Biomedical subjects

Jun Wang

Publications and source records attributed to Jun Wang.

At least 271 records · Page 15Linked to original sources

PubMed2005

A mitochondrial genome sequence of the Tibetan antelope (Pantholops hodgsonii).

To investigate genetic mechanisms of high altitude adaptations of native mammals on the Tibetan Plateau, we compared mitochondrial sequences of the endangered Pantholops hodgsonii with its lowland distant relatives Ovis aries and Capra hircus, as well as other mammals. The complete mitochondrial genome of P. hodgsonii (16,498 bp) revealed a similar gene order as of other mammals. Because of tandem duplications, the control region of P. hodgsonii mitochondrial genome is shorter than those of O. aries and C. hircus, but longer than those of Bos species. Phylogenetic analysis based on alignments of the entire cytochrome b genes suggested that P. hodgsonii is more closely related to O. aries and C. hircus, rather than to species of the Antilopinae subfamily. The estimated divergence time between P. hodgsonii and O. aries is about 2.25 million years ago. Further analysis on natural selection indicated that the COXI (cytochrome c oxidase subunit I) gene was under positive selection in P. hodgsonii and Bos grunniens. Considering the same climates and environments shared by these two mammalian species, we proposed that the mitochondrial COXI gene is probably relevant for these native mammals to adapt the high altitude environment unique to the Tibetan Plateau.

Amino Acid Sequence↗

PubMed2005

Anthrabenzoxocinones from Streptomyces sp. as liver X receptor ligands and antibacterial agents.

Liver X receptors (LXR) are nuclear hormone receptors that play a critical role in cholesterol homeostasis. They regulate the expression of the ABCA1 gene, which mediates the efflux of cholesterol out of cells. LXR agonists are expected to increase cholesterol efflux, lower LDL, and raise HDL levels. Screening of a natural product library of microbial extracts using a LXR-SPA binding assay and bioassay-guided fractionation of an active extract of a Streptomyces sp. (MA6657) led to the discovery of two new hexacyclic aromatic ketones, (-)-anthrabenzoxocinone [(-)-ABX (1)], an enantiomer of BE-24566B, and (-)-bischloroanthrabenzoxocinone [(-)-BABX (2)]. The IC50 values of LXRalpha-SPA binding are 2 microM for (-)-ABX and 10 microM for (-)-BABX. This extract was also found to inhibit type II fatty acid synthesis, and its active component, (-)-BABX, was responsible for the majority of the inhibition. All three compounds showed good Gram-positive antibacterial activity (MIC 0.5-2 microg/mL). Details of the isolation, structure elucidation, LXR ligand binding, antibacterial activity, and selectivity of inhibition of 1 and 2 are described.

Anthraquinones↗

PubMed2005

Molecular signaling aptamers for real-time fluorescence analysis of protein.

Aptamers are a new class of nucleic acids that are selected in vitro for binding target molecules with high affinity and selectivity. They are promising protein-binding molecular probes that rival conventional antibodies for protein analysis. There have been recent advances in the development of molecular signaling aptamers that can transduce target protein binding to sensitive fluorescence signal changes. This facilitates the real time protein monitoring in homogenous solution as well as potentially in vivo. Different signaling strategies of using dual labeled aptamers based on fluorescence resonance energy transfer (FRET), one fluorophore labeled aptamers based on fluorescence anisotropy assay, or other label-free aptamers are reviewed.

Anisotropy↗

PubMed2005

TNFR1- and TNFR2-mediated signaling pathways in human kidney are cell type-specific and differentially contribute to renal injury.

In normal kidney, TNFR1 is expressed in glomerular and peritubular capillary EC, and some tubular cells, and colocalizes with inactive apoptosis signal-regulating kinase-1 (ASK1) phosphorylated at serine 967. Biopsies of rejecting or ischemic renal allografts, which show both tubular cell injury and proliferation, display down-regulation of TNFR1 and activation of ASK1 as well as up-regulation of TNFR2 on tubular cells, where it colocalizes with phosphorylated endothelial/epithelial tyrosine kinase (Etk). We have exploited receptor-selective muteins and evaluated phosphorylation of receptor-specific kinases to study TNF responses in situ. In organ culture, a TNFR1-specific mutein changes phosphorylation of ASK1 to threonine 845, indicative of kinase activation. A TNFR2-specific mutein down-regulates TNFR1 in glomerular EC, up-regulates TNFR2 and Etk in tubular cells, and induces phosphorylation of Etk. Wild-type TNF induces TNFR2 and Etk and activates both ASK1 and Etk but does not down-regulate TNFR1. Wild-type TNF and TNFR1-specific mutein trigger tubular cell apoptosis whereas wild-type TNF and TNFR2-specific mutein induce tubular cells to express proliferating cell nuclear antigen. Differential activation of ASK1 and Etk by regulated TNFRs in patient-derived materials provides an explanation for diverse and opposing responses to TNF at distinct sites, and an in situ bioassay of TNFR signaling.

