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61.
Lina Fu Xiuling Xu Ruotong Ren Jun Wu Weiqi Zhang Jiping Yang Xiaoqing Ren Si Wang Yang Zhao Liang Sun Yang Yu Zhaoxia Wang Ze Yang Yun Yuan Jie Qiao Juan Carlos Izpisua Belmonte Jing Qu Guang-Hui Liu 《蛋白质与细胞》2016,7(3):210
Xeroderma pigmentosum (XP) is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patientspecific induced pluripotent stem cells (iPSCs) harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells (NSCs) or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clarify the molecular mechanisms of neurological abnormalities in the XP patients. 相似文献
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Although there are several species of ferns that are important components of many coastal ecosystems, the adaptations that allow these species to live in salty conditions have been studied only in two Acrostichum species. We have studied the effects of salt on germination, development of the gametophyte and sexual expression of the fern Asplenium marinum, which lives on coastal cliffs of Europe. Cultures at four different levels of salt concentration, 0%, 0.98%, 1.96% and 3.26%, were established for this purpose. Salt caused a significant delay in spore germination, and prevented it completely at high concentrations (3.26%). However, spores were able to recover germination ability after a period of seawater incubation once salinity concentrations decreased. Variable salinity conditions are a typical feature of sea cliffs where halophytes can grow. A salty culture medium also affects the development of the prothalli. Higher salinity of the substrate produced a significant decrease in gametophyte sizes, and affected the development of gametangia as well. Only males were found in a 0.98%-salt medium, and no gametangia were observed in cultures at 1.96%-salt medium. Recovered spores after one and a half month in high salinity concentration, 3.26%, were able, when transplanted to 0%-salt medium, to develop normal sexual prothalli, and this occurred in a shorter time than spores without any prior treatment. A. marinum can be considered as a halophyte fern that is able to germinate and grow in salty conditions. But it takes advantage of rainy periods that cause decrease of salt concentration, which seems to be important in particular for gametangia development and fertilization. 相似文献
64.
Elvira Valera Michael J. Isaacs Yasuhiko Kawakami Juan Carlos Izpisúa Belmonte Senyon Choe 《PloS one》2010,5(6)
Background
Bone Morphogenetic Protein (BMP) signaling pathways are involved in differentiation of stem cells into diverse cell types, and thus BMPs can be used as main guidance molecules for in vitro differentiation of human stem cells.Methodology/Principal Findings
We have analyzed the ability for inducing differentiation of the heterodimer BMP-2/BMP-6 (BMP-2/6) compared to the homodimers BMP-2 or BMP-6, using human embryonic stem (hES) cells H9 as model system. When incubated in a medium with high concentration of basic fibroblastic growth factor (FGF2), 100 ng/ml of human recombinant BMPs induced morphological changes and differentiation of hES cells in 24 to 48 hours. After 5 days, expression of differentiation markers was induced and quantified by quantitative PCR (qPCR) and flow cytometry. BMP-2/6 exhibited stronger activity for the induction of the expression of trophectodermal (CDX2) and endodermal (SOX17, GATA4, AFP) markers than BMP-2 or BMP-6 homodimers. BMP-2/6 also induced the expression of BMPR2 gene more effectively than BMP-2 or BMP-6 when used at the same concentration and time. Moreover, the percentage of cells expressing the surface endodermal marker CXCR4 was also increased for the heterodimer when compared to both homodimers. BMP-2/6 was a more potent activator of Smad-dependent (SMAD1/5) and Smad-independent signaling (mitogen-activated protein kinases ERK and p38) than BMP-2 and BMP-6, and the activation of these pathways might play a role in its increased potency for inducing hES cell differentiation.Conclusions/Significance
Therefore, we conclude that BMP-2/6 is more potent than BMP-2 or BMP-6 for inducing differentiation of hES cells, and it can be used as a more powerful substitute of these BMPs in in vitro differentiation guidance. 相似文献65.
