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991.
Paula Martínez Raúl Snchez-Vzquez Iole Ferrara-Romeo Rosa Serrano Juana M. Flores Maria A. Blasco 《PLoS genetics》2022,18(6)
The shelterin protein POT1 has been found mutated in many different familial and sporadic cancers, however, no mouse models to understand the pathobiology of these mutations have been developed so far. To address the molecular mechanisms underlying the tumorigenic effects of POT1 mutant proteins in humans, we have generated a mouse model for the human POT1R117C mutation found in Li-Fraumeni-Like families with cases of cardiac angiosarcoma by introducing this mutation in the Pot1a endogenous locus, knock-in for Pot1aR117C. We find here that both mouse embryonic fibroblasts (MEFs) and tissues from Pot1a+/ki mice show longer telomeres than wild-type controls. Longer telomeres in Pot1a+/ki MEFs are dependent on telomerase activity as they are not found in double mutant Pot1a+/ki Tert-/- telomerase-deficient MEFs. By using complementation assays we further show that POT1a pR117C exerts dominant-negative effects at telomeres. As in human Li-Fraumeni patients, heterozygous Pot1a+/ki mice spontaneously develop a high incidence of angiosarcomas, including cardiac angiosarcomas, and this is associated to the presence of abnormally long telomeres in endothelial cells as well as in the tumors. The Pot1a+/R117C mouse model constitutes a useful tool to understand human cancers initiated by POT1 mutations. 相似文献
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LACTATE-DEHYDROGENASE ISOENZYMES IN NERVOUS TISSUE—II 总被引:1,自引:0,他引:1
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Shay O’Farrell Brian E. Luckhurst Stephen J. Box Peter J. Mumby 《Coral reefs (Online)》2016,35(2):421-425
Parrotfishes are an ecologically and commercially important teleost group whose grazing contributes to maintaining coral-dominated states on hermatypic reefs. However, overfishing has skewed sex ratios of Atlantic parrotfishes because fishing has disproportionate impacts on larger individuals, and males are generally larger than females. Whether protection from fishing may allow sex ratios to return to equilibrium is unknown, as fishing can induce irreversible ecological and/or evolutionary shifts. Bermuda banned trap fishing in 1990, creating a unique opportunity to analyse long-term responses of Atlantic parrotfishes to release from fishing. We found that sex ratios of four common parrotfishes were initially skewed, with male proportions ranging from 0.04 to 0.18. However, male proportions rebounded within 3–4 yr, equilibrating at values ranging from 0.36 to 0.54, similar to those reported at unfished sites in the region. Our results are encouraging for regional efforts to recover lost grazing function by restoring overfished herbivore populations. 相似文献
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Gregg M. Recer 《Aerobiologia》2004,20(4):179-190
Exposure to fungal allergens is an important contributor to allergic respiratory disease, but information on the efficacy of residential fungal allergen-avoidance in allergic-disease management is lacking. Using vacuum cleaners with high-efficiency exhaust filtration is one method recommended for reducing residential allergen exposure levels, but their use to reduce fungal-spore exposure levels has not been evaluated. To evaluate the effectiveness of high-efficiency vacuuming to control airborne fungal-spore levels, fungal bioaerosols were repeatedly assessed over the course of 10 months in homes randomly assigned to groups using either conventionally filtered (control) or high-efficiency-filtered vacuum cleaners for routine vacuum cleaning. Air samples were analyzed for three fungal-spore categories representing taxa with predominantly outdoor sources and one representing taxa that commonly have indoor sources. In a two-way analysis of variance, sampling period had a significant effect on mean levels of all fungal-spore categories. Vacuum cleaner type had a marginally significant effect on the indoor spore category, with one high-efficiency vacuum group mean (of three) significantly lower than one control mean. No effect was observed of vacuum cleaner type on outdoor spore categories. Including home-environment variables in analysis of covariance models strengthened the effect of the vacuum-type treatment on the indoor spore category, with no effect on the three outdoor spore categories. Decreased indoor spore levels vs. controls were only observed in high-efficiency vacuum groups during the last sampling period, at the end of the heating season. The results suggest that using a vacuum with high-efficiency filtered exhaust could have some modest effectiveness in controlling airborne fungal-spore exposure in homes when infiltration of outdoor air is very limited. 相似文献
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Romeu Cardoso Guimarães 《Origins of life and evolution of the biosphere》2011,41(4):357-371
An investigation of the biosynthesis pathways producing glycine and serine was necessary to clarify an apparent inconsistency
between the self-referential model (SRM) for the formation of the genetic code and the model of coevolution of encodings and
of amino acid biosynthesis routes. According to the SRM proposal, glycine was the first amino acid encoded, followed by serine.
The coevolution model does not state precisely which the first encodings were, only presenting a list of about ten early assignments
including the derivation of glycine from serine—this being derived from the glycolysis intermediate glycerate, which reverses
the order proposed by the self-referential model. Our search identified the glycine-serine pathway of syntheses based on one-carbon
sources, involving activities of the glycine decarboxylase complex and its associated serine hydroxymethyltransferase, which
is consistent with the order proposed by the self-referential model and supports its rationale for the origin of the genetic
code: protein synthesis was developed inside an early metabolic system, serving the function of a sink of amino acids; the
first peptides were glycine-rich and fit for the function of building the early ribonucleoproteins; glycine consumption in
proteins drove the fixation of the glycine-serine pathway. 相似文献
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