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41.
Developmental study of fragile X syndrome using human embryonic stem cells derived from preimplantation genetically diagnosed embryos 总被引:1,自引:0,他引:1
Eiges R Urbach A Malcov M Frumkin T Schwartz T Amit A Yaron Y Eden A Yanuka O Benvenisty N Ben-Yosef D 《Cell Stem Cell》2007,1(5):568-577
We report on the establishment of a human embryonic stem cell (HESC) line from a preimplantation fragile X-affected embryo and demonstrate its value as an appropriate model to study developmentally regulated events that are involved in the pathogenesis of this disorder. Fragile X syndrome results from FMR1 gene inactivation due to a CGG expansion at the 5'UTR region of the gene. Early events in FMR1 silencing have not been fully characterized due to the lack of appropriate animal or cellular models. Here we show that, despite the presence of a full mutation, affected undifferentiated HESCs express FMR1 and are DNA unmethylated. However, epigenetic silencing by DNA methylation and histone modification occurs upon differentiation. Our unique cell system allows the dissection of the sequence by which these epigenetic changes are acquired and illustrates the importance of HESCs in unraveling developmentally regulated mechanisms associated with human genetic disorders. 相似文献
42.
Dalit Ben-Yosef Anat Talmor Lior Shwartz Yosef Granot Ruth Shalgi 《Molecular reproduction and development》1998,49(2):176-185
Fertilization in invertebrates results in tyrosine (Tyr) phosphorylation of several egg proteins. However, the involvement of Tyr phosphorylation in mediating mammalian egg activation has not yet been investigated. Using an antibody specific for phosphotyrosine (P-Tyr), immunoblotting, and densitometric analysis, we found that maturation of the oocyte is accompanied by a generalized increase in the P-Tyr content of almost all egg proteins detected. After sperm penetration, 5 of the 17 protein bands detected demonstrated a small increase in their P-Tyr content, while at the pronuclear (PN) stage the signal was markedly reduced. Ionomycin emulated the changes observed at fertilization in most protein bands detected, demonstrating a small increase in their P-Tyr content within 15 min of exposure. Analysis of the involvement of the tyrosyl-phosphorylated, mitogen-activated protein (MAP) kinase during meiosis revealed comigration of the phosphotyrosyl bands with the protein and a good correlation with its enzyme activity. Maturation was accompanied by an increase in MAP kinase activity. The activity dropped partially after sperm penetration and furthermore later at the PN stage. A larger quantity accompanied by a more significant change in the P-Tyr content implies for extracellular regulated kinase (ERK) 2 being the dominant isoform present in the rat egg. Our results indicate that fertilization in mammals involves changes in activity of protein tyrosine kinases (PTKs) or in the balance between PTKs and protein tyrosine phosphatases. The single, ionomycin-induced Ca2+ rise is sufficient to imitate fertilization-induced changes in MAP kinase activity, as well as in tyrosine phosphorylation of other proteins within the egg. Mol. Reprod. Dev. 49:176–185, 1998. © 1998 Wiley-Liss, Inc. 相似文献
43.
Toth E Gersner R Wilf-Yarkoni A Raizel H Dar DE Richter-Levin G Levit O Zangen A 《Journal of neurochemistry》2008,107(2):522-532
Exposure to chronic mild stress (CMS) is known to induce anhedonia in adult animals, and is associated with induction of depression in humans. However, the behavioral effects of CMS in young animals have not yet been characterized, and little is known about the long-term neurochemical effects of CMS in either young or adult animals. Here, we found that CMS induces anhedonia in adult but not in young animals, as measured by a set of behavioral paradigms. Furthermore, while CMS decreased neurogenesis and levels of brain-derived neurotrophic factor (BDNF) in the hippocampus of adult animals, it increased these parameters in young animals. We also found that CMS altered alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor GluR1 subunit levels in the hippocampus and the nucleus accumbens of adult, but not young animals. Finally, no significant differences were observed between the effects of CMS on circadian corticosterone levels in the different age groups. The substantially different neurochemical effects chronic stress exerts in young and adult animals may explain the behavioral resilience to such stress young animals possess. 相似文献
44.
Eph receptors and ephrins can sharpen domains within developing tissues by mediating repulsion at interfaces. An Eph receptor has now been shown also to regulate cell adhesion within tissue subdivisions. 相似文献
45.
Glaser F Pupko T Paz I Bell RE Bechor-Shental D Martz E Ben-Tal N 《Bioinformatics (Oxford, England)》2003,19(1):163-164
SUMMARY: We recently developed algorithmic tools for the identification of functionally important regions in proteins of known three dimensional structure by estimating the degree of conservation of the amino-acid sites among their close sequence homologues. Projecting the conservation grades onto the molecular surface of these proteins reveals patches of highly conserved (or occasionally highly variable) residues that are often of important biological function. We present a new web server, ConSurf, which automates these algorithmic tools. ConSurf may be used for high-throughput characterization of functional regions in proteins. AVAILABILITY: The ConSurf web server is available at:http://consurf.tau.ac.il. SUPPLEMENTARY INFORMATION: A set of examples is available at http://consurf.tau.ac.il under 'GALLERY'. 相似文献
46.
