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71.
Transposable elements (TEs) are abundant in mammalian genomes and have potentially contributed to their hosts' evolution by providing novel regulatory or coding sequences. We surveyed different classes of regulatory region in the human genome to assess systematically the potential contribution of TEs to gene regulation. Almost 25% of the analyzed promoter regions contain TE-derived sequences, including many experimentally characterized cis-regulatory elements. Scaffold/matrix attachment regions (S/MARs) and locus control regions (LCRs) that are involved in the simultaneous regulation of multiple genes also contain numerous TE-derived sequences. Thus, TEs have probably contributed substantially to the evolution of both gene-specific and global patterns of human gene regulation. 相似文献
72.
Thyroid hormone-regulated enhancer blocking: cooperation of CTCF and thyroid hormone receptor
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Lutz M Burke LJ LeFevre P Myers FA Thorne AW Crane-Robinson C Bonifer C Filippova GN Lobanenkov V Renkawitz R 《The EMBO journal》2003,22(7):1579-1587
The highly conserved, ubiquitously expressed, zinc finger protein CTCF is involved in enhancer blocking, a mechanism crucial for shielding genes from illegitimate enhancer effects. Interestingly, CTCF-binding sites are often flanked by thyroid hormone response elements (TREs), as at the chicken lysozyme upstream silencer. Here we identify a similar composite site positioned upstream of the human c-myc gene. For both elements, we demonstrate that thyroid hormone abrogates enhancer blocking. Relief of enhancer blocking occurs even though CTCF remains bound to the lysozyme chromatin. Furthermore, chromatin immunoprecipitation analysis of the lysozyme upstream region revealed that histone H4 is acetylated at the CTCF-binding site. Loss of enhancer blocking by the addition of T3 led to increased histone acetylation, not only at the CTCF site, but also at the enhancer and the promoter. Thus, when TREs are adjacent to CTCF-binding sites, thyroid hormone can regulate enhancer blocking, thereby providing a new property for what was previously thought to be constitutive enhancer shielding by CTCF. 相似文献
73.
Successful microbial-mediated remediation requires transformationpathways that maximize metabolism and minimize the accumulation of toxic products. Pseudomonas aeruginosa strain MX, isolated from munitions-contaminated soil, degraded 100 mg TNT L-1 in culture medium within 10 h under aerobic conditions. The major TNT products were 2-amino-4,6-dinitrotoluene (2ADNT, primarily in the supernatant) and 2,2'-azoxytoluene (2,2'AZT, primarily in the cell fraction), which accumulated as major products via the intermediate2-hydroxylamino-4,6-dinitrotoluene (2HADNT). The 2HADNT and2,2'AZT were relatively less toxic to the strain than TNT and 2ADNT. Aminodinitrotoluene (ADNT) production increased when yeast extract was added to the medium. While TNT transformation rate was not affected by pH, more HADNTs accumulated at pH 5.0 than at pH 8.0 and AZTs did not accumulate at the lower pH. The appearance of 2,6-diamino-4-nitrotoluene (2,6DANT) and 2,4-diamino-6-nitrotoluene (2,4DANT); dinitrotoluene (DNT) and nitrotoluene (NT); and 3,5-dinitroaniline (3,5DNA) indicated various routes of TNT metabolism and detoxification by P. aeruginosa strain MX. 相似文献
74.
Natural anti-NOR antibodies are common in human sera and agglutinate human erythrocytes of a rare NOR phenotype. The NOR phenotype-related antigens are unique neutral glycosphingolipids recognized by these antibodies and Griffonia simplicifolia IB4 isolectin (GSL-IB4). The oligosaccharide chains of NOR glycolipids are terminated by Galalpha1-4GalNAcbeta1-3Galalpha units. To characterize the specificity of anti-NOR antibodies and compare it with specificities of GSL-IB4 and known anti-Galalpha1,3Gal antibodies, alpha-galactosylated saccharides and saccharide-polyacrylamide conjugates were used. New synthetic oligosaccharides, corresponding to the terminal di- and trisaccharide sequence of NOR glycolipids and the conjugate of the NOR-tri with HSA were included. These compounds were tested by microtiter plate ELISA and hemagglutination inhibition. Anti-NOR antibodies reacted most strongly with Galalpha1-4GalNAcbeta1-3Gal (NOR-tri), and over 100 times less strongly with Galalpha1-4GalNAc (NOR-di). The antibodies reacted also with Galalpha1-4Gal and Galalpha1-4Galbeta1-4GlcNAc, similarly as with NOR-di but not with other tested compounds. In turn, anti-Galalpha1,3Gal antibodies reacted most strongly with Galalpha1-3Gal and were very weakly inhibited by the NOR-related oligosaccharides (weaker than by galactose), and NOR-tri was less active than NOR-di. GSL-IB4 reacted with all tested alpha-galactosylated saccharides and conjugates, including the similarly active NOR-tri and NOR-di. These results showed that anti-NOR represent a new species of anti-alpha-galactosyl antibodies with high affinity for the Galalpha1-4GalNAcbeta1-3Gal sequence present in rare NOR erythrocytes. 相似文献
75.
