Biomedical subjects

Wei Wang

Publications and source records attributed to Wei Wang.

At least 217 records · Page 12Linked to original sources

PubMed2006

Downregulation of KCC2 following LTP contributes to EPSP-spike potentiation in rat hippocampus.

GABAergic synaptic inhibition plays a critical role in regulating long-term potentiation (LTP) of glutamatergic synaptic transmission and circuit output. The K(+)-Cl(-) cotransporter 2 (KCC2) is an important factor in determining inhibitory GABAergic synaptic strength besides the contribution of GABA(A) receptor. Although much knowledge has been gained regarding activity-dependent downregulation of KCC2 in many pathological conditions, the potential change and contribution of KCC2 in LTP expression is still unknown. In this study, we found that downregulation of KCC2 was accompanied with the occurrence of LTP but not that of long-term depression in hippocampal CA1 region. Meanwhile, KCC2 level in CA3/DG and adjacent cortex was stable in the process of LTP expression in Schaffer collateral synapses. Blockade of NMDA receptor with APV not only prevented LTP induction also abolished the reduction of KCC2. Furthermore, the inhibition of KCC2 function with furosemide directly induced EPSP-spike (E-S) potentiation, an important component of LTP in hippocampus. The present data suggest a novel mechanism that LTP formation is accompanied by the downregulation of KCC2, which is underlying GABAergic strength and most likely contributes to the E-S potentiation following LTP.

Animals↗

PubMed2006

Identification of a novel VNTR polymorphism in C6orf37 and its association with colorectal cancer risk in Chinese population.

BACKGROUND: C6orf37 was a gene up-regulated in colorectal adenoma in our previous study. A variable region of C6orf37 sequence was found when we blasted its full sequence with NCBI nucleotide database. METHODS: RT-PCR and sequencing were conducted to identify the variable region of C6orf37 as VNTR. DHPLC was applied to detect the VNTR genotypes in 122 colorectal carcinoma patients and 166 healthy controls. RESULTS: A novel VNTR sequence found in C6orf37 second exon was composed of 15 base pair consensus sequence encoding 5-amino-acid (G-G-D-F-G). The repeat timePOST alleles contain three repeats (a), 4 repeats (b) and 5 repeats (c), respectively, which produced 3 homozygotes (a/a, b/b and c/c) and 3 heterozygotes (a/b, a/c and b/c). a, b, c allele frequencies were 0.145, 0.304, 0.551, respectively in Chinese population. Heterozygosity (H) was 0.583. Polymorphism information content (PIC) was 0.510. The distribution of genotypes and allele frequencies of the VNTR reached no significant difference between patients and healthy controls and there was no correlation between VNTR polymorphism and colorectal cancer clincopathological features. CONCLUSION: A novel VNTR polymorphism in C6orf37 exists in Chinese population and is not associated with colorectal cancer risk.

Adult↗

PubMed2006

Human neutrophils reaction to the biodegraded nano-hydroxyapatite/collagen and nano-hydroxyapatite/collagen/poly(L-lactic acid) composites.

The impact of biodegraded nano-hydroxyapatite/collagen (nHAC) composite and nano-hydroxyapatite/collagen/poly(L-lactic acid) (nHAC/PLA) scaffold composite on neutrophils reaction was evaluated in vitro. Neutrophils were separated from human peripheral blood of healthy subjects. The nHAC and nHAC/PLA materials were immersed in the D-Hanks' Balanced Salt Solution (D-HBSS) for 1 day, 7 days and 2, 4, 8 weeks (37 degrees C) as testing solution, which mixed with the neutrophils for 1 h. Both of the nHAC and nHAC/PLA materials were shown the same cell survival rate as blank control, but the lactate dehydrogenase (LDH) and tumor necrosis factor alpha (TNF-alpha) released from the neutrophils were increased significantly after the 2 weeks in nHAC sample. The possible reason relied on the high concentration of calcium due to the quick biodegradation of the nHAC material. Before 2 weeks, the LDH value of nHAC/PLA is higher than that of nHAC sample that corresponded to the initial PLA degradation in vitro. This study provided the biocompatibility test of neutrophils other than common methods, such as osteoblastic cells for biomimetic materials. Moreover, it demonstrated the calcium concentration stimulating effect for cytokine release from neutrophils.

