Biomedical subjects

Y Park

Publications and source records attributed to Y Park.

At least 73 records · Page 4Linked to original sources

PubMed2001

Differential splicing of the IA-2 mRNA in pancreas and lymphoid organs as a permissive genetic mechanism for autoimmunity against the IA-2 type 1 diabetes autoantigen.

Type 1 diabetes results from the autoimmune destruction of pancreatic beta-cells in genetically susceptible individuals. Growing evidence suggests that genetically determined variation in the expression of self-antigens in thymus may affect the shaping of the T-cell repertoire and susceptibility to autoimmunity. For example, both allelic variation and parent-of-origin effects influence the thymic expression of insulin (a known type 1 diabetes autoantigen), and insulin gene transcription levels in thymus inversely correlate with susceptibility in both humans and transgenic models. It is unclear why patients lose tolerance to IA-2 (insulinoma-associated tyrosine phosphatase-like protein, or islet cell antigen 512 [ICA512]), especially because IA-2 polymorphisms are not associated with type 1 diabetes. We report that alternative splicing determines differential IA-2 expression in islets compared with thymus and spleen. Islets express full-length mRNA and two alternatively spliced transcripts, whereas thymus and spleen exclusively express an alternatively spliced transcript lacking exon 13. This encodes for the transmembrane (TM) and juxta-membrane (JM) domains that comprise several type 1 diabetes target epitopes, supporting the concept that tolerance to IA-2 epitopes not expressed in lymphoid organs may not be achieved. We propose differential splicing as a regulatory mechanism of gene expression playing a permissive role in the development of autoimmune responses to IA-2. Our findings also show that candidate gene expression studies can help in dissecting the complex genetic determinants of a multifactorial disease such as type 1 diabetes.

Adult↗

PubMed2001

MICA polymorphism is associated with type 1 diabetes in the Korean population.

OBJECTIVE: Recent studies have demonstrated that MICA (major histocompatibility complex class I chain-related genes) on the short arm of the chromosome 6 are associated with susceptibility to various autoimmune diseases in Caucasians. The aim of our study was to investigate the role of MICA in type 1 diabetes susceptibility independent of the HLA DR-DQ polymorphism in genetically distinct Koreans. RESEARCH DESIGN AND METHODS: A total of 119 patients selected from Korean Seoul type 1 diabetes registry and 134 nondiabetic unrelated control subjects were typed for exon 5 polymorphism of MICA in addition to HLA DR-DQ typing. A total of 52 simplex families of type 1 diabetes were also studied. RESULTS: The MICA microsatellite allele consisting of six repetitions of GCT/AGC (A6) was present at a significantly lower frequency in the diabetic patient group (Pc < 0.01; Pc = P value after Bonferroni correction) than in the control population. The MICA microsatellite allele consisting of four repetitions (A4) was present at a higher frequency in diabetic patients (P < 0.05). This deviated distribution was not changed even after controlling for the HLA DRB1-DQB1 haplotype. Transmission/disequilibrium test revealed significant deviation of transmission for alleles at the A6 polymorphism within the MICA gene (P < 0.05). CONCLUSIONS: We could assess that the MICA gene might be associated with type 1 diabetes transracially independent of the HLA gene.

Adolescent↗

PubMed2001

Regulation of gonadotropin releasing hormone receptor mRNA expression in cultured rat granulosa cells.

The homologous regulation of pituitary Gonadotropin Releasing Hormone Receptor (GnRH-R) mRNA expression by GnRH has been well demonstrated. However, the regulation of the ovarian GnRH-R is poorly understood. The present study was performed to demonstrate the presence of GnRH transcripts in addition to GnRH-R mRNA and the regulation of GnRH-R mRNA expression in the granulosa cells isolated from small antral follicles. The GnRH and GnRH-R mRNA levels were determined by a competitive reverse transcription-polymerase chain reaction (RT-PCR). The granulosa cells were obtained from immature rats implanted with diethylstilbestrol for 3 days. When GnRH transcript expression was examined in isolated granulosa cells by RT-PCR, the PCR products showed two bands. The larger band contained intronic sequences and the smaller band was a fully processed GnRH gene transcript identical to hypothalamic GnRH. This suggests that authentic GnRH gene transcripts are expressed in ovarian granulosa cells and may act on the granulosa cells in a paracrine or autocrine manner. Since GnRH action in the granulosa cells is mediated by specific GnRH-R, it is of interest to examine whether GnRH-R is synthesized in the granulosa cells. When the granulosa cells were cultured in media only, GnRH-R mRNA levels increased abruptly within 3 h and gradually decreased thereafter during the 24 h culture period. However, GnRH itself did not alter the GnRH-R mRNA expression levels in cultured granulosa cells. Interestingly, treatment with FSH decreased the GnRH-R mRNA levels in a dose-dependent manner. A time-course analysis revealed that the GnRH-R mRNA levels were significantly lower up to 9 h after FSH treatment, and returned to the basal level between 12 h-24 h. Activation of adenylate cyclase with forskolin also decreased the GnRH-R mRNA levels. It is therefore concluded that in the granulosa cells of the small antral follicles GnRH-R mRNA expression was not homologously regulated by GnRH, while FSH may negatively regulate GnRH-R mRNA expression in the granulosa cells possibly through a cAMP-protein kinase A pathway.

