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61.
Eyngor M Chilmonczyk S Zlotkin A Manuali E Lahav D Ghittino C Shapira R Hurvitz A Eldar A 《FEMS microbiology letters》2007,277(2):238-248
By constructing a biological model based on in vitro culture of polarized rainbow trout primary skin epithelial cell monolayers, the series of early events that precede Streptococcus iniae infection, particularly colonization and translocation through external barriers, were analyzed. Streptococcus iniae promptly invades skin epithelial cells, but the rapid decline of viable intracellular bacteria points out the limited capability of intracellular survival for this bacterium. Translocation assays, supported by electron microscopy microphotographs, demonstrate that following successful in vitro invasion of skin epithelial cell, the bacterium exists free in the cytoplasm after release from the endosome, and translocates through the skin barrier. Bacterial invasion and transcytosis is not accompanied by apparent cell-line damages or disruption of host cells' tight junctions. It is hypothesized that the phenomenon of epithelial invasion coupled to the rapid translocation through the barrier plays a crucial role in Streptococcus iniae infection. 相似文献
62.
63.
Nanna M Jensen Trine Dalsgaard Maria Jakobsen Roni R Nielsen Charlotte B Sørensen Lars Bolund Thomas G Jensen 《Journal of biomedical science》2011,18(1):10
Transfer of full-length genes including regulatory elements has been the preferred gene therapy strategy for clinical applications.
However, with significant drawbacks emerging, targeted gene alteration (TGA) has recently become a promising alternative to
this method. By means of TGA, endogenous DNA repair pathways of the cell are activated leading to specific genetic correction
of single-base mutations in the genome. This strategy can be implemented using single-stranded oligodeoxyribonucleotides (ssODNs),
small DNA fragments (SDFs), triplex-forming oligonucleotides (TFOs), adeno-associated virus vectors (AAVs) and zinc-finger
nucleases (ZFNs). Despite difficulties in the use of TGA, including lack of knowledge on the repair mechanisms stimulated
by the individual methods, the field holds great promise for the future. The objective of this review is to summarize and
evaluate the different methods that exist within this particular area of human gene therapy research. 相似文献
64.
Karin Rand Irina Kobrinsky-Aaronowitz Yael Levy Orit Shaul Roni Aloni Yedidya Gafni 《Plant signaling & behavior》2011,6(6):815-820
Macromolecules may transfer between the cytoplasm and the nucleus only through specific gates—the nuclear pore complexes (NPCs). Translocation of nucleic acids and large proteins requires the presence of a nuclear localization signal (NLS) within the transported molecule. This NLS is recognized by a class of soluble transport receptors termed karyopherins α and β. We previously characterized the expression pattern of the tomato karyopherin α1 (LeKAPα1) promoter in transformed tobacco plants. Expression of LeKAPα1 was mainly observed in growing tissues where cell division and extension is rapid. The expression pattern of LeKAPα1 resembled that of auxin-responsive genes. This led us to suggest that auxin participates in the regulation of LeKAPα1 expression. Here we characterized the correlation between auxin level and the activity of the LeKAPα1 promoter. To this end, transgenic tobacco plants carrying the GUS reporter gene under the control of the LeKAPα1 promoter were treated with various levels of exogenous auxin. We also studied transgenic plants in which we increased the endogenous levels of auxin. For this, we expressed in plants both the LeKAPα1 promoter-GUS reporter and the Agrobacterium tumefaciens iaaM gene, which increases the endogenous levels of auxin. The results indicate that the auxin indole-3-acetic acid (IAA) can induce LeKAPα1 expression. We also identified that the sites and levels of LeKAPα1 expression correlated with the endogenous pathways of polar auxin transport.Key words: auxin, karyopherin α1, nuclear pore complex, TYLCV, plant virus 相似文献
65.
Yoram Nevo Shlomit Aga-Mizrachi Edva Elmakayes Nurit Yanay Keren Ettinger Moran Elbaz Zivia Brunschwig Oshrat Dadush Galit Elad-Sfadia Roni Haklai Yoel Kloog Joab Chapman Shimon Reif 《PloS one》2011,6(3)
The Ras superfamily of guanosine-triphosphate (GTP)-binding proteins regulates a diverse spectrum of intracellular processes involved in inflammation and fibrosis. Farnesythiosalicylic acid (FTS) is a unique and potent Ras inhibitor which decreased inflammation and fibrosis in experimentally induced liver cirrhosis and ameliorated inflammatory processes in systemic lupus erythematosus, neuritis and nephritis animal models. FTS effect on Ras expression and activity, muscle strength and fibrosis was evaluated in the dy2J/dy2J mouse model of merosin deficient congenital muscular dystrophy. The dy2J/dy2J mice had significantly increased RAS expression and activity compared with the wild type mice. FTS treatment significantly decreased RAS expression and activity. In addition, phosphorylation of ERK, a Ras downstream protein, was significantly decreased following FTS treatment in the dy2J/dy2J mice. Clinically, FTS treated mice showed significant improvement in hind limb muscle strength measured by electronic grip strength meter. Significant reduction of fibrosis was demonstrated in the treated group by quantitative Sirius Red staining and lower muscle collagen content. FTS effect was associated with significantly inhibition of both MMP-2 and MMP-9 activities. We conclude that active RAS inhibition by FTS was associated with attenuated fibrosis and improved muscle strength in the dy2J/dy2J mouse model of congenital muscular dystrophy. 相似文献
66.
