expression of gangliosides and their synthetic enzyme genes in malignant melanomas has been well studied, that in normal melanocytes has been scarcely analyzed. In particular, changes in expression levels of glycosyltransferase genes responsible for ganglioside synthesis during evolution of melanomas from melanocytes are very important to understand roles of gangliosides in melanomas. Here, expression of glycosyltransferase genes related to the ganglioside synthesis was analyzed using RNAs from cultured melanocytes and melanoma cell lines. Quantitative RT-PCR revealed that melanomas expressed high levels of mRNA of GD3 synthase and GM2/GD2 synthase genes and low levels of GM1/GD1b synthase genes compared with melanocytes. As a representative exogenous stimulation, effects of ultraviolet B (UVB) on the expression levels of 3 major ganglioside synthase genes in melanocytes were analyzed. Although direct UVB irradiation of melanocytes caused no marked changes, culture supernatants of UVB-irradiated keratinocytes (HaCaT cells) induced definite up-regulation of GD3 synthase and GM2/GD2 synthase genes. Detailed examination of the supernatants revealed that inflammatory cytokines such as TNFα and IL-6 enhanced GD3 synthase gene expression. These results suggest that inflammatory cytokines secreted from UVB-irradiated keratinocytes induced melanoma-associated ganglioside synthase genes, proposing roles of skin microenvironment in the promotion of melanoma-like ganglioside profiles in melanocytes. PMID:24548412

  7. Interaction of ganglioside GD3 with an EGF receptor sustains the self-renewal ability of mouse neural stem cells in vitro

    PubMed Central

    Wang, Jing; Yu, Robert K.

    2013-01-01

    Mounting evidence supports the notion that gangliosides serve regulatory roles in neurogenesis; little is known, however, about how these glycosphingolipids function in neural stem cell (NSC) fate determination. We previously demonstrated that ganglioside GD3 is a major species in embryonic mouse brain: more than 80% of the NSCs obtained by the neurosphere method express GD3. To investigate the functional role of GD3 in neurogenesis, we compared the properties of NSCs from GD3-synthase knockout (GD3S-KO) mice with those from their wild-type littermates. NSCs from GD3S-KO mice showed decreased self-renewal ability compared with those from the wild-type animals, and that decreased ability was accompanied by reduced expression of EGF receptor (EGFR) and an increased degradation rate of EGFR and EGF-induced ERK signaling. We also showed that EGFR switched from the low-density lipid raft fractions in wild-type NSCs to the high-density layers in the GD3S-KO NSCs. Immunochemical staining revealed colocalization of EGFR and GD3, and EGFR could be immunoprecipitated from the NSC lysate with an anti-GD3 antibody from the wild-type, but not from the GD3S-KO, mice. Tracking the localization of endocytosed EGFR with endocytosis pathway markers indicated that more EGFR in GD3S-KO NSCs translocated through the endosomal−lysosomal degradative pathway, rather than through the recycling pathway. Those findings support the idea that GD3 interacts with EGFR in the NSCs and that the interaction is responsible for sustaining the expression of EGFR and its downstream signaling to maintain the self-renewal capability of NSCs. PMID:24198336

  8. UVB-irradiated keratinocytes induce melanoma-associated ganglioside GD3 synthase gene in melanocytes via secretion of tumor necrosis factor α and interleukin 6

    SciTech Connect

    Miyata, Maiko; Ichihara, Masatoshi; Tajima, Orie; Sobue, Sayaka; Kambe, Mariko; Sugiura, Kazumitsu; Furukawa, Koichi; Furukawa, Keiko

    2014-03-07

    Highlights: • Melanocytes showed low ST8SIA1 and high B3GALT4 levels in contrast with melanomas. • Direct UVB irradiation of melanocytes did not induce ganglioside synthase genes. • Culture supernatants of UVB-irradiated keratinocytes induced ST8SIA1 in melanocytes. • TNFα and IL-6 secreted from keratinocytes enhanced ST8SIA1 expression in melanocytes. • Inflammatory cytokines induced melanoma-related ST8SIA1 in melanocytes. - Abstract: Although expression of gangliosides and their synthetic enzyme genes in malignant melanomas has been well studied, that in normal melanocytes has been scarcely analyzed. In particular, changes in expression levels of glycosyltransferase genes responsible for ganglioside synthesis during evolution of melanomas from melanocytes are very important to understand roles of gangliosides in melanomas. Here, expression of glycosyltransferase genes related to the ganglioside synthesis was analyzed using RNAs from cultured melanocytes and melanoma cell lines. Quantitative RT-PCR revealed that melanomas expressed high levels of mRNA of GD3 synthase and GM2/GD2 synthase genes and low levels of GM1/GD1b synthase genes compared with melanocytes. As a representative exogenous stimulation, effects of ultraviolet B (UVB) on the expression levels of 3 major ganglioside synthase genes in melanocytes were analyzed. Although direct UVB irradiation of melanocytes caused no marked changes, culture supernatants of UVB-irradiated keratinocytes (HaCaT cells) induced definite up-regulation of GD3 synthase and GM2/GD2 synthase genes. Detailed examination of the supernatants revealed that inflammatory cytokines such as TNFα and IL-6 enhanced GD3 synthase gene expression. These results suggest that inflammatory cytokines secreted from UVB-irradiated keratinocytes induced melanoma-associated ganglioside synthase genes, proposing roles of skin microenvironment in the promotion of melanoma-like ganglioside profiles in melanocytes.

  9. 9-O-Acetylation of sialic acids is catalysed by CASD1 via a covalent acetyl-enzyme intermediate.

    PubMed

    Baumann, Anna-Maria T; Bakkers, Mark J G; Buettner, Falk F R; Hartmann, Maike; Grove, Melanie; Langereis, Martijn A; de Groot, Raoul J; Mühlenhoff, Martina

    2015-01-01

    Sialic acids, terminal sugars of glycoproteins and glycolipids, play important roles in development, cellular recognition processes and host-pathogen interactions. A common modification of sialic acids is 9-O-acetylation, which has been implicated in sialoglycan recognition, ganglioside biology, and the survival and drug resistance of acute lymphoblastic leukaemia cells. Despite many functional implications, the molecular basis of 9-O-acetylation has remained elusive thus far. Following cellular approaches, including selective gene knockout by CRISPR/Cas genome editing, we here show that CASD1--a previously identified human candidate gene--is essential for sialic acid 9-O-acetylation. In vitro assays with the purified N-terminal luminal domain of CASD1 demonstrate transfer of acetyl groups from acetyl-coenzyme A to CMP-activated sialic acid and formation of a covalent acetyl-enzyme intermediate. Our study provides direct evidence that CASD1 is a sialate O-acetyltransferase and serves as key enzyme in the biosynthesis of 9-O-acetylated sialoglycans. PMID:26169044

  10. 9-O-Acetylation of sialic acids is catalysed by CASD1 via a covalent acetyl-enzyme intermediate

    PubMed Central

    Baumann, Anna-Maria T.; Bakkers, Mark J. G.; Buettner, Falk F. R.; Hartmann, Maike; Grove, Melanie; Langereis, Martijn A.; de Groot, Raoul J.; Mühlenhoff, Martina

    2015-01-01

    Sialic acids, terminal sugars of glycoproteins and glycolipids, play important roles in development, cellular recognition processes and host–pathogen interactions. A common modification of sialic acids is 9-O-acetylation, which has been implicated in sialoglycan recognition, ganglioside biology, and the survival and drug resistance of acute lymphoblastic leukaemia cells. Despite many functional implications, the molecular basis of 9-O-acetylation has remained elusive thus far. Following cellular approaches, including selective gene knockout by CRISPR/Cas genome editing, we here show that CASD1—a previously identified human candidate gene—is essential for sialic acid 9-O-acetylation. In vitro assays with the purified N-terminal luminal domain of CASD1 demonstrate transfer of acetyl groups from acetyl-coenzyme A to CMP-activated sialic acid and formation of a covalent acetyl-enzyme intermediate. Our study provides direct evidence that CASD1 is a sialate O-acetyltransferase and serves as key enzyme in the biosynthesis of 9-O-acetylated sialoglycans. PMID:26169044

  11. Molecular Mimicry: Sensitization of Lewis Rats With Campylobacter jejuni Lipopolysaccharides Induces Formation of Antibody Toward GD3 Ganglioside

    PubMed Central

    Usuki, Seigo; Thompson, Stuart A.; Rivner, Michael H.; Taguchi, Kyoji; Shibata, Keiko; Ariga, Toshio; Yu, Robert K.

    2009-01-01

    Recently we have reported cases of demyelinating inflammatory neuropathy showing elevated titers of anti-GD3 antibodies, which occurs rarely in Guillain-Barré syndrome. To examine the correlation between the anti-GD3 antibody titer and Campylobacter jejuni infection, we sensitized female Lewis rats with lipopolysaccharides (LPSs) from serotype HS19 of C. jejuni and examined changes in nerve conduction velocity and nerve conduction block (P/D ratio). After 16 weeks of sensitization, animals revealed decreases of nerve conduction velocity and conduction block (P/D ratio) and high titer of anti-GD3 antibodies. These anti-GD3 antibodies also blocked transmission in neuromuscular junctions of spinal cord-muscle cells cocultures. The GD3 epitope was verified to be located on the Schwann cell surface and nodes of Ranvier in rat sciatic nerve. To determine the target epitope for GD3 antibodies in causing nerve dysfunction, the LPS fraction containing the GD3 epitope was purified from the total LPS by using an anti-GD3 monoclonal antibody-immobilized affinity column. Subsequently, chemical analysis of the oligosaccharide portion was performed and confirmed the presence of a GD3-like epitope as having the following tetrasaccharide structure: NeuAcα2-8NeuAc2-3Galβ1-4Hep. Our data thus support the possibility of a contribution of GD3 mimicry as a potential pathogenic mechanism of peripheral nerve dysfunction. PMID:16342208

  12. A therapeutic trial of human melanomas with combined small interfering RNAs targeting adaptor molecules p130Cas and paxillin activated under expression of ganglioside GD3.

    PubMed

    Makino, Yusuke; Hamamura, Kazunori; Takei, Yoshifumi; Bhuiyan, Robiul Hasan; Ohkawa, Yuki; Ohmi, Yuhsuke; Nakashima, Hideyuki; Furukawa, Keiko; Furukawa, Koichi

    2016-08-01

    We previously demonstrated that focal adhesion kinase (FAK), p130Cas and paxillin are crucially involved in the enhanced malignant properties under expression of ganglioside GD3 in melanoma cells. Therefore, molecules existing in the GD3-mediated signaling pathway could be considered as suitable targets for therapeutic intervention in malignant melanoma. The aim of this study was to determine whether blockade of p130Cas and/or paxillin by RNAi suppresses melanoma growth. We found a suitable dose (40 μM siRNA, 25 μl/tumor) of the siRNA to suppress p130Cas in the xenografts generated in nu/nu mice. Based on these results, we performed intratumoral (i.t.) treatment with anti-p130Cas and/or anti-paxillin siRNAs mixed with atelocollagen as a drug delivery system in a xenograft tumor of a human melanoma cell line, SK-MEL-28. Mixture of atelocollagen (1.75%) and an siRNA (500 or 1000 pmol/tumor) was injected into the tumors every 3 days after the first injection. An siRNA against human p130Cas markedly suppressed tumor growth of the xenograft in a dose-dependent manner, whereas siRNA against human paxillin slightly inhibited the tumor growth. A control siRNA against firefly luciferase showed no effect. To our surprise, siRNA against human p130Cas (500 or 1000 pmol/tumor) combined with siRNA against human paxillin dramatically suppressed tumor growth. In agreement with the tumor suppression effects of the anti-p130Cas siRNA, reduction in Ki-67 positive cell number as well as in p130Cas expression was demonstrated by immunohistostaining. These results suggested that blockade of GD3-mediated growth signaling pathways by siRNAs might be a novel and promising therapeutic strategy against malignant melanomas, provided signaling molecules such as p130Cas and paxillin are significantly expressed in individual cases. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc. PMID:27068854

  13. Ganglioside biosynthesis in developing brains and apoptotic cancer cells: X. regulation of glyco-genes involved in GD3 and Sialyl-Lex/a syntheses.

    PubMed

    Basu, Subhash; Ma, Rui; Moskal, Joseph R; Basu, Manju

    2012-06-01

    Gangliosides, the acidic glycosphingolipids (GSLs) containing N-acetylgalactosamine and sialic acid are ubiquitous in the central nervous system. At least six DSL-glycosyltransferase activities (GLTs Gangliosides, the acidic glycosphingolipids (GSLs) containing N-acetylgalactosamine and sialic acid (or NAc-Neuraminic acid) are ubiquitous in the central nervous system. At least six GSL-glycosyltransferase activities (GLTs) of Basu-Roseman pathway catalyzing the biosynthesis of these gangliosides have been characterized in developing chicken brains. Most of these glyco-genes are expressed in the early stages (7-17 days) of brain development and lowered in the adult stage, but the cause of reduction of enzymatic activities of these GLTs in the adult stages is not known. In order to study glyco-gene regulation we used four clonal metastatic cancer cells of colon and breast cancer tissue origin (Colo-205, SKBR-3, MDA-468, and MCF-3). The glyco-genes for synthesis of SA-LeX and SA-LeA (which contain N-acetylglucosamine, sialic acid and fucose) in these cells were modulated differently at different phases (between 2 and 48 h) of apoptotic inductions. L-PPMP, D-PDMP (inhibitor of glucosylceramide biosynthesis), Betulinic Acid (a triterpinoid isolated from bark of certain trees and used for cancer treatment in China), Tamoxifen a drug in use in the west for treatment of early stages of the disease in breast cancer patients), and cis-platin (an inhibitor of DNA biosynthesis used for testicular cancer patients) were used for induction of apoptosis in the above-mentioned cell lines. Within 2-6 h, transcriptional modulation of a number of glyco-genes was observed by DNA-micro-array (containing over 300 glyco genes attached to the glass cover slips) studies. Under long incubation time (24-48 h) almost all of the glyco-genes were downregulated. The cause of these glyco-gene regulations during apoptotic induction in metastatic carcinoma cells is unknown and needs future

  14. Glycolipid GD3 and GD3 synthase are key drivers for glioblastoma stem cells and tumorigenicity.

    PubMed

    Yeh, Shih-Chi; Wang, Pao-Yuan; Lou, Yi-Wei; Khoo, Kay-Hooi; Hsiao, Michael; Hsu, Tsui-Ling; Wong, Chi-Huey

    2016-05-17

    The cancer stem cells (CSCs) of glioblastoma multiforme (GBM), a grade IV astrocytoma, have been enriched by the expressed marker CD133. However, recent studies have shown that CD133(-) cells also possess tumor-initiating potential. By analysis of gangliosides on various cells, we show that ganglioside D3 (GD3) is overexpressed on eight neurospheres and tumor cells; in combination with CD133, the sorted cells exhibit a higher expression of stemness genes and self-renewal potential; and as few as six cells will form neurospheres and 20-30 cells will grow tumor in mice. Furthermore, GD3 synthase (GD3S) is increased in neurospheres and human GBM tissues, but not in normal brain tissues, and suppression of GD3S results in decreased GBM stem cell (GSC)-associated properties. In addition, a GD3 antibody is shown to induce complement-dependent cytotoxicity against cells expressing GD3 and inhibition of GBM tumor growth in vivo. Our results demonstrate that GD3 and GD3S are highly expressed in GSCs, play a key role in glioblastoma tumorigenicity, and are potential therapeutic targets against GBM. PMID:27143722

  15. Serological response patterns of melanoma patients immunized with a GM2 ganglioside conjugate vaccine.

    PubMed

    Kitamura, K; Livingston, P O; Fortunato, S R; Stockert, E; Helling, F; Ritter, G; Oettgen, H F; Old, L J

    1995-03-28

    Gangliosides, such as GM2, GD2, GD3, and 9-O-acetyl GD3, are receiving attention as targets for antibody-based and vaccine-based therapies of melanoma. GM2 appears to be a particularly immunogenic ganglioside in humans, as indicated by the presence of naturally occurring IgM anti-GM2 antibodies in approximately 5% of humans and the fact that immunization with irradiated GM2-expressing melanoma cells or purified GM2 adherent to bacillus Calmette-Guérin elicits GM2 antibodies of low to moderate titers in a high proportion of vaccinated patients. To develop vaccines that consistently induce high titers of IgM as well as IgG anti-GM2 antibodies, vaccines containing GM2 conjugated to keyhole limpet hemocyanin as the carrier protein and QS-21 as the adjuvant have been constructed. The serological response of vaccinated patients was monitored by ELISA using purified GM2 ganglioside for IgM and IgG anti-GM2 antibodies and for GM2 cell surface-reactive antibodies by immune adherence assays and cytotoxic tests (IgM antibodies) and mixed hemadsorption assays (IgG antibodies). The majority of vaccinated patients developed IgM and IgG antibodies detectable by ELISA. In most cases, the results of IgM ELISA correlated with assays for cell surface-reactive IgM antibodies. This was not true for IgG anti-GM2 antibodies, where strong discrepancies were seen between high titers in ELISA and little or no reactivity in mixed hemadsorption tests for cell surface-reactive antibodies. These IgG antibodies (and the less frequent IgM antibodies that show similar discrepancies) may be directed against GM2 determinants that are buried, hidden, or not present on GM2-expressing target cells. With regard to a major objective of ganglioside vaccines--i.e., generation of cytotoxic antibodies--the GM2-keyhole limpet hemocyanin/QS-21 vaccine is clearly superior to the previously tested GM2/bacillus Calmette-Guérin vaccine. However, variability in patient response and lack of persistence of high

  16. Milk-derived GM(3) and GD(3) differentially inhibit dendritic cell maturation and effector functionalities.

    PubMed

    Brønnum, H; Seested, T; Hellgren, L I; Brix, S; Frøkiaer, H

    2005-06-01

    Gangliosides are complex glycosphingolipids, which exert immune-modulating effects on various cell types. Ganglioside GD(3) and GM(3) are the predominant gangliosides of human breast milk but during the early phase of lactation, the content of GD(3) decreases while GM(3) increases. The biological value of gangliosides in breast milk has yet to be elucidated but when milk is ingested, dietary gangliosides might conceptually affect immune cells, such as dendritic cells (DCs). In this study, we address the in vitro effect of GD(3) and GM(3) on DC effector functionalities. Treatment of bone marrow-derived DCs with GD(3) before lipopolysaccharide-induced maturation decreased the production of interleukin-6 (IL-6), IL-10, IL-12 and tumor necrosis factor-alpha as well as reduced the alloreactivity in mixed leucocyte reaction (MLR). In contrast, only IL-10 and IL-12 productions were significantly inhibited by GM(3,) and the potency of DCs to activate CD4(+) cells in MLR was unaffected by GM(3). However, both gangliosides suppressed expression of CD40, CD80, CD86 and major histocompatibility complex class II on DCs. Because GD(3) overall inhibits DC functionalities more than GM(3), the immune modulating effect of the ganglioside fraction of breast milk might be more prominent in the commencement of lactation during which the milk contains the most GD(3). PMID:15963050

  17. Synthesis of gangliosides by cultured oligodendrocytes

    SciTech Connect

    Mack, S.R.; Szuchet, S.; Dawson, G.

    1981-01-01

    Gangliosides are enriched in the nervous system compared to other tissues. The synthesis of gangliosides by monolayer cultures of isolated oligodendrocytes has not previously been investigated. Cells were labeled with (3H) galactose at preselected times and gangliosides isolated by phase partition, purified, and identified by chromatography. Cultured oligodendrocytes showed selectivity in their synthesis of gangliosides, which was expressed in the type of ganglioside synthesized as well as in the change of incorporation over time in culture. For the first ten days, there was very little incorporation of (3H) galactose in gangliosides, but this was followed by a stimulation of uptake for GM3, GM1/GD3, and GD1 gangliosides, reaching a maximum after approximately 25-30 days in vitro. There was little incorporation into GM2 or trisialogangliosides throughout the life of the cultures. Since oligodendrocytes synthesize extensive membranes during this period, one may speculate that the de novo-synthesized gangliosides are used for membranes.

  18. Elimination of GD3 synthase improves memory and reduces amyloid-beta plaque load in transgenic mice.

    PubMed

    Bernardo, Alexandra; Harrison, Fiona E; McCord, Meghan; Zhao, Jiali; Bruchey, Aleksandra; Davies, Sean S; Jackson Roberts, L; Mathews, Paul M; Matsuoka, Yasuji; Ariga, Toshio; Yu, Robert K; Thompson, Rebecca; McDonald, Michael P

    2009-11-01

    Gangliosides have been shown to be necessary for beta-amyloid (Abeta) binding and aggregation. GD3 synthase (GD3S) is responsible for biosynthesis of the b- and c-series gangliosides, including two of the four major brain gangliosides. We examined Abeta-ganglioside interactions in neural tissue from mice lacking the gene coding for GD3S (St8sia1), and in a double-transgenic (APP/PSEN1) mouse model of Alzheimer's disease cross-bred with GD3S-/- mice. In primary neurons and astrocytes lacking GD3S, Abeta-induced cell death and Abeta aggregation were inhibited. Like GD3S-/- and APP/PSEN1 double-transgenic mice, APP/PSEN1/GD3S-/- "triple-mutant" mice are indistinguishable from wild-type mice on casual examination. APP/PSEN1 double-transgenics exhibit robust impairments on a number of reference-memory tasks. In contrast, APP/PSEN1/GD3S-/- triple-mutant mice performed as well as wild-type control and GD3S-/- mice. Consistent with the behavioral improvements, both aggregated and unaggregated Abeta and associated neuropathology were almost completely eliminated in triple-mutant mice. These results suggest that GD3 synthase may be a novel therapeutic target to combat the cognitive deficits, amyloid plaque formation, and neurodegeneration that afflict Alzheimer's patients. PMID:18258340

  19. Neogenin, Defined as a GD3-associated Molecule by Enzyme-mediated Activation of Radical Sources, Confers Malignant Properties via Intracytoplasmic Domain in Melanoma Cells.

    PubMed

    Kaneko, Kei; Ohkawa, Yuki; Hashimoto, Noboru; Ohmi, Yuhsuke; Kotani, Norihiro; Honke, Koichi; Ogawa, Mitsutaka; Okajima, Tetsuya; Furukawa, Keiko; Furukawa, Koichi

    2016-08-01

    To investigate mechanisms for increased malignant properties in malignant melanomas by ganglioside GD3, enzyme-mediated activation of radical sources and subsequent mass spectrometry were performed using an anti-GD3 antibody and GD3-positive (GD3+) and GD3-negative (GD3-) melanoma cell lines. Neogenin, defined as a GD3-neighbored molecule, was largely localized in lipid/rafts in GD3+ cells. Silencing of neogenin resulted in the reduction of cell growth and invasion activity. Physical association between GD3 and neogenin was demonstrated by immunoblotting of the immunoprecipitates with anti-neogenin antibody from GD3+ cell lysates. The intracytoplasmic domain of neogenin (Ne-ICD) was detected in GD3+ cells at higher levels than in GD3- cells when cells were treated by a proteasome inhibitor but not when simultaneously treated with a γ-secretase inhibitor. Exogenous GD3 also induced increased Ne-ICD in GD3- cells. Overexpression of Ne-ICD in GD3- cells resulted in the increased cell growth and invasion activity, suggesting that Ne-ICD plays a role as a transcriptional factor to drive malignant properties of melanomas after cleavage with γ-secretase. γ-Secretase was found in lipid/rafts in GD3+ cells. Accordingly, immunocyto-staining revealed that GD3, neogenin, and γ-secretase were co-localized at the leading edge of GD3+ cells. All these results suggested that GD3 recruits γ-secretase to lipid/rafts, allowing efficient cleavage of neogenin. ChIP-sequencing was performed to identify candidates of target genes of Ne-ICD. Some of them actually showed increased expression after expression of Ne-ICD, probably exerting malignant phenotypes of melanomas under GD3 expression. PMID:27288875

  20. 9-O-acetylated sialic acids differentiating normal haematopoietic precursors from leukemic stem cells with high aldehyde dehydrogenase activity in children with acute lymphoblastic leukaemia.

    PubMed

    Chowdhury, Suchandra; Chandra, Sarmila; Mandal, Chitra

    2014-10-01

    Childhood acute lymphoblastic leukaemia (ALL) originates from mutations in haematopoietic progenitor cells (HPCs). For high-risk patients, treated with intensified post-remission chemotherapy, haematopoietic stem cell (HSC) transplantation is considered. Autologous HSC transplantation needs improvisation till date. Previous studies established enhanced disease-associated expression of 9-O-acetylated sialoglycoproteins (Neu5,9Ac2-GPs) on lymphoblasts of these patients at diagnosis, followed by its decrease with clinical remission and reappearance with relapse. Based on this differential expression of Neu5,9Ac2-GPs, identification of a normal HPC population was targeted from patients at diagnosis. This study identifies two distinct haematopoietic progenitor populations from bone marrow of diagnostic ALL patients, exploring the differential expression of Neu5,9Ac2-GPs with stem cell (CD34, CD90, CD117, CD133), haematopoietic (CD45), lineage-commitment (CD38) antigens and cytosolic aldehyde dehydrogenase (ALDH). Normal haematopoietic progenitor cells (ALDH(+)SSC(lo)CD45(hi)Neu5,9Ac2 -GPs(lo)CD34(+)CD38(-)CD90(+)CD117(+)CD133(+)) differentiated into morphologically different, lineage-specific colonies, being crucial for autologous HSC transplantation while leukemic stem cells (ALDH(+)SSC(lo)CD45(lo)Neu5,9Ac2 -GPs(hi)CD34(+)CD38(+)CD90(-)CD117(-)CD133(-)) lacking this ability can be potential targets for minimal residual disease detection and drug-targeted immunotherapy. PMID:25283637

  1. GD3 nuclear localization after apoptosis induction in HUT-78 cells

    SciTech Connect

    Tempera, Italo; Buchetti, Barbara; Lococo, Emanuela; Gradini, Roberto; Mastronardi, Annalisa; Mascellino, Maria Teresa; Sale, Patrizio; Mosca, Luciana; D'Erme, Maria Lenti, Luisa

    2008-04-11

    Glycosphingolipids are essential components of plasma membrane and act as antigens, mediators of cell adhesion, and modulators of signal transduction. Following activation of the Fas receptor, gangliosides are recuited in various intracellular compartments. We have evaluated whether the pro-apoptotic anti-CD95 antibody induces a nuclear localization of GD3 in HUT-78 cells. Our data shows that GD3 translocation from cytosol to nuclei is strongly correlated to concomitant rapid phosphorylation of histone H1 shortly after induction of apoptosis. This work advances the hypothesis that GD3 induces a post-translational modification of histone H1 thus influencing the apoptosis process through transcriptional activation/repression of specific genes.

  2. GD3 nuclear localization after apoptosis induction in HUT-78 cells.

    PubMed

    Tempera, Italo; Buchetti, Barbara; Lococo, Emanuela; Gradini, Roberto; Mastronardi, Annalisa; Mascellino, Maria Teresa; Sale, Patrizio; Mosca, Luciana; d'Erme, Maria; Lenti, Luisa

    2008-04-11

    Glycosphingolipids are essential components of plasma membrane and act as antigens, mediators of cell adhesion, and modulators of signal transduction. Following activation of the Fas receptor, gangliosides are recuited in various intracellular compartments. We have evaluated whether the pro-apoptotic anti-CD95 antibody induces a nuclear localization of GD3 in HUT-78 cells. Our data shows that GD3 translocation from cytosol to nuclei is strongly correlated to concomitant rapid phosphorylation of histone H1 shortly after induction of apoptosis. This work advances the hypothesis that GD3 induces a post-translational modification of histone H1 thus influencing the apoptosis process through transcriptional activation/repression of specific genes. PMID:18261989

  3. Ganglioside Biochemistry

    PubMed Central

    Kolter, Thomas

    2012-01-01

    Gangliosides are sialic acid-containing glycosphingolipids. They occur especially on the cellular surfaces of neuronal cells, where they form a complex pattern, but are also found in many other cell types. The paper provides a general overview on their structures, occurrence, and metabolism. Key functional, biochemical, and pathobiochemical aspects are summarized. PMID:25969757

  4. Gangliosides inhibit the development from monocytes to dendritic cells

    PubMed Central

    WÖLFL, M; BATTEN, W Y; POSOVSZKY, C; BERNHARD, H; BERTHOLD, F

    2002-01-01

    Dendritic cell (DC) development and function is critical in the initiation phase of any antigen-specific immune response against tumours. Impaired function of DC is one explanation as to how tumours escape immunosurveillance. In the presence of various soluble tumour-related factors DC precursors lose their ability to differentiate into mature DC and to activate T cells. Gangliosides are glycosphingolipids shed by tumours of neuroectodermal origin such as melanoma and neuroblastoma. In this investigation we address the question of whether gangliosides suppress the development and function of monocyte-derived DC in vitro. In the presence of gangliosides, the monocytic DC precursors showed increased adherence, cell spreading and a reduced number of dendrites. The expression of MHC class II molecules, co-stimulatory molecules and the GM-CSF receptor (CD116) on the ganglioside-treated DC was significantly reduced. Furthermore, the function of ganglioside-treated DC was impaired as observed in endocytosis, chemotactic and T cell proliferation assays. In contrast to monocytic DC precursors, mature DC were unaffected even when higher doses of gangliosides were added to the culture. With regard to their carbohydrate structure, five different gangliosides (GM2, GM3, GD2, GD3, GT1b), which are typically shed by melanoma and neuroblastoma, were tested for their ability to suppress DC development and function. Suppression was induced by GM2, but not by the other gangliosides. These data suggest that certain gangliosides impair DC precursors, implying a possible mechanism for tumour escape. PMID:12452834

  5. Effect of Dietary Complex Lipids on the Biosynthesis of Piglet Brain Gangliosides.

    PubMed

    Reis, Marlon M; Bermingham, Emma N; Reis, Mariza G; Deb-Choudhury, Santanu; MacGibbon, Alastair; Fong, Bertram; McJarrow, Paul; Bibiloni, Rodrigo; Bassett, Shalome A; Roy, Nicole C

    2016-02-17

    Gangliosides, found in mammalian milk, are known for their roles in brain development of the newborn. However, the mechanism involved in the impact of dietary gangliosides on brain metabolism is not fully understood. The impact of diets containing complex lipids rich in milk-derived ganglioside GD3 on the biosynthesis of gangliosides (assessed from the incorporation of deuterium) in the frontal lobe of a piglet model is reported. Higher levels of incorporation of deuterium was observed in the GM1 and GD1a containing stearic acid in samples from piglets fed milk containing 18.2 μg/mL of GD3 compared to that in those fed milk containing 25 μg/mL of GD3. This could suggest that the gangliosides from the diet may be used as a precursor for de novo biosynthesis of brain gangliosides or lead to the reduction of de novo biosynthesis of these gangliosides. This effect was more pronounced in the left compared to that in the right brain hemisphere. PMID:26808587

  6. Enhancement of the immune response to poorly immunogenic gangliosides after incorporation into very small size proteoliposomes (VSSP).

    PubMed

    Estevez, F; Carr, A; Solorzano, L; Valiente, O; Mesa, C; Barroso, O; Sierra, G V; Fernandez, L E

    1999-08-20

    Certain gangliosides are tumor-associated antigens that constitute potential targets for cancer immunotherapy. A major drawback in the design of ganglioside-based cancer vaccines, however, is the poor immunogenicity of these glycolipids. Here we report the immunological and physicochemical properties of very small size proteoliposomes (VSSP) obtained by using anionic detergents to incorporate gangliosides into the outer membrane protein complex (OMPC) of N. meningitidis. VSSP of three different gangliosides, GM3, NGcGM3 and GD3, were tested. These gangliosides differ in level of expression in normal tissues and in immunogenicity in different animal species. We show that the immunization with VSSP in an oil adjuvant consistently induced both IgM and IgG anti-ganglioside antibodies. In the mouse, the anti-ganglioside IgG fraction was not restricted to the typical T-independent isotype IgG3. Unexpectedly, significant levels of the T-dependent IgG1, IgG2a and particularly IgG2b were also found. VSSP-mediated enhancement of the immunogenicity was not restricted to the relatively immunogenic ganglioside GD3, satisfactory immune responses against highly tolerated GM3 and NGcGM3 were also obtained. Similar results were achieved in chickens and monkeys. No reactogenicity was observed even when self-gangliosides were used for immunization. VSSP overcame natural tolerance to gangliosides in an adjuvant dependent fashion. PMID:10501249

  7. Production of multiple brain-like ganglioside species is dispensable for fas-induced apoptosis of lymphoid cells.

    PubMed

    Popa, Iuliana; Therville, Nicole; Carpentier, Stéphane; Levade, Thierry; Cuvillier, Olivier; Portoukalian, Jacques

    2011-01-01

    Activation of an acid sphingomyelinase (aSMase) leading to a biosynthesis of GD3 disialoganglioside has been associated with Fas-induced apoptosis of lymphoid cells. The present study was undertaken to clarify the role of this enzyme in the generation of gangliosides during apoptosis triggered by Fas ligation. The issue was addressed by using aSMase-deficient and aSMase-corrected cell lines derived from Niemann-Pick disease (NPD) patients. Fas cross-linking elicited a rapid production of large amounts of complex a- and b-series species of gangliosides with a pattern and a chromatographic behavior as single bands reminiscent of brain gangliosides. The gangliosides were synthesized within the first ten minutes and completely disappeared within thirty minutes after stimulation. Noteworthy is the observation that GD3 was not the only ganglioside produced. The production of gangliosides and the onset of apoptotic hallmarks occurred similarly in both aSMase-deficient and aSMase-corrected NPD lymphoid cells, indicating that aSMase activation is not accountable for ganglioside generation. Hampering ganglioside production by inhibiting the key enzyme glucosylceramide synthase did not abrogate the apoptotic process. In addition, GM3 synthase-deficient lymphoid cells underwent Fas-induced apoptosis, suggesting that gangliosides are unlikely to play an indispensable role in transducing Fas-induced apoptosis of lymphoid cells. PMID:21629700

  8. Production of Multiple Brain-Like Ganglioside Species Is Dispensable for Fas-Induced Apoptosis of Lymphoid Cells

    PubMed Central

    Carpentier, Stéphane; Levade, Thierry; Cuvillier, Olivier; Portoukalian, Jacques

    2011-01-01

    Activation of an acid sphingomyelinase (aSMase) leading to a biosynthesis of GD3 disialoganglioside has been associated with Fas-induced apoptosis of lymphoid cells. The present study was undertaken to clarify the role of this enzyme in the generation of gangliosides during apoptosis triggered by Fas ligation. The issue was addressed by using aSMase-deficient and aSMase-corrected cell lines derived from Niemann-Pick disease (NPD) patients. Fas cross-linking elicited a rapid production of large amounts of complex a- and b-series species of gangliosides with a pattern and a chromatographic behavior as single bands reminiscent of brain gangliosides. The gangliosides were synthesized within the first ten minutes and completely disappeared within thirty minutes after stimulation. Noteworthy is the observation that GD3 was not the only ganglioside produced. The production of gangliosides and the onset of apoptotic hallmarks occurred similarly in both aSMase-deficient and aSMase-corrected NPD lymphoid cells, indicating that aSMase activation is not accountable for ganglioside generation. Hampering ganglioside production by inhibiting the key enzyme glucosylceramide synthase did not abrogate the apoptotic process. In addition, GM3 synthase-deficient lymphoid cells underwent Fas-induced apoptosis, suggesting that gangliosides are unlikely to play an indispensable role in transducing Fas-induced apoptosis of lymphoid cells. PMID:21629700

  9. Transfer of Excitation Energy from Pr3+ to Gd3+ in YF3:Pr3+,Gd3+

    NASA Astrophysics Data System (ADS)

    Hirai, Takeshi; Yoshida, Hisashi; Sakuragi, Shiro; Hashimoto, Satoshi; Ohno, Nobuhito

    2007-02-01

    Luminescence and excitation spectra for YF3:Gd3+, YF3:Pr3+, and YF3:Pr3+,Gd3+ have been studied in the vacuum ultraviolet (VUV) spectral region at room temperature. In YF3:Gd3+, Gd3+ ions absorb VUV light ranging from 150 to 200 nm due to 4 f-4 f transitions, yielding an ultraviolet (UV) luminescence line at 311 nm originating from the 4 f-4 f transition (6P7/2→8S7/2 state). In YF3:Pr3+,Gd3+, Pr3+ ions absorb the VUV light (150-200 nm) due to 4 f-5d transitions, and the absorption gives rise to the UV luminescence of Gd3+ ions that is much stronger than that of YF3:Gd3+. In this paper, we discuss the energy transfer process from Pr3+ to Gd3+ ions in YF3:Pr3+,Gd3+ excited by VUV light.

  10. Gangliosides as high affinity receptors for tetanus neurotoxin.

    PubMed

    Chen, Chen; Fu, Zhuji; Kim, Jung-Ja P; Barbieri, Joseph T; Baldwin, Michael R

    2009-09-25

    Tetanus neurotoxin (TeNT) is an exotoxin produced by Clostridium tetani that causes paralytic death to hundreds of thousands of humans annually. TeNT cleaves vesicle-associated membrane protein-2, which inhibits neurotransmitter release in the central nervous system to elicit spastic paralysis, but the molecular basis for TeNT entry into neurons remains unclear. TeNT is a approximately 150-kDa protein that has AB structure-function properties; the A domain is a zinc metalloprotease, and the B domain encodes a translocation domain and C-terminal receptor-binding domain (HCR/T). Earlier studies showed that HCR/T bound gangliosides via two carbohydrate-binding sites, termed the lactose-binding site (the "W" pocket) and the sialic acid-binding site (the "R" pocket). Here we report that TeNT high affinity binding to neurons is mediated solely by gangliosides. Glycan array and solid phase binding analyses identified gangliosides that bound exclusively to either the W pocket or the R pocket of TeNT; GM1a bound to the W pocket, and GD3 bound to the R pocket. Using these gangliosides and mutated forms of HCR/T that lacked one or both carbohydrate-binding pocket, gangliosides binding to both of the W and R pockets were shown to be necessary for high affinity binding to neuronal and non-neuronal cells. The crystal structure of a ternary complex of HCR/T with sugar components of two gangliosides bound to the W and R supported the binding of gangliosides to both carbohydrate pockets. These data show that gangliosides are functional dual receptors for TeNT. PMID:19602728

  11. Increased catabolism and decreased unsaturation of ganglioside in patients with inflammatory bowel disease

    PubMed Central

    Miklavcic, John J; Hart, Tasha DL; Lees, Gordon M; Shoemaker, Glen K; Schnabl, Kareena L; Larsen, Bodil MK; Bathe, Oliver F; Thomson, Alan BR; Mazurak, Vera C; Clandinin, M Tom

    2015-01-01

    AIM: To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease. METHODS: Intestinal mucosa from terminal ileum or colon was obtained from patients with ulcerative colitis or inflammatory Crohn’s disease (n = 11) undergoing bowel resection and compared to control samples of normal intestine from patients with benign colon polyps (n = 6) and colorectal cancer (n = 12) in this observational case-control study. Gangliosides and phospholipids of intestinal mucosa were characterized by class and ceramide or fatty acid composition using liquid chromatography triple-quad mass spectrometry. Content and composition of ganglioside classes GM1, GM3, GD3, GD1a, GT1 and GT3 were compared among subject groups. Content and composition of phospholipid classes phosphatidylcholine (PC) and phosphatidylethanolamine were compared among subject groups. Unsaturation index of individual ganglioside and phospholipid classes was computed and compared among subject groups. Ganglioside catabolism enzymes beta-hexosaminidase A (HEXA) and sialidase-3 (NEU3) were measured in intestinal mucosa using western blot and compared among subject groups. RESULTS: Relative GM3 ganglioside content was 2-fold higher (P < 0.05) in intestine from patients with inflammatory bowel disease (IBD) compared to control intestine. The quantity of GM3 and ratio of GM3/GD3 was also higher in IBD intestine than control tissue (P < 0.05). Control intestine exhibited 3-fold higher (P < 0.01) relative GD1a ganglioside content than IBD intestine. GD3 and GD1a species of ganglioside containing three unsaturated bonds were present in control intestine, but were not detected in IBD intestine. The relative content of PC containing more than two unsaturated bonds was 30% lower in IBD intestine than control intestine (P < 0.05). The relative content of HEXA in IBD intestine was increased 1.7-fold (P < 0.05) and NEU3 was

  12. In vivo modulation of epidermal growth factor receptor phosphorylation in mice expressing different gangliosides.

    PubMed

    Daniotti, Jose L; Crespo, Pilar M; Yamashita, Tadashi

    2006-12-01

    We studied in this work the in vivo phosphorylation of the epidermal growth factor receptor (EGFr) in skin from knockout mice lacking different ganglioside glycosyltransferases. Results show an enhancement of EGFr phosphorylation, after EGF stimulation, in skin from Sial-T2 knockout and Sial-T2/GalNAc-T double knockout mice as compared with wild-type and Sial-T1 knockout mice. Qualitative analysis of ganglioside composition in mice skin suggest that the increase of EGFr phosphorylation observed in skin from Sial-T2 knockout and Sial-T2/GalNAc-T double knockout mice in response to EGF might not be primary attributed to the expression of GD3 or a-series gangliosides in mice skin. These studies provide, for the first time, an approach for studying the molecular mechanisms involved in the in vivo regulation of EGFr function by gangliosides. PMID:16817235

  13. Gd3TCAS2: An Aquated Gd(3+)-Thiacalix[4]arene Sandwich Cluster with Extremely Slow Ligand Substitution Kinetics.

    PubMed

    Iki, Nobuhiko; Boros, Eszter; Nakamura, Mami; Baba, Ryo; Caravan, Peter

    2016-04-18

    In aqueous solution, Gd(3+) and thiacalix[4]arene-p-tetrasulfonate (TCAS) form the complex [Gd3TCAS2](7-), in which a trinuclear Gd(3+) core is sandwiched by two TCAS ligands. Acid-catalyzed dissociation reactions, as well as transmetalation and ligand exchange with physiological concentrations of Zn(2+) and phosphate, showed [Gd3TCAS2](7-) to be extremely inert compared to other Gd complexes. Luminescence lifetime measurements of the Tb analogue Tb3TCAS2 allowed estimation of the mean hydration number q to be 2.4 per Tb ion. The longitudinal relaxivity of [Gd3TCAS2](7-) (per Gd(3+)) was r1 = 5.83 mM(-1) s(-1) at 20 Hz (37 °C, pH 7.4); however, this relaxivity was limited by an extremely slow water exchange rate that was 5 orders of magnitude slower than the Gd(3+) aqua ion. Binding to serum albumin resulted in no relaxivity increase owing to the extremely slow water exchange kinetics. The slow dissociation and water exchange kinetics of [Gd3TCAS2](7-) can be attributed to the very rigid coordination geometry. PMID:27018719

  14. Cell surface molecules of human melanoma. Immunohistochemical analysis of the gp57, GD3, and mel-CSPG antigenic systems.

    PubMed Central

    Garin-Chesa, P.; Beresford, H. R.; Carrato-Mena, A.; Oettgen, H. F.; Old, L. J.; Melamed, M. R.; Rettig, W. J.

    1989-01-01

    The rapidly expanding list of monoclonal antibodies (MAbs) to human cell surface antigens provides reagents to probe the biology of malignant melanoma and to develop new diagnostic and therapeutic approaches to this disease. The criteria used to select MAb-defined antigens as targets for passive immunotherapy or immunolocalization of melanoma include: 1) consistent antigen expression in melanomas, 2) restricted antigen distribution in normal tissues and nonmelanocytic tumors, and 3) cytotoxic activity of the MAb or MAb conjugates. The present study examined the tissue distribution of three prototype melanoma cell surface antigens, the Mr 57,000 glycoprotein (gp57) recognized by MAb A42, the GD3 ganglioside, and the mel-CSPG chondroitin sulfate proteoglycan. The avidin-biotin immunoperoxidase method was used to examine a large panel of normal tissues and over 150 malignant tumors. It was found that A42 has a highly restricted distribution in normal tissues and is expressed in subsets of melanomas and nonmelanocytic tumors. It was also found that GD3 and mel-CSPG are more widely distributed in normal tissues and among tumors than was thought previously. These immunohistochemical patterns provide an essential data base to evaluate the ongoing clinical trials employing MAbs to GD3 and mel-CSPG for the therapy and immunolocalization of melanomas, and they identify gp57 as a potential marker for subsets of normal and transformed melanocytic cells. Images Figure 1 Figure 2 Figure 3 PMID:2916650

  15. Overcoming artificial broadening in Gd(3+)-Gd(3+) distance distributions arising from dipolar pseudo-secular terms in DEER experiments.

