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Biomedical subjects

J Zhang

Publications and source records attributed to J Zhang.

At least 415 records · Page 23Linked to original sources

Symmetry role on the preedge X-ray absorption fine structure at the metal K edge.

The preedge features in a system with "even" symmetry, apart from quadrupolar transition contribution, are mainly dipolar in character, associated with the existence of unoccupied states made up of mixed cation-4p with higher-neighboring cation-3d orbitals, and reflect the density of states due to the medium-range order of the system. In "odd" symmetry materials these preedge features are the result of a transition from the 1s to a final density of states of p symmetry due to an unsymmetrical mixing of the ligand wave functions with the central cation 3d orbitals, similar to atetrahedral configuration. These results are validated for Fe as a photoabsorber by comparing XAS spectra of Fe2SiO4 (fayalite) to ab initio full multiple scattering calculations at the Fe K edge, but pertain to all systems containing sixfold-coordinated cations.

Journal Article↗

XAFS studies on the local structures of Ti-HMS mesoporous molecular sieves and their photocatalytic properties.

Various Ti-containing HMS mesoporous molecular sieves having high surface areas and pore volumes have been prepared at ambient temperature. The Ti-HMS samples exhibited a well-defined XRD pattern of typical hexagonal lattice. UV-vis and XAFS spectral for the calcined forms of Ti-HMS indicated that the Ti ions are tetrahedrally coordinated in the framework of HMS for the samples of Ti-HMS(1) and Ti-HMS(2), while at least a fraction of Ti-oxides in Ti-HMS(10) is in octahedral coordination. UV irradiation of the Ti-HMS catalysts in the presence of NO was found to lead to the decomposition of NO to form N2, O2, and N2O at 273 K with different yields and product distributions. The photocatalytic performance of Ti-oxides appears to be completely modified by their incorporation structure and reaction environment. High efficiency and selectivity for the formation of N2 and O2 in the photocatalytic decomposition of NO was achieved with the Ti-HMS(1) having highly dispersed isolated tetrahedral titanium oxide species, while the reactivity decreased with an increase in the Ti content.

Journal Article↗

SH2 domain-mediated targeting, but not localization, of Syk in the plasma membrane is critical for FcepsilonRI signaling.

Aggregation of the high-affinity IgE receptor induces the tyrosine phosphorylation of subunits of the receptor and the subsequent association with the receptor of the cytosolic protein tyrosine kinase Syk. The current experiments examined the functional importance of membrane association of Syk and the role of the SH2 domain in receptor-mediated signal transduction. Wild-type Syk and chimeric Syk molecules with the c-Src myristylation sequence at the amino-terminus were expressed in a Syk-negative mast cell line. Chimeric Syk with the myristylation sequence was membrane associated, and a small fraction was constitutively colocalized with FcepsilonRI, Lyn, and LAT (linker for T-cell activation) in the glycolipid-enriched microdomains or rafts. However, even under these conditions, the tyrosine phosphorylation of Syk and the downstream propagation of signals required FcepsilonRI aggregation. This chimeric Syk was less active than wild-type Syk in FcepsilonRI-mediated signal transduction. In contrast, a truncated membrane-associated form of Syk that lacked the SH2 domains was not tyrosine phosphorylated by receptor aggregation and failed to transduce intracellular signals. These findings suggest that SH2 domain-mediated membrane translocation of Syk is essential for the FcepsilonRI-mediated activation of Syk for downstream signaling events leading to histamine release. Furthermore, the localization of Syk in glycolipid-enriched microdomains by itself is not enough to generate or enhance signaling events.

Animals↗

Experimental study of a subpicosecond pulse laser interacting with metallic and dielectric targets.

We have studied laser absorption, hot electron emission, and the energy spectrum of hot electrons produced during the interaction of a 150 fs, 5 mJ, 800 nm p-polarized laser pulse at 8x10(15) W/cm(2) with metallic and dielectric target materials. Because dielectric targets are much less conductive, the charge separation potential in dielectric targets is higher than that of metallic targets. This leads to a smaller laser absorption, fewer emitted electrons, and a lower hot electron temperature in dielectric than in metallic targets.

