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Biomedical subjects

X Jiang

Publications and source records attributed to X Jiang.

At least 19 recordsLinked to original sources

The use of tissue-engineered bone with human bone morphogenetic protein-4-modified bone-marrow stromal cells in repairing mandibular defects in rabbits.

In this study, the capacity of hBMP-4 gene therapy combined with tissue-engineering techniques to improve the repair of mandibular osseous defects in rabbits was explored. A mammalian plasmid vector expressing enhanced green fluorescent protein-human bone morphogenetic protein-4 (pEGFP-hBMP-4) was initially constructed through subcloning techniques. Bone-marrow stromal cells (bMSCs) from New Zealand White rabbits were cultured and either transfected with pEGFP-hBMP-4 or pEGFP, or left untransfected in vitro. Once the transfer efficiency was determined through the expression of EGFP, cells from the three groups were combined with natural non-organic bone (NNB) at a concentration of 50 x 10(6)cells/ml and placed in 15 mm x 6 mm bilateral, full-thickness, mandibular defects surgically made in 12 rabbits. Together with NNB control, there were six samples per group. Four weeks after surgery, the implants were harvested and evaluated histomorphologically. Under optimal experimental conditions, gene transfer efficiency reached a maximum of 38.2+/-9.4%. While the percentage of new bone area in the NNB control group was 8.8+/-3.1%, in the untransfected bMSC group 22.5+/-8.2%, and in the pEGFP group 18.1+/-9.0%, a significantly higher amount of 32.5+/-6.1% was observed in the pEGFP-hBMP-4 group. These results suggest that transfection of bMSCs with hBMP-4 enhances their inherent osteogenic capacity for maxillofacial bone tissue-engineering applications.

Animals↗

Preconditioning and neurotrophins: a model for brain adaptation to seizures, ischemia and other stressful stimuli.

The amino acid glutamate, the major excitatory neurotransmitter in the central nervous system, activates receptors coupled to calcium influx. Excessive activation of glutamate receptors in conditions such as severe epileptic seizures or stroke can kill neurons in a process called excitotoxicity. However, subtoxic levels of activation of the N-methyl-D-aspartate (NMDA) type of glutamate receptor elicit adaptive responses in neurons that enhance their ability to withstand more severe stress. A variety of stimuli induce adaptive responses to protect neurons. For example, sublethal ischemic episodes or a mild epileptic insult can protect neurons in a process referred to as tolerance. The molecular mechanisms that protect neurons by these different stressful stimuli are largely unknown but they share common features such as the transcription factor, nuclear factor kappa B (NF-kappaB), which is activated by ischemic and epileptic preconditioning as well as exposure to subtoxic NMDA concentrations. In this article, we describe stress-induced neuroprotective mechanisms highlighting the role of brain-derived neurotrophic factor (BDNF), a protein that plays a crucial role in neuronal survival and maintenance, neurogenesis and learning and memory.

Adaptation, Physiological↗

Evidence for an oncogenic role of AHI-1 in Sezary syndrome, a leukemic variant of human cutaneous T-cell lymphomas.

Ahi-1 (Abelson helper integration site 1) is a novel gene frequently activated by provirus insertional mutagenesis in murine leukemias and lymphomas. Its involvement in human leukemogenesis is demonstrated by gross perturbations in its expression in human leukemia cells, particularly in cutaneous T-cell lymphoma cell lines where increases in AHI-1 transcripts of 40-fold are seen. To test directly whether deregulated expression of AHI-1 contributes to their transformed properties, knockdown of AHI-1 expression in Hut78 cells, a cell line derived from a patient with Sezary syndrome (SS), was performed using retroviral-mediated RNA interference. Retroviral-mediated suppression specifically inhibited expression of AHI-1 and its isoforms in transduced cells by 80% and also reduced autocrine production of interleukin (IL)-2, IL-4 and tumor necrosis factor-alpha (TNFalpha) by up to 85%. It further significantly reduced their growth factor independence in vitro and the ability to produce tumors in immunodeficient mice. Interestingly, aberrant expression of AHI-1, particularly truncated isoforms, was present in CD4+CD7- Sezary cells from some patients with SS. Elevated expression of IL-2 and TNFalpha was also found in these cells. These findings provide strong evidence of the oncogenic activity of AHI-1 in human leukemogenesis and demonstrate that its deregulation may contribute to the development of SS.