    PubMed

    Cohen, Marie Ramirez; Frydman, Veronica; Milko, Petr; Iron, Mark A; Abdelkader, Elwy H; Lee, Michael D; Swarbrick, James D; Raitsimring, Arnold; Otting, Gottfried; Graham, Bim; Feintuch, Akiva; Goldfarb, Daniella

    2016-05-14

    By providing accurate distance measurements between spin labels site-specifically attached to bio-macromolecules, double electron-electron resonance (DEER) spectroscopy provides a unique tool to probe the structural and conformational changes in these molecules. Gd(3+)-tags present an important family of spin-labels for such purposes, as they feature high chemical stability and high sensitivity in high-field DEER measurements. The high sensitivity of the Gd(3+) ion is associated with its high spin (S = 7/2) and small zero field splitting (ZFS), resulting in a narrow spectral width of its central transition at high fields. However, under the conditions of short distances and exceptionally small ZFS, the weak coupling approximation, which is essential for straightforward DEER data analysis, becomes invalid and the pseudo-secular terms of the dipolar Hamiltonian can no longer be ignored. This work further explores the effects of pseudo-secular terms on Gd(3+)-Gd(3+) DEER measurements using a specifically designed ruler molecule; a rigid bis-Gd(3+)-DOTA model compound with an expected Gd(3+)-Gd(3+) distance of 2.35 nm and a very narrow central transition at the W-band (95 GHz). We show that the DEER dipolar modulations are damped under the standard W-band DEER measurement conditions with a frequency separation, Δν, of 100 MHz between the pump and observe pulses. Consequently, the DEER spectrum deviates considerably from the expected Pake pattern. We show that the Pake pattern and the associated dipolar modulations can be restored with the aid of a dual mode cavity by increasing Δν from 100 MHz to 1.09 GHz, allowing for a straightforward measurement of a Gd(3+)-Gd(3+) distance of 2.35 nm. The increase in Δν increases the contribution of the |-5/2〉→|-3/2〉 and |-7/2〉→|-5/2〉 transitions to the signal at the expense of the |-3/2 〉→|-1/2〉 transition, thus minimizing the effect of dipolar pseudo-secular terms and restoring the validity of the weak

  16. The new structure type Gd3Ni7Al14.

    PubMed

    Pukas, Svitlana; Gladyshevskii, Roman

    2015-11-01

    The crystal structure of Gd3Ni7Al14 (trigadolinium heptanickel tetradecaaluminide) belongs to a family of two-layer structures and can be described as an assembly of interpenetrating centred straight prisms. For the Ni atoms, trigonal prisms (Al4Gd2 and Al6) are observed, the Al atoms are inside tetragonal (Ni2Al2Gd4, Ni2Al4Gd2, Al4Gd4, Ni4Al4 and Al8) and pentagonal (Ni4Al6 and Al10) prisms, while the Gd atoms are at the centres of pentagonal (Ni4Al6) and hexagonal (Ni4Al8) prisms. In each case, the true coordination polyhedron is a capped prism, also including atoms from the same layer. The structural features of Gd3Ni7Al14 are similar to those of the intermetallides PrNi2Al3 and ZrNiAl. In all these structures, Ni-centred trigonal prisms form infinite columns via common triangular faces. The columns share prism edges and form a three-dimensional framework with six-membered rings in the (001) plane in the case of the PrNi2Al3 and ZrNiAl types. In the case of Gd3Ni7Al14, six-membered rings are also observed, but only two-thirds of the rings are interconnected via prism edges. PMID:26524174

  17. Expression of gangliosides on glial and neuronal cells in normal and pathological adult human brain.

    PubMed

    Marconi, Silvia; De Toni, Luca; Lovato, Laura; Tedeschi, Elisa; Gaetti, Luigi; Acler, Michele; Bonetti, Bruno

    2005-12-30

    Few studies have assessed the glycolipid phenotype of glial cells in the human central nervous system (CNS) in situ. We investigated by immunohistochemistry the expression and cellular distribution of a panel of gangliosides (GM1, GM2, acetyl-GM3, GD1a, GD1b, GD2, GD3, GT1b, GQ1b and the A2B5 antibody) in adult, human normal and pathological brain, namely multiple sclerosis (MS) and other neurological diseases (OND). In normal conditions, we found diffuse expression in the white matter of most gangliosides tested, with the exception of acetyl-GM3, GT1b and GQ1b. By double immunofluorescence with phenotypic markers, GM1 and GD1b were preferentially expressed on GFAP+ astrocytes, GD1a on NG2+ oligodendrocyte precursors, A2B5 immunostained both populations, while GD2 was selectively present on mature oligodendrocytes. In the gray matter, only GM1, GD2 and A2B5 were present on neuronal cells. Interestingly, those gangliosides present on astrocytes in normal conditions were preferentially expressed on NG2+ cells in chronic MS lesions and in OND. Selective expression of GT1b upon astrocytes and NG2+ cells was instead observed in MS lesions, but not in OND. The definition of the glycolipid phenotype of CNS glial cells may be useful to identify distinct biological glial subsets and provide insights on the potential autoantigenic role of gangliosides in CNS autoimmune diseases. PMID:16313974

  18. New trends in ganglioside chemistry

    SciTech Connect

    Sonnino, S.; Ghidoni, R.; Gazzotti, G.; Acquotti, D.; Tettamanti, G.

    1988-01-01

    New methods have been developed for the preparation of highly purified gangliosides, homogeneous in the saccharide, long chain base, and fatty acid moieties and gangliosides carrying different kinds of labelled probes. Gangliosides, homogeneous in the oligosaccharide portion, were prepared by preparative normal phase HPLC on a Lichrosorb-NH-2 column, using a gradient of acetonitrile-phosphate buffer, pH 5.6, as solvent system. Each class of ganglioside (from monosialo- to tetrasialogangliosides) was then submitted to reversed phase HPLC on a preparative RP-8 column, using acetonitrile-5 mM phosphate buffer, pH 7, as solvent system, to obtain gangliosides homogeneous in the long chain base moiety. Gangliosides containing C18 and C20 sphinganine were prepared by catalytic hydrogenation of the corresponding unsaturated gangliosides. GM1 with homogeneous acyl chain was prepared by alkaline hydrolysis in the presence of tetramethylammonium hydroxide, followed by re-N-acylation, carried out in the presence of dimethylaminopropyl, ethylcarbodiimide and natural fatty acids, or of mixed anhydride of ethylchloroformate and 14C-stearic acid, and re-N-acetylation performed with acetic anhydride or labelled acetic anhydride. The GM1 derivative, de-acetylated at the level of sialic acid, also produced by alkaline treatment of GM1, was submitted to re-N-acetylation with 14C-acetic anhydride to produce specifically 14C-labelled GM1. Re-N-acylation was carried out a) in the presence of dimethylaminopropyl, ethylcarbodiimide and natural fatty acids, b) with mixed anhydride of ethylchloroformate and 14C-stearic acid. After re-N-acylations, re-N-acetylation was performed with acetic anhydride or labelled acetic anhydride. 53 references.

  19. The biosynthesis of brain gangliosides. Separation of membranes with different ratios of ganglioside sialylating activity to gangliosides.

    PubMed Central

    Landa, C A; Maccioni, H J; Arce, A; Caputto, R

    1977-01-01

    Brain subcellular fractions were analysed for ganglioside-sialylating activity by measuring the incorporation of N-[3H]acetylneuraminic acid from CMP-N-[3H]acetylneuraminic acid into endogenous ganglioside acceptors (endogenous incorporation) and into exogenous lactosyceramide (haematoside synthetase activity). The ratios of endogenous incorporation to gangliosides and of haematoside synthetase to gangliosides for the synaptosomal and mitochondrial fractions from a washed crude mitochondrial fraction were lower than those obtained for other membrane fractions. The differences appear to reflect intrinsic characteristics of each membrane fraction. The results of labelling in vitro and the time course of labelling of gangliosides of the different subcellular fractions in vivo after injection of N-[3H]acetylmannosamine are consistent with the possibility of a subcellular site for synthesis of gangliosides different from that of ganglioside deposition. PMID:606237

  20. Ganglioside GD2 in reception and transduction of cell death signal in tumor cells

    PubMed Central

    2014-01-01

    Background Ganglioside GD2 is expressed on plasma membranes of various types of malignant cells. One of the most promising approaches for cancer immunotherapy is the treatment with monoclonal antibodies recognizing tumor-associated markers such as ganglioside GD2. It is considered that major mechanisms of anticancer activity of anti-GD2 antibodies are complement-dependent cytotoxicity and/or antibody-mediated cellular cytotoxicity. At the same time, several studies suggested that anti-GD2 antibodies are capable of direct induction of cell death of number of tumor cell lines, but it has not been investigated in details. In this study we investigated the functional role of ganglioside GD2 in the induction of cell death of multiple tumor cell lines by using GD2-specific monoclonal antibodies. Methods Expression of GD2 on different tumor cell lines was analyzed by flow cytometry using anti-GD2 antibodies. By using HPTLC followed by densitometric analysis we measured the amount of ganglioside GD2 in total ganglioside fractions isolated from tumor cell lines. An MTT assay was performed to assess viability of GD2-positive and -negative tumor cell lines treated with anti-GD2 mAbs. Cross-reactivity of anti-GD2 mAbs with other gangliosides or other surface molecules was investigated by ELISA and flow cytometry. Inhibition of GD2 expression was achieved by using of inhibitor for ganglioside synthesis PDMP and/or siRNA for GM2/GD2 and GD3 synthases. Results Anti-GD2 mAbs effectively induced non-classical cell death that combined features of both apoptosis and necrosis in GD2-positive tumor cells and did not affect GD2-negative tumors. Anti-GD2 mAbs directly induced cell death, which included alteration of mitochondrial membrane potential, induction of apoptotic volume decrease and cell membrane permeability. This cytotoxic effect was mediated exclusively by specific binding of anti-GD2 antibodies with ganglioside GD2 but not with other molecules. Moreover, the level of GD2

  1. Rapid Profiling of Bovine and Human Milk Gangliosides by Matrix-Assisted Laser Desorption/Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

    PubMed Central

    Lee, Hyeyoung; An, Hyun Joo; Lerno, Larry A.; German, J. Bruce; Lebrilla, Carlito B.

    2010-01-01

    Gangliosides are anionic glycosphingolipids widely distributed in vertebrate tissues and fluids. Their structural and quantitative expression patterns depend on phylogeny and are distinct down to the species level. In milk, gangliosides are exclusively associated with the milk fat globule membrane. They may participate in diverse biological processes but more specifically to host-pathogen interactions. However, due to the molecular complexities, the analysis needs extensive sample preparation, chromatographic separation, and even chemical reaction, which makes the process very complex and time-consuming. Here, we describe a rapid profiling method for bovine and human milk gangliosides employing matrix-assisted desorption/ionization (MALDI) Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS). Prior to the analyses of biological samples, milk ganglioside standards GM3 and GD3 fractions were first analyzed in order to validate this method. High mass accuracy and high resolution obtained from MALDI FTICR MS allow for the confident assignment of chain length and degree of unsaturation of the ceramide. For the structural elucidation, tandem mass spectrometry (MS/MS), specifically as collision-induced dissociation (CID) and infrared multiphoton dissociation (IRMPD) were employed. Complex ganglioside mixtures from bovine and human milk were further analyzed with this method. The samples were prepared by two consecutive chloroform/methanol extraction and solid phase extraction. We observed a number of differences between bovine milk and human milk. The common gangliosides in bovine and human milk are NeuAc-NeuAc-Hex-Hex-Cer (GD3) and NeuAc-Hex-Hex-Cer (GM3); whereas, the ion intensities of ganglioside species are different between two milk samples. Kendrick mass defect plot yields grouping of ganglioside peaks according to their structural similarities. Gangliosides were further probed by tandem MS to confirm the compositional and structural assignments

  2. Ganglioside and Non-ganglioside Mediated Host Responses to the Mouse Polyomavirus

    PubMed Central

    Velupillai, Palanivel; Castle, Sherry; Garcea, Robert L.; Benjamin, Thomas

    2015-01-01

    Gangliosides serve as receptors for internalization and infection by members of the polyomavirus family. Specificity is determined by recognition of carbohydrate moieties on the ganglioside by the major viral capsid protein VP1. For the mouse polyomavirus (MuPyV), gangliosides with terminal sialic acids in specific linkages are essential. Although many biochemical and cell culture experiments have implicated gangliosides as MuPyV receptions, the role of gangliosides in the MuPyV-infected mouse has not been investigated. Here we report results of studies using ganglioside-deficient mice and derived cell lines. Knockout mice lacking complex gangliosides were completely resistant to the cytolytic and pathogenic effects of the virus. Embryo fibroblasts from these mice were likewise resistant to infection, and supplementation with specific gangliosides restored infectibility. Although lacking receptors for viral infection, cells from ganglioside-deficient mice retained the ability to respond to the virus. Ganglioside-deficient fibroblasts responded rapidly to virus exposure with a transient induction of c-fos as an early manifestation of a mitogenic response. Additionally, splenocytes from ganglioside-deficient mice responded to MuPyV by secretion of IL-12, previously recognized as a key mediator of the innate immune response. Thus, while gangliosides are essential for infection in the animal, gangliosides are not required for mitogenic responses and innate immune responses to the virus. PMID:26474471

  3. Ganglioside and Non-ganglioside Mediated Host Responses to the Mouse Polyomavirus.

    PubMed

    You, John; O'Hara, Samantha D; Velupillai, Palanivel; Castle, Sherry; Levery, Steven; Garcea, Robert L; Benjamin, Thomas

    2015-10-01

    Gangliosides serve as receptors for internalization and infection by members of the polyomavirus family. Specificity is determined by recognition of carbohydrate moieties on the ganglioside by the major viral capsid protein VP1. For the mouse polyomavirus (MuPyV), gangliosides with terminal sialic acids in specific linkages are essential. Although many biochemical and cell culture experiments have implicated gangliosides as MuPyV receptions, the role of gangliosides in the MuPyV-infected mouse has not been investigated. Here we report results of studies using ganglioside-deficient mice and derived cell lines. Knockout mice lacking complex gangliosides were completely resistant to the cytolytic and pathogenic effects of the virus. Embryo fibroblasts from these mice were likewise resistant to infection, and supplementation with specific gangliosides restored infectibility. Although lacking receptors for viral infection, cells from ganglioside-deficient mice retained the ability to respond to the virus. Ganglioside-deficient fibroblasts responded rapidly to virus exposure with a transient induction of c-fos as an early manifestation of a mitogenic response. Additionally, splenocytes from ganglioside-deficient mice responded to MuPyV by secretion of IL-12, previously recognized as a key mediator of the innate immune response. Thus, while gangliosides are essential for infection in the animal, gangliosides are not required for mitogenic responses and innate immune responses to the virus. PMID:26474471

  4. Activation of human naïve Th cells increases surface expression of GD3 and induces neoexpression of GD2 that colocalize with TCR clusters.

    PubMed

    Villanueva-Cabello, Tania M; Mollicone, Rosella; Cruz-Muñoz, Mario E; López-Guerrero, Delia V; Martínez-Duncker, Iván

    2015-12-01

    CD4+ T helper lymphocytes (Th) orchestrate the immune response after their activation by antigen-presenting cells. Activation of naïve Th cells is reported to generate the reduction in surface epitopes of sialic acid (Sia) in α2,3 and α2,6 linkages. In this work, we report that in spite of this glycophenotype, anti-CD3/anti-CD28-activated purified human naïve Th cells show a significant increase in surface Sia, as assessed by metabolic labeling, compared with resting naïve Th cells, suggesting an increased flux of Sia toward Siaα2,8 glycoconjugates. To understand this increase as a result of ganglioside up-regulation, we observed that very early after activation, human naïve Th cells show an increased expression in surface GD3 and neoexpression of surface GD2 gangliosides, the latter clustering with the T cell receptor (TCR). Also, we report that in contrast to GM2/GD2 synthase null mice, lentiviral vector-mediated silencing of the GM2/GD2 synthase in activated human naïve Th cells reduced efficient TCR clustering and downstream signaling, as assessed by proliferation assays and IL-2 and IL-2R expression, pointing to an important role of this enzyme in activation of human naive Th cells. PMID:26263924

  5. Gangliosides of the Vertebrate Nervous System.

    PubMed

    Schnaar, Ronald L

    2016-08-14

    Gangliosides, sialylated glycosphingolipids, found on all vertebrate cells and tissues, are major molecular determinants on the surfaces of vertebrate nerve cells. Composed of a sialylated glycan attached to a ceramide lipid, the same four structures-GM1, GD1a, GD1b, and GT1b-represent the vast majority (>90%) of gangliosides in the brains of all mammals and birds. Primarily found on the outer surface of the plasma membrane with their glycans facing outward, gangliosides associate laterally with each other, sphingomyelin, cholesterol, and select proteins in lipid rafts-the dynamic functional subdomains of the plasma membrane. The functions of gangliosides in the human nervous system are revealed by congenital mutations in ganglioside biosynthetic genes. Mutations in ST3GAL5, which codes for an enzyme early in brain ganglioside biosynthesis, result in an early-onset seizure disorder with profound motor and cognitive decay, whereas mutations in B4GALNT1, a gene encoding a later step, result in hereditary spastic paraplegia accompanied by intellectual deficits. The molecular functions of brain gangliosides include regulation of receptors in the same membrane via lateral (cis) associations and regulation of cell-cell recognition by trans interaction with ganglioside binding proteins on apposing cells. Gangliosides also affect the aggregation of Aβ (Alzheimer's disease) and α-synuclein (Parkinson's Disease). As analytical, biochemical, and genetic tools advance, research on gangliosides promises to reveal mechanisms of molecular control related to nerve and glial cell differentiation, neuronal excitability, axon outgrowth after nervous system injury, and protein folding in neurodegenerative diseases. PMID:27261254

  6. Unique Ganglioside Recognition Strategies for Clostridial Neurotoxins

    SciTech Connect

    Benson, Marc A.; Fu, Zhuji; Kim, Jung-Ja P.; Baldwin, Michael R.

    2012-03-15

    Botulinum neurotoxins (BoNTs) and tetanus neurotoxin are the causative agents of the paralytic diseases botulism and tetanus, respectively. The potency of the clostridial neurotoxins (CNTs) relies primarily on their highly specific binding to nerve terminals and cleavage of SNARE proteins. Although individual CNTs utilize distinct proteins for entry, they share common ganglioside co-receptors. Here, we report the crystal structure of the BoNT/F receptor-binding domain in complex with the sugar moiety of ganglioside GD1a. GD1a binds in a shallow groove formed by the conserved peptide motif E ... H ... SXWY ... G, with additional stabilizing interactions provided by two arginine residues. Comparative analysis of BoNT/F with other CNTs revealed several differences in the interactions of each toxin with ganglioside. Notably, exchange of BoNT/F His-1241 with the corresponding lysine residue of BoNT/E resulted in increased affinity for GD1a and conferred the ability to bind ganglioside GM1a. Conversely, BoNT/E was not able to bind GM1a, demonstrating a discrete mechanism of ganglioside recognition. These findings provide a structural basis for ganglioside binding among the CNTs and show that individual toxins utilize unique ganglioside recognition strategies.

  7. Ganglioside Regulation of AMPA Receptor Trafficking

    PubMed Central

    Prendergast, Jillian; Umanah, George K.E.; Yoo, Seung-Wan; Lagerlöf, Olof; Motari, Mary G.; Cole, Robert N.; Huganir, Richard L.; Dawson, Ted M.; Dawson, Valina L.

    2014-01-01

    Gangliosides are major cell-surface determinants on all vertebrate neurons. Human congenital disorders of ganglioside biosynthesis invariably result in intellectual disability and are often associated with intractable seizures. To probe the mechanisms of ganglioside functions, affinity-captured ganglioside-binding proteins from rat cerebellar granule neurons were identified by quantitative proteomic mass spectrometry. Of the six proteins that bound selectively to the major brain ganglioside GT1b (GT1b:GM1 > 4; p < 10−4), three regulate neurotransmitter receptor trafficking: Thorase (ATPase family AAA domain-containing protein 1), soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (γ-SNAP), and the transmembrane protein Nicalin. Thorase facilitates endocytosis of GluR2 subunit-containing AMPA-type glutamate receptors (AMPARs) in an ATPase-dependent manner; its deletion in mice results in learning and memory deficits (J. Zhang et al., 2011b). GluR2-containing AMPARs did not bind GT1b, but bound specifically to another ganglioside, GM1. Addition of noncleavable ATP (ATPγS) significantly disrupted ganglioside binding, whereas it enhanced AMPAR association with Thorase, NSF, and Nicalin. Mutant mice lacking GT1b expressed markedly higher brain Thorase, whereas Thorase-null mice expressed higher GT1b. Treatment of cultured hippocampal neurons with sialidase, which cleaves GT1b (and other sialoglycans), resulted in a significant reduction in the size of surface GluR2 puncta. These data support a model in which GM1-bound GluR2-containing AMPARs are functionally segregated from GT1b-bound AMPAR-trafficking complexes. Release of ganglioside binding may enhance GluR2-containing AMPAR association with its trafficking complexes, increasing endocytosis. Disrupting ganglioside biosynthesis may result in reduced synaptic expression of GluR2-contianing AMPARs resulting in intellectual deficits and seizure susceptibility in mice and humans. PMID:25253868

  8. Surface enhanced Raman scattering of amino acids assisted by gold nanoparticles and Gd(3+) ions.

    PubMed

    López-Neira, Juan Pablo; Galicia-Hernández, José Mario; Reyes-Coronado, Alejandro; Pérez, Elías; Castillo-Rivera, Francisco

    2015-05-01

    The surface enhanced raman scattering (SERS) signal from the l-tyrosine (tyr) molecule adsorbed on gold nanoparticles (Au-tyr) is compared with the SERS signal assisted by the presence of gadolinium ions (Gd(3+)) coordinated with the Au-tyr system. An enhancement factor of the SERS signal in the presence of Gd(3+) ions was ∼5 times higher than that produced by l-tyrosine adsorbed on gold nanoparticles. The enhancement of the SERS signal can be attributed to a corresponding increase in the local electric field due to the presence of Gd(3+) ions in the vicinity of a gold dimer configuration. This scenario was confirmed by solving numerically Maxwell equations, showing an increase of 1 order of magnitude in the local electric scattered field when the Gd(3+) ion is located in between a gold dimer compared with naked gold nanoparticles. PMID:25860315

  9. Release of toxic Gd3+ ions to tumour cells by vitamin B12 bioconjugates.

    PubMed

    Siega, Patrizia; Wuerges, Jochen; Arena, Francesca; Gianolio, Eliana; Fedosov, Sergey N; Dreos, Renata; Geremia, Silvano; Aime, Silvio; Randaccio, Lucio

    2009-08-10

    Two probes consisting of vitamin B(12) (CNCbl) conjugated to Gd chelates by esterification of the ribose 5'-OH moiety, Gd-DTPA-CNCbl (1; DTPA = diethylenetriamine-N,N,N',N'',N''-pentaacetic acid) and Gd-TTHA-CNCbl (2; TTHA = triethylenetetramine-N,N,N',N'',N''',N'''-hexaacetic acid), have been synthesised and characterised. The crystal structure of a dimeric form of 1, obtained by crystallisation with an excess of GdCl(3), has been determined. The kinetics of binding to and dissociation from transcobalamin II show that 1 and 2 maintain high-affinity binding to the vitamin B(12) transport protein. Complex 2 is very stable with respect to Gd(3+) release owing to the saturated co-ordination of the Gd(3+) ion by four amino and five carboxylate groups. Hydrolysis of the ester functionality occurs on the time scale of several hours. The lack of saturation and the possible involvement of the ester functionality in co-ordination result in lower stability of 1 towards hydrolysis and in a considerable release of Gd(3+) in vitro. Gd(3+) ions released from 1 are avidly taken up by the K562 tumour cells to an extent corresponding to approximately 10(10) Gd(3+) per cell. The internalisation of toxic Gd(3+) ions causes a marked decrease in cell viability as assessed by Trypan blue and WST-1 tests. On the contrary, the experiments with the more stable 2 did not show any significant cell internalisation of Gd(3+) ions and any influence on cell viability. The results point to new avenues of in situ generation of cytotoxic pathways based on the release of toxic Gd(3+) ions by vitamin B(12) bioconjugates. PMID:19562781

  10. Structural and magnetic properties of Gd3+ ion substituted magnesium ferrite nanopowders

    NASA Astrophysics Data System (ADS)

    Elkady, Ashraf S.; Hussein, Shaban I.; Rashad, Mohamed M.

    2015-07-01

    Nanocrystalline MgGdxFe2-xO4 powders (where x=0, 0.05, 0.1, 0.2, 0.25, 0.3) have been synthesized by the ethylene diamine tetraacetic acid (EDTA)-based sol-gel combustion method. X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, high resolution transmission electron microscopy (HRTEM) and vibrating sample magnetometer (VSM) were applied in order to study the effect of variation of Gd3+ ion substitution and its impact on crystal structure, crystallite size, lattice parameters, nanostructure and magnetic properties of the formed powders. XRD indicated that, after doping and calcination at 400 °C for 2 h, all samples have two spinel ferrite structures namely cubic and tetragonal phases, which are dependent on Gd3+ ion concentration. The cubic phase is found to increase with increasing the Gd3+ ion molar ratio up to 0.1, compared to pure MgFe2O4 and higher Gd3+ content samples. Indeed, with increasing Gd3+ ion, the crystallite size was almost unchanged whereas the lattice parameter was found to increase. FT-IR spectrum showed broadening of the ν2 band and the presence of another band in the range (465-470 cm-1) upon adding Gd3+ ion, which confirm the presence of Gd3+ ion in addition to Fe3+ ion at octahedral site. Besides, these bands were assigned to the formation of (Gd3+-O2-) complexes at B-sites. HRTEM images showed that the studied samples consist of nanocrystallites having average particle sizes around 9 nm for pure MgFe2O4 up to 27 and 42 nm for the Gd3+ ion substituted MgFe2O4 of molar ratio 0.05 and 0.30, respectively. An examination of the magnetic properties revealed an increase in saturation magnetization with increasing Gd concentration incorporation up to x=0.1, as a result of the change of cubic and tetragonal spinel ratio and lattice parameters. Meanwhile, the formed powders exhibited superparamagnetic characteristics. Therefore, such newly synthesized superparamagnetic nanoparticles, containing Gd3+ ion can be considered as a

  11. Physiopathological function of hematoside (GM3 ganglioside)

    PubMed Central

    INOKUCHI, Jin-ichi

    2011-01-01

    Since I was involved in the molecular cloning of GM3 synthase (SAT-I), which is the primary enzyme for the biosynthesis of gangliosides in 1998, my research group has been concentrating on our efforts to explore the physiological and pathological implications of gangliosides especially for GM3. During the course of study, we demonstrated the molecular pathogenesis of type 2 diabetes and insulin resistance focusing on the interaction between insulin receptor and gangliosides in membrane microdomains and propose a new concept: Life style-related diseases, such as type 2 diabetes, are a membrane microdomain disorder caused by aberrant expression of gangliosides. We also encountered an another interesting aspect indicating the indispensable role of gangliosides in auditory system. After careful behavioral examinations of SAT-I knockout mice, their hearing ability was seriously impaired with selective degeneration of the stereocilia of hair cells in the organ of Corti. This is the first observation demonstrating a direct link between gangliosides and hearing functions. PMID:21558756

  12. Monitoring Diabetic Nephropathy by Circulating Gangliosides.

    PubMed

    Ene, Corina Daniela; Penescu, Mircea; Anghel, Amalia; Neagu, Monica; Budu, Vlad; Nicolae, Ilinca

    2016-01-01

    Gangliosides are multifunctional molecules, abundantly expressed in renal cell membrane but also in sera of patients with renal disease. The aim of this study was to quantify the serum levels of sialic acid-ganglioside in patients diagnosed with diabetes for an eventual biomarker stratification of patients with renal complications. We included 35 diabetic patients without metabolic complications, 35 patients with diabetic nephropathy, 35 non-diabetic individuals. We found that sialic acid ganglioside serum level was significantly increased in patients with diabetic nephropathy compared to the level obtained in patients with uncomplicated diabetes and to non-diabetic controls. A statistically significant positive correlation was obtained between serum levels of sialic acid gangliosides, HbA1c, and serum creatinine in patients with diabetes without complications. Moreover positive correlation was found between sialic acid ganglioside and blood glucose, HbA1c, urea, creatinine, microalbuminuria in patients with diabetic nephropathy. We can conclude that serum sialic acid-gangliosides are statistically increased in diabetic nephropathy positively correlated with microalbuminuria. PMID:26359623

  13. Physiopathological function of hematoside (GM3 ganglioside).

    PubMed

    Inokuchi, Jin-ichi

    2011-01-01

    Since I was involved in the molecular cloning of GM3 synthase (SAT-I), which is the primary enzyme for the biosynthesis of gangliosides in 1998, my research group has been concentrating on our efforts to explore the physiological and pathological implications of gangliosides especially for GM3. During the course of study, we demonstrated the molecular pathogenesis of type 2 diabetes and insulin resistance focusing on the interaction between insulin receptor and gangliosides in membrane microdomains and propose a new concept: Life style-related diseases, such as type 2 diabetes, are a membrane microdomain disorder caused by aberrant expression of gangliosides. We also encountered an another interesting aspect indicating the indispensable role of gangliosides in auditory system. After careful behavioral examinations of SAT-I knockout mice, their hearing ability was seriously impaired with selective degeneration of the stereocilia of hair cells in the organ of Corti. This is the first observation demonstrating a direct link between gangliosides and hearing functions. PMID:21558756

  14. Electronic structure and bonding in garnet crystals Gd3Sc2Ga3O12, Gd3Sc2Al3O12, and Gd3Ga3O12 compared to Y3Al3O12

    NASA Astrophysics Data System (ADS)

    Xu, Yong-Nian; Ching, W. Y.; Brickeen, B. K.

    2000-01-01

    The electronic structure and bonding of Gd3Sc2Ga3O12 (GSGG), Gd3Sc2Al3O12 (GSAG), and Gd3Ga5O12 (GGG) crystals with a garnet structure are studied by means of first-principles local-density calculations. The results are compared with a similar calculation on yttrium aluminum garnet [Y3Al5O12 (YAG)]. The calculated equilibrium volumes of the three crystals are close to the measured volumes with a slight overestimation for GGG. GGG also has a smaller bulk modulus than the other three crystals. The calculated density of states and their atomic and orbital decompositions are presented and contrasted. All four crystals show very similar band structures and interatomic bonding. However, it is found that in GSGG and GSAG crystals, the Sc atom at the octahedral site shows a higher covalent character and an increased bond order in comparison to Ga or Al at the same site. This result may provide some insight into the significant difference in the radiation hardness of Cr3+:Nd3+:GSGG as compared to Nd3+:YAG.

  15. The immune response to disialoganglioside GD3 vaccination in normal dogs: a melanoma surface antigen vaccine.

    PubMed

    Milner, R J; Salute, M; Crawford, C; Abbot, J R; Farese, J

    2006-12-15

    As a result of its metastatic potential, canine malignant melanoma like its human counterpart like its human counter part, has a poor response to conventional treatment protocols. This prompted us to investigate the possibility of enhancing the immune response against the melanoma cell surface antigen, disialoganglioside GD3. Initially a flow cytometric study was designed in which the incidence of GD3 on the cell surface, recognized by the monoclonal antibody Mel-1 (R24), was established in canine melanoma cell lines. Results from the flow cytometry found GD3 to be highly expressed (94.2%) in six out of seven canine melanoma cell lines. Since it was thus potentially a good target, a study in which normal dogs were vaccinated intradermally with a vaccine containing GD3 plus adjuvants was designed. The adjuvant included CpG oligodeoxynucleotide (CpG-ODN) sequences and RIBI-adjuvant, which are known to target toll-like receptors (TLR) of the innate immune system. From a cohort of 10 dogs, 4 were vaccinated 3 times, at 4 weekly intervals with GD3 plus adjuvant, and 4 received only RIBI-adjuvant, and 2 phosphate buffered saline. Caliper measurements were collected to assess skin reaction at the vaccination site and sera assayed for IgM and IgG antibodies against GD3 and cell-mediated cytotoxicity against a melanoma cell line. Results from the study found significant differences (P<0.05) in the vaccine site reactions, IgM/IgG levels and cell-mediated cytotoxicity in the vaccinated versus unvaccinated dogs. The addition of CpG-ODN sequences and increasing GD3 concentration in the vaccine increased the inflammation response at the injection site. GD3 IgG and IgM antibodies in vaccinated dogs showed increasing titers over time and achieved significance at weeks 9 and 12, respectively. Cell-mediated cytotoxicity was only detected in peripheral blood mononuclear cells from vaccinated dogs. In conclusion, by combining the tumor antigen GD3 (a known weak self-antigen) and an

  16. Gd3+ vibronic side band spectroscopy. New optical probe of Ca2+ binding sites applied to biological macromolecules.

    PubMed Central

    Iben, I E; Stavola, M; Macgregor, R B; Zhang, X Y; Friedman, J M

    1991-01-01

    A new spectroscopic technique is presented for obtaining infraredlike spectra of the binding sites of Ca2+ and other metals in biological macromolecules. The technique, based on the Ca(2+)-like binding properties of Gd3+, utilizes vibronic side bands (VSB) that appear in Gd3+ fluorescence. In the fluorescence spectrum of Gd3+, the separation in photon frequency between a VSB and its electronic origin at approximately 32,150 cm-1 (approximately 311 nm) is a direct measure of the vibrational frequency of a ligand coordinated to Gd3+ ion. As a consequence, the VSB are uncomplicated by molecular vibrations distant from the Gd3+ binding site. The vibrational spectra resulting from the VSB of Gd3+ coordinated to a Ca2+ binding protein, a phospholipid, and DNA are presented. PMID:1907866

  17. Approaches in the study of ganglioside metabolism

    SciTech Connect

    Tettamanti, G.; Ghidoni, R.; Sonnino, S.; Chigorno, V.; Venerando, B.; Giuliani, A.; Fiorilli, A.

    1984-01-01

    Ganglioside GM1, /sup 3/H-labeled in the sphingosine or terminal galactose moiety was injected into mice and its metabolic fate in the liver was followed. After administration of sphingosine-labeled GM1 all major liver gangliosides (GM3, GM2, GM1, GD1a-NeuAc, NeuG1) became radioactive, the radioactivity residing in all cases on the sphingosine moiety. The specific radioactivity was highest on GM1, followed by GM2, GM3 and GD1a-NeuAc, NeuG1. Several neutral glycosphingolipids and sphingomyelin were also formed. After administration of galactose-labelled GM1 the only radioactive gangliosides present in the liver were GM1 and GD1a-NeuAc, NeuG1, both carrying the radioactivity on the terminal galactose residue, with no formation of labelled neutral glycosphingolipids. Subcellular studies gave clear evidence that GM1, after being taken up by the liver, was mainly degraded to GM2, GM3 and neutral glycosphingolipids at the level of lysosomes. A part of it was sialylated to more complex gangliosides and some of its metabolic by-products were used for the biosynthesis of other sphingolipid species, likely at the level of the Golgi apparatus. All this suggests that exogenous GM1 is introduced in the metabolic routes of endogenous gangliosides and of other sphingolipids, which are operating in the liver.

  18. The gangliosides as a possible molecular coupling factor between the proportion of radiosensitive cells in vitro and the metastatic potential in vivo within a human melanoma cell line.

    PubMed Central

    Thomas, C. P.; Buronfosse, A.; Portoukalian, J.; Fertil, B.

    1997-01-01

    With an experimental model of spontaneous lung metastases in immunosuppressed newborn rats, seven clones and variants with different metastatic potential and gangliosides expression were derived from a single parental human melanoma cell line M4Be. The cellular radiosensitivity of M4Be and its seven sublines was estimated using an in vitro colony assay. The total amount of gangliosides in M4Be and its seven sublines was determined by cell extraction and thin-layer chromatography, while the expression of GD3 gangliosides was estimated by flow cytometry with a monoclonal antibody. The radiation-cell survival curves of most clones and variants derived from M4Be showed a zero dose extrapolation clearly lower than 100%, suggesting that two populations of cells of very different radiosensitivity coexist within each of these clones and variants. Although the proportion of radiosensitive cells could be estimated from the shape of the survival curve, its radiosensitivity is too high to be properly evaluated by the colony assay. The eight survival curves differ essentially in the proportion of radiosensitive cells--which varied from 0% to 40% among M4Be and its seven sublines--whereas the cellular radiosensitivity of the radioresistant population was similar among them. The metastatic potential in vivo of M4Be and its seven sublines was not significantly related to the cellular radiosensitivity of their corresponding radioresistant population, but significantly increased with the fraction of radiosensitive cells. This relationship is valid only when the highly metastatic cells are cultured for no more than five passages in vitro as the fraction of radiosensitive cells is rapidly lost during subcultures. The relationship remains valid in vivo as metastatic melanoma-bearing newborn rats whole body irradiated with 20 cGy show no lung metastasis compared with controls. The radiosensitive cell fraction is inversely correlated with both the total ganglioside content (r = 0.84, P

  19. Gangliosides, or sialic acid, antagonize ethanol intoxication

    SciTech Connect

    Klemm, W.R.; Boyles, R.; Matthew, J.; Cherian, L.

    1988-01-01

    Because ethanol elicits a dose-dependent hydrolysis of brain sialogangliosides, the authors tested the possibility that injected gangliosides might antagonize intoxicating doses of ethanol. Clear anti-intoxication effects were seen at 24 hr post-injection of mixed mouse-brain gangliosides at 125-130 mg/kg, but not at lower or higher doses. Sleep time was reduced on the order of 50%, and roto-rod agility was significantly enhanced. Sialic acid (SA) similarly antagonized ethanol; however, the precursor of SA, N-acetyl-D-mannosamine, as well as ceramide and asialoganglioside did not.

  20. Electron Spin resonance of Gd3+ in three dimensional topological insulator Bi2Se3

    NASA Astrophysics Data System (ADS)

    Garitezi, T. M.; Lesseux, G. G.; Jesus, C. B. R.; Grant, T.; Fisk, Z.; Urbano, R. R.; Rettori, C.; Pagliuso, P. G.

    2015-03-01

    Bi2Se3 has been claimed to be a three dimensional topological insulator (TI) with topologically protected metallic surface states with exotic properties. We have performed electron spin resonance (ESR) measurements on Gd3+ doped (x ≈ 0.01) Bi2Se3 single crystal grown from stoichiometric melt. For the studied crystals, our preliminary results revealed a partly resolved Gd3+ fine structure spectrum with Dysonian (metallic character) lines. At room temperature, the central line has a g ≈ 1.98, a linewidth ΔH ≈ 95 G and the spectra have a overall splitting of roughly 1300 Oe. As the temperature is decreased, the Gd3+ ESR ΔH of the central line presents a very small Korringa-like behavior b = ΔH/ΔT ≈ 0.013 Oe/K and nearly T-independent g-value. However, for T lesssim 40 K, ΔH shows a stronger narrowing effect evolving to Korringa-like behavior (b ≈ 0.15 Oe/K) for T lesssim 30 K. Concomitantly with the change in ΔH behavior, the Gd3+ central line g value starts to decrease reaching a value of 1.976 at T = 4.2 K. The ESR results are discussed in terms of possible effects of protected topological surface states enlightened by complementary data from macroscopic measurements.

  1. Pier GD3, view of top of deck and fender edge, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Pier GD-3, view of top of deck and fender edge, GD-4 beyond, taken from Dry Dock No. 2 Caisson - U.S. Naval Base, Pearl Harbor, Pier & Quay Walls, Entrance to Dry Dock No. 2 & Repair Wharfs, east & west sides of Dry Dock No. 2 & west side of Dry Dock No. 3, Pearl City, Honolulu County, HI

  2. GD4 with GD3 at oblique view on left U.S. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GD-4 with GD-3 at oblique view on left - U.S. Naval Base, Pearl Harbor, Pier & Quay Walls, Entrance to Dry Dock No. 2 & Repair Wharfs, east & west sides of Dry Dock No. 2 & west side of Dry Dock No. 3, Pearl City, Honolulu County, HI

  3. Pier GD3, oblique view taken from Pier GD2, Caisson of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Pier GD-3, oblique view taken from Pier GD-2, Caisson of Dry Dock No. 2 to left - U.S. Naval Base, Pearl Harbor, Pier & Quay Walls, Entrance to Dry Dock No. 2 & Repair Wharfs, east & west sides of Dry Dock No. 2 & west side of Dry Dock No. 3, Pearl City, Honolulu County, HI

  4. Overview of GD2 and GD3 with Caisson of Dry Dock ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Overview of GD-2 and GD-3 with Caisson of Dry Dock No. 2 in center - U.S. Naval Base, Pearl Harbor, Pier & Quay Walls, Entrance to Dry Dock No. 2 & Repair Wharfs, east & west sides of Dry Dock No. 2 & west side of Dry Dock No. 3, Pearl City, Honolulu County, HI

  5. GD2 and GD3 synthase: novel drug targets for cancer therapy

    PubMed Central

    Sphyris, Nathalie; Sarkar, Tapasree Roy; Battula, Venkata L; Andreeff, Michael; Mani, Sendurai A

    2015-01-01

    Our recent study suggests that targeting GD3 synthase (also known as ST8SIA1)—the rate-limiting enzyme in biosynthesis of the breast cancer stem cell marker GD2—abrogates metastasis and depletes the cancer stem cell populations within a tumor, thus providing an effective therapeutic strategy against metastatic breast cancers. PMID:27308452

  6. Mechanistic studies of Gd3+-based MRI contrast agents for Zn2+ detection: towards rational design.

    PubMed

    Bonnet, Célia S; Caillé, Fabien; Pallier, Agnès; Morfin, Jean-François; Petoud, Stéphane; Suzenet, Franck; Tóth, Éva

    2014-08-25

    A series of novel pyridine-based Gd(3+) complexes have been prepared and studied as potential MRI contrast agents for Zn(2+) detection. By independent assessment of molecular parameters affecting relaxivity, we could interpret the relaxivity changes observed upon Zn(2+) binding in terms of variations of the rotational motion. PMID:25116889

  7. Multifunctional Eu3+/Gd3+ dual-doped calcium phosphate vesicle-like nanospheres for sustained drug release and imaging.

    PubMed

    Chen, Feng; Huang, Peng; Zhu, Ying-Jie; Wu, Jin; Cui, Da-Xiang

    2012-09-01

    A facile room-temperature solution method is reported for the preparation of multifunctional Eu(3+) and Gd(3+) dual-doped calcium phosphate (CaP) (Eu(3+)/Gd(3+)-CaP) vesicle-like nanospheres in the presence of an amphiphilic block copolymer polylactide-block-monomethoxy(polyethyleneglycol) (PLA-mPEG). The photoluminescent (PL) and magnetic multifunctions of CaP vesicle-like nanospheres are realized by dual-doping with Eu(3+)/Gd(3+) ions. Under the excitation at 393 nm, Eu(3+)/Gd(3+)-CaP vesicle-like nanospheres exhibit a strong near-infrared (NIR) emission at 700 nm, and the PL intensity can be adjusted by varying Eu(3+) and Gd(3+) concentrations. Furthermore, Eu(3+)/Gd(3+)-CaP vesicle-like nanospheres can be used as the drug nanocarrier and have a high drug loading capacity and ultralong sustained drug release using ibuprofen as a model drug. The drug release from the drug delivery system of Eu(3+)/Gd(3+)-CaP vesicle-like nanospheres can sustain for a very long period of time (more than 80 days). The as-prepared Eu(3+)/Gd(3+)-CaP vesicle-like nanospheres exhibit essentially inappreciable toxicity to the cells in vitro. The noninvasive visualization of nude mice with subcutaneous injection indicates that the Eu(3+)/Gd(3+)-CaP vesicle-like nanospheres are suitable for in vivo bio-imaging. In vivo imaging tests using the subcutaneous injection model of nude mice indicate that Eu(3+)/Gd(3+)-CaP vesicle-like nanospheres can be used as an imaging agent for the NIR luminescence imaging. Thus, the Eu(3+)/Gd(3+)-CaP vesicle-like nanospheres are promising for applications in the biomedical fields such as multifunctional drug delivery systems and tissue engineering scaffolds with bio-imaging guidance. PMID:22721725

  8. Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: linker effects on the relaxivity.