Biocompatible Materials↗

PubMed2006

Exploiting sequence and structure homologs to identify protein-protein binding sites.

A rapid increase in the number of experimentally derived three-dimensional structures provides an opportunity to better understand and subsequently predict protein-protein interactions. In this study, structurally conserved residues were derived from multiple structure alignments of the individual components of known complexes and the assigned conservation score was weighted based on the crystallographic B factor to account for the structural flexibility that will result in a poor alignment. Sequence profile and accessible surface area information was then combined with the conservation score to predict protein-protein binding sites using a Support Vector Machine (SVM). The incorporation of the conservation score significantly improved the performance of the SVM. About 52% of the binding sites were precisely predicted (greater than 70% of the residues in the site were identified); 77% of the binding sites were correctly predicted (greater than 50% of the residues in the site were identified), and 21% of the binding sites were partially covered by the predicted residues (some residues were identified). The results support the hypothesis that in many cases protein interfaces require some residues to provide rigidity to minimize the entropic cost upon complex formation.

Adrenodoxin↗

PubMed2006

Folding mechanism of beta-hairpins studied by replica exchange molecular simulations.

The folding process of trpzip2 beta-hairpin is studied by the replica exchange molecular dynamics (REMD) and normal MD simulations, aiming to understand the folding mechanism of this unique small, stable, and fast folder, as well as to reveal the general principles in the folding of beta-hairpins. According to our simulations, the TS ensemble is mainly characterized by a largely formed turn and the interaction between the inner pair of hydrophobic core residues. The folding is a zipping up of hydrogen bonds. However, the nascent turn has to be stabilized by the partially formed hydrophobic core to cross the TS. Thus our folding picture is in essence a blend of hydrogen bond-centric and hydrophobic core-centric mechanism. Our simulations provide a direct evidence for a very recent experiment (Du et al., Proc Natl Acad Sci USA 2004;101:15915-15920), which suggests that the turn formation is the rate-limiting step for beta-hairpin folding and the unfolding is mainly determined by the hydrophobic interactions. Besides, the relationship between hydrogen bond stabilities and their relative importance in folding are investigated. It is found that the hydrogen bonds with higher stabilities need not play more important roles in the folding process, and vice versa.

Computer Simulation↗

PubMed2006

Ischemic acute renal failure following nephrectomy impairs long-term renal function.

Uninephrectomy is associated with increased glomerular filtration rate in both the donated and the remaining contralateral kidney. The long-term effects of ischemic acute renal failure (ARF) following uninephrectomy are unknown. This study examined renal function, histology and proteinuria 52 weeks after an episode of reversible ischemic ARF. Ischemic ARF was induced in uninephrectomised mice by renal pedicle clamping. At 52 weeks inulin clearance (muL/min/g) was 7.2+/-0.2 in sham, 5.0+/-0.1 in uninephrectomy (P<0.01 vs. sham) and 3.9+/-0.1 in uninephrectomy + ischemia (P<0.01 vs. sham, P<0.05 vs. uninephrectomy). Thus, mice subjected to uninephrectomy alone demonstrated compensatory hyperfiltration following reduction in renal mass. This response was prevented by ischemic ARF. At 52 weeks there was no difference in urine protein/creatinine, mean arterial pressure or scores of glomerulosclerosis or interstitial fibrosis. In conclusion, ischemic ARF following uninephrectomy in mice impairs long-term renal function.

Acute Kidney Injury↗

PubMed2006

Cloning, expression and characterization of a novel human CAP10-like gene hCLP46 from CD34(+) stem/progenitor cells.

