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排序方式: 共有171条查询结果,搜索用时 15 毫秒
1.
Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells 总被引:2,自引:0,他引:2
Koh KP Yabuuchi A Rao S Huang Y Cunniff K Nardone J Laiho A Tahiliani M Sommer CA Mostoslavsky G Lahesmaa R Orkin SH Rodig SJ Daley GQ Rao A 《Cell Stem Cell》2011,8(2):200-213
TET family enzymes convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. Here, we show that Tet1 and Tet2 are Oct4-regulated enzymes that together sustain 5hmC in mouse embryonic stem cells (ESCs) and are induced concomitantly with 5hmC during reprogramming of fibroblasts to induced pluripotent stem cells. ESCs depleted of Tet1 by RNAi show diminished expression of the Nodal antagonist Lefty1 and display hyperactive Nodal signaling and skewed differentiation into the endoderm-mesoderm lineage in embryoid bodies in?vitro. In Fgf4- and heparin-supplemented culture conditions, Tet1-depleted ESCs activate the trophoblast stem cell lineage determinant Elf5 and can colonize the placenta in midgestation embryo chimeras. Consistent with these findings, Tet1-depleted ESCs?form aggressive hemorrhagic teratomas with increased endoderm, reduced neuroectoderm, and ectopic appearance of trophoblastic giant cells. Thus, 5hmC is an epigenetic modification associated with the pluripotent state, and Tet1 functions to regulate the lineage differentiation potential of ESCs. 相似文献
2.
Hauke Thomsen Miguel Inacio da Silva Filho Michael Fuchs Sabine Ponader Elke Pogge von Strandmann Lewin Eisele Stefan Herms Per Hoffmann Andreas Engert Kari Hemminki Asta F?rsti 《PloS one》2016,11(4)
Genome-wide association studies (GWASs) have identified several, mainly co-dominantly acting, single-nucleotide polymorphisms (SNPs) associated with Hodgkin lymphoma (HL). We searched for recessively acting disease loci by performing an analysis of runs of homozygosity (ROH) based on windows of homozygous SNP-blocks and by calculating genomic inbreeding coefficients on a SNP-wise basis. We used data from a previous GWAS with 906 cases and 1217 controls from a population with a long history of no matings between relatives. Ten recurrent ROHs were identified among 25 055 ROHs across all individuals but their association with HL was not genome-wide significant. All recurrent ROHs showed significant evidence for natural selection. As a novel finding genomic inbreeding among cases was significantly higher than among controls (P = 2.11*10−14) even after correcting for covariates. Higher inbreeding among the cases was mainly based on a group of individuals with a higher average length of ROHs per person. This result suggests a correlation of higher levels of inbreeding with higher cancer incidence and might reflect the existence of recessive alleles causing HL. Genomic inbreeding may result in a higher expression of deleterious recessive genes within a population. 相似文献
3.
Carrai M Steinke V Vodicka P Pardini B Rahner N Holinski-Feder E Morak M Schackert HK Görgens H Stemmler S Betz B Kloor M Engel C Büttner R Naccarati A Vodickova L Novotny J Stein A Hemminki K Propping P Försti A Canzian F Barale R Campa D 《PloS one》2011,6(6):e20464
Molecular sensing in the lingual mucosa and in the gastro-intestinal tract play a role in the detection of ingested harmful drugs and toxins. Therefore, genetic polymorphisms affecting the capability of initiating these responses may be critical for the subsequent efficiency of avoiding and/or eliminating possible threats to the organism. By using a tagging approach in the region of Taste Receptor 2R38 (TAS2R38) gene, we investigated all the common genetic variation of this gene region in relation to colorectal cancer risk with a case-control study in a German population (709 controls and 602 cases) and in a Czech population (623 controls and 601 cases). We found that there were no significant associations between individual SNPs of the TAS2R38 gene and colorectal cancer in the Czech or in the German population, nor in the joint analysis. However, when we analyzed the diplotypes and the phenotypes we found that the non-taster group had an increased risk of colorectal cancer in comparison to the taster group. This association was borderline significant in the Czech population, (OR = 1.28, 95% CI 0.99–1.67; Pvalue = 0.058) and statistically significant in the German population (OR = 1.36, 95% CI 1.06–1.75; Pvalue = 0.016) and in the joint analysis (OR = 1.34, 95% CI 1.12–1.61; Pvalue = 0.001). In conclusion, we found a suggestive association between the human bitter tasting phenotype and the risk of CRC in two different populations of Caucasian origin. 相似文献
4.
