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991.
A Wettreich A Sebollela M A Carvalho S P Azevedo R Borojevic S T Ferreira T Coelho-Sampaio 《The Journal of biological chemistry》1999,274(44):31468-31475
Granulocyte-macrophage colony-stimulating factor (GM-CSF) controls growth and differentiation of hematopoietic cells. Previous reports have indicated that the mitogenic activity of GM-CSF may be modulated by the glycosidic moiety of proteoglycans associated with the membrane of stromal cells. In this work, we have performed in vitro studies of the interaction between GM-CSF and glycosaminoglycans. The addition of heparin promoted a marked blue shift in the fluorescence emission spectrum of GM-CSF as well as a 30-fold increase in the intensity of light scattering, which indicates formation of large molecular weight complexes between the two molecules. Interestingly, heparin-induced changes in the spectral properties of GM-CSF were only observed at acidic pH. The dependence on acidic pH, together with a strict dependence on glycosaminoglycan sulfation and the fact that high ionic strength destabilized the interaction, indicates that the association between GM-CSF and glycosaminoglycans is mediated by electrostatic interactions. These interactions probably involve sulfate groups in the glycosaminoglycans and positively charged histidine residues in GM-CSF. We propose that negatively charged glycolipids present on the plasma membrane of the hematopoietic and/or the stromal cell could promote an acidic microenvironment capable of triggering interaction between GM-CSF and membrane-bound proteoglycans in vivo. 相似文献
992.
993.
Maria Elisabete Sbrogio De Almeida Salete M. Newton Luís Carlos S. Ferreira 《Archives of microbiology》1999,172(2):102-108
Salmonella fIagellin has been repeatedly used as a carrier for heterologous peptide epitopes either as a parenterally delivered purified
antigen or as a parenterally/orally-administered, flagellated, live, attenuated vaccine. Nonetheless, the ability to induce
specific antibody responses against the flagellin moiety, fused or not with heterologous peptide, has not usually been reported
in mice orally inoculated with a live, attenuated, flagellated Salmonella strain. In this work we evaluated the immunogenicity of flagellin in mice following oral inoculation with an aroA Salmonella enterica serovar Dublin SL5929 strain, which expressed plasmid-encoded recombinant hybrid flagellin fused to the CTP3 epitope (amino
acids 50–64) of cholera toxin B-subunit. In contrast to parenterally immunized mice, no significant CTP3- or flagellin-specific
antibody responses either in sera (IgG) or feces (IgA) were detected following repeated oral delivery of the recombinant Salmonella strain to C57BL/6 mice. Similarly, flagellin-specific antibody responses were also not detected in mice immunized with strain
SL5930, which expressed a nonhybrid flagellin. The lack of flagellin-specific antibody responses was not associated with deficient
Peyer patch colonization or spleen invasion. Moreover, stabilization of the flagellin-coding gene by integration into the
host chromosome did not significantly improve flagellin-specific antibody responses following administration by the oral route.
Taken together, these results suggest that flagellin does not represent an efficient peptide carrier for activation of antibody
responses in mice orally immunized with live, attenuated Salmonella strains.
Received: 29 December 1998 / Accepted: 3 May 1999 相似文献
994.
Barbara Ben Yamin Sana AhmedSeghir Junya Tomida Emmanuelle Despras Caroline Pouvelle Andrey Yurchenko Jordane Goulas Raphael Corre Quentin Delacour Nathalie Droin Philippe Dessen Didier Goidin Sabine S Lange Sarita Bhetawal Maria Teresa MitjavilaGarcia Giuseppe Baldacci Sergey Nikolaev Jean Charles Cadoret Richard D Wood Patricia L Kannouche 《The EMBO journal》2021,40(21)
995.
The enzyme 4‐oxalocrotonate tautomerase catalyzes the ketonization of dienols, which after further processing become intermediates in the Krebs cycle. The enzyme uses a general acid–base mechanism for proton transfer: the amino‐terminal proline has been shown to function as the catalytic base and Arg39 has been implicated as the catalytic acid. We report the results of molecular docking simulations of 4‐oxalocrotonate tautomerase with two substrates, 2‐hydroxymuconate and 5‐carboxymethyl‐2‐hydroxymuconate. pKa calculations are also performed for the free enzyme. The predicted binding mode of 2‐hydroxymuconate is in agreement with experimental data. A model for the binding mode of 5‐carboxymethyl‐2‐hydroxymuconate is proposed which explains the lower catalytic efficiency of the enzyme toward this substrate. The pKa predictions and docking simulations support residue Arg39 as the general acid for the enzyme catalysis. © 1999 John Wiley & Sons, Inc. Biopoly 50: 319–328, 1999 相似文献
996.
