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Articles by L Wu
Total Records ( 8 ) for L Wu
  J Yang , X Liu , J Yu , L Sheng , Y Shi , Z Li , Y Hu , J Xue , L Wu , Y Liang , J Xia and D. Liang
 

Gene therapy has emerged as a promising approach for the lethal disorder of Duchenne muscular dystrophy (DMD). Using a novel non-viral delivery system, the human ribosomal DNA (hrDNA) targeting vector, we targeted a minidystrophin-GFP fusion gene into the hrDNA locus of HT1080 cells with a high site-specific integrated efficiency of 10–5, in which the transgene could express efficiently and continuously. The minidystrophin-GFP fusion protein was easily found to localize on the plasma membrane of HT1080 cells, indicating its possible physiologic performance. Our findings showed that the hrDNA-targeting vector might be highly useful for DMD gene therapy study.

  A McTiernan , J Wactawski Wende , L Wu , R. J Rodabough , R Freeman , S Hendrix and R. Jackson
 

Background: The effects of dietary changes on osteoporosis, low bone density, and frequent falls are unestablished.

Objective: We assessed the effect of the Women's Health Initiative Dietary Modification low-fat and increased fruit, vegetable, and grain intervention on incident hip, total, and site-specific fractures and self-reported falls, and, in a subset, on bone mineral density (BMD).

Design: Postmenopausal women (n = 48,835) aged 50–79 y (18.6% of minority race-ethnicity) were randomly assigned to receive the Dietary Modification intervention (40%, n = 19,541) (daily goal: ≤20% of energy as fat, ≥5 servings of vegetables and fruit, and ≥6 servings of grains) or to a comparison group that received no dietary changes (60%; n = 29,294).

Results: After a mean 8.1 y of follow-up, 215 women in the intervention group and 285 women in the comparison group (annualized rate: 0.14% and 0.12%, respectively) experienced a hip fracture (hazard ratio: 1.12; 95% CI: 0.94, 1.34; P = 0.21). The intervention group (n = 5423; annualized rate: 3.44%) had a lower rate of reporting ≥2 falls than did the comparison group (n = 8695; annualized rate: 3.67%) (HR: 0.92; 95% CI: 0.89, 0.96; P < 0.01). There was a significant interaction according to hormone therapy use; those in the comparison group receiving hormone therapy had the lowest incidence of hip fracture. In a subset of 3951 women, hip BMD at years 3, 6, and 9 was 0.4–0.5% lower in the intervention group than in the comparison group (P = 0.003).

Conclusions: A low-fat and increased fruit, vegetable, and grain diet intervention modestly reduced the risk of multiple falls and slightly lowered hip BMD but did not change the risk of osteoporotic fractures. This trial was registered at clinicaltrials.gov as NCT00000611.

  W Han , L Wu , S Chen and K.N. Yu
 

In the present work, the inhibitory effect of carbon monoxide (CO), generated by tricarbonyldichlororuthenium (II) dimer [CO-releasing molecule (CORM-2)], on the toxicity of radiation-induced bystander effect (RIBE) after -particle irradiation was studied in a mixed coculture system. CO (CORM-2) treatment showed a significant inhibitory effect to the formation of p53 binding protein 1 (BP1) and micronuclei (MN) induced by RIBE in a concentration-dependent manner, but in the directly irradiated cell population no distinct decreases of BP1 and MN formation were observed. In this mixed coculture system, nitric oxide (NO) or superoxide anion $${(\hbox{ O }}_{2}^{\cdot -})$$ was also proved to mediate the transduction of RIBE by using a NO synthase inhibitor or NADPH-oxidase-specific inhibitor treatment. The elevated $${\hbox{ O }}_{2}^{\cdot -}$$ was attenuated by CO (CORM-2) treatment in the bystander cells as measured by hydroethidine staining and fluorescence assessment. The exogenous NO (sper) or $${\hbox{ O }}_{2}^{\cdot -}$$ (H2O2) was used to mimic NO/O2-mediated RIBE, and CO (CORM-2) treatment also showed a protective effect to cells against the toxicity of these exogenous factors. Considering the inhibitory effect of CO on RIBE and the wide use of CO in therapy of diseases, it is hoped that a low concentration of CO can protect normal tissues against RIBE during radiotherapy.

  G. L Anderson , M McIntosh , L Wu , M Barnett , G Goodman , J. D Thorpe , L Bergan , M. D Thornquist , N Scholler , N Kim , K O'Briant , C Drescher and N. Urban
  Background

CA125, human epididymis protein 4 (HE4), mesothelin, B7-H4, decoy receptor 3 (DcR3), and spondin-2 have been identified as potential ovarian cancer biomarkers. Except for CA125, their behavior in the prediagnostic period has not been evaluated.

Methods

Immunoassays were used to determine concentrations of CA125, HE4, mesothelin, B7-H4, DcR3, and spondin-2 proteins in prediagnostic serum specimens (1–11 samples per participant) that were contributed 0–18 years before ovarian cancer diagnosis from 34 patients with ovarian cancer (15 with advanced-stage serous carcinoma) and during a comparable time interval before the reference date from 70 matched control subjects who were participating in the Carotene and Retinol Efficacy Trial. Lowess curves were fit to biomarker levels in cancer patients and control subjects separately to summarize mean levels over time. Receiver operating characteristic curves were plotted, and area-under-the curve (AUC) statistics were computed to summarize the discrimination ability of these biomarkers by time before diagnosis.

