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221.
DNA methylation profiling of human chromosomes 6, 20 and 22 总被引:24,自引:0,他引:24
222.
Chan TL Yuen ST Kong CK Chan YW Chan AS Ng WF Tsui WY Lo MW Tam WY Li VS Leung SY 《Nature genetics》2006,38(10):1178-1183
Epimutations in the germline, such as methylation of the MLH1 gene, may contribute to hereditary cancer syndrome in human, but their transmission to offspring has never been documented. Here we report a family with inheritance, in three successive generations, of germline allele-specific and mosaic hypermethylation of the MSH2 gene, without evidence of DNA mismatch repair gene mutation. Three siblings carrying the germline methylation developed early-onset colorectal or endometrial cancers, all with microsatellite instability and MSH2 protein loss. Clonal bisulfite sequencing and pyrosequencing showed different methylation levels in different somatic tissues, with the highest level recorded in rectal mucosa and colon cancer tissue, and the lowest in blood leukocytes. This mosaic state of germline methylation with different tissue distribution could act as the first hit and provide a mechanism for genetic disease inheritance that may deviate from the mendelian pattern and be overlooked in conventional leukocyte-based genetic diagnosis strategy. 相似文献
223.
Kertész A Váradi G Tóth GK Fajka-Boja R Monostori E Sármay G 《Cellular and molecular life sciences : CMLS》2006,63(22):2682-2693
Phosphopeptides interacting with src homology 2 (SH2) domains can activate essential signaling enzymes in vitro. When delivered to cells, they may disrupt protein-protein interactions, thereby influencing intracellular signaling. We
showed earlier that phosphopeptides corresponding to the inhibitory motif of Fcγ receptor IIb and a motif of the Grb2-associated
binder 1 adaptor protein activate SH2-containing tyrosine phosphatase 2 in vitro. To study the ex vivo effects of these peptides, we have now compared different methods for peptide delivery: (i) permeabilization of the target
cells and (ii) the use of cell-permeable vectors, which are potentially able to transport biologically active compounds into
B cells. We found octanoyl-Arg8 to be an optimal carrier for the delivery of phosphopeptides to the cells. With this strategy, the function of cell-permeable
SHP-2-binding phosphopeptides was analyzed. These peptides modulated the protein phosphorylation in B cells in a dose- and
time-dependent manner.
Received 27 July 2006; received after revision 4 September 2006; accepted 18 September 2006 相似文献
224.
Glycogen synthase kinase 3β and Alzheimer’s disease: pathophysiological and therapeutic significance 总被引:3,自引:0,他引:3
Balaraman Y Limaye AR Levey AI Srinivasan S 《Cellular and molecular life sciences : CMLS》2006,63(11):1226-1235
Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive and behavioral dysfunction and is the leading
cause of dementia in the elderly. Several studies have implicated molecular and cellular signaling cascades involving the
serine-threonine kinase, glycogen synthase kinase β(GSK-3β) in the pathogenesis of AD. GSK-3β may play an important role in
the formation of neurofibrillary tangles and senile plaques, the two classical pathological hallmarks of AD. In this review,
we discuss the interaction between GSK-3β and several key molecules involved in AD, including the presenilins, amyloid precursor
protein, tau, and β-amyloid. We identify the signal transduction pathways involved in the pathogenesis of AD, including Wnt,
Notch, and the PI3 kinase/Akt pathway. These may be potential therapeutic targets in AD.
Received 19 December 2005; received after revision 24 January 2006; accepted 6 February 2006 相似文献
225.
226.
