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Biomedical subjects

D Ding

Publications and source records attributed to D Ding.

At least 91 records · Page 5Linked to original sources
PubMed1993

Glial cell-specific expression of the serotonin 2 receptor gene: selective reactivation of a repressed promoter.

The 5' flanking region of the 5-HT2 receptor gene has been cloned, sequenced and its transcriptional regulatory functions analyzed. The promoter lacks an identifiable TATA motif, and utilizes at least 11 clustered start sites. Promoter function was analyzed by transient assays in rat C6 glioma cells, which were shown to express the endogenous 5-HT2 receptor gene, as well as in rat CREF and human HeLa cells which do not express the endogenous gene. The basal promoter functioned equally well in all three cell lines; and a repression domain, located upstream of the basal promoter, inhibited activity of the promoter in all three cell lines. A far upstream cell specific activator domain restored promoter activity in C6 glioma cells, but did not reactivate the silenced promoter in CREF or HeLa cells. The upstream activator domain, repressor domain and basal promoter functioned in concert to achieve cell type specific expression. The activator domain did not direct C6 glioma cell specific expression in the absence of the repressor domain or in constructs carrying a heterologous basal promoter. These results indicate that glial cell expression of the 5-HT2 receptor gene is achieved through a cell type specific reactivation of a repressed promoter.

Amino Acid Sequence↗
PubMed1993

A molecular screen for polar-localised maternal RNAs in the early embryo of Drosophila.

Localised, maternally synthesised RNAs and proteins play an important role in an early animal embryogenesis. In Drosophila, genetic screens have recovered a number of maternal effect loci that encode localised products in the embryo. However, only a third of Drosophila's genes have been genetically mutated. Consequently, we conducted a molecular screen for polar-localised RNAs in the early Drosophila embryo in order to identify additional maternal molecules that carry out spatially restricted functions during early embryogenesis. Total RNA was purified from anterior or posterior poles cut off early Drosophila embryos. These RNAs were used to construct directionally cloned anterior and posterior cDNA libraries which were used in a differential screen for cDNAs representing maternal RNAs localised to one or other pole of the embryo. Five such clones were identified, representing cyclin B RNA, Hsp83 RNA, 28S ribosomal RNA, mitochondrial cytochrome c oxidase subunit one RNA and mitochondrial 16S large ribosomal RNA. Mutations in the loci encoding these RNAs have not been recovered in genetic screens, confirming that our molecular approach complements genetic strategies for identifying maternal molecules that carry out spatially restricted functions in the early embryo. We consider the possible biological significance of localisation of each of these species of transcripts as well as the mechanism of their localisation, and discuss the potential use of our cDNA libraries in screens for rarer localised RNAs.

Animals↗
PubMed1993

Dynamic Hsp83 RNA localization during Drosophila oogenesis and embryogenesis.

Hsp83 is the Drosophila homolog of the mammalian Hsp90 family of regulatory molecular chaperones. We show that maternally synthesized Hsp83 transcripts are localized to the posterior pole of the early Drosophila embryo by a novel mechanism involving a combination of generalized RNA degradation and local protection at the posterior. This protection of Hsp83 RNA occurs in wild-type embryos and embryos produced by females carrying the maternal effect mutations nanos and pumilio, which eliminate components of the posterior polar plasm without disrupting polar granule integrity. In contrast, Hsp83 RNA is not protected at the posterior pole of embryos produced by females carrying maternal mutations that disrupt the posterior polar plasm and the polar granules--cappuccino, oskar, spire, staufen, tudor, valois, and vasa. Mislocalization of oskar RNA to the anterior pole, which has been shown to result in induction of germ cells at the anterior, leads to anterior protection of maternal Hsp83 RNA. These results suggest that Hsp83 RNA is a component of the posterior polar plasm that might be associated with polar granules. In addition, we show that zygotic expression of Hsp83 commences in the anterior third of the embryo at the syncytial blastoderm stage and is regulated by the anterior morphogen, bicoid. We consider the possible developmental significance of this complex control of Hsp83 transcript distribution.

Animals↗
PubMed1992

[Application of the regression orthogonal design to the fertilization of Psoralea corylifolia L. for optimum yield].

This paper probes into the determination of the optimum amount of fertilization by applying regression orthogonal design. After a significance test by regression equation, a regression equation can be set up, i. e. Y = 25.21 + 9.18 Xn + 15.68 Xp - 0.4 Xn2 - 0.98 Xp2 + 0.062 Xn Xp. This equation can be used to describe the relationship between yield and amount of fertilization.

