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Biomedical subjects

Z Wang

Publications and source records attributed to Z Wang.

At least 37 records · Page 2Linked to original sources

Progress in parasitic plant biology: host selection and nutrient transfer.

Host range varies widely among species of parasitic plants. Parasitic plants realize host selection through induction by chemical molecular signals, including germination stimulants and haustoria-inducing factors (HIFs). Research on parasitic plant biology has provided information on germination, haustorium induction, invasion, and haustorial structures and functions. To date, some molecular mechanisms have been suggested to explain how germination stimulants work, involving a chemical change caused by addition of a nucleophilic protein receptor, and direct or indirect stimulation of ethylene generation. Haustorium initiation is induced by HIFs that are generated by HIF-releasing enzymes from the parasite or triggered by redox cycling between electrochemical states of the inducers. Haustorium attachment is non-specific, however, the attachment to a host is facilitated by mucilaginous substances produced by haustorial hairs. Following the attachment, the intrusive cells of parasites penetrate host cells or push their way through the host epidermis and cortex between host cells, and some types of cell wall-degrading enzymes may assist in the penetration process. After the establishment of host-parasite associations, parasitic plants develop special morphological structures (haustoria) and physiological characteristics, such as high transpiration rates, high leaf conductance, and low water potentials in hemiparasites, for nutrient transfer and resource acquisition from their hosts. Therefore, they negatively affect the growth and development and even cause death of their hosts.

Biological Transport↗

A mutated human tumor necrosis factor-alpha improves the therapeutic index in vitro and in vivo.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine that has cytotoxic, cytostatic and immunomodulatory effects on malignant tumors. However, clinical trials have revealed high systemic toxicity and this has hampered its utilization as an anti-cancer agent. In this study, a human TNF-alpha mutant was created and tested for its anti-tumor effects. METHODS: The TNF mutant (recombinant mutated human TNF; rmhTNF) was prepared by protein engineering in which amino acids Pro, Ser and Asp at positions 8, 9 and 10 of TNF-alpha were substituted by Arg, Lys and Arg, and C terminal Leu157 was substituted by Phe, along with deletion of the first seven N-terminal amino acids. Prokaryotic expression recombinant vector pBV-mhTNF containing the PLPR promotor was constructed and transformed into E. coli DH5alpha. The rmhTNF was expressed in a partially soluble form in DH5alpha, purified from the supernatant of cell lysate by ammonia sulfate precipitation and two sequential chromatographic steps. RESULTS: The purified rmhTNF was >95% pure by SDS-PAGE stained with silver and high-pressure size exclusion chromatography (SEC-HPLC). Its yield was about 1.22 mg/g wet cell paste. The mutant rmhTNF exhibited an approximately 50-fold increase in cytotoxicity relative to the wild-type rhTNF on the mouse fibroblast cell line L929 in a standard cytotoxicity test, and at least and at least 50 times higher LD50 as wild type rhTNF in mice. In vivo biological activity studies carried out on tumor cell transplanted mice and nude mice also showed a more effective cytotoxicity of rmhTNF than rhTNF. DISCUSSION: These results suggest that rmhTNF has potential for developing an effective anti-tumor reagent for some tumors.

Animals↗

Use of the inhibitory effect of apoptotic cells on dendritic cells for graft survival via T-cell deletion and regulatory T cells.

Tolerance induction against donor allo-antigens (allo-Ag) remains one of the most challenging aspects of transplant immunology. The ability of dendritic cells (DC) to participate in immunity and tolerance makes them an excellent tool for tolerance induction. Here, we employed the immunosuppressive properties of apoptotic cells to deliver simultaneously an inhibitory signal and donor allo-Ag to recipient DC for treatment of allograft rejection. DC that captured apoptotic cells remained immature and activated deficiently anti-donor CD4(+) T cells that were unable to upregulate T-cell activation markers, to secrete IL-2 and IFN-gamma and to survive under homeostatic conditions due to low expression of Bcl-X(L), IL-7R and IL-15R. Administration of donor apoptotic cells decreased the systemic anti-donor T- and B-cell response and prolonged cardiac allograft survival in mice. The effect was donor specific and required the interaction of donor apoptotic cells with recipient quiescent CD8alpha(+) DC. When combined with CD40-CD154-blockade, administration of donor apoptotic cells resulted in indefinite graft survival mediated by generation of regulatory T cells. The use of the inhibitory effects of apoptotic cells on the anti-donor response provides a new approach to treat transplant rejection.