    PubMed

    Ferreira, Miguel F; Gonçalves, Janaina; Mousavi, Bibimaryam; Prata, Maria I M; Rodrigues, Sérgio P J; Calle, Daniel; López-Larrubia, Pilar; Cerdan, Sebastian; Rodrigues, Tiago B; Ferreira, Paula M; Helm, Lothar; Martins, José A; Geraldes, Carlos F G C

    2015-03-01

    The relaxivity displayed by Gd(3+) chelates immobilized onto gold nanoparticles is the result of the complex interplay between the nanoparticle size, the water exchange rate and the chelate structure. In this work we study the effect of the length of ω-thioalkyl linkers, anchoring fast water exchanging Gd(3+) chelates onto gold nanoparticles, on the relaxivity of the immobilized chelates. Gold nanoparticles functionalized with Gd(3+) chelates of mercaptoundecanoyl and lipoyl amide conjugates of the DO3A-N-(α-amino)propionate chelator were prepared and studied as potential CA for MRI. High relaxivities per chelate, of the order of magnitude 28-38 mM(-1) s(-1) (30 MHz, 25 °C), were attained thanks to simultaneous optimization of the rotational correlation time and of the water exchange rate. Fast local rotational motions of the immobilized chelates around connecting linkers (internal flexibility) still limit the attainable relaxivity. The degree of internal flexibility of the immobilized chelates seems not to be correlated with the length of the connecting linkers. Biodistribution and MRI studies in mice suggest that the in vivo behavior of the gold nanoparticles was determined mainly by size. Small nanoparticles (HD = 3.9 nm) undergo fast renal clearance and avoidance of the RES organs while larger nanoparticles (HD = 4.8 nm) undergo predominantly hepatobiliary excretion. High relaxivities, allied to chelate and nanoparticle stability and fast renal clearance in vivo suggest that functionalized gold nanoparticles hold great potential for further investigation as MRI contrast agents. This study contributes to a better understanding of the effect of linker length on the relaxivity of gold nanoparticles functionalized with Gd(3+) complexes. It is a relevant contribution towards "design rules" for nanostructures functionalized with Gd(3+) chelates as Contrast Agents for MRI and multimodal imaging. PMID:25611006

  9. Ganglioside-magnetosome complex formation enhances uptake of gangliosides by cells

    PubMed Central

    Guan, Feng; Li, Xiang; Guo, Jia; Yang, Ganglong; Li, Xiang

    2015-01-01

    Bacterial magnetosomes, because of their nano-scale size, have a large surface-to-volume ratio and are able to carry large quantities of bioactive substances such as enzymes, antibodies, and genes. Gangliosides, a family of sialic acid-containing glycosphingolipids, function as distinctive cell surface markers and as specific determinants in cellular recognition and cell-to-cell communication. Exogenously added gangliosides are often used to study biological functions, transport mechanisms, and metabolism of their endogenous counterparts. Absorption of gangliosides into cells is typically limited by their tendency to aggregate into micelles in aqueous media. We describe here a simple strategy to remove proteins from the magnetosome membrane by sodium dodecyl sulfate treatment, and efficiently immobilize a ganglioside (GM1 or GM3) on the magnetosome by mild ultrasonic treatment. The maximum of 11.7±1.2 µg GM1 and 11.6±1.5 μg GM3 was loaded onto 1 mg magnetosome, respectively. Complexes of ganglioside-magnetosomes stored at 4°C for certain days presented the consistent stability. The use of GM1-magnetosome complex resulted in the greatest enhancement of ganglioside incorporation by cells. GM3-magnetosome complex significantly inhibited EGF-induced phosphorylation of the epidermal growth factor receptor. Both of these effects were further enhanced by the presence of a magnetic field. PMID:26609230

  10. The photoluminescence, drug delivery and imaging properties of multifunctional Eu3+/Gd3+ dual-doped hydroxyapatite nanorods.

    PubMed

    Chen, Feng; Huang, Peng; Zhu, Ying-Jie; Wu, Jin; Zhang, Chun-Lei; Cui, Da-Xiang

    2011-12-01

    The design and synthesis of multifunctional systems with high biocompatibility are very significant for the future of clinical applications. Herein, we report a microwave-assisted rapid synthesis of multifunctional Eu(3+)/Gd(3+) dual-doped hydroxyapatite (HAp) nanorods, and the photoluminescence (PL), drug delivery and in vivo imaging of as-prepared Eu(3+)/Gd(3+) doped HAp nanorods. The photoluminescent and magnetic multifunctions of HAp nanorods are realized by the dual-doping with Eu(3+) and Gd(3+). The PL intensity of doped HAp nanorods can be adjusted by varying Eu(3+) and Gd(3+) concentrations. The magnetization of doped HAp nanorods increases with the concentration of doped Gd(3+). The as-prepared Eu(3+)/Gd(3+)-doped HAp nanorods exhibit inappreciable toxicity to the cells in vitro. More importantly, the Eu(3+)/Gd(3+)-doped HAp nanorods show a high drug adsorption capacity and sustained drug release using ibuprofen as a model drug, and the drug release is governed by a diffusion process. Furthermore, the noninvasive visualization of nude mice with subcutaneous injection indicates that the Eu(3+)/Gd(3+)-doped HAp nanorods with the photoluminescent function are suitable for in vivo imaging. In vitro and in vivo imaging tests indicate that Eu(3+)/Gd(3+)-doped HAp nanorods have a potential in applications such as a multiple-model imaging agent for magnetic resonance (MR) imaging, photoluminescence imaging and computed tomography (CT) imaging. The Eu(3+)/Gd(3+) dual-doped HAp nanorods are promising for applications in the biomedical fields such as multifunctional drug delivery systems with imaging guidance. PMID:21875748

  11. Investigation of UV-emitting Gd(3+) -doped LiCaBO3 phosphor.

    PubMed

    Tamboli, Sumedha; Rajeswari, B; Dhoble, S J

    2016-03-01

    Incorporating the Gd(3+) rare earth ion in the LiCaBO3 host lattice resulted in narrow-band UV-B emission peaking at 315 nm, with excitation at 274 nm. The LiCaBO3 :Gd(3+) phosphor was synthesized via the solid-state diffusion method. The structural, morphological and luminescence properties of this phosphor were characterized by X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM) and photoluminescence (PL) spectroscopy. Electron paramagnetic resonance (EPR) characterization of the as-prepared phosphors is also reported here. XRD studies confirmed the crystal formation and phase purity of the prepared phosphors. A series of different dopant concentrations was synthesized and the concentration-quenching effect was studied. Critical energy transfer distance between activator ions was determined and the mechanism governing the concentration quenching is also reported in this paper. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26278621

  12. Structural and dielectric behavior of Cr3+ and Gd3+ substituted Ni-Zn nano ferrites

    NASA Astrophysics Data System (ADS)

    Anupama M., K.; Jagadeesha Angadi, V.; Matteppanavar, Shidaling; Pattar, Vinayak; Rudraswamy, B.

    2016-05-01

    A series of Gd3+ doped nano crystalline Ni0.6Zn0.4Cr0.5GdxFe1.5-xO4 (where x=0. 00, 0.02, 0.04, 0.06) were prepared by solution combustion method using oxalyl dehydrazide (ODH) as a fuel. The Structural and dielectric behavior of as synthesized material was characterized through X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR). XRD pattern reveals that the formation of single phase with cubic spinel structure. The average crystallite size and lattice parameter were found to increase with increasing Gd3+ concentration. The FTIR spectra shows two strong absorption bands at 387 cm-1 and 564 cm-1 both represents tetrahedral and octahedral stretching bonds respectively. The dielectric properties were carried out as a function of frequency and composition with the frequency range 40Hz to 10MHz. All the samples show the collective contribution of n-type and p-type carriers. The permittivity were found to decrease with increasing of Gd3+ concentration this is due to hopping off electrons and charge transport which is typical characteristic of polar dielectrics. Complex impedance was studied to know the contribution of grains and grain boundary resistance has explained according to the Maxwell Wagener type two layer model.

  13. Impact of Gd3+ doping and glassing solvent deuteration on 13C DNP at 5 Tesla

    NASA Astrophysics Data System (ADS)

    Kiswandhi, Andhika; Lama, Bimala; Niedbalski, Peter; Goderya, Mudrekh; Long, Joanna; Lumata, Lloyd

    Dynamic nuclear polarization (DNP) is a technique which can be used to amplify signals in nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) by several thousand-fold. The most commonly available DNP system typically operates at the W-band field or 3.35 T, at which it has been shown that 13C NMR signal can be enhanced by deuteration and Gd3+ doping. In this work, we have investigated the applicability of these procedures at 5 T. Our results indicate that the deuteration of the glassing matrix still yields an enhancement of 13C DNP when 4-oxo-TEMPO free radical is used. The effect is attributed to the lower heat load of the deuterons compared to protons. An addition of a trace amount of Gd3+ gives a modest enhancement of the signal when trityl OX063 is used, albeit with a less pronounced relative enhancement compared to the results obtained at 3.35 T. The results suggest that the enhancement obtained via Gd3+ doping may become saturated at higher field. These results will be discussed using a thermodynamic model of DNP. This work is supported by US Dept of Defense Award No. W81XWH-14-1-0048 and Robert A. Welch Foundation Grant No. AT-1877.

  14. High-pressure laser spectroscopy of Cr3+:Gd3Sc2Ga3O12 and Cr3+:Gd3Ga5O12

    NASA Astrophysics Data System (ADS)

    Hömmerich, U.; Bray, K. L.

    1995-05-01

    We report on the effect of high pressure on the room-temperature emission spectra and lifetimes of Cr3+:GSGG (Gd3Sc2Ga3O12) and Cr3+:GGG (Gd3Ga5O12). In both systems we observed a dramatic change of the overall emission band shape upon increasing pressure, from a nearly structureless broadband (4T2-->4A2) to a highly structured narrow band (2E-->4A2). From the peak energy of the broadband emission, we estimated the pressure-induced blueshift of the 4T2-->4A2 transition to be 10 (+/-2) cm-1/kbar. High-resolution measurements in the R-line region (~700 nm) revealed that the 2E-->4A2 transition hardly shifts at low pressures (<40 kbar), whereas at higher pressures (>60 kbar) a nearly linear redshift of 0.65 (+/-0.05) cm-1/kbar is observed. Besides pressure-induced spectral changes, an enormous increase in the emission lifetime with increasing pressure was found for both systems. In the case of Cr3+:GSGG, the lifetime changed from 110 μs at ambient pressure to 4.4 ms at 125 kbar. For Cr3+:GGG, the lifetime increased from 168 μs to 7.3 ms for the same pressure range. The pressure-induced spectral and lifetime changes are described by a single configurational coordinate model that considers the effect of pressure on the thermal and spin-orbit coupling of the 2E and 4T2 states. A previously reported pressure-induced R-line-shift reversal in Cr3+:GSGG and the effect of high pressure on the lifetime in Cr3+:YAG are also discussed within the same framework.

  15. Gangliosides trigger inflammatory responses via TLR4 in brain glia.

    PubMed

    Jou, Ilo; Lee, Jee Hoon; Park, Soo Young; Yoon, Hee Jung; Joe, Eun-Hye; Park, Eun Jung

    2006-05-01

    Gangliosides participate in various cellular events of the central nervous system and have been closely implicated in many neuronal diseases. However, the precise molecular mechanisms underlying the pathological activity of gangliosides are poorly understood. Here we report that toll-like receptor 4 (TLR4) may mediate the ganglioside-triggered inflammation in glia, brain resident immune cells. Gangliosides rapidly altered the cell surface expression of TLR4 in microglia and astrocytes within 3 hours. Using TLR4-specific siRNA and a dominant-negative TLR4 gene, we clearly demonstrate the functional importance of TLR4 in ganglioside-triggered activation of glia. Inhibition of TLR4 expression by TLR4-siRNA suppressed nuclear factor (NF)-kappaB-binding activity, NF-kappaB-dependent luciferase activity, and transcription of inflammatory cytokines after exposure to gangliosides. Transient transfection of dominant-negative TLR4 also attenuated NF-kappaB-binding activity and interleukin-6 promoter activity. In contrast, these activities were slightly elevated in cells with wild-type TLR4. In addition, CD14 was required for ganglioside-triggered activation of glia, and lipid raft formation may be associated with ganglioside-stimulated signal propagation. Taken together, these results suggest that TLR4 may provide an explanation for the pathological ability of gangliosides to cause inflammatory conditions in the brain. PMID:16651628

  16. Anchored and soluble gangliosides contribute to myelosupportivity of stromal cells

    SciTech Connect

    Ziulkoski, Ana L.; Santos, Aline X.S. dos; Andrade, Claudia M.B.; Trindade, Vera M.T.; Daniotti, Jose Luis; Borojevic, Radovan; Guma, Fatima C.R.

    2009-10-09

    Stroma-mediated myelopoiesis depends upon growth factors and an appropriate intercellular microenvironment. Previous studies have demonstrated that gangliosides, produced by hepatic stromal cell types, are required for optimal myelosupportive function. Here, we compared the mielossuportive functions of a bone marrow stroma (S17) and skin fibroblasts (SF) regarding their ganglioside pattern of synthesis and shedding. The survival and proliferation of a myeloid precursor cell (FDC-P1) were used as reporter. Although the ganglioside synthesis of the two stromal cells was similar, their relative content and shedding were distinct. The ganglioside requirement for mielossuportive function was confirmed by the decreased proliferation of FDC-P1 cells in ganglioside synthesis-inhibited cultures and in presence of an antibody to GM3 ganglioside. The distinct mielossuportive activities of the S17 and SF stromata may be related to differences on plasma membrane ganglioside concentrations or to differences on the gangliosides shed and their subsequent uptake by myeloid cells, specially, GM3 ganglioside.

  17. Brain gangliosides in the presenile dementia of Pick.

    PubMed Central

    Kamp, P E; den Hartog Jager, W A; Maathuis, J; de Groot, P A; de Jong, J M; Bolhuis, P A

    1986-01-01

    Histochemical analysis of frontal and temporal lobes from four patients with Pick presenile dementia indicated intracellular and extracellular deposits of gangliosides. Thin layer chromatography of gangliosides disclosed the presence of an unknown ganglioside, a decrease of N-acetylgalactosamine-GDla and an increase of GTla and/or GD2 in white matter of Pick brain. Chromatography of gray matter and quantitation of the sialic acid content yielded results similar to controls. It is suggested that degradation and removal of gangliosides is incomplete in Pick disease. Images PMID:3746324

  18. Tuning the selectivity of Gd3N cluster endohedral metallofullerene reactions with Lewis acids.

    PubMed

    Stevenson, Steven; Rottinger, Khristina A; Fahim, Muska; Field, Jessica S; Martin, Benjamin R; Arvola, Kristine D

    2014-12-15

    We demonstrate the manipulation of the Lewis acid strength to selectively fractionate different types of Gd3N metallofullerenes that are present in complex mixtures. Carbon disulfide is used for all Lewis acid studies. CaCl2 exhibits the lowest reactivity but the highest selectivity by precipitating only those gadolinium metallofullerenes with the lowest first oxidation potentials. ZnCl2 selectively complexes Gd3N@C88 during the first 4 h of reaction. Reaction with ZnCl2 for an additional 7 days permits a selective precipitation of Gd3N@C84 as the dominant endohedral isolated. A third fraction is the filtrate, which possesses Gd3N@C86 and Gd3N@C80 as the two dominant metallofullerenes. The order of increasing reactivity and decreasing selectivity (left to right) is as follows: CaCl2 < ZnCl2 < NiCl2 < MgCl2 < MnCl2 < CuCl2 < WCl4 ≪ WCl6 < ZrCl4 < AlCl3 < FeCl3. As a group, CaCl2, ZnCl2, and NiCl2 are the weakest Lewis acids and have the highest selectivity because of their very low precipitation onsets, which are below +0.19 V (i.e., endohedrals with first oxidation potentials below +0.19 V are precipitated). For CaCl2, the precipitation threshold is estimated at a remarkably low value of +0.06 V. Because most endohedrals possess first oxidation potentials significantly higher than +0.06 V, CaCl2 is especially useful in its ability to precipitate only a select group of gadolinium metallofullerenes. The Lewis acids of intermediate reactivity (i.e., precipitation onsets estimated between +0.19 and +0.4 V) are MgCl2, MnCl2, CuCl2, and WCl4. The strongest Lewis acids (WCl6, ZrCl4, AlCl3, and FeCl3) are the least selective and tend to precipitate the entire family of gadolinium metallofullerenes. Tuning the Lewis acid for a specific type of endohedral should be useful in a nonchromatographic purification method. The ability to control which metallofullerenes are permitted to precipitate and which endohedrals would remain in solution is a key outcome of this work. PMID

  19. The Role of Gangliosides in Neurodevelopment

    PubMed Central

    Palmano, Kate; Rowan, Angela; Guillermo, Rozey; Guan, Jian; Mc Jarrow, Paul

    2015-01-01

    Gangliosides are important components of neuronal cell membranes and it is widely accepted that they play a critical role in neuronal and brain development. They are functionally involved in neurotransmission and are thought to support the formation and stabilization of functional synapses and neural circuits required as the structural basis of memory and learning. Available evidence, as reviewed herein, suggests that dietary gangliosides may impact positively on cognitive functions, particularly in the early postnatal period when the brain is still growing. Further, new evidence suggests that the mechanism of action may be through an effect on the neuroplasticity of the brain, mediated through enhanced synaptic plasticity in the hippocampus and nigro-striatal dopaminergic pathway. PMID:26007338

  20. Structural aspects of ganglioside-containing membranes.

    PubMed

    Cantu', Laura; Corti, Mario; Brocca, Paola; Del Favero, Elena

    2009-01-01

    The demand for understanding the physical role of gangliosides in membranes is pressing, due to the high number of diverse and crucial biological functions in which they are involved, needing a unifying thread. To this purpose, model systems including gangliosides have been subject of extensive structural studies. Although showing different levels of complication, all models share the need for simplicity, in order to allow for physico-chemical clarity, so they keep far from the extreme complexity of the true biological systems. Nonetheless, as widely agreed, they provide a basic hint on the structural contribution specific molecules can pay to the complex aggregate. This topic we address in the present review. Gangliosides are likely to play their physical role through metamorphism, cooperativity and demixing, that is, they tend to segregate and identify regions where they can dictate and modulate the geometry and the topology of the structure, and its mechanical properties. Strong three-dimensional organisation and cooperativity are exploited to scale up the local arrangement hierarchically from the nano- to the mesoscale, influencing the overall morphology of the structure. PMID:19063860

  1. Investigation of Gd3N@C2n (40 n 44) family by Raman and inelastic electron tunneling spectroscopy

    SciTech Connect

    Burke, Brian; Chan, Jack; Williams, Keith A; Ge, Jiechao; Shu, Chunying; Fu, Wujun; Dorn, Harry C; Kushmerick, James G; Puretzky, Alexander A; Geohegan, David B

    2010-01-01

    The structure and vibrational spectrum of Gd3N@C80 is studied through Raman and inelastic electron tunneling spectroscopy as well as density-functional theory and universal force eld calculations. Hindered rotations, shown by both theory and experiment, indicate the formation of a Gd3N-C80 bond which reduces the ideal icosahedral symmetry of the C80 cage. The vibrational modes involving the movement of the encapsulated species are a ngerprint of the interaction between the fullerene cage and the core complex. We present Raman data for the Gd3N@C2n 40 n 44 family as well as Y3N@C80, Lu3N@C80, and Y3N@C88 for comparison. Conductance measurements have been performed on Gd3N@C80 and reveal a Kondo effect similar to that observed in C60.

  2. Gd(3+) Spin Labels Report the Conformation and Solvent Accessibility of Solution and Vesicle-Bound Melittin.

    PubMed

    Manukovsky, Nurit; Frydman, Veronica; Goldfarb, Daniella

    2015-10-29

    Although Gd(3+)-based spin labels have been shown to be an alternative to nitroxides for double electron-electron resonance (DEER) distance measurements at high fields, their ability to provide solvent accessibility information, as nitroxides do, has not been explored. In addition, the effect of the label type on the measured distance distribution has not been sufficiently characterized. In this work, we extended the applicability of Gd(3+) spin labels to solvent accessibility measurements on a peptide in model membranes, namely, large unilamellar vesicles (LUVs) using W-band (2)H Mims electron-nuclear double resonance (ENDOR) and electron spin echo envelope modulation (ESEEM) techniques and Gd(3+)-ADO3A-labeled melittin. In addition, we carried out Gd(3+)-Gd(3+) DEER distance measurements to probe the peptide conformation in solution and when bound to LUVs. A comparison with earlier results reported for the same system with nitroxide labels shows that, although in both cases the peptide binds parallel to the membrane surface, the Gd(3+)-ADO3A label tends to protrude from the membrane into the solvent, whereas the nitroxide does the opposite. This can be explained on the basis of the hydrophilicity of the Gd(3+)-ADO3A labels in contrast with the hydrophobicity of nitroxides. The distance distributions obtained from different labels are accordingly different, with the Gd(3+)-ADO3A yielding consistently broader distributions. These discrepancies are most pronounced when the peptide termini are labeled, which implies that such labeling positions may be inadvisible. PMID:26001213

  3. Photoluminescence properties of MgY4Si3O13:Gd3+, Tb3+ under vacuum ultraviolet excitation

    NASA Astrophysics Data System (ADS)

    Zhao, Wenyu; An, Shengli; Fan, Bin; Li, Songbo

    2013-07-01

    Gd3+ and Tb3+ co-doped MgY4Si3O13 green phosphors were prepared by a solid-state reaction. The photoluminescence properties in vacuum ultraviolet-visible (VUV-vis) range and decay properties were investigated in details. The f-d transition of Gd3+ ions and spin-allowed f-d transition of Tb3+ ions locate at about 134 nm and 239 nm, respectively. Two charge transfer bands of O2- → Gd3+ and O2- → Tb3+ overlap at about 155 nm. Some f-f transition of Tb3+ and Gd3+ ions are confirmed in VUV-vis range. Upon excitation at 172 nm, the optimal composition of MgY3.3Si3O13:0.5Gd3+, 0.2Tb3+ phosphor exhibits the characteristic transitions of Gd3+ and Tb3+ with chromaticity coordinate of (0.2849, 0.5843). The phosphor has a shorter decay time (2.13 ms) than that of Zn2SiO4:Mn2+ (4.56 ms). The results suggest that this green phosphor is a potential candidate for mercury-free luminescence lamps and plasma display panels (PDPs) application.

  4. Zero field splitting fluctuations induced phase relaxation of Gd3+ in frozen solutions at cryogenic temperatures

    NASA Astrophysics Data System (ADS)

    Raitsimring, A.; Dalaloyan, A.; Collauto, A.; Feintuch, A.; Meade, T.; Goldfarb, D.

    2014-11-01

    Distance measurements using double electron-electron resonance (DEER) and Gd3+ chelates for spin labels (GdSL) have been shown to be an attractive alternative to nitroxide spin labels at W-band (95 GHz). The maximal distance that can be accessed by DEER measurements and the sensitivity of such measurements strongly depends on the phase relaxation of Gd3+ chelates in frozen, glassy solutions. In this work, we explore the phase relaxation of Gd3+-DOTA as a representative of GdSL in temperature and concentration ranges typically used for W-band DEER measurements. We observed that in addition to the usual mechanisms of phase relaxation known for nitroxide based spin labels, GdSL are subjected to an additional phase relaxation mechanism that features an increase in the relaxation rate from the center to the periphery of the EPR spectrum. Since the EPR spectrum of GdSL is the sum of subspectra of the individual EPR transitions, we attribute this field dependence to transition dependent phase relaxation. Using simulations of the EPR spectra and its decomposition into the individual transition subspectra, we isolated the phase relaxation of each transition and found that its rate increases with |ms|. We suggest that this mechanism is due to transient zero field splitting (tZFS), where its magnitude and correlation time are scaled down and distributed as compared with similar situations in liquids. This tZFS induced phase relaxation mechanism becomes dominant (or at least significant) when all other well-known phase relaxation mechanisms, such as spectral diffusion caused by nuclear spin diffusion, instantaneous and electron spin spectral diffusion, are significantly suppressed by matrix deuteration and low concentration, and when the temperature is sufficiently low to disable spin lattice interaction as a source of phase relaxation.

  5. Gangliosides in the Nervous System: Biosynthesis and Degradation

    NASA Astrophysics Data System (ADS)

    Yu, Robert K.; Ariga, Toshio; Yanagisawa, Makoto; Zeng, Guichao

    Gangliosides, abundant in the nervous system, are known to play crucial modulatory roles in cellular recognition, interaction, adhesion, and signal transduction, particularly during early developmental stages. The expression of gangliosides in the nervous system is developmentally regulated and is closely related to the differentiation state of the cell. Ganglioside biosynthesis occurs in intracellular organelles, from which gangliosides are transported to the plasma membrane. During brain development, the ganglioside composition of the nervous system undergoes remarkable changes and is strictly regulated by the activities of glycosyltransferases, which can occur at different levels of control, including glycosyltransferase gene transcription and posttranslational modification. Genes for glycosyltransferase involved in ganglioside biosynthesis have been cloned and classified into families of glycosyltransferases based on their amino acid sequence similarities. The donor and acceptor substrate specificities are determined by enzymatic analysis of the glycosyltransferase gene products. Cell-type specific regulation of these genes has also been studied. Gangliosides are degraded by lysosomal exoglycosidases. The action of these enzymes occurs frequently in cooperation with activator proteins. Several human diseases are caused by defects of degradative enzymes, resulting in massive accumulation of certain glycolipids, including gangliosides in the lysosomal compartment and other organelles in the brain and visceral organs. Some of the representative lysosomal storage diseases (LSDs) caused by the accumulation of lipids in late endosomes and lysosomes will be discussed.

  6. Autoantibodies against ganglioside GM3 are associated with narcolepsy-cataplexy developing after Pandemrix vaccination against 2009 pandemic H1N1 type influenza virus.

    PubMed

    Saariaho, Anna-Helena; Vuorela, Arja; Freitag, Tobias L; Pizza, Fabio; Plazzi, Giuseppe; Partinen, Markku; Vaarala, Outi; Meri, Seppo

    2015-09-01

    Following the mass vaccinations against pandemic influenza A/H1N1 virus in 2009, a sudden increase in juvenile onset narcolepsy with cataplexy (NC) was detected in several European countries where AS03-adjuvanted Pandemrix vaccine had been used. NC is a chronic neurological disorder characterized by excessive daytime sleepiness and cataplexy. In human NC, the hypocretin-producing neurons in the hypothalamus or the hypocretin signaling pathway are destroyed by an autoimmune reaction. Both genetic (e.g. HLA-DQB1*0602) and environmental risk factors (e.g. Pandemrix) contribute to the disease development, but the underlying and the mediating immunological mechanisms are largely unknown. Influenza virus hemagglutinin is known to bind gangliosides, which serve as host cell virus receptors. Anti-ganglioside antibodies have previously been linked to various neurological disorders, like the Guillain-Barré syndrome which may develop after infection or vaccination. Because of these links we screened sera of NC patients and controls for IgG anti-ganglioside antibodies against 11 human brain gangliosides (GM1, GM2, GM3, GM4, GD1a, GD1b, GD2, GD3, GT1a, GT1b, GQ1b) and a sulfatide by using a line blot assay. Samples from 173 children and adolescents were analyzed: 48 with Pandemrix-associated NC, 20 with NC without Pandemrix association, 57 Pandemrix-vaccinated and 48 unvaccinated healthy children. We found that patients with Pandemrix-associated NC had more frequently (14.6%) anti-GM3 antibodies than vaccinated healthy controls (3.5%) (P = 0.047). Anti-GM3 antibodies were significantly associated with HLA-DQB1*0602 (P = 0.016) both in vaccinated NC patients and controls. In general, anti-ganglioside antibodies were more frequent in vaccinated (18.1%) than in unvaccinated (7.3%) individuals (P = 0.035). Our data suggest that autoimmunity against GM3 is a feature of Pandemrix-associated NC and that autoantibodies against gangliosides were induced by Pandemrix vaccination. PMID

  7. Energy transfer between Ce(3+)  → Gd(3+) or Tb(3+) in KNaSO4 microphosphor.

    PubMed

    Manik, Urvashi; Gedam, S C; Dhoble, S J

    2016-05-01

    KNaSO4 microphosphor doped with Ce,Gd and Ce,Tb and prepared by a wet chemical method was studied using X-ray diffraction (XRD), scanning electron microscopy (SEM) and photoluminescence (PL) characterization. KNaSO4 has a 5-µm particle size detected by SEM. KNaSO4 :Ce(3+) ,Tb(3+) showed blue and green emission (at 494 nm, 557 nm, 590 nm) of Tb(3+) due to (5) D4  → (7) FJ (J = 4, 5, 6) transitions. KNaSO4 :Ce(3+) ,Gd(3+) showed luminescence in the ultraviolet (UV) light region at 314 nm for an excitation at 271 nm wavelength. It was observed that efficient energy transfer took place from Ce(3+)  → Gd(3+) and Ce(3+)  → Tb(3+) sublattices indicating that Ce(3+) could effectively sensitize Gd(3+) or Tb(3+) (green emission). Ce(3+) emission weakened and Gd(3+) or Tb(3+) enhanced the emission significantly in KNaSO4 . This paper discusses the development and understanding of photoluminescence and the effect of Tb(3+) and Gd(3+) on KNaSO4 :Ce(3+) . Copyright © 2015 John Wiley & Sons, Ltd. PMID:26044916

  8. Inhibition of hemopoiesis in vitro by neuroblastoma-derived gangliosides.

    PubMed

    Sietsma, H; Nijhof, W; Dontje, B; Vellenga, E; Kamps, W A; Kok, J W

    1998-11-01

    Hemopoiesis is disturbed in bone marrow-involving cancers like leukemia and neuroblastoma. Shedding of gangliosides by tumor cells may contribute to this tumor-induced bone marrow suppression. We studied in vitro the inhibitory effects of murine neuroblastoma cells (Neuro-2a and C1300) and their gangliosides on hemopoiesis using normal murine hemopoietic progenitor colony-forming assays. Transwell cultured neuroblastoma cells showed a dose-dependent inhibition on hemopoiesis, indicating that a soluble factor was responsible for this effect. Furthermore, the supernatant of Neuro-2a cultured cells inhibited hemopoietic proliferation and differentiation. To determine whether the inhibitory effect was indeed due to shed gangliosides and not, for instance, caused by cytokines, the effect of DL-threo-1 -phenyl-2-decanoylamino-3-morpholino-1-propanol (DL-PDMP) on Neuro-2a cells was studied. DL-PDMP is a potent inhibitor of glucosylceramide synthase, resulting in inhibition of the synthesis and shedding of gangliosides. The initially observed inhibitory effect of supernatant of Neuro-2a cells was abrogated by culturing these cells for 3 days in the presence of 10 microM DL-PDMP. Moreover, gangliosides isolated from Neuro-2a cell membranes inhibited hemopoietic growth. To determine whether the described phenomena in vitro are a reflection of bone marrow suppression occurring in vivo, gangliosides isolated from plasma of neuroblastoma patients were tested for their effects on human hemopoietic progenitor colony-forming assays. These human neuroblastoma-derived gangliosides inhibited normal erythropoiesis (colony-forming unit-erythroid/burst-forming unit-erythroid) and myelopoiesis (colony-forming unit-granulocyte/macrophage) to a higher extent compared with gangliosides isolated from control plasma. Altogether these results suggest that gangliosides shed by neuroblastoma cells inhibit hemopoiesis and may contribute to the observed bone marrow depression in neuroblastoma

  9. The physical properties of Gd3Ru: A real candidate for a practical cryogenic refrigerator

    NASA Astrophysics Data System (ADS)

    Monteiro, J. C. B.; dos Reis, R. D.; Gandra, F. G.

    2015-05-01

    The magnetization, the specific heat, and the magnetocaloric effect (MCE) for Gd3Ru are presented as function of temperature at different magnetic fields. The results show a maximum entropy change - Δ S = 30 J/kg K @ 5 T, which is the highest value for the R3M compounds. With a non-hysteretic transition of first order type at TC = 54 K, it presents a temperature change ΔTmax = 5.7 K around 59 K with a refrigerating cooling power of 700 J/kg and these results are comparable to values found for giant MCE materials. This compound is stable and able to operate at temperatures between 90 K and 40 K with a minimum - Δ S = 5 J/kg K. These figures were obtained by sweeping the magnetic field without using sample preparation routines. This methodology is appropriate to evaluate the MCE for the cycling process of a cryogenic magnetic refrigerator.

  10. Scintillation properties of Gd3Al2Ga3O12:Ce3+ single crystal scintillators

    NASA Astrophysics Data System (ADS)

    Sakthong, Ongsa; Chewpraditkul, Weerapong; Wanarak, Chalerm; Kamada, Kei; Yoshikawa, Akira; Prusa, Petr; Nikl, Martin

    2014-07-01

    The scintillation properties of Gd3Al2Ga3O12:Ce3+ (GAGG:Ce) single crystals grown by the Czochralski method with 1 at% cerium in the melt were investigated and results were compared with so far published results in the literature. The light yield (LY) and energy resolution were measured using a XP5200B photomultiplier. Despite about twice higher LY for GAGG:Ce, the energy resolution is only slightly better than that of LuAG:Ce due to its worse intrinsic resolution and non-proportionality of LY. The LY dependences on the sample thickness and amplifier shaping time were measured. The estimated photofraction in pulse height spectra of 320 and 662 keV γ-rays and the total mass attenuation coefficient at 662 keV γ-rays were also determined and compared with the theoretical ones calculated using the WinXCom program.

  11. Enhanced relaxivity of Gd3+-based contrast agents geometrically confined within porous nanoconstructs

    PubMed Central

    Sethi, Richa; Ananta, Jeyarama S.; Karmonik, Christof; Zhong, Meng; Fung, Steve H.; Liu, Xuewu; Li, King; Ferrari, Mauro; Wilson, Lon J.; Decuzzi, Paolo

    2013-01-01

    Gadolinium chelates, which are currently approved for clinical MRI use, provide relaxivities well below their theoretical limit, and they also lack tissue specificity. Recently, the geometrical confinement of Gd3+-based contrast agents (CAs) within porous structures has been proposed as a novel, alternative strategy to improve relaxivity without chemical modification of the CA. Here, we have characterized and optimized the performance of MRI nanoconstructs obtained by loading [Gd(DTPA)(H2O)]2− (Magnevist®) into the pores of injectable mesoporous silicon particles. Nanoconstructs with three different pore sizes were studied, and at 60 MHz, they exhibited longitudinal relaxivities of ~ 24 mM−1s−1 for 5 – 10 nm pores and ~ 10 mM−1s−1 for 30 – 40 nm pores. No enhancement in relaxivity was observed for larger pores sizes. Using an outer-sphere compound, [GdTTHA]−3, and mathematical modeling, it was demonstrated that the relaxivity enhancement is due to the increase in rotational correlation times (CA adsorbed on the pore walls) and diffusion correlation times (reduced mobility of the water molecules), as the pore sizes decreases. It was also observed that extensive CA adsorption on the outer surface of the silicon particles negates the advantages offered by nanoscale confinement. Upon incubation with HeLa cells, the nanoconstructs did not demonstrate significant cytotoxicity for up to 3 days post incubation, at different particle/cell ratios. In addition, the nanoconstructs showed complete degradation after 24h of continuous agitation in PBS. These data support and confirm the hypothesis that the geometrical confinement of Gd3+-chelate compounds into porous structures offers MRI nanoconstructs with enhanced relaxivity (up to 6 times for [Gd(DTPA)(H2O)]2−, and 4 times for [GdTTHA]−3) and, potentially, improved stability, reduced toxicity and tissue specificity. PMID:22991316

  12. GM1 Ganglioside: Past Studies and Future Potential.

    PubMed

    Aureli, Massimo; Mauri, Laura; Ciampa, Maria Grazia; Prinetti, Alessandro; Toffano, Gino; Secchieri, Cynthia; Sonnino, Sandro

    2016-04-01

    Gangliosides (sialic acid-containing glycosphingolipids) are abundant in neurons of all animal species and play important roles in many cell physiological processes, including differentiation, memory control, cell signaling, neuronal protection, neuronal recovery, and apoptosis. Gangliosides also function as anchors or entry points for various toxins, bacteria, viruses, and autoantibodies. GM1, a ganglioside component of mammalian brains, is present mainly in neurons. GM1 is one of the best studied gangliosides, and our understanding of its properties is extensive. Simple and rapid procedures are available for preparation of GM1 as a natural compound on a large scale, or as a derivative containing an isotopic radionuclide or a specific probe. Great research interest in the properties of GM1 arose from the discovery in the early 1970s of its role as receptor for the bacterial toxin responsible for cholera pathogenesis. PMID:25762012

  13. GM1 ganglioside and Alzheimer's disease.

    PubMed

    Yanagisawa, Katsuhiko

    2015-05-01

    Assembly and deposition of amyloid ß-protein (Aß) is an invariable and fundamental event in the pathological process of Alzheimer's disease (AD). To decipher the AD pathogenesis and also to develop disease-modifying drugs for AD, clarification of the molecular mechanism underlying the Aß assembly into amyloid fibrils in the brain has been a crucial issue. GM1-ganglioside-bound Aß (GAß), with unique molecular characteristics such as having an altered conformation and the capability to accelerate Aß assembly, was discovered in an autopsied brain showing early pathological changes of AD in 1995. On the basis of these findings, it was hypothesized that GAß is an endogenous seed for amyloid fibril formation in the AD brain. A body of evidence that supports this GAß hypothesis has been growing over this past 20 years. In this article, seminal GAß studies that have been carried out to date, including recent ones using unique animal models, are reviewed. PMID:25903682

  14. Biosynthesis and transport of gangliosides in peripheral nerve

    SciTech Connect

    Yates, A.J.; Tipnis, U.R.; Hofteig, J.H.; Warner, J.K.

    1984-01-01

    Radiolabelled glucosamine was injected into L-7 dorsal root ganglion (DRG) of rabbits. At several different times after injection DRG, lumbosacral trunks (LST) and sciatic nerves (SN) were removed and gangliosides extracted. Two and 3 weeks after injection the amounts of radioactivity in the ganglioside fractions of LST and SN were significantly higher than at days 1 and 2. The TCA soluble radioactivity decreased dramatically over the same time period. Colchicine prevented the appearance of radiolabelled lipid in LST and SN. From these experiments the authors conclude that some ganglioside is synthesized in the neuronal cell bodies of DRG and transported in the axons of the sciatic nerve. In another experiment the sciatic nerve was transected and ends separated to prevent regeneration. There was no difference in the amount of radiolabelled ganglioside that was isolated from DRG or LST of transected nerves compared with control nerves. The behavior of several potential acid soluble contaminants was studied in several steps used to isolate gangliosides. Of those studied only CMP-NeuAc could cause significant contamination of the final ganglioside preparation.

  15. Association of Anti-GT1a Antibodies with an Outbreak of Guillain-Barré Syndrome and Analysis of Ganglioside Mimicry in an Associated Campylobacter jejuni Strain

    PubMed Central

    Cao, Fangfang; Li, Jianjun; Liu, Hongying; Li, Qun; Meng, Fanliang; Zhang, Jianzhong

    2015-01-01

    An outbreak of Guillain-Barré syndrome (GBS), subsequent to Campylobacter jejuni enteritis, occurred in China in 2007. Serum anti-ganglioside antibodies were measured in GBS patients and controls. Genome sequencing was used to determine the phylogenetic relationship among three C. jejuni strains from a patient with GBS (ICDCCJ07001), a patient with gastroenteritis (ICDCCJ07002) and a healthy carrier (ICDCCJ07004), which were all associated with the outbreak. The ganglioside-like structures of the lipo-oligosaccharides of these strains were determined by mass spectrometry. Seventeen (53%) of the GBS patients had anti-GT1a IgG antibodies. GT1a mimicry was found in the lipo-oligosaccharides of strain ICDCCJ07002 and ICDCCJ07004; but a combination of GM3/GD3 mimics was observed in ICDCCJ07001, although this patient had anti-GT1a IgG antibodies. A single-base deletion in a glycosyltransferase gene caused the absence of GT1a mimicry in ICDCCJ07001. The phylogenetic tree showed that ICDCCJ07002 and ICDCCJ07004 were genetically closer to each other than to ICDCCJ07001. C. jejuni, bearing a GT1a-like lipo-oligosaccharide, might have caused the GBS outbreak and the loss of GT1a mimicry may have helped ICDCCJ07001 to survive in the host. PMID:26197476

  16. Sol-gel synthesis, characterization, and optical properties of Gd3+-doped CdO sub-micron materials

    NASA Astrophysics Data System (ADS)

    Alemi, Abdolali; Joo, Sang Woo; Khademinia, Shahin; Dolatyari, Mahboubeh; Bakhtiari, Akbar; Moradi, Hossein; Saeidi, Sorayya

    2013-05-01

    Highly crystalline Gd3+-doped cadmium oxide micro-structure was synthesized by calcining the obtained precursor of a sol-gel reaction. The reaction was carried out with cadmium nitrate (Cd(NO3)2·4H2O), gadolinium oxide, and ethylene glycol (C2H6O2) reactants without any additives at 80°C for 2 h. The resulting gel was calcined at 900°C with increasing temperature rate of 15°C/min for 12 h in a furnace. As a result of heating, the organic section of the gel was removed, and the Gd3+-doped cadmium oxide micro-structure was produced. The obtained compound from the sol-gel technique possesses a cubic crystalline structure at a micro scale. XRD study indicates that the obtained Gd3+-doped CdO has a cubic phase. Also, the SEM images showed that the resulting material is composed of particles with cluster structure. Also, FT-IR spectroscopy was employed to characterize the Gd3+-doped CdO micro-structures.

  17. Extending the distance range accessed with continuous wave EPR with Gd3+ spin probes at high magnetic fields†

    PubMed Central

    Edwards, Devin T.; Ma, Zhidong; Meade, Thomas J.; Goldfarb, Daniella; Han, Songi

    2014-01-01

    Interspin distances between 0.8 nm and 2.0 nm can be measured through the dipolar broadening of the continuous wave (cw) EPR spectrum of nitroxide spin labels at X-band (9.4 GHz, 0.35 T). We introduce Gd3+ as a promising alternative spin label for distance measurements by cw EPR above 7 Tesla, where the |−1/2〉 to |1/2〉 transition narrows below 1 mT and becomes extremely sensitive to dipolar broadening. To estimate the distance limits of cw EPR with Gd3+, we have measured spectra of frozen solutions of GdCl3 at 8.6 T (240 GHz) and 10 K at concentrations ranging from 50 mM to 0.1 mM, covering a range of average interspin distances. These experiments show substantial dipolar broadening at distances where line broadening cannot be observed with nitroxides at X-band. This data, and its agreement with calculated dipolar-broadened lineshapes, show Gd3+ to be sensitive to distances as long as ~3.8 nm. Further, the linewidth of a bis-Gd3+ complex with a flexible ~1.6 nm bridge is strongly broadened as compared to the mono-Gd3+ complex, demonstrating the potential for application to pairwise distances. Gd-DOTA-based chelates that can be functionalized to protein surfaces display linewidths narrower than aqueous GdCl3, implying they should be even more sensitive to dipolar broadening. Therefore, we suggest that the combination of tailored Gd3+ labels and high magnetic fields can extend the longest interspin distances measurable by cw EPR from 2.0 nm to 3.8 nm. cw EPR data at 260 K demonstrate that the line broadening remains clear out to similar average interspin distances, offering Gd3+ probes as promising distance rulers at temperatures higher than possible with conventional pulsed EPR distance measurements. PMID:23732863

  18. Specific ganglioside binding to receptor sites on T lymphocytes that couple to ganglioside-induced decrease of CD4 expression

    SciTech Connect

    Morrison, W.J. ); Offner, H. ); Vandenbark, A.A. )

    1989-01-01

    The binding of different gangliosides to rat T-helper lymphocytes was characterized under conditions that decrease CD4 expression on different mammalian T-helper lymphoctyes. Saturation binding by monosialylated ({sub 3}H)-GM{sub 1} to rat T-lymphocytes was time- and temperature-dependent, had a dissociation constant (K{sub D}) of 2.2 {plus minus} 1.4 {mu}M and a binding capacity near 2 fmoles/cell. Competitive inhibition of ({sup 3}H)- GM{sub 1} binding demonstrated a structural-activity related to the number of unconstrained sialic acid moieties on GM{sub 1}-congeneric gangliosides. A comparison between the results of these binding studies and gangliosides-induced decrease of CD4 expression demonstrated that every aspect of ({sup 3}H)-GM{sub 1} binding concurs with ganglioside modulation of CD4 expression. It is concluded that the specific decrease of CD4 expression induced by pretreatment with gangliosides involves the initial process of gangliosides binding to specific sites on CD4{sup {double dagger}} T-helper lymphocytes.