Journal Article↗

Hydrodynamic characteristics of transient Ni-like x-ray lasers.

A simple similarity model is presented to study the hydrodynamics of transient collisional excitation nickellike x-ray lasers. Scaling laws for the temperature, scale length, and electron density are obtained by analytic derivation. The hydrodynamic characteristics of transient Ni-like Pd x-ray lasers are investigated using this model. The calculations agree well with Dunn's experimental results.

Journal Article↗

Preparation of alpha-(2,2-diphenylhydrazino)lactones and related compounds by radical cyclization: use of glyoxylic acid hydrazone derivatives.

Glyoxylic acid diphenylhydrazone (2a) and the corresponding O-benzyloxime (2b) are easily esterified in high yield by beta-bromo alcohols. The resulting esters undergo radical cyclization to alpha-(2,2-diphenylhydrazino)- or alpha-[(phenylmethoxy)amino]lactones on treatment with tributyltin hydride. Esters for radical cyclization were also made using a beta-(phenylseleno) alcohol and an enol ether. Several derivatives of glyoxylic acid were evaluated, but none was as effective as 2a or 2b. The imine 28 was prepared by an indirect route; it undergoes radical cyclization with displacement of the nitrogen substituent (28 --> 30) so that an alpha-amino lactone can be generated by acid hydrolysis of the cyclization product.

Journal Article↗

Mouse phosphoglycerate mutase M and B isozymes: cDNA cloning, enzyme activity assay and mapping.

Two mouse cDNAs encoding the non-muscle-specific or brain isoform (type B, Pgam1) and the muscle-specific isoform (type M, Pgam2) of phosphoglycerate mutase (PGAM) were isolated and characterized. Pgam1 contains a 765 bp open reading frame (ORF) coding for a 254-residue protein while Pgam2 contains a 762 bp ORF coding for a 253-residue protein. The deduced proteins of mouse Pgam1 and Pgam2 are highly similar to those of human and rat (> or = 93% similarity). Northern blot analysis showed that the expression patterns of Pgam1 and Pgam2 were distinct. Pgam1 was expressed as a 2.1-kb transcript highly in brain and kidney and moderately in liver, thyroid, stomach and heart, whereas Pgam2 was expressed as a 1.0-kb transcript highly in muscle, testis and moderately in heart and lung, but was not detectable in the other six tissues examined. Transfecting the cDNA fragments containing the entire ORFs of these two cDNAs into COS7 cells for transient expression, respectively, the enzyme activities of mouse Pgam1 and Pgam2 were detected to be 2.2-2.5 times of those of COS7 cells and COS7 cells transfected with vector, proving the validity of mouse Pgam1 and Pgam2 cDNAs we report here. Pgam1 and Pgam2 were assigned to 116.16 cR from D19Mit52 and 29.57 cR from D11Mit129, respectively, by radiation hybrid method. The partial genomic sequence of Pgam2 was determined, which showed that mouse Pgam2 consisted at least three exons and two introns. In addition, a pseudogene of Pgam1, Pgam1-ps1, was identified from mouse genomic sequence.

Amino Acid Sequence↗

The sequence of the human genome.

A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

Algorithms↗

Il-10 is a central regulator of cyclooxygenase-2 expression and prostaglandin production.

