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71.
Weihua Qin Enes Ugur Christopher B Mulholland Sebastian Bultmann Irina Solovei Miha Modic Martha Smets Michael Wierer Ignasi Forn Axel Imhof M Cristina Cardoso Heinrich Leonhardt 《Nucleic acids research》2021,49(13):7406
Heterochromatin binding protein HP1β plays an important role in chromatin organization and cell differentiation, however the underlying mechanisms remain unclear. Here, we generated HP1β−/− embryonic stem cells and observed reduced heterochromatin clustering and impaired differentiation. We found that during stem cell differentiation, HP1β is phosphorylated at serine 89 by CK2, which creates a binding site for the pluripotency regulator KAP1. This phosphorylation dependent sequestration of KAP1 in heterochromatin compartments causes a downregulation of pluripotency factors and triggers pluripotency exit. Accordingly, HP1β−/− and phospho-mutant cells exhibited impaired differentiation, while ubiquitination-deficient KAP1−/− cells had the opposite phenotype with enhanced differentiation. These results suggest that KAP1 regulates pluripotency via its ubiquitination activity. We propose that the formation of subnuclear membraneless heterochromatin compartments may serve as a dynamic reservoir to trap or release cellular factors. The sequestration of essential regulators defines a novel and active role of heterochromatin in gene regulation and represents a dynamic mode of remote control to regulate cellular processes like cell fate decisions. 相似文献
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Muzaffer Tas Mehmet Zulkuf Akdag Umut Cirit Korkut Yegin Ugur Seker 《Electromagnetic biology and medicine》2014,33(3):216-222
The purpose of this study is to bridge this gap by investigating effects of long term 900?MHz mobile phone exposure on reproductive organs of male rats. The study was carried out on 14 adult Wistar Albino rats by dividing them randomly into two groups (n: 7) as sham group and exposure group. Rats were exposed to 900?MHz radiofrequency (RF) radiation emitted from a GSM signal generator. Point, 1?g and 10?g specific absorption rate (SAR) levels of testis and prostate were found as 0.0623?W/kg, 0.0445?W/kg and 0.0373?W/kg, respectively. The rats in the exposure group were subject to RF radiation 3?h per day (7?d a week) for one year. For the sham group, the same procedure was applied, except the generator was turned off. At the end of the study, epididymal sperm concentration, progressive sperm motility, abnormal sperm rate, all-genital organs weights and testis histopathology were evaluated. Any differences were not observed in sperm motility and concentration (p?>?0.05). However, the morphologically normal spermatozoa rates were found higher in the exposure group (p?0.05). Although histological examination showed similarity in the seminiferous tubules diameters in both groups, tunica albuginea thickness and the Johnsen testicular biopsy score were found lower in the exposure group (p?0.05, p?0.0001). In conclusion, we claim that long-term exposure of 900?MHz RF radiation alter some reproductive parameters. However, more supporting evidence and research is definitely needed on this topic. 相似文献
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Increased antigen presentation efficiency by coupling antigens to MHC class I trafficking signals 总被引:1,自引:0,他引:1
Kreiter S Selmi A Diken M Sebastian M Osterloh P Schild H Huber C Türeci O Sahin U 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(1):309-318
Genetic modification of vaccines by linking the Ag to lysosomal or endosomal targeting signals has been used to route Ags into MHC class II processing compartments for improvement of CD4+ T cell responses. We report in this study that combining an N-terminal leader peptide with an MHC class I trafficking signal (MITD) attached to the C terminus of the Ag strongly improves the presentation of MHC class I and class II epitopes in human and murine dendritic cells (DCs). Such chimeric fusion proteins display a maturation state-dependent subcellular distribution pattern in immature and mature DCs, mimicking the dynamic trafficking properties of MHC molecules. T cell response analysis in vitro and in mice immunized with DCs transfected with Ag-encoding RNA showed that MITD fusion proteins have a profoundly higher stimulatory capacity than wild-type controls. This results in efficient expansion of Ag-specific CD8+ and CD4+ T cells and improved effector functions. We used CMVpp65 and NY-ESO-1 Ags to study preformed immune responses in CMV-seropositive individuals and cancer patients. We show that linking these Ags to the MITD trafficking signal allows simultaneous, polyepitopic expansion of CD8+ and CD4+ T cells, resulting in distinct CD8+ T cell specificities and a surprisingly broad and variable Ag-specific CD4+ repertoire in different individuals. 相似文献
76.
