Search PubMed⌕ Search

Biomedical subjects

G Yu

Publications and source records attributed to G Yu.

At least 37 records · Page 2Linked to original sources
PubMed2004

A comparative study of the hydrolysis pathways of substituted aryl phosphoramidate versus aryl thiophosphoramidate derivatives of stavudine.

A comparative study of aryl phosphoramidate and aryl thiophosphoramidate derivatives of 2',3'-didehydro-2',3'-dideoxythymidine (d4T) was performed. The study focused on the nature of the substituents and the influence of a thiophosphoramidate in the structure of these derivatives. The rate of alkaline hydrolysis of these two types of d4T derivatives indicated that replacement of oxygen with sulfur decreases the rate of hydrolysis by twofold. Additionally, the activation energy (E(a)) for the sulfur analogs is comparatively higher than that of the oxygen analogs. Notably, an intermediate was formed in the hydrolysis reaction of the sulfur analogs of d4T that was absent in the case of the oxygen analog, and the tentative structure of the intermediate was proposed based on LC/mass spectroscopy data. Using both HPLC and (31)P-NMR techniques, we identified the hydrolysis product of the phosphoramidate derivatives and were able to show in in vitro studies that porcine liver esterase can hydrolyze the methyl ester portion of the phosphoramidate derivatives. Aryl phosphoramidate derivatives of d4T were 1000-fold more active than the corresponding aryl thiophosphoramidate derivatives, indicating that the energy of activation of hydrolysis of these phosphoramidate derivatives plays a significant role in their biological potency.

Amides↗
PubMed2004

Molecular structural characteristics governing biocatalytic chlorination of PAHs by chloroperoxidase from Caldariomyces fumago.

Based on some fundamental quantum chemical descriptors computed by PM3 Hamiltonian, a quantitative structure-property relationship (QSPR) for specific activity of 17 polycyclic aromatic hydrocarbons (PAHs) of biocatalytic chlorination by chloroperoxidase (CPO) from Caldariomyces fumago was developed using partial least squares (PLS) regression. The model can be used to estimate biocatalytic chlorination reaction rates of PAHs. The main factors affecting specific activity of PAHs of biocatalytic chlorination by CPO from Caldariomyces fumago are absolute hardness, dipole moment, absolute electronegativity, and molecular bulkness of the PAH molecules. The biocatalytic chlorination reaction rates of PAHs with large values of absolute hardness, absolute electronegativity, and molecular bulkness tend to be slow. Increasing dipole moment of PAHs leads to increase the specific activity.

Ascomycota↗
PubMed2004

Quantitative structure-property relationships on direct photolysis of PCDD/Fs on surfaces of fly ash.

Fly ash samples containing polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were generated by combustion of polyvinyl chloride, wood, high-density polyethylene and styrene. By partial least-squares (PLS) regression, quantitative structure-property relationship (QSPR) models were developed for photolysis half-lives (t(1/2)) of PCDD/Fs adsorbed on fly ash surfaces and irradiated by UV-B of simulated sunlight. Quantum chemical descriptors computed by PM3 hamiltonian were used as predictor variables. The cross validated value for the optimal QSPR model was 0.678, indicating robustness and good predictive abilities of the model. The QSPR results showed that the stability of the PCDD/F molecules increased with the increase of chlorine atoms in the parent molecules. Increasing the energy of the highest occupied molecular orbital (E(HOMO)), the energy of the lowest unoccupied molecular orbital (E(LUMO)), E(LUMO)+E(HOMO) and E(LUMO)-E(HOMO) values of the PCDD/Fs led to decrease of log t(1/2) values. Increasing the most negative atomic charge on the oxygen atom of PCDD/Fs led to elevated log t(1/2) values. The log t(1/2) values of PCDD/Fs increased with the decrease of the largest negative atomic charge on a carbon atom.

Benzofurans↗
PubMed2004

Characterization and functional study of five novel monoclonal antibodies against human OX40L highlight reverse signalling: enhancement of IgG production of B cells and promotion of maturation of DCs.