Results

Smoothed mean concentrations of CA125, HE4, and mesothelin (but not of B7-H4, DcR3, and spondin-2) began to increase (visually) in cancer patients relative to control subjects approximately 3 years before diagnosis but reached detectable elevations only within the final year before diagnosis. In descriptive receiver operating characteristic analyses, the discriminatory power of these biomarkers was limited (AUC statistics range = 0.56–0.75) but showed increasing accuracy with time approaching diagnosis (eg, AUC statistics for CA125 were 0.57, 0.68, and 0.74 for ≥4, 2–4, and <2 years before diagnosis, respectively).

Conclusion

Serum concentrations of CA125, HE4, and mesothelin may provide evidence of ovarian cancer 3 years before clinical diagnosis, but the likely lead time associated with these markers appears to be less than 1 year.

  H Inada , L Wu , J Wall , D Su and Y. Zhu
 

We report the performance of the first aberration-corrected scanning transmission electron microscope (STEM) manufactured by Hitachi. We describe its unique features and versatile capabilities in atomic-scale characterization and its applications in materials research. We also discuss contrast variation of the STEM images obtained from different annular dark-field (ADF) detectors of the instrument, and the increased complexity in contrast interpretation and quantification due to the increased convergent angles of the electron probe associated with the aberration corrector. We demonstrate that the intensity of atomic columns in an ADF image depends strongly on a variety of imaging parameters, sample thickness, as well as the nuclear charge and the deviation from their periodic position of the atoms we are probing. Image simulations are often required to correctly interpret the atomic structure of an ADF-STEM image.

  L Wu and H. Q. Yang
 

Plants have evolved complex mechanisms to defend themselves against pathogens. It has been shown that several defense responses are influenced by light, and the red/far-red light photoreceptor phytochromes (PHY) modulate plant defense responses in Arabidopsis. Blue light receptor cryptochromes (CRY) work together with PHY to regulate many light-controlled responses, including photomorphogenesis, floral induction, and entrainment of the circadian clock. We report here that the Arabidopsis blue light photoreceptor CRY1 positively regulates inducible resistance to Pseudomonas syringae under continuous light conditions. By challenging plants with P. syringae pv. tomato (Pst.) DC3000 carrying avrRpt2, we demonstrate that effector-triggered local resistance is down-regulated in the cry1 mutant, leading to more pathogen multiplication. In plants overexpressing CRY1 (CRY1-ovx), however, local resistance is significantly up-regulated. We also show that systemic acquired resistance (SAR) is positively regulated by CRY1, and that salicylic acid (SA)-induced pathogenesis-related gene PR-1 expression is reduced in the cry1 mutant, but enhanced in CRY1-ovx plants. However, our results indicate that CRY1 only modestly influences SA accumulation and has no effect on hypersensitive cell death. These results suggest that CRY1 may positively regulate R protein-mediated resistance to P. syringae with increased PR gene expression.

  G. B Kyei , C Dinkins , A. S Davis , E Roberts , S. B Singh , C Dong , L Wu , E Kominami , T Ueno , A Yamamoto , M Federico , A Panganiban , I Vergne and V. Deretic
 

Autophagy is a cytoplasmic degradative pathway that can participate in biosynthetic processes, as in the yeast Cvt pathway, but is more commonly known for its functions in removing damaged or surplus organelles and macromolecular complexes. Here, we find that autophagy intersects with human immunodeficiency virus (HIV) biogenesis, mirroring the above dichotomy. Early, nondegradative stages of autophagy promoted HIV yields. HIV Gag-derived proteins colocalized and interacted with the autophagy factor LC3, and autophagy promoted productive Gag processing. Nevertheless, when autophagy progressed through maturation stages, HIV was degraded. This, however, does not occur, as the HIV protein Nef acts as an antiautophagic maturation factor through interactions with the autophagy regulatory factor Beclin 1, thus protecting HIV from degradation. The dual interaction of HIV with the autophagy pathway enhances viral yields by using the early stages while inhibiting the late stages of autophagy. The role of Nef in the latter process enhances yields of infectious HIV and may be of significance for progression to clinical AIDS.

  H Lauterbach , B Bathke , S Gilles , C Traidl Hoffmann , C. A Luber , G Fejer , M. A Freudenberg , G. M Davey , D Vremec , A Kallies , L Wu , K Shortman , P Chaplin , M Suter , M O'Keeffe and H. Hochrein
 

Polyinosinic:polycytidylic acid (poly IC), a double-stranded RNA, is an effective adjuvant in vivo. IFN-s (also termed IL-28/29) are potent immunomodulatory and antiviral cytokines. We demonstrate that poly IC injection in vivo induces large amounts of IFN-, which depended on hematopoietic cells and the presence of TLR3 (Toll-like receptor 3), IRF3 (IFN regulatory factor 3), IRF7, IFN-I receptor, Fms-related tyrosine kinase 3 ligand (FL), and IRF8 but not on MyD88 (myeloid differentiation factor 88), Rig-like helicases, or lymphocytes. Upon poly IC injection in vivo, the IFN- production by splenocytes segregated with cells phenotypically resembling CD8+ conventional dendritic cells (DCs [cDCs]). In vitro experiments revealed that CD8+ cDCs were the major producers of IFN- in response to poly IC, whereas both CD8+ cDCs and plasmacytoid DCs produced large amounts of IFN- in response to HSV-1 or parapoxvirus. The nature of the stimulus and the cytokine milieu determined whether CD8+ cDCs produced IFN- or IL-12p70. Human DCs expressing BDCA3 (CD141), which is considered to be the human counterpart of murine CD8+ DCs, also produced large amounts of IFN- upon poly IC stimulation. Thus, IFN- production in response to poly IC is a novel function of mouse CD8+ cDCs and their human equivalents.

 
 
 
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