Animals↗

PubMed2001

Extracellular polymeric substances in relation to nutrient removal from a sequencing batch biofilm reactor.

Experimental investigations were performed to determine the possibility of simultaneous biological nitrogen and phosphorus removal during various biofilm processes in conjunction with biofilm characterisation, especially extracellular polymeric substance (EPS). Since biologial nitrogen removal requires an alternating exposure of anaerobic-anoxic-oxic conditions in the bulk liquid that surrounds the biofilm growth media, a sequencing batch reactor (SBR)-type operation was used. Various materials including expanded clay, polystyrene, polyurethane, and acrylic materials were used as the biofilm growth support medium. Simultaneous nitrogen and phosphorus removal was possible with SBR, but it was postulated that nutrient removal efficiencies varied with film thickness. Thinner biofilm promoted nitrification and phosphorus removal, but thicker biofilm enhanced denitrification and reduced phosphorus removal. EPS contents were similar regardless of support media types or biofilm configuration, but EPS contents gradually increased as the film growth continued after backwashing. EPS contents were increased with increased nitrogen removal, but it was difficult to define its relation with phosphorus removal. In addition, suspended solids removal was correlated well with the EPS content in the biofilms.

Biofilms↗

PubMed2001

Progesterone together with estrogen attenuates homologous upregulation of gonadotropin-releasing hormone receptor mRNA in primary cultured rat pituitary cells.

In a previous study, we clearly demonstrated that an application of gonadotropin-releasing hormone (GnRH) to cultured rat pituitary cells increased the expression of GnRH receptor (GnRH-R) mRNA through transcriptional activation of GnRH-R gene rather than suppression of the turnover rate of GnRH-R mRNA. Along with GnRH, gonadal steroids seem to be an important regulator for GnRH-R expression in the pituitary gland. Recent in vivo studies reported that an application of gonadal steroids to gonadectomized animals modulated GnRH-R mRNA expression in the pituitary gland. However, it has not been clearly understood whether steroids may act directly at the pituitary or indirectly via modulation of hypothalamic GnRH release. Therefore, we assessed the effects of estrogen and progesterone on GnRH-R mRNA expression in primary cultured female rat pituitary cells. Neither estradiol nor progesterone modulates the basal expression of GnRH-R mRNA in primary cultured pituitary cells. When cultured pituitary cells were exposed to different doses of estradiol in combination with GnRH (0.2 nM), the GnRH-stimulated increment of GnRH-R mRNA expression was not significantly changed by estradiol at any given doses. However, when different doses of progesterone were added to primary cultured pituitary cells in combination with GnRH (0.2 nM), GnRH-induced increases in GnRH-R mRNA levels were reduced in a dose-related manner, showing a significant reduction at 100 nM progesterone. Furthermore, the addition of estradiol reinforced the suppressive effect of progesterone on the homologous upregulation of GnRH-R mRNA expression. Collectively, our results clearly demonstrated that progesterone directly attenuates the homologous upregulation of GnRH-R mRNA expression at the pituitary level, and that estradiol potentiates the effect of progesterone.

Animals↗

PubMed2001

The expression of functional LPS receptor proteins CD14 and toll-like receptor 4 in human corneal cells.