OX40 ligand (OX40L), a molecule originally identified as human gp34, is an important co-stimulatory molecule during immune response. In this study, we report on five functional mouse anti-human OX40L monoclonal antibodies named as 9H10, 4C12, 8D10, 4H4 and 1G1, characterized by means of flow cytometry, Western blot and competition assay. These monoclonal antibodies bound to distinct OX40L epitopes on activated B cells and dendritic cells (DCs) and two of them could suppress the proliferation of T lymphocytes co-stimulated by mature DCs. Furthermore, we demonstrated that our monoclonal antibodies, such as 9H10 and 4C12, could trigger OX40L reverse signal that enhanced IgG production of B cells and promoted maturation of DCs as evidenced by the upexpression of CD80, CD86, CD83 and CXCR4 and monoclonal antibody 9H10 could also promote anti-CD40 monoclonal-antibody-stimulated DCs in order to induce T cells to secrete more interleukin-2 and interferon-gamma, which suggested that OX40L signals could strengthen the effect of CD40 signals on promoting Th1 differentiation.

Animals↗
PubMed2004

Intracerebral xenotransplantation of GFP mouse bone marrow stromal cells in intact and stroke rat brain: graft survival and immunologic response.

The present study characterized survival and immunologic response of bone marrow stromal cells (BMSCs) following transplantation into intact and stroke brains. In the first study, intrastriatal transplantation of BMSC (60,000 in 3 microl) or vehicle was performed in normal adult Sprague-Dawley male rats that subsequently received daily cyclosporin A (CsA, 10 mg/kg, IP in 3 ml) or vehicle (olive oil, similar volume) starting on day of surgery up to 3 days posttransplantation. Animals were euthanized at 3 or 30 days posttransplantation and brains were processed either for green fluorescent protein (GFP) microscopy or flow cytometry (FACS). Both GFP epifluorescence and FACS scanning revealed GFP+ BMSCs in both groups of transplanted rats with or without CsA, although significantly increased (1.6- to 3-fold more) survival of GFP+ BMSCs was observed in the immunosuppressed animals. Further histologic examination revealed widespread dispersal of BMSCs away from the graft core accompanied by many long outgrowth processes in non-CsA-transplanted animals, whereas a very dense graft core, with cells expressing only sporadic short outgrowth processes, was observed in CsA-transplanted animals. There were no detectable GFP+ BMSCs in nontransplanted rats that received CsA or vehicle. Immunologic response via FACS analysis revealed a decreased presence of cytotoxic cells, characterized by near complete absence of CD8+ cells, and lack of activation depicted by low CD69 expression in CsA-treated transplanted animals. In contrast, elevated levels of CD8+ cells and increased activation of CD69 expression were observed in transplanted animals that received vehicle alone. CD4+ helper cells were almost nondetectable in transplanted rats that received CsA, but also only minimally elevated in transplanted rats that received vehicle. Nontransplanted rats that received either CsA or vehicle displayed very minimal detectable levels of all three lymphocyte markers. In the second study, a new set of male Sprague-Dawley rats initially received bilateral stereotaxic intrastriatal transplantation of BMSCs and 3 days after were subjected to unilateral transient occlusion of middle cerebral artery. The animals were allowed to survive for 3 days after stroke without CsA immunosuppression. Epifluorescence microscopy revealed significantly higher (5-fold more) survival of transplanted GFP+ BMSCs in the stroke striatum compared with the intact striatum. The majority of the grafts remained within the original dorsal striatal transplant site, characterized by no obvious migration in intact striatum, but with long-distance migration along the ischemic penumbra in the stroke striatum. Moreover, FACS scanning analyses revealed low levels of immunologic response of grafted BMSCs in both stroke and intact striata. These results, taken together, suggest that xenotransplantation of mouse BMSCs into adult rats is feasible. Immunosuppression therapy can enhance xenograft survival and reduce graft-induced immunologic response; however, in the acute phase posttransplantation, BMSCs can survive in intact and stroke brain, and may even exhibit long-distance migration and increased outgrowth processes without immunosuppression.

Animals↗
PubMed2003

Sequencing and characterization of the full-length gene encoding the single-stranded DNA binding protein of a novel Chelonian herpesvirus.