Animals↗

Transplanted endothelial cells enhance orthotopic bone regeneration.

The aim of this study was to determine if endothelial cells could enhance bone marrow stromal-cell-mediated bone regeneration in an osseous defect. Using poly-lactide-co-glycolide scaffolds as cell carriers, we transplanted bone marrow stromal cells alone or with endothelial cells into 8.5-mm calvarial defects created in nude rats. Histological analyses of blood vessel and bone formation were performed, and microcomputed tomography (muCT) was used to assess mineralized bone matrix. Though the magnitude of the angiogenic response between groups was the same, muCT analysis revealed earlier mineralization of bone in the co-transplantation condition. Ultimately, there was a significant increase (40%) in bone formation in the co-transplantation group (33 +/- 2%), compared with the transplantation of bone marrow stromal cells alone (23 +/- 3%). Analysis of these data demonstrates that, in an orthotopic site, transplanted endothelial cells can influence the bone-regenerative capacity of bone marrow stromal cells.

Absorbable Implants↗

Testosterone induces apoptosis via Fas/FasL-dependent pathway in bone marrow-derived macrophages.

The detailed mechanisms behind the apoptosis of macrophages induced by testosterone are not clear. In the present study, we tried to delineate the effect of testosterone on the apoptosis of bone marrow-derived macrophages (BMMs) and the function of Fas/FasL (Fas ligand) pathway in this course. BMMs were stimulated with testosterone in the presence of macrophage colony stimulating factor (M-CSF) or without. Flow cytometry was used to quantify the apoptosis of BMMs. Real-time RT-PCR and Western blot were performed to analyze the expression of caspase-8, caspase-3, and poly(ADP-ribose) polymerase (PARP) during the Fas/FasL pathway. Our data showed that testosterone could induce the apoptosis of BMMs, similar to removing growth factor M-CSF from the culture medium. They were both associated with the enhanced expression of caspase-8, caspase-3, and PARP. And the phosphorothioate antisense oligodeoxynucleotides to fas-associated death domain protein (FADD) could block the expression of FADD, which is an upstream factor of caspase-8 in the Fas/FasL pathway. It led to the reduced obvious expression of caspase-8 and decreasing apoptosis of BMMs. These results suggest that the Fas/FasL pathway may play an important role in the testosterone-induced apoptosis of macrophages.

Animals↗

Relationships of feedlot feed efficiency, performance, and feeding behavior with metabolic rate, methane production, and energy partitioning in beef cattle.

