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Jesse Jackson 《Current biology : CB》2018,28(17):R937-R939
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Adrenocortical dysplasia (acd) is a spontaneous autosomal recessive mouse mutation exhibiting caudal truncation, vertebral segmentation defects, hydronephrosis, limb hypoplasia, and perinatal lethality. Acd encodes TPP1, a component of the shelterin complex that maintains telomere integrity, and consequently acd mutant mice have telomere dysfunction and genomic instability. We previously showed that apoptosis is the primary mechanism causing the acd skeletal phenotype, and that p53 deficiency rescues the skeletal defects of the acd phenotype but has no effect on the perinatal lethality. The Trp63 gene encodes multiple isoforms, which play a role in proliferation, apoptosis, and stem/progenitor cell maintenance. Different p63 isoforms exhibit both proapoptotic (TAp63) and antiapoptotic (ΔNp63) functions. We hypothesized that deficiency of proapoptotic TAp63 isoforms might rescue the acd skeletal phenotype, similar to our previous observations with deficiency of p53. Mice heterozygous for a null allele of TAp63 were crossed to heterozygous acd mice to determine the effect of TAp63 deficiency on the acd mutant phenotype. In contrast to our results with the acd?×?p53 cross, skeletal anomalies were not rescued by deficiency of TAp63. In fact, the limb and vertebral anomalies observed in double-mutant embryos were more severe than those of embryos with the acd mutation alone, demonstrating a dose-dependent effect. These studies suggest that TAp63 isoforms do not facilitate p53-like apoptosis during development in response to acd-mediated telomere dysfunction and are consistent with the proposed roles of TAp63 in maintaining genomic stability. 相似文献
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The Lin28/let-7 axis regulates glucose metabolism 总被引:3,自引:0,他引:3
Zhu H Shyh-Chang N Segrè AV Shinoda G Shah SP Einhorn WS Takeuchi A Engreitz JM Hagan JP Kharas MG Urbach A Thornton JE Triboulet R Gregory RI;DIAGRAM Consortium;MAGIC Investigators Altshuler D Daley GQ 《Cell》2011,147(1):81-94
The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by inhibiting let-7 biogenesis. We have uncovered unexpected roles for the Lin28/let-7 pathway in regulating metabolism. When overexpressed in mice, both Lin28a and LIN28B promote an insulin-sensitized state that resists high-fat-diet induced diabetes. Conversely, muscle-specific loss of Lin28a or overexpression of let-7 results in insulin resistance and impaired glucose tolerance. These phenomena occur, in part, through the let-7-mediated repression of multiple components of the insulin-PI3K-mTOR pathway, including IGF1R, INSR, and IRS2. In addition, the mTOR inhibitor, rapamycin, abrogates Lin28a-mediated insulin sensitivity and enhanced glucose uptake. Moreover, let-7 targets are enriched for genes containing SNPs associated with type 2 diabetes and control of fasting glucose in human genome-wide association studies. These data establish the Lin28/let-7 pathway as a central regulator of mammalian glucose metabolism. 相似文献
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Agnese Mancini Jesse Senko Ricardo Borquez-Reyes Juan Guzman Póo Jeffrey A. Seminoff Volker Koch 《Human ecology: an interdisciplinary journal》2011,39(6):743-756
Despite complete legal protection, improvements in infrastructure, and market conditions that provide easier access to other
protein sources, illegal poaching of sea turtles for consumption in Baja California Sur (BCS), Mexico remains a major threat
to their recovery. Few studies have focused on understanding the economic and social drivers behind this activity, which is
fundamental to determining best practices for discouraging it. From June 2007 to April 2008 we conducted eight in-depth, semi-structured
interviews with sea turtle poachers at five coastal communities in BCS to determine the drivers influencing them. The most
prevalent reasons for illegal poaching were direct economic benefits, lack of law enforcement and ease of escape from or bribery
of authorities, and strong family tradition. Our results suggest that to reduce illegal poaching it will be necessary to better
enforce existing environmental laws, reduce social acceptance of sea turtle hunting throughout the region, educate fishers
on the ecological importance of sea turtles, and show fishers direct economic benefits from non-consumptive use of sea turtles,
such as ecotourism. 相似文献
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Identification and molecular characterization of the nicotianamine synthase gene family in bread wheat 下载免费PDF全文
Julien Bonneau Ute Baumann Jesse Beasley Yuan Li Alexander A. T. Johnson 《Plant biotechnology journal》2016,14(12):2228-2239
Nicotianamine (NA) is a non‐protein amino acid involved in fundamental aspects of metal uptake, transport and homeostasis in all plants and constitutes the biosynthetic precursor of mugineic acid family phytosiderophores (MAs) in graminaceous plant species. Nicotianamine synthase (NAS) genes, which encode enzymes that synthesize NA from S‐adenosyl‐L‐methionine (SAM), are differentially regulated by iron (Fe) status in most plant species and plant genomes have been found to contain anywhere from 1 to 9 NAS genes. This study describes the identification of 21 NAS genes in the hexaploid bread wheat (Triticum aestivum L.) genome and their phylogenetic classification into two distinct clades. The TaNAS genes are highly expressed during germination, seedling growth and reproductive development. Fourteen of the clade I NAS genes were up‐regulated in root tissues under conditions of Fe deficiency. Protein sequence analyses revealed the presence of endocytosis motifs in all of the wheat NAS proteins as well as chloroplast, mitochondrial and secretory transit peptide signals in four proteins. These results greatly expand our knowledge of NAS gene families in graminaceous plant species as well as the genetics underlying Fe nutrition in bread wheat. 相似文献
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