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81.
82.
Cdc6 expression represses E-cadherin transcription and activates adjacent replication origins 总被引:2,自引:0,他引:2
83.
Isabelle Stévant Françoise Kühne Andy Greenfield Marie-Christine Chaboissier Emmanouil T. Dermitzakis Serge Nef 《Cell reports》2019,26(12):3272-3283.e3
84.
Nikolaos I Panousis Maria Gutierrez-Arcelus Emmanouil T Dermitzakis Tuuli Lappalainen 《Genome biology》2014,15(9)
Background
RNA sequencing (RNA-seq) is the current gold-standard method to quantify gene expression for expression quantitative trait locus (eQTL) studies. However, a potential caveat in these studies is that RNA-seq reads carrying the non-reference allele of variant loci can have lower probability to map correctly to the reference genome, which could bias gene quantifications and cause false positive eQTL associations. In this study, we analyze the effect of this allelic mapping bias in eQTL discovery.Results
We simulate RNA-seq read mapping over 9.5 M common SNPs and indels, with 15.6% of variants showing biased mapping rate for reference versus non-reference reads. However, removing potentially biased RNA-seq reads from an eQTL dataset of 185 individuals has a very small effect on gene and exon quantifications and eQTL discovery. We detect only a handful of likely false positive eQTLs, and overall eQTL SNPs show no significant enrichment for high mapping bias.Conclusion
Our results suggest that RNA-seq quantifications are generally robust against allelic mapping bias, and that this does not have a severe effect on eQTL discovery. Nevertheless, we provide our catalog of putatively biased loci to allow better controlling for mapping bias to obtain more accurate results in future RNA-seq studies.Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0467-2) contains supplementary material, which is available to authorized users. 相似文献85.
Different degree of paternal mtDNA leakage between male and female progeny in interspecific Drosophila crosses
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Maternal transmission of mitochondrial DNA (mtDNA) in animals is thought to prevent the spread of selfish deleterious mtDNA mutations in the population. Various mechanisms have been evolved independently to prevent the entry of sperm mitochondria in the embryo. However, the increasing number of instances of paternal mtDNA leakage suggests that these mechanisms are not very effective. The destruction of sperm mitochondria in mammalian embryos is mediated by nuclear factors. Also, the destruction of paternal mitochondria in intraspecific crosses is more effective than in interspecific ones. These observations have led to the hypothesis that leakage of paternal mtDNA (and consequently mtDNA recombination owing to ensuing heteroplasmy) might be more common in inter‐ than in intraspecific crosses and that it should increase with phylogenetic distance of hybridizing species. We checked paternal leakage in inter‐ and intraspecific crosses in Drosophila and found little evidence for this hypothesis. In addition, we have observed a higher level of leakage among male than among female progeny from the same cross. This is the first report of sex‐specific leakage of paternal mtDNA. It suggests that paternal mtDNA leakage might not be a stochastic result of an error‐prone mechanism, but rather, it may be under complex genetic control. 相似文献
86.
Adams D Altucci L Antonarakis SE Ballesteros J Beck S Bird A Bock C Boehm B Campo E Caricasole A Dahl F Dermitzakis ET Enver T Esteller M Estivill X Ferguson-Smith A Fitzgibbon J Flicek P Giehl C Graf T Grosveld F Guigo R Gut I Helin K Jarvius J Küppers R Lehrach H Lengauer T Lernmark Å Leslie D Loeffler M Macintyre E Mai A Martens JH Minucci S Ouwehand WH Pelicci PG Pendeville H Porse B Rakyan V Reik W Schrappe M Schübeler D Seifert M Siebert R Simmons D Soranzo N Spicuglia S Stratton M 《Nature biotechnology》2012,30(3):224-226
87.
