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Biomedical subjects

G Wang

Publications and source records attributed to G Wang.

At least 19 recordsLinked to original sources

Development of RS1-specific ACMG/AMP variant classification criteria with pilot variant curation.

Gene-based therapies are being developed for retinal diseases, including RS1-related X-linked retinoschisis. Therefore it is essential to determine which variants are pathogenic and which are benign when enrolling patients. The Clinical Genome Resource (ClinGen) X-Linked Inherited Retinal Diseases (XLRD) Variant Curation Expert Panel (VCEP) brings together clinician scientists, molecular biologists, and geneticists to apply their expertise and review the clinical, genetic, population, and functional evidence for variants. American College of Medical Genetics (ACMG) guidelines have been modified for RS1 to develop a highly systematic and conservative framework for evaluating variants. The curation process involves applying 28 different codes, each with 4 strength levels (very strong, strong, moderate, supporting) across different domains of phenotype, population data, computational assessment, functional impact, and segregation. With RS1-specific rules, a total of 54 pilot variants were tested. These included 47 variants in ClinVar. Of these 21 variants were re-classified: 2 likely pathogenic variants and one likely benign were changed to variants of uncertain significance and 4 previously unclassified variants were changed to pathogenic, likely pathogenic and likely benign. Other changes resolved conflicts or multiple classifications.

Humans↗

Influence of acute normovolaemic haemodilution on the dose-response relationship and time course of action of cisatracurium besylate.

BACKGROUND: Acute normovolaemic haemodilution (ANH) is an efficacious blood conservation strategy aiming at avoiding allogeneic blood transfusion. ANH was shown to increase the potency of vecuronium, atracurium, and rocuronium. The aim of our study was to investigate whether cisatracurium potency is altered with ANH. METHODS: Using the Relaxometer mechanomyograph, we compared cisatracurium dose-response relationship and time course of action in 60 patients randomly allocated to the ANH or control groups. Patients in each group were randomly allocated to receive one of three cisatracurium doses (30, 40, 50 microg kg(-1)) followed by a second supplemental dose to reach a total of 100 microg kg(-1). RESULTS: ANH did not result in a significant shift in cisatracurium log dose-probit dose-response curve. There was no significant difference in mean (95% confidence intervals) ED(50), ED(90), and ED(95) (effective doses required for 50, 90, and 95% first twitch depression) between the ANH group [29.5 (27-32), 50.4 (47.4-53.4), 58.7 (55.3-62) microg kg(-1)] and the control group [28.2 (25.3-31), 47.6 (44.9-50.3), 55.3 (52.5-58.1) microg kg(-1)], whereas there was no difference in mean (SD) Dur(25) and Dur(0.8) (time until 25% first twitch and 0.8 train-of-four ratio recoveries) between the ANH group [40.8 (5.9), 64.7 (8.4) min] and the control group [42.2 (7.6), 66.5 (10.7) min]. CONCLUSIONS: Our results demonstrated that unlike other previously reported neuromuscular blocking drugs, ANH did not alter cisatracurium potency. Thus, cisatracurium would be the neuromuscular blocking drug of choice in patients who undergo surgery with ANH, as no dose adjustments are required.

Adult↗

Repeated epicutaneous exposures to ovalbumin progressively induce atopic dermatitis-like skin lesions in mice.

