Biomedical subjects

C Deng

Publications and source records attributed to C Deng.

At least 19 recordsLinked to original sources

PubMed2006

Fatty acids differentially affect serotonin receptor and transporter binding in the rat brain.

The aim of this study was to examine the influence of different fat diets on serotonin receptor and transporter binding. Male Sprague-Dawley rats were fed a diet of either high saturated fat, omega-6 polyunsaturated fatty acid, omega-3 polyunsaturated fatty acid or low fat (control) for eight weeks. Using Beta-Imager quantification techniques, [(3)H]ketanserin, [(3)H]mesulergine and [(3)H]paroxetine binding to serotonin (5-HT)(2A), 5-HT(2C) receptors and 5-HT transporters (5-HTT) was measured throughout the brain in all four groups. All three high fatty acid diets influenced serotonin receptor binding, however the most pronounced effects were that compared with the low fat control group, i) 5-HT(2A) receptor binding was increased in the caudate putamen, but reduced in the mammillary nucleus in high saturated fat and high omega-6 polyunsaturated fatty acid diet groups; ii) 5-HT(2C) receptor binding was reduced in the mamillary nucleus of saturated fat group and reduced in prefrontal cortex of the omega-6 polyunsaturated fatty acid and omega-3 polyunsaturated fatty acid groups; and iii) 5-HTT binding was reduced in the hippocampus in the omega-6 polyunsaturated fatty acid group. Overall, the omega-6 polyunsaturated fatty acid diet exerted the most influence on serotonin receptor and transporter binding. These results may be of importance in relation to neuropsychiatric diseases such as schizophrenia, where associations between altered fatty acid levels and the serotonergic system have been made.

Analysis of Variance↗

PubMed2004

Corticosterone treatment of the chick embryo affects light-stimulated development of the thalamofugal visual pathway.

By injecting a single 60 microg dose of corticosterone into the eggs of domestic chicks on day 18 of incubation, we have shown that elevated levels of this hormone affect the development of asymmetry in the visual projections from the thalamus to the Wulst regions in the left and right hemispheres of the forebrain. In vehicle-treated (control) embryos this visual pathway develops asymmetry in response to light stimulation during the final stages of incubation, when the embryo is oriented so that its left eye is occluded by its body and its right eye can be stimulated by light entering through the egg shell. Pre-hatching exposure to light leads to more projections from the left side of the thalamus to the right Wulst than from the right side of the thalamus to the left Wulst, as confirmed here by injection of the tracers Fluorogold and Rhodamine into the left and right Wulst followed by counting the number of labelled cell bodies in the thalamus (asymmetry greater in males than females). The chicks injected with corticosterone pre-hatching did not develop any group bias for asymmetry in response to light exposure before hatching. They were random with respect to presence/absence of lateralization and, when present, the lateralization was not as strong as in the controls and its direction was random. The corticosterone-treated group had fewer projections from the left side of the thalamus to the right Wulst than did the controls. The results are considered with respect to maternal deposits of the hormone in the yolk and pre-hatching stress of the embryo.

Animals↗

PubMed2003

Molecular characterization of a distinct potyvirus from whitegrass in China.

Apotyvirus isolated from perennial whitegrass ( Pennisetum centrasiaticum Tzvel.) in North China was characterized at the molecular level. The 3' terminal nucleotide (nt) sequence of 1669 nt of the viral RNA genome has been determined, which covered the coding region of the C-terminal part of the large nuclear inclusion protein (NIb, RNA polymerase), capsid protein (CP) gene and the 3' nontranslated region (NTR). The CP gene consisted of 909 nt (including the stop codon) encoding 302 amino acid residues, and the 3' NTR was 241 nt in length excluding the polyadenylated tract. Sequence comparison of the amino acids of CPs showed that this virus was most closely related to Sorghum mosaic virus and Maize dwarf mosaic virus with percent identities of 77% to 78% while that of the 3' NTRs suggested that it was most closely related to Zea mosaic virus with identity of 72%. This virus isolate was to some extent closely related to other members of the Sugarcane mosaic virus subgroup of potyviruses for the CP amino acid sequences. Phylogenetic analyses of the sequences indicated that this virus isolate represented a distinct potyvirus, and the name Pennisetum mosaic virus (PenMV) is proposed.