The objective of this investigation was to evaluate the effect of repeated handling and the use of a mask on the order of entry, temperament, cortisol concentration and heart and respiratory rates of Brahman cattle during restraint in a squeeze chute. In the first experiment, 18 cows were restrained in the chute for 10min on 19 test-days and blood samples were collected during five of the trials. Habituation to handling was reflected by a decrease in cortisol concentration as the study advanced (P<0.01). In the second experiment, conducted 6 months later, animals were randomly allotted to two groups, alternating the use of a mask over test-days while restraining the cows in the chute for 3min. Respiratory and heart rates were measured at the beginning and end of each 3min trial. A blood sample was also taken at the end of each trial. Respiratory rates decreased while the animals were restrained and this decrease tended to be greater (P=0.09) when the animals were wearing masks (3.06) than when not (2.2breaths/min). Heart rates also decreased and more so for masked animals (10.6beats/min) than for non-masked (5.0, P<0.01). Cortisol values tended to be higher (9.9 versus 4.7ng/ml, P=0.08) when animals were restrained without a mask. Temperament scores were lower (P>0.01) when cows were masked and have a relative high correlation (r=0.58) with flight distance values, (P<0.05). Finally, the order of entrance was found consistent over test-days, (P<0.01). It is concluded that Brahman cattle: (a) habituate to repeat handling in a squeeze chute; (b) are less emotionally reactive when their eyes were covered during this process and (c) establish a repeatable order of entrance to the chute. 相似文献
76.
The regulation of pH in the apoplast, cytosol and chloroplasts of intact leaves was studied by means of fluorescent pH indicators
and as a response of photosynthesis to acid stress. The apoplastic pH increased under anaerobiosis. Aeration reversed this
effect. Apoplastic responses to CO2, HCl or NH3 differed considerably. Whereas HCl and ammonia caused rapid acidification or alkalinization, the return to initial pH values
was slow after cessation of fumigation. Addition of CO2 either did not produce the acidification expected on the basis of known apoplastic buffering or even caused some alkalinization.
Removal of CO2 shifted the apoplastic pH into the alkaline range before the pH returned to initial steady-state levels. In the presence
of vanadate, the alkaline shift was absent and the apoplastic pH returned slowly to the initial level when CO2 was removed from the atmosphere. In contrast to the response of the apoplast, anaerobiosis acidified the cytosol or, in some
species, had little effect on its pH. Acidification was rapidly reversed upon re-admission of oxygen. The CO2-dependent pH changes were very fast in the cytosol. Considerable alkalinization was observed after removal of CO2 under aerobic, but not under anaerobic conditions. Rates of the re-entry of protons into the cytosol during recovery from
CO2 stress increased in the presence of oxygen with the length of previous exposure to high CO2. Effective pH regulation in the chloroplasts was indicated by the recovery of photosynthesis after the transient inhibition
of photosynthetic electron flow when CO2 was increased from 0.038% to 16% in air. As photosynthesis became inhibited under high CO2, reduction of the electron transport chain increased transiently. The time required for recovery of photosynthesis from inhibition
during persistent CO2 stress was similar to the time required for establishing steady-state pH values in the cytosol under acid stress. The high
capacity of leaf cells for the rapid re-attainment of pH homeostasis in the apoplast and the cytoplasm under acid or alkaline
stress suggested the rapid activation or deactivation of membrane-localised proton-transporting enzymes and corresponding
ion channel regulation for co-transport of anions or counter-transport of cations together with proton fluxes. Acidification
of the cytoplasm appeared to activate energy-dependent proton export primarily into the vacuoles whereas apoplastic alkalinization
resulted in the pumping of protons into the apoplast. Proton export rates from the cytosol into the apoplast after anaerobiosis
were about 100 nmol (m2 leaf area)−1 s−1 or less. Proton export under acid stress into the vacuole was about 1200 nmol m−2 s−1. The kinetics of pH responses to the addition or withdrawal of CO2 indicated the presence of carbonic anhydrase in the cytosol, but not in the apoplast.
Received: 19 July 1999 / Accepted: 29 December 1999 相似文献
77.