Apoptosis↗

PubMed2005

T-cell/histiocyte-rich large B-cell lymphoma displays a heterogeneity similar to diffuse large B-cell lymphoma: a clinicopathologic, immunohistochemical, and molecular study of 30 cases.

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL), a proliferating peripheral B-cell neoplasm, is a morphologic variant of diffuse large B-cell lymphoma (DLBCL), which may be confused with Hodgkin's lymphoma, non-Hodgkin's lymphoma, and reactive lymphadenopathies. Though more recent studies suggested that it might be a distinct clinicopathologic entity and/or a heterogeneous entity with derivation from germinal center B cells, its histogenetic derivation remains controversial. The authors analyzed 30 cases of THRLBCL to further characterize the origin of the neoplastic cells using immunohistochemical and molecular studies for expression of Bcl-6, CD10, and CD138, as well as rearrangements of IgH/bcl-2 genes on paraffin-embedded tissue. Half of the cases (15/30) showed Bcl-6 expression and five cases (19%) showed CD10 expression, but none had CD138 expression (0/20). Only three cases showed coexpression of both Bcl-6 and CD10. Molecular studies performed in 21 cases detected rearrangement of immunoglobulin heavy gene in 18 cases, with none having detectable Bcl-2 gene rearrangement. These data indicate that similar to DLBCL, the cell origin of neoplastic cells in THRLBCL is composed of a heterogeneous group of proliferating peripheral B cells, with only some cases originating from germinal center B cells and others derived from heterogeneous origins. Lack of Bcl-2 gene rearrangements seems to argue against a possible progression from preexisting follicular lymphoma. Thus, the normal counterpart of the neoplastic cells cannot at this time be the sole basis for the subclassification of THRLBCL.

Adolescent↗

PubMed2005

Primary diffuse large B-cell lymphoma of the uterus presenting solely as an endometrial polyp.

We report a primary diffuse large B-cell lymphoma of endometrial polyp in a 44-year-old woman who presented with irregular vaginal spotting and was found to have a polyp protruding from the cervical os. Histology of the polyp showed an atypical diffuse infiltration by large, mononuclear cells within the stroma and between endometrial glands in one of the polypoid fragments. Immunohistochemistry and testing for immunoglobulin heavy chain gene rearrangement showed a B-cell lineage, consistent with diffuse large B-cell lymphoma. Staging procedures including detailed gynecology examination, body computed tomography scan, and bone marrow examination, as well as total hysterectomy, showed no evidence of lymphoma outside of the polyp. To our knowledge, this represents the first well-documented instance of primary lymphoma of the uterus presenting as an endometrial polyp. The differential diagnosis of endometrial biopsies containing an atypical lymphoid infiltrate should include the rather rare possibility of primary uterine lymphoma arising in an endometrial polyp. Immunohistochemistry and/or molecular analysis for antigen receptor gene rearrangements are critical in arriving at the correct diagnosis.

Adult↗

PubMed2005

Initial endometriosis showing direct morphologic evidence of metaplasia in the pathogenesis of ovarian endometriosis.

It is believed that ovarian endometriosis may be generated by a celomic metaplastic process from existing epithelium in the ovary. However, no morphologic evidence of metaplastic process has been described. In this study, we intended to identify the earliest morphologic changes of endometriosis within the ovary to examine if evidence of metaplasia exists. Included in this study were 110 ovarian endometriosis cases and 30 benign ovaries without endometriosis but with ovarian epithelial inclusions (OEIs). Among the 110 well-established ovarian endometriosis cases, 34 cases showed areas of initial endometriosis (IE), which is defined as lesions showing direct transitions from normal-looking ovarian tissue to areas of minimal formation of endometriosis and/or to areas of full-blown endometriosis. We further divided IE into two types: type I IE was present on the ovarian surface, which was associated with ovarian surface epithelia; type II was located within the ovarian cortex, which was associated with OEIs. Sections containing IE, OEIs, and well-formed endometriosis were subject to CD10 and aromatase immunostaining. In IE lesions, the number of CD10-positive cells were significantly higher than the number of that in OEIs, but lower than that of well-formed endometriosis areas (p < 0.05). Aromatase expression was detected in both epithelial and stromal components of the IE lesions, indicating that estrogen local production may be involved in this initial process of endometriosis. Microvessel density was higher in IE lesions than in areas of OEI (p < 0.05). Based on the morphologic characteristics of IE, we believe that IE represent a spectrum of the earliest morphologic changes of endometriosis identifiable by routine microscopy. The morphologic transitions from ovarian surface epithelium or OEI to IE lesions provide direct metaplastic evidence for the pathogenesis of ovarian endometriosis. This metaplastic process may not only involve the ovarian epithelial cells, but also stromal components. Local production of estrogen, probably in high-levels, may be related to the initial process of endometriosis, although detailed mechanisms remain to be clarified.