Capsid Proteins↗

PubMed2003

Comparison of water and lipid content measurements using diffuse optical spectroscopy and MRI in emulsion phantoms.

We present a quantitative comparison of lipid and water signals obtained from broadband Diffuse Optical Spectroscopy (DOS) and Magnetic Resonance Imaging (MRI). DOS and MRI measurements were performed on an identical set of emulsion phantoms that were composed of different water/soybean oil fractions. Absolute concentrations of water and lipid ranging from 35-94% and 63-6%, respectively were calculated from quantitative broadband near-infrared (NIR) absorption spectra (650-1000 nm). MR images of fat and water were separated using the three-point Dixon technique. DOS and MRI measured water and lipid were highly correlated (R(2) = 0.98 and R(2) = 0.99, respectively) suggesting that these techniques are complementary over a broad range of physiologically relevant water and lipid values. In addition, comparison of DOS derived concentrations to the MRI "gold standard" technique validates our quantitation approach and permits estimation of DOS accuracy and sensitivity in vivo.

Emulsions↗

PubMed2003

M1-M5 muscarinic receptor knockout mice as novel tools to study the physiological roles of the muscarinic cholinergic system.

A large body of evidence indicates that muscarinic acetylcholine receptors (mAChRs) play critical roles in regulating the activity of many important functions of the central and peripheral nervous systems. However, identification of the physiological and pathophysiological roles of the individual mAChR subtypes (M(1)-M(5)) has proven a difficult task, primarily due to the lack of ligands endowed with a high degree of receptor subtype selectivity and the fact that most tissues and organs express multiple mAChRs. To circumvent these difficulties, we used gene targeting technology to generate mutant mouse lines containing inactivating mutations of the M(1)-M(5) mAChR genes. The different mAChR mutant mice and the corresponding wild-type control animals were subjected to a battery of physiological, pharmacological, behavioral, biochemical, and neurochemical tests. The M(1)-M(5) mAChR mutant mice were viable and reproduced normally. However, each mutant line displayed specific functional deficits, suggesting that each mAChR subtype mediates distinct physiological functions. These results should offer new perspectives for the rational development of novel muscarinic drugs.

Animals↗

PubMed2002

Smad 3 may regulate follicular growth in the mouse ovary.

Although Smad 3 is known to serve as a signaling intermediate for the transforming growth factor beta (TGFbeta) family in nonreproductive tissues, its role in the ovary is unknown. Thus, we used a recently generated Smad 3-deficient (Smad 3-/-) mouse model to test the hypothesis that Smad 3 alters female fertility and regulates the growth of ovarian follicles from the primordial stage to the antral stage. In addition, we tested whether Smad 3 affects the levels of proteins that control apoptosis, survival, and proliferation in the ovarian follicle. To test this hypothesis, breeding studies were conducted using Smad 3-/- and wild-type mice. In addition, ovaries were collected from Smad 3-/- and wild-type mice on Postnatal Days 2-90. One ovary from each animal was used to estimate the total number of primordial, primary, and antral follicles. The other ovary was used for immunohistochemical analysis of selected members of the B-cell lymphoma/leukemia-2 family of protooncogenes (Bax, Bcl-2, Bcl-x), proliferating cell nuclear antigen (PCNA), and cyclin-dependent kinase 2 (Cdk-2). The results indicate that Smad 3-/- mice have reduced fertility compared with wild type mice. The results also indicate that Smad 3 may not affect the size of the primordial follicle pool at birth, but it may regulate growth of primordial follicles to the antral stage. Further, the results indicate that Smad 3 may regulate the expression of Bax and Bcl-2, but not Bcl-x, Cdk-2, and PCNA. Collectively, these data suggest that Smad 3 may play an important role in the regulation of ovarian follicle growth and female fertility.