  19. Antibody Recognition of Cancer-Related Gangliosides and Their Mimics Investigated Using in silico Site Mapping

    PubMed Central

    Agostino, Mark; Yuriev, Elizabeth; Ramsland, Paul A.

    2012-01-01

    Modified gangliosides may be overexpressed in certain types of cancer, thus, they are considered a valuable target in cancer immunotherapy. Structural knowledge of their interaction with antibodies is currently limited, due to the large size and high flexibility of these ligands. In this study, we apply our previously developed site mapping technique to investigate the recognition of cancer-related gangliosides by anti-ganglioside antibodies. The results reveal a potential ganglioside-binding motif in the four antibodies studied, suggesting the possibility of structural convergence in the anti-ganglioside immune response. The structural basis of the recognition of ganglioside-mimetic peptides is also investigated using site mapping and compared to ganglioside recognition. The peptides are shown to act as structural mimics of gangliosides by interacting with many of the same binding site residues as the cognate carbohydrate epitopes. These studies provide important clues as to the structural basis of immunological mimicry of carbohydrates. PMID:22536387

  20. Gangliosides and gangliosidoses: principles of molecular and metabolic pathogenesis.

    PubMed

    Sandhoff, Konrad; Harzer, Klaus

    2013-06-19

    Gangliosides are the main glycolipids of neuronal plasma membranes. Their surface patterns are generated by coordinated processes, involving biosynthetic pathways of the secretory compartments, catabolic steps of the endolysosomal system, and intracellular trafficking. Inherited defects in ganglioside biosynthesis causing fatal neurodegenerative diseases have been described so far almost exclusively in mouse models, whereas inherited defects in ganglioside catabolism causing various clinical forms of GM1- and GM2-gangliosidoses have long been known. For digestion, gangliosides are endocytosed and reach intra-endosomal vesicles. At the level of late endosomes, they are depleted of membrane-stabilizing lipids like cholesterol and enriched with bis(monoacylglycero)phosphate (BMP). Lysosomal catabolism is catalyzed at acidic pH values by cationic sphingolipid activator proteins (SAPs), presenting lipids to their respective hydrolases, electrostatically attracted to the negatively charged surface of the luminal BMP-rich vesicles. Various inherited defects of ganglioside hydrolases, e.g., of β-galactosidase and β-hexosaminidases, and of GM2-activator protein, cause infantile (with tetraparesis, dementia, blindness) and different protracted clinical forms of GM1- and GM2-gangliosidoses. Mutations yielding proteins with small residual catabolic activities in the lysosome give rise to juvenile and adult clinical forms with a wide range of clinical symptomatology. Apart from patients' differences in their genetic background, clinical heterogeneity may be caused by rather diverse substrate specificities and functions of lysosomal hydrolases, multifunctional properties of SAPs, and the strong regulation of ganglioside catabolism by membrane lipids. Currently, there is no treatment available for neuronal ganglioside storage diseases. Therapeutic approaches in mouse models and patients with juvenile forms of gangliosidoses are discussed. PMID:23785136

  1. Magnetooptics of the luminescent transitions in Tb3+:Gd3Ga5O12

    NASA Astrophysics Data System (ADS)

    Valiev, Uygun V.; Gruber, John B.; Ivanov, Igor'A.; Burdick, Gary W.; Liang, Hongbin; Zhou, Lei; Fu, Dejun; Pelenovich, Oleg V.; Pelenovich, Vasiliy O.; Lin, Zhou

    2015-08-01

    The spectra of the luminescence and magnetic circular polarization of luminescence in terbium-gadolinium gallium garnet Tb3+:Gd3Ga5O12 (Tb3+:GGG) were studied within the visible spectral range at temperatures T = 90 and 300 K in an external magnetic field of 0.45 T. The Zeeman effect in the luminescence "green" band associated with 4f → 4f transition 5D4 → 7F5 of Tb3+:GGG was also studied at T = 90 K in an external field of 0.55 T. Measurement of the Zeeman effect in Tb3+:GGG carried out for some doublet lines of the luminescence band 5D4 → 7F5 at T = 90 K shows that a magnetooptical effect of the intensity change of the emitted light is observed on these lines, in contrast to pure Zeeman splitting of the emission lines measured in the luminescence band 5D4 → 7F6. For the systems we have studied, the maximal value of the magnetooptical effect of the intensity change of the luminescence line at low temperatures has been achieved in paramagnetic garnet Tb0.2Y2.8Al5O12 at comparatively low magnetic fields.

  2. Surfactant-free Gd3+-ion-containing carbon nanotube MRI contrast agents for stem cell labeling

    NASA Astrophysics Data System (ADS)

    Gizzatov, Ayrat; Hernández-Rivera, Mayra; Keshishian, Vazrik; Mackeyev, Yuri; Law, Justin J.; Guven, Adem; Sethi, Richa; Qu, Feifei; Muthupillai, Raja; Cabreira-Hansen, Maria Da Graça; Willerson, James T.; Perin, Emerson C.; Ma, Qing; Bryant, Robert G.; Wilson, Lon J.

    2015-07-01

    There is an ever increasing interest in developing new stem cell therapies. However, imaging and tracking stem cells in vivo after transplantation remains a serious challenge. In this work, we report new, functionalized and high-performance Gd3+-ion-containing ultra-short carbon nanotube (US-tube) MRI contrast agent (CA) materials which are highly-water-dispersible (ca. 35 mg ml-1) without the need of a surfactant. The new materials have extremely high T1-weighted relaxivities of 90 (mM s)-1 per Gd3+ ion at 1.5 T at room temperature and have been used to safely label porcine bone-marrow-derived mesenchymal stem cells for MR imaging. The labeled cells display excellent image contrast in phantom imaging experiments, and TEM images of the labeled cells, in general, reveal small clusters of the CA material located within the cytoplasm with 109 Gd3+ ions per cell.There is an ever increasing interest in developing new stem cell therapies. However, imaging and tracking stem cells in vivo after transplantation remains a serious challenge. In this work, we report new, functionalized and high-performance Gd3+-ion-containing ultra-short carbon nanotube (US-tube) MRI contrast agent (CA) materials which are highly-water-dispersible (ca. 35 mg ml-1) without the need of a surfactant. The new materials have extremely high T1-weighted relaxivities of 90 (mM s)-1 per Gd3+ ion at 1.5 T at room temperature and have been used to safely label porcine bone-marrow-derived mesenchymal stem cells for MR imaging. The labeled cells display excellent image contrast in phantom imaging experiments, and TEM images of the labeled cells, in general, reveal small clusters of the CA material located within the cytoplasm with 109 Gd3+ ions per cell. Electronic supplementary information (ESI) available: NMRD profiles, the Fourier transforms of the EXAFS data, EXAFS curve fitting data, cell viability data. See DOI: 10.1039/c5nr02078f

  3. Molecular Recognition of Gangliosides and Their Potential for Cancer Immunotherapies

    PubMed Central

    Krengel, Ute; Bousquet, Paula A.

    2014-01-01

    Gangliosides are sialic-acid-containing glycosphingolipids expressed on all vertebrate cells. They are primarily positioned in the plasma membrane with the ceramide part anchored in the membrane and the glycan part exposed on the surface of the cell. These lipids have highly diverse structures, not the least with respect to their carbohydrate chains, with N-acetylneuraminic acid (NeuAc) and N-glycolylneuraminic acid (NeuGc) being the two most common sialic-acid residues in mammalian cells. Generally, human healthy tissue is deficient in NeuGc, but this molecule is expressed in tumors and in human fetal tissues, and was hence classified as an onco-fetal antigen. Gangliosides perform important functions through carbohydrate-specific interactions with proteins, for example, as receptors in cell–cell recognition, which can be exploited by viruses and other pathogens, and also by regulating signaling proteins, such as the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR), through lateral interaction in the membrane. Through both mechanisms, tumor-associated gangliosides may affect malignant progression, which makes them attractive targets for cancer immunotherapies. In this review, we describe how proteins recognize gangliosides, focusing on the molecular recognition of gangliosides associated with cancer immunotherapy, and discuss the importance of these molecules in cancer research. PMID:25101077

  4. Ganglioside Composition in Beef, Chicken, Pork, and Fish Determined Using Liquid Chromatography-High-Resolution Mass Spectrometry.

    PubMed

    Fong, Bertram Y; Ma, Lin; Khor, Geok Lin; van der Does, Yvonne; Rowan, Angela; McJarrow, Paul; MacGibbon, Alastair K H

    2016-08-17

    Gangliosides (GA) are found in animal tissues and fluids, such as blood and milk. These sialo-glycosphingolipids have bioactivities in neural development, the gastrointestinal tract, and the immune system. In this study, a high-performance liquid chromatography-mass spectrometry (HPLC-MS) method was validated to characterize and quantitate the GA in beef, chicken, pork, and fish species (turbot, snapper, king salmon, and island mackerel). For the first time, we report the concentration of GM3, the dominant GA in these foods, as ranging from 0.35 to 1.1 mg/100 g and 0.70 to 5.86 mg/100 g of meat and fish, respectively. The minor GAs measured were GD3, GD1a, GD1b, and GT1b. Molecular species distribution revealed that the GA contained long- to very-long-chain acyl fatty acids attached to the ceramide moiety. Fish GA contained only N-acetylneuraminic acid (NeuAc) sialic acid, while beef, chicken, and pork contained GD1a/b species that incorporated both NeuAc and N-glycolylneuraminic acid (NeuGc) and hydroxylated fatty acids. PMID:27436425

  5. Electrical and electromechanical studies in ferroelectric Gd3+ modified lead potassium niobate ceramics

    NASA Astrophysics Data System (ADS)

    Sambasiva Rao, K.; Krishna, P. Murali; Dasari, Madhava P.; Lee, J. H.

    2011-08-01

    The change in dielectric constant relaxation time over temperature (35-590 °C) and frequency (45 Hz-5 MHz) in ceramics of Pb0.77K0.115Gd0.115Nb2O6 (PKGN, Tc = 340 °c) has been studied. Powder X-ray diffraction revealed the single-phase formation with orthorhombic crystal structure. The P-E hysteresis loop parameters are Ps = 21.77 μC/cm2, Pr = 17.09 μC/cm2, Ec = 11.86 kV/cm; the piezoelectric constants, Kp = 31.7%, Kt = 47%, d33 = 115 × 10-12 C/N, d31 = -41 × 10-12 C/N, are determined in the material and some transducer applications are discussed. Cole-Cole (Zll vs. Zl) plots showed a non-Debye type relaxation. Conductivity obeyed Jonscher's universal power law, σ = σ0 + Aωn. The theoretical values of ɛl and σ are computed using the parameters `A(T)' and `n(T)' (0 < n < 1) and are well fitted with the experimental data. The hopping ion frequency (ωp) and charge carrier concentration (Kl) have been analyzed using Almond-West formalism. The dielectric relaxation processes are associated with localized oxygen vacancies conduction at high frequency region. A long-range conductivity by Gd3+ ions is found to be predominant at low frequency region. The activation energies from impedance and modulus formalisms revealed the ionic type conduction in PKGN.

  6. Controlling the Two-Photon-Induced Photon Cascade Emission in a Gd3+/Tb3+-Codoped Glass for Multicolor Display

    NASA Astrophysics Data System (ADS)

    Yuan, Mao-Hui; Fan, Hai-Hua; Li, Hui; Lan, Sheng; Tie, Shao-Long; Yang, Zhong-Min

    2016-02-01

    We reported the first observation of the two-photon-induced quantum cutting phenomenon in a Gd3+/Tb3+-codoped glass in which two photons at ~400 nm are simultaneously absorbed, leading to the cascade emission of three photons in the visible spectral region. The two-photon absorption induced by femtosecond laser pulses allows the excitation of the energy states in Gd3+ which are inactive for single-photon excitation and enables the observation of many new electric transitions which are invisible in the single-photon-induced luminescence. The competition between the two-photon-induced photon cascade emission and the single-photon-induced emission was manipulated to control the luminescence color of the glass. We demonstrated the change of the luminescence color from red to yellow and eventually to green by varying either the excitation wavelength or the excitation power density.

  7. Controlling the Two-Photon-Induced Photon Cascade Emission in a Gd3+/Tb3+-Codoped Glass for Multicolor Display

    PubMed Central

    Yuan, Mao-Hui; Fan, Hai-Hua; Li, Hui; Lan, Sheng; Tie, Shao-Long; Yang, Zhong-Min

    2016-01-01

    We reported the first observation of the two-photon-induced quantum cutting phenomenon in a Gd3+/Tb3+-codoped glass in which two photons at ~400 nm are simultaneously absorbed, leading to the cascade emission of three photons in the visible spectral region. The two-photon absorption induced by femtosecond laser pulses allows the excitation of the energy states in Gd3+ which are inactive for single-photon excitation and enables the observation of many new electric transitions which are invisible in the single-photon-induced luminescence. The competition between the two-photon-induced photon cascade emission and the single-photon-induced emission was manipulated to control the luminescence color of the glass. We demonstrated the change of the luminescence color from red to yellow and eventually to green by varying either the excitation wavelength or the excitation power density. PMID:26899189

  8. Controlling the Two-Photon-Induced Photon Cascade Emission in a Gd(3+)/Tb(3+)-Codoped Glass for Multicolor Display.

    PubMed

    Yuan, Mao-Hui; Fan, Hai-Hua; Li, Hui; Lan, Sheng; Tie, Shao-Long; Yang, Zhong-Min

    2016-01-01

    We reported the first observation of the two-photon-induced quantum cutting phenomenon in a Gd(3+)/Tb(3+)-codoped glass in which two photons at ~400 nm are simultaneously absorbed, leading to the cascade emission of three photons in the visible spectral region. The two-photon absorption induced by femtosecond laser pulses allows the excitation of the energy states in Gd(3+) which are inactive for single-photon excitation and enables the observation of many new electric transitions which are invisible in the single-photon-induced luminescence. The competition between the two-photon-induced photon cascade emission and the single-photon-induced emission was manipulated to control the luminescence color of the glass. We demonstrated the change of the luminescence color from red to yellow and eventually to green by varying either the excitation wavelength or the excitation power density. PMID:26899189

  9. Nd 3+—Cr 3+ pairs in Gd 3Sc 2Ga 3O 12 garnet crystals

    NASA Astrophysics Data System (ADS)

    Han, T. P. J.; Scott, M. A.; Jaqué, F.; Gallagher, H. G.; Henderson, B.

    1993-06-01

    Several crystals of Gd 3Sc 2Ga 3O 12 (GSGG) with different concentrations of Nd 3+ and Cr 3+ ions have been grown using the Czochralski technique. Optical absorption and site-selective luminescence spectra have been measured in the wavelength range 350-900 nm at low temperatures (15-77 K). These spectral reveal the presence of Nd 3+ ions in two different crystal field sites. Some Nd 3+ ions substitute for Gd 3+ ions in unit cells in which the central octahedral site is occupied by Sc 3+ ions. However, in a significant fraction of unit cells containing Nd 3+ the central octahedral site is occupied by Cr 3+ ions. These centres are labelled Nd 3+ (Sc 3+ and Nd 3+ (Cr 3+), respectively. The spectroscopic characteristics of these perturbed Nd 3+ centres are reported and their relevance to the enhanced Nd 3+ laser efficiency of Cr 3+:Nd 3+:GSGG relative to Nd 3+:GSGG is discussed.

  10. The effects of Gd3+ doping on the physical structure and photocatalytic performance of Bi2MoO6 nanoplate crystals

    NASA Astrophysics Data System (ADS)

    Yu, Changlin; Wu, Zhen; Liu, Renyue; He, Hongbo; Fan, Wenhong; Xue, Shuangshuang

    2016-06-01

    Gd3+ doped Bi2MoO6 nanoplate crystals were fabricated by solvothermal combined calcination method. The effects of Gd3+ doping with different concentrations on the texture, crystal and optical properties of Bi2MoO6 were investigated by N2 physical adsorption, X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR) and ultraviolet-visible diffuse reflection spectrum (UV-vis DRS), photoluminescence (PL) spectroscopy, and X-ray photoelectron spectroscopy (XPS). Under simulated solar light irradiation, the influences of Gd3+doping on photocatalytic activity of Bi2MoO6 were evaluated by photocatalytic degradation of Rhodamine B. The characterization results showed that with Gd3+ doping, a contraction of lattice and a decrease in crystallite size occurred. Meanwhile, an increase in surface area over Gd3+ doped Bi2MoO6 was observed. Moreover, Gd3+ doping could obviously enhance the visible light harvesting of Bi2MoO6 and promoted the separation of photogenerated electrons and holes. With optimum Gd3+(6 wt%) doping, Gd/Bi2MoO6 exhibited the best activity and stability in degradation of Rhodamine B.

  11. Double-phase transition and giant positive magnetoresistance in the quasi-skutterudite Gd3Ir4Sn13

    NASA Astrophysics Data System (ADS)

    Nair, Harikrishnan S.; Ghosh, Sarit K.; Ramesh Kumar, K.; Strydom, André M.

    2016-03-01

    The magnetic, thermodynamic, and electrical/thermal transport properties of the caged-structure quasi-skutterudite Gd3Ir4Sn13 are re-investigated. The magnetization M(T), the specific heat C p ( T ) , and the resistivity ρ ( T ) reveal a double-phase transition—at TN1 ˜ 10 K and at TN2 ˜ 8.8 K—which was not observed in the previous report on this compound. The antiferromagnetic transition is also visible in the thermal transport data, thereby suggesting a close connection between the electronic and lattice degrees of freedom in this Sn-based quasi-skutterudite. The temperature dependence of ρ ( T ) is analyzed in terms of a power-law for resistivity pertinent to Fermi liquid picture. Giant, positive magnetoresistance (MR) ≈ 80% is observed in Gd3Ir4Sn13 at 2 K with the application of 9 T. The giant MR and the double magnetic transition can be attributed to the quasi-cages and layered antiferromagnetic structure of Gd3Ir4Sn13 vulnerable to structural distortions and/or dipolar or spin-reorientation effects. The giant value of MR observed in this class of 3:4:13 type alloys, especially in a Gd-compound, is the highlight of this work.

  12. GM1 and GM2 gangliosides: recent developments.

    PubMed

    Bisel, Blaine; Pavone, Francesco S; Calamai, Martino

    2014-03-01

    GM1 and GM2 gangliosides are important components of the cell membrane and play an integral role in cell signaling and metabolism. In this conceptual overview, we discuss recent developments in our understanding of the basic biological functions of GM1 and GM2 and their involvement in several diseases. In addition to a well-established spectrum of disorders known as gangliosidoses, such as Tay-Sachs disease, more and more evidence points at an involvement of GM1 in Alzheimer's and Parkinson's diseases. New emerging methodologies spanning from single-molecule imaging in vivo to simulations in silico have complemented standard studies based on ganglioside extraction. PMID:25372744

  13. Cholera Toxin and Cell Growth: Role of Membrane Gangliosides

    PubMed Central

    Hollenberg, Morley D.; Fishman, Peter H.; Bennett, Vann; Cuatrecasas, Pedro

    1974-01-01

    The binding of cholera toxin to three transformed mouse cell lines derived from the same parent strain, and the effects of the toxin on DNA synthesis and adenylate cyclase activity, vary in parallel with the ganglioside composition of the cells. TAL/N cells of early passage, which contain large quantities of gangliosides GM3, GM2, GM1, and GDla, as well as the glycosyltransferases necessary for the synthesis of these gangliosides, bind the most cholera toxin and are the most sensitive to its action. TAL/N cells of later passage, which lack chemically detectable GM1 and GDla and which have no UDP-Gal:GM2 galactosyltransferase activity, are intermediate in binding and response to the toxin. SVS AL/N cells, which lack GM2 in addition to GM1 and GDla and which have little detectable UDP-GalNAc:GM3N-acetylgalactosaminyltransferase activity, bind the least amount of toxin. The SVS AL/N cells are the least responsive to inhibition of DNA synthesis and stimulation of adenylate cyclase activity by cholera toxin. Gangliosides (especially GM1), which appear to be the natural membrane receptors for cholera toxin, may normally have important roles in the regulation of cell growth and cAMP-mediated responses. PMID:4530298

  14. Exogenous gangliosides may affect methylation mechanisms in neuronal cell cultures

    SciTech Connect

    Ferret, B.; Hubsch, A.; Dreyfus, H.; Massarelli, R. )

    1991-02-01

    Primary neurons in culture from chick embryo cerebral hemispheres were treated with a mixture of gangliosides added to the growth medium (final concentration: 10(-5)M and 10(-8)M) from the 3rd to the 6th day in vitro. Under these conditions methylation processes measured with (3H) and (35S) methionine and (3H)ethanolamine as precursors showed an increased methylation of (3H)ethanolamine containing phospholipids, a correspondent increased conversion of these compounds to (3H)choline containing phospholipids, and a general increased methylation of trichloroacetic acid precipitable macromolecules containing labeled methionine. A small increase in protein synthesis was observed after incubation of neurons with (3H)- and (35S)methionine. This was confirmed after electrophoretic separation of a protein extract with increased 3H- and 35S-labeling in protein bands with moecular weights between 50 and 60 KDaltons. A protein band of about 55 KDaltons appeared to be preferentially labelled when (3H) methionine was the precursor. The treatment with gangliosides increased the incorporation of (methyl-3H) label after incubation of neurons with (3H) methionine, into total DNA and decreased that of total RNA. The treatment of neurons in culture with exogenous gangliosides hence affects differently methylation processes, a finding which may confirm the involvement of gangliosides on the intracellular mediation of neuronal information mechanisms.

  15. The detection limit of a Gd3+-based T1 agent is substantially reduced when targeted to a protein microdomain

    PubMed Central

    Hanaoka, Kenjiro; Lubag, Angelo Josue M.; Castillo-Muzquiz, Aminta; Kodadek, Thomas; Sherry, A. Dean

    2008-01-01

    Simple low MW chelates of Gd3+ such as those currently used in clinical MR imaging are considered too insensitive for most molecular imaging applications. Here, we evaluated the detection limit of a molecularly targeted, low MW Gd3+-based, T1 agent in a model where the receptor concentration was precisely known. The data demonstrate that receptors clustered together to form a microdomain of high local concentration can be imaged successfully even when the bulk concentration of the receptor is quite low. A GdDO3A-peptide identified by phage display to target the anti-FLAG antibody was synthesized, purified and characterized. T1 weighted MR images were compared with the agent bound to antibody in bulk solution and with the agent bound to the antibody localized on agarose beads. Fluorescence competition binding assays show that the agent has a high binding affinity (KD = 150 nM) for the antibody while the fully bound relaxivity of the GdDO3A-peptide:anti-FLAG antibody in solution was a relatively modest 17 mM−1s−1. The agent:antibody complex was MR silent at concentrations below ~9 µM but was detectable down to 4 µM bulk concentrations when presented to antibody clustered together on the surface of agarose beads. These results provided an estimate of the detection limits for other T1-based agents with higher fully bound relaxivities or multimeric structures bound to clustered receptor molecules. The results demonstrate that the sensitivity of molecularly-targeted contrast agents depends on the local microdomain concentration of the target protein and the molecular relaxivity of the bound complex. A model is presented which predicts that for a molecularly targeted agent consisting of a single Gd3+ complex with bound relaxivity of 100 mM−1s−1 or, more reasonably, four tethered Gd3+ complexes each having a bound relaxivity of 25 mM−1s−1, the detection limit of a protein microdomain is ~690 nM at 9.4T. These experimental and extrapolated detection limits are

  16. Effect of Ce concentration on luminescence properties of Gd3Ga3Al2O12:Ce nanocrystals

    NASA Astrophysics Data System (ADS)

    Singh, K. V.; Singh, J. P.; Shinde, S.; Singh, A. K.; Tyagi, M.

    2016-05-01

    Gd3Ga3Al2O12 (GGAG) polycrystalline nano-powders doped with different Ce concentrations were prepared by a co-precipitation method followed by heat treatment at 1000°C for 24 h in air and Ar ambient. Structural and morphological studies show that the synthesized powder is pure phase having nanometer (30-50 nm) particle size. Luminescence studies carried out using UV and X-ray excitations revealed a decrease in the luminescence intensity for a Ce concentration greater than 0.5 mol% due to the concentration quenching.

  17. Cr,Nd:Gd3Sc2Ga3O12 laser pumped by high-power visible laser diodes

    NASA Astrophysics Data System (ADS)

    Scheps, Richard

    1992-06-01

    Visible laser diodes are used to pump a co-doped Cr,Nd:Gd3Sc2Ga3O12 (Cr,Nd:GSGG) laser rod, demonstrating efficient operation at 1.06 (mu) . Using a 10 cm ROC HR output coupler, the absorbed power required to reach threshold was 938 (mu) W. The round trip losses in the 5 mm long rod were measured to be 4 X 10-3. The best slope efficiency was 42.1%, obtained with a 97% R output coupler. The photon slope efficiency was 66.8%.

  18. Simultaneous dual-wavelength laser operation at 937 and 1062 nm in Nd3+:Gd3Ga5O12

    NASA Astrophysics Data System (ADS)

    Gao, F.; Sun, G. C.; Li, Y. D.; Dong, Y.; Li, S. T.

    2013-08-01

    Diode-end-pumped continuous-wave (cw) simultaneous dual-wavelength laser operation at 937 and 1062 nm in a single Nd3+:Gd3Ga5O12 (Nd:GGG) crystal was demonstrated. A total output power of 1.12 W at the two fundamental wavelengths was achieved at incident pump power of 17.6 W. The optical-to-optical conversion was up to 6.4% with respect to the incident pump power. To the best of our knowledge, this is first work on cw simultaneous dual-wavelength operation at 937 and 1062 nm in Nd:GGG crystal.

  19. A Structural Study of Facet and Off-Facet Parts of Rare-Earth Garnets, Gd 3Sc 2Al 3O 12, Gd 3Sc 2Ga 3O 12, and La 3Lu 2Ga 3O 12

    NASA Astrophysics Data System (ADS)

    Yamazaki, Satoru; Marumo, Fumiyuki; Tanaka, Kiyoaki; Morikawa, Hideki; Kodama, Nobuhiro; Kitamura, Kenji; Miyazawa, Yasuto

    1994-01-01

    The crystal structures of facet and off-facet parts of rare-earth garnets Gd 3Sc 2Al 3O 12 (GSAG), Gd 3Sc 2Ga 3O 12 (GSGG), and La 3Lu 2Ga 3O 12 (LLGG) have been refined with the single-crystal X-ray diffraction method. The crystals are cubic with the space group Ia3 d, containing eight formula units in a unit cell. The final weighted reliability factors are 0.014, 0.017, and 0.020 for 1786, 2318, and 2331 reflections of the facet parts of GSAG, GSGG, and LLGG, respectively, and 0.014, 0.017, and 0.019 for 2143, 2190, and 2420 reflections of the off-facet parts of the respective crystals. The bond lengths between the tetrahedral cations ( T) and the oxygen atoms in GSAG and GSGG as well as those between the dodecahedral cations ( M viii) and oxygen atoms in all the examined crystals are in accordance with the sums of ionic radii both in facet and off-facet parts, whereas the octahedral cations ( M vi) in all the crystals and the tetrahedral cation in LLGG have bond lengths longer than the sums of the ionic radii. A cation replacement at the T sites was not observed, whereas the M vi and M viii sites were revealed to be partly replaced by cations with smaller ionic radii.

  20. Assessment of the Molecular Expression and Structure of Gangliosides in Brain Metastasis of Lung Adenocarcinoma by an Advanced Approach Based on Fully Automated Chip-Nanoelectrospray Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Zamfir, Alina D.; Serb, Alina; Vukeli, Željka; Flangea, Corina; Schiopu, Catalin; Fabris, Dragana; Kalanj-Bognar, Svjetlana; Capitan, Florina; Sisu, Eugen

    2011-12-01

    Gangliosides (GGs), sialic acid-containing glycosphingolipids, are known to be involved in the invasive/metastatic behavior of brain tumor cells. Development of modern methods for determination of the variations in GG expression and structure during neoplastic cell transformation is a priority in the field of biomedical analysis. In this context, we report here on the first optimization and application of chip-based nanoelectrospray (NanoMate robot) mass spectrometry (MS) for the investigation of gangliosides in a secondary brain tumor. In our work a native GG mixture extracted and purified from brain metastasis of lung adenocarcinoma was screened by NanoMate robot coupled to a quadrupole time-of-flight MS. A native GG mixture from an age-matched healthy brain tissue, sampled and analyzed under identical conditions, served as a control. Comparative MS analysis demonstrated an evident dissimilarity in GG expression in the two tissue types. Brain metastasis is characterized by many species having a reduced N-acetylneuraminic acid (Neu5Ac) content, however, modified by fucosylation or O-acetylation such as Fuc-GM4, Fuc-GM3, di- O-Ac-GM1, O-Ac-GM3. In contrast, healthy brain tissue is dominated by longer structures exhibiting from mono- to hexasialylated sugar chains. Also, significant differences in ceramide composition were discovered. By tandem MS using collision-induced dissociation at low energies, brain metastasis-associated GD3 (d18:1/18:0) species as well as an uncommon Fuc-GM1 (d18:1/18:0) detected in the normal brain tissue could be structurally characterized. The novel protocol was able to provide a reliable compositional and structural characterization with high analysis pace and at a sensitivity situated in the fmol range.

  1. Recycling of glucosylceramide and sphingosine for the biosynthesis of gangliosides and sphingomyelin in rat liver.

    PubMed Central

    Trinchera, M; Ghidoni, R; Sonnino, S; Tettamanti, G

    1990-01-01

    It was previously shown that sphingomyelin and gangliosides can be biosynthesized starting from sphingosine or sphingosine-containing fragments which originated in the course of GM1 ganglioside catabolism. In the present paper we investigated which fragments were specifically re-used for sphingomyelin and ganglioside biosynthesis in rat liver. At 30 h after intravenous injection of GM1 labelled at the level of the fatty acid ([stearoyl-14C]GM1) or of the sphingosine ([Sph-3H]) moiety, it was observed that radioactive sphingomyelin was formed almost exclusively after the sphingosine-labelled-GM1 administration. This permitted the recognition of sphingosine as the metabolite re-used for sphingomyelin biosynthesis. Conversely, gangliosides more complex than GM1 were similarly radiolabelled after the two treatments, thus ruling out sphingosine re-utilization for ganglioside biosynthesis. For the identification of the lipid fragment re-used for ganglioside biosynthesis, we administered to rats neutral glycosphingolipids (galactosylceramide, glucosylceramide and lactosylceramide) each radiolabelled in the sphingosine moiety or in the terminal sugar residue. Thereafter we compared the formation of radiolabelled gangliosides in the liver with respect to the species administered and the label location. After galactosylceramide was injected, no radiolabelled gangliosides were formed. After the administration of differently labelled glucosylceramide, radiolabelled gangliosides were formed, regardless of the position of the label. After lactosylceramide administration, the ganglioside fraction became more radioactive when the long-chain-base-labelled precursors were used. These results suggest that glucosylceramide, derived from glycosphingolipid and ganglioside catabolism, is recycled for ganglioside biosynthesis. Images Fig. 1. PMID:2241913

  2. Role of Ce4+ in the scintillation mechanism of codoped Gd3Ga3Al2O12:Ce

    DOE PAGESBeta

    Wu, Yuntao; Meng, Fang; Li, Qi; Koschan, Merry; Melcher, Charles L.

    2014-10-17

    To control the time-response performance of widely used cerium-activated scintillators in cutting-edge medical-imaging devices, such as time-of-flight positron-emission tomography, a comprehensive understanding of the role of Ce valence states, especially stable Ce4+, in the scintillation mechanism is essential. However, despite some progress made recently, an understanding of the physical processes involving Ce4+ is still lacking. The aim of this work is to clarify the role of Ce4+ in scintillators by studying Ca2+ codoped Gd3Ga3Al2O12∶Ce (GGAG∶Ce). By using a combination of optical absorption spectra and x-ray absorption near-edge spectroscopies, the correlation between Ca2+codoping content and the Ce4+ fraction is seen. The energy-levelmore » diagrams of Ce3+ and Ce4+ in the Gd3Ga3Al2O12 host are established by using theoretical and experimental methods, which indicate a higher position of the 5d1 state of Ce4+ in the forbidden gap in comparison to that of Ce3+. Underlying reasons for the decay-time acceleration resulting from Ca2+ codoping are revealed, and the physical processes of the Ce4+-emission model are proposed and further demonstrated by temperature-dependent radioluminescence spectra under x-ray excitation.« less

  3. Garnet-to-perovskite transition in Gd3Sc2Ga3O12 at high pressure and high temperature.

    PubMed

    Lin, Chuanlong; Liu, Jing; Lin, Jung-Fu; Li, Xiaodong; Li, Yanchun; Zhang, Qingli; Xiong, Lun; Li, Rui

    2013-01-01

    The structural phase transition of gadolinium-scandium-gallium garnet (Gd(3)Sc(2)Ga(3)O(12), GSGG) has been studied at high pressure and high temperature using the synchrotron X-ray diffraction technique in a laser-heated diamond anvil cell. The GSGG garnet transformed to an orthorhombic perovskite structure at approximately 24 GPa after laser heating to 1500-2000 K. The garnet-to-perovskite phase transition is associated with an ∼8% volume reduction and an increase in the coordination number of the Ga(3+) or Sc(3+) ion. The orthorhombic perovskite GSGG has bulk modulus B(0) = 194(15) GPa with B(0)' = 5.3(8), exhibiting slightly less compression than the cubic garnet structure of GSGG with B(0) = 157(15) GPa and B(0)' = 6.5(10). Upon compression at room temperature, the cubic GSGG garnet became amorphous at ∼65 GPa. Coupled with the amorphous-to-perovskite phase transition in Y(3)Fe(5)O(12) and Gd(3)Ga(5)O(12) at high-pressure-temperature conditions, we conclude that amorphization should represent a new thermodynamic state resulting from hindrance of the garnet-to-perovskite phase transition, whereas the garnet-to-amorphous transition in rare-earth garnets should be kinetically hindered at room temperature. PMID:23240758

  4. Electron paramagnetic resonance linewidth narrowing of Gd3+ ions in Y-doped ceria nanocrystals with decreasing crystallite size.

    PubMed

    Rakhmatullin, R M; Aminov, L K; Kurkin, I N; Böttcher, R; Pöppl, A; Avila-Paredes, H; Kim, S; Sen, S

    2009-09-28

    Electron paramagnetic resonance (EPR) spectra of Gd(3+) ions in crystalline Ce(1-x-y)Gd(x)Y(y)O(2-[0.5*(x+y)]) (x=0.0025, y=0.10, and 0.25) with crystallite sizes ranging from 600 nm down to 5 nm have been measured at X-band and at Q-band near liquid He and room temperatures. The EPR line shape is controlled by the low-symmetry surrounding of Gd(3+) ions in a coordination environment with one oxygen-vacancy and seven oxygen nearest-neighbors forming GdO(7) polyhedra. These coordination polyhedra are characterized by a wide distribution of crystal field parameters that primarily controls the EPR linewidth. The EPR linewidth of the central (-1/2 <--> +1/2) transition is observed to decrease systematically with decreasing crystallite size. This observation implies that the size of the crystallites in the nanoregime may have important influence on the energetics of vacancy distribution in crystalline materials. PMID:19791902

  5. Luminescence Enhanced Eu(3+)/Gd(3+) Co-Doped Hydroxyapatite Nanocrystals as Imaging Agents In Vitro and In Vivo.

    PubMed

    Xie, Yunfei; He, Wangmei; Li, Fang; Perera, Thalagalage Shalika Harshani; Gan, Lin; Han, Yingchao; Wang, Xinyu; Li, Shipu; Dai, Honglian

    2016-04-27

    Biocompatible, biodegradable, and luminescent nano material can be used as an alternative bioimaging agent for early cancer diagnosis, which is crucial to achieve successful treatment. Hydroxyapatite (HAP) nanocyrstals have good biocompatibility and biodegradability, and can be used as an excellent host for luminescent rare earth elements. In this study, based on the energy transfer from Gd(3+) to Eu(3+), the luminescence enhanced imaging agent of Eu/Gd codoping HAP (HAP:Eu/Gd) nanocrystals are obtained via coprecipitation with plate-like shape and no change in crystal phase composition. The luminescence can be much elevated (up to about 120%) with a nonlinear increase versus Gd doping content, which is due to the energy transfer ((6)PJ of Gd(3+) → (5)HJ of Eu(3+)) under 273 nm and the possible combination effect of the cooperative upconversion and the successive energy transfer under 394 nm, respectively. Results demonstrate that the biocompatible HAP:Eu/Gd nanocrystals can successfully perform cell labeling and in vivo imaging. The intracellular HAP:Eu/Gd nanocrystals display good biodegradability with a cumulative degradation of about 65% after 72 h. This biocompatible, biodegradable, and luminescence enhanced HAP:Eu/Gd nanocrystal has the potential to act as a fluorescent imaging agent in vitro and in vivo. PMID:27043792

  6. Luminescent properties of Pr3+-sensitized LaPO4:Gd3+ ultraviolet-B phosphor under vacuum-ultraviolet light excitation

    NASA Astrophysics Data System (ADS)

    Okamoto, Shinji; Uchino, Rika; Kobayashi, Keisuke; Yamamoto, Hajime

    2009-07-01

    Luminescent properties of Pr3+-sensitized LaPO4:Gd3+ under vacuum-ultraviolet (vuv) light excitation have been investigated. The energy transfer probably occurs from the 5d levels in Pr3+ ions to Gd3+ ions under 172nm light excitation. LaPO4:Gd3+,Pr3+ shows efficient ultraviolet-B (uv-B) emission at 312nm, whose peak intensity reaches its maximum at Gd =35mol% and Pr =5mol%. (La0.65Gd0.35)0.95Pr0.05PO4 is about 1.6 times higher than a typical uv-B phosphor for vuv lamp, Y0.75Gd0.25Al3(BO3)4, in Gd3+-emission intensity under 172nm light excitation. This result implies that the Pr3+-sensitized LaPO4:Gd3+ is a candidate of uv-B phosphors for xenon-excimer discharge vuv lamps. In order to evaluate the effect of the narrow-band uv-B emission by LaPO4:Gd3+,Pr3+ phosphor, irradiation test on DNA was performed. The irradiation damage of pUC 18 DNA by the narrow-band uv-B light from the LaPO4:Gd3+,Pr3+ phosphor is in the same magnitude as that by uv-A light from a filtered Hg lamp, even though the uv-B lamp is higher than the uv-A lamp in power density and photon energy.

  7. Anti-ganglioside antibodies are removed from circulation in mice by neuronal endocytosis

    PubMed Central

    Cunningham, Madeleine E.; McGonigal, Rhona; Meehan, Gavin R.; Barrie, Jennifer A.; Yao, Denggao; Halstead, Susan K.

    2016-01-01

    See van Doorn and Jacobs (doi:10.1093/brain/aww078) for a scientific commentary on this article.   In axonal forms of Guillain-Barré syndrome, anti-ganglioside antibodies bind gangliosides on nerve surfaces, thereby causing injury through complement activation and immune cell recruitment. Why some nerve regions are more vulnerable than others is unknown. One reason may be that neuronal membranes with high endocytic activity, including nerve terminals involved in neurotransmitter recycling, are able to endocytose anti-ganglioside antibodies from the cell surface so rapidly that antibody-mediated injury is attenuated. Herein we investigated whether endocytic clearance of anti-ganglioside antibodies by nerve terminals might also be of sufficient magnitude to deplete circulating antibody levels. Remarkably, systemically delivered anti-ganglioside antibody in mice was so avidly cleared from the circulation by endocytosis at ganglioside-expressing plasma membranes that it was rapidly rendered undetectable in serum. A major component of the clearance occurred at motor nerve terminals of neuromuscular junctions, from where anti-ganglioside antibody was retrogradely transported to the motor neuron cell body in the spinal cord, recycled to the plasma membrane, and secreted into the surrounding spinal cord. Uptake at the neuromuscular junction represents a major unexpected pathway by which pathogenic anti-ganglioside antibodies, and potentially other ganglioside binding proteins, are cleared from the systemic circulation and also covertly delivered to the central nervous system. PMID:27017187

  8. Anti-ganglioside antibodies are removed from circulation in mice by neuronal endocytosis.

    PubMed

    Cunningham, Madeleine E; McGonigal, Rhona; Meehan, Gavin R; Barrie, Jennifer A; Yao, Denggao; Halstead, Susan K; Willison, Hugh J

    2016-06-01

    SEE VAN DOORN AND JACOBS DOI101093/BRAIN/AWW078 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE  : In axonal forms of Guillain-Barré syndrome, anti-ganglioside antibodies bind gangliosides on nerve surfaces, thereby causing injury through complement activation and immune cell recruitment. Why some nerve regions are more vulnerable than others is unknown. One reason may be that neuronal membranes with high endocytic activity, including nerve terminals involved in neurotransmitter recycling, are able to endocytose anti-ganglioside antibodies from the cell surface so rapidly that antibody-mediated injury is attenuated. Herein we investigated whether endocytic clearance of anti-ganglioside antibodies by nerve terminals might also be of sufficient magnitude to deplete circulating antibody levels. Remarkably, systemically delivered anti-ganglioside antibody in mice was so avidly cleared from the circulation by endocytosis at ganglioside-expressing plasma membranes that it was rapidly rendered undetectable in serum. A major component of the clearance occurred at motor nerve terminals of neuromuscular junctions, from where anti-ganglioside antibody was retrogradely transported to the motor neuron cell body in the spinal cord, recycled to the plasma membrane, and secreted into the surrounding spinal cord. Uptake at the neuromuscular junction represents a major unexpected pathway by which pathogenic anti-ganglioside antibodies, and potentially other ganglioside binding proteins, are cleared from the systemic circulation and also covertly delivered to the central nervous system. PMID:27017187

  9. Protective effects of exogenous gangliosides on ROS-induced changes in human spermatozoa.

    PubMed

    Gavella, Mirjana; Lipovac, Vaskresenija

    2013-05-01

    This article summarizes the available evidence on the efficacy of gangliosides to reduce the degree of reactive oxygen species (ROS)-mediated damage. The antioxidative efficacy of exogenous gangliosides in protecting different cells encouraged us to examine their ability to protect human spermatozoa. Gangliosides are sialic acid-containing glycosphingolipids with strong amphiphilic character due to the bulky headgroup made of several sugar rings with sialic acid residues and the double-tailed hydrophobic lipid moiety. The amphiphilicity of gangliosides allows them to exist as micelles in aqueous media when they are present at a concentration above their critical micellar concentration. The protective effect of ganglioside micelles on spermatozoa is believed to stem from their ability to scavenge free radicals and prevent their damaging effects. In our study, we particularly focused our attention on the protective effect of ganglioside micelles on DNA in human spermatozoa exposed to cryopreservation. The results indicate that ganglioside micelles can modulate the hydrophobic properties of the sperm membrane to increase tolerance to DNA fragmentation, thus protecting the DNA from cryopreservation-induced damage. Further actions of ganglioside micelles, which were documented by biochemical and biophysical studies, included (i) the modulation of superoxide anion generation by increasing the diffusion barrier for membrane events responsible for signal translocation to the interior of the cell; (ii) the inhibition of iron-catalysed hydroxyl radical formation due to the iron chelation potential of gangliosides; and (iii) inhibition of hydrogen peroxide diffusion across the sperm membrane. PMID:23503425

  10. Zika virus and neurologic autoimmunity: the putative role of gangliosides.

    PubMed

    Anaya, Juan-Manuel; Ramirez-Santana, Carolina; Salgado-Castaneda, Ignacio; Chang, Christopher; Ansari, Aftab; Gershwin, M Eric

    2016-01-01

    An increasing number of severe neurological complications associated with Zika virus (ZIKV), chiefly Guillain-Barré syndrome (GBS) and primary microcephaly, have led the World Health Organization to declare a global health emergency. Molecular mimicry between glycolipids and surface molecules of infectious agents explain most of the cases of GBS preceded by infection, while a direct toxicity of ZIKV on neural cells has been raised as the main mechanism by which ZIKV induces microcephaly. Gangliosides are crucial in brain development, and their expression correlates with neurogenesis, synaptogenesis, synaptic transmission, and cell proliferation. Targeting the autoimmune response to gangliosides may represent an underexploited opportunity to examine the increased incidence of neurological complications related to ZIKV infection. PMID:27001187

  11. Ganglioside storage diseases: on the road to management.

    PubMed

    Seyfried, Thomas N; Rockwell, Hannah E; Heinecke, Karie A; Martin, Douglas R; Sena-Esteves, Miguel

    2014-01-01

    Although the biochemical and genetic basis for the GM1 and GM2 gangliosidoses has been known for decades, effective therapies for these diseases remain in early stages of development. The difficulty with many therapeutic strategies for treating the gangliosidoses comes largely from their inability to remove stored ganglioside once it accumulates in central nervous system (CNS) neurons and glia. This chapter highlights advances made using substrate reduction therapy and gene therapy in reducing CNS ganglioside storage. Information obtained from mouse and feline models provides insight on therapeutic strategies that could be effective in human clinical trials. In addition, information is presented showing how a calorie-restricted diet might facilitate therapeutic drug delivery to the CNS. The development of multiple new therapeutic approaches offers hope that longer-term management of these diseases can be achieved. It is also clear that multiple therapeutic strategies will likely be needed to provide the most complete management. PMID:25151393

  12. Magnetic and magnetocaloric properties of the new rare-earth-transition-metal intermetallic compound Gd3Co29Ge4B10

    NASA Astrophysics Data System (ADS)

    Hill, P.; Dubenko, Igor; Samanta, Tapas; Quetz, Abdiel; Ali, Naushad

    2012-04-01

    The compounds Gd3-xYxCo29Ge4B10 (x = 0, 0.5, 1.0, 1.5, and 3.0), Gd3Co29Al4B10, and Gd3Co29Al4B10 were synthesized by arc melting, and their magnetic properties investigated as a function of temperature and applied magnetic field. X-ray measurements showed primarily single-phase samples with the tetragonal crystal structure P4/nmm. It was found that Gd3Co29Ge4B10 orders ferromagnetically at TC = 212 K and shows a compensation point at 128 K, indicating a ferrimagnetic ordering of the Co and Gd moments. An entropy change of -ΔS = 0.5 J/kgK was observed in a 5-T field at TC for this sample, while a change in sign for this quantity was observed both at the maximum value of magnetization (around 200 K) and then again at the compensation point. Substitution of Y for Gd in Gd3Co29Ge4B10 does not affect the Curie temperature, but shifts the compensation point to lower temperatures. This indicates that a decrease in Gd concentration does not affect the d-d exchange interaction, but has a pronounced effect on the f-d exchange interaction.

