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排序方式: 共有217条查询结果,搜索用时 15 毫秒
121.
In this study, we assessed the genetic integrity of over 400 samples of human multipotent stem cells using gene expression data sets. Our analysis reveals that neural and mesenchymal stem cells acquire characteristic large chromosomal aberrations at a similar, or somewhat lower, frequency to that seen in pluripotent stem cells, sometimes within a few passages in culture. Some of the identified chromosomal abnormalities can also be detected in human tumors of the respective tissues. 相似文献
122.
Yoav Mayshar Ofra Yanuka Nissim Benvenisty 《Journal of cellular and molecular medicine》2011,15(6):1393-1401
Teratogens are substances that may cause defects in normal embryonic development while not necessarily being toxic in adults. Identification of possible teratogenic compounds has been historically beset by the species‐specific nature of the teratogen response. To examine teratogenic effects on early human development we performed non‐biased expression profiling of differentiating human embryonic and induced pluripotent stem cells treated with several drugs – ethanol, lithium, retinoic acid (RA), caffeine and thalidomide, which is known to be highly species specific. Our results point to the potency of specific teratogens and their affected tissues and pathways. Specifically, we could show that ethanol caused dramatic increase in endodermal differentiation, RA caused misregulation of neural development and thalidomide affected both these processes. We thus propose this method as a valuable addition to currently available animal screening approaches. 相似文献
123.
International Stem Cell Initiative Amps K Andrews PW Anyfantis G Armstrong L Avery S Baharvand H Baker J Baker D Munoz MB Beil S Benvenisty N Ben-Yosef D Biancotti JC Bosman A Brena RM Brison D Caisander G Camarasa MV Chen J Chiao E Choi YM Choo AB Collins D Colman A Crook JM Daley GQ Dalton A De Sousa PA Denning C Downie J Dvorak P Montgomery KD Feki A Ford A Fox V Fraga AM Frumkin T Ge L Gokhale PJ Golan-Lev T Gourabi H Gropp M Lu G Hampl A Harron K Healy L Herath W Holm F Hovatta O Hyllner J 《Nature biotechnology》2011,29(12):1132-1144
The International Stem Cell Initiative analyzed 125 human embryonic stem (ES) cell lines and 11 induced pluripotent stem (iPS) cell lines, from 38 laboratories worldwide, for genetic changes occurring during culture. Most lines were analyzed at an early and late passage. Single-nucleotide polymorphism (SNP) analysis revealed that they included representatives of most major ethnic groups. Most lines remained karyotypically normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed haphazardly with no link to time in culture. Structural variants, determined from the SNP arrays, also appeared sporadically. No common variants related to culture were observed on chromosomes 1, 12 and 17, but a minimal amplicon in chromosome 20q11.21, including three genes expressed in human ES cells, ID1, BCL2L1 and HM13, occurred in >20% of the lines. Of these genes, BCL2L1 is a strong candidate for driving culture adaptation of ES cells. 相似文献
124.
Uri Ben-David Qing-Fen Gan Tamar Golan-Lev Payal Arora Ofra Yanuka Yifat S. Oren Alicia Leikin-Frenkel Martin Graf Ralph Garippa Markus Boehringer Gianni Gromo Nissim Benvenisty 《Cell Stem Cell》2013,12(2):167-179
Highlights? High-throughput screen identifies selective cytotoxic inhibitors of hPSCs ? The most potent and selective compound inhibits stearoyl-coA desaturase (SCD1) ? Pluripotent cells uniquely depend on oleate metabolism for their viability ? SCD1 inhibition rapidly and robustly eliminates undifferentiated cells from culture 相似文献
125.