Animals↗

PubMed2001

Targeted mutagenesis of Smad1 reveals an essential role in chorioallantoic fusion.

The Smad family of intracellular signaling intermediates transduce signals downstream from the transforming growth factor beta (TGF-beta) family of receptor serine threonine kinases. The original member of this family, Smad1, has been shown to mediate signals from receptors for the bone morphogenetic proteins (BMPs), a large group of ligands in the TGF-beta superfamily that mediate important developmental events. We have targeted the Smad1 gene in mice and created mutants null at this locus. Smad1 mutant mice die at approximately 9.5 days postcoitum due to defects in allantois formation. In Smad1 mutant mice, the allantois fails to fuse to the chorion, resulting in a lack of placenta and failure to establish a definitive embryonic circulation. Although vasculogenesis is initiated in the mutant allantois, the vessels formed are disorganized, and VCAM-1 protein, a marker for distal allantois development, is not expressed. Smad1 null fibroblasts are still able to respond to BMP2, however, suggesting that the defect observed in the developing extraembryonic tissue is caused by a very specific loss of transcriptional activity regulated by Smad1. Our data further demonstrate that although highly similar structurally, Smad proteins are not functionally homologous.

Allantoin↗

PubMed2001

[Association of tumor necrosis factor microsatellite polymorphism with chronic atrophic gastritis and gastric adenocarcinoma].

OBJECTIVE: To investigate whether TNFd and TNFe microsatellite polymorphisms correlate with chronic atrophic gastritis and gastric adenocarcinoma in Chinese Han population. METHODS: In 164 healthy controls, 53 patients with chronic atrophic gastritis, and 56 patients with gastric adenocarcinoma, TNFd and TNFe microsatellite alleles were typed using PCR technique, followed by high-voltage denaturing PAGE, with silver staining. At the same time, the PCR products were cloned and sequenced. RESULTS: Fight alleles at the TNFd locus and four alleles at the TNFe locus were detected. A new allele was found and identified, its accession number of Genebank is AF315593. Statistical analysis showed that there existed a very strong linkage equilibrium between TNFd8 and TNFe4 allele. No difference was observed between patients and healthy controls in the distribution of alleles at the TNFd and TNFe loci (P > 0.05). The frequence of d2/d6 genotype was significantly higher in patients with gastric adenocarcinoma than in healthy individuals (P = 0.028). d2/d6 genotype wasn't related to age or gender or grade of differentiation or clinicopathologic stage in gastric adenocarcinoma. CONCLUSION: d8e4 haplotype appears to be specific of Chinese population. d2/d6 genotype is associated with the susceptibility to gastric adenocarcinoma.

Adenocarcinoma↗

PubMed2001

Antagonistic effects of Smad2 versus Smad7 are sensitive to their expression level during tooth development.

Members of the transforming growth factor-beta (TGF-beta) superfamily regulate cell proliferation, differentiation, and apoptosis, controlling the development and maintenance of most tissues. TGF-beta signal is transmitted through the phosphorylation of Smad proteins by TGF-beta receptor serine/threonine kinase. During early tooth development, TGF-beta inhibits proliferation of enamel organ epithelial cells but the underlying molecular mechanisms are largely unknown. Here we tested the hypothesis that antagonistic effects between Smad2 and Smad7 regulate TGF-beta signaling during tooth development. Attenuation of Smad2 gene expression resulted in significant advancement of embryonic tooth development with increased proliferation of enamel organ epithelial cells, while attenuation of Smad7 resulted in significant inhibition of embryonic tooth development with increased apoptotic activity within enamel organ epithelium. These findings suggest that different Smads may have differential activities in regulating TGF-beta-mediated cell proliferation and death. Furthermore, functional haploinsufficiency of Smad2, but not Smad3, altered TGF-beta-mediated tooth development. The results indicate that Smads are critical factors in orchestrating TGF-beta-mediated gene regulation during embryonic tooth development. The effectiveness of TGF-beta signaling is highly sensitive to the level of Smad gene expression.

