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Direct Alteration (direct + alteration)
Selected AbstractsDisruption of Cortical Microtubules by Overexpression of Green Fluorescent Protein-Tagged ,-Tubulin 6 Causes a Marked Reduction in Cell Wall SynthesisJOURNAL OF INTEGRATIVE PLANT BIOLOGY, Issue 1 2006David H. Burk Abstract It has been known that the transverse orientation of cortical microtubules (MTs) along the elongation axis is essential for normal cell morphogenesis, but whether cortical MTs are essential for normal cell wall synthesis is still not clear. In the present study, we have investigated whether cortical MTs affect cell wall synthesis by direct alteration of the cortical MT organization in Arabidopsis thaliana. Disruption of the cortical MT organization by expression of an excess amount of green fluorescent protein-tagged ,-tubulin 6 (GFP-TUA6) in transgenic Arabidopsis plants was found to cause a marked reduction in cell wall thickness and a decrease in the cell wall sugars glucose and xylose. Concomitantly, the stem strength of the GFP-TUA6 overexpressors was markedly reduced compared with the wild type. In addition, expression of excess GFP-TUA6 results in an alteration in cell morphogenesis and a severe effect on plant growth and development. Together, these results suggest that the proper organization of cortical MTs is essential for the normal synthesis of plant cell walls. (Managing editor: Wei Wang) [source] Tibolone Rapidly Attenuates the GABAB Response in Hypothalamic NeuronesJOURNAL OF NEUROENDOCRINOLOGY, Issue 12 2008J. Qiu Tibolone is primarily used for the treatment of climacteric symptoms. Tibolone is rapidly converted into three major metabolites: 3,- and 3,-hydroxy (OH)-tibolone, which have oestrogenic effects, and the ,4-isomer (,4-tibolone), which has progestogenic and androgenic effects. Because tibolone is effective in treating climacteric symptoms, the effects on the brain may be explained by the oestrogenic activity of tibolone. Using whole-cell patch clamp recording, we found previously that 17,-oestradiol (E2) rapidly altered ,-aminobutyric acid (GABA) neurotransmission in hypothalamic neurones through a membrane oestrogen receptor (mER). E2 reduced the potency of the GABAB receptor agonist baclofen to activate G-protein-coupled, inwardly rectifying K+ (GIRK) channels in hypothalamic neurones. Therefore, we hypothesised that tibolone may have some rapid effects through the mER and sought to elucidate the signalling pathway of tibolone's action using selective inhibitors and whole cell recording in ovariectomised female guinea pigs and mice. A sub-population of neurones was identified post hoc as pro-opiomelanocortin (POMC) neurones by immunocytochemical staining. Similar to E2, we have found that tibolone and its active metabolite 3,OH-tibolone rapidly reduced the potency of the GABAB receptor agonist baclofen to activate GIRK channels in POMC neurones. The effects were blocked by the ER antagonist ICI 182 780. Other metabolites of tibolone (3,OH-tibolone and ,4-tibolone) had no effect. Furthermore, tibolone (and 3,OH-tibolone) was fully efficacious in ER, knockout (KO) and ER,KO mice to attenuate GABAB responses. The effects of tibolone were blocked by phospholipase C inhibitor U73122. However, in contrast to E2, the effects of tibolone were not blocked by protein kinase C inhibitors or protein kinase A inhibitors. It appears that tibolone (and 3,OH-tibolone) activates phospholipase C leading to phosphatidylinositol bisphosphate metabolism and direct alteration of GIRK channel function. Therefore, tibolone may enhance synaptic efficacy through the Gq signalling pathways of mER in brain circuits that are critical for maintaining homeostatic functions. [source] X-linked mental retardation and epigeneticsJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2006Guy Froyen Abstract The search for the genetic defects in constitutional diseases has so far been restricted to direct methods for the identification of genetic mutations in the patients' genome. Traditional methods such as karyotyping, FISH, mutation screening, positional cloning and CGH, have been complemented with newer methods including array-CGH and PCR-based approaches (MLPA, qPCR). These methods have revealed a high number of genetic or genomic aberrations that result in an altered expression or reduced functional activity of key proteins. For a significant percentage of patients with congenital disease however, the underlying cause has not been resolved strongly suggesting that yet other mechanisms could play important roles in their etiology. Alterations of the ,native' epigenetic imprint might constitute such a novel mechanism. Epigenetics, heritable changes that do not rely on the nucleotide sequence, has already been shown to play a determining role in embryonic development, X-inactivation, and cell differentiation in mammals. Recent progress in the development of techniques to study these processes on full genome scale has stimulated researchers to investigate the role of epigenetic modifications in cancer as well as in constitutional diseases. We will focus on mental impairment because of the growing evidence for the contribution of epigenetics in memory formation and cognition. Disturbance of the epigenetic profile due to direct alterations at genomic regions, or failure of the epigenetic machinery due to genetic mutations in one of its components, has been demonstrated in cognitive derangements in a number of neurological disorders now. It is therefore tempting to speculate that the cognitive deficit in a significant percentage of patients with unexplained mental retardation results from epigenetic modifications. [source] Gene expression in chorionic villous samples at 11 weeks' gestation from women destined to develop preeclampsiaPRENATAL DIAGNOSIS, Issue 10 2008Antonio Farina Abstract Objective To evaluate the direct alterations in mRNA expression among chorionic villous samples from 11 weeks' pregnant women who would develop preeclampsia (PE) later in the pregnancy. Method Case-control study encompassing five women destined to develop PE [cases matched 1:5 for gestational age (GA) with 25 controls]. We quantified mRNA expression on tissue samples from chorionic villous sampling (CVS) of normal and PE patients. We then assessed mRNA expressions of vascular endothelial growth factor (VEGFA), VEGFA receptor 1 (Flt-1), endoglin (Eng), placental growth factor (PlGF), transforming growth factor-,1 (TGF-,1), heme oxygenase-1 (HO-1) and superoxide dismutase (SOD). Data were analyzed by nonparametric rank analysis. Results For all the mRNA species considered in this study, all the mean observed ranks in the PE group were significantly altered compared to the rank expectation among controls. mRNA for Eng and TGF-,1 were the markers with the highest degree of aberration in PE, in respect to controls. The results are consistent with those already reported for the corresponding circulating proteins. mRNA for HO-1 and SOD were instead associated with the lowest aberration. Conclusion It is assumed that the pathogenesis of PE is associated with pathophysiological alterations to trophoblasts in early gestation. Our study has directly proved that gene expressions relating to angiogenesis or oxidative stress are altered in the first trimester trophoblasts that go on to develop PE later. These results would put the basis for a possible screening method for PE by using residual CVS. Copyright © 2008 John Wiley & Sons, Ltd. [source] | |||||||||||||