  13. Broadband Yellowish-Green Emitting Ba4Gd3Na3(PO4)6F2:Eu(2+) Phosphor: Structure Refinement, Energy Transfer, and Thermal Stability.

    PubMed

    Fu, Xiaopeng; Lü, Wei; Jiao, Mengmeng; You, Hongpeng

    2016-06-20

    A series of Ba4Gd3Na3(PO4)6F2:Eu(2+) phosphors with a broad emitting band have been synthesized by a traditional solid state reaction. The crystal structural and photoluminescence properties of Ba4Gd3Na3(PO4)6F2:Eu(2+) are investigated. The different crystallographic sites of Eu(2+) in Ba4Gd3Na3(PO4)6F2:Eu(2+) phosphors have been verified by means of their photoluminescence (PL) properties and decay times. Energy transfer between Eu(2+) ions, analyzed by excitation, emission, and PL decay behavior, has been indicated to be a dipole-dipole mechanism. Moreover, the luminescence quantum yield as well as the thermal stability of the Ba4Gd3Na3(PO4)6F2:Eu(2+) phosphor have been investigated systematically. The as-prepared Ba4Gd3Na3(PO4)6F2:Eu(2+) phosphor can act as a promising candidate for n-UV convertible white LEDs. PMID:27249557

  14. Novel Ganglioside-mediated Entry of Botulinum Neurotoxin Serotype D into Neurons

    SciTech Connect

    Kroken, Abby R.; Karalewitz, Andrew P.-A.; Fu, Zhuji; Kim, Jung-Ja P.; Barbieri, Joseph T.

    2012-02-07

    Botulinum Neurotoxins (BoNTs) are organized into seven serotypes, A-G. Although several BoNT serotypes enter neurons through synaptic vesicle cycling utilizing dual receptors (a ganglioside and a synaptic vesicle-associated protein), the entry pathway of BoNT/D is less well understood. Although BoNT/D entry is ganglioside-dependent, alignment and structural studies show that BoNT/D lacks key residues within a conserved ganglioside binding pocket that are present in BoNT serotypes A, B, E, F, and G, which indicate that BoNT/D-ganglioside interactions may be unique. In this study BoNT/D is shown to have a unique association with ganglioside relative to the other BoNT serotypes, utilizing a ganglioside binding loop (GBL, residues Tyr-1235-Ala-1245) within the receptor binding domain of BoNT/D (HCR/D) via b-series gangliosides, including GT1b, GD1b, and GD2. HCR/D bound gangliosides and entered neurons dependent upon the aromatic ring of Phe-1240 within the GBL. This is the first BoNT-ganglioside interaction that is mediated by a phenylalanine. In contrast, Trp-1238, located near the N terminus of the ganglioside binding loop, was mostly solvent-inaccessible and appeared to contribute to maintaining the loop structure. BoNT/D entry and intoxication were enhanced by membrane depolarization via synaptic vesicle cycling, where HCR/D colocalized with synaptophysin, a synaptic vesicle marker, but immunoprecipitation experiments did not detect direct association with synaptic vesicle protein 2. Thus, BoNT/D utilizes unique associations with gangliosides and synaptic vesicles to enter neurons, which may facilitate new neurotoxin therapies.

  15. Sensitized deep-ultraviolet up-conversion emissions of Gd3+ via Tm3+ and Yb3+ in hexagonal NaYF4 nanorods

    NASA Astrophysics Data System (ADS)

    Zhang, Y. Y.; Yang, L. W.; Xu, C. F.; Zhong, J. X.; Sun, C. Q.

    2010-02-01

    Deep-ultraviolet (UV) up-conversion (UC) emissions in the region of 270˜330 nm of Gd3+ under the excitation of a 980 nm laser diode in hexagonal Yb3+-Tm3+-Gd3+ triply doped NaYF4 nanorods synthesized using a hydrothermal method are reported. Spectral analyses indicate that the UV UC emissions originate from highly efficient energy transfer from Yb3+ to Tm3+, then to Gd3+ions, and the intensity of the emission as well as the ratios of the emission peaks are strongly dependent on the doping concentrations and pump power. The materials are envisioned to have potential applications in anti-counterfeiting, optical and magnetic dual modal nanoprobes for biomedicine, solution-based scintillator materials and UV compact solid-state lasers.

  16. Study of ferroelectric phase transition in Pb5Ge3O11 by paramagnetic resonance of Gd3+ centres

    NASA Astrophysics Data System (ADS)

    Vazhenin, V. A.; Rumyantsev, E. L.; Artyomov, M. Yu.; Potapov, A. P.

    2016-06-01

    The temperature dependence of the fine structure of trigonal paramagnetic Gd3+ centres in Pb5Ge3O11 was investigated in a wide temperature range in the vicinity of structural phase transition. The temperature dependence of the squared order parameter has been constructed based on the obtained data. It was shown that for the adequate description of its behaviour, the sixth-power term in polarization must be taken into account in the expansion of the thermodynamic potential. The orientational dependence of anomalous broadening of electron paramagnetic resonance signals in the vicinity of ferroelectric phase transition was studied. By comparison of the observed behaviour with the angular dependences of the line width that are characteristic of various broadening mechanisms, it was inferred that it can be attributed to defect induced statistical dispersion of fine structure triclinic parameters.

  17. Mechanochemical preparation of nanocrystalline NaYF4:Gd3+/Yb3+/Tm3+: An efficient upconversion phosphor

    NASA Astrophysics Data System (ADS)

    Zhang, Jun; Riesen, Hans

    2015-11-01

    We report on a mechanochemical preparation route for NaYF4:Gd3+/Yb3+/Tm3+ nanoparticles by ball-milling NaF, YF3, GdF3, YbF3 and TmF3 at room temperature. An analysis by XRD and TEM demonstrates that the resulting materials are mainly (∼88% after 4 h ball-milling) in the hexagonal phase and are on the nanoscale with an average crystallite size of ∼20 nm. The prepared nanoparticles display efficient upconversion emission; upon excitation by a 980 nm laser diode, bright visible blue light emission can be observed. However, in accord with previous results, the strongest emission is observed in the NIR at 800 nm.

  18. Highly biocompatible TiO2:Gd3+ nano-contrast agent with enhanced longitudinal relaxivity for targeted cancer imaging

    NASA Astrophysics Data System (ADS)

    Chandran, Parwathy; Sasidharan, Abhilash; Ashokan, Anusha; Menon, Deepthy; Nair, Shantikumar; Koyakutty, Manzoor

    2011-10-01

    We report the development of a novel magnetic nano-contrast agent (nano-CA) based on Gd3+ doped amorphous TiO2 of size ~25 nm, exhibiting enhanced longitudinal relaxivity (r1) and magnetic resonance (MR) contrasting together with excellent biocompatibility. Quantitative T1 mapping of phantom samples using a 1.5 T clinical MR imaging system revealed that the amorphous phase of doped titania has the highest r1 relaxivity which is ~2.5 fold higher than the commercially used CA Magnevist™. The crystalline (anatase) samples formed by air annealing at 250 °C and 500 °C showed significant reduction in r1 values and MR contrast, which is attributed to the loss of proton-exchange contribution from the adsorbed water and atomic re-arrangement of Gd3+ ions in the crystalline host lattice. Nanotoxicity studies including cell viability, plasma membrane integrity, reactive oxygen stress and expression of pro-inflammatory cytokines, performed on human primary endothelial cells (HUVEC), human blood derived peripheral blood mononuclear cells (PBMC) and nasopharyngeal epidermoid carcinoma (KB) cell line showed excellent biocompatibility up to relatively higher doses of 200 μg ml-1. The potential of this nano-CA to cause hemolysis, platelet aggregation and plasma coagulation were studied using human peripheral blood samples and found no adverse effects, illustrating the possibility of the safe intravenous administration of these agents for human applications. Furthermore, the ability of these agents to specifically detect cancer cells by targeting molecular receptors on the cell membrane was demonstrated on folate receptor (FR) positive oral carcinoma (KB) cells, where the folic acid conjugated nano-CA showed receptor specific accumulation on cell membrane while leaving the normal fibroblast cells (L929) unstained. This study reveals that the Gd3+ doped amorphous TiO2 nanoparticles having enhanced magnetic resonance contrast and high biocompatibility is a promising candidate for

  19. GM1 Ganglioside Treatment Facilitates Behavioral Recovery from Bilateral Brain Damage

    NASA Astrophysics Data System (ADS)

    Sabel, Bernhard A.; Slavin, Mary D.; Stein, Donald G.

    1984-07-01

    Adult rats with bilateral lesions of the caudate nucleus were treated with GM1 ganglioside. Although animals injected with a control solution were severely impaired in their ability to learn a complex spatial task, those treated with ganglioside were able to learn spatial reversals.

  20. Pathophysiological actions of neuropathy-related anti-ganglioside antibodies at the neuromuscular junction

    PubMed Central

    Plomp, Jaap J; Willison, Hugh J

    2009-01-01

    The outer leaflet of neuronal membranes is highly enriched in gangliosides. Therefore, specific neuronal roles have been attributed to this family of sialylated glycosphingolipids, e.g. in modulation of ion channels and transporters, neuronal interaction and recognition, temperature adaptation, Ca2+ homeostasis, axonal growth, (para)node of Ranvier stability and synaptic transmission. Recent developmental, ageing and injury studies on transgenic mice lacking subsets of gangliosides indicate that gangliosides are involved in maintenance rather than development of the nervous system and that ganglioside family members are able to act in a mutually compensatory manner. Besides having physiological functions, gangliosides are the likely antigenic targets of autoantibodies present in Guillain-Barré syndrome (GBS), a group of neuropathies with clinical symptoms of motor- and/or sensory peripheral nerve dysfunction. Antibody binding to peripheral nerves is thought to either interfere with ganglioside function or activate complement, causing axonal damage and thereby disturbed action potential conduction. The presynaptic motor nerve terminal at the neuromuscular junction (NMJ) may be a prominent target because it is highly enriched in gangliosides and lies outside the blood–nerve barrier, allowing antibody access. The ensuing neuromuscular synaptopathy might contribute to the muscle weakness in GBS patients. Several groups, including our own, have studied the effects of anti-ganglioside antibodies in ex vivo and in vivo experimental settings at mouse NMJs. Here, after providing a background overview on ganglioside synthesis, localization and physiology, we will review those studies, which clearly show that anti-ganglioside antibodies are capable of binding to NMJs and thereby can exert a variety of pathophysiological effects. Furthermore, we will discuss the human clinical electrophysiological and histological evidence produced so far of the existence of a neuromuscular

  1. JAK-STAT signaling mediates gangliosides-induced inflammatory responses in brain microglial cells.

    PubMed

    Kim, Ohn Soon; Park, Eun Jung; Joe, Eun-hye; Jou, Ilo

    2002-10-25

    Neuronal cell membranes are particularly rich in gangliosides, which play important roles in brain physiology and pathology. Previously, we reported that gangliosides could act as microglial activators and are thus likely to participate in many neuronal diseases. In the present study we provide evidence that JAK-STAT inflammatory signaling mediates gangliosides-stimulated microglial activation. Both in rat primary microglia and murine BV2 microglial cells, gangliosides stimulated nuclear factor binding to GAS/ISRE elements, which are known to be STAT-binding sites. Consistent with this, gangliosides rapidly activated JAK1 and JAK2 and induced phosphorylation of STAT1 and STAT3. In addition, gangliosides increased transcription of the inflammation-associated genes inducible nitric-oxide synthase, ICAM-1, and MCP-1, which are reported to contain STAT-binding elements in their promoter regions. AG490, a JAK inhibitor, reduced induction of these genes, nuclear factor binding activity, and activation of STAT1 and -3 in gangliosides-treated microglia. AG490 also inhibited gangliosides-induced release of nitric oxide, an inflammation hallmark. Furthermore, AG490 markedly reduced activation of ERK1/2 MAPK, indicating that ERKs act downstream of JAK-STAT signaling during microglial activation. However, AG490 did not affect activation of p38 MAPK. We also report that the sialic acid residues present on gangliosides may be one of the essential components in activation of JAK-STAT signaling. The present study indicates that JAK-STAT signaling is an early event in gangliosides-induced brain inflammatory responses. PMID:12191995

  2. Prevalence, specificity and functionality of anti-ganglioside antibodies in neuropathy associated with IgM monoclonal gammopathy.

    PubMed

    Stork, Abraham C J; Jacobs, Bart C; Tio-Gillen, Anne P; Eurelings, Marijke; Jansen, Marc D; van den Berg, Leonard H; Notermans, Nicolette C; van der Pol, W-Ludo

    2014-03-15

    IgM antibodies against gangliosides and their complexes were studied in sera from 54 patients with polyneuropathy and IgM monoclonal gammopathy (IgM-PNP) without anti-MAG antibodies. Anti-ganglioside antibodies were found in 19 (35%) patients. Five (9%) patients had antibodies against ganglioside complexes. IgM antibodies against gangliosides activated complement in vitro. Light chain usage was restricted to kappa or lambda in most, but not all patients. In conclusion, anti-ganglioside antibodies in IgM-PNP are common, display pathogenic properties and do not always arise from a monoclonal B cell proliferation. PMID:24529728

  3. Synthesis and Photoluminescence Characteristics of CaIn2O4:Dy3+ Phosphors Co-Doped with Gd3+, Zn2+ or AI3+ Ions.

    PubMed

    Gou, Jing; Wang, Jing; Yu, Binxun; Zhang, Dongyang

    2016-04-01

    Novel warm-white emitting phosphors CaIn2O4:Dy3+ co-doped with Gd3+, Zn2+, or Al3+ ions were prepared by solid state reaction. In this paper, a strategy of co-doping with different ions was used with the aim of affecting the luminescence properties of CaIn204:0.6%Dy3+ under NUV excitation. The luminescence intensities of CaIn2O4:0.6%Dy3+ were enhanced by 0.2% Gd3+ or 0.2% Zn2+ ions co-doping under 367 nm excitation, but lowered by co-doping with 0.2% Al3+ ions. Furthermore, the chromaticity coordinates of CaIn2O4:0.6%Dy3+ can be tuned from the cold-white region to warm-white region with Gd3+ or Zn2+ ions co-doping. These findings show that CaIn2O4:0.6%Dy3+,0.2% Gd3+, and CaIn2O4:0.6%Dy3+,0.2% Zn2+ have potential application value as new warm-white LED phosphors. PMID:27451749

  4. Time-resolved study of luminescence in soda-lime silicate glasses co-doped with Gd 3+ and Eu 3+

    NASA Astrophysics Data System (ADS)

    Kondo, Yasutaka; Tanaka, Katsuhisa; Ota, Rikuo; Fujii, Tomoki; Ishikawa, Yo-ichi

    2005-05-01

    Energy transfer process in soda-lime glasses co-doped with Gd 3+ and Eu 3+, where a ground state of Gd 3+, 8S 7/2, was selectively excited to a 6I J state by a 275-nm pulsed laser irradiation, was studied based on a time-resolved luminescence spectroscopy. The luminescence decay rate at 313 nm (Gd 3+: 6P 7/2 → 8S 7/2) was observed to be (1.5 ± 0.2) × 10 2 s -1 ( τ = 6.6 ± 0.6 ms) without Eu 3+ and to increase monotonously with increasing co-doped Eu 3+ concentration, giving an apparent quenching rate constant of (5.0 ± 0.5) × 10 -18 ion -1 cm 3 s -1 (≈(1.9 ± 0.2) × 10 3 mol% -1 s -1) for a 6P 7/2 state of Gd 3+ ion with Eu 3+. The relaxation rate of a 6I J state to a luminescent state 6P 7/2 in Gd 3+ ion was estimated to be (1.8 ± 0.2) × 10 6 s -1 from the rise rate at 313-nm luminescence ( τrise ≈ 0.56 μs), which was observed to be almost independent of the Eu 3+ concentration. The luminescence intensity from Eu 3+ at 591 nm and 613 nm monotonously increased with increasing Eu 3+ concentration up to 0.33-mol% Eu 3+, while it started decreasing at concentration of Eu 3+ higher than 0.33-mol%, which was interpreted in terms of the resonant energy transfer to nearby Eu 3+ resulting in the excitation to the Eu 3+-O - charge transfer states.

  5. A method for profiling gangliosides in animal tissues using electrospray ionization-tandem mass spectrometry.

    PubMed

    Tsui, Zhao-Chun; Chen, Qi-Rui; Thomas, Michael J; Samuel, Michael; Cui, Zheng

    2005-06-15

    Gangliosides are critical in many functions of mammalian cells but present as a minor lipid component with many molecular species of subtle differences. Conventional strategies for profiling gangliosides suffer from poor reproducibility, low sensitivity, and low-throughput capacity. Prior separation of gangliosides by thin-layer chromatography and/or high-performance liquid chromatography not only was laborious and tedious but also could introduce uneven losses of molecular species. We developed a new strategy of using electrospray ionization-tandem mass spectrometry (ESI-MS/MS) to profile gangliosides with high-throughput potential. This strategy involves three new findings: (i) collision-induced fragmentation of gangliosides gave rise to a common ion of m/z 290, a derivative of N-acetylneuraminic acid; (ii) phospholipids exert a profound suppression of ganglioside detection in ESI-MS/MS to prevent a direct detection in total cellular lipid extracts; and (iii) enrichment of gangliosides in the aqueous phase from total cellular lipid extracts eliminates the damping effect of phospholipids and permits direct precursor scan. PMID:15907870

  6. Direct evidence that ganglioside is an integral component of the thyrotropin receptor.

    PubMed

    Kielczynski, W; Harrison, L C; Leedman, P J

    1991-03-01

    Gangliosides were extracted from purified human and porcine thyrotropin (TSH) receptors (TSH-R) and were detected by probing with an 125I-labeled sialic acid-specific lectin, Limax flavus agglutinin. Gangliosides copurified with human and porcine TSH-R migrated between monosialoganglioside GM1 and disialoganglioside GD1a. Ceramide glycanase digestion of the purified human TSH-R-associated glycolipid confirmed its ganglioside nature. It was resistant to Vibrio cholerae sialidase, which digests all gangliosides except GM1, but was sensitive to Arthrobacter ureafaciens sialidase, which digests all gangliosides including GM1. These findings indicate that the human TSH-R contains ganglioside that belongs to the galactosyl(beta 1----3)-N-acetylgalactosaminyl (beta 1----4)-[N-acetylneuraminyl(alpha 2----3)]galactosyl(beta 1----4) glucosyl(beta 1----1)ceramide (GM1) family. Its intimate association with receptor protein implies a key role for ganglioside in the structure and function of the TSH-R. PMID:2000404

  7. Direct evidence that ganglioside is an integral component of the thyrotropin receptor

    SciTech Connect

    Kielczynski, W.; Harrison, L.C.; Leedman, P.J. )

    1991-03-01

    Gangliosides were extracted from purified human and porcine thyrotropin (TSH) receptors (TSH-R) and were detected by probing with an {sup 125}I-labeled sialic acid-specific lectin, Limax flavus agglutinin. Gangliosides copurified with human and porcine TSH-R migrated between monosialoganglioside GM1 and disialoganglioside GD1a. Ceramide glycanase digestion of the purified human TSH-R-associated glycolipid confirmed its ganglioside nature. It was resistant to Vibrio cholerae sialidase, which digest all gangliosides except GM1, but was sensitive to Arthrobacter ureafaciens sialidase, which digests all gangliosides including GM1. These findings indicate that the human TSH-R contains ganglioside that belongs to the galactosyl({beta}1{r arrow} 3)-N-acetylgalactosaminyl({beta}1{r arrow} 4)-(N-acetylneuraminyl({alpha}2{r arrow} 3))galactosyl({beta}1 {r arrow} 4)glucosyl({beta}1 {r arrow} 1)ceramide (GM1) family. Its intimate association with receptor protein implies a key role for ganglioside in the structure and function of the TSH-R.

  8. Alteration of Ganglioside Biosynthesis Responsible for Complex Hereditary Spastic Paraplegia

    PubMed Central

    Boukhris, Amir; Schule, Rebecca; Loureiro, José L.; Lourenço, Charles Marques; Mundwiller, Emeline; Gonzalez, Michael A.; Charles, Perrine; Gauthier, Julie; Rekik, Imen; Acosta Lebrigio, Rafael F.; Gaussen, Marion; Speziani, Fiorella; Ferbert, Andreas; Feki, Imed; Caballero-Oteyza, Andrés; Dionne-Laporte, Alexandre; Amri, Mohamed; Noreau, Anne; Forlani, Sylvie; Cruz, Vitor T.; Mochel, Fanny; Coutinho, Paula; Dion, Patrick; Mhiri, Chokri; Schols, Ludger; Pouget, Jean; Darios, Frédéric; Rouleau, Guy A.; Marques, Wilson; Brice, Alexis; Durr, Alexandra; Zuchner, Stephan; Stevanin, Giovanni

    2013-01-01

    Hereditary spastic paraplegias (HSPs) form a heterogeneous group of neurological disorders. A whole-genome linkage mapping effort was made with three HSP-affected families from Spain, Portugal, and Tunisia and it allowed us to reduce the SPG26 locus interval from 34 to 9 Mb. Subsequently, a targeted capture was made to sequence the entire exome of affected individuals from these three families, as well as from two additional autosomal-recessive HSP-affected families of German and Brazilian origins. Five homozygous truncating (n = 3) and missense (n = 2) mutations were identified in B4GALNT1. After this finding, we analyzed the entire coding region of this gene in 65 additional cases, and three mutations were identified in two subjects. All mutated cases presented an early-onset spastic paraplegia, with frequent intellectual disability, cerebellar ataxia, and peripheral neuropathy as well as cortical atrophy and white matter hyperintensities on brain imaging. B4GALNT1 encodes β-1,4-N-acetyl-galactosaminyl transferase 1 (B4GALNT1), involved in ganglioside biosynthesis. These findings confirm the increasing interest of lipid metabolism in HSPs. Interestingly, although the catabolism of gangliosides is implicated in a variety of neurological diseases, SPG26 is only the second human disease involving defects of their biosynthesis. PMID:23746551

  9. Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia.

    PubMed

    Boukhris, Amir; Schule, Rebecca; Loureiro, José L; Lourenço, Charles Marques; Mundwiller, Emeline; Gonzalez, Michael A; Charles, Perrine; Gauthier, Julie; Rekik, Imen; Acosta Lebrigio, Rafael F; Gaussen, Marion; Speziani, Fiorella; Ferbert, Andreas; Feki, Imed; Caballero-Oteyza, Andrés; Dionne-Laporte, Alexandre; Amri, Mohamed; Noreau, Anne; Forlani, Sylvie; Cruz, Vitor T; Mochel, Fanny; Coutinho, Paula; Dion, Patrick; Mhiri, Chokri; Schols, Ludger; Pouget, Jean; Darios, Frédéric; Rouleau, Guy A; Marques, Wilson; Brice, Alexis; Durr, Alexandra; Zuchner, Stephan; Stevanin, Giovanni

    2013-07-11

    Hereditary spastic paraplegias (HSPs) form a heterogeneous group of neurological disorders. A whole-genome linkage mapping effort was made with three HSP-affected families from Spain, Portugal, and Tunisia and it allowed us to reduce the SPG26 locus interval from 34 to 9 Mb. Subsequently, a targeted capture was made to sequence the entire exome of affected individuals from these three families, as well as from two additional autosomal-recessive HSP-affected families of German and Brazilian origins. Five homozygous truncating (n = 3) and missense (n = 2) mutations were identified in B4GALNT1. After this finding, we analyzed the entire coding region of this gene in 65 additional cases, and three mutations were identified in two subjects. All mutated cases presented an early-onset spastic paraplegia, with frequent intellectual disability, cerebellar ataxia, and peripheral neuropathy as well as cortical atrophy and white matter hyperintensities on brain imaging. B4GALNT1 encodes β-1,4-N-acetyl-galactosaminyl transferase 1 (B4GALNT1), involved in ganglioside biosynthesis. These findings confirm the increasing interest of lipid metabolism in HSPs. Interestingly, although the catabolism of gangliosides is implicated in a variety of neurological diseases, SPG26 is only the second human disease involving defects of their biosynthesis. PMID:23746551

  10. Cholesterol transfer between lipid vesicles. Effect of phospholipids and gangliosides.

    PubMed Central

    Thomas, P D; Poznansky, M J

    1988-01-01

    The effect of lipid composition on the rate of cholesterol movement between cellular membranes is investigated using lipid vesicles. The separation of donor and acceptor vesicles required for rate measurement is achieved by differential centrifugation so that the lipid effect can be quantified in the absence of a charged lipid generally used for ion-exchange-based separation. The rate of cholesterol transfer from small unilamellar vesicles (SUVs) containing 50 mol% cholesterol to a common large unilamellar vesicle (LUV) acceptor containing 20 mol% cholesterol decreases with increasing mol% of sphingomyelin in the SUVs, while phosphatidylethanolamine and phosphatidylserine have no appreciable effect at physiologically relevant levels. There is a large decrease in rate when phosphatidylethanolamine constitutes 50 mol% of donor phospholipids. Interestingly, gangliosides which have the same hydrocarbon moiety as sphingomyelin exert an opposite effect. The effect of spingomyelin seems to be mediated by its ability to decrease the fluidity of the lipid matrix, while that of gangliosides may arise from a weakening of phosphatidylcholine-cholesterol interactions or from a more favourable (less polar) microenvironment for the desorption of cholesterol provided by the head-group interactions involving sugar residues. If the effect of asymmetric transbilayer distribution of lipids is taken into consideration, the observed composition-dependent rate changes could partly account for the large difference in the rates of cholesterol desorption from the inner and outer layers of plasma membrane. Such rate differences may be responsible for an unequal steady-state distribution of cholesterol among various cellular membranes and lipoproteins. PMID:3390160

  11. Spectroscopy and Laser Properties of Yb-Doped Gd3AlxGa5-xO12 Crystal

    NASA Astrophysics Data System (ADS)

    Zhang, Bai-Tao; He, Jing-Liang; Jia, Zhi-Tai; Li, Yan-Bin; Liu, Shan-De; Wang, Zhao-Wei; Wang, Rui-Hua; Liu, Xun-Min; Tao, Xu-tang

    2013-08-01

    We report the room-temperature spectroscopic properties and the continuous-wave and passive Q-switching laser operations of a new disorder crystal, Yb-doped Gd3AlxGa5-xO12 (Yb:GAGG). The peak absorption cross section is 0.56×10-20 cm2 at 942 nm, while the main emission band is centered at 1024 nm with a peak cross section of 1.05×10-20 cm2 and the full width at half maximum (FWHM) of 13.8 nm. The highest continuous-wave output power of 5.33 W is obtained with the optical-optical conversion efficiency of 41.6% and slope efficiency of 53.2%. In the passive Q-switching regime, with a V3+:YAG crystal as the saturable absorber, the highest output power, shortest pulse width, largest pulse energy and highest peak power achieved are 4.68 W, 24.7 ns, 93.8 µJ, and 3.8 kW, respectively. The results indicates that Yb:GAGG could be a potential laser crystal for high-power and ultrashort pulse generation.

  12. Recovery from Experimental Parkinsonism in Primates with GM1 Ganglioside Treatment

    NASA Astrophysics Data System (ADS)

    Schneider, J. S.; Pope, Anne; Simpson, Kimberly; Taggart, James; Smith, M. G.; Distefano, L.

    1992-05-01

    A parkinsonian syndrome can be produced in nonhuman primates by administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Parkinsonian-like symptoms induced acutely by MPTP were ameliorated after treatment with GM1 ganglioside, a substance shown to have neurotrophic effects on the damaged dopamine system in rodents. Treatment with GM1 ganglioside also increased striatal dopamine and metabolite levels and enhanced the dopaminergic innervation of the striatum as demonstrated by tyrosine hydroxylase immunohistochemistry. These results suggest that GM1 ganglioside may hold promise as a therapeutic agent for the treatment of Parkinson's disease.

  13. Gd3+ and Calcium Sensitive, Sodium Leak Currents Are Features of Weak Membrane-Glass Seals in Patch Clamp Recordings

    PubMed Central

    Chemin, Jean; Monteil, Arnaud; Spafford, J. David

    2014-01-01

    The properties of leaky patch currents in whole cell recording of HEK-293T cells were examined as a means to separate these control currents from expressed sodium and calcium leak channel currents from snail NALCN leak channels possessing both sodium (EKEE) and calcium (EEEE) selectivity filters. Leak currents were generated by the weakening of gigaohm patch seals by artificial membrane rupture using the ZAP function on the patch clamp amplifier. Surprisingly, we found that leak currents generated from the weakened membrane/glass seal can be surprisingly stable and exhibit behavior that is consistent with a sodium leak current derived from an expressible channel. Leaky patch currents differing by 10 fold in size were similarly reduced in size when external sodium ions were replaced with the large monovalent ion NMDG+. Leaky patch currents increased when external Ca2+ (1.2 mM) was lowered to 0.1 mM and were inhibited (>40% to >90%) with 10 µM Gd3+, 100 µM La3+, 1 mM Co2+ or 1 mM Cd2+. Leaky patch currents were relatively insensitive (<30%) to 1 mM Ni2+ and exhibited a variable amount of block with 1 mM verapamil and were insensitive to 100 µM mibefradil or 100 µM nifedipine. We hypothesize that the rapid changes in leak current size in response to changing external cations or drugs relates to their influences on the membrane seal adherence and the electro-osmotic flow of mobile cations channeling in crevices of a particular pore size in the interface between the negatively charged patch electrode and the lipid membrane. Observed sodium leak conductance currents in weak patch seals are reproducible between the electrode glass interface with cell membranes, artificial lipid or Sylgard rubber. PMID:24945283

  14. Magnetic behavior of Gd3Ru4Al12, a layered compound with distorted kagomé net

    NASA Astrophysics Data System (ADS)

    Chandragiri, Venkatesh; Iyer, Kartik K.; Sampathkumaran, E. V.

    2016-07-01

    The magnetic behavior of the compound, Gd3Ru4Al12, which was reported about two decades ago to crystallize in a hexagonal structure (space group P63/mmc), has not been investigated in the past literature despite interesting structural features (that is, magnetic layers and triangular as well as kagomé-lattice features favoring frustrated magnetism) characterizing this compound. We report here the results of studies of magnetization, heat capacity and magnetoresistance in the temperature range T  =  1.8–300 K. The results establish that there is a long-range magnetic order of antiferromagnetic type below (T N  =) 18.5 K, despite a much larger value (~80 K) of paramagnetic Curie temperature with a positive sign characteristic of ferromagnetic interaction. We attribute this to geometric frustration. The most interesting finding is that there is an additional magnetic anomaly below ~55 K before the onset of long-range order in the magnetic susceptibility data. Concurrent with this observation, the sign of isothermal change in entropy, ΔS  =  S(0)  ‑  S(H), where H is the externally applied magnetic field, remains positive above T N, with a broad peak. This observation indicates the presence of ferromagnetic clusters before the onset of long-range magnetic order. Thus, this compound may serve as an example of a situation in which magnetic frustration due to geometrical reasons faces competition from such magnetic precursor effects. There is also a reversal of the sign of  ‑ΔS in the curves for lower final fields (H  <  30 kOe) on entering the magnetically ordered state consistent with the entrance to an antiferromagetic state. The magnetoresistance behavior is consistent with the above conclusions.

  15. Mice deficient in Neu4 sialidase exhibit abnormal ganglioside catabolism and lysosomal storage.

    PubMed

    Seyrantepe, Volkan; Canuel, Maryssa; Carpentier, Stéphane; Landry, Karine; Durand, Stéphanie; Liang, Feng; Zeng, Jibin; Caqueret, Aurore; Gravel, Roy A; Marchesini, Sergio; Zwingmann, Claudia; Michaud, Jacques; Morales, Carlos R; Levade, Thierry; Pshezhetsky, Alexey V

    2008-06-01

    Mammalian sialidase Neu4, ubiquitously expressed in human tissues, is located in the lysosomal and mitochondrial lumen and has broad substrate specificity against sialylated glycoconjugates. To investigate whether Neu4 is involved in ganglioside catabolism, we transfected beta-hexosaminidase-deficient neuroglia cells from a Tay-Sachs patient with a Neu4-expressing plasmid and demonstrated the correction of storage due to the clearance of accumulated GM2 ganglioside. To further clarify the biological role of Neu4, we have generated a stable loss-of-function phenotype in cultured HeLa cells and in mice with targeted disruption of the Neu4 gene. The silenced HeLa cells showed reduced activity against gangliosides and had large heterogeneous lysosomes containing lamellar structures. Neu4(-/-) mice were viable, fertile and lacked gross morphological abnormalities, but showed a marked vacuolization and lysosomal storage in lung and spleen cells. Lysosomal storage bodies were also present in cultured macrophages preloaded with gangliosides. Thin-layer chromatography showed increased relative level of GD1a ganglioside and a markedly decreased level of GM1 ganglioside in brain of Neu4(-/-) mice suggesting that Neu4 may be important for desialylation of brain gangliosides and consistent with the in situ hybridization data. Increased levels of cholesterol, ceramide and polyunsaturated fatty acids were also detected in the lungs and spleen of Neu4(-/-) mice by high-resolution NMR spectroscopy. Together, our data suggest that Neu4 is a functional component of the ganglioside-metabolizing system, contributing to the postnatal development of the brain and other vital organs. PMID:18270209

  16. Effects of Gangliosides on the Activity of the Plasma Membrane Ca2+-ATPase

    PubMed Central

    Jiang, Lei; Bechtel, Misty D.; Bean, Jennifer L.; Winefield, Robert; Williams, Todd D.; Zaidi, Asma; Michaelis, Elias K.; Michaelis, Mary L.

    2014-01-01

    Control of intracellular calcium concentrations ([Ca2+]i) is essential for neuronal function, and the plasma membrane Ca2+-ATPase (PMCA) is crucial for the maintenance of low [Ca2+]i. We previously reported on loss of PMCA activity in brain synaptic membranes during aging. Gangliosides are known to modulate Ca2+ homeostasis and signal transduction in neurons. In the present study, we observed age-related changes in the ganglioside composition of synaptic plasma membranes. This led us to hypothesize that alterations in ganglioside species might contribute to the age-associated loss of PMCA activity. To probe the relationship between changes in endogenous ganglioside content or composition and PMCA activity in membranes of cortical neurons, we induced depletion of gangliosides by treating neurons with D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP). This caused a marked decrease in the activity of PMCA, which suggested a direct correlation between ganglioside content and PMCA activity. Neurons treated with neuraminidase exhibited an increase in GM1 content, a loss in poly-sialoganglioside content, and a decrease in PMCA activity that was greater than that produced by D-PDMP treatment. Thus, it appeared that poly-sialogangliosides had a stimulatory effect whereas mono-sialogangliosides had the opposite effect. Our observations add support to previous reports of PMCA regulation by gangliosides by demonstrating that manipulations of endogenous ganglioside content and species affect the activity of PMCA in neuronal membranes. Furthermore, our studies suggest that age-associated loss in PMCA activity may result in part from changes in the lipid environment of this Ca2+ transporter. PMID:24434060

  17. Electrospray Ionization Ion Mobility Mass Spectrometry of Human Brain Gangliosides.

    PubMed

    Sarbu, Mirela; Robu, Adrian C; Ghiulai, Roxana M; Vukelić, Željka; Clemmer, David E; Zamfir, Alina D

    2016-05-17

    The progress of ion mobility spectrometry (IMS), together with its association to mass spectrometry (MS), opened new directions for the identification of various metabolites in complex biological matrices. However, glycolipidomics of the human brain by IMS MS represents an area untouched up to now, because of the difficulties encountered in brain sampling, analyte extraction, and IMS MS method optimization. In this study, IMS MS was introduced in human brain ganglioside (GG) research. The efficiency of the method in clinical glycolipidomics was demonstrated on a highly complex mixture extracted from a normal fetal frontal lobe (FL37). Using this approach, a remarkably rich molecular ion pattern was discovered, which proved the presence of a large number of glycoforms and an unpredicted diversity of the ceramide chains. Moreover, the results showed for the first time the occurrence of GGs in the human brain with a much higher degree of sialylation than previously reported. Using IMS MS, the entire series starting from mono- up to octasialylated GGs was detected in FL37. These findings substantiate early clinical reports on the direct correlation between GG sialylation degree and brain developmental stage. Using IMS CID MS/MS, applied here for the first time to gangliosides, a novel, tetrasialylated O-GalNAc modified species with a potential biomarker role in brain development was structurally characterized. Under variable collision energy, a high number of sequence ions was generated for the investigated GalNAc-GQ1(d18:1/18:0) species. Several fragment ions documented the presence of the tetrasialo element attached to the inner Gal, indicating that GalNAc-GQ1(d18:1/18:0) belongs to the d series. PMID:27088833

  18. Single cell ganglioside catabolism in primary cerebellar neurons and glia

    PubMed Central

    Essaka, David C.; Prendergast, Jillian; Keithley, Richard B.; Hindsgaul, Ole; Palcic, Monica M.

    2013-01-01

    Cell-to-cell heterogeneity in ganglioside catabolism was determined by profiling fluorescent tetramethylrhodamine-labeled GM1 (TMR-GM1) breakdown in individual primary neurons and glia from the rat cerebellum. Cells isolated from 5–6 day old rat cerebella were cultured for 7 days, and then incubated for 14 h with TMR-GM1. Intact cells were recovered from cultures by mild proteolysis, paraformaldehyde fixed, and subjected to single cell analysis. Individual cells were captured in a capillary, lysed, and the released single-cell contents subjected to capillary electrophoresis with quantitative laser-induced fluorescent detection of the catabolic products. Non-neuronal cells on average took up much more exogenous TMR-GM1 than neuronal cells, and catabolized it more extensively. After 14 h of incubation, non-neuronal cells retained only 14% of the TMR products as GM1 and GM2, compared to >50% for neurons. On average, non-neuronal cells contained 74% of TMR-labeled product as TMR-ceramide, compared to only 42% for neurons. Non-neuronal cells retained seven times as much TMR-GM3 (7%) compared to neuronal cells (1%). To confirm the observed single cell metabolomics, we lysed and compared TMR-GM1 catabolic profiles from mixed neuron/glial cell cultures and from cultures depleted of non-neuronal cells by treatment with the antimitotic agent cytosine arabinoside. The whole culture catabolic profiles were consistent with the average profiles of single neurons and glia. We conclude that the ultrasensitive analytic methods described accurately reflect single cell ganglioside catabolism in different cell populations from the brain. PMID:22407243

  19. The Protective Effect of Gangliosides on Lead (Pb)-Induced Neurotoxicity Is Mediated by Autophagic Pathways.

    PubMed

    Meng, Hongtao; Wang, Lan; He, Junhong; Wang, Zhufeng

    2016-01-01

    Lead (Pb) is a ubiquitous environmental and industrial pollutant and can affect intelligence development and the learning ability and memory of children. Therefore, necessary measures should be taken to protect the central nervous system (CNS) from Pb toxicity. Gangliosides are sialic acid-containing glycosphingolipids that are constituents of mammalian cell membranes and are more abundantly expressed in the CNS. Studies have shown that gangliosides constitute a useful tool in the attempt to promote functional recovery of CNS and can reverse Pb-induced impairments of synaptic plasticity in rats. However, the detailed mechanisms have yet to be fully understood. In our present study, we tried to investigate the role of gangliosides in Pb-induced injury in hippocampus neurons and to further confirm the detailed mechanism. Our results show that Pb-induced injuries in the spatial reference memory were associated with a reduction of cell viability and cell apoptosis, and treatment with gangliosides markedly ameliorated the Pb-induced injury by inhibition of apoptosis action. Gangliosides further attenuated Pb-induced the abnormal autophagic process by regulation of mTOR pathways. In summary, our study establishes the efficacy of gangliosides as neuroprotective agents and provides a strong rationale for further studies on the underlying mechanisms of their neuroprotective functions. PMID:27023584

  20. Number of Sialic Acid Residues in Ganglioside Headgroup Affects Interactions with Neighboring Lipids

    PubMed Central

    Frey, Shelli L.; Lee, Ka Yee C.