Guðmundur J. Óskarsson Asta Gudmundsdottir Sveinn Sveinbjörnsson Þorsteinn Sigurðsson 《Marine Biology Research》2016,12(1):16-29
The Northeast Atlantic mackerel (Scomber scombrus) has been extending its summer feeding distribution north and west, including around Iceland, since around 2006. The objective of this study is to quantify the weight gain and total food consumption of mackerel and to evaluate the food competition between mackerel and herring (Clupea harengus) feeding in the marine ecosystem around Iceland during the summers 2009–2011. Mackerel feeding in Icelandic waters gained around 43% on average in weight during these summers. Based on swept-area abundance estimates of mackerel from an international survey in 2011 and available estimates of food conversion efficiency in mackerel, the weight gain in Icelandic waters in 2011 corresponded to a total consumption of around 3.4 (2.4?4.5) million tonnes. Overall, 98% of 2314 mackerel, 91% of 398 Icelandic summer-spawning herring and 96% of 424 Norwegian spring-spawning herring stomachs, collected over the summers 2009?2011, contained food. The mean weight of the stomach content of mackerel was higher than for herring in all the years. While the stomach content weight of mackerel was generally highest in southeastern and southwestern areas, it was highest for herring in western, eastern and northern areas. Analysis of stomach contents showed that Copepoda were the most important food of mackerel in most areas, while Copepoda and Euphausiacea were the most important food items for herring. Fish prey contributed a higher proportion in stomachs of mackerel than herring, although relatively low for both species. 相似文献
5.
Arnfinn Hykkerud Steindal Tran Thi Thu Tam Xiao Yun Lu Asta Juzeniene Johan Moan 《Photochemical & photobiological sciences》2008,7(7):814-818
5-Methyltetrahydrofolate (5MTHF) is the main form of folate in human plasma, and an important vitamin for human health. Photodegradation of folates may have played a role in the development of different human skin colours. 5MTHF can be degraded directly by exposure to ultraviolet radiation or by exposure to visible light in the presence of endogenous sensitizers like riboflavin (RF). These photochemical reactions were studied by absorption spectroscopy. While 5MTHF is stable under UV and visible light exposure in pure aqueous media, it is quickly degraded in the presence of RF during UVA and blue light exposure. The degradation of 5MTHF is dependent on the concentration of RF, but not on the concentration of 5MTHF itself. UVA and blue light gave similar reactions. Further investigations are necessary to evaluate the consequences of large light exposures in vivo in humans. Our findings should be taken into the ongoing discussion about the development of human skin colours. Due to the presence of RF in human blood, folate can be significantly degraded during prolonged or intense blue light exposure. Thus, a dark skin colour may be favourable for prevention of folate degradation under high solar fluence rates, such as in equatorial areas. 相似文献
6.
7.
Martina Ferraguti Sergio Magallanes Jéssica Jiménez-Peñuela Josué Martínez-de la Puente Luz Garcia-Longoria Jordi Figuerola Jaime Muriel Tamer Albayrak Staffan Bensch Camille Bonneaud Rohan H. Clarke Gábor Á. Czirják Dimitar Dimitrov Kathya Espinoza John G. Ewen Farah Ishtiaq Wendy Flores-Saavedra László Zsolt Garamszegi Olof Hellgren Dita Horakova Kathryn P. Huyvaert Henrik Jensen Asta Križanauskienė Marcos R. Lima Charlene Lujan-Vega Eyðfinn Magnussen Lynn B. Martin Kevin D. Matson Anders Pape Møller Pavel Munclinger Vaidas Palinauskas Péter L. Pap Javier Pérez-Tris Swen C. Renner Robert Ricklefs Sergio Scebba Ravinder N. M. Sehgal Manuel Soler Eszter Szöllősi Gediminas Valkiūnas Helena Westerdahl Pavel Zehtindjiev Alfonso Marzal 《Global Ecology and Biogeography》2023,32(5):809-823
Aim
The increasing spread of vector-borne diseases has resulted in severe health concerns for humans, domestic animals and wildlife, with changes in land use and the introduction of invasive species being among the main possible causes for this increase. We explored several ecological drivers potentially affecting the local prevalence and richness of avian malaria parasite lineages in native and introduced house sparrows (Passer domesticus) populations.Location
Global.Time period
2002–2019.Major taxa studied
Avian Plasmodium parasites in house sparrows.Methods
We analysed data from 2,220 samples from 69 localities across all continents, except Antarctica. The influence of environment (urbanization index and human density), geography (altitude, latitude, hemisphere) and time (bird breeding season and years since introduction) were analysed using generalized additive mixed models (GAMMs) and random forests.Results
Overall, 670 sparrows (30.2%) were infected with 22 Plasmodium lineages. In native populations, parasite prevalence was positively related to urbanization index, with the highest prevalence values in areas with intermediate urbanization levels. Likewise, in introduced populations, prevalence was positively associated with urbanization index; however, higher infection occurred in areas with either extreme high or low levels of urbanization. In introduced populations, the number of parasite lineages increased with altitude and with the years elapsed since the establishment of sparrows in a new locality. Here, after a decline in the number of parasite lineages in the first 30 years, an increase from 40 years onwards was detected.Main conclusions
Urbanization was related to parasite prevalence in both native and introduced bird populations. In invaded areas, altitude and time since bird introduction were related to the number of Plasmodium lineages found to be infecting sparrows. 相似文献8.
