Malaria Research and Reference Reagent Resource Center.
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Biological Specimen Banks↗
Biomedical subjects
Y Wu
Publications and source records attributed to Y Wu.
Inhibitory glutamatergic regulation of evoked dopamine release in striatum.
Certain aspects of schizophrenia and Parkinson's disease suggest that glutamate might have an inhibitory effect on dopamine release. Several studies have reported that the excitatory actions of ionotropic glutamate agonists on extracellular dopamine levels in striatum are resistant to tetrodotoxin, which suggests that glutamate excites an impulse-independent mechanism of dopamine release. We tested the hypothesis that an inhibitory action of glutamate on dopamine terminals in the striatum specifically involves an impulse-dependent mechanism of dopamine release. We used voltammetry to monitor electrically-evoked dopamine release in striatal slices, which is completely tetrodotoxin- and Ca(2+)-sensitive and so provides a model of impulse-dependent dopamine release. Agonists of the ionotropic glutamate receptors significantly decreased the amplitude of the response, while antagonists significantly increased the amplitude of the response, by as much as approximately 60% in the case of kynurenic acid. These results support the hypothesis that ionotropic glutamate receptors can inhibit impulse-dependent dopamine release by a mechanism that acts locally within the striatum. This finding contrasts with previous reports that glutamate can excite impulse-independent dopamine release. This extends earlier findings that glutamate may both excite and inhibit subcortical dopamine systems by suggesting that the excitatory and inhibitory actions of striatal ionotropic glutamate receptors are specifically associated with impulse-independent and impulse-dependent dopamine release, respectively.
Animals↗
Radial magnetic resonance imaging and pathological findings of acetabular labrum in dysplastic hips.
Radial MRI findings and pathological changes were comparatively examined in the acetabular labrum of 11 hips of 11 patients, who underwent total hip arthroplasty for osteoarthritis due to acetabular dysplasia. Diffuse high signal pattern on the radial MR images corresponded to histological degeneration of the labrum. High signal pattern which was equivalent to the synovial fluid, showed an intralabral tear. In the obscure areas of MR images, severe impairment of the labrum such as rupture, detachment, and displacement were found.
Journal Article↗
Gene regulation by thyroid hormone.
Regulation of gene expression by thyroid hormones (T3, T4) is mediated via thyroid hormone receptors (TRs). TRs are DNA-binding transcription factors that function as molecular switches in response to ligand. TRs can activate or repress gene transcription depending on the promoter context and ligand-binding status. In most cases, in the absence of ligand, TRs interact with a corepressor complex containing histone deacetylase activity, which actively inhibits transcription. The binding of ligand triggers a conformational change in the TR that results in the replacement of the corepressor complex by a coactivator complex containing histone acetyltransferase activity, through which the chromatin structure is remodeled, thereby leading to activation of transcription. In addition, the finding that several TR-interacting coregulators act more directly on the basal transcriptional machinery suggests that mechanisms independent of histone acetylation and deacetylation also are involved in TR action.
Animals↗
Cytoskeletal protein PSTPIP1 directs the PEST-type protein tyrosine phosphatase to the c-Abl kinase to mediate Abl dephosphorylation.
A search for c-Abl interacting proteins resulted in the recovery of PSTPIP1, originally identified as a binding protein of the PEST-type protein tyrosine phosphatases (PTP). PSTPIP1 was phosphorylated by c-Abl, and growth factor-induced PSTPIP1 phosphorylation was diminished in Abl null fibroblasts. PSTPIP1 was able to bridge c-Abl to the PEST-type PTPs. Several experiments suggest that the PEST-type PTPs negatively regulate c-Abl activity: c-Abl was hyperphosphorylated in PTP-PEST-deficient cells; disruption of the c-Abl-PSTPIP1-PEST-type PTP ternary complex by overexpression of PSTPIP1 mutants increased c-Abl phosphotyrosine content; and PDGF-induced c-Abl kinase activation was prolonged in PTP-PEST-deficient cells. Dephosphorylation of c-Abl by PEST-type PTP represents a novel mechanism by which c-Abl activity is regulated.