Animals↗

PubMed2001

Similarity of the song nuclei of male and female Australian magpies (Gymnorhina tibicen).

The organisation of the song control nuclei of the Australian magpie (Gymnorhina tibicen), a species with highly complex song, was investigated. In contrast to most of the songbirds studied so far, the Australian magpie sings throughout the year and both males and females sing. All of the forebrain song nuclei, including the high vocal centre (HVC), the robust nucleus of the archistriatum (RA), Area X and the lateral and medial magnocellular nuclei of the anterior neostriatum (lMAN and mMAN) were found to be well developed in both male and female magpies. Consistent with the known vocal competence of juvenile magpies, all of the song nuclei were also well-developed in juvenile magpies (2--3 months old). HVC in both male and female magpies consists of a rostrolateral and a caudomedial region. The ventromedial part of RA differs from the dorsolateral part by having medium-sized neurons packed in higher density. The HVC to RA projections were labelled anterogradely by DiI and DiA. However, no HVC to Area X projections were labeled by DiI or DiA, suggesting a possible difference from songbirds studied previously.

Animals↗

PubMed2001

Overexpression of Smad2 reveals its concerted action with Smad4 in regulating TGF-beta-mediated epidermal homeostasis.

Members of the transforming growth factor-beta (TGF-beta) superfamily are critical regulators for epithelial growth and can alter the differentiation of keratinocytes. Transduction of TGF-beta signaling depends on the phosphorylation and activation of Smad proteins by heteromeric complexes of ligand-specific type I and II receptors. To understand the function of TGF-beta and activin-specific Smad, we generated transgenic mice that overexpress Smad2 in epidermis under the control of keratin 14 promoter. Overexpression of Smad2 increases endogenous Smad4 and TGF-beta 1 expression while heterozygous loss of Smad2 reduces their expression levels, suggesting a concerted action of Smad2 and -4 in regulating TGF-beta signaling during skin development. These transgenic mice have delayed hair growth, underdeveloped ears, and shorter tails. In their skin, there is severe thickening of the epidermis with disorganized epidermal architecture, indistinguishable basement membrane, and dermal fibrosis. These abnormal phenotypes are due to increased proliferation of the basal epidermal cells and abnormalities in the program of keratinocyte differentiation. The ectodermally derived enamel structure is also abnormal. Collectively, our study presents the first in vivo evidence that, by providing an auto-feedback in TGF-beta signaling, Smad2 plays a pivotal role in regulating TGF-beta-mediated epidermal homeostasis.

Animals↗

PubMed2001

Functional characterization of transforming growth factor beta signaling in Smad2- and Smad3-deficient fibroblasts.

A prominent pathway of transforming growth factor (TGF)-beta signaling involves receptor-dependent phosphorylation of Smad2 and Smad3, which then translocate to the nucleus to activate transcription of target genes. To investigate the relative importance of these two Smad proteins in TGF-beta1 signal transduction, we have utilized a loss of function approach, based on analysis of the effects of TGF-beta1 on fibroblasts derived from mouse embryos deficient in Smad2 (S2KO) or Smad3 (S3KO). TGF-beta1 caused 50% inhibition of cellular proliferation in wild-type fibroblasts as assessed by [(3)H]thymidine incorporation, whereas the growth of S2KO or S3KO cells was only weakly inhibited by TGF-beta1. Lack of Smad2 or Smad3 expression did not affect TGF-beta1-induced fibronectin synthesis but resulted in markedly suppressed induction of plasminogen activator inhibitor-1 by TGF-beta1. Moreover, TGF-beta1-mediated induction of matrix metalloproteinase-2 was selectively dependent on Smad2, whereas induction of c-fos, Smad7, and TGF-beta1 autoinduction relied on expression of Smad3. Investigation of transcriptional activation of TGF-beta-sensitive reporter genes in the different fibroblasts showed that activation of the (Smad binding element)(4)-Lux reporter by TGF-beta1 was dependent on expression of Smad3, but not Smad2, whereas activation of the activin response element-Lux reporter was strongly suppressed in S2KO fibroblasts but, on the contrary, enhanced in S3KO cells. Our findings indicate specific roles for Smad2 and Smad3 in TGF-beta1 signaling.