Gene polymorphism in Netherton and common atopic disease. 总被引:13,自引:0,他引:13
A J Walley S Chavanas M F Moffatt R M Esnouf B Ubhi R Lawrence K Wong G R Abecasis E Y Jones J I Harper A Hovnanian W O Cookson 《Nature genetics》2001,29(2):175-178
Atopic dermatitis (AD) and asthma are characterized by IgE-mediated atopic (allergic) responses to common proteins (allergens), many of which are proteinases. Loci influencing atopy have been localized to a number of chromosomal regions, including the chromosome 5q31 cytokine cluster. Netherton disease is a rare recessive skin disorder in which atopy is a universal accompaniment. The gene underlying Netherton disease (SPINK5) encodes a 15-domain serine proteinase inhibitor (LEKTI) which is expressed in epithelial and mucosal surfaces and in the thymus. We have identified six coding polymorphisms in SPINK5 (Table 1) and found that a Glu420-->Lys variant shows significant association with atopy and AD in two independent panels of families. Our results implicate a previously unrecognized pathway for the development of common allergic illnesses. 相似文献
227.
The Wnt/beta-catenin/TCF4 pathway plays critical roles in the maintenance of small intestinal epithelium; however, downstream
targets of the beta-catenin/TCF4 complex are not extensively characterized. We identified miR-30e as an immediate target activated
by the beta-catenin/TCF4 complex. miR-30e was detected in the peri-nuclear region of the intestinal crypt IEC-6 cells. Bioinformatics
analysis revealed clustered beta-catenin/TCF4 binding sites within the miR-30e promoter region. This promoter region was cloned
into pGL3-control luciferase reporter vector, with the enhancer region removed. Transfection of pCMV-SPORT6-beta-catenin expression
vector dose-dependently increased luciferase activity, and co-transfection of pCMV-SPORT6-TCF4 expression vector further enhanced
the promoter activity. Dexamethasone-induced IEC-6 cells differentiation caused a 2.5-fold increase in miR-30e expression,
and upon beta-catenin siRNA transfection, miR-30e increased 1.3-fold. Electrophoretic mobility shift assay and chromatin immunoprecipitation
assay confirmed the binding between beta-catenin/TCF4 complexes from IEC-6 nuclear extracts and the putative sequences in
the miR-30e promoter. These results demonstrate that beta-catenin/TCF4 transactivates miR-30e during intestinal cell differentiation. 相似文献
228.
In coal mines in such countries as China and Russia,most of the coal mine methane(CMM) generated during mining is emitted to the atmosphere without any effective usage,because the methane concentration of CMM is relatively low and not allowed to be used as fuel for safety reasons.Methane is one of the greenhouse gases.Therefore,if it becomes possible to concentrate CMM to an acceptable level for use as fuel,this will greatly contribute to reduction of greenhouse gas emissions.With the aim of gaining approva... 相似文献
229.
The idea of atomic-resolution holography has its roots in the X-ray work of Bragg and in Gabor's electron interference microscope. Gabor's lensless microscope was not realized in his time, but over the past twelve years there has been a steady increase in the number of reports on atomic-resolution holography. All of this work involves the use of electrons or hard X-rays to produce the hologram. Neutrons are often unique among scattering probes in their interaction with materials: for example, the relative visibility of hydrogen and its isotopes is a great advantage in the study of polymers and biologically relevant materials. Recent work proposed that atomic-resolution holography could be achieved with thermal neutrons. Here we use monochromatic thermal neutrons, adopting the inside-source concept of Sz?ke, to image planes of oxygen atoms located above and below a single hydrogen atom in the oxide mineral simpsonite. 相似文献
230.
Maternal control of resting-egg production in Daphnia. 总被引:1,自引:0,他引:1
Many planktonic organisms produce 'resting' stages when the environmental conditions deteriorate. Like seeds, resting stages can survive unfavourable conditions. The crustacean Daphnia normally reproduces by means of parthenogenetically produced normal, not resting, eggs-but occasionally switches to bisexual reproduction, which results in two resting eggs encased in a robust structure carried on the back of the female. This 'ephippium' is shed with the next moult, and can survive dormant for many years. The induction of resting-egg production requires multiple environmental stimuli, one of them being photoperiod. The switch from production of parthenogenetic eggs to resting eggs in Daphnia has recently been shown to be influenced by a maternal food effect. Here we present evidence that female Daphnia transmit information not only about food but also on photoperiod to their offspring, and influence the production of resting eggs in the next generation. The combined maternal effects can be relevant for the correct timing of resting-egg production-for example, in discriminating between spring and autumn conditions. 相似文献