Leonarda Troiano Antonio R.M. Granata Andrea Cossarizza Galina Kalashnikova Rita Bianchi Gabriella Pini Franco Tropea Cesare Carani Claudio Franceschi 《Experimental cell research》1998,241(2):384
Sperm cells from control donors of proven fertility and men from barren couples were studied by conventional procedures, i.e., light microscopy as well as flow cytometry. Light microscopy analysis of semen included the measurement of spermatozoa concentration, morphology, and motility. All the men from barren couples were asthenozoospermic at the conventional analysis of semen samples. Flow cytometry was applied to study two important parameters of sperm cells: mitochondrial membrane potential (MMP) assessed by the cationic dye JC-1 and DNA stainability with propidium iodide (PI). JC-1 staining was more reliable than the classical procedure used for this purpose, i.e., rhodamine 123 (Rh123) staining, and allowed us to show a positive correlation between MMP and spermatozoa motility. Regarding DNA analysis, a higher relative percentage of immature spermatozoa, showing a high accessibility of DNA to the intercalating PI fluorochrome, was found in men from barren couples compared to donors of proven fertility. The relative percentage of immature spermatozoa was significantly higher in semen from oligoasthenozoospermic subjects. Moreover, a positive correlation was found between immature spermatozoa, as evaluated by PI staining, and cells with depolarized mitochondria, as evaluated by JC-1 staining, suggesting that spermatozoa defective for nuclear maturity could be functionally defective cells. No correlation between immature spermatozoa determined by FCM and immature spermatozoa determined by light microscopy was found, suggesting that these two techniques assess sperm cell maturity at different levels. 相似文献
78.
Svetlana A. Dambinova Oleg K. Granstrem Alexandre Tourov †Roberto Salluzzo †Filippa Castello Galina A. Izykenova 《Journal of neurochemistry》1998,71(5):2088-2093
Abstract: We have monitored EEG spontaneous spiking activity and analyzed serum from rats with cobalt-induced epilepsy for the presence of autoreactive antibodies to α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) glutamate receptor subunits. The presence and the level of autoantibodies were assessed using immunoblot and ELISA with synthetic peptide specific to the N-terminus domain of the GluR1 subunit of the AMPA receptor. Rats with cobalt-induced epilepsy exhibited strong GluR1 immunoreactivity at the end of the first week after surgery compared with vehicle-treated rats. We showed that GluR1 autoantibodies in blood serum of rats with cobalt-induced epilepsy preceded the spiking activity maximum in the EEG. Levels of autoantibodies to GluR1 detected in blood of these rats remained elevated when EEG spiking activity was significantly reduced and seizures disappeared. The EEG monitoring of spiking activity showed a correlation with accumulation of GluR1 autoantibodies in blood serum of rats with cobalt-induced epilepsy. 相似文献
79.
Daekyu Sun Galina Melman Nickolas J. LeTourneau Allison M. Hays Artem Melman 《Bioorganic & medicinal chemistry letters》2010,20(2):458-460
We synthesized and evaluated new specific tridentate iron(III) chelators of 2,6-bis[hydroxyamino]-1,3,5-triazine (BHT) family for use in iron deprivation cancer therapy. Physical properties of BHT chelators are easily customizable allowing easy penetration through cellular membranes. Antiproliferative activity of new BHT chelators was studied on MDA-MB-231 and MiaPaCa cells and compared to a clinically available new oral iron chelator, deferasirox (DFX). The antiproliferative activity of new chelators was found to correlate with iron(III) chelation ability and some of analogs showed substantially higher antiproliferative activity than DFX. 相似文献
80.
Dionizio Ramos-Filho Gustavo Chicaybam Eduardo de-Souza-Ferreira Camila Guerra Martinez Eleonora Kurtenbach Gustavo Casimiro-Lopes Antonio Galina 《PloS one》2015,10(6)
High intensity interval training (HIIT) is characterized by vigorous exercise with short rest intervals. Hydrogen peroxide (H2O2) plays a key role in muscle adaptation. This study aimed to evaluate whether HIIT promotes similar H2O2 formation via O2 consumption (electron leakage) in three skeletal muscles with different twitch characteristics. Rats were assigned to two groups: sedentary (n=10) and HIIT (n=10, swimming training). We collected the tibialis anterior (TA-fast), gastrocnemius (GAST-fast/slow) and soleus (SOL-slow) muscles. The fibers were analyzed for mitochondrial respiration, H2O2 production and citrate synthase (CS) activity. A multi-substrate (glycerol phosphate (G3P), pyruvate, malate, glutamate and succinate) approach was used to analyze the mitochondria in permeabilized fibers. Compared to the control group, oxygen flow coupled to ATP synthesis, complex I and complex II was higher in the TA of the HIIT group by 1.5-, 3.0- and 2.7-fold, respectively. In contrast, oxygen consumed by mitochondrial glycerol phosphate dehydrogenase (mGPdH) was 30% lower. Surprisingly, the oxygen flow coupled to ATP synthesis was 42% lower after HIIT in the SOL. Moreover, oxygen flow coupled to ATP synthesis and complex II was higher by 1.4- and 2.7-fold in the GAST of the HIIT group. After HIIT, CS activity increased 1.3-fold in the TA, and H2O2 production was 1.3-fold higher in the TA at sites containing mGPdH. No significant differences in H2O2 production were detected in the SOL. Surprisingly, HIIT increased H2O2 production in the GAST via complex II, phosphorylation, oligomycin and antimycin by 1.6-, 1.8-, 2.2-, and 2.2-fold, respectively. Electron leakage was 3.3-fold higher in the TA with G3P and 1.8-fold higher in the GAST with multiple substrates. Unexpectedly, the HIIT protocol induced different respiration and electron leakage responses in different types of muscle. 相似文献