Lazrak A Jurkuvenaite A Chen L Keeling KM Collawn JF Bedwell DM Matalon S 《American journal of physiology. Lung cellular and molecular physiology》2011,301(4):L557-L567
We sought to establish whether the cystic fibrosis transmembrane conductance regulator (CFTR) regulates the activity of amiloride-sensitive sodium channels (ENaC) in alveolar epithelial cells of wild-type, heterozygous (Cftr(+/-)), knockout (Cftr(-/-)), and ΔF508-expressing mice in situ. RT-PCR studies confirmed the presence of CFTR message in freshly isolated alveolar type II (ATII) cells from wild-type mice. We patched alveolar type I (ATI) and ATII cells in freshly prepared lung slices from these mice and demonstrated the presence of 4-pS ENaC channels with the following basal open probabilities (P(o)): wild-type=0.21 ± 0.015: Cftr(+/-)=0.4 ± 0.03; ΔF508=0.55 ± 0.01; and Cftr(-/-)=and 0.81 ± 0.016 (means ± SE; n ≥ 9). Forskolin (5 μM) or trypsin (2 μM), applied in the pipette solution, increased the P(o) and number of channels in ATII cells of wild-type, Cftr(+/-), and ΔF508, but not in Cftr(-/-) mice, suggesting that the latter were maximally activated. Western blot analysis showed that lungs of all groups of mice had similar levels of α-ENaC; however, lungs of Cftr(+/-) and Cftr(-/-) mice had significantly higher levels of an α-ENaC proteolytic fragment (65 kDa) that is associated with active ENaC channels. Our results indicate that ENaC activity is inversely correlated to predicted CFTR levels and that CFTR heterozygous and homozygous mice have higher levels of proteolytically processed ENaC fragments in their lungs. This is the first demonstration of functional ENaC-CFTR interactions in alveolar epithelial cells in situ. 相似文献
9.
The metabolism of poly(ADP-ribose) is known to play important roles in the nuclear function of the mammalian cells. In this study, changes in the activities and gene expressions of poly(ADP-ribose) glycohydrolases (PARG) in HL-60 cells treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or a PARG inhibitor, tannic acid, were investigated. Nuclear PARG activities of HL-60 cells treated with TPA were reduced to 30-40% of the activity in untreated cells at 24 h, while PARG activities in the cytoplasm remained unchanged. The transient decrease in the nuclear PARG activity by TPA treatment was accompanied by differentiation as measured by the nitroblue tetrazolium (NBT) reducing activity and adhesion to the culture dishes. In the presence of H7, an inhibitor of protein kinase C (PKC), both the decrease in nuclear PARG activity and the induction of differentiation by TPA treatment were suppressed. On the other hand, treatment with tannic acid caused the nuclear PARG activity to decrease continuously while the NBT reducing activity increased, but no morphological differentiation to macrophage-like cells was apparent. In order to analyze PARG gene expression, we isolated the human PARG cDNA by the RT-PCR technique. RT-PCR analysis revealed that TPA treatment leads to a reduction in the PARG gene expression prior to the phenotypic expression of macrophage-like cell differentiation, which was diminished by the presence of H7. Also, PARG gene expression was reduced by tannic acid treatment. These results provide the first evidence that a transient decrease in nuclear PARG activity is important for the onset of differentiation of HL-60 cells to macrophage-like cells. 相似文献
10.
Juzenas P Juzeniene A Moan J 《Biochemical and biophysical research communications》2005,332(2):388-391
Effect of the iron chelator deferoxamine (DF) on the production of endogenous porphyrins was studied in adenocarcinoma WiDr cells and erythroid K562 cells in vitro. Porphyrin fluorescence was observed in the cells in vitro incubated with DF. The fluorescence spectra recorded in the cells were similar to that of protoporphyrin IX (PpIX). The amount of PpIX generated by DF was around 5% of the ALA effect. Around 90% of the WiDr cells incubated in vitro with DF (0.5 mM, 24 h) and then exposed to light (400-460 nm, 20 min) were photodynamically inactivated. In conclusion, the present study describes a novel approach of using iron chelating agents without 5-aminolevulinic acid (ALA) to photosensitize cancer cells. 相似文献