Adult↗

PubMed2005

Pseudogene accumulation might promote the adaptive microevolution of Yersinia pestis.

Plague is a natural focus-based disease, and for better understanding of this disease it is crucial to determine the molecular mechanisms of its pathogen, Yersinia pestis, for adapting to different foci. Gene inactivation, loss and acquisition are the main mechanisms that contribute to a pathogen's fitness. Determination of the whole-genome sequences of three Y. pestis strains, CO92, KIM and 91001, provided a good opportunity to probe into its genome in minute detail. Many genetic variations were found between the three strains. The present work focused on adaptive microevolutionary analysis of Y. pestis from different natural plague foci in China based on pseudogene profiles. Twenty-four mutations that led to inactivation in the corresponding genes were analysed, and a PCR-based screening method was employed to investigate the distribution of these mutations among Y. pestis isolates from different foci and also among seven strains of Yersinia pseudotuberculosis. It was found that Y. pestis isolates from the same focus had identical mutation profiles, and 260 isolates of Y. pestis were divided into eight genotypes, while Y. pseudotuberculosis harboured wild-type alleles for all the mutations. The isolates of three known biovars were grouped into distinct branches in the phylogenetic tree, which supports the proposition that biovars mediaevalis and orientalis directly arose from biovar antiqua individually. The constructed phylogenetic tree suggests that the isolates from focus B should be the oldest lineage of Y. pestis in China except for isolates from foci L and M, which might be a special lineage of Y. pestis and originated differently to the others.

Adaptation, Physiological↗

PubMed2005

A microarray analysis of the rice transcriptome and its comparison to Arabidopsis.

Arabidopsis and rice are the only two model plants whose finished phase genome sequence has been completed. Here we report the construction of an oligomer microarray based on the presently known and predicted gene models in the rice genome. This microarray was used to analyze the transcriptional activity of the gene models in representative rice organ types. Expression of 86% of the 41,754 known and predicted gene models was detected. A significant fraction of these expressed gene models are organized into chromosomal regions, about 100 kb in length, that exhibit a coexpression pattern. Compared with similar genome-wide surveys of the Arabidopsis transcriptome, our results indicate that similar proportions of the two genomes are expressed in their corresponding organ types. A large percentage of the rice gene models that lack significant Arabidopsis homologs are expressed. Furthermore, the expression patterns of rice and Arabidopsis best-matched homologous genes in distinct functional groups indicate dramatic differences in their degree of conservation between the two species. Thus, this initial comparative analysis reveals some basic similarities and differences between the Arabidopsis and rice transcriptomes.

Arabidopsis↗

PubMed2005

A recurrent neural network for solving nonlinear convex programs subject to linear constraints.

In this paper, we propose a recurrent neural network for solving nonlinear convex programming problems with linear constraints. The proposed neural network has a simpler structure and a lower complexity for implementation than the existing neural networks for solving such problems. It is shown here that the proposed neural network is stable in the sense of Lyapunov and globally convergent to an optimal solution within a finite time under the condition that the objective function is strictly convex. Compared with the existing convergence results, the present results do not require Lipschitz continuity condition on the objective function. Finally, examples are provided to show the applicability of the proposed neural network.

Neural Networks, Computer↗

PubMed2005

Global exponential periodicity of a class of recurrent neural networks with oscillating parameters and time-varying delays.

In this paper, we present the analytical results on the global exponential periodicity of a class of recurrent neural networks with oscillating parameters and time-varying delays. Sufficient conditions are derived for ascertaining the existence, uniqueness and global exponential periodicity of the oscillatory solution of such recurrent neural networks by using the comparison principle and mixed monotone operator method. The periodicity results extend or improve existing stability results for the class of recurrent neural networks with and without time delays.

Animals↗

PubMed2005

A primal-dual neural network for online resolving constrained kinematic redundancy in robot motion control.