IL-10 is a potent anti-inflammatory and immune regulatory cytokine. IL-10(-/-) mice produce exaggerated amounts of inflammatory cytokines when stimulated with LPS, indicating that endogenous IL-10 is a central regulator of inflammatory cytokine production in vivo. PGs are lipid mediators that are also produced in large amounts during the inflammatory response. To study the role of IL-10 in the regulation of PG production during the acute inflammatory response, we evaluated LPS-induced cyclooxygenase (COX) expression and PG production in wild-type (wt) and IL-10(-/-) mice. LPS-induced PGE(2) production from IL-10(-/-) spleen cells was 5.6-fold greater than that from wt spleen cells. LPS stimulation resulted in the induction of COX-2 mRNA and protein in both wt and IL-10(-/-) spleen cells; however, the magnitude of increase in COX-2 mRNA was 5.5-fold greater in IL-10(-/-) mice as compared with wt mice. COX-1 protein levels were not affected by LPS stimulation in either wt or IL-10(-/-) mice. Neutralization of IFN-gamma, TNF-alpha, or IL-12 markedly decreased the induction of COX-2 in IL-10(-/-) spleen cells, suggesting that increased inflammatory cytokine production mediates much of the COX-2 induction in IL-10(-/-) mice. Treatment of IL-10(-/-) mice with low doses of LPS resulted in a marked induction of COX-2 mRNA in the spleen, whereas wt mice had minimal expression of COX-2 mRNA. These findings indicate that, in addition to IL-10's central role in the regulation of inflammatory cytokines, endogenous IL-10 is an important regulator of PG production in the response to LPS.

Animals↗

Chiral doublet structures in odd-odd n = 75 isotones: chiral vibrations.

New sideband partners of the yrast bands built on the pi(h11/2)nu(h11/2) configuration were identified in 55Cs, 57La, and 61Pm N = 75 isotones of 134Pr. These bands form with 134Pr unique doublet-band systematics suggesting a common basis. Aplanar solutions of 3D tilted axis cranking calculations for triaxial shapes define left- and right-handed chiral systems out of the three angular momenta provided by the valence particles and the core rotation, which leads to spontaneous chiral symmetry breaking and the doublet bands. Small energy differences between the doublet bands suggest collective chiral vibrations.

Journal Article↗

Axonal projections and synapses from the supratrigeminal region to hypoglossal motoneurons in the rat.

Neural circuits from the supratrigeminal region (Vsup) to the hypoglossal motor nucleus were studied in rats using anterograde and retrograde neuroanatomical tracing methodologies. Iontophoretic injection of 10% biotinylated dextran amine (BDA) unilaterally into the Vsup anterogradely labeled axons and axon terminals bilaterally in the hypoglossal nucleus (XII) as well as other regions of the brainstem. In the ipsilateral XII, the highest density of BDA labeling was found in the dorsal compartment and the ventromedial subcompartment of the ventral compartment, where BDA labeling formed a dense, patchy distribution. Microinjection of 20% horseradish peroxidase (HRP) ipsilaterally or bilaterally into the tongue resulted in retrograde labeling of XII motoneurons confined to the dorsal and ventral compartments of the hypoglossal motor nucleus. Under light microscopical examination, BDA-labeled terminals were observed closely apposing the somata and primary dendrites of HRP-labeled hypoglossal motoneurons. Two hundred and sixty-five of these BDA-labeled terminals were examined at the ultrastructural level. One hundred and twelve BDA-labeled axon terminals were observed synapsing with either the somata (39%, 44/112) or the large or medium-size dendrites (61%, 68/112) of retrogradely labeled hypoglossal motoneurons. Axon terminals containing spherical vesicles (S-type) formed asymmetric synapses with HRP-labeled hypoglossal motoneuron dendrites. In contrast to this, F(F)-type axon terminals, containing flattened vesicles, formed symmetric synapses with both the somata and dendrites of HRP-labeled hypoglossal motoneurons with a preponderance of the contacts on their somata. Axon terminals containing pleomorphic vesicles (F(P)-type) were noted forming both symmetric and asymmetric synapses with HRP-labeled hypoglossal motoneuron somata and dendrites. The present study provides anatomical evidence of neuronal projections and synaptic connections from the supratrigeminal region to hypoglossal motoneurons. These data suggest that the supratrigeminal region, as one of the premotor neuronal pools of the hypoglossal nucleus, may coordinate and modulate the activity of tongue muscles during oral motor behaviors.

