[Correlation and Significance of E-cadherin and N-cadherin Expression in Prostate Cancer]

Ai Zheng = Aizheng = Chinese Journal of Cancer. Nov, 2002  |  Pubmed ID: 12526217

Decreased expression of E-Cadherin correlated with many kinds of cancer, but inappropriate expression of N-cadherin has been reported in breast cancer recently, which has a more distinct and direct role in promoting cancer cell motility than E-cadherin. The aim of this study was to investigate the correlation between E-Cadherin and N-Cadherin expression with the grade and stage of prostate cancer and their relationship with prostate specific antigen (PSA).

Cloning and Characterization of a Novel Human STAR Domain Containing CDNA KHDRBS2

Molecular Biology Reports. Dec, 2002  |  Pubmed ID: 12549823

KHDRBS2, KH domain containing, RNA binding, signal transduction associated 2, is an RNA-binding protein that is tyrosine phosphorylated by Src during mitosis. It contains a KH domain,which is embedded in a larger conserved domain called the STAR domain. This protein has a 99% sequence identity with rat SLM-1 (the Sam68-like mammalian protein 1) and 98% sequence identity with mouse SLM-1 in its STAR domain. KHDRBS2 has the characteristic Sam68 SH2 and SH3 domain binding sites. RT-PCR analysis showed its transcript is ubiquitously expressed. The characterization of KHDRBS2 indicates it may link tyrosine kinase signaling cascades with some aspect of RNA metabolism.

Four-dimensional Wavelet Compression of Arbitrarily Sized Echocardiographic Data

IEEE Transactions on Medical Imaging. Sep, 2002  |  Pubmed ID: 12564885

Wavelet-based methods have become most popular for the compression of two-dimensional medical images and sequences. The standard implementations consider data sizes that are powers of two. There is also a large body of literature treating issues such as the choice of the "optimal" wavelets and the performance comparison of competing algorithms. With the advent of telemedicine, there is a strong incentive to extend these techniques to higher dimensional data such as dynamic three-dimensional (3-D) echocardiography [four-dimensional (4-D) datasets]. One of the practical difficulties is that the size of this data is often not a multiple of a power of two, which can lead to increased computational complexity and impaired compression power. Our contribution in this paper is to present a genuine 4-D extension of the well-known zerotree algorithm for arbitrarily sized data. The key component of our method is a one-dimensional wavelet algorithm that can handle arbitrarily sized input signals. The method uses a pair of symmetric/antisymmetric wavelets (10/6) together with some appropriate midpoint symmetry boundary conditions that reduce border artifacts. The zerotree structure is also adapted so that it can accommodate noneven data splitting. We have applied our method to the compression of real 3-D dynamic sequences from clinical cardiac ultrasound examinations. Our new algorithm compares very favorably with other more ad hoc adaptations (image extension and tiling) of the standard powers-of-two methods, in terms of both compression performance and computational cost. It is vastly superior to slice-by-slice wavelet encoding. This was seen not only in numerical image quality parameters but also in expert ratings, where significant improvement using the new approach could be documented. Our validation experiments show that one can safely compress 4-D data sets at ratios of 128:1 without compromising the diagnostic value of the images. We also display some more extreme compression results at ratios of 2000:1 where some key diagnostically relevant key features are preserved.

[Tumor Relevance Analysis of a Highly Conserved Gene by Using Gene Microarray Hybridization]

Yi Chuan = Hereditas / Zhongguo Yi Chuan Xue Hui Bian Ji. May, 2002  |  Pubmed ID: 16126669

Preliminary function research of a highly conserved human gene,which was cloned from human fetal cDNA library during large-scale cDNA sequencing,is illustrated in this article. Bioinformatics analysis indicates that this gene is highly conserved in human, mouse, fruit fly, thaliana and fission yeast. Other bioinformatics analysis implies its relevance with tumors. RT-PCR analysis shows its wide-ranging expression patterns. Its expression in 16 cancer cases (including 7 liver cancer cases, 5 pancreas cancer cases, 2 larynx cancer cases and 2 lung cancer cases) is studied by using gene microarray analysis. The result shows its relevance with tumors and implies it may have different status in different classification of tumors.