PURPOSE: Gram-negative bacterial infections of the eye can lead to corneal bacterial keratitis, visual impairment, and blindness. Many of these pathologic changes may be mediated by bacterially derived products such as lipopolysaccharide (LPS). In this investigation, it has been established for the first time that human corneal cells are capable of expressing the functional LPS receptor complex proteins, CD14 and Toll-like receptor 4 (TLR4). METHODS: CD14 and TLR4 mRNA expression in human corneal cells was determined by RT-PCR and Northern blot analysis, and cell surface expression of these proteins was measured by flow cytometry. LPS-mediated corneal cell activation was determined by measuring intracellular calcium mobilization. Cellular cytokine and chemokine secretion in response to LPS was measured by ELISA. The expression and localization of CD14 in whole human cornea was determined by immunohistochemistry. RESULTS: Human corneal epithelial, stromal, and endothelial cells expressed CD14 mRNA and cell surface CD14. LPS binding to cornea CD14 resulted in a rapid intracellular calcium response and the secretion of multiple proinflammatory cytokines and chemokines. CD14 mRNA expression in corneal epithelial cells was upregulated by LPS. In addition to CD14, corneal epithelial cells expressed the functional LPS receptor-signaling protein TLR4, which was also augmented by LPS. CONCLUSIONS: The cornea expresses functional CD14 and TLR4 LPS receptor proteins. Understanding the function and biology of the corneal LPS receptor complex may lead to novel therapies for the management of ocular Gram-negative bacterial infections.

Base Sequence↗

PubMed2000

Functional and evolutionary consequences of pyrethroid resistance mutations in S6 transmembrane segments of a voltage-gated sodium channel.

Pyrethroids are a class of voltage-dependent sodium channel modifiers widely used as insecticides for control of disease vectors and agricultural pests. Many insect populations have developed resistance to pyrethroids linked to nervous system insensitivity and structural mutations in neuronal sodium channels. Pyrethroid resistant strains of the moth Heliothis virescens carry single point mutations leading to amino acid substitutions in either transmembrane segment I-S6 (V421M) or II-S6 (L1029H) of the para-homologous sodium channel. We analyzed the consequences of V421M and L1029H mutations constructed in the Drosophila para sodium channel heterologously expressed in Xenopus oocytes, and found that both mutations confer channel insensitivity to permethrin, with the L1029H mutation having a more pronounced effect. Both mutations also modify the intrinsic voltage-dependent gating properties of the channel, but L1029H less so than V421M. These results suggest that mutation V421M exacts a higher fitness cost than L1029H, providing a plausible explanation for genetic succession observed in field strains, where V421M was replaced by L1029H during the past decade.

Amino Acid Sequence↗

PubMed2000

Eicosanoids rescue Spodoptera exigua infected with Xenorhabdus nematophilus, the symbiotic bacteria to the entomopathogenic nematode Steinernema carpocapsae.

Xenorhabdus nematophilus is a pathogenic bacterium causing insect haemolymph septicemia, which leads to host insect death. To address the fundamental mechanisms underlying this haemolymph septicemia, or the immunodepressive response of the host insects following bacterial infection, we tested a hypothesis that the insect immune-mediating eicosanoid pathway is blocked by inhibitory action of the bacterium. Haemocoelic injection of the bacteria into the fifth instar larvae of Spodoptera exigua reduced the total number of living haemocytes with postinjection time and resulted in host death in 16 h at 25 degrees C. The lethal efficacy, described by the median lethal bacterial dose (LD(50)), was estimated as 33 colony-forming units per fifth instar larva of S. exigua. The lethal effect of the bacteria on the infected larvae decreased significantly with the addition of exogenous arachidonic acid (10 µg), a precursor of eicosanoids. In comparison, injections of dexamethasone (10 µg), a specific inhibitor of phospholipase A(2), and other eicosanoid biosynthesis inhibitors elevated significantly the bacterial pathogenicity. Live X. nematophilus induced the infected larvae to form less nodules than did the heat-killed bacteria, but the addition of arachidonic acid increased the number of nodules formed significantly in response to live bacterial injection. The treatment with dexamethasone and other inhibitors, however, decreased the nodule formation after injection of heat-killed bacteria. These results indicate that eicosanoids play a role in the immune response of S. exigua, and suggest strongly that X. nematophilus inhibits its eicosanoid pathway, which then results in immunodepressive haemolymph septicemia.

Journal Article↗

PubMed2000

Effects of a hexameric deoxyriboguanosine run conjugation into CpG oligodeoxynucleotides on their immunostimulatory potentials.