    2013-01-01

    Monolayers of binary mixtures of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and asialo-(GA1), disialo-(GD1b) and trisialo-(GT1b) gangliosides were used to determine the effect of ganglioside headgroup charge and geometry on its interactions with the neighboring zwitterionic lipid. Surface pressure versus molecular area isotherm measurements along with concurrent fluorescence microscopy of the monolayers at the air-water interface were complemented with atomic force microscopy imaging of monolayers deposited on solid substrates. Results were used to further develop a proposed geometric packing model that the complementary geometry of DPPC and monosialoganglioside GM1 headgroups affects their close molecular packing, inducing condensation of the layer at small mol % of ganglioside. For GA1, GD1b, and GT1b, a similar condensing effect, followed by a fluidizing effect is seen that varies with glycosphingolipid concentration, but results do not directly follow from geometric arguments because less DPPC is needed to condense ganglioside molecules with larger cross-sectional areas. The variations in critical packing mole ratios can be explained by global effects of headgroup charge and resultant dipole moments within the monolayer. Atomic force microscopy micrographs further support the model of ganglioside-induced DPPC condensation with condensed domains composed of a striped phase of condensed DPPC and DPPC/ganglioside geometrically packed complexes at low concentrations. PMID:24047994

  1. Number of sialic acid residues in ganglioside headgroup affects interactions with neighboring lipids.

    PubMed

    Frey, Shelli L; Lee, Ka Yee C

    2013-09-17

    Monolayers of binary mixtures of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and asialo-(GA1), disialo-(GD1b) and trisialo-(GT1b) gangliosides were used to determine the effect of ganglioside headgroup charge and geometry on its interactions with the neighboring zwitterionic lipid. Surface pressure versus molecular area isotherm measurements along with concurrent fluorescence microscopy of the monolayers at the air-water interface were complemented with atomic force microscopy imaging of monolayers deposited on solid substrates. Results were used to further develop a proposed geometric packing model that the complementary geometry of DPPC and monosialoganglioside GM1 headgroups affects their close molecular packing, inducing condensation of the layer at small mol % of ganglioside. For GA1, GD1b, and GT1b, a similar condensing effect, followed by a fluidizing effect is seen that varies with glycosphingolipid concentration, but results do not directly follow from geometric arguments because less DPPC is needed to condense ganglioside molecules with larger cross-sectional areas. The variations in critical packing mole ratios can be explained by global effects of headgroup charge and resultant dipole moments within the monolayer. Atomic force microscopy micrographs further support the model of ganglioside-induced DPPC condensation with condensed domains composed of a striped phase of condensed DPPC and DPPC/ganglioside geometrically packed complexes at low concentrations. PMID:24047994

  2. The Protective Effect of Gangliosides on Lead (Pb)-Induced Neurotoxicity Is Mediated by Autophagic Pathways

    PubMed Central

    Meng, Hongtao; Wang, Lan; He, Junhong; Wang, Zhufeng

    2016-01-01

    Lead (Pb) is a ubiquitous environmental and industrial pollutant and can affect intelligence development and the learning ability and memory of children. Therefore, necessary measures should be taken to protect the central nervous system (CNS) from Pb toxicity. Gangliosides are sialic acid-containing glycosphingolipids that are constituents of mammalian cell membranes and are more abundantly expressed in the CNS. Studies have shown that gangliosides constitute a useful tool in the attempt to promote functional recovery of CNS and can reverse Pb-induced impairments of synaptic plasticity in rats. However, the detailed mechanisms have yet to be fully understood. In our present study, we tried to investigate the role of gangliosides in Pb-induced injury in hippocampus neurons and to further confirm the detailed mechanism. Our results show that Pb-induced injuries in the spatial reference memory were associated with a reduction of cell viability and cell apoptosis, and treatment with gangliosides markedly ameliorated the Pb-induced injury by inhibition of apoptosis action. Gangliosides further attenuated Pb-induced the abnormal autophagic process by regulation of mTOR pathways. In summary, our study establishes the efficacy of gangliosides as neuroprotective agents and provides a strong rationale for further studies on the underlying mechanisms of their neuroprotective functions. PMID:27023584

  3. Conjugation of glucosamine with Gd3+-based nanoporous silica using a heterobifunctional ANB-NOS crosslinker for imaging of cancer cells

    PubMed Central

    Mehravi, Bita; Ahmadi, Mohsen; Amanlou, Massoud; Mostaar, Ahmad; Ardestani, Mehdi Shafiee; Ghalandarlaki, Negar

    2013-01-01

    Background The aim of this study was to synthesize Gd3+-based silica nanoparticles that conjugate easily with glucosamine and to investigate their use as a nanoprobe for detection of human fibrosarcoma cells. Methods Based on the structure of the 2-fluoro-2-deoxy-D-glucose molecule (18FDG), a new compound consisting of D-glucose (1.1 nm) was conjugated with a Gd3+-based mesoporous silica nanoparticle using an N-5-azido-2-nitrobenzoyloxy succinimide (ANB-NOS) crosslinker The contrast agent obtained was characterized using a variety of methods, including Fourier transform infrared spectroscopy, nitrogen physisorption, thermogravimetric analysis, scanning and transmission electron microscopy, and inductively coupled plasma atomic emission spectrometry (ICP-AES). In vitro studies included cell toxicity, apoptosis, tumor necrosis factor-alpha, and hexokinase assays, and in vivo tests consisted of evaluation of blood glucose levels using the contrast compound and tumor imaging. The cellular uptake study was validated using ICP-AES. Magnetic resonance relaxivity of the contrast agent was determined using a 1.5 Tesla scanner. Results ANB-NOS was found to be the preferred linker for attaching glucosamine onto the surface of the mesoporous silica nanospheres. The r1 relaxivity for the nanoparticles was 17.70 mM−1s−1 per Gd3+ ion, which is 4.4 times larger than that for Magnevist® (r1 approximately 4 mM−1s−1 per Gd3+ ion). The compound showed suitable cellular uptake (75.6% ± 2.01%) without any appreciable cytotoxicity. Conclusion Our results suggest that covalently attaching glucosamine molecules to mesoporous silica nanoparticles enables effective targeted delivery of a contrast agent. PMID:24101868

  4. Cr4 + :Gd3Sc2Ga3O12 passive Q-switch for the Cr3 + :LiCaAlF6 laser

    NASA Astrophysics Data System (ADS)

    Kuo, Yen-Kuang; Yang, Yang; Birnbaum, Milton

    1994-05-01

    A Cr4+:Gd3Sc2Ga3O12 (Cr4+:GSGG) broad-band saturable absorber has been demonstrated to be an excellent passive Q-switch for the flashlamp-pumped tunable Cr3+:LiCaAlF6 (Cr:LiCAF) laser at room temperature. A single Q-switched laser output pulse of 11 mJ in energy and 37 ns in duration at 778 nm was obtained in a nonoptimized laser.

  5. Enhancement of encaged electron concentration by Sr(2+) doping and improvement of Gd(3+) emission through controlling encaged anions in conductive C12A7 phosphors.

    PubMed

    Zhang, Meng; Liu, Yuxue; Zhu, Hancheng; Yan, Duanting; Yang, Jian; Zhang, Xinyang; Liu, Chunguang; Xu, Changshan

    2016-07-28

    Conductive C12A7:0.1%Gd(3+),y%Sr(2+) powders with different Sr(2+) doping concentrations have been prepared in a H2 atmosphere by a solid state method in combination with subsequent UV-irradiation. The encaged electron concentration could be modulated through tuning Sr(2+) doping and its maximum value reaches 2.3 × 10(19) cm(-3). This is attributed to the competition between enhanced uptake and the release of the encaged anions during their formation and diffusion processes and the suppression of encaged electrons generation due to the increased encaged OH(-) anions and the decreased encaged O(2-) anions. Although there exists encaged electrons and different encaged anions (O(2-), H(-) and OH(-)) in C12A7 conductive powders prepared through the hydrogen route, a dominant local environment around Gd(3+) could be observed using electron spin resonance (ESR) detection. It can be ascribed to the stronger coupling of the encaged OH(-) to the framework of C12A7 than those of the encaged electrons, O(2-) and H(-) anions. In addition, emission of Gd(3+) ions is enhanced under UV or low voltage electron beam excitation and a new local environment around Gd(3+) ions appears through the thermal annealing in air because of the decrease of the encaged OH(-) anions and the increase of the encaged O(2-) anions. Our results suggested that Sr(2+) doping in combination with thermal annealing in air is an effective strategy for increasing the conductive performance and enhancing the emission of rare earth ions doped into C12A7 conductive phosphors for low-voltage field emission displays (FEDs). PMID:27079823

  6. W-band orientation selective DEER measurements on a Gd3+/nitroxide mixed-labeled protein dimer with a dual mode cavity

    NASA Astrophysics Data System (ADS)

    Kaminker, Ilia; Tkach, Igor; Manukovsky, Nurit; Huber, Thomas; Yagi, Hiromasa; Otting, Gottfried; Bennati, Marina; Goldfarb, Daniella

    2013-02-01

    Double electron-electron resonance (DEER) at W-band (95 GHz) was applied to measure the distance between a pair of nitroxide and Gd3+ chelate spin labels, about 6 nm apart, in a homodimer of the protein ERp29. While high-field DEER measurements on systems with such mixed labels can be highly attractive in terms of sensitivity and the potential to access long distances, a major difficulty arises from the large frequency spacing (about 700 MHz) between the narrow, intense signal of the Gd3+ central transition and the nitroxide signal. This is particularly problematic when using standard single-mode cavities. Here we show that a novel dual-mode cavity that matches this large frequency separation dramatically increases the sensitivity of DEER measurements, allowing evolution times as long as 12 μs in a protein. This opens the possibility of accessing distances of 8 nm and longer. In addition, orientation selection can be resolved and analyzed, thus providing additional structural information. In the case of W-band DEER on a Gd3+-nitroxide pair, only two angles and their distributions have to be determined, which is a much simpler problem to solve than the five angles and their distributions associated with two nitroxide spin labels.

  7. Ultraviolet upconversion enhancement in triply doped NaYF4:Tm3+, Yb3+ particles: The role of Nd3+ or Gd3+ Co-doping

    NASA Astrophysics Data System (ADS)

    Pokhrel, Madhab; Valdes, Carolina; Mao, Yuanbing

    2016-08-01

    Upconversion (UC) particles are currently under intensive investigation, normally for their visible instead of ultraviolet (UV) light luminescence under near-infrared (NIR) irradiation. As a commonly studied host, NaYF4 in particular is known to have low phonon energy and high UC efficiency. Here, we present our work on enhancing UC luminescence in the UV region by adding a third dopant into a binary-doped NaYF4:Yb3+,Tm3+ host. More specifically, neodymium (Nd3+) or gadolinium (Gd3+) ions was co-doped into parent NaYF4:20mol%Yb3+,0.5mol%Tm3+ UC particles to enhance their UV UC luminescence. Experimental results demonstrated that these particles exhibited the highest degree of UV UC enhancements when co-doped with 0.05mol% Nd3+ or 2.0mol% Gd3+, expanding the potential of this type of materials into many possible applications by directly converting NIR irradiation into UV light. Fundamentally, the UV UC emission dependence of these triply doped NaYF4:Yb3+,Tm3+ particles with different Nd3+ and Gd3+ doping concentrations was investigated in terms of ground state absorption, excited state absorption and energy transfer UC mechanisms.

  8. Synthesis, crystal structure, and physical properties of the Gd3BiO3 and Gd8Bi3O8 phases

    NASA Astrophysics Data System (ADS)

    Forbes, Scott; Yuan, Fang; Kosuda, Kosuke; Kolodiazhnyi, Taras; Mozharivskyj, Yurij

    2016-01-01

    The second and third known rare-earth bismuthide oxides, Gd3BiO3 and Gd8Bi3O8, have been discovered via high temperature reactions at 1300 °C. Like its Gd-Sb-O counterparts, the Gd3BiO3 and Gd8Bi3O8 phases crystallize in the monoclinic C2/m space group, with the latter containing disordered Bi atoms along the b direction of the unit cell. Unlike the RE8Sb3O8 series, the formation of the Gd3BiO3 phase does not necessarily precede the formation of Gd8Bi3O8, which is likely due to the difficulty of accommodating bismuth in the RE-O framework due to its larger size. Physical property measurements performed on a pure Gd8Bi3O8 sample reveal semiconducting behavior. Although electronic structure calculations predict metallic behavior due to an unbalanced electron count, the semiconducting behavior originates from the Anderson localization of the Bi p states near the Fermi level as a result of atomic disorder.

  9. Facile preparation of Gd3+ doped carbon quantum dots: Photoluminescence materials with magnetic resonance response as magnetic resonance/fluorescence bimodal probes

    NASA Astrophysics Data System (ADS)

    Ren, X. Y.; Yuan, X. X.; Wang, Y. P.; Liu, C. L.; Qin, Y.; Guo, L. P.; Liu, L. H.

    2016-07-01

    There are a few bimodal molecular imaging probes constructed by gadolinium (3+) ions in combination with carbon quantum dots (CQDs), and the reported ones show such obvious drawbacks as low luminous efficiency and weak MRI contrast. In the paper, a kind of CQDs photoluminescence materials with magnetic resonance response was prepared by hydrothermal method and employing gadopentetate monomeglumine (GdPM) as a precusor. Here, the GdPM plays a role of not only carbon source, but also gadolinium (3+) sources. When the GdPM aqueous solution with a concentration of 4 mg mL-1 was pyrolyzed under 220 °C and 2.0 MPa for 8 h, an optimal CQDs was obtained which are doped with gadolinium (3+) ions in both chelates and Gd2O3 (named as Gd3+-CQDs). The average diameter of the Gd3+-CQDs is about 1.6 nm, which show a high photoluminescence quantum yield of 7.1%, as well as high longitudinal relaxivity (r1) of 9.87 mM-1 s-1. And owing to the unconspicuous cell toxicity, the Gd3+-CQDs show big possibility for clinical application in magnetic resonance/fluorescence bimodal molecular imaging.

  10. Binary and Ternary Heterometallic (La3+, Gd3+, Y3+)-Eu3+ Functionalized SBA-15 Mesoporous Hybrids: Chemically Bonded Assembly and Photoluminescence

    NASA Astrophysics Data System (ADS)

    Yan, Bing; Kong, Li-Li

    2010-07-01

    A novel kind of organic-inorganic monomer SUASi has been achieved by modifying 5-sulfosalicylic acid (SUA) with 3-aminopropyltrimethoxysilane (APS), subsequently binary and ternary Eu3+ mesoporous hybrid materials with 5-sulfosalicylic acid (SUA)-functionalized SBA-15 and 1,10-phenanthroline (phen) are synthesized by co-condensation of SUASi and TEOS in the presence of Eu3+ complex and Pluronic P123 as a template. Finally, luminescent hybrid mesoporous materials consisting of active rare earth ions (Eu3+)—inert rare earth ions (Y3+, La3+, Gd3+) complex covalently bonded to the mesoporous materials network have been obtained via this sol-gel approach. The physical characterization and photoluminescence of all these resulting materials are studied in detail. Especially the luminescent behavior has been studied with the different ratios of Eu3+-(Y3+, La3+, Gd3+), which suggests that the existence of inert rare earth ions can enhance the luminescence intensity of Eu3+. This may be due to the intramolecular energy transfer between Y3+, La3+, Gd3+, and Eu3+ through the covalently bonded mesoporous framework.

  11. Effect of Mg2+ ions co-doping on timing performance and radiation tolerance of Cerium doped Gd3Al2Ga3O12 crystals

    NASA Astrophysics Data System (ADS)

    Lucchini, M. T.; Babin, V.; Bohacek, P.; Gundacker, S.; Kamada, K.; Nikl, M.; Petrosyan, A.; Yoshikawa, A.; Auffray, E.

    2016-04-01

    Inorganic scintillators with high density and high light yield are of major interest for applications in medical imaging and high energy physics detectors. In this work, the optical and scintillation properties of Mg co-doped Ce:Gd3Al2Ga3O12 crystals, grown using Czochralski technique, have been investigated and compared with Ce:Gd3Al2Ga3O12 ones prepared with identical technology. Improvements in the timing performance of the Mg co-doped samples with respect to Ce:Gd3Al2Ga3O12 ones have been measured, namely a substantial shortening of the rise time and scintillation decay components and lower afterglow were achieved. In particular, a significantly better coincidence time resolution of 233 ps FWHM, being a fundamental parameter for TOF-PET devices, has been observed in Mg co-doped crystals. The samples have also shown a good radiation tolerance under high doses of γ-rays, making them suitable candidates for applications in harsh radiation environments, such as detectors at future collider experiments.

  12. Enhanced UVB emission and analysis of chemical states of Ca5(PO4)3OH:Gd3+,Pr3+ phosphor prepared by co-precipitation

    NASA Astrophysics Data System (ADS)

    Mokoena, P. P.; Nagpure, I. M.; Kumar, Vinay; Kroon, R. E.; Olivier, E. J.; Neethling, J. H.; Swart, H. C.; Ntwaeaborwa, O. M.

    2014-08-01

    Hydroxyapatite (Ca5(PO4)3OH) is a well-known bioceramic material used in medical applications because of its ability to form direct chemical bonds with living tissues. This mineral is currently used as a host for rare-earth ions (e.g. Gd3+, Pr3+, Tb3+, etc.) to prepare phosphors that can be used in light emitting devices of different types. In this study Ca5(PO4)3OH:Gd3+,Pr3+ phosphors were prepared by the co-precipitation method and were characterised by x-ray diffraction, x-ray photoelectron spectroscopy, scanning electron microscopy, high resolution transmission electron microscopy, energy dispersive x-ray spectroscopy and photoluminescence spectroscopy. The x-ray diffraction pattern was consistent with the hexagonal phase of Ca5(PO4)3OH referenced in JCPDS card number 73-0293. The x-ray photoelectron spectroscopy data indicated that Ca2+ occupied two different lattice sites, referred to as Ca1 and Ca2. The photoluminescence data exhibited a narrowband emission located at 313 nm, which is associated with the 6P7/2→8S7/2 transition of the Gd3+ ion. This emission is classified as ultraviolet B and it is suitable for use in phototherapy lamps to treat various skin diseases. The photoluminescence intensity of the 313 nm emission was enhanced considerably by Pr3+ co-doping.

  13. Combination of ESI and MALDI mass spectrometry for qualitative, semi-quantitative and in situ analysis of gangliosides in brain

    PubMed Central

    Zhang, Yangyang; Wang, Jun; Liu, Jian’an; Han, Juanjuan; Xiong, Shaoxiang; Yong, Weidong; Zhao, Zhenwen

    2016-01-01

    Gangliosides are a family of complex lipids that are abundant in the brain. There is no doubt the investigations about the distribution of gangliosides in brian and the relationship between gangliosides and Alzheimer’s disease is profound. However, these investigations are full of challenges due to the structural complexity of gangliosides. In this work, the method for efficient extraction and enrichment of gangliosides from brain was established. Moreover, the distribution of gangliosides in brain was obtained by matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI). It was found that 3-aminoquinoline (3-AQ) as matrix was well-suited for MALDI MS analysis of gangliosides in negative ion mode. In addition, the pretreatment by ethanol (EtOH) cleaning brain section and the addition of ammonium formate greatly improved the MS signal of gangliosides in the brain section when MALDI MSI analysis was employed. The distribution of ganliosides in cerebral cortex, hippocampus and cerebellum was respectively acquired by electrospray ionization (ESI) MS and MALDI MSI, and the data were compared for reliability evaluation of MALDI MSI. Further, applying MALDI MSI technology, the distribution of gangliosides in amyloid precursor protein transgenic mouse brain was obtained, which may provide a new insight for bioresearch of Alzheimer’s disease (AD). PMID:27142336

  14. The biological activity of botulinum neurotoxin type C is dependent upon novel types of ganglioside binding sites.

    PubMed

    Strotmeier, Jasmin; Gu, Shenyan; Jutzi, Stephan; Mahrhold, Stefan; Zhou, Jie; Pich, Andreas; Eichner, Timo; Bigalke, Hans; Rummel, Andreas; Jin, Rongsheng; Binz, Thomas

    2011-07-01

    The seven botulinum neurotoxins (BoNT) cause muscle paralysis by selectively cleaving core components of the vesicular fusion machinery. Their extraordinary activity primarily relies on highly specific entry into neurons. Data on BoNT/A, B, E, F and G suggest that entry follows a dual receptor interaction with complex gangliosides via an established ganglioside binding region and a synaptic vesicle protein. Here, we report high resolution crystal structures of the BoNT/C cell binding fragment alone and in complex with sialic acid. The WY-motif characteristic of the established ganglioside binding region was located on an exposed loop. Sialic acid was co-ordinated at a novel position neighbouring the binding pocket for synaptotagmin in BoNT/B and G and the sialic acid binding site in BoNT/D and TeNT respectively. Employing synaptosomes and immobilized gangliosides binding studies with BoNT/C mutants showed that the ganglioside binding WY-loop, the newly identified sialic acid-co-ordinating pocket and the area corresponding to the established ganglioside binding region of other BoNTs are involved in ganglioside interaction. Phrenic nerve hemidiaphragm activity tests employing ganglioside deficient mice furthermore evidenced that the biological activity of BoNT/C depends on ganglioside interaction with at least two binding sites. These data suggest a unique cell binding and entry mechanism for BoNT/C among clostridial neurotoxins. PMID:21542861

  15. Combination of ESI and MALDI mass spectrometry for qualitative, semi-quantitative and in situ analysis of gangliosides in brain.

    PubMed

    Zhang, Yangyang; Wang, Jun; Liu, Jian'an; Han, Juanjuan; Xiong, Shaoxiang; Yong, Weidong; Zhao, Zhenwen

    2016-01-01

    Gangliosides are a family of complex lipids that are abundant in the brain. There is no doubt the investigations about the distribution of gangliosides in brian and the relationship between gangliosides and Alzheimer's disease is profound. However, these investigations are full of challenges due to the structural complexity of gangliosides. In this work, the method for efficient extraction and enrichment of gangliosides from brain was established. Moreover, the distribution of gangliosides in brain was obtained by matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI). It was found that 3-aminoquinoline (3-AQ) as matrix was well-suited for MALDI MS analysis of gangliosides in negative ion mode. In addition, the pretreatment by ethanol (EtOH) cleaning brain section and the addition of ammonium formate greatly improved the MS signal of gangliosides in the brain section when MALDI MSI analysis was employed. The distribution of ganliosides in cerebral cortex, hippocampus and cerebellum was respectively acquired by electrospray ionization (ESI) MS and MALDI MSI, and the data were compared for reliability evaluation of MALDI MSI. Further, applying MALDI MSI technology, the distribution of gangliosides in amyloid precursor protein transgenic mouse brain was obtained, which may provide a new insight for bioresearch of Alzheimer's disease (AD). PMID:27142336

  16. Proton NMR study of spin dynamics in the magnetic organic chains M (hfac)3 NITEt (M =Eu3 +,Gd3 + )

    NASA Astrophysics Data System (ADS)

    Mariani, M.; Lascialfari, A.; Caneschi, A.; Ammannato, L.; Gatteschi, D.; Rettori, A.; Pini, M. G.; Cucci, C.; Borsa, F.

    2016-04-01

    In this work, we present a nuclear magnetic resonance (NMR) study of the spin dynamics in the rare-earth-based low-dimensional molecular magnetic chains Eu (hfac) 3NITEt and Gd (hfac) 3NITEt (in short, Eu-Et and Gd-Et). Although both samples are based on the same chemical building block, [(hfac) 3NITEt ] , their magnetic properties change dramatically when the Eu3 + ion, which is nonmagnetic at low temperatures, is substituted by the magnetic Gd3 + ion. The present proton NMR investigation shows that, down to the lowest investigated temperature (T =1.5 K for Gd-Et and T =3 K for Eu-Et), the Eu-Et chain behaves as a one-dimensional Heisenberg model with antiferromagnetic exchange coupling (J =-20 K) between s =1 /2 organic radicals, and has a T -independent exchange frequency (ωe=2.6 ×1012 rad/s). In the Gd-Et chain, in contrast, a competition arises between nearest-neighbor ferromagnetic coupling and next-nearest-neighbor antiferromagnetic coupling; moreover, two phase transitions have previously been found, in agreement with Villain's conjecture: a first transition, at T0=2.2 K, from a high temperature paramagnetic phase to a chiral spin liquid phase, and a second transition, at TN=1.9 K, to a three-dimensional helical spin solid phase. Contrary to the Eu-Et chain (whose three-dimensional ordering temperature is estimated to insurge at very low, TN≈0.3 K), critical spin dynamics effects have been measured in the Gd-Et chain on approaching TN=1.9 K: namely, a divergence of the proton nuclear spin-lattice relaxation rate 1 /T1 , which in turn produces a sudden wipe-out of the NMR signal in a very narrow (Δ T ˜0.04 K) temperature range above TN. Below TN, an inhomogeneous broadening of the NMR line indicates a complete spin freezing. At T0=2.2 K, instead, such critical effects are not observed because NMR measurements probe the two-spin correlation function, while the chiral spin liquid phase transition is associated with a divergence of the four

  17. Leukemia-induced bone marrow depression: effects of gangliosides on erythroid cell production.

    PubMed

    Sietsma, H; Kamps, W A; Dontje, B; Hendriks, D; Kok, J W; Vellenga, E; Nijhof, W

    1999-07-01

    Bone marrow depression is a common feature in hematological malignancies or other bone marrow-involving cancers. The mechanism of this hemopoietic suppression resulting in pancytopenia and especially anemia has not been elucidated. Gangliosides can be shed by cancer cells. Therefore, we investigated the effects of exogenously added gangliosides on erythropoiesis in a human and murine in vitro system. A dose-dependent inhibition of murine colony-forming-unit-erythroid (CFU-E) and burst-forming-unit-erythroid (BFU-E) colony growth was observed. Furthermore the maturation of BFU-Es into CFU-Es was inhibited. The inhibition by gangliosides was not abolished by increasing the dose of erythropoietin (10 U/ml). FACS-analysis studies with human CD34+ cells cultured with gangliosides (GM3), erythropoietin (EPO) and stem cell factor (SCF) demonstrated a strong inhibition on cell growth. This resulted in a significantly higher percentage of immature cells (CD34+/GpA-, 24% vs. 3%), and a lower percentage of mature erythroid cells (CD34-/GpA+, 36% vs. 89%). Under these circumstances the effects on erythroid cell growth were much higher than on other cell lineages. The inhibitory effect of gangliosides isolated from acute lymphoblastic leukemic patients on in vitro erythropoiesis suggests that in vivo hemopoietic suppression might have its origin in the gangliosides present and probably shed by the malignant cells in the microenvironment and plasma. Our results show that gangliosides inhibit erythropoiesis in vitro at several stages of development, by a mechanism involving modulation of the maturation of erythroid cells. PMID:10360826

  18. Mutations in B4GALNT1 (GM2 synthase) underlie a new disorder of ganglioside biosynthesis

    PubMed Central

    Lehman, Anna; Chioza, Barry; Baple, Emma L.; Maroofian, Reza; Cross, Harold; Sreekantan-Nair, Ajith; Priestman, David A.; Al-Turki, Saeed; McEntagart, Meriel E.; Proukakis, Christos; Royle, Louise; Kozak, Radoslaw P.; Bastaki, Laila; Patton, Michael; Wagner, Karin; Coblentz, Roselyn; Price, Joy; Mezei, Michelle; Schlade-Bartusiak, Kamilla; Hurles, Matthew E.

    2013-01-01

    Glycosphingolipids are ubiquitous constituents of eukaryotic plasma membranes, and their sialylated derivatives, gangliosides, are the major class of glycoconjugates expressed by neurons. Deficiencies in their catabolic pathways give rise to a large and well-studied group of inherited disorders, the lysosomal storage diseases. Although many glycosphingolipid catabolic defects have been defined, only one proven inherited disease arising from a defect in ganglioside biosynthesis is known. This disease, because of defects in the first step of ganglioside biosynthesis (GM3 synthase), results in a severe epileptic disorder found at high frequency amongst the Old Order Amish. Here we investigated an unusual neurodegenerative phenotype, most commonly classified as a complex form of hereditary spastic paraplegia, present in families from Kuwait, Italy and the Old Order Amish. Our genetic studies identified mutations in B4GALNT1 (GM2 synthase), encoding the enzyme that catalyzes the second step in complex ganglioside biosynthesis, as the cause of this neurodegenerative phenotype. Biochemical profiling of glycosphingolipid biosynthesis confirmed a lack of GM2 in affected subjects in association with a predictable increase in levels of its precursor, GM3, a finding that will greatly facilitate diagnosis of this condition. With the description of two neurological human diseases involving defects in two sequentially acting enzymes in ganglioside biosynthesis, there is the real possibility that a previously unidentified family of ganglioside deficiency diseases exist. The study of patients and animal models of these disorders will pave the way for a greater understanding of the role gangliosides play in neuronal structure and function and provide insights into the development of effective treatment therapies. PMID:24103911

  19. Mutations in B4GALNT1 (GM2 synthase) underlie a new disorder of ganglioside biosynthesis.

    PubMed

    Harlalka, Gaurav V; Lehman, Anna; Chioza, Barry; Baple, Emma L; Maroofian, Reza; Cross, Harold; Sreekantan-Nair, Ajith; Priestman, David A; Al-Turki, Saeed; McEntagart, Meriel E; Proukakis, Christos; Royle, Louise; Kozak, Radoslaw P; Bastaki, Laila; Patton, Michael; Wagner, Karin; Coblentz, Roselyn; Price, Joy; Mezei, Michelle; Schlade-Bartusiak, Kamilla; Platt, Frances M; Hurles, Matthew E; Crosby, Andrew H

    2013-12-01

    Glycosphingolipids are ubiquitous constituents of eukaryotic plasma membranes, and their sialylated derivatives, gangliosides, are the major class of glycoconjugates expressed by neurons. Deficiencies in their catabolic pathways give rise to a large and well-studied group of inherited disorders, the lysosomal storage diseases. Although many glycosphingolipid catabolic defects have been defined, only one proven inherited disease arising from a defect in ganglioside biosynthesis is known. This disease, because of defects in the first step of ganglioside biosynthesis (GM3 synthase), results in a severe epileptic disorder found at high frequency amongst the Old Order Amish. Here we investigated an unusual neurodegenerative phenotype, most commonly classified as a complex form of hereditary spastic paraplegia, present in families from Kuwait, Italy and the Old Order Amish. Our genetic studies identified mutations in B4GALNT1 (GM2 synthase), encoding the enzyme that catalyzes the second step in complex ganglioside biosynthesis, as the cause of this neurodegenerative phenotype. Biochemical profiling of glycosphingolipid biosynthesis confirmed a lack of GM2 in affected subjects in association with a predictable increase in levels of its precursor, GM3, a finding that will greatly facilitate diagnosis of this condition. With the description of two neurological human diseases involving defects in two sequentially acting enzymes in ganglioside biosynthesis, there is the real possibility that a previously unidentified family of ganglioside deficiency diseases exist. The study of patients and animal models of these disorders will pave the way for a greater understanding of the role gangliosides play in neuronal structure and function and provide insights into the development of effective treatment therapies. PMID:24103911

  20. Properties of ganglioside GM1 in phosphatidylcholine bilayer membranes.

    PubMed

    Reed, R A; Shipley, G G

    1996-03-01

    Gangliosides have been shown to function as cell surface receptors, as well as participating in cell growth, differentiation, and transformation. In spite of their multiple biological functions, relatively little is known about their structure and physical properties in membrane systems. The thermotropic and structural properties of ganglioside GM1 alone and in a binary system with 1,2-dipalmitoyl phosphatidylcholine (DPPC) have been investigated by differential scanning calorimetry (DSC) and x-ray diffraction. By DSC hydrated GM1 undergoes a broad endothermic transition TM = 26 degrees C (delta H = 1.7 kcal/mol GM1). X-ray diffraction below (-2 degrees C) and above (51 degrees C) this transition indicates a micellar structure with changes occurring only in the wide angle region of the diffraction pattern (relatively sharp reflection at 1/4.12 A-1 at -2 degrees C; more diffuse reflection at 1/4.41 A-1 at 51 degrees C). In hydrated binary mixtures with DPPC, incorporation of GM1 (0-30 mol%; zone 1) decreases the enthalpy of the DPPC pretransition at low molar compositions while increasing the TM of both the pre- and main transitions (limiting values, 39 and 44 degrees C, respectively). X-ray diffraction studies indicate the presence of a single bilayer gel phase in zone 1 that can undergo chain melting to an L alpha bilayer phase. A detailed hydration study of GM1 (5.7 mol %)/DPPC indicated a conversion of the DPPC bilayer gel phase to an infinite swelling system in zone 1 due to the presence of the negatively charged sialic acid moiety of GM1. At 30-61 mol % GM1 (zone 2), two calorimetric transitions are observed at 44 and 47 degrees C, suggesting the presence of two phases. The lower transition reflects the bilayer gel --> L alpha transition (zone 1), whereas the upper transition appears to be a consequence of the formation of a nonbilayer, micellar or hexagonal phase, although the structure of this phase has not been defined by x-ray diffraction. At > 61 mol % GM

  1. Raft-based interactions of gangliosides with a GPI-anchored receptor.

    PubMed

    Komura, Naoko; Suzuki, Kenichi G N; Ando, Hiromune; Konishi, Miku; Koikeda, Machi; Imamura, Akihiro; Chadda, Rahul; Fujiwara, Takahiro K; Tsuboi, Hisae; Sheng, Ren; Cho, Wonhwa; Furukawa, Koichi; Furukawa, Keiko; Yamauchi, Yoshio; Ishida, Hideharu; Kusumi, Akihiro; Kiso, Makoto

    2016-06-01

    Gangliosides, glycosphingolipids containing one or more sialic acid(s) in the glyco-chain, are involved in various important physiological and pathological processes in the plasma membrane. However, their exact functions are poorly understood, primarily because of the scarcity of suitable fluorescent ganglioside analogs. Here, we developed methods for systematically synthesizing analogs that behave like their native counterparts in regard to partitioning into raft-related membrane domains or preparations. Single-fluorescent-molecule imaging in the live-cell plasma membrane revealed the clear but transient colocalization and codiffusion of fluorescent ganglioside analogs with a fluorescently labeled glycosylphosphatidylinisotol (GPI)-anchored protein, human CD59, with lifetimes of 12 ms for CD59 monomers, 40 ms for CD59's transient homodimer rafts in quiescent cells, and 48 ms for engaged-CD59-cluster rafts, in cholesterol- and GPI-anchoring-dependent manners. The ganglioside molecules were always mobile in quiescent cells. These results show that gangliosides continually and dynamically exchange between raft domains and the bulk domain, indicating that raft domains are dynamic entities. PMID:27043189

  2. Localization and imaging of gangliosides in mouse brain tissue sections by laserspray ionization inlet.

    PubMed

    Richards, Alicia L; Lietz, Christopher B; Wager-Miller, James; Mackie, Ken; Trimpin, Sarah

    2012-07-01

    A new ionization method for the analysis of fragile gangliosides without undesired fragmentation or salt adduction is presented. In laserspray ionization inlet (LSII), the matrix/analyte sample is ablated at atmospheric pressure, and ionization takes place in the ion transfer capillary of the mass spectrometer inlet by a process that is independent of a laser wavelength or voltage. The softness of LSII allows the identification of gangliosides up to GQ1 with negligible sialic acid loss. This is of importance to the field of MS imaging, as undesired fragmentation has made it difficult to accurately map the spatial distribution of fragile ganglioside lipids in tissue. Proof-of-principle structural characterization of endogenous gangliosides using MS(n) fragmentation of multiply charged negative ions on a LTQ Velos and subsequent imaging of the GD1 ganglioside is demonstrated. This is the first report of multiply charged negative ions using inlet ionization. We find that GD1 is detected at higher levels in the mouse cortex and hippocampus compared with the thalamus. In LSII with the laser aligned in transmission geometry relative to the inlet, images were obtained in approximately 60 min using an inexpensive nitrogen laser. PMID:22262808

  3. Partial synthesis of ganglioside and lysoganglioside lipoforms as internal standards for MS quantification

    PubMed Central

    Gantner, Martin; Schwarzmann, Günter; Sandhoff, Konrad; Kolter, Thomas

    2014-01-01

    Within recent years, ganglioside patterns have been increasingly analyzed by MS. However, internal standards for calibration are only available for gangliosides GM1, GM2, and GM3. For this reason, we prepared homologous internal standards bearing nonnatural fatty acids of the major mammalian brain gangliosides GM1, GD1a, GD1b, GT1b, and GQ1b, and of the tumor-associated gangliosides GM2 and GD2. The fatty acid moieties were incorporated after selective chemical or enzymatic deacylation of bovine brain gangliosides. For modification of the sphingoid bases, we developed a new synthetic method based on olefin cross metathesis. This method was used for the preparation of a lyso-GM1 and a lyso-GM2 standard. The total yield of this method was 8.7% for the synthesis of d17:1-lyso-GM1 from d20:1/18:0-GM1 in four steps. The title compounds are currently used as calibration substances for MS quantification and are also suitable for functional studies. PMID:25341943

  4. Localization and imaging of gangliosides in mouse brain tissue sections by laserspray ionization inlet[S

    PubMed Central

    Richards, Alicia L.; Lietz, Christopher B.; Wager-Miller, James; Mackie, Ken; Trimpin, Sarah

    2012-01-01

    A new ionization method for the analysis of fragile gangliosides without undesired fragmentation or salt adduction is presented. In laserspray ionization inlet (LSII), the matrix/analyte sample is ablated at atmospheric pressure, and ionization takes place in the ion transfer capillary of the mass spectrometer inlet by a process that is independent of a laser wavelength or voltage. The softness of LSII allows the identification of gangliosides up to GQ1 with negligible sialic acid loss. This is of importance to the field of MS imaging, as undesired fragmentation has made it difficult to accurately map the spatial distribution of fragile ganglioside lipids in tissue. Proof-of-principle structural characterization of endogenous gangliosides using MSn fragmentation of multiply charged negative ions on a LTQ Velos and subsequent imaging of the GD1 ganglioside is demonstrated. This is the first report of multiply charged negative ions using inlet ionization. We find that GD1 is detected at higher levels in the mouse cortex and hippocampus compared with the thalamus. In LSII with the laser aligned in transmission geometry relative to the inlet, images were obtained in approximately 60 min using an inexpensive nitrogen laser. PMID:22262808

  5. Oligosaccharide-specific receptors for gangliosides in the central nervous system

    SciTech Connect

    Tiemeyer, M.J.

    1989-01-01

    Synthetic ganglioside-derivatized proteins were prepared, radiolabeled, and used as ligands to search for specific receptors on rat brain membranes. Chemical derivatization schemes were designed to covalently link gangliosides (specifically, G{sub T1b}) to bovine serum albumin (BSA) via their ceramide portions leaving the glycolipid oligosaccharides intact and limiting the ability of the ganglioside moiety to interact with brain membranes non-specifically by insertion or hydrophobic adsorption. Following characterization and tyrosine-radioiodination, {sup 125}I-(G{sub T1b}){sub 4} BSA (BSA derivatized with 4 G{sub T1b} moieties/protein molecule), revealed a high affinity and saturable binding site on rat brain membranes. Pretreatment of brain membranes with low concentrations of trypsin blocked binding, consistent with the presence of a proteinaceous ganglioside-receptor. The most potent lipid inhibitors of {sup 125}I-(G{sub T1b}){sub 4}BSA binding were the gangliosides G{sub T1b}, G{sub D1b}, and G{sub Q1b} which share common structural features in their oligosaccharide portions; maximal inhibitory potency required a full length gangliotetraose oligosaccharide core and {alpha}2-8 linked sialic acid.

  6. Effect of Gd3+ doping on structural, optical and frequency-dependent dielectric response properties of pseudo-cubic BaTiO3 nanostructures

    NASA Astrophysics Data System (ADS)

    Borah, Manjit; Mohanta, Dambarudhar

    2014-06-01

    We report on the structural, optical and dielectric characterization of solid state derived, pseudo-cubic nanoscale barium titanates (BTs) with gadolinium (Gd3+) as substitutional dopant. Referring to X-ray diffractograms, apart from the BT peaks related to perovskite structure, the non-existence of any additional peaks due to byproducts has revealed that Gd3+ has undergone substitutional doping into the BT host lattice. The well-separated BT nanoparticles of typical size ˜10-15 nm were observed through electron microscopy studies. Following a direct, allowed type carrier transition ( n=1/2), a reduction in the optical band gap value (from 3.28 to 3.255 eV) was observed when the Gd-doping level was varied within 0-7 %. Conversely, the Urbach energy followed an increasing trend, from a value of 0.741 to 1.879 eV. Furthermore, the dielectric constant showed a decreasing tendency with doping content and with increasing frequency. However, in the low-frequency region, the loss tangent (tan δ), which is the combined result of orientational polarization and electrical conduction, was found to be quite high in the doped samples as compared to their un-doped counterpart. The frequency-dependent electrical data were also analyzed in the framework of conductivity and impedance formalisms. In particular, the ac conductivity which varies as ˜ ω s approaches ideal Debye behavior ( s→1) for a low Gd level and a higher doping concentration did not show improved dielectric feature of the host. The incorporation of rare-earth (Gd3+) ions into the BT host system could greatly manifest dielectric relaxation and carrier conduction mechanisms, in a given frequency range, and thus can find immense scope in miniaturized nanoelectronic elements including ceramic capacitors and transducers.

  7. Investigation of cyano-bridged coordination nanoparticles Gd(3+)/[Fe(CN)6](3-)/D-mannitol as T1-weighted MRI contrast agents.

    PubMed

    Perrier, M; Gallud, A; Ayadi, A; Kennouche, S; Porredon, C; Gary-Bobo, M; Larionova, J; Goze-Bac, Ch; Zanca, M; Garcia, M; Basile, I; Long, J; de Lapuente, J; Borras, M; Guari, Y

    2015-07-28

    Cyano-bridged Gd(3+)/[Fe(CN)6](3-) coordination polymer nanoparticles of 3-4 nm stabilized with D-mannitol presenting a high r1 relaxivity value of 11.4 mM(-1) s(-1) were investigated in vivo as contrast agents (CA) for Magnetic Resonance Imaging (MRI). They allow an increase of the MR image contrast and can act as an efficient intravascular T1 CA with a relatively long blood-circulation lifetime (60 min) without specific toxicity. PMID:25967733

  8. Nondestructive detection of gangliosides with lipophilic fluorochromes and their employment for preparative high-performance thin-layer chromatography.

    PubMed

    Müthing, J; Heitmann, D

    1993-01-01

    A simple and effective procedure for the isolation and purification of gangliosides by preparative thin-layer chromatography is described. The method is based on nondestructive visualization of gangliosides on silica gel-precoated thin-layer chromatography plates by staining with uncharged lipophilic fluorochromes. Fluorescent dyes were added in low concentrations into the mobile phase (0.002%, w/v) without any interference of the ganglioside separation. After uv localization, the fluorescent zones were scraped off the plate and the silica gel was extracted with chloroform/methanol/water (30/60/8). In the following step fluorochromes were removed from gangliosides containing crude extracts by anion-exchange chromatography on DEAE-Sepharose. After desalting, impurities were removed by Iatrobeads chromatography. The method described offers an easy to handle and successful preparative thin-layer chromatography strategy to obtain pure gangliosides in microgram and miligram quantities. PMID:8434781

  9. 5-Methoxysalicylic Acid Matrix for Ganglioside Analysis with Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Lee, Dongkun; Cha, Sangwon

    2015-03-01

    In this note, we report that high quality ganglioside profiles with minimal loss of sialic acid residues can be obtained in the positive ion mode by using a 5-methoxysalicylic acid (MSA) matrix for matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). Our results showed that MSA produced much less sialic acid losses from gangliosides than DHB, although MSA and DHB are differ only by their functional groups at their 5-positions (-OH for DHB and -OCH3 for MSA). Furthermore, our data also demonstrated that addition of an alkali metal additive was effective for simplifying ganglioside profiles, but not necessary for stabilizing glycosidic bonds of gangliosides if MSA was used as a matrix. This suggests that MALDI MS with MSA has a potential to gain additional benefits from the positive-ion mode analyses without losing performance in ganglioside profiling.

  10. NGcGM3 ganglioside: a privileged target for cancer vaccines.

    PubMed

    Fernandez, Luis E; Gabri, Mariano R; Guthmann, Marcelo D; Gomez, Roberto E; Gold, Silvia; Fainboim, Leonardo; Gomez, Daniel E; Alonso, Daniel F

    2010-01-01

    Active specific immunotherapy is a promising field in cancer research. N-glycolyl (NGc) gangliosides, and particularly NGcGM3, have received attention as a privileged target for cancer therapy. Many clinical trials have been performed with the anti-NGc-containing gangliosides anti-idiotype monoclonal antibody racotumomab (formerly known as 1E10) and the conjugated NGcGM3/VSSP vaccine for immunotherapy of melanoma, breast, and lung cancer. The present paper examines the role of NGc-gangliosides in tumor biology as well as the available preclinical and clinical data on these vaccine products. A brief discussion on the relevance of prioritization of cancer antigens in vaccine development is also included. PMID:21048926

  11. NGcGM3 Ganglioside: A Privileged Target for Cancer Vaccines

    PubMed Central

    Fernandez, Luis E.; Gabri, Mariano R.; Guthmann, Marcelo D.; Gomez, Roberto E.; Gold, Silvia; Fainboim, Leonardo; Gomez, Daniel E.; Alonso, Daniel F.