BACKGROUND: Atopic dermatitis (AD) is a chronic skin disease in which environmental factors play a great role. A widely used murine model for AD has provided a useful tool to study the disease. OBJECTIVE: The purpose of this study is to investigate kinetically the induction of this AD model and the processes involved in the development of AD due to extrinsic allergen exposures. METHODS: BALB/c mice were epicutaneously exposed to ovalbumin (OVA) for 3 weeks; each week was separated by a 2-week resting period. Mice were killed after each exposure week. Skin biopsies and blood were obtained for histological study, RNA isolation and antibody analysis. RESULTS: There was a progressive and significant thickening of the epidermis and dermis in OVA-exposed mice. Significantly increased dermal cell infiltration of eosinophils, mast cells and total inflammatory cells, including CD3 and CD4 cells, was found after each OVA exposure week. Total IgE, IgG2a and OVA-specific IgE were significantly increased after the second and third exposure week, while OVA-specific IgG2a was significantly induced after the third exposure week. Gradual and/or significant increases in mRNA expression of IL-1beta, TNF-alpha, IL-4, IL-10, IL-13, IFN-gamma and IL-12p35 were found after each exposure week. Chemokines and their receptors involved in both T-helper type 1 (Th1)- and Th2-type cell recruitment (CCL1, CCL8, CCL11, CCL24, CXCL9, CXCL10, CCR1, CCR3, CCR5, CCR8 and CXCR3) were up-regulated significantly at different time-points. CONCLUSION: This study provides an insight into the dynamic nature and time-dependent transition of skin inflammation and systemic immune responses in a murine AD model induced by repeated epicutaneous exposures to OVA.

Allergens↗

Object recognition learning differentiates the representations of objects at the ERP component N1.

OBJECTIVE: Even if viewed from different angles, one can identify an object among similar distractors through learning. This study was designed to investigate the changes in neuronal activity related to learning. METHODS: Human subjects were asked to train themselves with novel objects by performing an object recognition task, in which the images of an object had to be discriminated from those of other objects regardless of the viewpoint. RESULTS: The ERP component-N1, the first negative peak at posterior electrodes, showed a significant increase in the amplitude variation across the objects during the learning process, while the variation across viewpoints decreased. CONCLUSIONS: These results suggest that object recognition learning differentiates between the representations of the objects, at least, at the N1 level. SIGNIFICANCE: The results may support the notion that object recognition differentiates among the functional representations of the trained objects in our brain.

Adolescent↗

Subcellular localization of nicotinamide adenine dinucleotide phosphate oxidase subunits in neurons and astroglia of the rat medial nucleus tractus solitarius: relationship with tyrosine hydroxylase immunoreactive neurons.

Superoxide produced by the enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase mediates crucial intracellular signaling cascades in the medial nucleus of the solitary tract (mNTS), a brain region populated by catecholaminergic neurons, as well as astroglia that play an important role in autonomic function. The mechanisms mediating NADPH oxidase (phagocyte oxidase) activity in the neural regulation of cardiovascular processes are incompletely understood, however the subcellular localization of superoxide produced by the enzyme is likely to be an important regulatory factor. We used immunogold electron microscopy to determine the phenotypic and subcellular localization of the NADPH oxidase subunits p47(phox), gp91(phox,) and p22(phox) in the mNTS in rats. The mNTS contains a large population of neurons that synthesize catecholamines. Significantly, catecholaminergic signaling can be modulated by redox reactions. Therefore, the relationship of NADPH oxidase subunit labeled neurons or glia with respect to catecholaminergic neurons was also determined by dual labeling for the superoxide producing enzyme and tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. In the mNTS, NADPH oxidase subunits were present primarily in somatodendritic processes and astrocytes, some of which also contained TH, or were contacted by TH-labeled axons, respectively. Immunogold quantification of NADPH oxidase subunit localization showed that p47(phox) and gp91(phox) were present on the surface membrane, as well as vesicular organelles characteristic of calcium storing smooth endoplasmic reticula in dendritic and astroglial processes. These results indicate that NADPH oxidase assembly and consequent superoxide formation are likely to occur near the plasmalemma, as well as on vesicular organelles associated with intracellular calcium storage within mNTS neurons and glia. Thus, NADPH oxidase-derived superoxide may participate in intracellular signaling pathways linked to calcium regulation in diverse mNTS cell types. Moreover, NADPH oxidase-derived superoxide in neurons and glia may directly or indirectly modulate catecholaminergic neuron activity in the mNTS.

Animals↗

Radial structure of Alfvén eigenmodes in the DIII-D tokamak through electron-cyclotron-emission measurements.