Animals↗

PubMed2001

A Ser(365)-->Cys mutation of fibroblast growth factor receptor 3 in mouse downregulates Ihh/PTHrP signals and causes severe achondroplasia.

Missense mutations in fibroblast growth factor receptor 3 (FGFR3) result in several types of human skeletal dysplasia, including the neonatally lethal dwarfism known as thanatophoric dysplasia. An engineered Ser(365)-->Cys substitution in mouse FGFR3, which is equivalent to a mutation associated with thanatophoric dysplasia-I in humans, has now been shown to cause severe dwarfism but not neonatal death. The mutant mice exhibit shortened limbs as a result of markedly reduced proliferation and impaired differentiation of growth plate chondrocytes. The receptor-activating mutation also resulted in downregulation of expression of the Indian hedgehog (IHH) and parathyroid hormone-related protein (PTHrP) receptor genes, both of which are important for bone growth. Interactions between FGFR3- and PTHrP-receptor-mediated signals during endochondral ossification were examined with embryonic metatarsal bones maintained in culture under defined conditions. Consistent with the in vivo observations, FGF2 inhibited bone growth in culture and induced downregulation of IHH and PTHrP receptor gene expression. Furthermore, PTHrP partially reversed the inhibition of long bone growth caused by activation of FGFR3; however, it impaired the differentiation of chondrocytes in an FGFR3-independent manner. These observations suggest that FGFR3 and IHH-PTHrP signals are transmitted by two interacting parallel pathways that mediate both overlapping and distinct functions during endochondral ossification.

Achondroplasia↗

PubMed2001

Fas/Fas ligand pathway, apoptosis, and clonal anergy involved in systemic acetylcholine receptor T cell epitope tolerance.

The cellular mechanisms of high dose systemic acetylcholine receptor (AChR) T cell epitope, alpha 146--162 peptide-induced tolerance in experimental myasthenia gravis were examined. CD4 cells are the prime target for alpha 146--162 peptide-induced tolerance. The expression of CD69, Fas, and B7.2 molecules on AChR-immune lymphocytes was enhanced within 4--12 h after tolerance induction. A high dose of alpha 146--162 peptide in IFA failed to suppress T cell proliferation and/or clinical myasthenia gravis in lpr and gld mice deficient in Fas and Fas ligand, respectively. A high dose of alpha 146--162 peptide in IFA in AChR-immunized mice induced apoptosis of BV6 cells. Further, reconstitution of IL-2 in vitro-recovered alpha 146--162 peptide tolerized T cell proliferation, IFN-gamma, and IL-10 production. The findings implicate the possible role of Fas-/Fas ligand-mediated apoptosis and the resulting clonal anergy as the mechanisms of high dose AChR alpha 146--162 peptide-induced tolerance on CD4 cells.

Adjuvants, Immunologic↗

PubMed2001

Lymphotoxin-alpha deficiency completely protects C57BL/6 mice from developing clinical experimental autoimmune myasthenia gravis.

A complete prevention of clinical experimental autoimmune myasthenia gravis (EAMG) was observed in lymphotoxin (LT)-alpha deficient (LT-alpha(-/-)) mice compared to LT-alpha(+/+) mice when immunized with acetylcholine receptor. However, only a partial prevention of clinical EAMG incidence was observed in LT-beta(-/-) mice compared to LT-beta(+/+) mice. LT-alpha(-/-)and LT-beta(-/-) mice had lower mean titers of total IgG, IgG(1), IgG(2a) and IgG(2b) and higher or equal mean titers of IgM anti-AChR antibodies compared to controls. Therefore, LT-alpha(-/-)and LT-beta(-/-) AChR immunized mice are capable of mounting a primary (IgM) humoral immune response to AChR, but are less capable of switching to the pathogenic anti-AChR IgG isotypes. LT could play a significant role in the pathogenesis of myasthenia gravis.