Behavioral responses of an animal vary even when they are elicited by the same stimulus. This variability is due to stochastic processes within the nervous system and to the changing internal states of the animal. To what extent does the variability of neuronal responses account for the overall variability at the behavioral level? To address this question we evaluate the neuronal variability at the output stage of the blowfly''s (Calliphora vicina) visual system by recording from motion-sensitive interneurons mediating head optomotor responses. By means of a simple modelling approach representing the sensory-motor transformation, we predict head movements on the basis of the recorded responses of motion-sensitive neurons and compare the variability of the predicted head movements with that of the observed ones. Large gain changes of optomotor head movements have previously been shown to go along with changes in the animals'' activity state. Our modelling approach substantiates that these gain changes are imposed downstream of the motion-sensitive neurons of the visual system. Moreover, since predicted head movements are clearly more reliable than those actually observed, we conclude that substantial variability is introduced downstream of the visual system. 相似文献
67.
68.
Ferrando-Miguel R Rosner M Freilinger A Lubec G Hengstschläger M 《Neurochemical research》2005,30(11):1413-1419
Tuberous sclerosis complex (TSC) is a common genetic disorder in which affected individuals develop mental retardation, developmental
brain defects and seizures. The TSC gene products, hamartin and tuberin, form a complex, of which tuberin is assumed to be
the functional component being involved in a wide variety of different cellular processes. Here we report that tuberin protein
levels are decreased in the frontal cortex of patients with Alzheimer’s disease. In addition, tuberin levels are also decreased
in Down syndrome brain samples positive for β-amyloid plaques and neurofibrillary tangles. Analysis of NeuN revealed that
this regulation is not a consequence of differences in the amount of postmitotic neurons. This first connection of tuberin
to another common disease beside TSC stimulates new approaches to investigate the molecular development and to establish new
therapeutic strategies. 相似文献
69.
Loss of function of a lupus-associated FcgammaRIIb polymorphism through exclusion from lipid rafts 总被引:2,自引:0,他引:2
Floto RA Clatworthy MR Heilbronn KR Rosner DR MacAry PA Rankin A Lehner PJ Ouwehand WH Allen JM Watkins NA Smith KG 《Nature medicine》2005,11(10):1056-1058
Dysfunction of receptors for IgG (FcgammaRs) has been thought to be involved in the pathogenesis of systemic lupus erythematosus (SLE). We show that a recently described SLE-associated polymorphism of FcgammaRIIb (FcgammaRIIbT(232)), encoding a single transmembrane amino acid substitution, is functionally impaired. FcgammaRIIbT(232) is unable to inhibit activatory receptors because it is excluded from sphingolipid rafts, resulting in the unopposed proinflammatory signaling thought to promote SLE. 相似文献
70.
Monks J Rosner D Geske FJ Lehman L Hanson L Neville MC Fadok VA 《Cell death and differentiation》2005,12(2):107-114
Clearance of apoptotic cells is critical to tissue homeostasis and resolution of inflammatory lesions. Macrophages are known to remove dying cells and release anti-inflammatory mediators in response; however, many cells traditionally thought of as poor phagocytes can mediate this function as well. In the lactating mammary gland following weaning, alveolar epithelial cell death is massive, yet the gland involutes rapidly, attaining its prepregnancy state in a matter of days. We found histologic evidence of apoptotic cell phagocytosis by viable mammary epithelial cells (MEC) in the involuting mouse mammary gland. Cultured MEC were able to engulf apoptotic cells in vitro, utilizing many of the same receptors used by macrophages, including the phosphatidylserine receptor (PSR), CD36, the vitronectin receptor alpha(v)beta3, and CD91. In addition, MEC, like macrophages, produced TGFbeta in response to stimulation of the PSR by apoptotic cells or the anti-PSR ab 217G8E9, and downregulated endotoxin-stimulated proinflammatory cytokine production. These data support the hypothesis that amateur phagocytes play a significant role in apoptotic cell clearance and its regulation of inflammation. 相似文献