Fertilizers↗
PubMed1990

Induction of cytochrome P(1)450 RNA and benzo[a]pyrene metabolism in primary human hepatocyte cultures with benzanthracene.

Exposure of cells to microsomal enzyme inducers can modify the potency of many carcinogens. We have examined the steady-state level of RNA from the P(1)450 gene and the metabolism of benzo[a]pyrene (BP) in primary cultures of human hepatocytes exposed for up to 4 days to 12.5 microM benzanthracene (BA), and in uninduced control cultures. While the steady-state levels of RNA from the P(1)450 gene were nondetectable in uninduced (DMSO only) human hepatocytes, 12.5 microM BA-induced AHH activity, BP metabolism, and/or P(1)450-specific RNA in hepatocytes from seven human cases were investigated. RNA levels specific for the P(1)450 gene appeared maximal at 24 hr following exposure to BA, whereas, the protein, as determined by AHH enzyme activity from BA-induced hepatocytes, continued to increase up to the last time point examined, 72 hr. BA induction for 96 hr increased metabolism of BP (initial concentration of BP, 10 microM) over a time course of 3, 6, 12, and 24 hr of incubation with BP compared with that of controls. The major metabolites of BP produced by human hepatocytes in culture were the unidentified polar BP metabolite(s), possibly polyhydroxylated. BA induction caused approximately a twofold increase in these metabolites. BA-induced cultures showed an increase in glutathione conjugation compared to that in controls. The percentage of glucuronide and sulfate conjugates remains similar in all cultures. Total binding of tritium label BP to DNA was 1.3-fold to fivefold greater in induced cultures, and related more to total metabolism than to production of a specific metabolite. Exposure of human hepatocytes in vitro to BA leads to a large increase in the steady-state level of the RNA specific for the P(1)450 gene and an increase metabolism of BP.

Adolescent↗
PubMed1990

[Nutritive physiology of Psoralea corylifolia L].

Our study has shown that P. corylifolia absorbs and accumulates N2 and K2O most speedily in the periods of branching, flowering and fruiting, while P2O5 in the period of full flowering and fruiting. P2O5 is accumulated mainly in the seed and K2O in the stem. The nutriment accumulation is positively correlated with that of dry substances. To produce 100 kg of P. corylifolia an absorption of 10.59 kg of N2, 3.68 kg of P2O5 and 10.21 kg of K2O is needed.

Fabaceae↗
PubMed1990

[Effect of seed soaking in plant hormone and trace element fertilizer on the growth of Psoralea corylifolia L].

Our study shows that seed soaking in triacontanol, ammonium molybdate and gibberellin can promote the growth of P. corylifolia, reduce its premature flower and fruit drop, raise the fruit-bearing rate by 6.5-17.4%, and fruit-bearing number by 21.6-28.4%, so as to increase the yield per unit area by 31.5-34.8%. Seed soaking in naphthylacetic acid and boric acid does not give such a marked effect.

Fabaceae↗
PubMed1990

[Biological characteristics of Psoralea corylifolia L].

A study has been made on the biological characteristics of Psoralea corylifolia under general cultivating conditions. To search for the laws of growth and development so as to facilitate further studies on the cultivating techniques for higher production of Psoralea corylifolia.

Fabaceae↗
PubMed1982

Mutant din-21, a variant of polyoma virus containing a mouse DNA sequence in the viral genome.

An unusual non-defective mutant of polyoma virus with an anomalously large genome, designated din-21, has been isolated. The viral chromosome lacks 49 base pairs of the putative control region between the origin of replication and the initiation codon for the early proteins, the T-antigens. In their stead , 95 base pairs, with limited homology to the deleted sequence and apparently of mouse origin, have been inserted. The primary sequence of the insert DNA has been determined and some of the biological properties of the mutant examined. It transforms rat-1 cells slightly better than wild-type virus and grows slightly less well in lytically infected mouse cells. It does not interfere with the growth of wild-type polyoma virus. The properties of this mutant suggest that it is a natural isolate of mouse cells. The mutant was presumably generated by reciprocal recombination between polyoma DNA and mouse host DNA. This could be associated with the integration of a viral DNA sequence into the host chromosome during the viral replicative cycle.

Base Sequence↗
PubMed1982

mlt Mutants of polyoma virus.