A novel human gene, named as human CAP10-like protein 46 kDa (hCLP46), was isolated and identified from human acute myeloid leukemia transformed from myelodysplastic syndrome (MDS-AML) CD34(+) cells. hCLP46 (3q13.33) contains 11 exons encoding a putative protein of 392 amino acids, with a highly conserved CAP10 domain, a hydrophobic signal peptide at its N-terminus, and an endoplasmic reticulum (ER) retention signal motif KTEL at the C-terminus. The homologs of hCLP46 exist in different organisms from plants to animal kingdoms. Subcellular localization analysis showed that hCLP46 is an ER-resident protein. hCLP46 expressed in most human adult tissues at different intensities, with lengths of 3.5 kb and 1.9 kb. Transcript of hCLP46 was not detectable in colon, thymus, and small intestine, but was abundant in liver, indicating that hCLP46 may be involved in important physiological functions in the liver. hCLP46 over-expressed U937 cells had higher growth rate than the cells without exogenic hCLP46 protein expression, suggesting that hCLP46 protein possess the ability of promoting cell proliferation.

Amino Acid Sequence↗

PubMed2006

Short- and long-term regulation of adenylyl cyclase activity by delta-opioid receptor are mediated by Galphai2 in neuroblastoma N2A cells.

Activation of the opioid receptor results in short-term inhibition of intracellular cAMP levels followed by receptor desensitization and subsequent increase of cAMP above the control level (adenylyl cyclase superactivation). Using adenovirus to deliver pertussis toxin-insensitive mutants of the alpha-subunits of G(i/o) that are expressed in neuroblastoma Neuro2A cells (Galpha(i2), Galpha(i3), and Galpha(o)), we examined the identities of the G proteins involved in the short- and long-term action of the delta-opioid receptor (DOR). Pertussis toxin pretreatment completely abolished the ability of [d-Pen(2), d-Pen(5)]-enkephalin (DPDPE) to inhibit forskolin-stimulated intracellular cAMP production. Expression of the C352L mutant of Galpha(i2), and not the C351L mutants of Galpha(i3) or Galpha(o), rescued the short-term effect of DPDPE after pertussis toxin treatment. The ability of Galpha(i2) in mediating DOR inhibition of adenylyl cyclase activity was also reflected in the ability of Galpha(i2), not Galpha(i3) or Galpha(o), to coimmunoprecipitate with DOR. Coincidently, after long-term DPDPE treatment, pertussis toxin treatment eliminated the antagonist naloxone-induced superactivation of adenylyl cyclase activity. Again, only the C352L mutant of Galpha(i2) restored the adenylyl cyclase superactivation after pertussis toxin treatment. More importantly, the C352L mutant of Galpha(i2) remained associated with DOR after long-term agonist and pertussis toxin treatment whereas the wild-type Galpha(i2) did not. These data suggest that Galpha(i2) serves as the signaling molecule in both DOR-mediated short- and long-term regulation of adenylyl cyclase activity.

Adenoviridae↗

PubMed2006

NAD(P)H oxidase in paraventricular nucleus contributes to the effect of angiotensin II on cardiac sympathetic afferent reflex.