Animals↗

The activity of guanine exchange factor NET1 is essential for transforming growth factor-beta-mediated stress fiber formation.

To examine signaling pathways underlying transforming growth factor-beta (TGF-beta)-mediated changes in cell morphology, we used a microarray system to identify downstream target genes that may play a role in this process. Through this approach, we found that the NET1 gene was induced upon TGF-beta treatment in several cell types. NET1 is a guanine nucleotide exchange factor for RhoA whose activity has been implicated in stress fiber formation. In the Swiss 3T3 cell line, TGF-beta induces NET1 expression, and this correlated with an increase in stress fiber formation. Overexpression of the wild type NET1 gene increases stress fiber formation, and overexpression of a dominant negative NET1 mutant (L392E) prevented TGF-beta dependent increase in stress fiber formation. Furthermore, treatment of the cells with a RhoA kinase inhibitor Y-27632 blocks TGF-beta-induced stress fiber formation. By using a stable cell line expressing dominant negative Smad3, we found that the Smad signaling pathway is essential for the induction of NET1, which in turn leads to the increase of Rho activity. Taken together, those data suggest that induction of NET1 is important for the increase of Rho activity upon TGF-beta treatment, which may represent the critical trigger for a variety of downstream events in different cells. Our results support the presence of a novel signaling pathway by which TGF-beta may regulate the formation of stress fibers and reorganization of cytoskeletal structures.

3T3 Cells↗

Inhibition of poly(ADP-ribose) polymerase activity is insufficient to induce tetraploidy.

Poly(ADP-ribose) polymerase (PARP) knockout mice are resistant to murine models of human diseases such as cerebral and myocardial ischemia, traumatic brain injury, diabetes, Parkinsonism, endotoxic shock and arthritis, implicating PARP in the pathogenesis of these diseases. Potent selective PARP inhibitors are therefore being evaluated as novel therapeutic agents in the treatment of these diseases. Inhibition or depletion of PARP, however, increases genomic instability in cells exposed to genotoxic agents. We recently demonstrated the presence of a genomically unstable tetraploid population in PARP(-/-) fibroblasts and its loss after stable transfection with PARP cDNA. To elucidate whether the genomic instability is attributable to PARP deficiency or lack of PARP activity, we investigated the effects of PARP inhibition on development of tetraploidy. Immortalized wild-type and PARP(-/-) fibroblasts were exposed for 3 weeks to 20 microM GPI 6150 (1,11b-dihydro-[2H:]benzopyrano[4,3,2-de]isoquinolin-3-one), a novel small molecule specific competitive inhibitor of PARP (K(i) = 60 nM) and one of the most potent PARP inhibitors to date (IC(50) = 0.15 microM). Although GPI 6150 initially decreased cell growth in wild-type cells, there was no effect on cell growth or viability after 24 h. GPI 6150 inhibited endogenous PARP activity in wild-type cells by approximately 91%, to about the residual levels in PARP(-/-) cells. Flow cytometric analysis of unsynchronized wild-type cells exposed for 3 weeks to GPI 6150 did not induce the development of tetraploidy, suggesting that, aside from its catalytic function, PARP may play other essential roles in the maintenance of genomic stability.

Animals↗

Complete nucleotide sequence of the S10 genome segment of grass carp reovirus (GCRV).

Hemorrhagic disease, caused by the grass carp reovirus (GCRV), is one of the major diseases of grass carp in China. Little is known about the structure and function of the gene segments of this reovirus. The S10 genome segment of GCRV was cloned and the complete nucleotide sequence is reported here. The S10 is 909 nucleotides long and contains a large open reading frame (ORF) encoding a protein of 276 amino acids with a deduced molecular weight of approximately 29.7 kDa. Comparisons of the deduced amino acid sequence of GCRV S10 with those of other reoviruses revealed no significant homologies. However, GCRV S10 shared a putative zinc-finger sequence and a similar distribution of hydrophilic motifs with the outer capsid proteins encoded by Coho salmon aquareovirus (SCSV) S10, striped bass reovirus (SBRV) S10, and mammalian reovirus (MRV) S4. It was predicted that this segment gene encodes an outer capsid protein.

