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191.
Aneuploid embryonic stem cells exhibit impaired differentiation and increased neoplastic potential 下载免费PDF全文
Meili Zhang Li Cheng Yuyan Jia Guang Liu Cuiping Li Shuhui Song Allan Bradley Yue Huang 《The EMBO journal》2016,35(21):2285-2300
Aneuploidy leads to severe developmental defects in mammals and is also a hallmark of cancer. However, whether aneuploidy is a driving cause or a consequence of tumor formation remains controversial. Paradoxically, existing studies based on aneuploid yeast and mouse fibroblasts have shown that aneuploidy is usually detrimental to cellular fitness. Here, we examined the effects of aneuploidy on mouse embryonic stem (ES) cells by generating a series of cell lines that each carries an extra copy of single chromosomes, including trisomy 6, 8, 11, 12, or 15. Most of these aneuploid cell lines had rapid proliferation rates and enhanced colony formation efficiencies. They were less dependent on growth factors for self‐renewal and showed a reduced capacity to differentiate in vitro. Moreover, trisomic stem cells formed teratomas more efficiently, from which undifferentiated cells can be recovered. Further investigations demonstrated that co‐culture of wild‐type and aneuploid ES cells or supplementation with extracellular BMP4 rescues the differentiation defects of aneuploid ES cells. 相似文献
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Bradley D. Holbrook 《Birth defects research. Part C, Embryo today : reviews》2016,108(2):181-192
Maternal smoking during pregnancy continues to represent a major public health concern. Nicotine is extremely harmful to the developing fetus through many different mechanisms, and the harms increase with later gestational age at exposure. Pregnancies complicated by maternal nicotine use are more likely to have significant adverse outcomes. Nicotine‐exposed children tend to have several health problems throughout their lives, including impaired function of the endocrine, reproductive, respiratory, cardiovascular, and neurologic systems. Poor academic performance and significant behavioral disruptions are also common, including ADHD, aggressive behaviors, and future substance abuse. To diminish the adverse effects from cigarette smoking, some women are turning to electronic cigarettes, a new trend that is increasing in popularity worldwide. They are largely perceived as being safer to use in pregnancy than traditional cigarettes, although there is not adequate evidence to support this claim. At this time, electronic cigarette use during pregnancy cannot be recommended. Birth Defects Research (Part C) 108:181–192, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
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Sheel V. Singh Nicky Staes Elaine E. Guevara Steven J. Schapiro John J. Ely William D. Hopkins Chet C. Sherwood Brenda J. Bradley 《Genes, Brain & Behavior》2019,18(7)
Studying genetic mechanisms underlying primate brain morphology can provide insight into the evolution of human brain structure and cognition. In humans, loss‐of‐function mutations in the gene coding for ASPM (Abnormal Spindle Microtubule Assembly) have been associated with primary microcephaly, which is defined by a significantly reduced brain volume, intellectual disability and delayed development. However, less is known about the effects of common ASPM variation in humans and other primates. In this study, we characterized the degree of coding variation at ASPM in a large sample of chimpanzees (N = 241), and examined potential associations between genotype and various measures of brain morphology. We identified and genotyped five non‐synonymous polymorphisms in exons 3 (V588G), 18 (Q2772K, K2796E, C2811Y) and 27 (I3427V). Using T1‐weighted magnetic resonance imaging of brains, we measured total brain volume, cerebral gray and white matter volume, cerebral ventricular volume, and cortical surface area in the same chimpanzees. We found a potential association between ASPM V588G genotype and cerebral ventricular volume but not with the other measures. Additionally, we found that chimpanzee, bonobo, and human lineages each independently show a signature of accelerated ASPM protein evolution. Overall, our results suggest the potential effects of ASPM variation on cerebral cortical development, and emphasize the need for further functional studies. These results are the first evidence suggesting ASPM variation might play a role in shaping natural variation in brain structure in nonhuman primates. 相似文献
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Ridoutt Bradley Motoshita Masaharu Pfister Stephan 《The International Journal of Life Cycle Assessment》2019,24(9):1620-1630
The International Journal of Life Cycle Assessment - So far, land occupation impact assessment models in life-cycle assessment have predominantly considered biodiversity, ecosystem quality and... 相似文献
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Julia Busch Vinayak Agarwal Michelle Schorn Henrique Machado Bradley S. Moore Greg W. Rouse Lone Gram Paul R. Jensen 《Environmental microbiology》2019,21(5):1575-1585
The production of pentabromopseudilin and related brominated compounds by Pseudoalteromonas spp. has recently been linked to the bmp biosynthetic gene cluster. This study explored the distribution and evolutionary history of this gene cluster in the genus Pseudoalteromonas. A phylogeny of the genus revealed numerous clades that do not contain type strains, suggesting considerable species level diversity has yet to be described. Comparative genomics revealed four distinct versions of the gene cluster distributed among 19 of the 101 Pseudoalteromonas genomes examined. These were largely localized to the least inclusive clades containing the Pseudoalteromonas luteoviolacea and Pseudoalteromonas phenolica type strains and show clear evidence of gene and gene cluster loss in certain lineages. Bmp gene phylogeny is largely congruent with the Pseudoalteromonas species phylogeny, suggesting vertical inheritance within the genus. However, the gene cluster is found in three different genomic environments suggesting either chromosomal rearrangement or multiple acquisition events. Bmp conservation within certain lineages suggests the encoded products are highly relevant to the ecology of these bacteria. 相似文献