CpG oligodeoxynucleotides (ODNs) are promising immunomodulatory agents for treating human diseases and vaccine development. Phosphodiester CpG ODNs were demonstrated to have poor immunostimulatory potentials for cytokine production. However, the conjugation of consecutive deoxyriboguanosine residues, called a dG run, at the 3' terminus of phosphodiester CpG ODNs significantly enhanced TNF-alpha and IL-12 production from mouse splenic dendritic cells (DCs). The optimal induction of cytokine production was achieved by the addition of a hexameric dG (dG6) run. In contrast, the existence of a dG6 run either at the 5' terminus of phosphodiester CpG ODNs or at the 3' terminus of phosphorothioate CpG ODNs diminished CpG-mediated cytokine induction, suggesting that the effects of a dG run depend on its location and the chemical property of the ODN backbone, respectively. In addition, we provided the evidence that the conjugation of a dG6 run caused the structural transformation of CpG ODNs, which facilitates their targeting into mouse APCs such as splenic DCs, B cells, and peritoneal macrophages with a scavenger receptor type A ligand specificity. Among primary APCs, DCs were the most potent for CpG ODN-mediated IL-12 production. Furthermore, we demonstrated that the conjugation of a dG6 run into the 3' terminus of phosphodiester CpG ODNs was crucial for their ability to generate Th1 immunity in vivo. Thus, the conjugation of a dG6 run into phosphodiester CpG ODNs would be an alternative way to optimize their immunostimulatory potentials in vitro and in vivo.

3' Untranslated Regions↗

PubMed2000

Strategies for maintaining the particle size of peptide DNA condensates following freeze-drying.

The particle size of peptide DNA condensates were studied after freeze-drying and rehydration as a function of sugar excipient, concentration, pH, DNA concentration, and peptide condensing agent. In the absence of an excipient, freeze-dried 50 microg/ml AlkCWK(18) (iodoacetic acid alkylated Cys-Typ-Lys(18)) DNA condensates formed large fibrous flocculates on rehydration. Of the sugars tested as lyoprotectants, sucrose proved most effective at preserving particle size during rehydration. The addition of 5 wt/vol% sucrose preserved a mean particle diameter of less than 50 nm during rehydration of AlkCWK(18) DNA condensates prepared at DNA concentrations up to 200 microg/ml; however, higher DNA concentrations led to the formation of insoluble fibrous flocculates. Substitution of polyethylene glycol (PEG)-CWK(18) as a DNA condensing peptide eliminated the need for sucrose, resulting in peptide DNA condensates that retained particle size when rehydrated in water or normal saline at concentrations up to 5 mg/ml. The results suggest that sucrose functions primarily as a bulking agent during freeze-drying that only preserves the particle size of AlkCWK(18) DNA condensates up to a maximum concentration of 200 microg/ml. Alternatively, the steric layer created on the surface of PEG-CWK(18) DNA condensates provides far more efficient lyoprotection, preserving their particle size at a concentration of 5 mg/ml without a bulking agent.

DNA↗

PubMed2000

Inhibition of hepatic stearoyl-CoA desaturase activity by trans-10, cis-12 conjugated linoleic acid and its derivatives.

Conjugated linoleic acid (CLA) has been reported to decrease stearoyl-CoA desaturase (SCD) activity by decreasing mRNA expression. This investigation was designed to determine whether structurally related compounds of CLA have a direct inhibitory effect on SCD activity. Trans-10,cis-12 CLA had strong inhibitory activity on SCD while cis-9,trans-11, and trans-9,trans-11 isomers had no effect. Trans-10 octadecenoate was not inhibitory, whereas cis-12 octadecenate was inhibitory, but not as effective as trans-10,cis-12 CLA. Of the oxygenated derivatives, 9-peroxy-cis/trans-10, trans-12 octadecadienoate was a more effective inhibitor than trans-10,cis-12 CLA, whereas 9-hydroxy-trans-10, cis-12 octadecadienoate was less effective. Interestingly, cis-11 octadecadienoate and cis-12 octadecen-10-ynoate were slightly inhibitory. However, trans-9 and trans-11 octadecenoates, and trans-9,cis-12 octadecadienoate were all inactive under test condition, as were linoleate, oleate, and arachidonate. Derivatives of CLA acid modified to alcohol, amide or chloride were all inactive. A cis-12 double bond appears to be a key structural feature for inhibiting SCD activity, especially when coupled with a trans-10 double, whereas a cis-11 double bond is less effective.

Animals↗

PubMed2000

Comparison of G-protein activation in the brain by mu-, delta-, and kappa-opioid receptor agonists in mu-opioid receptor knockout mice.