    2010-01-01

    Active specific immunotherapy is a promising field in cancer research. N-glycolyl (NGc) gangliosides, and particularly NGcGM3, have received attention as a privileged target for cancer therapy. Many clinical trials have been performed with the anti-NGc-containing gangliosides anti-idiotype monoclonal antibody racotumomab (formerly known as 1E10) and the conjugated NGcGM3/VSSP vaccine for immunotherapy of melanoma, breast, and lung cancer. The present paper examines the role of NGc-gangliosides in tumor biology as well as the available preclinical and clinical data on these vaccine products. A brief discussion on the relevance of prioritization of cancer antigens in vaccine development is also included. PMID:21048926

  12. Cross-Linking Mast Cell Specific Gangliosides Stimulates the Release of Newly Formed Lipid Mediators and Newly Synthesized Cytokines.

    PubMed

    Filho, Edismauro Garcia Freitas; da Silva, Elaine Zayas Marcelino; Zanotto, Camila Ziliotto; Oliver, Constance; Jamur, Maria Célia

    2016-01-01

    Mast cells are immunoregulatory cells that participate in inflammatory processes. Cross-linking mast cell specific GD1b derived gangliosides by mAbAA4 results in partial activation of mast cells without the release of preformed mediators. The present study examines the release of newly formed and newly synthesized mediators following ganglioside cross-linking. Cross-linking the gangliosides with mAbAA4 released the newly formed lipid mediators, prostaglandins D2 and E2, without release of leukotrienes B4 and C4. The effect of cross-linking these gangliosides on the activation of enzymes in the arachidonate cascade was then investigated. Ganglioside cross-linking resulted in phosphorylation of cytosolic phospholipase A2 and increased expression of cyclooxygenase-2. Translocation of 5-lipoxygenase from the cytosol to the nucleus was not induced by ganglioside cross-linking. Cross-linking of GD1b derived gangliosides also resulted in the release of the newly synthesized mediators, interleukin-4, interleukin-6, and TNF-α. The effect of cross-linking the gangliosides on the MAP kinase pathway was then investigated. Cross-linking the gangliosides induced the phosphorylation of ERK1/2, JNK1/2, and p38 as well as activating both NFκB and NFAT in a Syk-dependent manner. Therefore, cross-linking the mast cell specific GD1b derived gangliosides results in the activation of signaling pathways that culminate with the release of newly formed and newly synthesized mediators. PMID:27578923

  13. Cross-Linking Mast Cell Specific Gangliosides Stimulates the Release of Newly Formed Lipid Mediators and Newly Synthesized Cytokines

    PubMed Central

    Zanotto, Camila Ziliotto

    2016-01-01

    Mast cells are immunoregulatory cells that participate in inflammatory processes. Cross-linking mast cell specific GD1b derived gangliosides by mAbAA4 results in partial activation of mast cells without the release of preformed mediators. The present study examines the release of newly formed and newly synthesized mediators following ganglioside cross-linking. Cross-linking the gangliosides with mAbAA4 released the newly formed lipid mediators, prostaglandins D2 and E2, without release of leukotrienes B4 and C4. The effect of cross-linking these gangliosides on the activation of enzymes in the arachidonate cascade was then investigated. Ganglioside cross-linking resulted in phosphorylation of cytosolic phospholipase A2 and increased expression of cyclooxygenase-2. Translocation of 5-lipoxygenase from the cytosol to the nucleus was not induced by ganglioside cross-linking. Cross-linking of GD1b derived gangliosides also resulted in the release of the newly synthesized mediators, interleukin-4, interleukin-6, and TNF-α. The effect of cross-linking the gangliosides on the MAP kinase pathway was then investigated. Cross-linking the gangliosides induced the phosphorylation of ERK1/2, JNK1/2, and p38 as well as activating both NFκB and NFAT in a Syk-dependent manner. Therefore, cross-linking the mast cell specific GD1b derived gangliosides results in the activation of signaling pathways that culminate with the release of newly formed and newly synthesized mediators. PMID:27578923

  14. Gangliosides do not affect ABC transporter function in human neuroblastoma cells.

    PubMed

    Dijkhuis, Anne-Jan; Klappe, Karin; Kamps, Willem; Sietsma, Hannie; Kok, Jan Willem

    2006-06-01

    Previous studies have indicated a role for glucosylceramide synthase (GCS) in multidrug resistance (MDR), either related to turnover of ceramide (Cer) or generation of gangliosides, which modulate apoptosis and/or the activity of ABC transporters. This study challenges the hypothesis that gangliosides modulate the activity of ABC transporters and was performed in two human neuroblastoma cell lines, expressing either functional P-glycoprotein (Pgp) or multidrug resistance-related protein 1 (MRP1). Two inhibitors of GCS, D,L-threo-1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol (t-PPPP) and N-butyldeoxynojirimycin (NB-dNJ), very efficiently depleted ganglioside content in two human neuroblastoma cell lines. This was established by three different assays: equilibrium radiolabeling, cholera toxin binding, and mass analysis. Fluorescence-activated cell sorting (FACS) analysis showed that ganglioside depletion only slightly and in the opposite direction affected Pgp- and MRP1-mediated efflux activity. Moreover, both effects were marginal compared with those of well-established inhibitors of either MRP1 (i.e., MK571) or Pgp (i.e., GF120918). t-PPPP slightly enhanced cellular sensitivity to vincristine, as determined by 3-[4,5-dimethylthiazol-2-yl]2,5-diphenyl tetrazolium bromide analysis, in both neuroblastoma cell lines, whereas NB-dNJ was without effect. MRP1 expression and its localization in detergent-resistant membranes were not affected by ganglioside depletion. Together, these results show that gangliosides are not relevant to ABC transporter-mediated MDR in neuroblastoma cells. PMID:16547352

  15. Anti-ganglioside antibody-induced tumor cell death by loss of membrane integrity.

    PubMed

    Roque-Navarro, Lourdes; Chakrabandhu, Krittalak; de León, Joel; Rodríguez, Sandra; Toledo, Carlos; Carr, Adriana; de Acosta, Cristina Mateo; Hueber, Anne-Odile; Pérez, Rolando

    2008-07-01

    Gangliosides have been involved in multiple cellular processes such as growth, differentiation and adhesion, and more recently as regulators of cell death signaling pathways. Some of these molecules can be considered as tumor-associated antigens, in particular, N-glycolyl sialic acid-containing gangliosides, which are promising candidates for cancer-targeted therapy because of their low expression in normal human tissues. In this study, we provided the molecular and cellular characterization of a novel cell death mechanism induced by the anti-NGcGM3 14F7 monoclonal antibody (mAb) in L1210 murine tumor cell line but not in mouse normal cells (B and CD4(+) T lymphocytes) that expressed the antigen. Impairment of ganglioside synthesis in tumor cells abrogated the 14F7 mAb cytotoxic effect; however, exogenous reincorporation of the ganglioside did not restore tumor cell sensitivity to 14F7 mAb-induced cytotoxicity. 14F7 F(ab')(2) but not Fab fragments retained the cytotoxic capacity of the whole mAb. By contrary, other mAb, which recognizes N-glycolylated gangliosides, did not show any cytotoxic effect. These mAbs showed quite different capacities to bind NGcGM3-positive cell lines measured by binding inhibition experiments. Interestingly, this complement-independent cell death mechanism did not resemble apoptosis, because no DNA fragmentation, caspase activation, or Fas mediation were observed. However, NGcGM3 ganglioside-mediated 14F7 mAb-induced cell death was accompanied by cellular swelling, membrane lesion formation, and cytoskeleton activation, suggesting an oncosis-like phenomenon. This novel mechanism of cell death lets us to support further therapeutic approaches using NGcGM3 as a molecular target for antibody-based cancer immunotherapy. PMID:18645013

  16. Determination of the absolute configuration of sialic acids in gangliosides from the sea cucumber Cucumaria echinata.

    PubMed

    Kisa, Fumiaki; Yamada, Koji; Miyamoto, Tomofumi; Inagaki, Masanori; Higuchi, Ryuichi

    2007-07-01

    Enantiomeric pairs of sialic acid, D- and L-NeuAc (N-acetylneuraminic acid), were converted to D- and L-arabinose, respectively, by chemical degradation. Using this method, the absolute configuration of the sialic acid residues, NeuAc and NeuGc (N-glycolylneuraminic acid), in the gangliosides from the sea cucumber Cucumaria echinata was determined to be the D-form. Although naturally occurring sialic acids have been believed to be the D-form on the basis of biosynthetic evidence, this is the first report of the determination of the absolute configuration of the sialic acid residues in gangliosides using chemical methods. PMID:17603199

  17. Ganglioside GM3 as a gatekeeper of obesity-associated insulin resistance: Evidence and mechanisms.

    PubMed

    Lipina, Christopher; Hundal, Harinder S

    2015-10-24

    Gangliosides constitute a large family of sialic acid-containing glycosphingolipids which play a key regulatory role in a diverse array of cellular processes, including receptor-associated signalling. Accordingly, the aberrant production of the ganglioside GM3 has been linked to pathophysiological changes associated with obesity, which in turn can lead to metabolic disorders such as insulin resistance and type 2 diabetes mellitus. This review examines the role of GM3 in mediating obesity-induced perturbations in metabolic function, including impaired insulin action. By doing so, we highlight the potential use of therapies targeting GM3 biosynthesis in order to counteract obesity-related metabolic disorders. PMID:26434718

  18. Charge deformation and orbital hybridization: intrinsic mechanisms on tunable chromaticity of Y3Al5O12:Ce3+ luminescence by doping Gd3+ for warm white LEDs

    NASA Astrophysics Data System (ADS)

    Chen, Lei; Chen, Xiuling; Liu, Fayong; Chen, Haohong; Wang, Hui; Zhao, Erlong; Jiang, Yang; Chan, Ting-Shan; Wang, Chia-Hsin; Zhang, Wenhua; Wang, Yu; Chen, Shifu

    2015-07-01

    The deficiency of Y3Al5O12:Ce (YAG:Ce) luminescence in red component can be compensated by doping Gd3+, thus lead to it being widely used for packaging warm white light-emitting diode devices. This article presents a systematic study on the photoluminescence properties, crystal structures and electronic band structures of (Y1-xGdx)3Al5O12: Ce3+ using powerful experimental techniques of thermally stimulated luminescence, X-ray diffraction, X-ray absorption near edge structure (XANES), extended X-ray absorption fine structure (EXAFS) and ultraviolet photoelectron spectra (UPS) of the valence band, assisted with theoretical calculations on the band structure, density of states (DOS), and charge deformation density (CDD). A new interpretation from the viewpoint of compression deformation of electron cloud in a rigid structure by combining orbital hybridization with solid-state energy band theory together is put forward to illustrate the intrinsic mechanisms that cause the emission spectral shift, thermal quenching, and luminescence intensity decrease of YAG: Ce upon substitution of Y3+ by Gd3+, which are out of the explanation of the classic configuration coordinate model. The results indicate that in a rigid structure, the charge deformation provides an efficient way to tune chromaticity, but the band gaps and crystal defects must be controlled by comprehensively accounting for luminescence thermal stability and efficiency.

  19. Charge deformation and orbital hybridization: intrinsic mechanisms on tunable chromaticity of Y3Al5O12:Ce3+ luminescence by doping Gd3+ for warm white LEDs

    PubMed Central

    Chen, Lei; Chen, Xiuling; Liu, Fayong; Chen, Haohong; Wang, Hui; Zhao, Erlong; Jiang, Yang; Chan, Ting-Shan; Wang, Chia-Hsin; Zhang, Wenhua; Wang, Yu; Chen, Shifu

    2015-01-01

    The deficiency of Y3Al5O12:Ce (YAG:Ce) luminescence in red component can be compensated by doping Gd3+, thus lead to it being widely used for packaging warm white light-emitting diode devices. This article presents a systematic study on the photoluminescence properties, crystal structures and electronic band structures of (Y1−xGdx)3Al5O12: Ce3+ using powerful experimental techniques of thermally stimulated luminescence, X-ray diffraction, X-ray absorption near edge structure (XANES), extended X-ray absorption fine structure (EXAFS) and ultraviolet photoelectron spectra (UPS) of the valence band, assisted with theoretical calculations on the band structure, density of states (DOS), and charge deformation density (CDD). A new interpretation from the viewpoint of compression deformation of electron cloud in a rigid structure by combining orbital hybridization with solid-state energy band theory together is put forward to illustrate the intrinsic mechanisms that cause the emission spectral shift, thermal quenching, and luminescence intensity decrease of YAG: Ce upon substitution of Y3+ by Gd3+, which are out of the explanation of the classic configuration coordinate model. The results indicate that in a rigid structure, the charge deformation provides an efficient way to tune chromaticity, but the band gaps and crystal defects must be controlled by comprehensively accounting for luminescence thermal stability and efficiency. PMID:26175141

  20. Charge deformation and orbital hybridization: intrinsic mechanisms on tunable chromaticity of Y3Al5O12:Ce3+ luminescence by doping Gd3+ for warm white LEDs.

    PubMed

    Chen, Lei; Chen, Xiuling; Liu, Fayong; Chen, Haohong; Wang, Hui; Zhao, Erlong; Jiang, Yang; Chan, Ting-Shan; Wang, Chia-Hsin; Zhang, Wenhua; Wang, Yu; Chen, Shifu

    2015-01-01

    The deficiency of Y3Al5O12:Ce (YAG:Ce) luminescence in red component can be compensated by doping Gd(3+), thus lead to it being widely used for packaging warm white light-emitting diode devices. This article presents a systematic study on the photoluminescence properties, crystal structures and electronic band structures of (Y1-xGdx)3Al5O12: Ce(3+) using powerful experimental techniques of thermally stimulated luminescence, X-ray diffraction, X-ray absorption near edge structure (XANES), extended X-ray absorption fine structure (EXAFS) and ultraviolet photoelectron spectra (UPS) of the valence band, assisted with theoretical calculations on the band structure, density of states (DOS), and charge deformation density (CDD). A new interpretation from the viewpoint of compression deformation of electron cloud in a rigid structure by combining orbital hybridization with solid-state energy band theory together is put forward to illustrate the intrinsic mechanisms that cause the emission spectral shift, thermal quenching, and luminescence intensity decrease of YAG: Ce upon substitution of Y(3+) by Gd(3+), which are out of the explanation of the classic configuration coordinate model. The results indicate that in a rigid structure, the charge deformation provides an efficient way to tune chromaticity, but the band gaps and crystal defects must be controlled by comprehensively accounting for luminescence thermal stability and efficiency. PMID:26175141

  1. Investigation of cyano-bridged coordination nanoparticles Gd3+/[Fe(CN)6]3-/d-mannitol as T1-weighted MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Perrier, M.; Gallud, A.; Ayadi, A.; Kennouche, S.; Porredon, C.; Gary-Bobo, M.; Larionova, J.; Goze-Bac, Ch.; Zanca, M.; Garcia, M.; Basile, I.; Long, J.; de Lapuente, J.; Borras, M.; Guari, Y.

    2015-07-01

    Cyano-bridged Gd3+/[Fe(CN)6]3- coordination polymer nanoparticles of 3-4 nm stabilized with d-mannitol presenting a high r1 relaxivity value of 11.4 mM-1 s-1 were investigated in vivo as contrast agents (CA) for Magnetic Resonance Imaging (MRI). They allow an increase of the MR image contrast and can act as an efficient intravascular T1 CA with a relatively long blood-circulation lifetime (60 min) without specific toxicity.Cyano-bridged Gd3+/[Fe(CN)6]3- coordination polymer nanoparticles of 3-4 nm stabilized with d-mannitol presenting a high r1 relaxivity value of 11.4 mM-1 s-1 were investigated in vivo as contrast agents (CA) for Magnetic Resonance Imaging (MRI). They allow an increase of the MR image contrast and can act as an efficient intravascular T1 CA with a relatively long blood-circulation lifetime (60 min) without specific toxicity. Electronic supplementary information (ESI) available: Experimental details and procedures, toxicological data, physical characterization. See DOI: 10.1039/c5nr01557j

  2. (1)H relaxivity of water in aqueous suspensions of Gd(3+)-loaded NaY nanozeolites and AlTUD-1 mesoporous material: the influence of Si/Al ratio and pore size.

    PubMed

    Norek, Małgorzata; Neves, Isabel C; Peters, Joop A

    2007-07-23

    The results of a (1)H nuclear magnetic relaxation dispersion (NMRD) and EPR study on aqueous suspensions of Gd(3+)-loaded NaY nanozeolites and AlTUD-1 mesoporous material are described. Upon increase of the Si/Al ratio from 1.7 to 4.0 in the Gd(3+)-loaded zeolites, the relaxation rate per mM Gd(3+) (r1) at 40 MHz and 25 degrees C increases from 14 to 27 s(-)1 mM(-1). The NMRD and EPR data were fitted with a previously developed two-step model that considers the system as a concentrated aqueous solution of Gd(3+) in the interior of the zeolite that is in exchange with the bulk water outside the zeolite. The results show that the observed increase in relaxivity can mainly be attributed to the residence lifetime of the water protons in the interior of the material, which decreased from 0.3 to 0.2 micros, upon the increase of the Si/Al ratio. This can be explained by the decreased interaction of water with the zeolite walls as a result of the increased hydrophobicity. The importance of the exchange rate of water between the inside and the outside of the material was further demonstrated by the relatively high relaxivity (33 s(-1) mM(-1) at 40 MHz, 25 degrees C) observed for a suspension of the Gd(3+)-loaded mesoporous material AlTUD-1. Unfortunately, Gd(3+) leaches rather easily from that material, but not from the Gd(3+)-loaded NaY zeolites, which may have potential as contrast agents for magnetic resonance imaging. PMID:17589991

  3. Dissecting the Role of Anti-ganglioside Antibodies in Guillain-Barré Syndrome: an Animal Model Approach.

    PubMed

    Asthana, Pallavi; Vong, Joaquim Si Long; Kumar, Gajendra; Chang, Raymond Chuen-Chung; Zhang, Gang; Sheikh, Kazim A; Ma, Chi Him Eddie

    2016-09-01

    Guillain-Barré syndrome (GBS) is an autoimmune polyneuropathy disease affecting the peripheral nervous system (PNS). Most of the GBS patients experienced neurological symptoms such as paresthesia, weakness, pain, and areflexia. There are also combinations of non-neurological symptoms which include upper respiratory tract infection and diarrhea. One of the major causes of GBS is due largely to the autoantibodies against gangliosides located on the peripheral nerves. Gangliosides are sialic acid-bearing glycosphingolipids consisting of a ceramide lipid anchor with one or more sialic acids attached to a neutral sugar backbone. Molecular mimicry between the outer components of oligosaccharide of gangliosides on nerve membrane and lipo-oligosaccharide of microbes is thought to trigger the autoimmunity. Intra-peritoneal implantation of monoclonal ganglioside antibodies secreting hybridoma into animals induced peripheral neuropathy. Recent studies demonstrated that injection of synthesized anti-ganglioside antibodies raised by hybridoma cells into mice initiates immune response against peripheral nerves, and eventually failure in peripheral nerve regeneration. Accumulating evidences indicate that the conjugation of anti-ganglioside monoclonal antibodies to activating FcγRIII present on the circulating macrophages inhibits axonal regeneration. The activation of RhoA signaling pathways is also involved in neurite outgrowth inhibition. However, the link between these two molecular events remains unresolved and requires further investigation. Development of anti-ganglioside antagonists can serve as targeted therapy for the treatment of GBS and will open a new approach of drug development with maximum efficacy and specificity. PMID:26374552

  4. Specific Synthesis of Neurostatin and Gangliosides O-Acetylated in the Outer Sialic Acids Using a Sialate Transferase

    PubMed Central

    Romero-Ramírez, Lorenzo; García-Álvarez, Isabel; Campos-Olivas, Ramón; Gilbert, Michel; Goneau, Marie-France; Fernández-Mayoralas, Alfonso; Nieto-Sampedro, Manuel

    2012-01-01

    Gangliosides are sialic acid containing glycosphingolipids, commonly found on the outer leaflet of the plasma membrane. O-acetylation of sialic acid hydroxyl groups is one of the most common modifications in gangliosides. Studies on the biological activity of O-acetylated gangliosides have been limited by their scarcity in nature. This comparatively small change in ganglioside structure causes major changes in their physiological properties. When the ganglioside GD1b was O-acetylated in the outer sialic acid, it became the potent inhibitor of astroblast and astrocytoma proliferation called Neurostatin. Although various chemical and enzymatic methods to O-acetylate commercial gangliosides have been described, O-acetylation was nonspecific and produced many side-products that reduced the yield. An enzyme with O-acetyltransferase activity (SOAT) has been previously cloned from the bacteria Campylobacter jejuni. This enzyme catalyzed the acetylation of oligosaccharide-bound sialic acid, with high specificity for terminal alpha-2,8-linked residues. Using this enzyme and commercial gangliosides as starting material, we have specifically O-acetylated the gangliosides’ outer sialic acids, to produce the corresponding gangliosides specifically O-acetylated in the sialic acid bound in alpha-2,3 and alpha-2,8 residues. We demonstrate here that O-acetylation occurred specifically in the C-9 position of the sialic acid. In summary, we present a new method of specific O-acetylation of ganglioside sialic acids that permits the large scale preparation of these modified glycosphingolipids, facilitating both, the study of their mechanism of antitumoral action and their use as therapeutic drugs for treating glioblastoma multiform (GBM) patients. PMID:23226505

  5. Fluorescently-tagged anti-ganglioside antibody selectively identifies peripheral nerve in living animals

    PubMed Central

    Massaad, Cynthia A.; Zhang, Gang; Pillai, Laila; Azhdarinia, Ali; Liu, Weiqiang; Sheikh, Kazim A.

    2015-01-01

    Selective in vivo delivery of cargo to peripheral nervous system (PNS) has broad clinical and preclinical applications. An important applicability of this approach is systemic delivery of fluorescently conjugated ligands that selectively label PNS, which could allow visualization of peripheral nerves during any surgery. We examine the use of an anti-ganglioside monoclonal antibody (mAb) as selective neuronal delivery vector for surgical imaging of peripheral nerves. Systemic delivery of an anti-ganglioside mAb was used for selective intraneuronal/axonal delivery of fluorescent agents to visualize nerves by surgical imaging in living mice. In this study, we show that intact motor, sensory, and autonomic nerve fibers/paths are distinctly labeled following a single nanomolar systemic injection of fluorescently labeled anti-ganglioside mAb. Tissue biodistribution studies with radiolabeled mAb were used to validate neuronal uptake of fluorescently labeled mAb. Implications of this proof of concept study are that fluorescent conjugates of anti-ganglioside mAbs are valuable delivery vectors to visualize nerves during surgery to avoid nerve injury and monitor nerve degeneration and regeneration after injury. These findings support that antibodies, and their derivatives/fragments, can be used as selective neuronal delivery vector for transport of various cargos to PNS in preclinical and clinical settings. PMID:26514366

  6. Beyond gangliosides: Multiple forms of glycan mimicry exhibited by Campylobacter jejuni in its lipooligosaccharide (LOS)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Campylobacter jejuni is well known for synthesizing ganglioside mimics within the glycan component of its lipooligosaccharide (LOS), which have been implicated in triggering Guillain-Barré syndrome (GBS). We now confirm that this pathogen is capable of synthesizing a much broader spectrum of host g...

  7. GM1 Ganglioside is Involved in Epigenetic Activation Loci of Neuronal Cells.

    PubMed

    Tsai, Yi-Tzang; Itokazu, Yutaka; Yu, Robert K

    2016-02-01

    Gangliosides are sialic acid-containing glycosphingolipids that are most abundant in the nerve tissues. The quantity and expression pattern of gangliosides in brain change drastically throughout development and are mainly regulated through stage-specific expression of glycosyltransferase (ganglioside synthase) genes. We previously demonstrated that acetylation of histones H3 and H4 on the N-acetylgalactosaminyltransferase I (GalNAcT, GA2/GM2/GD2/GT2-synthase) gene promoter resulted in recruitment of trans-activation factors. In addition, we reported that epigenetic activation of the GalNAcT gene was also detected as accompanied by an apparent induction of neuronal differentiation in neural stem cells responding to an exogenous supplement of ganglioside GM1. Here, we present evidence supporting the concept that nuclear GM1 is associated with gene regulation in neuronal cells. We found that nuclear GM1 binds acetylated histones on the promoters of the GalNAcT and NeuroD1 genes in differentiated neurons. Our study demonstrates for the first time that GM1 interacts with chromatin via acetylated histones at the nuclear periphery of neuronal cells. PMID:26498762

  8. Mass spectrometry of gangliosides in extracranial tumors: Application to adrenal neuroblastoma.

    PubMed

    Robu, Adrian C; Vukelić, Željka; Schiopu, Catalin; Capitan, Florina; Zamfir, Alina D

    2016-09-15

    We report here on the introduction of mass spectrometry (MS) for profiling of native gangliosides from an extracranial tumor. The analytical approach was based on a modern platform combining the superior sensitivity and reproducibility of fully automated chip-based nanoelectrospray ionization (nanoESI) with the high resolution and mass accuracy provided by a hybrid quadrupole time-of-flight (QTOF) instrument. The feasibility of the method for the analysis of gangliosides, which are much less expressed in extracranial tissues, was here tested using as the model substrate an adrenal neuroblastoma (NB) specimen located in the abdominal region of a 2-year-old infant. Under properly optimized conditions, MS profiling revealed information on at least 61 different gangliosides exhibiting heterogeneity of the glycan and lipid compositions. NB was found dominated by species bearing short-chain oligosaccharide cores with a reduced overall Neu5Ac content. By chip-nanoESI MS, preceding findings related to the GD2 role in NB were confirmed. Moreover, the screening experiments offered novel information supporting the possible biomarker role of GM4, GM3, and GM1 ganglioside classes. Structural analysis of GM1(d18:1/18:2) and GD1(d18:0/19:0) possibly tumor-associated markers, carried out by tandem MS (MS/MS) using collision-induced dissociation (CID) at low energies, indicated that both GM1a and GD1b isomers are present in NB. PMID:27311552

  9. Glycosylated SV2 and Gangliosides as Dual Receptors for Botulinum Neurotoxin Serotype F

    SciTech Connect

    Fu, Zhuji; Chen, Chen; Barbieri, Joseph T.; Kim, Jung-Ja P.; Baldwin, Michael R.

    2010-02-22

    Botulinum neurotoxin causes rapid flaccid paralysis through the inhibition of acetylcholine release at the neuromuscular junction. The seven BoNT serotypes (A-G) have been proposed to bind motor neurons via ganglioside-protein dual receptors. To date, the structure-function properties of BoNT/F host receptor interactions have not been resolved. Here, we report the crystal structures of the receptor binding domains (HCR) of BoNT/A and BoNT/F and the characterization of the dual receptors for BoNT/F. The overall polypeptide fold of HCR/A is essentially identical to the receptor binding domain of the BoNT/A holotoxin, and the structure of HCR/F is very similar to that of HCR/A, except for two regions implicated in neuronal binding. Solid phase array analysis identified two HCR/F binding glycans: ganglioside GD1a and oligosaccharides containing an N-acetyllactosamine core. Using affinity chromatography, HCR/F bound native synaptic vesicle glycoproteins as part of a protein complex. Deglycosylation of glycoproteins using {alpha}(1-3,4)-fucosidase, endo-{beta}-galactosidase, and PNGase F disrupted the interaction with HCR/F, while the binding of HCR/B to its cognate receptor, synaptotagmin I, was unaffected. These data indicate that the HCR/F binds synaptic vesicle glycoproteins through the keratan sulfate moiety of SV2. The interaction of HCR/F with gangliosides was also investigated. HCR/F bound specifically to gangliosides that contain {alpha}2,3-linked sialic acid on the terminal galactose of a neutral saccharide core (binding order GT1b = GD1a GM3; no binding to GD1b and GM1a). Mutations within the putative ganglioside binding pocket of HCR/F decreased binding to gangliosides, synaptic vesicle protein complexes, and primary rat hippocampal neurons. Thus, BoNT/F neuronal discrimination involves the recognition of ganglioside and protein (glycosylated SV2) carbohydrate moieties, providing a structural basis for the high affinity and specificity of BoNT/F for neurons.

  10. Ganglioside-Dependent Neural Stem Cell Proliferation in Alzheimer's Disease Model Mice.

    PubMed

    Koon, Noah A; Itokazu, Yutaka; Yu, Robert K

    2015-01-01

    The aggregation and formation of amyloid plaques by amyloid β-peptides (Aβs) is believed to be one of the pathological hallmarks of Alzheimer's disease (AD). Intriguingly, Aβs have also been shown to possess proliferative effects on neural stem cells (NSCs). Many essential cellular processes in NSCs, such as fate determination and proliferation, are heavily influenced by cell surface glycoconjugates, including gangliosides. It has recently been shown that Aβ1-42 alters several key glycosyltransferases and glycosidases. To further define the effects of Aβs and to clarify the potential mechanisms of action of those peptides on NSCs, NSCs were cultured from embryonic brains of the double-transgenic mouse model of AD [B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J] coexpressing mutants of amyloid precursor protein (APPswe) and presenilin1 (PSEN1dE9). We found that Aβs not only promoted cell proliferation but also altered expression of several key glycogenes for glycoconjugate metabolism, such as sialyltransferases II and III (ST-II & -III) in AD NSCs. In addition, we found upregulation of epidermal growth factor receptor and Notch1 intracellular domain. Moreover, the increased expression of ST-II and -III coincided with the elevated levels of c-series gangliosides (A2B5+ antigens) in AD NSCs. Further, we revealed that epidermal growth factor signaling and gangliosides are necessary components on Aβ-stimulated NSC proliferation. Our present study has thus provided a novel mechanism for the upregulation of c-series ganglioside expression and increases in several NSC markers to account for the proliferative effect of Aβs on NSCs in AD mouse brain. These observations support the potential beneficial effects of Aβs and gangliosides in promoting neurogenesis in AD brain. PMID:26699276

  11. Ethylenedioxy-PIP2 oxalate reduces ganglioside storage in juvenile Sandhoff disease mice.

    PubMed

    Arthur, Julian R; Wilson, Michael W; Larsen, Scott D; Rockwell, Hannah E; Shayman, James A; Seyfried, Thomas N

    2013-04-01

    Sandhoff disease is an incurable neurodegenerative disorder caused by mutations in the lysosomal hydrolase β-hexosaminidase. Deficiency in this enzyme leads to excessive accumulation of ganglioside GM2 and its asialo derivative, GA2, in brain and visceral tissues. Small molecule inhibitors of ceramide-specific glucosyltransferase, the first committed step in ganglioside biosynthesis, reduce storage of GM2 and GA2. Limited brain access or adverse effects have hampered the therapeutic efficacy of the clinically approved substrate reduction molecules, eliglustat tartrate and the imino sugar NB-DNJ (Miglustat). The novel eliglustat tartrate analog, 2-(2,3-dihydro-1H-inden-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1, 4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)acetamide (EtDO-PIP2, CCG-203586 or "3h"), was recently reported to reduce glucosylceramide in murine brain. Here we assessed the therapeutic efficacy of 3h in juvenile Sandhoff (Hexb-/-) mice. Sandhoff mice received intraperitoneal injections of phosphate buffered saline (PBS) or 3h (60 mg/kg/day) from postnatal day 9 (p-9) to postnatal day 15 (p-15). Brain weight and brain water content was similar in 3h and PBS-treated mice. 3h significantly reduced total ganglioside sialic acid, GM2, and GA2 content in cerebrum, cerebellum and liver of Sandhoff mice. Data from the liver showed that 3h reduced the key upstream ganglioside precursor (glucosylceramide), providing evidence for an on target mechanism of action. No significant differences were seen in the distribution of cholesterol or of neutral and acidic phospholipids. These data suggest that 3h can be an effective alternative to existing substrate reduction molecules for ganglioside storage diseases. PMID:23417430

  12. Roles of gangliosides in mouse embryogenesis and embryonic stem cell differentiation

    PubMed Central

    Kwak, Dong Hoon; Seo, Byoung Boo; Chang, Kyu Tae

    2011-01-01

    Gangliosides have been suggested to play important roles in various functions such as adhesion, cell differentiation, growth control, and signaling. Mouse follicular development, ovulation, and luteinization during the estrous cycle are regulated by several hormones and cell-cell interactions. In addition, spermatogenesis in seminiferous tubules of adult testes is also regulated by several hormones, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and cell-cell interactions. The regulation of these processes by hormones and cell-cell interactions provides evidence for the importance of surface membrane components, including gangliosides. During preimplantation embryo development, a mammalian embryo undergoes a series of cleavage divisions whereby a zygote is converted into a blastocyst that is sufficiently competent to be implanted in the maternal uterus and continue its development. Mouse embryonic stem (mES) cells are pluripotent cells derived from mouse embryo, specifically, from the inner cell mass of blastocysts. Differentiated neuronal cells are derived from mES cells through the formation of embryonic bodies (EBs). EBs recapitulate many aspects of lineage-specific differentiation and temporal and spatial gene expression patterns during early embryogenesis. Previous studies on ganglioside expression during mouse embryonic development (including during in vitro fertilization, ovulation, spermatogenesis, and embryogenesis) reported that gangliosides were expressed in both undifferentiated and differentiated (or differentiating) mES cells. In this review, we summarize some of the advances in our understanding of the functional roles of gangliosides during the stages of mouse embryonic development, including ovulation, spermatogenesis, and embryogenesis, focusing on undifferentiated and differentiated mES cells (neuronal cells). PMID:21654188

  13. Early Supplementation of Phospholipids and Gangliosides Affects Brain and Cognitive Development in Neonatal Piglets123

    PubMed Central

    Liu, Hongnan; Radlowski, Emily C; Conrad, Matthew S; Li, Yao; Dilger, Ryan N; Johnson, Rodney W

    2014-01-01

    Background: Because human breast milk is a rich source of phospholipids and gangliosides and breastfed infants have improved learning compared with formula-fed infants, the importance of dietary phospholipids and gangliosides for brain development is of interest. Objective: We sought to determine the effects of phospholipids and gangliosides on brain and cognitive development. Methods: Male and female piglets from multiple litters were artificially reared and fed formula containing 0% (control), 0.8%, or 2.5% Lacprodan PL-20 (PL-20; Arla Foods Ingredients), a phospholipid/ganglioside supplement, from postnatal day (PD) 2 to PD28. Beginning on PD14, performance in a spatial T-maze task was assessed. At PD28, brain MRI data were acquired and piglets were killed to obtain hippocampal tissue for metabolic profiling. Results: Diet affected maze performance, with piglets that were fed 0.8% and 2.5% PL-20 making fewer errors than control piglets (80% vs. 75% correct on average; P < 0.05) and taking less time to make a choice (3 vs. 5 s/trial; P < 0.01). Mean brain weight was 5% higher for piglets fed 0.8% and 2.5% PL-20 (P < 0.05) than control piglets, and voxel-based morphometry revealed multiple brain areas with greater volumes and more gray and white matter in piglets fed 0.8% and 2.5% PL-20 than in control piglets. Metabolic profiling of hippocampal tissue revealed that multiple phosphatidylcholine-related metabolites were altered by diet. Conclusion: In summary, dietary phospholipids and gangliosides improved spatial learning and affected brain growth and composition in neonatal piglets. PMID:25411030

  14. Probing shallow electron traps in cerium-doped Gd3Al2Ga3O12 scintillators by UV-induced absorption spectroscopy

    NASA Astrophysics Data System (ADS)

    Kitaura, Mamoru; Kamada, Kei; Kurosawa, Shunsuke; Azuma, Junpei; Ohnishi, Akimasa; Yamaji, Akihiro; Hara, Kazuhiko

    2016-07-01

    From measuring absorption spectra of cerium-doped Gd3Al2Ga3O12 (Ce:GAGG) and undoped GAGG crystals at low temperatures under UV-light irradiation, we find that they exhibit a broad band at around 12000 cm‑1. This band is enhanced by high-temperature annealing under a hydrogen atmosphere. On the basis of present experimental results, the UV-induced band is assigned to shallow electron traps of defect complexes associated with oxygen vacancies. The UV-induced band completely disappears with Mg2+ codoping. We conclude that the Mg2+ codoping has the effect of inhibiting the formation of shallow electron traps, which realizes a faster scintillation response of Ce:GAGG.

  15. Magnetic-Field-Induced Low-Energy Spin Excitations in YBa2Cu4O8 Measured by High Field Gd3+ Electron Spin Resonance

    NASA Astrophysics Data System (ADS)

    Fehér, Titusz; Jánossy, András; Oszlányi, Gábor; Simon, Ferenc; Dabrowski, Bogdan; Klamut, Piotr W.; Horvatić, Mladen; Williams, Grant V.

    2000-12-01

    We have measured the spin susceptibility, χs, of the CuO2 planes in the underdoped high Tc superconductor, YBa2Cu4O8 by Gd3+ electron spin resonance (ESR) in single crystals and aligned powders in fields up to 15.4 T. At low temperatures and high fields, χs is enhanced slightly in the B∥c orientation with respect to the B⊥c orientation. The enhancement at 15.4 T ( ~0.15Hc2) at 16 K ( 0.2 Tc) is small: approximately 10% of χs\\(Tc\\), suggesting that the second critical field of superconductivity, Hc2~100 T, would not suppress the pseudogap. This work demonstrates the potential of high field ESR in single crystals for studying high Tc superconductors.

  16. Constituents of Holothuroidea, 17. Isolation and structure of biologically active monosialo-gangliosides from the sea cucumber Cucumaria echinata.

    PubMed

    Kisa, Fumiaki; Yamada, Koji; Miyamoto, Tomofumi; Inagaki, Masanori; Higuchi, Ryuichi

    2006-07-01

    Three new monosialo-gangliosides, CEG-3 (3), CEG-4 (4), and CEG-5 (5), were obtained, together with two known gangliosides, SJG-1 (1) and CG-1 (2), from the lipid fraction of the chloroform/methanol extract of the sea cucumber Cucumaria echinata. The structures of the new gangliosides were determined on the basis of chemical and spectroscopic evidence to be 1-O-[4-O-acetyl-alpha-L-fucopyranosyl-(1-->11)-(N-glycolyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (3) and 1-O-[alpha-L-fucopyranosyl-(1-->11)-(N-glycolyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (4, 5). The ceramide moieties of each compound were composed of heterogeneous sphingosine or phytosphingosine bases, and 2-hydroxy or nonhydroxylated fatty acid units. These gangliosides showed neuritogenic activity toward the rat pheochromocytoma cell line PC-12 in the presence of nerve growth factor. PMID:16819216

  17. Effects of Ganglioside on Working Memory and the Default Mode Network in Individuals with Subjective Cognitive Impairment: A Randomized Controlled Trial.

    PubMed

    Jeon, Yujin; Kim, Binna; Kim, Jieun E; Kim, Bori R; Ban, Soonhyun; Jeong, Jee Hyang; Kwon, Oran; Rhie, Sandy Jeong; Ahn, Chang-Won; Kim, Jong-Hoon; Jung, Sung Ug; Park, Soo-Hyun; Lyoo, In Kyoon; Yoon, Sujung

    2016-01-01

    This randomized, double-blind, placebo-controlled trial examined whether the administration of ganglioside, an active ingredient of deer bone extract, can improve working memory performance by increasing gray matter volume and functional connectivity in the default mode network (DMN) in individuals with subjective cognitive impairment. Seventy-five individuals with subjective cognitive impairment were chosen to receive either ganglioside (330[Formula: see text][Formula: see text]g/day or 660[Formula: see text][Formula: see text]g/day) or a placebo for 8 weeks. Changes in working memory performance with treatment of either ganglioside or placebo were assessed as cognitive outcome measures. Using voxel-based morphometry and functional connectivity analyses, changes in gray matter volume and functional connectivity in the DMN were also assessed as brain outcome measures. Improvement in working memory performance was greater in the ganglioside group than in the placebo group. The ganglioside group, relative to the placebo group, showed greater increases in gray matter volume and functional connectivity in the DMN. A significant relationship between increased functional connectivity of the precuneus and improved working memory performance was observed in the ganglioside group. The current findings suggest that ganglioside has cognitive-enhancing effects in individuals with subjective cognitive impairment. Ganglioside-induced increases in gray matter volume and functional connectivity in the DMN may partly be responsible for the potential nootropic effects of ganglioside. The clinical trial was registered with ClinicalTrials.gov (identifier: NCT02379481). PMID:27109158

  18. Effect of tin ions on enhancing the intensity of narrow luminescence line at 311 nm of Gd3+ ions in Li2Osbnd PbOsbnd P2O5 glass system

    NASA Astrophysics Data System (ADS)

    Gandhi, Y.; Rajanikanth, P.; Sundara Rao, M.; Ravi Kumar, V.; Veeraiah, N.; Piasecki, M.

    2016-07-01

    This study is mainly focused on enriching the UVB 311 narrow emission band of Gd3+ ions in Li2Osbnd PbOsbnd P2O5 glasses doped with 1.0 mol% of Gd2O3 and mixed with different concentrations of SnO2 (0-7.0 mol%). The emission spectra SnO2 free glasses exhibited intense narrow UVB band at 311 nm due to 6P7/2 → 8S7/2 transition of Gd3+ ions when excited at 273 nm. The intensity of this band is found to be enhanced nearly four times when the glasses are mixed with 3.0 mol% of SnO2. The reasons for this enhancement have been explored in the light of energy transfer from Sn4+ to Gd3+ ions with the help of rate equations. The declustering of Gd3+ ions (that reduce cross relaxation losses) by tin ions is also found to the other reason for such enrichment. The 311 nm radiation is an efficient in the treatment of various skin diseases and currently it is one of the most desirable and commonly utilised UVB in the construction of phototherapy devices.

  19. O-acetylated N-acetylneuraminic acid as a novel target for therapy in human pre-B acute lymphoblastic leukemia

    PubMed Central

    Parameswaran, Reshmi; Lim, Min; Arutyunyan, Anna; Abdel-Azim, Hisham; Hurtz, Christian; Lau, Kam; Müschen, Markus; Yu, Robert K.; von Itzstein, Mark; Groffen, John

    2013-01-01

    The development of resistance to chemotherapy is a major cause of relapse in acute lymphoblastic leukemia (ALL). Though several mechanisms associated with drug resistance have been studied in detail, the role of carbohydrate modification remains unexplored. Here, we investigated the contribution of 9-O-acetylated N-acetylneuraminic acid (Neu5Ac) to survival and drug resistance development in ALL cells. A strong induction of 9-O-acetylated Neu5Ac including 9-O-acetyl GD3 was detected in ALL cells that developed resistance against vincristine or nilotinib, drugs with distinct cytotoxic mechanisms. Removal of 9-O-acetyl residues from Neu5Ac on the cell surface by an O-acetylesterase made ALL cells more vulnerable to such drugs. Moreover, removal of intracellular and cell surface–resident 9-O-acetyl Neu5Ac by lentiviral transduction of the esterase was lethal to ALL cells in vitro even in the presence of stromal protection. Interestingly, expression of the esterase in normal fibroblasts or endothelial cells had no effect on their survival. Transplanted mice induced for expression of the O-acetylesterase in the ALL cells exhibited a reduction of leukemia to minimal cell numbers and significantly increased survival. This demonstrates that Neu5Ac 9-O-acetylation is essential for survival of these cells and suggests that Neu5Ac de-O-acetylation could be used as therapy to eradicate drug-resistant ALL cells. PMID:23478187

  20. High-throughput imaging method for direct assessment of GM1 ganglioside levels in mammalian cells

    PubMed Central

    Acosta, Walter; Martin, Reid; Radin, David N.; Cramer, Carole L.