Guner I Sahin G Yelmen NK Aksu U Oruc T Yildirim Z 《The Chinese journal of physiology》2008,51(3):136-145
Hypoxia causes changes in the rate of synthesis or release of neurotransmitters in the brain. The accumulation of serotonin (5-HT) in the central nervous system might cause hypoxic respiratory depression. In the present study, we aimed to examine the role of central 5-HT on normoxic and acute hypoxic ventilatory depression (AHVD) in peripheral chemoreceptors denervated rabbits. All experiments were performed in peripherally chemodenervated rabbits anesthetized with intravenous injection of urethane (400 mg/kg) and alpha-chloralose (40 mg/kg). For intracerebroventricular (ICV) administration of 5-HT (20 microg/kg) and ketanserin (10 microg/kg), a cannula was placed in left lateral ventricle by stereotaxic method. Respiratory frequency (fR), tidal volume (VT), ventilation minute volume (VE) and systemic arterial bood pressure (BP) were recorded in each experimental phases and mean arterial pressure was calculated (MAP). Heart rate (HR) was also determined from the pulsation of BP. The effects of ICV serotonin and ICV ketanserin on the indicated parameters during air breathing (normoxia) and breathing of hypoxia (8% O2--92% N2) were investigated. During hypoxia, fR, VT, VE, MAP and HR decreased, and AHVD was thus obtained. ICV injection of 5-HT during normoxia caused significant increases in VT (P < 0.001) and in VE (P < 0.01). On the other hand, ICV 5-HT injection reduced the degree of AHVD in peripherally chemodenervated rabbits during hypoxia (fR; P < 0.05, VT; P < 0.05 and VE; P < 0.01). After ICV injection of ketanserin, the enhancement of 5-HT on VE was prevented during normoxia. On the breathing of hypoxic gas after ICV ketanserin, the degree of AHVD was augmented. In conclusion, our findings suggested that central 5-HT increases normoxic ventilation and reduces the degree of AHVD during hypoxia and that ICV ketanserin prevents the stimulatory effect of 5-HT on respiration and augments AHVD. 相似文献
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Yalcin O Ulker P Yavuzer U Meiselman HJ Baskurt OK 《American journal of physiology. Heart and circulatory physiology》2008,295(5):H2098-H2105
When recovering from heart failure (HF), the myocardium displays a marked plasticity and can regain normal gene expression and function; however, recovery of substrate oxidation capacity has not been explored. We tested whether cardiac functional recovery is matched by normalization of energy substrate utilization during post-HF recovery. HF was induced in dogs by pacing the left ventricle (LV) at 210-240 beats/min for 4 wk. Tachycardia was discontinued, and the heart was allowed to recover. An additional group was studied in HF, and healthy dogs served as controls (n = 8/group). Cardiac free fatty acids (FFAs) and glucose oxidation were measured with [3H]oleate and [14C]glucose. At 10 days of recovery, hemodynamic parameters returned to control values; however, the contractile response to dobutamine remained depressed, LV end-diastolic volume was 28% higher than control, and the heart mass-to-body mass ratio was increased (9.8 +/- 0.4 vs. 7.5 +/- 0.2 g/kg, P < 0.05). HF increased glucose oxidation (76.8 +/- 19.7 nmol.min(-1).g(-1)) and decreased FFA oxidation (20.7 +/- 6.4 nmol.min(-1).g(-1)), compared with normal dogs (24.5 +/- 6.3 and 51.7 +/- 9.6 nmol.min(-1).g(-1), respectively), and reversed to normal values at 10 days of recovery (25.4 +/- 6.0 and 46.6 +/- 6.7 nmol.min(-1).g(-1), respectively). However, similar to HF, the recovered dogs failed to increase glucose and fatty acid uptake in response to pacing stress. The activity of myocardial citrate synthase and aconitase was significantly decreased during recovery compared with that in control dogs (58 and 27% lower, respectively, P < 0.05), indicating a persistent reduction in mitochondrial oxidative capacity. In conclusion, cardiac energy substrate utilization is normalized in the early stage of post-HF recovery at baseline, but not under stress conditions. 相似文献