This paper proposes a primal-dual neural network with a one-layer structure for online resolution of constrained kinematic redundancy in robot motion control. Unlike the Lagrangian network, the proposed neural network can handle physical constraints, such as joint limits and joint velocity limits. Compared with the existing primal-dual neural network, the proposed neural network has a low complexity for implementation. Compared with the existing dual neural network, the proposed neural network has no computation of matrix inversion. More importantly, the proposed neural network is theoretically proved to have not only a finite time convergence, but also an exponential convergence rate without any additional assumption. Simulation results show that the proposed neural network has a faster convergence rate than the dual neural network in effectively tracking for the motion control of kinematically redundant manipulators.

Algorithms↗

PubMed2005

Chromosomal DNA transfer in Mycobacterium smegmatis is mechanistically different from classical Hfr chromosomal DNA transfer.

Classical conjugal DNA transfer of chromosomal DNA in bacteria requires the presence of a cis-acting site, oriT, in the chromosome. Acquisition of an oriT occurs if a conjugative plasmid integrates into the chromosome to form an Hfr donor strain, which can transfer extensive regions of chromosomal DNA. Because oriT sequences are unique, and because transfer occurs in a 5' to 3' direction, the frequency with which a particular gene is inherited by the recipient depends on the gene's location: those closest to the 3' side of oriT are transferred most efficiently. In addition, as the entire chromosome must be transferred to regenerate oriT, Hfr transconjugants never become donors. Here we describe novel aspects of a chromosomal DNA transfer system in Mycobacterium smegmatis. We demonstrate that there are multiple transfer initiations from a donor chromosome and, as a result, the inheritance of any gene is location-independent. Transfer is not contiguous; instead, multiple non-linked segments of DNA can be inherited in a recipient. However, we show that, with appropriate selection, segments of DNA at least 266 kb in length can be transferred. In further contrast to Hfr transfer, transconjugants can become donors, suggesting that the recipient chromosome contains multiple cis-acting sequences required for transfer, but lacks the trans-acting transfer functions. We exploit these observations to map a donor-determining locus in the M. smegmatis chromosome using genetic linkage analysis. Together, these studies further underline the unique nature of the M. smegmatis chromosomal transfer system.

Blotting, Southern↗

PubMed2005

The effect of aging on the subcellular distribution of estrogen receptor-alpha in the cholinergic neurons of transgenic and wild-type mice.

The degeneration of the basal forebrain cholinergic system plays an important role in cognitive deterioration in aging and Alzheimer's disease. Brain cholinergic neurons and their projections are affected by changes in the circulating levels of estrogens, which exert their effects mainly through the estrogen receptors. In this study, we investigated the effect of aging, estrogen status and transgenic genotype on the number of cholinergic neurons and the estrogen receptor alpha (ERalpha) content in the medial septum-vertical limb of the diagonal band of Broca. We used 6- and 12-month-old female double transgenic mice carrying mutated human amyloid precursor protein (APPswe) and presenilin-1 (PS1-A246E), and their nontransgenic littermate controls, which had been sham-operated or ovariectomized at the age of 3 months. Brain sections were double immunostained for choline acetyltransferase (ChAT) and ERalpha and used for stereological cell counting. We found that the number of ChAT-immunoreactive (ir) neurons containing nuclear ERalpha-ir was significantly lower in 12- than in 6-month-old mice. However, the age of the mice, the transgenic genotype or ovariectomy had no effect on the total number of ChAT-ir neurons, or on the number and percentage of all ChAT-ir neurons that contained ERalpha. These results indicate that aging is associated with translocation of ERalphas from the nucleus to the cytoplasm. We propose that this phenomenon is linked to those age-related processes known to be involved in inhibiting ERalpha binding to nuclei.

Acetylcholine↗

PubMed2005

Sp1 and Sp3 activate transcription of the human dopamine transporter gene.

The dopamine transporter is a plasma membrane protein that controls extracellular concentrations of the neurotransmitter dopamine. The physiological importance of the DAT provides the impetus for studies aimed at understanding the molecular mechanisms underlying regulation of the DAT gene. In this study, we identified a DAT-expressing neuroblastoma cell line (SK-N-AS) and employed it to investigate the transcriptional regulation of the human DAT gene. Two GC boxes (located at -130 and -60, respectively, relative to the transcriptional start site) were identified as important cis-acting elements mediating DAT promoter activity in dopaminergic SK-N-AS cells. Utilizing Sp-deficient Drosophila Schneider line (SL-2) cells, we showed that both Sp1 and Sp3 are strong activators of DAT transcriptional activity. Differential binding of Sp1 and Sp3 to the two GC boxes was demonstrated by electrophoretic mobility shift assays and super-shift assays. Our results indicate that the Sp1 family of proteins plays an important role in controlling the expression of the dopamine transporter gene within dopaminergic neurons.