Cloning and Characterization of a Novel Human Transcription Factor AP-2 Beta Like Gene (TFAP2BL1)

The International Journal of Biochemistry & Cell Biology. Jan, 2002  |  Pubmed ID: 11733187

The AP-2 transcription factor has been shown to play an important role in development, morphogenesis, apoptosis, cell-cycle control and has also been implicated in mammary oncogenesis. Here we report the cloning and characterization of a novel human transcription factor AP-2 like gene (TFAP2BL1), which is located on human chromosome 6p12.1-21.1. The TFAP2BL1 cDNA is 2076 base pairs in length, encoding a 452-amino acid polypeptide related to human Ap-2protein. TFAP2BL1 gene has significantly high homology to transcription factor AP-2 gene of human, mouse, chicken, sheep, fruit fly, and C. elegans at amino acid level. RT-PCR analysis shows its relatively high expression level in adult thymus, prostate, small intestine, skeletal muscle, placenta, brain, and testis tissues.

Identification and Characterization of AGTRAP, a Human Homolog of Murine Angiotensin II Receptor-Associated Protein (Agtrap)

The International Journal of Biochemistry & Cell Biology. Jan, 2002  |  Pubmed ID: 11733189

Several classes of cytoplasmic proteins have been found to interact specifically with the carboxyl-terminal cytoplasmic region of the angiotensin II type 1 (AT(1)) receptor to regulate different aspects of AT(1) receptor physiology. The murine Angiotensin II Receptor-Associated Protein (Agtrap) is a new member of them. We have recently cloned a new human gene cDNA that codes for a homolog of the murine Agtrap protein from a human fetal brain cDNA library. The deduced polypeptide product of the cDNA is 22 kDa in size, and its DNA and amino acid sequences are 85 and 77% identical to those of the mouse Agtrap gene, respectively. Hence we have named it the human Angiotensin II Receptor-Associated Protein (AGTRAP) gene. The mRNA of AGTRAP was most abundantly expressed in kidney, heart, pancreas and thyroid. Using the yeast two-hybrid screening of a human fetal brain cDNA library, we have identified a new interaction partner of the human AGTRAP protein, RACK1 (Receptor of Activated Protein C Kinase). The AGTRAP-RACK1 interaction was confirmed by GST fusion protein pull-down assays, co-immunoprecipitation and surface plasmon resonance. We suggest that the AGTRAP-RACK1 interaction may help to recruit signaling complex to the AT(1) receptor to affect AT(1) receptor signaling.

Shh Establishes an Nkx3.2/Sox9 Autoregulatory Loop That is Maintained by BMP Signals to Induce Somitic Chondrogenesis

Genes & Development. Aug, 2002  |  Pubmed ID: 12154128

Prior work has established that transient Shh signals from the notochord and floor plate confer a competence in somitic tissue for subsequent BMP signals to induce chondrogenesis. We have therefore proposed that Shh induces a factor(s) that renders somitic cells competent to chondrify in response to subsequent BMP signals. Recently, we have shown that forced expression of Nkx3.2, a transcriptional repressor induced by Shh, is able to confer chondrogenic competence in somites. In this work, we show that administration of Shh or forced Nkx3.2 expression induces the expression of the transcription factor Sox9 in the somitic tissue. Forced expression of Sox9 can, in turn, induce robust chondrogenesis in somitic mesoderm, provided that BMP signals are present. We have found that in the presence of BMP signals, Sox9 and Nkx3.2 induce each other's expression. Thus, Nkx3.2 may promote axial chondrogenesis by derepressing the expression of Sox9 in somitic mesoderm. Furthermore, forced expression of either Sox9 or Nkx3.2 not only activates expression of cartilage-specific genes in somitic mesoderm, but also promotes the proliferation and survival of the induced chondrocytes in the presence of BMP signals. However, unlike Nkx3.2, Sox9 is able to induce de novo cartilage formation in non-cartilage-forming tissues. Our findings suggest that Shh and BMP signals work in sequence to establish a positive regulatory loop between Sox9 and Nkx3.2, and that Sox9 can subsequently initiate the chondrocyte differentiation program in a variety of cellular environments.

A Novel Splice Variant of the Cell Adhesion Molecule Contactin 4 ( CNTN4) is Mainly Expressed in Human Brain

Journal of Human Genetics. 2002  |  Pubmed ID: 12202991

Axon-associated cell adhesion molecules (AxCAMs) of the immunoglobulin superfamily play important roles in the formation, maintenance, and plasticity of functional neuronal networks. Contactin4 ( CNTN4, BIG-2) is a member of the TAG-1/F3 subgroup of AxCAMs. We have cloned a novel splice variant of CNTN4, and term it CNTN4A. The complete nucleotide sequence of CNTN4 is also obtained by combining the insert sequences of two clones, which were isolated when screening the human fetal brain cDNA library with CNTN4A as a probe. CNTN4A protein has an N-terminal cleavable signal peptide, two FNIII-like domains, and a glycosyl phosphatidylinositol-anchoring domain. According to the search of the human genome database, CNTN4 was mapped to 3p25-26, a region very close to the breakpoints of the 3p syndrome. Expression analysis of CNTN4A shows that CNTN4A is mainly expressed in brain.