Respect for confidentiality is firmly established in codes of ethics and law. Medical care and the patients' trust depend on the ability of the doctors to maintain confidentiality. Without a guarantee of confidentiality, many patients would want to avoid seeking medical assistance The principle of confidentiality, however, is not absolute and may be overridden by public interests. On some occasions (birth, death, infectious disease) there is a legal obligation on the part of the doctor to disclose but only to the appropriate authorities. Permissible disclosure can be granted by the patients' consent, for example, for the purpose of insurance they may wish to take out. Moreover, there are some ambivalent situations (such as criminal acts, or notification of sexual partner in case of a patient with AIDS) for which Greek law does not include relevant provisions, and the Codes of Medical Ethics do not offer clear guidelines. Therefore, the Greek doctor is called to estimate the situation and assume full responsibility for his decision. Finally, new considerations have arisen in the context of the recent advances in the field of telemedicine and electronic archiving. The paper discusses the current situation and legislation in Greece. 相似文献
88.
Cathepsin L is required for endothelial progenitor cell-induced neovascularization 总被引:15,自引:0,他引:15
Urbich C Heeschen C Aicher A Sasaki K Bruhl T Farhadi MR Vajkoczy P Hofmann WK Peters C Pennacchio LA Abolmaali ND Chavakis E Reinheckel T Zeiher AM Dimmeler S 《Nature medicine》2005,11(2):206-213
Infusion of endothelial progenitor cells (EPC), but not of mature endothelial cells, promotes neovascularization after ischemia. We performed gene expression profiling of EPC and endothelial cells to identify genes that might be important for the neovascularization capacity of EPC. Notably, the protease cathepsin L (CathL) was highly expressed in EPC as opposed to endothelial cells and was essential for matrix degradation and invasion by EPC in vitro. CathL-deficient mice showed impaired functional recovery following hind limb ischemia, supporting the concept of a crucial role for CathL in postnatal neovascularization. Infused CathL-deficient progenitor cells neither homed to sites of ischemia nor augmented neovascularization. Forced expression of CathL in mature endothelial cells considerably enhanced their invasive activity and sufficed to confer their capacity for neovascularization in vivo. We concluded that CathL has a critical role in the integration of circulating EPC into ischemic tissue and is required for EPC-mediated neovascularization. 相似文献
89.
Differentiation of circulating endothelial progenitor cells to a cardiomyogenic phenotype depends on E-cadherin 总被引:4,自引:0,他引:4
Koyanagi M Urbich C Chavakis E Hoffmann J Rupp S Badorff C Zeiher AM Starzinski-Powitz A Haendeler J Dimmeler S 《FEBS letters》2005,579(27):6060-6066
Progenitor cells may contribute to cardiac regeneration. Here, we investigated the role of cadherins and integrins for differentiation of human adult circulating endothelial progenitor cells (EPCs) into cardiomyocytes (CM) in a co-culture system. N- and E-cadherin were expressed in EPCs and were localized at the interface between EPCs and CM. Incubation of a blocking antibody against E-cadherin reduced the expression of CM marker protein in EPCs. Blocking antibodies against N- or P-cadherin or the beta1- and beta2-integrins were not effective. These data suggested that cell-to-cell communication mediated by E-cadherin contributes to the acquirement of a cardiomyogenic phenotype of human endothelial progenitor cells. 相似文献
90.
Resolving the excited state equilibrium of peridinin in solution 总被引:1,自引:0,他引:1
Papagiannakis E Larsen DS van Stokkum IH Vengris M Hiller RG van Grondelle R 《Biochemistry》2004,43(49):15303-15309
The carotenoid peridinin is abundant in the biosphere, as it is the main pigment bound by the light-harvesting complexes of dinoflagellates, where it collects blue and green sunlight and transfers energy to chlorophyll a with high efficiency. Its molecular structure is particularly complex, giving rise to an intricate excited state manifold, which includes a state with charge-transfer character. To disentangle the excited states of peridinin and understand their function in vivo, we applied dispersed pump-probe and pump-dump-probe spectroscopy. The preferential depletion of population from the intramolecular charge transfer state by the dump pulse demonstrates that the S(1) and this charge transfer state are distinct entities. The ensuing dump-induced dynamics illustrates the equilibration of the two states which occurs on the time scale of a few picoseconds. Additionally, the dump pulse populates a short-lived ground state intermediate, which is suggestive of a complex relaxation pathway, probably including structural reorientation or solvation of the ground state. These findings indicate that the unique intramolecular charge transfer state of peridinin is an efficient energy donor to chlorophyll a in the peridinin-chlorophyll-protein complex and thus plays a significant role in global light harvesting. 相似文献