Chris Hughes Angelica Sette Michael Seed Fulvio D’Acquisto Antonio Manzo Tonia L Vincent Ngee Han Lim Ahuva Nissim 《Arthritis research & therapy》2014,16(4):R151
Introduction
We previously demonstrated that a single-chain fragment variable (scFv) specific to collagen type II (CII) posttranslationally modified by reactive oxygen species (ROS) can be used to target anti-inflammatory therapeutics specifically to inflamed arthritic joints. The objective of the present study was to demonstrate the superior efficacy of anti-inflammatory cytokines when targeted to inflamed arthritic joints by the anti-ROS modified CII (anti-ROS-CII) scFv in a mouse model of arthritis.Methods
Viral interleukin-10 (vIL-10) was fused to anti-ROS-CII scFv (1-11E) with a matrix-metalloproteinase (MMP) cleavable linker to create 1-11E/vIL-10 fusion. Binding of 1-11E/vIL-10 to ROS-CII was determined by enzyme-linked immunosorbent assay (ELISA), Western blotting, and immune-staining of arthritic cartilage, whereas vIL-10 bioactivity was evaluated in vitro by using an MC-9 cell-proliferation assay. Specific in vivo localization and therapeutic efficacy of 1-11E/vIL-10 was tested in the mouse model of antigen-induced arthritis.Results
1-11E/vIL-10 bound specifically to ROS-CII and to damaged arthritic cartilage. Interestingly, the in vitro vIL-10 activity in the fusion protein was observed only after cleavage with MMP-1. When systemically administered to arthritic mice, 1-11E/vIL-10 localized specifically to the arthritic knee, with peak accumulation observed after 3 days. Moreover, 1-11E/vIL-10 reduced inflammation significantly quicker than vIL-10 fused to the control anti-hen egg lysozyme scFv (C7/vIL10).Conclusions
Targeted delivery of anti-inflammatory cytokines potentiates their anti-arthritic action in a mouse model of arthritis. Our results further support the hypothesis that targeting biotherapeutics to arthritic joints may be extended to include anti-inflammatory cytokines that lack efficacy when administered systemically. 相似文献126.
Nissim I Horyn O Nissim I Daikhin Y Caldovic L Barcelona B Cervera J Tuchman M Yudkoff M 《The Journal of biological chemistry》2011,286(25):22055-22068
We previously reported that isobutylmethylxanthine (IBMX), a derivative of oxypurine, inhibits citrulline synthesis by an as yet unknown mechanism. Here, we demonstrate that IBMX and other oxypurines containing a 2,6-dione group interfere with the binding of glutamate to the active site of N-acetylglutamate synthetase (NAGS), thereby decreasing synthesis of N-acetylglutamate, the obligatory activator of carbamoyl phosphate synthase-1 (CPS1). The result is reduction of citrulline and urea synthesis. Experiments were performed with (15)N-labeled substrates, purified hepatic CPS1, and recombinant mouse NAGS as well as isolated mitochondria. We also used isolated hepatocytes to examine the action of various oxypurines on ureagenesis and to assess the ameliorating affect of N-carbamylglutamate and/or l-arginine on NAGS inhibition. Among various oxypurines tested, only IBMX, xanthine, or uric acid significantly increased the apparent K(m) for glutamate and decreased velocity of NAGS, with little effect on CPS1. The inhibition of NAGS is time- and dose-dependent and leads to decreased formation of the CPS1-N-acetylglutamate complex and consequent inhibition of citrulline and urea synthesis. However, such inhibition was reversed by supplementation with N-carbamylglutamate. The data demonstrate that xanthine and uric acid, both physiologically occurring oxypurines, inhibit the hepatic synthesis of N-acetylglutamate. An important and novel concept emerging from this study is that xanthine and/or uric acid may have a role in the regulation of ureagenesis and, thus, nitrogen homeostasis in normal and disease states. 相似文献
127.