Through 4 consecutive genomic walks employing a recently modified inverse polymerase chain reaction technique, a 4,054-bp DNA fragment of a newfound green turtle herpesvirus (GTHV) was obtained from tumor tissues of a green turtle with fibropapillomas. This newly identified viral DNA fragment contains two non-overlapping open reading frames (ORF) oriented in the 3' to 5' direction. The first ORF is 59% G+C rich and contains the full-length genomic sequence of the DNA binding protein (DBP) gene (3,585 bp) encoding a protein of 1,195 amino acid residues in length. The second ORF encodes a partial peptide of the UL28 gene. Phylogenetic analysis of the GTHV DBP gene confirmed and substantiated that this novel Chelonian herpesvirus is closely related to the subfamily Alphaherpesvirinae. Examination of the translated amino acid sequence further supports this categorization since GTHV DBP comprises a highly conserved zinc finger motif (CXLCX4RX2C) and a putative DNA binding domain, and exhibits high sequence homology to other alphaherpesviruses. Cloning and sequencing the genome of this putative herpesvirus will facilitate current understanding of its role in causing GTFP and the development of molecular- and immuno-based methods for the diagnosis and prevention of this devastating disease of green turtles.

Alphaherpesvirinae↗
PubMed2003

Fate and assessment of persistent organic pollutants in water and sediment from Minjiang River Estuary, Southeast China.

Persistent organochlorine compounds were analyzed in surface water, porewater and surficial sediment samples from Minjiang River Estuary, which is the first large river in Fujian Province, Southeast of China. The total concentrations of 18 organochlorine pesticides were 214.4-1819, 4541-13,699 ng/l, 28.79-52.07 ng/g in surface water, porewater and sediments (dry weight) respectively, and those of 21 polychlorinated biphenyls (PCBs) in the three phases were: 203.9-2473, 3192-10,855 ng/l, 15.14-57.93 ng/g respectively. The results showed that the concentrations of these selected organochlorine pesticides and PCBs in porewater were higher than those in surface water. It may be due to the fact that these organic hydrophobic pollutants tend to stay in the sediments, and then re-suspend from the sedimentary phase to the upper water. We have analyzed the distribution characteristics of individual organochlorine pesticide components and PCBs, and found that alpha-HCH, DDE, Heptachlor, Endosulfan II, Methoxychlor were the most common organochlorine pesticides contaminants. Considering the groups of HCHs (HCHs=alpha-HCH+beta-HCH+gamma-HCH+delta-HCH) and DDTs (DDTs=DDT+DDD+DDE), the predominance of beta-HCH, DDE in all water, porewater and sediment samples was clearly observed. This observation suggested that beta-HCH was resistant to biodegradation and the DDTs had been transformed to its metabolites, DDE and DDD, of which DDE that was more un-degradable. The PCB congeners containing 3-6 chlorines had the great preponderance in the three phase. These results were compared with those present in other estuaries and harbors. A risk assessment was evaluated for the persistent organic pollutants in the Minjiang River Estuary.

China↗
PubMed2002

Occurrence and behaviour of organophosphorus insecticides in the River Wuchuan, southeast China.

Organophosphorus (OP) insecticides are used worldwide, yet their persistence in the environment is not well understood. This paper summarises recent research on 17 OP insecticides in the River Wuchuan, an important catchment in China, by determining their concentrations in water, soil, sediment and plants by gas chromatography with flame photometric detection (GC-FPD). The concentrations of the total OP insecticides ranged from 92.77 to 229 ng l-1 in river water, 1.61 to 9.93 ng g-1 dry weight in soil, 1.24 to 7.56 ng g-1 dry weight in sediment and 75.28 to 326 ng g-1 dry weight in plants. There was a relatively high abundance of methamidophos, dichlorvos, malathion, omethoate and dimethoate in all water, soil, sediment and plant samples. On average, these five compounds collectively accounted for 64%, 71%, 71% and 54% of the total OP insecticide concentration in water, soil, sediment and plants, respectively, which was similar to the composition of OP insecticides in application formulations used in our study area and in China as a whole. The results therefore reflect the application pattern to some extent, and suggest that the sources of the OP insecticides are mainly from current usage. When compared with other areas, the levels of OP insecticides in the River Wuchuan were moderate. The animal and human risks from exposure to OP insecticides in water and plants were evaluated against relevant threshold values. The results therefore provide important information on the current contamination status of a key agricultural watershed in China, and point to the need for urgent action to control the use of some excessively applied and potentially persistent agrochemicals, such as methamidophos, omethoate and dimethoate.

China↗
PubMed2002

Dissolved insecticides and polychlorinated biphenyls in the Pearl River Estuary and South China Sea.