We previously reported that reactive oxygen species (ROS) in paraventricular nucleus (PVN) modulated cardiac sympathetic afferent reflex (CSAR) and mediated the effect of angiotensin II (Ang II) in the PVN on the CSAR. In the present study, we investigated whether the NAD(P)H oxidase in the PVN was a key source of ROS which modulated the CSAR and contributed to the effect of Ang II on the CSAR. In anesthetized rats with sinoaortic denervation and vagotomy, renal sympathetic nerve activity (RSNA) and arterial pressure were recorded. The CSAR was evaluated by the RSNA response to epicardial application of bradykinin (BK). The NAD(P)H oxidase activity in the PVN was measured with lucigenin-enhanced chemiluminescent method. Microinjection of the NAD(P)H oxidase inhibitor, either apocynin (1.0 nmol) or phenylarsine oxide (PAO, 1.0 nmol), into the PVN significantly inhibited the CSAR. Microinjection of Ang II (0.3 nmol) into the PVN significantly augmented the CSAR. The effects of Ang II were not only abolished by pretreatment with either apocynin or PAO in the PVN but also partially inhibited by xanthine oxidase inhibitor allopurinol. Either epicardial application of BK or microinjection of Ang II into the PVN significantly increased NAD(P)H oxidase activity in the PVN. The effect of Ang II on NAD(P)H oxidase activity was abolished by pretreatment with AT(1) receptor antagonist losartan in the PVN. These findings suggested that NAD(P)H oxidase in the PVN was a major source of the ROS in modulating the CSAR, and the NAD(P)H oxidase contributes to the effect of Ang II on the CSAR.

Afferent Pathways↗

PubMed2006

Sodium nitrite-induced cytotoxicity in cultured human gastric epithelial cells.

To investigate the effect of sodium nitrite on the viability of the human gastric adenocarcinoma epithelial cell line, AGS, cultured AGS cells were exposed to various concentrations of sodium nitrite for 24, 48 or 72 h. The cytotoxic response was assessed using a cell proliferation assay, and the extent of the response was evaluated on the basis of intracellular and extracellular levels of interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), interleukin 8 (IL-8) and tumor necrosis factor (TNF-alpha). Both mRNA and protein levels were measured for each cytokine. Sodium nitrite had a significant effect on AGS cell proliferation after a 72-h exposure. At low sodium nitrite concentrations (up to 6.25 mM), cell proliferation increased in a dose-dependent manner; however, exposure to higher concentrations resulted in a dose-dependent decrease in cell proliferation. Sodium nitrite at a low concentration (6.25 mM) increased IL-8 release, whereas IL-1 beta, IL-6, and TNF-alpha release increased only after exposure to high sodium nitrite concentration (25 mM). Our data demonstrate that sodium nitrite can induce the release of these inflammatory cytokines and that high concentrations of sodium nitrite decrease AGS cell proliferation.

Cell Line, Tumor↗

PubMed2006

Comparative all-atomic study of unfolding pathways for proteins chymotrypsin inhibitor 2 and barnase.

The features of transition states and intermediates are important in the study on protein folding. However, transition states and intermediates could not be obviously identified from trajectories obtained by dynamic simulations. In this work, a different method to identify and characterize the transition states and intermediates by combining the root mean square deviation of C(alpha) atoms and the similarity factor Q to the native state is proposed. The unfolding processes based on all-atomic simulations for proteins chymotrypsin inhibitor 2 and barnase are studied, and the related transition states and intermediates are identified by observing an unfolding factor U = 1-F. Comparisons between the conformational cluster analysis and experimental results are also made. The various analyses on the unfolding behaviors indicate that our method can well define the transition states and intermediates, and the factor U (or F) can be used as a reaction coordinate of the folding and unfolding process. It is also found that three-state folding proteins might experience more complicated pathways and have more rugged energy landscapes than two-state folding proteins.

Bacterial Proteins↗

PubMed2006

Cerebral information processing in personality disorders: I. Intensity dependence of auditory evoked potentials.