Mice lacking the mu-opioid receptor gene have been developed by a gene knockout procedure. In this study, the activity of opioid receptor coupled G-proteins was examined to investigate whether there is a change in the extent of coupling for mu, delta-, and kappa-opioid receptors in mu-opioid receptor knockout mice. Selective agonists of mu- (DAMGO), delta- (DPDPE), and kappa- (U-69,593) opioid receptors stimulated [(35)S]GTPgammaS binding in the caudate putamen and cortex of wild-type mice. In contrast, only U-69,593 stimulated [(35)S]GTPgammaS binding in these regions of mu-opioid receptor knockout mice. These results confirmed the absence of G-protein activation by a mu-opioid receptor agonist in mu-opioid receptor knockout mice, and demonstrated that coupling of the kappa-opioid receptor to G-proteins is preserved in these mice. However, G-protein activation by the delta-opioid receptor agonist, DPDPE, was reduced in the mu-opioid receptor knockout mice, at least in the brain regions studied using autoradiography.

Alleles↗

PubMed2000

Involvement of mu-opioid receptors in potentiation of apomorphine-induced climbing behavior by morphine: studies using mu-opioid receptor gene knockout mice.

The present study examined the hypothesis that mu-opioid receptors contribute to a behavioral stimulation produced by stimulation of dopamine receptors by comparing responses in mu-opioid receptor knockout and wild type mice. Apomorphine-induced climbing behavior was augmented by 65%, in wild type mice, but not in mu-knockout, following subcutaneous administration of morphine (15 mg/kg). Moreover, pretreatment with either naloxone (an opioid receptor antagonist) or haloperidol (a mixed D(1)/D(2) receptor antagonist) eliminated the enhancement by morphine of climbing behavior in wild type mice. These results indicate that expression of mu-opioid receptors plays an important role in the enhancement of climbing behavior induced by the dopamine receptor agonist, apomorphine. Furthermore, this augmentation is mediated by interaction between dopamine and mu-opioid receptors.

Analgesics, Opioid↗

PubMed2000

Effect of gestational and lactational 2,3,7, 8-tetrachlorodibenzo-p-dioxin exposure on the level and catalytic activities of hepatic microsomal CYP1A in prepubertal and adult rats.

We determined the inducibility, as well as the persistence of the induction, of hepatic microsomal CYP1A1 and CYP1A2 (by western blot analysis), and their catalytic activities (as measured by resorufin ether O-dealkylation) in prepubertal (25-day-old) and adult (120-day-old) offspring of timed-pregnant Sprague-Dawley rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD treatment was subcutaneous, at a low dose of 0.1 microg/kg, on gestational days 7, 14, and 20, and on lactational days 7 and 14. CYP1A1 protein was induced significantly (23-fold) in prepubertal but not in adult offspring of TCDD-exposed dams, whereas ethoxyresorufin O-deethylase (EROD) activity, which is CYP1A1-preferential, was induced less extensively (5-fold) and slightly (1.7-fold) in the prepubertal and adult offspring, respectively. Benzyloxyresorufin O-debenzylase (BROD) activity, which is CYP2B-preferential but has been reported to be catalyzed by CYP1A1, was also induced 5- and 6-fold in prepubertal and adult offspring, respectively, of TCDD-exposed dams. However, the induced BROD activity was neither inhibited by antibody against CYP1A1 nor accompanied by an elevated level of microsomal CYP2B. CYP1A2 was induced slightly only in prepubertal offspring of TCDD-treated dams. There was suggestive evidence of enhanced lipid peroxidation in hepatic microsomes from prepubertal but not adult offspring of TCDD-treated dams. These data showed that in utero plus lactational TCDD exposure effected transient induction of hepatic microsomal CYP1A1 but sustained induction of BROD activity, which may be catalyzed by enzymes other than CYP1A or CYP2B.

Animals↗

PubMed2000

kappa-opioid agonist stimulated regional distribution of [(35)S]GTPgammas binding in butorphanol continuously infused rat.