The spatial structure of toroidal Alfvén eigenmodes and reversed shear Alfvén eigenmodes in DIII-D is obtained from electron-cyclotron-emission measurements. Peak measured temperature perturbations are of similar magnitude for both toroidal Alfvén eigenmodes and reversed shear Alfvén eigenmodes and found to be deltaT(e)/T(e) approximately equal to 0.5%. Simultaneous measurements of density fluctuations using beam-emission spectroscopy indicate deltan(e)/n(e) approximately equal to 0.25%. Predictions of the measured temperature and density perturbation profiles as well as deltaT(e)/deltan(e) from the ideal magnetohydrodynamic code NOVA are in close agreement with experiment.

Journal Article↗

Calmodulin concentrates at the apex of growing hyphae and localizes to the Spitzenkörper in Aspergillus nidulans.

The calmodulin (CaM) localization pattern in the growing hyphal tip of Aspergillus nidulans was studied with the functional GFP::CaM fusion protein. A faint tip-high gradient of CaM was found in the growing hyphal tip, with CaM highly localized in the region corresponding to the Spitzenkörper forming a bright granule. The position of highly concentrated CaM in the extreme apex seemed to determine the orientation of the hypha. The normal pattern of CaM localization was also shown to be dependent on the integrated actin cytoskeleton. When the growth of the hyphal tip ceased, CaM failed to localize in the bright granule and was evenly distributed in the hyphal tip. These findings suggest that CaM may play an important role in establishing and maintaining apical organization, morphogenesis, and growth in Aspergillus nidulans.

Actins↗

Expression of gentisate 1,2-dioxygenase (gdoA) genes involved in aromatic degradation in two haloarchaeal genera.

Gentisate-1,2-dioxygenase genes (gdoA), with homology to a number of bacterial dioxygenases, and genes encoding a putative coenzyme A (CoA)-synthetase subunit (acdB) and a CoA-thioesterase (tieA) were identified in two haloarchaeal isolates. In Haloarcula sp. D1, gdoA was expressed during growth on 4-hydroxybenzoate but not benzoate, and acdB and tieA were not expressed during growth on any of the aromatic substrates tested. In contrast, gdoA was expressed in Haloferax sp. D1227 during growth on benzoate, 3-hydroxybenzoate, cinnamate and phenylpropionate, and both acdB and tieA were expressed during growth on benzoate, cinnamate and phenylpropionate, but not on 3-hydroxybenzoate. This pattern of induction is consistent with these genes encoding steps in a CoA-mediated benzoate pathway in this strain.

Benzoates↗

Response of ferrogels subjected to an ac magnetic field.

When a ferrogel, which is chemically cross-linked polymer networks swollen with a ferrofluid, consisting of magnetic particles having nonlinear characteristics is subjected to an alternating current (ac) magnetic field, the magnetic response will generally consist of ac fields at frequencies of the higher-order harmonics. By using a perturbation approach, we investigate nonlinear ac responses of ferrogels, under an ac magnetic field either coupled with a dc magnetic field or not. It is shown that it is possible to detect the volume fraction and shape of particles in ferrogels by measuring such ac responses. Our results are very well understood in spectral representation and are favorably compared with the experimental observations of suspensions being beyond ferrogels.

Gels↗

Identification of genes targeted by the androgen and PKA signaling pathways in prostate cancer cells.

Progression of prostate cancer to androgen independence is suspected to involve the androgen and protein kinase A (PKA) signaling pathways. Here for the first time, the transcriptomes associated with each pathway and common transcriptional targets in response to stimulation of both pathways were identified in human prostate cancer cells using Affymetrix GeneChip technology (Human Genome U133 plus2). Statistically significant changes in the levels of 858 genes in response to androgen and 303 genes in response to activation of the PKA pathway were determined using GeneSpring software. Expression of a subset of these genes (22) that were transcriptional targets for the androgen and/or PKA pathways were validated by reverse transcriptase-polymerase chain reaction and Western blot analyses. Application of small interfering RNAs to the androgen receptor (AR) revealed that in addition to KLK3, levels of expression of KLK2 and SESN1 were regulated by AR activated by both the androgen and PKA signaling pathways. SESN1 was identified as a gene repressed by activated AR. These results provide a broad view of the effects of the androgen and PKA signaling pathways on the transcriptional program of prostate cancer cells and indicate that only a limited number of genes are targeted by cross-talk between AR and PKA pathways.