Patients with personality disorders such as the histrionic type exaggerate their responses when receiving external social or environmental stimuli. We speculated that they might also show an augmenting pattern of the auditory evoked potential N1-P2 component in response to stimuli with increasing levels of intensity, a response pattern that is thought to be inversely correlated with cerebral serotonin (5-HT) activity. To test this hypothesis, we collected auditory evoked potentials in 191 patients with personality disorders (19 patients with the paranoid type, 12 schizoid, 14 schizotypal, 18 antisocial, 15 borderline, 13 histrionic, 17 narcissistic, 25 avoidant, 30 dependent and 28 obsessive-compulsive) and 26 healthy volunteers. Their personality traits were measured using the Dimensional Assessment of Personality Pathology-Basic Questionnaire (DAPP-BQ). Compared with healthy subjects and other patient groups, the histrionic group scored higher on the basic traits Affective Instability, Stimulus Seeking, Rejection and Narcissism, and on the higher traits Emotional Dysregulation and Dissocial, than the other groups, and the schizoid group scored lower on most of the DAPP-BQ basic and higher traits. In addition, the histrionic group showed steeper amplitude/stimulus intensity function (ASF) slopes at three midline scalp electrodes than the healthy controls or the other patient groups. The ASF slopes were not correlated with any DAPP-BQ traits in the total sample of 217 subjects. However, the DAPP-BQ basic trait Rejection was positively correlated with the ASF slopes at all three electrode sites in the histrionic group. The increased intensity dependence of the auditory N1-P2 component might indicate that cerebral 5-HT neuronal activity is, on average, weak in the histrionic patients.

Adult↗

PubMed2006

Experimental study of coherence vortices: local properties of phase singularities in a spatial coherence function.

By controlling the irradiance of an extended quasimonochromatic, spatially incoherent source, an optical field is generated that exhibits spatial coherence with phase singularities, called coherence vortices. A simple optical geometry for direct visualization of coherence vortices is proposed, and the local properties and the spatial evolution of coherence vortex are experimentally investigated. To our knowledge, this is the first direct and quantitative experimental measurement of a generic coherence vortex.

Journal Article↗

PubMed2006

Two key residues in ephrinB3 are critical for its use as an alternative receptor for Nipah virus.

EphrinB2 was recently discovered as a functional receptor for Nipah virus (NiV), a lethal emerging paramyxovirus. Ephrins constitute a class of homologous ligands for the Eph class of receptor tyrosine kinases and exhibit overlapping expression patterns. Thus, we examined whether other ephrins might serve as alternative receptors for NiV. Here, we show that of all known ephrins (ephrinA1-A5 and ephrinB1-B3), only the soluble Fc-fusion proteins of ephrinB3, in addition to ephrinB2, bound to soluble NiV attachment protein G (NiV-G). Soluble NiV-G bound to cell surface ephrinB3 and B2 with subnanomolar affinities (Kd = 0.58 nM and 0.06 nM for ephrinB3 and B2, respectively). Surface plasmon resonance analysis indicated that the relatively lower affinity of NiV-G for ephrinB3 was largely due to a faster off-rate (K(off) = 1.94 x 10(-3) s(-1) versus 1.06 x 10(-4) s(-1) for ephrinB3 and B2, respectively). EphrinB3 was sufficient to allow for viral entry of both pseudotype and live NiV. Soluble ephrinB2 and B3 were able to compete for NiV-envelope-mediated viral entry on both ephrinB2- and B3-expressing cells, suggesting that NiV-G interacts with both ephrinB2 and B3 via an overlapping site. Mutational analysis indicated that the Leu-Trp residues in the solvent exposed G-H loop of ephrinB2 and B3 were critical determinants of NiV binding and entry. Indeed, replacement of the Tyr-Met residues in the homologous positions in ephrinB1 with Leu-Trp conferred NiV receptor activity to ephrinB1. Thus, ephrinB3 is a bona fide alternate receptor for NiV entry, and two residues in the G-H loop of the ephrin B-class ligands are critical determinants of NiV receptor activity.

Animals↗

PubMed2006

Up-regulation of matrix in bovine articular cartilage explants by electric fields.