Persistent organic pollutants (POPs) such as organochlorine (OCl) insecticides and polychlorinated biphenyls (PCB), together with the new generation of organophosphorus (OP) insecticides, are of global concern, due to their widespread occurrence, persistence, bioaccumulation and hormone disruption potential. This paper represents an attempt to study the source and transportation of such pollutants in estuarine and coastal environments as an integrated ecosystem, by determining the levels of 18 OCl insecticides, 21 PCB congeners, and 17 OP insecticides in the Pearl River Estuary and South China Sea. The total concentrations varied from 126-1198 ng l(-1) for OCl insecticides, 33.38-1064 ng l(-1) for PCB congeners, and 4.44-6356 ng l(-1) for OP insecticides in the Pearl River Estuary. In comparison, their levels in the South China Sea were significantly lower, varying from 57.09-202 ng l(-1) for OCl insecticides, 21.72-144 ng l(-1) for PCBs, and 1.27-122 ng l(-1) for OP insecticides, respectively. The predominance of beta-HCH in HCHs, and DDE in DDTs in all water samples was clearly observed, suggesting beta-HCH and DDE's resistance to further degradation. The PCBs were dominated by those with 3-6 chlorines. The distribution characteristic of OP insecticides shows that five compounds (methamidophos, dimethoate, malathion, dichlorvos and omethoate) accounted for 56% and 72% of the total OP insecticide concentration. The relationship between pollutant concentrations and salinity in the estuary showed that they were all removed during the mixing process, therefore behaving non-conservatively.

China↗
PubMed2001

APH-2/nicastrin functions in LIN-12/Notch signaling in the Caenorhabditis elegans somatic gonad.

Nicastrin is a recently identified member of high-molecular weight complexes containing presenilin. The Caenorhabditis elegans homolog of nicastrin, aph-2, was shown to be required for GLP-1/Notch signaling in the early embryo. In addition to the maternal-effect embryonic lethal phenotype, aph-2 mutant animals also display an egg-laying defect. We show that this latter defect is related to the SEL-12/presenilin egg-laying defect. We also show that aph-2 and sel-12 genetically interact and cooperate to regulate LIN-12/Notch signaling in the development of the somatic gonad. In addition, aph-2 and lin-12/Notch genetically interact. We illustrate a new role for aph-2 in facilitating lin-12 signaling in the somatic gonad, thus providing evidence that APH-2 is involved in both GLP-1/Notch- and LIN-12/Notch-mediated signaling events. Finally, we demonstrate that nicastrin can partially substitute for aph-2, suggesting a conservation of function between these proteins.

Amyloid Precursor Protein Secretases↗
PubMed2001

Wild-type and mutated nicastrins do not display aminopeptidase M- and B-like activities.

Nicastrin is a recently discovered protein interacting with presenilins and the beta-amyloid precursor protein, the proteins playing key roles in Alzheimer's disease and which, when mutated, appear responsible for early-onset familial forms of Alzheimer's disease. Nicastrin was reported to modulate beta-amyloid production, a phenotype affected differently by missense mutations or deletions of a conserved hydrophilic domain. In addition to such a function, nicastrin was recently suggested to possess putative catalytic activity based on its sequence homology with enzymes of the aminopeptidase family. We set up stably transfected human HEK293 cells expressing either wild-type or mutated nicastrins and we show that these proteins do not exhibit aminopeptidase M- and B-like activities.

Alzheimer Disease↗
PubMed2001

Should stroke subtype influence anticoagulation decisions to prevent recurrence in stroke patients with atrial fibrillation?

BACKGROUND AND PURPOSE: Long-term anticoagulation is routinely used for secondary stroke prevention in atrial fibrillation, often regardless of stroke subtype. Although the role of warfarin in cardioembolic stroke is established, it may not prevent recurrence in other stroke subtypes, even in the presence of atrial fibrillation. METHODS: This was a 2-year, prospective, intervention study conducted in a district general hospital. Participants included 386 acute stroke patients with atrial fibrillation. Subjects were characterized for stroke subtype on clinical, neuroimaging, carotid ultrasonographic, and echocardiographic criteria. Eligible patients were treated with adjusted-dose warfarin (international normalized ratio, 2.0 to 3.0). Aspirin (75 to 300 mg/d) was used in patients with contraindications or those who refused anticoagulation. The main outcome measures were rate of recurrent stroke by subtype and major and minor bleeding complications. RESULTS: The aspirin group (n=172) was comparable to the warfarin group (n=214) in terms of age, sex, risk factors, and initial stroke subtype. The rate of recurrent stroke was higher (9.5% versus 4.9%, P<0.02) but that of major bleeding was lower (0.6% versus 2.5%, P<0.05) with aspirin. The increased stroke rate with aspirin was due predominantly to cardioembolic recurrence in patients presenting initially with cardioembolic stroke (8.4% versus 1.9%, P<0.01). The recurrence rate in aspirin-treated patients who presented with lacunar stroke and atrial fibrillation was similar to that seen in patients receiving warfarin (8.8% versus 8.9%). CONCLUSIONS: In this cohort of stroke patients with atrial fibrillation, anticoagulation was superior to aspirin in preventing cardioembolic but not lacunar recurrence. Determination of stroke subtype may be important in anticoagulation decisions for secondary prevention, and further studies are required.