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Ayhan Kocer Fabrice Saez Kevin Mouzat Patrick Vernet Jean -Marc A. Lobaccaro Joël R. Drevet 《Andrologie》2006,16(1):11-23
Liver X receptors (LXRs) are involved in cholesterol homeostasis and lipid metabolism.Ixr knock-out mice for the two isoformsIxra andIxrb exhibit severe disruption of the structure of caput epididymidis segment 1 and 2 epithelium and increased sperm fragility. These defects generate infertility in 10-month-old male mice. The role of LXRs in the epididymis have not yet been investigated. A cell line obtained from mouse caput epididymidis (B2 cells) was used to screen for LXR epididymal target genesin vitro. The presence of one isoform of LXR (LXRα) was detected by immunocytochemistry and the capacity of B2 cells to respond to a synthetic agonist of LXRs (T0901317) was verified. These results validated the use of B2 cells as a model. Bidimensional electrophoresis was performed on B2 cells treated with T0901317. Eight proteins up-regulated by LXRs were isolated. Only one protein has been identified: polyubiquitin, which has already been reported to be involved in cellular cholesterol homeostasis. 相似文献
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This article is a taxonomic study of all spongy radiolarian taxa with five to six coplanar and four tetrahedrally disposed spines or spongy arms occurring in the middle Carnian from the Köseyahya section, near the town of Elbistan, SE Turkey. This fauna is characteristic of the Tetraporobrachia haeckeli radiolarian Zone, and comes from an 8 m thick succession of clayey–cherty limestones occurring at the lower part of the section. In addition, a few species from the Middle and Upper Triassic from other areas have been also included in this study to improve some generic diagnoses and to better understand the diversity and evolutionary trends of some genera, subfamilies and families. The taxonomy at the generic and suprageneric levels is based primarily on the types of microsphere. This new approach allowed new taxonomic arrangements of genera and suprageneric units, and suggested new and unexpected phylogenetic relationships among these radiolarians and between them and younger radiolarians. The authors discuss and describe 42 species, of which 36 are new, and 12 genera of which three are new (Charlottalum, Pentaspongodisculus, and Trimiducaella). The genera Pseudohagiastrum Pessagno, Natraglia Pessagno, Cantalum Pessagno and others are reinterpreted. All the genera studied, except Charlottalum, are assigned to three subfamilies, of which two (Pseudohagiastrinae and Trimiducinae) are new, and to two families (Angulobracchiidae and Relindellidae). The genus Charlottalum is described to replace the genus Cantalum, which has been erroneously used until present for Late Triassic pantanelliids with four tetrahedrally disposed three-bladed spines. 相似文献
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Martin Müller Ugur Üçer Wolfgang Engel 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》1983,762(1):135-137
After treatment of the ovarian and testicular membranes from several mammalian species an elevation in the specific binding of human [125I]-labelled CG could be observed. With the assumption that this effect is due to sialic acid-masked receptors, the presence of such receptors seem to be a common property of most mammalian gonads. An interesting observation was the abnormally high hormone binding capacity of the Syrian hamster ovary, as compared to other hamster species, and the lack of a neuraminidase effect in the ovary of the Syrian hamster. 相似文献