Adaptor Proteins, Signal Transducing↗

Influence of current on field-driven domain wall motion in permalloy nanowires from time resolved measurements of anisotropic magnetoresistance.

The motion of magnetic domain walls in permalloy nanowires is investigated by real-time resistance measurements. The domain wall velocity is measured as a function of the magnetic field in the presence of a current flowing through the nanowire. We show that the current can significantly increase or decrease the domain wall velocity, depending on its direction. These results are understood within a one-dimensional model of the domain wall dynamics which includes the spin transfer torque.

Journal Article↗

Evaluation of accelerated dechlorination of p,p'-DDT in acidic paddy soil.

The reductive dechlorination and behavior of p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) was investigated in a paddy soil. Treatment with 5% (w/w) metallic iron (Fe(0)) resulted in sharp decrease of p,p'-DDT, whereas there was no extra effect when 2% (w/w) aluminum sulfate (Al(2)(SO(4))(3)) was added to the Fe(0) treatment. These results suggest that Fe(0) could effectively promote the reductive dechlorination of p,p'-DDT and its metabolites while Al(2)(SO(4))(3) did not show any effect on those processes. Furthermore, p,p'-DDT and its daughter compounds inhibited holistic soil respiration greatly at first but could be metabolized by certain species of indigenous microorganisms after a period of adaptation time in the soil. When treated with Fe(0), the polluted soil produced much less CO(2) while the addition of Al(2)(SO(4))(3) counteracted its negative effect to much extent.

Agriculture↗

Parity-violating electron scattering from 4He and the strange electric form factor of the nucleon.

We have measured the parity-violating electroweak asymmetry in the elastic scattering of polarized electrons from 4He at an average scattering angle = 5.7 degrees and a four-momentum transfer Q2 = 0.091 GeV2 . From these data, for the first time, the strange electric form factor of the nucleon G(E)s can be isolated. The measured asymmetry of A(PV) = (6.72 +/- 0.84(stat) +/- 0.21(syst) x 10(-6) yields a value of G(E)s = -0.038 +/- 0.042(stat) +/- 0.010(syst), consistent with zero.

Journal Article↗

The unveiling of hidden T-cell determinants of a native antigen by defined mediators of inflammation: implications for the pathogenesis of autoimmunity.

A major hypothesis for the induction of autoimmunity invokes the enhanced display of previously hidden (cryptic) epitopes under inflammatory conditions leading to the activation of self-reactive T cells. However, there is meager data that directly validate the influence of specific immune mediators on the upregulation of the presentation of cryptic determinants in vivo. We tested the effect on well-defined cryptic epitopes of hen eggwhite lysozyme (HEL) of the availability locally of a cytokine (IL-2, IL-4, IL-6, IL-10, TNF-alpha or granulocyte-macrophage colony-stimulating factor) at the antigen delivery site, or of the pretreatment of the immunogen with a cathepsin (Cat B, D, L or S) prior to use in vivo. Each of the three mouse strains (H-2(b/d/k)) tested revealed a unique profile of T-cell reactivity to different cryptic epitopes of HEL in response to a particular cytokine or cathepsin. These results provide proof of principle for the reversal of crypticity of self-epitopes by immune mediators in the local milieu. Moreover, co-immunization with an antigen and a cytokine offers a simple and reliable tool for studying the role of cryptic epitopes in autoimmunity. Our results also strengthen the rationale for the use of inhibitors of cytokine/cathepsin activity in the treatment of autoimmune diseases.

Animals↗

Q2 dependence of the neutron spin structure function g2(n) at low Q2.

We present the first measurement of the Q2 dependence of the neutron spin structure function g2(n) at five kinematic points covering 0.57 (GeV/c)2 < or = Q2 < or = 1.34 (GeV/c)2 at x approximately = 0.2. Though the naive quark-parton model predicts g2 = 0, nonzero values occur in more realistic models of the nucleon which include quark-gluon correlations, finite quark masses, or orbital angular momentum. When scattering from a noninteracting quark, g2(n) can be predicted using next-to-leading order fits to world data for g1(n). Deviations from this prediction provide an opportunity to examine QCD dynamics in nucleon structure. Our results show a positive deviation from this prediction at lower Q2, indicating that contributions such as quark-gluon interactions may be important. Precision data obtained for g1(n) are consistent with next-to-leading order fits to world data.