Adaptor Proteins, Signal Transducing↗
Organization of the basal ganglia: the importance of axonal collateralization.
Recent neuroanatomical data obtained with single-axon or single-cell labeling procedures in both rodents and primates have revealed the presence of various types of projection neurons with profusely collateralized axons within each of the major components of the basal ganglia. Such findings call for a reappraisal of current concepts of the anatomical and functional organization of the basal ganglia,which play such a crucial role in the control of motor behavior. The basal ganglia now stand as a widely distributed neuronal network, whose elements are endowed with a highly patterned set of axon collaterals. The elucidation of this finely tuned network is needed to understand the complex spatiotemporal sequence of neural events that ensures the flow of cortical information through the basal ganglia.
Animals↗
Evidence of hydroxyl-ion deficiency in bone apatites: an inelastic neutron-scattering study.
The novelty of very large neutron-scattering intensity from the nuclear-spin incoherence in hydrogen has permitted the determination of atomic motion of hydrogen in synthetic hydroxyapatite and in deproteinated isolated apatite crystals of bovine and rat bone without the interference of vibrational modes from other structural units. From an inelastic neutron-scattering experiment, we found no sharp excitations characteristic of the vibrational mode and stretch vibrations of OH ions around 80 and 450 meV (645 and 3630 cm(-1)), respectively, in the isolated, deproteinated crystals of bone apatites; such salient features were clearly seen in micron- and nanometer-size crystals of pure hydroxyapatite powders. Thus, the data provide additional definitive evidence for the lack of OH(-) ions in the crystals of bone apatite. Weak features at 160-180 and 376 meV, which are clearly observed in the apatite crystals of rat bone and possibly in adult mature bovine bone, but to a much lesser degree, but not in the synthetic hydroxyapatite, are assigned to the deformation and stretch modes of OH ions belonging to HPO(4)-like species.
Animals↗
Letter to the editor: 1H, 13C and 15N resonance assignments of Aquifex aeolicus shikimate kinase in complex with the substrate shikimate.
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Bacteria↗
Lanthanide ions inhibit the activity of dihydrofolate reductase from chicken liver.
The influences of mono-, bi- and trivalent metal ions (as chloride salts) on the activity of dihydrofolate reductase (DHFR) from chicken liver have been studied to elucidate the mechanism of ion-activation of this enzyme. The results show that monovalent ions (Na+ and K+) activate DHFR at low concentration reaching a maximum activation of about 2.5 fold at 0.4-0.5 M and declining at higher concentrations. Ca2+ shows similar activation but at lower concentration, reaching a maximum at 0.1 M; activity declines with further increases in concentration. At very high concentration (> 0.4 M), Ca2+ is inhibitory. The trivalent lanthanide ions, however, show a dramatic inhibition of activity of DHFR even at very low concentration. The activity of DHFR declines to 50% of that of the control at 0.02 mM EuCl3. Intrinsic fluorescence measurements show that the ion-dependent activation in the presence of mono- and bivalent metal ions is due to the conformational changes in the protein. Energy transfer phenomenon suggests that the specific interaction of Eu3+ with Trp24 located in a loop at the active site of DHFR is responsible for the strong inhibition. The possible mechanism for the ion-inhibition is proposed and discussed.
Animals↗
Kinetic studies of imidazole and its methyl derivative binding to metmyoglobin: effects of substitute methyl on the binding affinity.
The binding of imidazole and imidazole derivatives (4- and 2-MeIm) to the metMb was studied by 1H NMR spectroscopy to elucidate the effects of different methyl substitution positions on the affinity and kinetics of binding to metMb. These exogenous ligands can form stable complexes with metMb except 2-MeIm. Kinetics and equilibrium data for the binding of imidazole and 4-MeIm to metMb have been obtained by 2D EXSY, and the reasons for the different affinity are also discussed.