Bioreactors Mediate the Effectiveness of Tissue Engineering Scaffolds

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology. Oct, 2002  |  Pubmed ID: 12207008

We hypothesized that the mechanically active environment present in rotating bioreactors mediates the effectiveness of three-dimensional (3D) scaffolds for cartilage tissue engineering. Cartilaginous constructs were engineered by using bovine calf chondrocytes in conjunction with two scaffold materials (SM) (benzylated hyaluronan and polyglycolic acid); three scaffold structures (SS) (sponge, non-woven mesh, and composite woven/non-woven mesh); and two culture systems (CS) (a bioreactor system and petri dishes). Construct size, composition [cells, glycosaminoglycans (GAG), total collagen, and type-specific collagen mRNA expression and protein levels], and mechanical function (compressive modulus) were assessed, and individual and interactive effects of model system parameters (SM, SS, CS, SM*CS and SS*CS) were demonstrated. The CS affected cell seeding (higher yields of more spatially uniform cells were obtained in bioreactor-grown than dish-grown 3-day constructs) and subsequently affected chondrogenesis (higher cell numbers, wet weights, wet weight GAG fractions, and collagen type II levels were obtained in bioreactor-grown than dish-grown 1-month constructs). In bioreactors, mesh-based scaffolds yielded 1-month constructs with lower type I collagen levels and four-fold higher compressive moduli than corresponding sponge-based scaffolds. The data imply that interactions between bioreactors and 3D tissue engineering scaffolds can be utilized to improve the structure, function, and molecular properties of in vitro-generated cartilage.

Cloning, Expression and Characterization of a Novel Human VMP Gene

Molecular Biology Reports. Sep, 2002  |  Pubmed ID: 12463420

We report here cloning and characterization of a novel human gene, termed VMP, which is a vesicular membrane protein. RT-PCR analysis shows that VMP is expressed exclusively in brain of the 16 tissues examined, suggesting that it is a neuron-specific membrane protein. The cDNA encodes 195 amino acid with a putative molecular weight of about 24 KDa. VMP contains two putative membrane spanning domains and a hydrophilic tail homologous to the microtubule-binding domain of MAPs. So it is speculated that VMP may associated with microtubules through its C-terminal and plays an important role in vesicular organelles transport and nerve signals.

Identification of a Novel Human DDX40gene, a New Member of the DEAH-box Protein Family

Journal of Human Genetics. 2002  |  Pubmed ID: 12522690

The DExH/D-box superfamily of RNA helicases seems to play key roles during RNA metabolism, such as pre-mRNA splicing, ribosome biogenesis, and others. We have cloned a new gene of the DEAH-box protein subgroup, designated DDX40 (DEAD/H-box polypeptide 40 gene). DDX40 contains 3656 nucleotides and codes for a putative 779-amino-acid protein. Sequence analysis of the cDNA product revealed that it contained a DEAH (Asp-Glu-Ala-His) sequence motif and other conserved motifs. The DDX40 protein shared 53% and 43% amino acid identity with human DDX8 and yeast Drh1, respectively, in the conserved region. Northern blot analysis showed that DDX40 was expressed ubiquitously in the eight tissues examined, implying a general physiological function of the protein. We speculate that, like other members of the DExH/D-box superfamily, DDX40 may play roles in pre-mRNA splicing, ribosome biogenesis and other RNA processing functions.

Cloning and Characterization of a Novel Splice Variant of the Brain-specific Protein Densin-180

International Journal of Molecular Medicine. Feb, 2003  |  Pubmed ID: 12525888

Densin-180 is a brain-specific synaptic protein of the o-sialoglycoprotein family. It functions in specific adhesion between presynaptic and postsynaptic membranes at glutamatergic synapses. We have cloned a novel splice variant of densin-180 from a fetal brain cDNA library and termed it LRRC7. It is located on 1p31 and consists of 8 exons. It encodes a putative protein of 216 amino acids which contains a nuclear localization signal and four leucine-rich repeats (LRRs). LRRs are 20-29 residue sequence motifs present in a number of proteins with diverse functions. Expression analysis of LRRC7 shows it is expressed ubiquitously while its splice variant densin-180 is brain-specific.