Antonio Verdejo‐García Manuel Pérez‐Expósito Jacqueline Schmidt‐Río‐Valle Maria J. Fernández‐Serrano Francisco Cruz Miguel Pérez‐García Gemma López‐Belmonte Miguel Martín‐Matillas Jose A. Martín‐Lagos Ascension Marcos Cristina Campoy 《Obesity (Silver Spring, Md.)》2010,18(8):1572-1578
Increasing evidence underscores overlapping neurobiological pathways to addiction and obesity. In both conditions, reward processing of preferred stimuli is enhanced, whereas the executive control system that would normally regulate reward‐driven responses is altered. This abnormal interaction can be greater in adolescence, a period characterized by relative immaturity of executive control systems coupled with the relative maturity of reward processing systems. The aim of this study is to explore neuropsychological performance of adolescents with excess weight (n = 27, BMI range 24–51 kg/m2) vs. normal‐weight adolescents (n = 34, BMI range 17–24 kg/m2) on a comprehensive battery of executive functioning tests, including measures of working memory (letter‐number sequencing), reasoning (similarities), planning (zoo map), response inhibition (five‐digit test (FDT)–interference and Stroop), flexibility (FDT–switching and trail‐making test (TMT)), self‐regulation (revised‐strategy application test (R‐SAT)), and decision‐making (Iowa gambling task (IGT)). We also aimed to explore personality traits of impulsivity and sensitivity to reward. Independent sample t‐ and Z Kolmogorov–Smirnov tests showed significant differences between groups on indexes of inhibition, flexibility, and decision‐making (excess‐weight participants performed poorer than controls), but not on tests of working memory, planning, and reasoning, nor on personality measures. Moreover, regression models showed a significant association between BMI and flexibility performance. These results are indicative of selective alterations of particular components of executive functions in overweight adolescents. 相似文献
66.
Fei Yi Jing Qu Mo Li Keiichiro Suzuki Na Young Kim Guang-Hui Liu Juan Carlos Izpisua Belmonte 《蛋白质与细胞》2012,3(11):855
The combination of disease-specific human induced pluripotent stem cells (iPSC) and directed cell differentiation offers an ideal platform for modeling and studying many inherited human diseases. Wilson’s disease (WD) is a monogenic disorder of toxic copper accumulation caused by pathologic mutations of the ATP7B gene. WD affects multiple organs with primary manifestations in the liver and central nervous system (CNS). In order to better investigate the cellular pathogenesis of WD and to develop novel therapies against various WD syndromes, we sought to establish a comprehensive platform to differentiate WD patient iPSC into both hepatic and neural lineages. Here we report the generation of patient iPSC bearing a Caucasian population hotspot mutation of ATP7B. Combining with directed cell differentiation strategies, we successfully differentiated WD iPSC into hepatocyte-like cells, neural stem cells and neurons. Gene expression analysis and cDNA sequencing confirmed the expression of the mutant ATP7B gene in all differentiated cells. Hence we established a platform for studying both hepatic and neural abnormalities of WD, which may provide a new tool for tissue-specific disease modeling and drug screening in the future. 相似文献
67.
Theodore J. Abatzopoulos Francisco Amat Athanasios D. Baxevanis Genuario Belmonte Francisco Hontoria Stefania Maniatsi Salvatore Moscatello Graziella Mura Nickolaj V. Shadrin 《International Review of Hydrobiology》2009,94(5):560-579
Artemia urmiana (a species previously considered endemic of Lake Urmia, NW Iran) has been found in Lake Koyashskoe, a hypersaline lake on the Black Sea coast of the Crimean peninsula (Ukraine). Therefore, this is the first record of A. urmiana in Europe which updates its distribution. The species identification was based on an integrated and interdisciplinary approach using discriminant analysis of the morphometric characters, scanning electron microscopy, and molecular profile analysis. The data derived from the above mentioned approaches converge to significant similarity of the population under investigation with A. urmiana. The updated geographic distribution of the species, deriving from the present report, asks for additional contribution of other disciplines (e.g., avian dispersal of cysts, history of salt trade) to be finally clarified. At present we suggest that the punctuated geographic distribution of A. urmiana is probably linked to its low dispersal capability, and we suppose that its presence in two distant sites could be explained by historical human salt trade between Lake Urmia and the ancient port of Kimmerik, whose remains have been found in the present Lake Koyashskoe. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) 相似文献
68.
The apparent symmetry of the vertebrate body conceals profound asymmetries in the development and placement of internal organs. Asymmetric organ development is controlled in part by genes expressed asymmetrically in the early embryo, and alterations in the activities of these genes can result in severe defects during organogenesis. Recently, data from different vertebrates have allowed researchers to put forward a model of genetic interactions that explains how asymmetric patterns of gene expression in the early embryo are translated into spatial patterns of asymmetric organ development. This model helps us to understand the molecular basis of a number of congenital malformations in humans. 相似文献
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70.
Clair Rose Rodrigo Belmonte Stuart D. Armstrong Gemma Molyneux Lee R. Haines Michael J. Lehane Jonathan Wastling Alvaro Acosta-Serrano 《PLoS neglected tropical diseases》2014,8(4)