Journal Article↗

Recoil polarization for delta excitation in pion electroproduction.

We measured angular distributions of recoil-polarization response functions for neutral pion electroproduction for W = 1.23 GeV at Q(2) = 1.0 (GeV/c)(2), obtaining 14 separated response functions plus 2 Rosenbluth combinations; of these, 12 have been observed for the first time. Dynamical models do not describe quantities governed by imaginary parts of interference products well, indicating the need for adjusting magnitudes and phases for nonresonant amplitudes. We performed a nearly model-independent multipole analysis and obtained values for Re (S(1+)/M(1+)) = -(6.84 +/- 0.15)% and Re (E(1+)/M(1+)) = -(2.91 +/- 0.19)% that are distinctly different from those from the traditional Legendre analysis based upon M1+ dominance and ll(pi) < or = 1 truncation.

Journal Article↗

Quasielastic 3He(e,e'p)2H reaction at Q2 = 1.5 GeV2 for recoil momenta up to 1 GeV/c.

We have studied the quasielastic 3He(e,e(')p)2H reaction in perpendicular coplanar kinematics, with the energy and the momentum transferred by the electron fixed at 840 MeV and 1502 MeV/c, respectively. The 3He(e,e(')p)2H cross section was measured for missing momenta up to 1000 MeV/c, while the A(TL) asymmetry was extracted for missing momenta up to 660 MeV/c. For missing momenta up to 150 MeV/c, the cross section is described by variational calculations using modern 3He wave functions. For missing momenta from 150 to 750 MeV/c, strong final-state interaction effects are observed. Near 1000 MeV/c, the experimental cross section is more than an order of magnitude larger than predicted by available theories. The A(TL) asymmetry displays characteristic features of broken factorization with a structure that is similar to that generated by available models.

Journal Article↗

Measurement of the 3He(e,e'p)pn reaction at high missing energies and momenta.

Results of the Jefferson Lab Hall A quasielastic 3He(e,e'p)pn measurements are presented. These measurements were performed at fixed transferred momentum and energy, q=1502 MeV/c and omega=840 MeV, respectively, for missing momenta p(m) up to 1 GeV/c and missing energies in the continuum region, up to pion threshold; this kinematic coverage is much more extensive than that of any previous experiment. The cross section data are presented along with the effective momentum density distribution and compared to theoretical models.

Journal Article↗

Genomics and variation of ionotropic glutamate receptors: implications for neuroplasticity.

We used two approaches to identify sequence variants in ionotropic glutamate receptor (IGR) genes: high-throughput screening and resequencing techniques, and "information mining" of public (e.g. dbSNP, ENSEMBL) and private (i.e. Celera Discovery System) sequence databases. Each of the 16 known IGRs is represented in these databases, their positions on a canonical physical map are established. Comparisons of mouse, rat, and human sequences revealed substantial conservation among these genes, which are located on different chromosomes but found within syntenic groups of genes. The IGRs are members of a phylogenetically ancient gene family, sharing similarities with glutamate-like receptors in plants. Parsimony analysis of amino acid sequences groups the IGRs into three distinct clades based on ligand-binding specificity and structural features, such as the channel pore and membrane spanning domains. A collection of 38 variants with amino acid changes was obtained by combining screening, resequencing, and informatics approaches for several of the IGR genes. This represents only a fraction of the sequence variation across these genes, but in fact these may constitute a large fraction of the common polymorphisms at these genes and these polymorphisms are a starting point for understanding the role of these variants in function. Genetically influenced human neurobehavioral phenotypes are likely to be linked to IGR genetic variants. Because ionotropic glutamate receptor activation leads to calcium entry, which is fundamental in brain development and in forms of synaptic plasticity essential for learning and memory and is essential for neuronal survival, it is likely that sequence variants in IGR genes may have profound functional roles in neuronal activation and survival mechanisms.