Amino Acid Sequence↗

[Flow cytometry in datecting lymph node micrometastasis in colorectal cancer].

OBJECTIVE: To study the methodology and significance of flow cytometry in detecting lymph node micrometastasis of colorectal cancer. METHODS: One hundred sixty-two cellular suspensions were prepared with lymph nodes which were resected radically on 25 patients with colorectal cancer and in which no cancer cells were found by HE staining. Different concentrations of cultured Lovo colorectal cancer cells were added into the celular suspension prepared from lymph node tissue of persons without colorectal cancer in order to prepare a control model. Dual staining with CK/FTTC and PI was made to the sedimetns from those 2 kinds of suspension. Flow cytometry was used to detect cancer cells. RESULTS: An ideal correlation was obtained between the detection value and the theoretical value of cancer cells in the specimen suspensions and control models (r = 0.097 6) with a sensitivity rate of 10/10(5). Cancer cells were detected from 7 out of the 25 patients and 30 of the 162 cellular suspensions. The detection rate was correlated with the size and infiltrating depth of the cancer. CONCLUSION: Flow cytometry is a reliable, rapid, and quantitative method for detecting lymph node micrometastasis in colorectal cancer.

Colorectal Neoplasms↗

Functional proteomic analysis of protein kinase C epsilon signaling complexes in the normal heart and during cardioprotection.

Using two-dimensional electrophoresis, mass spectrometry, immunoblotting, and affinity pull-down assays, we found that myocardial protein kinase C epsilon (PKCepsilon) is physically associated with at least 36 known proteins that are organized into structural proteins, signaling molecules, and stress-responsive proteins. Furthermore, we found that the cardioprotection induced by activation of PKCepsilon is coupled with dynamic modulation and recruitment of PKCepsilon-associated proteins. The results suggest heretofore-unrecognized functions of PKCepsilon and provide an integrated framework for the understanding of PKCepsilon-dependent signaling architecture and cardioprotection.

Animals↗

Directed evolution of operon of trehalose-6-phosphate synthase/phosphatase from Escherichia coli.

Trehalose is a nonspecific protective agent for biomacromolecules. Trehalose-6-phosphate synthase (OtsA)/phosphatase (OtsB), which is encoded by the gene operon otsBA located at -42 of the Escherichia coli genome, is the main enzyme system that catalyzes the synthesis of trehalose in E. coli. We cloned the operon and modified it by directed evolution. Unlike in the previously reported work, we modified the whole operon and screened the positive mutant simultaneously. Thus we believe that the gene complex solves the negative effects between two enzymes if one of them diversifies its structure or functions and finds the form most suitable for trehalose synthesis. It thus mimics the natural process, in which the functional improvement of organisms is related to alterations in coordinated enzymes. The evolution procedure was carried out in a sequence of error-prone PCR, shuffling PCR, and then strict screening of the mutants. After screening of a library of more than 4000 colonies, about 15 positive colonies were analyzed, resulting in a higher concentration of trehalose than control. One of them, E. coli TS7, shows 12.3-fold higher trehalose synthesis ability than E. coli DH5alpha. In contrast, we introduced the cDNA sequence of the tps1 gene from Saccharomyces cerevisiae, which has 54% identity with the gene otsA, as one of the templates in shuffling PCR. By hybrid evolution and screening, we obtained 10 positive colonies with higher concentrations of trehalose than control. E. coli TS22 appears to have 5.3-fold higher trehalose synthesis ability than E. coli DH5alpha and 1.6-fold more than E. coli DEF3(pOTS11). This result demonstrated that coevolution and hybrid evolution, as powerful protocols in protein engineering, are effective in modifying enzyme. It indicates that repeating the process of genomic evolution in nature is feasible.

Directed Molecular Evolution↗