Aged↗
PubMed2001

Evidence that GRIP, a PDZ-domain protein which is expressed in the embryonic forebrain, co-activates transcription with DLX homeodomain proteins.

The DLX homeodomain proteins control development of the basal ganglia and branchial arches. To identify co-factors that regulate DLX function we utilized the yeast two-hybrid assay, and found a DLX interacting protein (DIP2) which binds to the N-terminal region of DLX2 via a PDZ domain. DIP2 appears to be an alternatively spliced form of GRIP1, a protein known to bind AMPA glutamate receptors via PDZ domains. Thus, we named it GRIP1b. We provide evidence that GRIP1b can function as a transcriptional co-activator of DLX2 and DLX5. Glutamate receptors inhibit this co-activation. These results suggest that some PDZ proteins may regulate transcription via their interactions with homeodomain proteins. Furthermore, these results suggest a link between glutamate receptors, PDZ proteins and the DLX transcription factors, all of which are co-expressed in the developing basal ganglia.

Alternative Splicing↗
PubMed2001

Palaeovegetation. Diversity of temperate plants in east Asia.

The exceptionally broad species diversity of vascular plant genera in east Asian temperate forests, compared with their sister taxa in North America, has been attributed to the greater climatic diversity of east Asia, combined with opportunities for allopatric speciation afforded by repeated fragmentation and coalescence of populations through Late Cenozoic ice-age cycles. According to Qian and Ricklefs, these opportunities occurred in east Asia because temperate forests extended across the continental shelf to link populations in China, Korea and Japan during glacial periods, whereas higher sea levels during interglacial periods isolated these regions and warmer temperatures restricted temperate taxa to disjunct refuges. However, palaeovegetation data from east Asia show that temperate forests were considerably less extensive than today during the Last Glacial Maximum, calling into question the coalescence of tree populations required by the hypothesis of Qian and Ricklefs.

Biological Evolution↗
PubMed2001

Repression of AIM-1 kinase mRNA as part of a program of genes regulated by Mpl ligand.

Megakaryocytes give rise to platelets that are essential for thrombosis and hemostasis. During development, megakaryocytes undergo an endomitotic cell cycle by which they skip late anaphase and cytokinesis to yield high ploidy cells. This process is regulated by the c-Mpl receptor ligand. In the current study we used differential display PCR as well as degenerate cloning of kinases to identify part of the program of genes regulated during Mpl ligand-induced differentiation. Several of the induced genes were identified as encoding metabolic proteins as carnitine palmitolytransferase, while other altered genes were identified as encoding kinases. Of these, AIM-1 kinase mRNA was severely downregulated by Mpl ligand at the onset of polyploidy in megakaryocytes. This effect was not related to message stability, but rather to a change in transcriptional rate. These data point to the potential importance of the transcriptional regulation of the AIM-1 gene for promoting megakaryocyte polyploidization.

Animals↗
PubMed2001

ISMh2, a novel insertion sequence-like element associated with nifA from Mesorhizobium huakuii.

Sequence analysis of the nifA gene, including its 5' flanking region, of Mesorhizobium huakuii revealed the presence of a novel IS-like element called ISMh2. It is 828 bp in length and possesses two imperfect terminal inverted repeats of 14 bp with only one mismatch. The putative transposase encoded by ISMh2 is composed of 204 amino acids. In comparison with other insertion sequences ISMh2 likely belongs to the IS6 family. Multiple copies of ISMh2 were detected in the genome of M. huakuii 159 by Southern hybridization. RT-PCR analysis showed that nifA and ISMh2 cotranscribed. Attempts to detect the transposition ability of ISMh2 were unsuccessful.

Alphaproteobacteria↗