Electric stimulation has long been used as a tool to promote connective tissue healing, but the mechanism(s) by which this is accomplished are not yet known. We have previously determined, using mass cultures of fetal bovine articular chondrocytes, a specific set of capacitively coupled electrical stimulation parameters (e.g., duration of stimulation, response time, amplitude, frequency, and duty cycle) that significantly elevated production of collagen and proteoglycan, and up-regulated type II collagen and aggrecan mRNA expression in vitro. In the present study, we applied our best signal parameters (30-min continuous stimulation (100% duty cycle) followed by a pulsed (1h on, 5h off, 4x/day) 50% (1 min on, 1 min off) duty cycle) to cultures of adult bovine articular cartilage explants and obtained similar results. Since the latter system more closely mimics the in vivo chondrocyte environment, these data argue for the utility of electric stimulation for the maintenance of adult cartilage matrix in situ.

Aggrecans↗

PubMed2006

Simultaneous determination of MHD and DMD in dog plasma by high-performance liquid chromatography with fluorescence detection and its application to pharmacokinetic studies.

A rapid, reproducible high-performance liquid chromatographic (HPLC) method with fluorescence detection for the simultaneous determination of 3(or 8)-(1-methoxyethyl)-8(or 3)-(1-hydroxyethyl)-deuteroporphyrin IX (MHD) and 3,8-di-(1-methoxyethyl)-deuteroporphyrin IX (DMD) in dog plasma was described. Fluorescein was used as an internal standard. A simple extraction step with ethyl acetate was performed before chromatography on a Diamonsil C18 column (5 microm, 4.6 mm x 150 mm). The chromatography used 0.02 mol L(-1) sodium acetate/tetrahydrofuran (66:34 v/v). The analytical curve was linear over the concentration range 0.025-2.5 microg mL(-1). For a 100 microL dog plasma sample, the limit of determination for both MHD and DMD was 0.025 microg mL(-1). The recoveries of MHD and DMD were more than 76% and 89%, respectively. The intra-assay (within-run) and interassay (between-run) coefficients of variation (precisions) for MHD and DMD were less than 15%. This method was found to be suitable for the analysis of biosamples and was successfully applied to pharmacokinetic studies of Deuxemether in dogs.

Animals↗

PubMed2006

Appearance of immature/transitional B cells in HIV-infected individuals with advanced disease: correlation with increased IL-7.

Progression of HIV disease is associated with the appearance of numerous B cell defects. We describe herein a population of immature/transitional B cells that is overly represented in the peripheral blood of individuals with advancing HIV disease. These B cells, identified by the expression of CD10, were unresponsive by proliferation to B cell receptor triggering and possessed a phenotype and an Ig diversity profile that confirmed their immature/transitional stage of differentiation. Consistent with an immature status, their lack of proliferation to B cell receptor triggering was reversed with CD40 ligand, but not B cell activation factor. Finally, levels of CD10 expression on B cells were directly correlated with serum levels of IL-7, suggesting that increased levels of IL-7 modulate human B cell maturation either directly or indirectly by means of a homeostatic effect on lymphopenia. Taken together, these data offer insight into human B cell development as well as B cell dysfunction in advanced HIV disease that may be linked to IL-7-dependent homeostatic events.

B-Lymphocytes↗

PubMed2006

Cry1Ab protein from Bt transgenic rice does not residue in rhizosphere soil.

Expression of Cry1Ab protein in Bt transgenic rice (KMD) and its residue in the rhizosphere soil during the whole growth in field, as well as degradation of the protein from KMD straw in five soils under laboratory incubation were studied. The residue of Cry1Ab protein in KMD rhizosphere soil was undetectable (below the limit of 0.5 ng/g air-dried soil). The Cry1Ab protein contents in the shoot and root of KMD were 3.23-8.22 and 0.68-0.89 microg/g (fresh weight), respectively. The half-lives of the Cry1Ab protein in the soils amended with KMD straw (4%, w/w) ranged from 11.5 to 34.3d. The residence time of the protein varied significantly in a Fluvio-marine yellow loamy soil amended with KMD straw at the rate of 3, 4 and 7%, with half-lives of 9.9, 13.8 and 18d, respectively. In addition, an extraction method for Cry1Ab protein in soil was developed, with extraction efficiencies of 46.4-82.3%.

Bacillus thuringiensis Toxins↗