Residual feed intake (RFI) is the difference between the actual and expected feed intake of an animal based on its BW and growth rate over a specified period. The biological mechanisms underlying the variation in feed efficiency in animals with similar BW and growth rate are not well understood. This study determined the relationship of feedlot feed efficiency, performance, and feeding behavior with digestion and energy partitioning of 27 steers. The steers were selected from a total of 306 animals based on their RFI following feedlot tests at the University of Alberta Kinsella Research Station. Selected steers were ranked into high RFI (RFI > 0.5 SD above the mean, n = 11), medium RFI (RFI +/- 0.5 SD above and below the mean, n = 8), and low RFI (RFI < -0.5 SD below the mean, n = 8). The respective BW +/- SD for the RFI groups were 495.6 +/- 12.7, 529.1 +/- 18.6, and 501.2 +/- 15.5 kg. Digestibility and calorimetry trials were performed on a corn-or barley-based concentrate diet in yr 1 and 2, respectively, at 2.5 x maintenance requirements. Mean DMI (g/kg of BW(0.75)) during the measurements for high-, medium-, and low-RFI groups, respectively, were 82.7 +/- 2.0, 78.8 +/- 2.6, and 81.8 +/- 2.5 and did not differ (P > 0.10). Residual feed intake was correlated with daily methane production and energy lost as methane (r = 0.44; P < 0.05). Methane production was 28 and 24% less in low-RFI animals compared with high- and medium-RFI animals, respectively. Residual feed intake tended to be associated (P < 0.10) with apparent digestibilities of DM (r = -0.33) and CP (r = -0.34). The RFI of steers was correlated with DE (r = -0.41; P < 0.05), ME (r = -0.44; P < 0.05), heat production (HP; r = 0.68; P < 0.001), and retained energy (RE; r = -0.67; P < 0.001; energy values are expressed in kcal/kg of BW(0.75)). Feedlot partial efficiency of growth was correlated (P < 0.01) with methane production (r = -0.55), DE (r = 0.46), ME (r = 0.49), HP (r = -0.50), and RE (r = 0.62). With the exception of HP (r = 0.37; P < 0.05), feed conversion ratio was unrelated to the traits considered in the study. Feeding duration was correlated (P < 0.01) with apparent digestibility of DM (r = -0.55), CP (r = -0.47), methane production (r = 0.51), DE (r = -0.52), ME (r = -0.55), and RE (r = -0.60). These results have practical implications for the selection of animals that eat less at a similar BW and growth rate and for the environmental sustainability of beef production.

Animal Feed↗

Test duration for growth, feed intake, and feed efficiency in beef cattle using the GrowSafe System.

This study was conducted to determine the optimum test duration and the effect of missing data on accuracy of measuring feed efficiency and its 4 related traits ADG, DMI, feed conversion ratio, and residual feed intake in beef cattle using data from 456 steers with 5,397 weekly averaged feed intakes and BW repeated measurements taken over 91 d. Data were collected using the GrowSafe System at the University of Alberta Kinsella Research Station. The changes and relative changes in phenotypic residual variances and correlations (Pearson and Spearman) among data from shortened test durations (7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, or 84 d) and a 91-d test were used to determine the optimum test duration for the 4 traits. The traits were fitted to a mixed model with repeated measures using SAS. Test durations for ADG, DMI, feed conversion ratio, and residual feed intake could be shortened to 63, 35, 42, and 63 d, respectively, without significantly reducing the accuracy of the tests when BW was measured weekly. The accuracy of the test was not compromised when up to 30% of the records were randomly removed after the first 35 d on test. These results have valuable and practical implications for performance and feed efficiency testing in beef cattle.

Animals↗

Adaptation of the WHO guideline for residual DNA in parenteral vaccines produced on continuous cell lines to a limit for oral vaccines.

Although there is a WHO guidance for a limit on residual DNA for parenterally administered vaccines produced on continuous cell lines, there is no corresponding guidance for oral vaccines. To help determine an oral limit, we performed a study of Vero cell DNA uptake in rats, in which the relative uptake and persistence of Vero cell DNA administered orally was compared to its uptake when delivered intramuscularly (IM). The results of this study allowed the generation of an empirically derived IM versus oral factor (10(6)) representing the relative inefficiency of DNA uptake by oral administration. This factor was then applied to the WHO recommended parenteral limit of 10 ng/dose to determine a corresponding upper limit on the level of residual Vero cell DNA for an oral vaccine of 10 mg. As a conservative approach, this empirically determined limit was reduced 100-fold to 100 microg. Thus, the results of this animal study, together with additional evidence in the literature, support a residual DNA safety limit of 100 microg per dose for an oral vaccine produced on a continuous cell line.

Administration, Oral↗

Toxicological mechanisms of Aconitum alkaloids.