New mlt deletion mutants of polyoma virus were isolated, and their abilities to produce a lytic response in mouse cells or to transform rat cells were assessed. Their properties were analyzed in terms of the sequences deleted and their effects upon the structure and functions of the viral middle and large T-antigens.

Amino Acid Sequence↗
PubMed1980

Electric dichroism and sedimentation velocity studies of DNA-Hg(II) and DNA-Ag(I) complexes.

The cause of the induced CD bands of DNA-Hg2+ and DNA-Ag+ complexes has been interpreted as a condensed psi state (Walter, A. and Luck, G. (1977) Nucl. Acids Res. 4, 539-550). Electric dichroism and sedimentation velocity experiments indicate that there is no tertiary structure formation of DNA-heavy-metal-ion complexes to support a psi state. The increase of the sedimentation coefficient of DNA-heavy-metal-ion complexes can be accounted for by an increase in molecular weight and a decrease in the partial specific volume upon the binding of Hg2+ and Ag+. Electric dichroism measurements show that the new optical bands produced by the binding of Hg2+ to DNA and the mode I binding of Ag+ to DNA result in transition moments polarized in the plane of the bases. Binding mode II of the DNA-Ag+ complex at 265 nm gives an optical perturbation where the transition moment has an out-of-plane contribution. The CD studies reported in the following paper give further insight into the binding sites and binding modes of these two metal ions.

Animals↗
PubMed1980

A circular dichroism study on the structure of DNA and the nucleosomal core particle using Hg(II) and Ag(I).

CD studies of known sequence DNA-like polynucleotide-Hg2+ complexes have established a cross-strand binding of Hg2+ to the two thymines of the base-paired first-neighbor unit TpA, as the type I binding mode of poly[d(A-T) x d(A-T)] and other polynucleotides with high TpA incidence. The amino group of adenine is the most probable Hg2+ site for poly(A) and for the binding mode II of poly[d(A-T) x d(A-T)]. The binding of Hg2+ to the natural DNAs shows two binding modes with two different degrees of CD perturbation. The two proposed binding modes are substantiated by Hg2+ binding studies with the DNa-poly(L-lysine) complexes. The increase of sedimentation coefficient of the nucleosomal core particle-heavy metal ion complexes can be accounted for by the binding of heavy metal ions. From the CD experiments with Hg2+ and Ag+, it is estimated that 80 +/- 10% of the DNA in the nucleosomal core particle is involved in the wrapping around the histone core. An out-of-plane transition of the DNA-Ag+ binding mode II is proposed as the cause for the large CD perturbation at 270 nm, but the origin of optical activity of the DNA-Hg2+ complex is still unknown.

Animals↗
PubMedDate not supplied

Design and analysis of RNA structure-specific agents as potential antivirals.

A number of pathogenic RNA viruses, such as HIV-1, have extensive folded RNA conformations with imperfect A-form duplexes that are essential for virus function, and could serve as targets for structure-specific antiviral drugs. A method for the discovery of such drugs involves evaluation of the interactions with RNA of a wide variety of compounds that are known to bind to nucleic acids by different mechanisms. This approach has been initiated by using corresponding sequence RNA and DNA polymers as initial test systems for analysis of RNA binding strength and selectivity. Compounds that bind exclusively in the minor groove in AT sequences of DNA do not have significant interactions with RNA. Polycations, however, can show significant RNA affinity and binding selectivity, probably through complex formation in the RNA major groove. Some intercalators and a group of diphenylfuran cations have strong interactions with RNA that are very dependent on compound structure. RNA hairpin model systems for the RRE binding site of HIV-1 Rev protein were constructed for more detailed investigations. The diphenylfuran cations bind strongly to RRE and selectively inhibit Rev binding. CD, NMR, and fluorescence binding studies indicate that the active compounds bind in the internal loop region of RRE (with binding constants > 10(7)M-1), and cause a conformational change in the RNA. None of the standard nucleic acid binding modes appears to fit the results for complexes of the active compounds with RRE, and it is proposed that the diphenylfuran system threads through the internal loop region of RRE. Such a model allows contacts of the furan cationic substituents with both grooves of RRE in addition to the intercalation interactions with the bases.

Antiviral Agents↗
PubMedDate not supplied

Age-related cochlear hair cell loss is enhanced in mice lacking copper/zinc superoxide dismutase.