Androgens↗

Co-transplantation of bone marrow stromal cells transduced with IL-7 gene enhances immune reconstitution after allogeneic bone marrow transplantation in mice.

Allogeneic bone marrow transplantation (allo-BMT) is followed by a period of profound immune deficiency, which results in significant susceptibility to infections and limits the extensive application of this approach in clinic. Here, we transduced human interleukin-7 (IL-7) gene into donor-derived bone marrow stromal cells (MSCs) using adenovirus vector, and transplanted this gene-engineered MSCs (MSC-IL-7) into lethally irradiated C57BL/6 mice to investigate their effects on immune reconstitution following allo-BMT. Recipient mice receiving MSC-IL-7 cells plus T-cell-depleted bone marrow cells of BALB/c mice showed a significant increase in thymopoiesis and homeostatic expansion of peripheral T lymphocytes. Furthermore, injection of MSC-IL-7 cells following allo-BMT protected the host from the lethality caused by acute graft-versus-host disease (GVHD) and prevented the occurrence of GVHD induced by transplanted T cells. Thus, the use of MSC-IL-7 cells may be therapeutically useful for enhancing immune reconstitution without aggravating GVHD in allo-BMT mice.

Adenoviridae↗

Navigated open-wedge high tibial osteotomy: advantages and disadvantages compared to the conventional technique in a cadaver study.

High tibial osteotomy (HTO) is an established therapy for the treatment of symptomatic varus malaligned knees. A main reason for disappointing clinical results after HTO is the under- and overcorrection of the mechanical axis due to insufficient intraoperative visualisation. Twenty legs of fresh human cadaver were randomly assigned to navigated open-wedge HTO (n=10) or conventional HTO using the cable method (n=10). Regardless of the pre-existing alignment, the aim of all operations was to align the mechanical axis to pass through 80% of the tibial plateau (beginning with 0% at the medial edge of the tibial plateau and ending with 100% at the lateral edge). This overcorrection was chosen to ensure a sufficient amount of correction. Thus, the medial proximal tibia angle (MPTA) increased by 9.1+/-2.9 degrees (range 5.2 degrees -12.3 degrees ) on the average after navigated HTO and by 8.9+/-2.9 degrees (range 4.7 degrees -12.6 degrees ) after conventional HTO. After stabilization with a fixed angle implant, the alignment was measured by CT. After navigated HTO, the mechanical axis passed the tibial plateau through 79.7% (range 75.5-85.8%). In contrast, after conventional HTO, the average intersection of the mechanical axis was at 72.1% (range 60.4-82.4%) (P=0.020). Additionally, the variability of the mean corrections was significantly lower in the navigated group (3.3% vs. 7.2%, P=0.012). Total fluoroscopic radiation time was significantly lower in the navigated group (P=0.038) whereas the mean dose area product was not significantly different (P=0.231). The time of the operative procedure was 23 min shorter after conventional HTO (P<0.001). Navigation systems provide intraoperative 3-dimensional real time control of the frontal, sagittal, and transverse axis and may increase the accuracy of open-wedge HTO. Future studies have to analyse the clinical effects of navigation on corrective osteotomies.

Adult↗

Limits on spin-independent interactions of weakly interacting massive particles with nucleons from the two-tower run of the cryogenic dark matter search.

We report new results from the Cryogenic Dark Matter Search (CDMS II) at the Soudan Underground Laboratory. Two towers, each consisting of six detectors, were operated for 74.5 live days, giving spectrum-weighted exposures of 34 (12) kg d for the Ge (Si) targets after cuts, averaged over recoil energies 10-100 keV for a weakly interacting massive particle (WIMP) mass of 60 GeV/c2. A blind analysis was conducted, incorporating improved techniques for rejecting surface events. No WIMP signal exceeding expected backgrounds was observed. When combined with our previous results from Soudan, the 90% C.L. upper limit on the spin-independent WIMP-nucleon cross section is 1.6 x 10(-43) cm2 from Ge and 3 x 10(-42) cm2 from Si, for a WIMP mass of 60 GeV/c2. The combined limit from Ge (Si) is a factor of 2.5 (10) lower than our previous results and constrains predictions of supersymmetric models.