    2016-01-01

    GM1-gangliosidosis is an inherited autosomal recessive disorder caused by mutations in the gene GLB1, which encodes acid β-galactosidase (β-gal). The lack of activity in this lysosomal enzyme leads to accumulation of GM1 gangliosides (GM1) in cells. We have developed a high-content-imaging method to assess GM1 levels in fibroblasts that can be used to evaluate substrate reduction in treated GLB1−/− cells [1]. This assay allows fluorescent quantification in a multi-well system which generates unbiased and statistically significant data. Fluorescently labeled Cholera Toxin B subunit (CTXB), which specifically binds to GM1 gangliosides, was used to detect in situ GM1 levels in a fixed monolayer of fibroblasts. This sensitive, rapid, and inexpensive method facilitates in vitro drug screening in a format that allows a high number of replicates using low working volumes. PMID:26958633

  1. The Total Synthesis of Starfish Ganglioside GP3 Bearing a Unique Sialyl Glycan Architecture.

    PubMed

    Goto, Kenta; Sawa, Maki; Tamai, Hideki; Imamura, Akihiro; Ando, Hiromune; Ishida, Hideharu; Kiso, Makoto

    2016-06-01

    The total synthesis of ganglioside GP3, which is found in the starfish Asterina pectinifera, has been accomplished through stereoselective and effective glycosylation reactions. The sialic acid embedded octasaccharide moiety of the target compound was constructed by [4+4] convergent coupling. A tetrasaccharyl donor and acceptor that contained internal sialic acid residues were synthesized with an orthogonally protected N-Troc sialic acid donor as the key common synthetic unit, and they underwent highly stereoselective glycosidation. The resulting sialosides were subsequently transformed into reactive glycosyl acceptors. [4+4] coupling furnished the octasaccharide framework in 91 % yield as a single stereoisomer. Final conjugation of the octasaccharyl donor and glucosyl ceramide acceptor produced the protected target compound in high yield, which underwent global deprotection to successfully deliver ganglioside GP3. PMID:27172064

  2. High-throughput imaging method for direct assessment of GM1 ganglioside levels in mammalian cells.

    PubMed

    Acosta, Walter; Martin, Reid; Radin, David N; Cramer, Carole L

    2016-03-01

    GM1-gangliosidosis is an inherited autosomal recessive disorder caused by mutations in the gene GLB1, which encodes acid β-galactosidase (β-gal). The lack of activity in this lysosomal enzyme leads to accumulation of GM1 gangliosides (GM1) in cells. We have developed a high-content-imaging method to assess GM1 levels in fibroblasts that can be used to evaluate substrate reduction in treated GLB1(-/-) cells [1]. This assay allows fluorescent quantification in a multi-well system which generates unbiased and statistically significant data. Fluorescently labeled Cholera Toxin B subunit (CTXB), which specifically binds to GM1 gangliosides, was used to detect in situ GM1 levels in a fixed monolayer of fibroblasts. This sensitive, rapid, and inexpensive method facilitates in vitro drug screening in a format that allows a high number of replicates using low working volumes. PMID:26958633

  3. Anti-amyloidogenic effects of glycosphingolipid synthesis inhibitors occur independently of ganglioside alterations.

    PubMed

    Noel, Anastasia; Ingrand, Sabrina; Barrier, Laurence

    2016-09-01

    Evidence has suggested that ganglioside abnormalities may be linked to the proteolytic processing of amyloid precursor protein (APP) in Alzheimer's disease (AD) and that pharmacological inhibition of ganglioside synthesis may reduce amyloid β-peptide (Aβ) production. In this study, we assessed the usefulness of two well-established glycosphingolipid (GSL) synthesis inhibitors, the synthetic ceramide analog D-PDMP (1-phenyl 2-decanoylamino-3-morpholino-1-propanol) and the iminosugar N-butyldeoxynojirimycin (NB-DNJ or miglustat), as anti-amyloidogenic drugs in a human cellular model of AD. We found that both GSL inhibitors were able to markedly inhibit Aβ production, although affecting differently the APP cleavage. Surprisingly, the L-enantiomer of PDMP, which promotes ganglioside accumulation, acted similarly to D-PDMP to inhibit Aβ production. Concurrently, both D- and L-PDMP strongly and equally reduced the levels of long-chain ceramides. Altogether, our data suggested that the anti-amyloidogenic effects of PDMP agents are independent of the altered cellular ganglioside composition, but may result, at least in part, from their ability to reduce ceramide levels. Moreover, our current study established for the first time that NB-DNJ, a drug already used as a therapeutic for Gaucher disease (a lysosomal storage disorder), was also able to reduce Aβ production in our cellular model. Therefore, our study provides novel information regarding the possibilities to target amyloidogenic processing of APP through modulation of sphingolipid metabolism and emphasizes the potential of the iminosugar NB-DNJ as a disease modifying therapy for AD. PMID:27373967

  4. Cytofluorimetric evaluation of N-glycolylated GM3 ganglioside expression on murine leukocytes.

    PubMed

    Miranda, A; de León, J; Roque-Navarro, L; Fernández, L E

    2011-06-30

    Gangliosides are considered relevant components of lipid rafts at the plasma membrane. Antigen encounter, immunological synapse assembly and signal transduction modify lipid raft composition and distribution on immune system cells. On the contrary of other gangliosides, differential expression of the N-glycolylated variant of GM3 (NGcGM3) on murine leukocytes has received limited attention. In particular, whether cell activation modulates the expression of NGcGM3 on lymphoid and myeloid cells is still unexplored. Availability of the NGcGM3 specific 14F7 MAb allows us to characterize by cytofluorimetric assays the presence of this molecule on resting and activated immune system cells. On T cells, preferential expression of NGcGM3 was detected on CD4(+) single positive thymocytes, peripheral CD4(+) lymphocytes and natural occurring regulatory T cells. In comparison with peritoneal B1 cells, reduced expression of NGcGM3 was observed in peritoneal B2 and splenic B cell subpopulations. Of note, activation of CD4(+) and NK 1.1(+) cells abrogated NGcGM3 expression while LPS-maturated DC increased the ganglioside level at the plasma membrane. Modifications on the presence of NGcGM3 mediated by cell activation did not influence the expression of the N-acetylated variant of GM3 (NAcGM3). In addition to extend previous descriptions of NGcGM3 expression on immunity cell subpopulations, this work highlights the opposite effect of cellular activation over NGcGM3 levels on lymphoid and myeloid cellular series. Obtained results complement the evaluation of a tumor-specific, non-human sialic acid containing ganglioside that has been considered an attractive target for cancer immunotherapy. PMID:21324343

  5. Amplified ELISA to detect autoantibodies to N-glycolyl-GM3 ganglioside.

    PubMed

    Iznaga, N; Carr, A; Fernández, L E; Solozabal, J; Núñez, G; Perdomo, Y; Morales, A

    1996-01-01

    Numerous immunochemical methods are now available for the detection of antibodies to gangliosides. An amplified ELISA method for detection of autoantibodies to NGcGM3 ganglioside in the sera of patients with various type of renal diseases was developed. IgM antibodies were found in 39 out of 53 sera of patients using 30 normal healthy blood donor as a negative control. For human IgG conjugate no reactivity to NGcGM3 was seen in the sera. Positive ELISA results were confirmed by TLC-immunostaining using GM3, NGcGM3, NGcGM2 and Standard bovine gangliosides (GM1, GD1a, GD1b and GT1b). All sera were also assayed for reactivity with GM3 in ELISA to determine the line specificity of these antibodies. Based on these results, a protocol for a sensitive and reproducible amplification ELISA system for serum anti-NGcGM3 antibodies in patients with renal or other diseases is presented. The ELISA method described here in appear to be useful adjunt to measure antiNGcGM3 antibodies in sera of patients with various type of renal or other diseases. PMID:16296265

  6. Imbalance in Fatty-Acid-Chain Length of Gangliosides Triggers Alzheimer Amyloid Deposition in the Precuneus

    PubMed Central

    Oikawa, Naoto; Matsubara, Teruhiko; Fukuda, Ryoto; Yasumori, Hanaki; Hatsuta, Hiroyuki; Murayama, Shigeo; Sato, Toshinori; Suzuki, Akemi; Yanagisawa, Katsuhiko

    2015-01-01

    Amyloid deposition, a crucial event of Alzheimer’s disease (AD), emerges in distinct brain regions. A key question is what triggers the assembly of the monomeric amyloid ß-protein (Aß) into fibrils in the regions. On the basis of our previous findings that gangliosides facilitate the initiation of Aß assembly at presynaptic neuritic terminals, we investigated how lipids, including gangliosides, cholesterol and sphingomyelin, extracted from synaptic plasma membranes (SPMs) isolated from autopsy brains were involved in the Aß assembly. We focused on two regions of the cerebral cortex; precuneus and calcarine cortex, one of the most vulnerable and one of the most resistant regions to amyloid deposition, respectively. Here, we show that lipids extracted from SPMs isolated from the amyloid-bearing precuneus, but neither the amyloid-free precuneus nor the calcarine cortex, markedly accelerate the Aß assembly in vitro. Through liquid chromatography-mass spectrometry of the lipids, we identified an increase in the ratio of the level of GD1b-ganglioside containing C20:0 fatty acid to that containing C18:0 as a cause of the enhanced Aß assembly in the precuneus. Our results suggest that the local glycolipid environment play a critical role in the initiation of Alzheimer amyloid deposition. PMID:25798597

  7. N-butyldeoxygalactonojirimycin reduces brain ganglioside and GM2 content in neonatal Sandhoff disease mice.

    PubMed

    Baek, Rena C; Kasperzyk, Julie L; Platt, Frances M; Seyfried, Thomas N

    2008-05-01

    Sandhoff disease involves the CNS accumulation of ganglioside GM2 and asialo-GM2 (GA2) due to inherited defects in the beta-subunit gene of beta-hexosaminidase A and B (Hexb gene). Accumulation of these glycosphingolipids (GSLs) produces progressive neurodegeneration, ultimately leading to death. Substrate reduction therapy (SRT) aims to decrease the rate of glycosphingolipid (GSL) biosynthesis to compensate for the impaired rate of catabolism. The imino sugar, N-butyldeoxygalactonojirimycin (NB-DGJ) inhibits the first committed step in GSL biosynthesis. NB-DGJ treatment, administered from postnatal day 2 (p-2) to p-5 (600 mg/kg/day)), significantly reduced total brain ganglioside and GM2 content in the Sandhoff disease (Hexb(-/-)) mice, but did not reduce the content of GA2. We also found that NB-DGJ treatment caused a slight, but significant elevation in brain sialidase activity. The drug had no adverse effects on viability, body weight, brain weight, or brain water content in the mice. No significant alterations in neutral lipids or acidic phospholipids were observed in the NB-DGJ-treated Hexb(-/-) mice. Our results show that NB-DGJ is effective in reducing total brain ganglioside and GM2 content at early neonatal ages. PMID:18207611

  8. Isolation of two glycolipid transfer proteins from bovine brain: reactivity toward gangliosides and neutral glycosphingolipids.

    PubMed

    Gammon, C M; Vaswani, K K; Ledeen, R W

    1987-09-22

    Two glycolipid transfer proteins that catalyze the transfer of gangliosides and neutral glycosphingolipids from phosphatidylcholine vesicles to erythrocyte ghosts have been isolated from calf brain. Purification procedures included differential centrifugation, precipitation at pH 5.1, ammonium sulfate precipitation, and gel filtration on Sephadex G-50 and G-75. The final stage employed fast protein liquid chromatography (Mono S), producing two peaks of activity. Apparent purity of the major peak (TP I) was approximately 85-90%, as judged by sodium dodecyl sulfate/urea-polyacrylamide gel electrophoresis. That of the minor fraction (TP II) was less. The major band of both fractions had a molecular mass of approximately 20,000 daltons. Both proteins catalyzed the transfer of ganglioside GM1 as well as asialo-GM1, but transfer protein I was more effective with di- and trisialogangliosides. Transfer protein II appeared to be somewhat more specific for neutral glycolipids in that GA1 was transferred more rapidly than any of the gangliosides; however, lactosylceramide transfer was relatively slow. Neither protein catalyzed transfer of phosphatidylcholine. PMID:3689771

  9. Degradation of gangliosides by the lysosomal sialidase requires an activator protein.

    PubMed

    Fingerhut, R; van der Horst, G T; Verheijen, F W; Conzelmann, E

    1992-09-15

    Lysosomal sialidase, which was formerly believed to degrade only water-soluble substrates but not glycolipids, cleaves ganglioside substrates II3NeuNAc-LacCer, IV3NeuNAc, II3NeuNAc-GgOse4Cer, IV3 NeuNAc, II3(NeuNAc)2-GgOse4Cer when these are dispersed either with an appropriate detergent (taurodeoxycholate) or with the sulfatide activator protein, a physiologic lipid solubilizer required for the lysosomal hydrolysis of other glycolipids by water-soluble hydrolases. In the presence of the activator protein, time and protein dependence were linear within wide limits, while the detergent rapidly inactivated the enzyme. The disialo group of the b-series gangliosides was only poorly attacked by the enzyme when the lipids were dispersed with the activator protein, whereas in the presence of the detergent, they were hydrolyzed as fast as terminal sialic acid residues. With the appropriate assay method, significant ganglioside sialidase activity could be demonstrated in the secondary lysosome fraction of normal skin fibroblasts but not of sialidosis fibroblasts. Our results support the notion that there is only one lysosomal sialidase, which degrades both the water-soluble and the membrane-bound sialyl glycoconjugates. PMID:1396669

  10. Broad neutralization of calcium-permeable amyloid pore channels with a chimeric Alzheimer/Parkinson peptide targeting brain gangliosides.

    PubMed

    Di Scala, Coralie; Yahi, Nouara; Flores, Alessandra; Boutemeur, Sonia; Kourdougli, Nazim; Chahinian, Henri; Fantini, Jacques

    2016-02-01

    Growing evidence supports a role for brain gangliosides in the pathogenesis of neurodegenerative diseases including Alzheimer's and Parkinson's. Recently we deciphered the ganglioside-recognition code controlling specific ganglioside binding to Alzheimer's β-amyloid (Aβ1-42) peptide and Parkinson's disease-associated protein α-synuclein. Cracking this code allowed us to engineer a short chimeric Aβ/α-synuclein peptide that recognizes all brain gangliosides. Here we show that ganglioside-deprived neural cells do no longer sustain the formation of zinc-sensitive amyloid pore channels induced by either Aβ1-42 or α-synuclein, as assessed by single-cell Ca(2+) fluorescence microscopy. Thus, amyloid channel formation, now considered a key step in neurodegeneration, is a ganglioside-dependent process. Nanomolar concentrations of chimeric peptide competitively inhibited amyloid pore formation induced by Aβ1-42 or α-synuclein in cultured neural cells. Moreover, this peptide abrogated the intracellular calcium increases induced by Parkinson's-associated mutant forms of α-synuclein (A30P, E46K and A53T). The chimeric peptide also prevented the deleterious effects of Aβ1-42 on synaptic vesicle trafficking and decreased the Aβ1-42-induced impairment of spontaneous activity in rat hippocampal slices. Taken together, these data show that the chimeric peptide has broad anti-amyloid pore activity, suggesting that a common therapeutic strategy based on the prevention of amyloid-ganglioside interactions is a reachable goal for both Alzheimer's and Parkinson's diseases. PMID:26655601

  11. Effects of Homogenization on Hot Deformation Behavior of As-Cast Mg-8Gd-3Y-1Nd-0.5Zr Magnesium Alloy

    NASA Astrophysics Data System (ADS)

    Qin, Qingfeng; Tan, Yingxin; Zhang, Zhimin; Wang, Qiang; Yang, Yongbiao

    2016-01-01

    The flow stress behaviors of both the as-cast and homogenized Mg-8Gd-3Y-1Nd-0.5Zr alloy were investigated using a Gleeble-1500 thermal simulation test machine in the temperature range of 460-520 °C and strain rate range of 0.001-1 s-1. The processing maps for the two alloys were developed on the basis of flow stress data obtained at a strain of 0.5. It was found that the processing maps of both the as-cast alloy and homogenized alloy consisted of one stability and one instability domains. According to the processing maps and the microstructural observations, the optimum hot-working parameters for the two alloys were determined to be at a temperature of 500 °C and at a strain rate of 0.01 s-1. The hot workability of the homogenized alloy was better than the as-cast alloy in the safe domain, while the homogenization treatment increased the instability domain. The microvoids, which initiated along the dynamic recrystallized (DRX) grain boundaries and led to intercrystalline cracking, were an important factor contributing to the expanded instability domains for the homogenized alloy. Dynamic precipitation in the DRX grain in the as-cast alloy contributed to a lower DRX, hence prevented the formation of microvoids, which resulted in a reduced tendency for DRX intercrystalline cracking during hot deformation.

  12. Real-time tracking of dissociation of hyperpolarized 89Y-DTPA: a model for degradation of open-chain Gd3+ MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Ferguson, Sarah; Niedbalski, Peter; Parish, Christopher; Kiswandhi, Andhika; Kovacs, Zoltan; Lumata, Lloyd

    Gadolinium (Gd) complexes are widely used relaxation-based clinical contrast agents in magnetic resonance imaging (MRI). Gd-based MRI contrast agents with open-chain ligand such as Gd-DTPA, commercially known as magnevist, are less stable compared to Gd complexes with macrocyclic ligands such as GdDOTA (Dotarem). The dissociation of Gd-DPTA into Gd ion and DTPA ligand under certain biological conditions such as high zinc levels can potentially cause kidney damage. Since Gd is paramagnetic, direct NMR detection of the Gd-DTPA dissociation is quite challenging due to ultra-short relaxation times. In this work, we have investigated Y-DTPA as a model for Gd-DPTA dissociation under high zinc content solutions. Using dissolution dynamic nuclear polarization (DNP), the 89Y NMR signal is amplified by several thousand-fold. Due to the the relatively long T1 relaxation time of 89Y which translates to hyperpolarization lifetime of several minutes, the dissociation of Y-DTPA can be tracked in real-time by hyperpolarized 89Y NMR spectroscopy. Dissociation kinetic rates and implications on the degradation of open-chain Gd3+ MRI contrast agents will be discussed. This work was supported by the U.S. Department of Defense Award Number W81XWH-14-1-0048 and by the Robert A. Welch Foundation research Grant Number AT-1877.

  13. Dynamic compression of dense oxide (Gd3Ga5O12) from 0.4 to 2.6 TPa: Universal Hugoniot of fluid metals

    PubMed Central

    Ozaki, N.; Nellis, W. J.; Mashimo, T.; Ramzan, M.; Ahuja, R.; Kaewmaraya, T.; Kimura, T.; Knudson, M.; Miyanishi, K.; Sakawa, Y.; Sano, T.; Kodama, R.

    2016-01-01

    Materials at high pressures and temperatures are of great current interest for warm dense matter physics, planetary sciences, and inertial fusion energy research. Shock-compression equation-of-state data and optical reflectivities of the fluid dense oxide, Gd3Ga5O12 (GGG), were measured at extremely high pressures up to 2.6 TPa (26 Mbar) generated by high-power laser irradiation and magnetically-driven hypervelocity impacts. Above 0.75 TPa, the GGG Hugoniot data approach/reach a universal linear line of fluid metals, and the optical reflectivity most likely reaches a constant value indicating that GGG undergoes a crossover from fluid semiconductor to poor metal with minimum metallic conductivity (MMC). These results suggest that most fluid compounds, e.g., strong planetary oxides, reach a common state on the universal Hugoniot of fluid metals (UHFM) with MMC at sufficiently extreme pressures and temperatures. The systematic behaviors of warm dense fluid would be useful benchmarks for developing theoretical equation-of-state and transport models in the warm dense matter regime in determining computational predictions. PMID:27193942

  14. Dynamic compression of dense oxide (Gd3Ga5O12) from 0.4 to 2.6 TPa: Universal Hugoniot of fluid metals

    NASA Astrophysics Data System (ADS)

    Ozaki, N.; Nellis, W. J.; Mashimo, T.; Ramzan, M.; Ahuja, R.; Kaewmaraya, T.; Kimura, T.; Knudson, M.; Miyanishi, K.; Sakawa, Y.; Sano, T.; Kodama, R.

    2016-05-01

    Materials at high pressures and temperatures are of great current interest for warm dense matter physics, planetary sciences, and inertial fusion energy research. Shock-compression equation-of-state data and optical reflectivities of the fluid dense oxide, Gd3Ga5O12 (GGG), were measured at extremely high pressures up to 2.6 TPa (26 Mbar) generated by high-power laser irradiation and magnetically-driven hypervelocity impacts. Above 0.75 TPa, the GGG Hugoniot data approach/reach a universal linear line of fluid metals, and the optical reflectivity most likely reaches a constant value indicating that GGG undergoes a crossover from fluid semiconductor to poor metal with minimum metallic conductivity (MMC). These results suggest that most fluid compounds, e.g., strong planetary oxides, reach a common state on the universal Hugoniot of fluid metals (UHFM) with MMC at sufficiently extreme pressures and temperatures. The systematic behaviors of warm dense fluid would be useful benchmarks for developing theoretical equation-of-state and transport models in the warm dense matter regime in determining computational predictions.

  15. Dynamic compression of dense oxide (Gd3Ga5O12) from 0.4 to 2.6 TPa: Universal Hugoniot of fluid metals.

    PubMed

    Ozaki, N; Nellis, W J; Mashimo, T; Ramzan, M; Ahuja, R; Kaewmaraya, T; Kimura, T; Knudson, M; Miyanishi, K; Sakawa, Y; Sano, T; Kodama, R

    2016-01-01

    Materials at high pressures and temperatures are of great current interest for warm dense matter physics, planetary sciences, and inertial fusion energy research. Shock-compression equation-of-state data and optical reflectivities of the fluid dense oxide, Gd3Ga5O12 (GGG), were measured at extremely high pressures up to 2.6 TPa (26 Mbar) generated by high-power laser irradiation and magnetically-driven hypervelocity impacts. Above 0.75 TPa, the GGG Hugoniot data approach/reach a universal linear line of fluid metals, and the optical reflectivity most likely reaches a constant value indicating that GGG undergoes a crossover from fluid semiconductor to poor metal with minimum metallic conductivity (MMC). These results suggest that most fluid compounds, e.g., strong planetary oxides, reach a common state on the universal Hugoniot of fluid metals (UHFM) with MMC at sufficiently extreme pressures and temperatures. The systematic behaviors of warm dense fluid would be useful benchmarks for developing theoretical equation-of-state and transport models in the warm dense matter regime in determining computational predictions. PMID:27193942

  16. Influence of Pressure and Temperature on Microstructure and Mechanical Behavior of Squeeze Cast Mg-10Gd-3Y-0.5Zr Alloy

    NASA Astrophysics Data System (ADS)

    Wang, Cunlong; Lavernia, Enrique J.; Wu, Guohua; Liu, Wencai; Ding, Wenjiang

    2016-08-01

    The influence of applied pressure and pouring temperature on the microstructure and mechanical properties of a squeeze cast (SC) Mg-10Gd-3Y-0.5Zr (GW103K) alloy was systematically investigated. Our results show that increasing the applied pressure leads to microstructure refinement of the GW103K alloy with accompanying enhancement of tensile yield strength (TYS), ultimate tensile strength (UTS), and elongation to failure ( E f); a decrease in pouring temperature also leads to grain refinement and increases of TYS while decreasing the UTS and E f. Our results show that, for the range of parameters studied herein, an applied pressure of ~160 MPa, in combination with a pouring temperature of ~993 K (720 °C), represents optimum process parameters for squeeze casting of GW103K. Using these process parameters, the TYS, UTS, and E f of squeeze cast GW103K alloy are 151 MPa, 232 MPa, and 3.0 pct in the as-cast state, and 264 MPa, 383 MPa, and 1.5 pct, respectively, in the as-T6 heat-treated state, both of which represent significant improvements over those of the gravity cast (GC) counterpart material.

  17. Angular dependant micro-ESR characterization of a locally doped Gd3+:Al2O3 hybrid system for quantum applications

    NASA Astrophysics Data System (ADS)

    Wisby, I. S.; de Graaf, S. E.; Gwilliam, R.; Adamyan, A.; Kubatkin, S. E.; Meeson, P. J.; Tzalenchuk, A. Ya.; Lindstrom, T.

    Rare-earth doped crystals interfaced with superconducting quantum circuitry are an attractive platform for quantum memory and transducer applications. Here we present a detailed characterization of a locally implanted Gd3+ in Al2O3 system coupled to a superconducting micro-resonator, by performing angular dependent micro-electron-spin-resonance (micro-ESR) measurements at mK temperatures. The device is fabricated using a hard Si3N4 mask to facilitate a local ion-implantation technique for precision control of the dopant location. The technique is found not to degrade the internal quality factor of the resonators which remains above 105 (1). We find the measured angular dependence of the micro-ESR spectra to be in excellent agreement with the modelled Hamiltonian, supporting the conclusion that the dopant ions are successfully integrated into their relevant lattice sites whilst maintaining crystalline symmetries. Furthermore, we observe clear contributions from individual microwave field components of our micro-resonator, emphasising the need for controllable local implantation. 1 Wisby et al. Appl. Phys. Lett. 105, 102601 (2014)

  18. A Eu(3+)/Gd(3+)-EDTA-doped structurally controllable hollow mesoporous carbon for improving the oral bioavailability of insoluble drugs and in vivo tracing.

    PubMed

    Liu, Jia; Zhao, Yating; Cui, Yu; Yue, Yang; Gao, Yikun; Zhao, Qinfu; Liu, Jie; Wang, Siling

    2016-08-01

    A structurally controllable fluorescence-labeled hollow mesoporous carbon (HMC) was simply prepared to improve the oral bioavailability of insoluble drugs and further trace their delivery process in vivo. The hollow structure was derived from an inverse replica process using mesoporous silica as a template and the fluorescent label was prepared by doping the carboxylated HMC with a confinement of Eu(3+)/Gd(3+)-EDTA. The physicochemical properties of the composites were systematically characterized by transmission electron microscopy, Fourier transform infrared spectroscopy and photoluminescence spectra tests prior to studying their effects on drug-release behavior and biodistribution. As a result, the thickness of the carrier's shell was adjusted from 70 nm to 130 nm and the maximum drug loading was up to 73.6%. The model drug carvedilol (CAR) showed sustained release behavior compared to CAR commercial capsules, and the dissolution rate slowed down as the shells got thicker. AUC0-48h and Tmax were enlarged 2.2 and 6.5 fold, respectively, which demonstrated that oral bioavailability was successfully improved. Bioimaging tests showed that the novel carbon vehicle had a long residence time in the gastrointestinal tract. In short, the newly designed HMC is a promising drug carrier for both oral bioavailability improvement and in vivo tracing. PMID:27334550

  19. Dynamic compression of dense oxide (Gd3Ga5O12) from 0.4 to 2.6 TPa: Universal Hugoniot of fluid metals

    DOE PAGESBeta

    Ozaki, N.; Nellis, W. J.; Mashimo, T.; Ramzan, M.; Ahuja, R.; Kaewmaraya, T.; Kimura, T.; Knudson, M.; Miyanishi, K.; Sakawa, Y.; et al

    2016-05-19

    Materials at high pressures and temperatures are of great current interest for warm dense matter physics, planetary sciences, and inertial fusion energy research. Shock-compression equation-of-state data and optical reflectivities of the fluid dense oxide, Gd3Ga5O12 (GGG), were measured at extremely high pressures up to 2.6 TPa (26 Mbar) generated by high-power laser irradiation and magnetically-driven hypervelocity impacts. Above 0.75 TPa, the GGG Hugoniot data approach/reach a universal linear line of fluid metals, and the optical reflectivity most likely reaches a constant value indicating that GGG undergoes a crossover from fluid semiconductor to poor metal with minimum metallic conductivity (MMC). Thesemore » results suggest that most fluid compounds, e.g., strong planetary oxides, reach a common state on the universal Hugoniot of fluid metals (UHFM) with MMC at sufficiently extreme pressures and temperatures. Lastly, the systematic behaviors of warm dense fluid would be useful benchmarks for developing theoretical equation-of-state and transport models in the warm dense matter regime in determining computational predictions.« less

  20. Continuous wave and passively Q-switched laser performance of Nd:LuxGd3-xGa5O12 crystal at 1062 nm

    NASA Astrophysics Data System (ADS)

    Fu, X. W.; Jia, Z. T.; Yang, H.; Li, Y. B.; Yuan, D. S.; Zhang, B. T.; Dong, C. M.; He, J. L.; Tao, X. T.

    2012-12-01

    Continuous wave (CW) and passively Q-switched (PQS) laser properties at 1062 nm of the Nd:LuxGd3-xGa5O12 (Nd:LGGG) disordered crystal have been demonstrated. The doping concentrations of Nd3+ and Lu3+ in the as obtained crystal were measured to be 0.96 and 0.66 at.%, respectively. In the CW regime, the output power of 9.73 W was obtained with an optical-to-optical efficiency as high as 60.7% and slope efficiency of 61.2%. During the passively Q-switched operation, the maximum output power of 1.24 W was achieved under the absorbed pump power of 6.86 W. The maximum peak power of 14.20 kW and single pulse energy of 148 μJ were obtained with the Toc = 10% under the absorbed pump power of 6.36 W. The results are much better than those obtained with Nd:LGGG crystal doped with 13.6 at.% Lu3+ and 0.53 at.% Nd3+ ions.

  1. A Eu3+/Gd3+-EDTA-doped structurally controllable hollow mesoporous carbon for improving the oral bioavailability of insoluble drugs and in vivo tracing

    NASA Astrophysics Data System (ADS)

    Liu, Jia; Zhao, Yating; Cui, Yu; Yue, Yang; Gao, Yikun; Zhao, Qinfu; Liu, Jie; Wang, Siling

    2016-08-01

    A structurally controllable fluorescence-labeled hollow mesoporous carbon (HMC) was simply prepared to improve the oral bioavailability of insoluble drugs and further trace their delivery process in vivo. The hollow structure was derived from an inverse replica process using mesoporous silica as a template and the fluorescent label was prepared by doping the carboxylated HMC with a confinement of Eu3+/Gd3+-EDTA. The physicochemical properties of the composites were systematically characterized by transmission electron microscopy, Fourier transform infrared spectroscopy and photoluminescence spectra tests prior to studying their effects on drug-release behavior and biodistribution. As a result, the thickness of the carrier’s shell was adjusted from 70 nm to 130 nm and the maximum drug loading was up to 73.6%. The model drug carvedilol (CAR) showed sustained release behavior compared to CAR commercial capsules, and the dissolution rate slowed down as the shells got thicker. AUC0-48h and Tmax were enlarged 2.2 and 6.5 fold, respectively, which demonstrated that oral bioavailability was successfully improved. Bioimaging tests showed that the novel carbon vehicle had a long residence time in the gastrointestinal tract. In short, the newly designed HMC is a promising drug carrier for both oral bioavailability improvement and in vivo tracing.

  2. Influence of Pressure and Temperature on Microstructure and Mechanical Behavior of Squeeze Cast Mg-10Gd-3Y-0.5Zr Alloy

    NASA Astrophysics Data System (ADS)

    Wang, Cunlong; Lavernia, Enrique J.; Wu, Guohua; Liu, Wencai; Ding, Wenjiang

    2016-05-01

    The influence of applied pressure and pouring temperature on the microstructure and mechanical properties of a squeeze cast (SC) Mg-10Gd-3Y-0.5Zr (GW103K) alloy was systematically investigated. Our results show that increasing the applied pressure leads to microstructure refinement of the GW103K alloy with accompanying enhancement of tensile yield strength (TYS), ultimate tensile strength (UTS), and elongation to failure (E f); a decrease in pouring temperature also leads to grain refinement and increases of TYS while decreasing the UTS and E f. Our results show that, for the range of parameters studied herein, an applied pressure of ~160 MPa, in combination with a pouring temperature of ~993 K (720 °C), represents optimum process parameters for squeeze casting of GW103K. Using these process parameters, the TYS, UTS, and E f of squeeze cast GW103K alloy are 151 MPa, 232 MPa, and 3.0 pct in the as-cast state, and 264 MPa, 383 MPa, and 1.5 pct, respectively, in the as-T6 heat-treated state, both of which represent significant improvements over those of the gravity cast (GC) counterpart material.

  3. Radiometric assay for ganglioside sialidase applied to the determination of the enzyme subcellular location in culture human fibroblasts

    SciTech Connect

    Chigorno, V.; Cardace, G.; Pitto, M.; Sonnino, S.; Ghidoni, R.; Tettamanti, G.

    1986-03-01

    A radiometric method for the assay of ganglioside sialidase in cultured human fibroblasts was set up. As substrate, highly radioactive (1.28 Ci/mmol) ganglioside GD/sub 1a/ isotopically tritium-labeled at carbon C-3 of the long chain base was employed; the liberated, and TLC separated (/sup 3/H)GM/sub 1/ was determined by computer-assisted radiochromatoscanning. Under experimental conditions that provided a low and quite acceptable (4-5%) coefficient of variation, the detection limit of the method was 0.1 nmol of liberated GM/sub 1/, using as low as 10 ..mu..g of fibroblast homogenate as protein. The detection limit could be lowered to 0.02-0.03 nmol, adopting conditions that, however, carried a higher analytical error (coefficient of variation over 10%). The content of ganglioside sialidase in human fibroblasts cultured in 75-cm/sup 2/ plastic flasks was 5.8 -/+ 2.5 (SD) nmol liberated GM/sub 1/ h/sup -1/ mg protein/sup -1/. Subfractionation studies performed on fibroblast homogenate showed that the ganglioside sialidase was mainly associated with the light membrane subfraction that was rich in plasma and intracellular membranes. This subfraction displayed almost no sialidase activity on the artificial substrate 4-methylumbelliferyl-D-N-acetylneuraminic acid. A small but measurable ganglioside sialidase activity was also present in the lysosome-enriched subfraction, which contained a very high sialidase activity on the above artificial substrate.

  4. Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration

    PubMed Central

    Vyas, Alka A.; Patel, Himatkumar V.; Fromholt, Susan E.; Heffer-Lauc, Marija; Vyas, Kavita A.; Dang, Jiyoung; Schachner, Melitta; Schnaar, Ronald L.

    2002-01-01

    Myelin-associated glycoprotein (MAG) binds to the nerve cell surface and inhibits nerve regeneration. The nerve cell surface ligand(s) for MAG are not established, although sialic acid-bearing glycans have been implicated. We identify the nerve cell surface gangliosides GD1a and GT1b as specific functional ligands for MAG-mediated inhibition of neurite outgrowth from primary rat cerebellar granule neurons. MAG-mediated neurite outgrowth inhibition is attenuated by (i) neuraminidase treatment of the neurons; (ii) blocking neuronal ganglioside biosynthesis; (iii) genetically modifying the terminal structures of nerve cell surface gangliosides; and (iv) adding highly specific IgG-class antiganglioside mAbs. Furthermore, neurite outgrowth inhibition is mimicked by highly multivalent clustering of GD1a or GT1b by using precomplexed antiganglioside Abs. These data implicate the nerve cell surface gangliosides GD1a and GT1b as functional MAG ligands and suggest that the first step in MAG inhibition is multivalent ganglioside clustering. PMID:12060784

  5. Constituents of ophiuroidea. 1. Isolation and structure of three ganglioside molecular species from the brittle star Ophiocoma scolopendrina.

    PubMed

    Inagaki, M; Shibai, M; Isobe, R; Higuchi, R

    2001-12-01

    Three ganglioside molecular species, OSG-0 (1), OSG-1 (2), and OSG-2 (3) have been obtained from the polar lipid fraction of the chloroform/methanol extract of the brittle star Ophiocoma scolopendrina. The structures of these gangliosides have been determined on the basis of chemical and spectroscopic evidence as 1-O-[(N-glycolyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (1), 1-O-[8-O-sulfo-(N-acetyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyll-ceramide (2) and 1-O-[(N-glycolyl-alpha-D-neuraminosyl)-(2-->8)-(N-acetyl- and N-glycolyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (3). The ceramide moieties were composed of heterogeneous unsubstituted fatty acid, 2-hydroxy fatty acid and phytosphingosine units. Compounds 2 and 3 represent new ganglioside molecular species. PMID:11767069

  6. Gangliosides of myelosupportive stroma cells are transferred to myeloid progenitors and are required for their survival and proliferation

    PubMed Central

    Ziulkoski, Ana L.; Andrade, Cláudia M. B.; Crespo, Pilar M.; Sisti, Elisa; Trindade, Vera M. T.; Daniotti, Jose L.; Guma, Fátima C. R.; Borojevic, Radovan

    2005-01-01

    In previous studies, we have shown that the myelopoiesis dependent upon myelosupportive stroma required production of growth factors and heparan-sulphate proteoglycans, as well as generation of a negatively charged sialidase-sensitive intercellular environment between the stroma and the myeloid progenitors. In the present study, we have investigated the production, distribution and role of gangliosides in an experimental model of in vitro myelopoiesis dependent upon AFT-024 murine liver-derived stroma. We used the FDC-P1 cell line, which is dependent upon GM-CSF (granulocyte/macrophage colony-stimulating factor) for both survival and proliferation, as a reporter system to monitor bioavailability and local activity of GM-CSF. GM3 was the major ganglioside produced by stroma, but not by myeloid cells, and it was required for optimal stroma myelosupportive function. It was released into the supernatant and selectively incorporated into the myeloid progenitor cells, where it segregated into rafts in which it co-localized with the GM-CSF-receptor α chain. This ganglioside was also metabolized further by myeloid cells into gangliosides of the a and b series, similar to endogenous GM3. In these cells, GM1 was the major ganglioside and it was segregated at the interface by stroma and myeloid cells, partially co-localizing with the GM-CSF-receptor α chain. We conclude that myelosupportive stroma cells produce and secrete the required growth factors, the cofactors such as heparan sulphate proteoglycans, and also supply gangliosides that are transferred from stroma to target cells, generating on the latter ones specific membrane domains with molecular complexes that include growth factor receptors. PMID:16321139

  7. Ganglioside GD1a promotes oocyte maturation, furthers preimplantation development, and increases blastocyst quality in pigs.

    PubMed

    Kim, Jin-Woo; Park, Hyo-Jin; Chae, Sung-Kyu; Ahn, Jae-Hyun; DO, Geon-Yeop; Choo, Young-Kug; Park, Joung Jun; Jung, Bae Dong; Kim, Sun-Uk; Chang, Kyu-Tae; Koo, Deog-Bon

    2016-06-17

    Gangliosides are key lipid molecules required for the regulation of cellular processes such as proliferation, differentiation, and cell signaling, including signaling of epidermal growth factor receptor (EGFR). Epidermal growth factor (EGF) has long been considered a potential regulator of meiotic and cytoplasmic maturation in mammalian oocytes. However, there is no report on the direct effect of ganglioside GD1a in porcine oocyte maturation. In this study, we first investigated a functional link between GD1a and meiotic maturation during in vitro maturation (IVM) of porcine embryos. Moreover, we confirmed the effect of exogenous GD1a treatment on blastocyst development, quality, and fertilization rate in early embryonic development. First, we observed that the protein level of ST3GAL2, a GD1a synthesizing enzyme, significantly increased (P < 0.01) in cumulus-oocyte-complexes (COCs) during IVM progress. The proportion of arrested germinal vesicles (GV) increased in oocytes treated with EGF+GD1a (41.6 ± 1.5%) at the IVM I stage. Upon completion of meiotic maturation, the proportion of metaphase II (M II) was significantly higher (P < 0.05) in the EGF+GD1a (89.9 ± 3.6%) treated group. After IVF, the percentage of penetrated oocytes was significantly higher (P < 0.05) in the EGF+GD1a (89.1 ± 2.3%) treated group than in the control group. Furthermore, exogenous GD1a treatment improved the developmental competence and quality of blastocysts during preimplantation embryo development stage. These results suggest that ganglioside GD1a may play an important role in IVM mechanisms of porcine maturation capacity. Furthermore, our findings will be helpful for better promoting the embryo development and blastocyst quality in pigs. PMID:26860251

  8. Condensing and Fluidizing Effects of Ganglioside GM1 on Phospholipid Films

    PubMed Central

    Frey, Shelli L.; Chi, Eva Y.; Arratia, Cristóbal; Majewski, Jaroslaw; Kjaer, Kristian; Lee, Ka Yee C.

    2008-01-01

    Mixed monolayers of the ganglioside GM1 and the lipid dipalmitoylphosphatidlycholine (DPPC) at air-water and solid-air interfaces were investigated using various biophysical techniques to ascertain the location and phase behavior of the ganglioside molecules in a mixed membrane. The effects induced by GM1 on the mean molecular area of the binary mixtures and the phase behavior of DPPC were followed for GM1 concentrations ranging from 5 to 70 mol %. Surface pressure isotherms and fluorescence microscopy imaging of domain formation indicate that at low concentrations of GM1 (<25 mol %), the monolayer becomes continually more condensed than DPPC upon further addition of ganglioside. At higher GM1 concentrations (>25 mol %), the mixed monolayer becomes more expanded or fluid-like. After deposition onto a solid substrate, atomic force microscopy imaging of these lipid monolayers showed that GM1 and DPPC pack cooperatively in the condensed phase domain to form geometrically packed complexes that are more ordered than either individual component as evidenced by a more extended total height of the complex arising from a well-packed hydrocarbon tail region. Grazing incidence x-ray diffraction on the DPPC/GM1 binary mixture provides evidence that ordering can emerge when two otherwise fluid components are mixed together. The addition of GM1 to DPPC gives rise to a unit cell that differs from that of a pure DPPC monolayer. To determine the region of the GM1 molecule that interacts with the DPPC molecule and causes condensation and subsequent expansion of the monolayer, surface pressure isotherms were obtained with molecules modeling the backbone or headgroup portions of the GM1 molecule. The observed concentration-dependent condensing and fluidizing effects are specific to the rigid, sugar headgroup portion of the GM1 molecule. PMID:18192361

  9. Condensing and fluidizing effects of ganglioside GM1 on phospholipid films.

    PubMed

    Frey, Shelli L; Chi, Eva Y; Arratia, Cristóbal; Majewski, Jaroslaw; Kjaer, Kristian; Lee, Ka Yee C

    2008-04-15

    Mixed monolayers of the ganglioside G(M1) and the lipid dipalmitoylphosphatidlycholine (DPPC) at air-water and solid-air interfaces were investigated using various biophysical techniques to ascertain the location and phase behavior of the ganglioside molecules in a mixed membrane. The effects induced by G(M1) on the mean molecular area of the binary mixtures and the phase behavior of DPPC were followed for G(M1) concentrations ranging from 5 to 70 mol %. Surface pressure isotherms and fluorescence microscopy imaging of domain formation indicate that at low concentrations of G(M1) (<25 mol %), the monolayer becomes continually more condensed than DPPC upon further addition of ganglioside. At higher G(M1) concentrations (>25 mol %), the mixed monolayer becomes more expanded or fluid-like. After deposition onto a solid substrate, atomic force microscopy imaging of these lipid monolayers showed that G(M1) and DPPC pack cooperatively in the condensed phase domain to form geometrically packed complexes that are more ordered than either individual component as evidenced by a more extended total height of the complex arising from a well-packed hydrocarbon tail region. Grazing incidence x-ray diffraction on the DPPC/G(M1) binary mixture provides evidence that ordering can emerge when two otherwise fluid components are mixed together. The addition of G(M1) to DPPC gives rise to a unit cell that differs from that of a pure DPPC monolayer. To determine the region of the G(M1) molecule that interacts with the DPPC molecule and causes condensation and subsequent expansion of the monolayer, surface pressure isotherms were obtained with molecules modeling the backbone or headgroup portions of the G(M1) molecule. The observed concentration-dependent condensing and fluidizing effects are specific to the rigid, sugar headgroup portion of the G(M1) molecule. PMID:18192361

  10. Fucosyl-GM1a, an endoglycoceramidase-resistant ganglioside of porcine brain.

    PubMed

    Xu, Xu; Monjusho, Hatsumi; Inagaki, Masanori; Hama, Yoichiro; Yamaguchi, Kuniko; Sakaguchi, Keishi; Iwamori, Masao; Okino, Nozomu; Ito, Makoto

    2007-01-01

    The use of bovine brain has been prohibited in many countries because of the world-wide prevalence of mad cow disease, and thus porcine brain is expected to be a new source for the preparation of gangliosides. Here, we report the presence of a ganglioside in porcine brain which is strongly resistant to hydrolysis by endoglycoceramidase, an enzyme capable of cleaving the glycosidic linkage between oligosaccharides and ceramides of various glycosphingolipids. Five major gangliosides (designated PBG-1, 2, 3, 4, 5) were extracted from porcine brain by Folch's partition, followed by mild alkaline hydrolysis and PBA column chromatography. We found that PBG-2, but not the others, was strongly resistant to hydrolysis by the enzyme. After the purification of PBG-2 with Q-Sepharose, Silica gel 60 and Prosep-PB chromatographies, the structure of PBG-2 was determined by GC, GC-MS, FAB-MS and NMR spectroscopy as Fucalpha1-2Galbeta1-3GalNAcbeta1-4(NeuAcalpha2-3)Galbeta1-4Glcbeta1-1'Cer (fucosyl-GM1a). The ceramide was mainly composed of C18:0 and C20:0 fatty acids and d18:1 and d20:1 sphingoid bases. The apparent kcat/Km for fucosyl-GM1a was found to be 30 times lower than that for GM1a, indicating that terminal fucosylation makes GM1a resistant to hydrolysis by the enzyme. This report indicates the usefulness of endoglycoceramidase to prepare fucosyl-GM1a from porcine brain. PMID:17167042