The toxic effects of Aconitum alkaloids are known to affect mainly the central nervous system, heart and muscle tissues. Their toxicological mechanisms may involve interaction with voltage-dependent Na+ channels, modulation of neurotransmitter release and related receptors, promotion of lipid peroxidation and induction of cell apoptosis in heart, liver or other organs. Of them, the mechanism of interaction with voltage-dependent Na+ channels is quite well known, but the other factors are still unclear, and need to be further studied. This review focuses on the toxicological mechanisms of Aconitum alkaloids.

Aconitum↗

Saccular aneurysms on straight and curved vessels are subject to different hemodynamics: implications of intravascular stenting.

Our aim was to examine hemodynamic implications of intravascular stenting in the canine venous pouch (sidewall or straight-vessel) and rabbit elastase (curved-vessel) aneurysm models. Flow dynamics in stented (Wallstent) and nonstented versions were studied by using computational fluid dynamics simulations and in vitro flow visualization, with a focus on stent placement effects on aneurysmal flow stagnancy and flow impingement. Results show that sidewall and curved aneurysm models have fundamentally different hemodynamics (shear-driven versus inertia-driven) and thus stent placement outcomes.

Animals↗

Age-associated changes in MAPK activation in fast- and slow-twitch skeletal muscle of the F344/NNiaHSD X Brown Norway/BiNia rat model.

We compared the tissue content, basal phosphorylation, and stretch-induced phosphorylation of the mitogen-activated protein kinase (MAPK) members; extracellular-signal-regulated kinases (ERK 1/2), p38, and c-Jun NH2-terminal kinase (JNK) in the fast-twitch extensor digitorium longus (EDL) and slow-twitch soleus of young adult (6 month), aged (30 month), and very aged (36 month) F344/NNiaHSD X Brown Norway/BiNia (F344/NXBN) rats. The expression and basal phosphorylation of the ERK 1/2, p38, and JNK MAPK proteins were regulated differently with aging in the EDL and soleus. Stretch induced significant phosphorylation of each signaling molecule in both muscle types of young adult and aged animals. In the very aged animals, stretch stimulated ERK 1/2 MAPK phosphorylation; however, EDL stretch failed to induce JNK MAPK phosphorylation, while soleus stretch was unable to induce the phosphorylation of p38 MAPK. The results suggest that skeletal muscle mechanotransduction processes are affected in very aged F344/NXBN rats and that aging alters load-induced signaling in fast- and slow-twitch muscle types differently.

Aging↗

Fermi surface evolution and Luttinger theorem in Na(x)CoO2: a systematic photoemission study.

We report a systematic angle-resolved photoemission study on Na(x)CoO2 for a wide range of Na concentrations (0.3 < or = x < or = 0.72). In all the metallic samples at different x, we observed (i) only a single holelike Fermi surface centered around gamma and (ii) its area changes with x according to the Luttinger theorem. We also observed a surface state that exhibits a larger Fermi surface area. The e'(g) band and the associated small Fermi surface pockets near the K points predicted by band calculations are found to sink below the Fermi energy in a manner almost independent of the doping and temperature.

Journal Article↗

Improved morphed potentials for Ar-HBr including scaling to the experimentally determined dissociation energy.

A lead salt diode infrared laser spectrometer has been employed to investigate the rotational predissociation in Ar-HBr for transitions up to J' = 79 in the v(1) HBr stretching vibration of the complex using a slit jet and static gas phase. Line-shape analysis and modeling of the predissociation lifetimes have been used to determine a ground-state dissociation energy D(0) of 130(1) cm(-1). In addition, potential energy surfaces based on ab initio calculations are scaled, shifted, and dilated to generate three-dimensional morphed potentials for Ar-HBr that reproduce the measured value of D(0) and that have predictive capabilities for spectroscopic data with nearly experimental uncertainty. Such calculations also provide a basis for making a comprehensive comparison of the different morphed potentials generated using the methodologies applied.

Journal Article↗

Emission of ammonia from indoor concrete wall and assessment of human exposure.