Adriana Marcelo Inês T. Afonso Ricardo Afonso-Reis David V. C. Brito Rafael G. Costa Ana Rosa Joo Alves-Cruzeiro Benedita Ferreira Carina Henriques Rui J. Nobre Carlos A. Matos Luís Pereira de Almeida Clvio Nbrega 《Cell death & disease》2021,12(12)
Spinocerebellar ataxia type 2 (SCA2) is an incurable and genetic neurodegenerative disorder. The disease is characterized by progressive degeneration of several brain regions, resulting in severe motor and non-motor clinical manifestations. The mutation causing SCA2 disease is an abnormal expansion of CAG trinucleotide repeats in the ATXN2 gene, leading to a toxic expanded polyglutamine segment in the translated ataxin-2 protein. While the genetic cause is well established, the exact mechanisms behind neuronal death induced by mutant ataxin-2 are not yet completely understood. Thus, the goal of this study is to investigate the role of autophagy in SCA2 pathogenesis and investigate its suitability as a target for therapeutic intervention. For that, we developed and characterized a new striatal lentiviral mouse model that resembled several neuropathological hallmarks observed in SCA2 disease, including formation of aggregates, neuronal marker loss, cell death and neuroinflammation. In this new model, we analyzed autophagic markers, which were also analyzed in a SCA2 cellular model and in human post-mortem brain samples. Our results showed altered levels of SQSTM1 and LC3B in cells and tissues expressing mutant ataxin-2. Moreover, an abnormal accumulation of these markers was detected in SCA2 patients’ striatum and cerebellum. Importantly, the molecular activation of autophagy, using the compound cordycepin, mitigated the phenotypic alterations observed in disease models. Overall, our study suggests an important role for autophagy in the context of SCA2 pathology, proposing that targeting this pathway could be a potential target to treat SCA2 patients.Subject terms: Diseases of the nervous system, Molecular neuroscience 相似文献
997.
998.
Daria Sicari Federica G Centonze Raphael Pineau PierreJean Le Reste Luc Negroni Sophie Chat M Aiman Mohtar Daniel Thomas Reynald Gillet Ted Hupp Eric Chevet Aeid Igbaria 《EMBO reports》2021,22(5)
In the past decades, many studies reported the presence of endoplasmic reticulum (ER)‐resident proteins in the cytosol. However, the mechanisms by which these proteins relocate and whether they exert cytosolic functions remain unknown. We find that a subset of ER luminal proteins accumulates in the cytosol of glioblastoma cells isolated from mouse and human tumors. In cultured cells, ER protein reflux to the cytosol occurs upon ER proteostasis perturbation. Using the ER luminal protein anterior gradient 2 (AGR2) as a proof of concept, we tested whether the refluxed proteins gain new functions in the cytosol. We find that refluxed, cytosolic AGR2 binds and inhibits the tumor suppressor p53. These data suggest that ER reflux constitutes an ER surveillance mechanism to relieve the ER from its contents upon stress, providing a selective advantage to tumor cells through gain‐of‐cytosolic functions—a phenomenon we name ER to Cytosol Signaling (ERCYS). 相似文献
999.
1000.
Eder Marques da Silva Geraldo Felipe Ferreira e Silva Débora Brussolo Bidoia Mariana da Silva Azevedo Frederico Almeida de Jesus Lilian Ellen Pino Lázaro Eustáquio Pereira Peres Esther Carrera Isabel López‐Díaz Fabio Tebaldi Silveira Nogueira 《The Plant journal : for cell and molecular biology》2017,92(1):95-109
The transition from flowering to fruit production, namely fruit set, is crucial to ensure successful sexual plant reproduction. Although studies have described the importance of hormones (i.e. auxin and gibberellins) in controlling fruit set after pollination and fertilization, the role of microRNA‐based regulation during ovary development and fruit set is still poorly understood. Here we show that the microRNA159/GAMYB1 and ‐2 pathway (the miR159/GAMYB1/2 module) is crucial for tomato ovule development and fruit set. MiR159 and SlGAMYBs were expressed in preanthesis ovaries, mainly in meristematic tissues, including developing ovules. SlMIR159‐overexpressing tomato cv. Micro‐Tom plants exhibited precocious fruit initiation and obligatory parthenocarpy, without modifying fruit shape. Histological analysis showed abnormal ovule development in such plants, which led to the formation of seedless fruits. SlGAMYB1/2 silencing in SlMIR159‐overexpressing plants resulted in misregulation of pathways associated with ovule and female gametophyte development and auxin signalling, including AINTEGUMENTA‐like genes and the miR167/SlARF8a module. Similarly to SlMIR159‐overexpressing plants, SlGAMYB1 was downregulated in ovaries of parthenocarpic mutants with altered responses to gibberellins and auxin. SlGAMYBs likely contribute to fruit initiation by modulating auxin and gibberellin responses, rather than their levels, during ovule and ovary development. Altogether, our results unveil a novel function for the miR159‐targeted SlGAMYBs in regulating an agronomically important trait, namely fruit set. 相似文献