Folding simulations of polyalanine peptides were carried out using an off-lattice Monte Carlo simulation technique. The peptide was represented as a chain of residues, each of which contains two interaction sites: one corresponding to the C(alpha) atom and the other to the side chain. A statistical potential was used to describe the interaction between these sites. The preferred conformations of the peptide chain on the energy surface, starting from several initial conditions, were searched by perturbations on its generalized coordinates with the Metropolis criterion. We observed that, at low temperatures, the effective energy was low and the helix content high. The calculated helix propagation (s) and nucleation (sigma) parameters of the Zimm-Bragg model were in reasonable agreement with the empirical data. Exploration of the energy surface of the alanine-based peptides (AAQAA)(3) and AAAAA(AAARA)(3)A demonstrated that their behavior is similar to that of polyalanine, in regard to their effective energy, helix content, and the temperature-dependence of their helicity. In contrast, stable secondary structures were not observed for (Gly)(20) at similar temperatures, which is consistent with the nonfolder nature of this peptide. The fluctuations in the slowest dynamics mode, which describe the elastic behavior of the chain, showed that as the temperature decreases, the polyalanine peptides become stiffer and retain conformations with higher helix content. Clustering of conformations during the folding phase implied that polyalanine folds into a helix through fewer numbers of intermediate conformations as the temperature decreases. 相似文献
47.
Sirota-Madi A Olender T Helman Y Brainis I Finkelshtein A Roth D Hagai E Leshkowitz D Brodsky L Galatenko V Nikolaev V Gutnick DL Lancet D Ben-Jacob E 《Journal of bacteriology》2012,194(8):2127-2128
Paenibacillus dendritiformis is a Gram-positive, soil-dwelling, spore-forming social microorganism. An intriguing collective faculty of this strain is manifested by its ability to switch between different morphotypes, such as the branching (T) and the chiral (C) morphotypes. Here we report the 6.3-Mb draft genome sequence of the P. dendritiformis C454 chiral morphotype. 相似文献
48.
Hen G Yosefi S Shinder D Or A Mygdal S Condiotti R Galun E Bor A Sela-Donenfeld D Friedman-Einat M 《PloS one》2012,7(5):e36531
The lack of affordable techniques for gene transfer in birds has inhibited the advancement of molecular studies in avian species. Here we demonstrate a new approach for introducing genes into chicken somatic tissues by administration of a lentiviral vector, derived from the feline immunodeficiency virus (FIV), into the chorioallantoic membrane (CAM) of chick embryos on embryonic day 11. The FIV-derived vectors carried yellow fluorescent protein (YFP) or recombinant alpha-melanocyte-stimulating hormone (α-MSH) genes, driven by the cytomegalovirus (CMV) promoter. Transgene expression, detected in chicks 2 days after hatch by quantitative real-time PCR, was mostly observed in the liver and spleen. Lower expression levels were also detected in the brain, kidney, heart and breast muscle. Immunofluorescence and flow cytometry analyses confirmed transgene expression in chick tissues at the protein level, demonstrating a transduction efficiency of ~0.46% of liver cells. Integration of the viral vector into the chicken genome was demonstrated using genomic repetitive (CR1)-PCR amplification. Viability and stability of the transduced cells was confirmed using terminal deoxynucleotidyl transferase (dUTP) nick end labeling (TUNEL) assay, immunostaining with anti-proliferating cell nuclear antigen (anti-PCNA), and detection of transgene expression 51 days post transduction. Our approach led to only 9% drop in hatching efficiency compared to non-injected embryos, and all of the hatched chicks expressed the transgenes. We suggest that the transduction efficiency of FIV vectors combined with the accessibility of the CAM vasculature as a delivery route comprise a new powerful and practical approach for gene delivery into somatic tissues of chickens. Most relevant is the efficient transduction of the liver, which specializes in the production and secretion of proteins, thereby providing an optimal target for prolonged study of secreted hormones and peptides. 相似文献
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50.
Tsvia Frumkin Mira Malcov Michael Telias Veronica Gold Tamar Schwartz Foad Azem Ami Amit Yuval Yaron Dalit Ben-Yosef 《In vitro cellular & developmental biology. Animal》2010,46(3-4):327-336
Human embryonic stem cells (HESCs) carrying specific mutations potentially provide a valuable tool for studying genetic disorders in humans. One preferable approach for obtaining these cell lines is by deriving them from affected preimplantation genetically diagnosed embryos. These unique cells are especially important for modeling human genetic disorders for which there are no adequate research models. They can be further used to gain new insights into developmentally regulated events that occur during human embryo development and that are responsible for the manifestation of genetically inherited disorders. They also have great value for the exploration of new therapeutic protocols, including gene-therapy-based treatments and disease-oriented drug screening and discovery. Here, we report the establishment of 15 different mutant human embryonic stem cell lines derived from genetically affected embryos, all donated by couples undergoing preimplantation genetic diagnosis in our in vitro fertilization unit. For further information regarding access to HESC lines from our repository, for research purposes, please email dalitb@tasmc.health.gov.il. 相似文献