Addition of urea-based antifreeze admixtures during cement mixing can make it possible to produce concrete cement in construction of buildings in cold weather; this, however, has led to increasing indoor air pollution due to continuous transformation and emission from urea to gaseous ammonia in indoor concrete wall. It is believed that ammonia is harmful to human body and exposure to ammonia can cause some serious symptoms such as headaches, burns, and even permanent damage to the eyes and lungs. In order to understand the emission of ammonia from indoor concrete wall in civil building and assess the health risk of people living in these buildings, the experimental pieces of concrete wall were first prepared by concreting cement and urea-based antifreeze admixtures to simulate the indoor wall in civil building in this work. Then environmental chamber was adopted for studying the effect of temperature, relative humility and air exchange rate on emission of ammonia from experimental pieces of concrete wall. Also the field experiment was made at selected rooms in given civil buildings. Exposure and potential dose of adult and children exposed to indoor/outdoor ammonia in summer and in winter are calculated and evaluated by using Scenario Evaluation Approach. The results indicated that high air exchange rate leads to decreased ammonia concentration, and elevation of temperature causes increasing ammonia concentration and volatilizing rate in chamber. The complete emission of ammonia from the wall containing urea-based antifreeze admixtures needs more than 10 years in general. Ventilating or improving air exchange can play a significant role in reducing ammonia concentration in actual rooms in field experiments. Urea-based antifreeze admixtures in concrete wall can give rise to high exposure and potential dose, especially in summer. Generally, adults have a high potential dose than children, while children have personal average dose rate beyond adults in the same conditions.

Adult↗

Temperature-dependent energy thresholds for ion-stimulated defect formation in solids.

Recent simulations and experiments have hinted that the solid temperature may affect the dynamics of defect formation when the energies of bombarding ions fall below about 100 eV. The present work offers direct experimental confirmation of this phenomenon through measurements of the energy thresholds for ion-enhanced surface diffusion of indium on silicon and germanium, where transport rates depend upon surface defect formation. Such temperature-dependent energy thresholds may offer a new means for modulating sputtering and defect formation in a variety of ion processing applications.

Journal Article↗

Coherent multiple charge transfer in a superconducting NbN tunnel junction.

We measured shot noise and submillimeter-wave response in a superconducting NbN tunnel junction that had a subharmonic gap structure on the current-voltage (I-V) curve. We found that the observed effective charge, defined from the noise-current ratio, tends to a steplike function of voltage. In the presence of submillimeter-wave radiation of frequency v, novel step structures spaced by hv/2e below and above the half-gap voltage clearly appeared on the I-V curve, overlapping the ordinary photon-assisted tunneling steps spaced by hv/e. Observation of these features provides clear evidence that coherent multiple Andreev reflection processes occur in the NbN tunnel junction with low barrier transparency.

Journal Article↗

A new yeast display vector permitting free scFv amino termini can augment ligand binding affinities.

Yeast surface display and sorting by flow cytometry are now widely used to direct the evolution of protein binding such as single-chain antibodies or scFvs. The available commercial yeast display vector pYD1 (Invitrogen) displays the protein of interest flanked on the N-terminus by Aga2, the disulfide of which binds the myristylated surface membrane protein Aga1. We have noted that two anti-CD3epsilon scFvs expressed as fusion proteins suffer a 30- to 100-fold loss of affinity when placed NH(2) terminal to either truncated toxins or human serum albumin. In the course of affinity maturing one of these scFv (FN18) using pYD1 we noted that the affinity towards the ectodomain of monkey CD3epsilongamma was too low to measure. Consequently we rebuilt pYD1 tethering the scFv off the NH(2) terminus of Aga2. This display vector, pYD5, now gave a positive signal displaying FN18 scFv with its ligand, monkey CD3epsilongamma. The apparent equilibrium association constant of the higher affinity scFv directed at human CD3epsilongamma increased approximately 3-fold when displayed on pYD5 compared with pYD1. These data show that for certain yeast-displayed scFvs a carboxy-tethered scFv can result in increased ligand-scFv equilibrium association constants and thereby extend the low range of affinity maturation measurements.

Amino Acid Sequence↗