Butorphanol is a mixed agonist/antagonist opioid analgesic agent, which exerts its effects mainly by interaction with the kappa-opioid receptor. Opioid receptors are coupled to G proteins of G(i)/G(o) family, and recently a decrease in micro-opioid activation of G proteins has been reported in specific brainstem nuclei after chronic morphine administration. The influence of centrally administered butorphanol on agonist-stimulated G protein coupling was examined in the rat brain, using in situ guanylyl-5'-O-(gamma-[(35)S]thio)-triphosphate (GTPgammaS) binding autoradiography. Rats were treated with butorphanol (26 nmol/microl/h) by intracerebroventricular infusion via osmotic minipumps for 3 days. The distribution of [(35)S]GTPgammaS binding in the brain 7 h after the termination of butorphanol infusion was measured in the presence or absence of the selective kappa-opioid agonist, U-50,488. This agonist significantly increased [(35)S]GTPgammaS binding in the parietal cortex, caudate putamen, thalamus, and central gray of control rats, but not in those regions of the butorphanol-infused animals. These results suggest that chronic administration of butorphanol developed tolerance and abolished U-50,488 activation of G proteins in these brain areas.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed2000

Ordered assembly of roX RNAs into MSL complexes on the dosage-compensated X chromosome in Drosophila.

BACKGROUND: In the male Drosophila, the X chromosome is transcriptionally upregulated to achieve dosage compensation, in a process that depends on association of the MSL proteins with the X chromosome. A role for non-coding RNAs has been suggested in recent studies. The roX1 and roX2 RNAs are male-specific, non-coding RNAs that are produced by, and also found associated with, the dosage-compensated male X chromosome. Whether roX RNAs are physically part of the MSL complex has not been resolved. RESULTS: We found that roX RNAs colocalize with the MSL proteins and are highly unstable unless the MSL complex is coexpressed, suggesting a physical interaction. We were able to immunoprecipitate roX2 RNA from male tissue-culture cells with antibodies to the proteins Msl1 and Mle, consistent with an integral association with MSL complexes. Localization of roX1 and roX2 RNAs in mutants indicated an order of MSL-complex assembly in which roX2 RNA is incorporated early in a process requiring the Mle helicase. We also found that the roX2 gene, like roX1, is a nucleation site for MSL complex spreading into flanking chromatin in cis. CONCLUSIONS: Our results support a model in which MSL proteins assemble at specific chromatin entry sites (including the roX1 and roX2 genes); the roX RNAs join the complex at their sites of synthesis; and complete complexes spread in cis to dosage compensate most genes on the X chromosome.

Animals↗

PubMed2000

Biodistribution, metabolism, and in vivo gene expression of low molecular weight glycopeptide polyethylene glycol peptide DNA co-condensates.

The biodistribution, metabolism, cellular targeting, and gene expression of a nonviral peptide DNA gene delivery system was examined. (125)I-labeled plasmid DNA was condensed with low molecular weight peptide conjugates and dosed i.v. in mice to determine the influence of peptide DNA formulation parameters on specific gene targeting to hepatocytes. Optimal targeting to hepatocytes required the combined use of a triantennary glycopeptide (Tri-CWK(18)) and a polyethylene glycol-peptide (PEG-CWK(18)) to mediate specific recognition by the asialoglycoprotein receptor and to reduce nonspecific uptake by Kupffer cells. Tri-CWK(18)/PEG-CWK(18) DNA co-condensates were stabilized and protected from metabolism by glutaraldehyde crosslinking. An optimized formulation targeted 60% of the dose to the liver with 80% of the liver targeted DNA localized to hepatocytes. Glutaraldehyde crosslinking of DNA condensates reduced the liver elimination rate from a t((1/2)) of 0.8 to 3.6 h. An optimized gene delivery formulation produced detectable levels of human alpha1-antitrypsin in mouse serum which peaked at day 7 compared to no expression using control formulations. The results demonstrate the application of formulation optimization to improve the targeting selectivity and gene expression of a peptide DNA delivery system.

Animals↗

PubMed2000

Environmental conditions modulate the expression of the sspA and sspB genes in Streptococcus gordonii.

The SspA and SspB surface proteins of Streptococcus gordonii are multifunctional adhesins encoded by tandemly arranged genes. The transcriptional regulation of the sspA and sspB genes was investigated by generating chromosomal promoter- cat gene fusions and measuring CAT enzyme activity. The sspA promoter was found to be three-fold more active than the sspB promoter. In addition, sspA transcriptional activity increased throughout growth, whereas sspB activity decreased in stationary phase. Promoter activity of both sspA and sspB was regulated in response to temperature, pH and osmolarity; however the two promoters showed a different pattern of regulation. Changes in promoter activity were reflected in levels of surface protein and in adherence of S. gordonii to Porphyromonas gingivalis, a phenotypic property dependent on Ssp proteins. The results show that S. gordonii strain DL1 differentially regulates sspA and sspB transcription in response to oral environmental cues, suggesting that the SspA and SspB polypeptides may have distinct functional roles in cell adherence to oral substrates.

Adhesins, Bacterial↗