Journal Article↗

A novel isoform of prostate apoptosis response 4 (PAR-4) that co-distributes with F-actin and prevents apoptosis in neural stem cells.

The elevated expression of prostate apoptosis response-4 (PAR-4) induces apoptosis in differentiating mouse embryonic stem (ES) cells. In embryoid body (EB) cells and the E15.5 stage of embryonic mouse brain, PAR-4 is expressed as two isoforms (38 and 33 kDa). Using mouse EB-derived RNA as a template we have cloned and characterized a novel isoform of PAR-4 (PAR-4/p33) that lacks exon 3 and shows a bona fide splice junction of exons 2 and 4. The molecular mass for PAR-4/p33 is estimated to be 33 kDa, corresponding to the short form found in the EB cells and E15.5 mouse brain. The fluorescent fusion protein of PAR-4/p33 is mainly found in the cytosol and is co-distributed with F-actin filaments, while that of the 38 kDa full length PAR-4/p38 is predominantly translocated to the nucleus. In contrast to the full length PAR-4 (PAR-4/p38), ectopic expression of PAR-4/p33 does not result in the activation of caspase 3 and the induction of apoptosis. PAR-4/p33 forms a complex with PAR-4/p38, which inhibits its nuclear translocation and the induction of apoptosis. PAR-4/p33 is suggested to be a dominant negative isoform of PAR-4/p38 and may regulate PAR-4-dependent apoptosis.

Actins↗

Periodic ZnO nanorod arrays defined by polystyrene microsphere self-assembled monolayers.

We demonstrate a low-cost and effective method to fabricate hexagonally patterned, vertically aligned ZnO nanorod arrays. Selective wet-etching is used to develop the catalyzing gold particle hexagonal pattern with the aid of a polystyrene microsphere self-assembled monolayer. The gold particles have tunable sizes independent of the polystyrene microsphere's diameter and are inherently round in shape. Each ZnO rod is grown individually from a catalyzing site via catalyst-initiated epitaxy, and the original hexagonal periodicity is well-preserved. The rods have flat ends, and the diameters of the rods can be controlled well by the amount of source materials. This method provides a promising way to create ZnO one-dimensional nanostructures for applications as two-dimensional photonic crystal, sensor arrays, nanolaser arrays, and optoelectronic devices.

Crystallization↗

Comparison between anagrelide and hydroxycarbamide in their activities against haematopoietic progenitor cell growth and differentiation: selectivity of anagrelide for the megakaryocytic lineage.

Anagrelide (ANA) and hydroxycarbamide (HC) are two distinct pharmacological agents used to treat thrombocythaemia associated with myeloproliferative disorders. Although both drugs have been in clinical use for a number of years, comparative studies of their selectivity and mode of action are still lacking. Here, we have evaluated the activities of ANA and HC on the growth and differentiation of human haematopoietic progenitor cells in liquid culture. Both drugs inhibited thrombopoietin-induced megakaryocytopoiesis in a dose-dependent manner, but with strikingly different potencies (IC(50)=26 nM for ANA and 30 muM for HC) and modes of action. Whereas HC inhibited cell proliferation, ANA acted primarily on the differentiation process. At doses that abrogated megakaryocytopoiesis, HC also inhibited the expansion of CD34(+) cells stimulated by stem cell factor, interleukin-3 and Flt-3 ligand and also induced apoptosis. Furthermore, HC inhibited erythroid and myelomonocytic cell growth, induced by erythropoietin or granulocyte-macrophage colony-stimulating factor, respectively. In contrast, ANA showed none of these additional effects. Taken together, these results demonstrate that ANA is a potent and selective inhibitor of megakaryocytopoiesis, having no significant activity against haematopoietic progenitor cell expansion or differentiation into other lineages. In contrast, the anti-megakaryocytopoietic activity of HC cannot be dissociated from its more general cytoreductive and cytotoxic actions.

Antigens, CD34↗