Animals↗
Calmodulin kinase determines calcium-dependent facilitation of L-type calcium channels.
A dynamic positive feedback mechanism, known as 'facilitation', augments L-type calcium-ion currents (ICa) in response to increased intracellular Ca2+ concentrations. The Ca2+-binding protein calmodulin (CaM) has been implicated in facilitation, but the single-channel signature and the signalling events underlying Ca2+/CaM-dependent facilitation are unknown. Here we show that the Ca2+/CaM-dependent protein kinase II (CaMK) is necessary and possibly sufficient for ICa facilitation. CaMK induces a channel-gating mode that is characterized by frequent, long openings of L-type Ca2+ channels. We conclude that CaMK-mediated phosphorylation is an essential signalling event in triggering Ca2+/CaM-dependent ICa facilitation.
Animals↗
A critical role for interleukin 4 in activating alloreactive CD4 T cells.
To generate antigen-specific responses, T cells and antigen presenting cells (APCs) must physically associate with each other and elaborate soluble factors that drive the full differentiation of each cell type. Immediately after T cell activation, CD4 T cells can produce both interferon gamma (IFN-gamma) and interleukin 4 (IL-4) before polarization into distinct T helper subsets. Inhibition of IL-4 during mixed allogeneic lymphocyte culture resulted in a defect in the ability of APCs to generate sufficient costimulatory signals for activation of alloreactive T cells. In vivo, a deficiency in IL-4 production inhibited the activation of alloreactive IL-2-, IL-4- and IFN-gamma-producing CD4 T cells in mice challenged with allogeneic skin grafts, resulting in prolonged skin graft survival. Thus, production of IL-4 by CD4T cells helps activate alloreactive T cells by affecting APC function.
Animals↗
Immunotherapy of tumors with xenogeneic endothelial cells as a vaccine.
The breaking of immune tolerance against autologous angiogenic endothelial cells should be a useful approach for cancer therapy. Here we show that immunotherapy of tumors using fixed xenogeneic whole endothelial cells as a vaccine was effective in affording protection from tumor growth, inducing regression of established tumors and prolonging survival of tumor-bearing mice. Furthermore, autoreactive immunity targeting to microvessels in solid tumors was induced and was probably responsible for the anti-tumor activity. These observations may provide a new vaccine strategy for cancer therapy through the induction of an autoimmune response against the tumor endothelium in a cross-reaction.
Amino Acid Sequence↗
Fungal pathogen protection in potato by expression of a plant defensin peptide.
Defensins are small cysteine-rich peptides with antimicrobial activity. We demonstrate that the alfalfa antifungal peptide (alfAFP) defensin isolated from seeds of Medicago sativa displays strong activity against the agronomically important fungal pathogen Verticillium dahliae. Expression of the alfAFP peptide in transgenic potato plants provides robust resistance in the greenhouse. Importantly, this resistance is maintained under field conditions. There have been no previous demonstrations of a single transgene imparting a disease resistance phenotype that is at least equivalent to those achieved through current practices using fumigants.
Amino Acid Sequence↗
Gene transfer facilitated by a cellular targeting molecule, reovirus protein sigma1.
To facilitate eventual genetic vaccination of mucosal tissues, a receptor-mediated gene transfer system was devised using the reovirus adhesin, protein sigma1. Highly efficient uptake and internalization of protein sigma1 polylysine (PL) DNA complexes could be demonstrated by fluorescent microscopy. Successful cellular transfection of rodent and human cell lines was obtained with the recombinant protein sigma1 as a PL-DNA complex, and could be shown to be receptor-specific. Transfection efficiency was dependent upon the ratio of DNA complexed to protein sigma1-PL and chloroquine treatment improved transfection efficiency dramatically. To test its ability to bind a mucosal inductive tissue, recombinant protein sigma1 was specifically bound to the nasal-associated lymphoid tissues (NALT). Thus, recombinant protein sigma1-PL-DNA conjugates can efficiently bind and transfect cells that express the receptor for protein sigma1. Gene Therapy (2000) 7, 61-69.