Age-related hearing loss in humans and many strains of mice is associated with a base-to-apex gradient of cochlear hair cell loss. To determine if copper/zinc superoxide dismutase (Cu/Zn SOD) deficiency influences age-related cochlear pathology, we compared hair cell losses in cochleas obtained from 2-, 7-, and 17- to 19-month-old wild type (WT) mice with normal levels of Cu/Zn SOD and mutant knockout (KO) mice with a targeted deletion of Sod1, the gene that codes for Cu/Zn SOD. WT and KO mice exhibited similar patterns of hair cell loss with age, i.e., a baso-apical progression of hair cell loss, with greater loss of outer hair cells than inner hair cells. Within each age group, the magnitude of loss was much greater in KO mice compared to WT mice. The results indicate that Cu/Zn SOD deficiency potentiates cochlear hair cell degeneration, presumably through metabolic pathways involving the superoxide radical.

Aging↗
PubMedDate not supplied

Acute adaptation of mice to hypoxic hypoxia.

Tolerance to hypoxia in vivo and in vitro was significantly increased by acute and repetitive exposure of mice to autoprogressive hypoxia. The average tolerance times of the successive 2nd, 3rd, 4th and 5th runs of exposure were, respectively, 2, 4, 6 and 8 times as long as that of the first exposure. The survival times under hypobaric chamber and cyanide toxification in the 4th exposure were, respectively, 10 (and even as much as 86) and 4 times those in control mice without exposure to hypoxia. Mandibular respiration and spinal reflex in vitro in hypoxia-resistant animals lasted 5-6 times as long as in control animals not previously exposed to hypoxia. Animals that received brain homogenate from hypoxia-resistant mice remained alive in a hypobaric chamber 2 times as long as those that received homogenate from controls and those that received saline. These results indicate that a kind of quickly developing adaptation with increased tolerance is achieved by acute and repetitive exposure of mice to progressive autohypoxia and some plastic or adaptive changes occur in the brain of hypoxia-resistant animals, including the production of some kind of water-soluble antihypoxic factors.

Adaptation, Physiological↗
PubMedDate not supplied

Early damage in the chinchilla vestibular sensory epithelium from carboplatin.

Carboplatin, a second-generation platinum drug used in the treatment of cancer, can damage the hair cells in the vestibular system; however, little is known about the time course of its vestibulotoxic effects. The present study examined the acute vestibulotoxic effects of carboplatin (50 mg/kg) in the chinchilla. The duration of the nystagmus response evoked by cold caloric stimulation was significantly reduced 6 h following carboplatin treatment and showed a maximum, permanent reduction of approximately 50% by 24 h after injection. Light-microscopic observations at 6 h subsequent to injection revealed swollen afferent dendrites beneath type-I hair cells and the appearance of small vacuoles within the type-I hair cells; these changes were most pronounced in the crista ampullaris of the semicircular canals compared to the maculae of the utricle and saccule. Many mitochondria were swollen and partially depleted of their membranous infoldings. The mitochondrial abnormalities tended to be somewhat more severe in the hair cells than in their afferent terminals. The structural abnormalities in the mitochondria were more severe at 24 h following injection resulting in the appearance of larger and more numerous vacuoles in the hair cells. By 3 days after injection, many type-I hair cells were filled with large vacuoles which often caused severe distortion of the nucleus and disruption of the plasma membrane. Small vacuoles were occasionally observed in type-II hair cells, mainly in the crista ampullaris. These results indicate that the vestibulotoxic effects of carboplatin occur quite rapidly and cause significant disruption of the mitochondria in hair cells and their afferent terminals.

Animals↗
PubMedDate not supplied

Magnitude and pattern of inner and outer hair cell loss in chinchilla as a function of carboplatin dose.

We examined the relationship between carboplatin dose and pattern of IHC and OHC loss in five groups of chinchillas treated with carboplatin: (I) single dose, 38 mg/kg, (II) double dose, 38 mg/kg, (III) double dose, 63 mg/kg, (IV) double dose, 75 mg/kg, and (V) double dose, 100 mg/kg. The pattern of IHC loss was relatively uniform along the length of the cochlea with all doses. Average IHC loss increased from approximately 20 per cent in group I to approximately 100 per cent in groups III, IV and V. Average OHC loss was small or negligible in groups I, II, III and IV; only group V consistently showed large (> 40 per cent) OHC losses. OHC loss progressed along a base-to-apex gradient. The dose of carboplatin which reliably destroyed OHCs was four to five times greater than that needed to damage IHCs.

Animals↗