Werther Guidi Nissim Hafssa Kadri Frederic E. Pitre 《International journal of phytoremediation》2015,17(8):745-752
In this preliminary screening study, we tested the phytoextraction potential of nine Canadian native/well-adapted plant species on a soil highly polluted by trace elements (TE) from a copper refinery. Plant physiological parameters and soil cover index were monitored for a 12-week period. At the end of the trial, biomass yield, bioconcentration (BFC) and translocation (TF) factors for the main TE as well as phytoextraction potential were determined. Most plants were severely injured by the high pollution levels, showing symptoms of toxicity including chlorosis, mortality and very low biomass yield. However, Indian mustard showed the highest selenium extraction potential (65 mg m?2), even under harsh growing conditions. Based on our results, tall fescue and ryegrass, which mainly stored As, Cu, Pb and Zn within roots, could be used effectively for phytostabilization. 相似文献
128.
Li C Matter A Kelly A Petty TJ Najafi H MacMullen C Daikhin Y Nissim I Lazarow A Kwagh J Collins HW Hsu BY Nissim I Yudkoff M Matschinsky FM Stanley CA 《The Journal of biological chemistry》2006,281(22):15064-15072
Glutamate dehydrogenase (GDH) plays an important role in insulin secretion as evidenced in children by gain of function mutations of this enzyme that cause a hyperinsulinism-hyperammonemia syndrome (GDH-HI) and sensitize beta-cells to leucine stimulation. GDH transgenic mice were generated to express the human GDH-HI H454Y mutation and human wild-type GDH in islets driven by the rat insulin promoter. H454Y transgene expression was confirmed by increased GDH enzyme activity in islets and decreased sensitivity to GTP inhibition. The H454Y GDH transgenic mice had hypoglycemia with normal growth rates. H454Y GDH transgenic islets were more sensitive to leucine- and glutamine-stimulated insulin secretion but had decreased response to glucose stimulation. The fluxes via GDH and glutaminase were measured by tracing 15N flux from [2-15N]glutamine. The H454Y transgene in islets had higher insulin secretion in response to glutamine alone and had 2-fold greater GDH flux. High glucose inhibited both glutaminase and GDH flux, and leucine could not override this inhibition. 15NH4Cl tracing studies showed 15N was not incorporated into glutamate in either H454Y transgenic or normal islets. In conclusion, we generated a GDH-HI disease mouse model that has a hypoglycemia phenotype and confirmed that the mutation of H454Y is disease causing. Stimulation of insulin release by the H454Y GDH mutation or by leucine activation is associated with increased oxidative deamination of glutamate via GDH. This study suggests that GDH functions predominantly in the direction of glutamate oxidation rather than glutamate synthesis in mouse islets and that this flux is tightly controlled by glucose. 相似文献
129.
Nissim I Horyn O Nissim I Daikhin Y Wehrli SL Yudkoff M Matschinsky FM 《The Biochemical journal》2012,444(3):537-551
GKAs (glucokinase activators) are promising agents for the therapy of Type 2 diabetes, but little is known about their effects on hepatic intermediary metabolism. We monitored the fate of (13)C-labelled glucose in both a liver perfusion system and isolated hepatocytes. MS and NMR spectroscopy were deployed to measure isotopic enrichment. The results demonstrate that the stimulation of glycolysis by GKA led to numerous changes in hepatic metabolism: (i) augmented flux through the TCA (tricarboxylic acid) cycle, as evidenced by greater incorporation of (13)C into the cycle (anaplerosis) and increased generation of (13)C isotopomers of citrate, glutamate and aspartate (cataplerosis); (ii) lowering of hepatic [Pi] and elevated [ATP], denoting greater phosphorylation potential and energy state; (iii) stimulation of glycogen synthesis from glucose, but inhibition of glycogen synthesis from 3-carbon precursors; (iv) increased synthesis of N-acetylglutamate and consequently augmented ureagenesis; (v) increased synthesis of glutamine, alanine, serine and glycine; and (vi) increased production and outflow of lactate. The present study provides a deeper insight into the hepatic actions of GKAs and uncovers the potential benefits and risks of GKA for treatment of diabetes. GKA improved hepatic bioenergetics, ureagenesis and glycogenesis, but decreased gluconeogenesis with a potential risk of lactic acidosis and fatty liver. 相似文献
130.