Animals↗
Antibody from mice immunized with DNA encoding the carboxyl-disintegrin and cysteine-rich domain (JD9) of the haemorrhagic metalloprotease, Jararhagin, inhibits the main lethal component of viper venom.
Envenoming by the Brazilian pit viper, Bothrops jararaca, induces extensive local and systemic haemorrhage in humans. The severe and occasionally lethal outcome of envenoming is prevented only by administration of antivenom which is conventionally prepared by hyperimmunization of large animals with an individual venom or a range of venoms. Since snake venoms typically consist of numerous molecules, only some of which are toxic, antivenoms are antigenically crude preparations whose therapeutic value would theoretically be enhanced by restricting antibody specificity to toxic venom molecules. We report here that high-titre IgG antibody from mice immunized by the GeneGun with DNA encoding the carboxy-terminal JD9 domain of Jararhagin, a haemorrhage-inducing metalloprotease in B. jararaca venom, extensively neutralized the main lethal component of B. jararaca venom. This is to our knowledge the first study to apply DNA-based methods to preparation of antivenom; it represents a novel approach with greater immunological specificity and fewer hazards than conventional systems of antivenom production.
ADAM Proteins↗
A comparison of the bioscreen method and microscopy for the determination of lag times of individual cells of listeria monocytogenes.
Lag phase durations (tLag) of individual Listeria monocytogenes cells were analysed using the NightOwl Molecular Imaging System, and results were compared with mean individual cell lag times (tL) obtained from the detection time (td) method using Bioscreen. With Bioscreen, an average tL of 6.39+/-0.89 h was obtained from five separate experiments. With the NightOwl method, an average tLag of 2.73+/-0.06 h was obtained from three experiments consisting of eight total replicates. Lag values from the NightOwl and Bioscreen are related by the equation: tLag = tL + DT, where DT is the doubling time. The equivalent tLag mean value for the Bioscreen method was 7.11+/-0.84 h. Individual lag times measured by both methods were normally distributed (r2 for Bioscreen and NightOwl ranged from 0.951 to 0.999 and from 0.884 to 0.982, respectively). The results suggest that the NightOwl method can provide accurate estimates of individual cell lag times, which will facilitate the development of combined discrete continuous models for bacterial growth.
Biosensing Techniques↗
Direct computation of multiple 3D flow convergence isovelocity surfaces from digital 3D reconstruction of colour Doppler data of the flow convergence region: an in vitro study with differently shaped orifices.
AIMS: Evaluation of the accuracy of direct computation of multiple three-dimensional (3D) flow convergence (FC) isovelocities by using digital reconstruction of colour Doppler data of the flow convergence region. METHODS AND RESULTS: We used a conventional ultrasound system (ATL HDI 3000) connected to a computer workstation via Ethernet link. The digital 3D datasets were directly transferred to a Silicon Graphic Imaging Octane workstation for later measurement. We generated nine pulsatile flows (20-60 ml/beat), with peak flow rates (67-180 ml/s), through three orifices (circular, rectangular and triangular, S=0.24 cm(2)). The 3D reconstructions of FC surface areas from multi-threshold velocities, including aliasing velocities were analysed to quantify the peak flow rate. For all orifices, linear regression demonstrated excellent correlation between the 3D calculated and electromagnetic flow meter recorded data. While there was a high correlation for 3D computation of flow rate from the single best Nyquist of 24 cm/s (r=0.97-0.98, SEE=7 .75-12.58 ml/s), the ability to average three threshold velocities (15, 18 and 24 cm/s) yielded an improved correlation (r=0.98-0.99, SEE=5.70-7.73 ml/s). CONCLUSIONS: Direct computation of multiple 3D FC isovelocities from digital reconstruction of colour Doppler data of the FC region provides the potential to accurately quantify the complex asymmetric spatial flow events at any selected velocity.
Blood Flow Velocity↗