Animals↗

PubMed2005

Dopamine neurons express multiple isoforms of the nuclear receptor nurr1 with diminished transcriptional activity.

Nurr1 (NR4A2) is an orphan nuclear receptor required for the development and maintenance of the dopaminergic phenotype in neurons of the ventral midbrain. This study demonstrates that multiple splice variants of nurr1 are produced in rat and human dopamine neurons. Formed by alternative RNA splicing in exon 7, nurr1a has a truncated carboxy-terminus, nurr1b has an internal deletion in the ligand-binding domain and nurr1c, newly identified in this study, has a novel carboxy-terminus produced by a frame shift downstream of the splice junction. Alternative RNA splicing in exon 3 produces the isoform known as the transcriptionally-inducible nuclear receptor (TINUR), lacking the amino-terminus. Nurr2 and the newly identified nurr2c are produced by utilization of both exon 3 and exon 7 alternative splice sites. In rat midbrain, variants other than full-length nurr1 constitute 20-35% of NR4A2 transcripts. Transfection studies in dopaminergic SK-N-AS cells demonstrate that nurr1a, nurr1b, nurr1c and TINUR have significantly reduced transcriptional activities compared with full-length nurr1, while nurr2 and nurr2c are inactive. Furthermore, in these experiments, nurr2 and nurr2c both act as dominant negatives. Production of these nurr1 variants in vivo as demonstrated here could represent a novel regulatory mechanism of nurr1 transcriptional activity and therefore, dopaminergic phenotype.

Animals↗

PubMed2005

cDNA cloning, sequence analysis of the porcine LIM and cysteine-rich domain 1 gene.

LIM domain proteins are important regulators in cell growth, cell fate determination, cell differentiation and remodeling of the cell cytoskeleton by their interaction with various structural proteins, kinases and transcriptional regulators. Using molecular biology combined with in silico cloning, we have cloned the complete coding sequence of pig LIM and the cysteine-rich domain 1 gene (LMCD1) which encodes a 363 amino acid protein. The estimated molecular weight of the LMCD1 protein is 40,788 Da with a pI of 8.39. It was found to be highly expressed in both skeletal muscle and cardiac muscle. Alignment analysis revealed that the deduced protein sequence shares 86%, 91% and 93% homology with that of its human, mouse and rat counterparts, respectively. The LMCD1 protein was predicted by bioinformatics software to contain a novel cysteine-rich domain in the N-terminal region, two LIM domains in the C-terminal region, nine potential protein kinase C phosphorylation sites, seven casein kinase II phosphorylation sites, a tyrosine kinase phosphorylation site, seven N-glycosylation and N-myristoylation sites and a single potential N-glycosylation site, which is similar to the protein's human counterpart. Phylogenetic tree was constructed by aligning the amino acid sequences of the LIM domain from different species. In addition, four base mutations were detected by comparing the sequences of Large White pigs with those of Chinese Meishan pigs. The G294A mutation site was confirmed by polymerase chain reaction-single-strand conformation polymorphism analysis. Its allele frequencies were studied in five pig breeds.

Amino Acid Sequence↗

PubMed2005

Convergence of protein kinase C and JAK-STAT signaling on transcription factor GATA-4.

Angiotensin II (AII), a potent vasoactive hormone, acts on numerous organs via G-protein-coupled receptors and elicits cell-specific responses. At the level of the heart, AII stimulation alters gene transcription and leads to cardiomyocyte hypertrophy. Numerous intracellular signaling pathways are activated in this process; however, which of these directly link receptor activation to transcriptional regulation remains undefined. We used the atrial natriuretic factor (ANF) gene (NPPA) as a marker to elucidate the signaling cascades involved in AII transcriptional responses. We show that ANF transcription is activated directly by the AII type 1 receptor and precedes the development of myocyte hypertrophy. This response maps to STAT and GATA binding sites, and the two elements transcriptionally cooperate to mediate signaling through the JAK-STAT and protein kinase C (PKC)-GATA-4 pathways. PKC phosphorylation enhances GATA-4 DNA binding activity, and STAT-1 functionally and physically interacts with GATA-4 to synergistically activate AII and other growth factor-inducible promoters. Moreover, GATA factors are able to recruit STAT proteins to target promoters via GATA binding sites, which are sufficient to support synergy. Thus, STAT proteins can act as growth factor-inducible coactivators of tissue-specific transcription factors. Interactions between STAT and GATA proteins may provide a general paradigm for understanding cell specificity of cytokine and growth factor signaling.

Adenoviridae↗