Amino Acid Substitution↗

Highly spin-polarized room-temperature tunnel injector for semiconductor spintronics using MgO(100).

The spin polarization of current injected into GaAs from a CoFe/MgO(100) tunnel injector is inferred from the electroluminescence polarization from GaAs/AlGaAs quantum well detectors. The polarization reaches 57% at 100 K and 47% at 290 K in a 5 T perpendicular magnetic field. Taking into account the field dependence of the luminescence polarization, the spin injection efficiency is at least 52% at 100 K, and 32% at 290 K. We find a nonmonotonic temperature dependence of the polarization which can be attributed to spin relaxation in the quantum well detectors.

Journal Article↗

Investigation of the conjectured nucleon deformation at low momentum transfer.

We report new precise H(e,e(')p)pi(0) measurements at the Delta(1232) resonance at Q(2)=0.127 (GeV/c)(2) obtained at the MIT-Bates out-of-plane scattering facility which are particularly sensitive to the transverse electric amplitude (E2) of the gamma(*)N-->Delta transition. The new data have been analyzed together with those of earlier measurements to yield precise quadrupole to dipole amplitude ratios: Re(E(3/2)(1+)/M(3/2)(1+))=(-2.3+/-0.3(stat+syst)+/-0.6(model))% and Re(S(3/2)(1+)/M(3/2)(1+))=(-6.1+/-0.2(stat+syst)+/-0.5(model))% for M(3/2)(1+)=(41.4+/-0.3(stat+syst)+/-0.4(model))(10(-3)/m(pi(+))). The derived amplitudes give credence to the conjecture of deformation in hadrons favoring, at low Q2, the dominance of mesonic effects.

Journal Article↗

Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitors.

This study examines the basis of resistance and sensitivity of normal and transformed cells to histone deacetylase inhibitor (HDACi)-induced cell death, specifically the role of caspases and thioredoxin (Trx). An important attribute of HDACis is that they induce cancer cell death at concentrations to which normal cells are relatively resistant, making them well suited for cancer therapy. The mechanism underlying this selectivity has not been understood. In this study we found that the HDACi suberoylanilide hydroxamic acid (SAHA) and MS-275, a benzamide, cause an accumulation of reactive oxygen species (ROS) and caspase activation in transformed but not normal cells. Inhibition of caspases does not block HDACi-induced cell death. These studies provide a possible mechanism that can explain why normal but not certain transformed cells are resistant to HDACi-induced cell death. The HDACi causes an increase in the level of Trx, a major reducing protein for many targets, in normal cells but not in transformed cells. The SAHA-induced increase in Trx activity in normal cells is associated with no increase in ROS accumulation. Transfection of transformed cells with Trx small interfering RNA caused a marked decrease in the level of Trx protein with an increase in ROS, a decrease in cell proliferation, and an increase in sensitivity to SAHA-induced cell death. Thus, Trx, independent of the caspase apoptotic pathway, is an important determinant of resistance of cells to HDACi-induced cell death.

Apoptosis↗

Visualizing levels of osteoblast differentiation by a two-color promoter-GFP strategy: Type I collagen-GFPcyan and osteocalcin-GFPtpz.

A 3.9 kb DNA fragment of human osteocalcin promoter and 3.6 kb DNA fragment of the rat collagen type1a1 promoter linked with visually distinguishable GFP isomers, topaz and cyan, were used for multiplex analysis of osteoblast lineage progression. Three patterns of dual transgene expression can be appreciated in primary bone cell cultures derived from the transgenic mice and by histology of their corresponding bones. Our data support the interpretation that strong pOBCol3.6GFPcyan alone is found in newly formed osteoblasts, while strong pOBCol3.6GFPcyan and hOC-GFPtpz are present in osteoblasts actively making a new matrix. Osteoblasts expressing strong hOC-GFPtpz and weak pOBCol3.6GFPcyan are also present and may or may not be producing mineralized matrix. This multiplex approach reveals the heterogeneity within the mature osteoblast population that cannot be appreciated by current histological methods. It should be useful to identify and isolate populations of cells within an osteoblast lineage as they progress through stages of differentiation.

Animals↗