Animals↗

PubMed2001

Role of nerve growth factor in experimental autoimmune encephalomyelitis.

The expression of neural regulatory molecules by immune cells that infiltrate the nervous system upon injury may be a mechanism for cross-regulation between the nervous system and the immune system. Several lines of evidence implicate nerve growth factor (NGF) signaling through its receptors (TrkA and p75(NGFR)) as a potential source of communication between the two systems. We observed changes in NGF mRNA expression and protein secretion by T lymphocytes polarized toward the Th2 phenotype. The presence of NGF did not affect T cell proliferation or cytokine production in vitro. Mice treated with NGF by i. p. injection following induction of experimental autoimmune encephalomyelitis, an inflammatory, demyelinating disease of the central nervous system, showed a delayed onset of disease and lower clinical scores during the course of disease. These data suggest a role for NGF signaling in the regulation of the immune response, possibly by enhancing sympathetic innervation of lymphoid tissues.

Animals↗

PubMed2001

Decreased Ras-mitogen-activated protein kinase signaling may cause DNA hypomethylation in T lymphocytes from lupus patients.

OBJECTIVE: Previous studies have shown that inhibiting T cell DNA methylation causes a lupus-like disease by modifying gene expression. T cells from patients with lupus exhibit diminished levels of DNA methyltransferase (MTase) enzyme activity, hypomethylated DNA, and changes in gene expression similar to those exhibited by T cells treated with methylation inhibitors, suggesting that DNA hypomethylation may contribute to human lupus. Since it is known that DNA MTase levels are regulated by the ras-mitogen-activated protein kinase (MAPK) pathway, this study sought to determine whether decreased ras-MAPK signaling could account for the DNA hypomethylation in lupus T cells. METHODS: DNA MTase messenger RNA (mRNA) from lupus patients and from healthy controls was quantitated by Northern analysis, and ras-MAPK signaling was determined by immunoblotting with antibodies to the activated forms of extracellular receptor-associated kinase (ERK). Results were compared with those in T cells in which ras-MAPK signaling was inhibited with a soluble inhibitor of MAPK ERK I (MEK1). RESULTS: T cells from patients with active lupus had diminished DNA MTase mRNA levels and decreased signaling through the ras-MAPK pathway. Inhibiting signaling through the ras-MAPK pathway with the MEK1 inhibitor decreased DNA MTase mRNA and enzyme activity to the levels seen in lupus T cells, and resulted in DNA hypomethylation resembling that seen in lupus T cells. CONCLUSION: These results suggest that a decrease in signaling through the ras-MAPK pathway may be responsible for the decreased MTase activity and DNA hypomethylation in patients with lupus.

Adolescent↗

PubMed2001

RIM4 encodes a meiotic activator required for early events of meiosis in Saccharomyces cerevisiae.

RIM4 was previously found to be required for both the IME1- and IME2-dependent pathways of meiotic gene expression in Saccharomyces cerevisiae. We now demonstrate that RIM4 is also required for meiotic division and recombination. Furthermore, rim4Delta mutants show defects in premeiotic DNA synthesis, which can be suppressed by deletion of the SIC1 gene, which encodes a Cdk inhibitor. Expression of RIM4 is induced early in meiosis, and is dependent on IME1 but not IME2. Indeed, RIM4 itself is essential for the meiotic expression of IME2. These results suggest that RIM4 is epistatic to IME2, and is required for multiple steps during sporulation. In agreement with this interpretation, overexpression of RIM4 induces low levels of sporulation in rich medium.

Blotting, Northern↗