PTP Alpha Regulates Integrin-stimulated FAK Autophosphorylation and Cytoskeletal Rearrangement in Cell Spreading and Migration

The Journal of Cell Biology. Jan, 2003  |  Pubmed ID: 12515828

We investigated the molecular and cellular actions of receptor protein tyrosine phosphatase (PTP) alpha in integrin signaling using immortalized fibroblasts derived from wild-type and PTP alpha-deficient mouse embryos. Defects in PTP alpha-/- migration in a wound healing assay were associated with altered cell shape and focal adhesion kinase (FAK) phosphorylation. The reduced haptotaxis to fibronectin (FN) of PTP alpha-/- cells was increased by expression of active (but not inactive) PTP alpha. Integrin-mediated formation of src-FAK and fyn-FAK complexes was reduced or abolished in PTP alpha-/- cells on FN, concomitant with markedly reduced phosphorylation of FAK at Tyr397. Reintroduction of active (but not inactive) PTP alpha restored FAK Tyr-397 phosphorylation. FN-induced cytoskeletal rearrangement was retarded in PTP alpha-/- cells, with delayed filamentous actin stress fiber assembly and focal adhesion formation. This mimicked the effects of treating wild-type fibroblasts with the src family protein tyrosine kinase (Src-PTK) inhibitor PP2. These results, together with the reduced src/fyn tyrosine kinase activity in PTP alpha-/- fibroblasts (Ponniah et al., 1999; Su et al., 1999), suggest that PTP alpha functions in integrin signaling and cell migration as an Src-PTK activator. Our paper establishes that PTP alpha is required for early integrin-proximal events, acting upstream of FAK to affect the timely and efficient phosphorylation of FAK Tyr-397.

Molecular Cloning and Characterization of a Novel Dual-specificity Phosphatase18 Gene from Human Fetal Brain

Biochimica Et Biophysica Acta. Feb, 2003  |  Pubmed ID: 12591617

Dual-specificity protein phosphatases (DSPs), a new family of protein tyrosine phosphatases (PTPs), are characterized by the ability to dephosphorylate both phospho-tyrosyl and phospho-seryl/threonyl residues. It has been known that most of the enzymes play important roles in the regulation of mitogenic signal transduction and control the cell cycle in response to extracellular stimuli. In this study, a novel human DSP gene named Dual-specificity Phosphatase18 (DUSP18) was isolated by large-scale sequencing analysis of a human fetal brain cDNA library. DUSP18 is localized at Chromosome 22 q12.1. Its cDNA is 2450 base pairs in length, encoding a 188-amino acid polypeptide in which a DSP motif but not a CH2 domain is included. RT-PCR revealed that the DUSP18 was widely expressed in different tissues. GST-DUSP18 fusion protein showed distinctive phosphatase activity toward p-nitrophenyl phosphate (pNPP), as well as oligopeptides containing pThr and pTyr, indicating that DUSP18 is a protein phosphatase with dual substrate specificity. The optimal condition for the reaction was pH 6.0 and 55 degrees C. Addition of Mn(2+) ions was able to enhance the enzyme activity while the activity was strongly inhibited by iodoaretic acid. Mutations in selected sites showed the importance of Asp-73, Cys-104, Arg-110 and Ser-111 in phosphatase activity of DUSP18.

Identification of a Novel Human Angiopoietin-like Gene Expressed Mainly in Heart

Journal of Human Genetics. 2003  |  Pubmed ID: 12624729

The angiopoietins are an important family of growth factors specific for vascular endothelium. Most of them bind to the TIE2 receptor and are related to regulation of angiogenesis. During large-scale DNA sequencing of the human fetal brain cDNA library, we cloned a novel human angiopoietin-like cDNA and termed it human angiopoietin-like 5 ( ANGPTL5). Like other members of the angiopoietin family, ANGPTL5-deduced protein also has an N-terminal cleavable signal peptide, a predicted coiled-coil domain, and a fibrinogen-like domain. The search against the human genome database indicated that ANGPTL5 maps to 11q22. Expression analysis of ANGPTL5 shows that it is mainly expressed in adult human heart.

Transurethral Electrochemical Treatment of Benign Prostatic Hyperplasia

Chinese Medical Journal. Jan, 2003  |  Pubmed ID: 12667399

To study the mechanism and feasibility of transurethral electrochemical therapy for the treatment of benign prostatic hyperplasia (BPH).

Isolation and Characterization of a Novel Human Putative Anemia-related Gene Homologous to Mouse Sideroflexin

Biochemical Genetics. Apr, 2003  |  Pubmed ID: 12670026

Cloning and Expression of a Novel Human C5orf12 Gene*, a Member of the TMS_TDE Family

Molecular Biology Reports. Mar, 2003  |  Pubmed ID: 12688535

We report here cloning and characterization of a novel human gene, termed C5orf12, which is a putative membrane protein belonging to the TMS_TDE family. The cDNA encodes 423 amino acid with a putative molecular weight of about 47 KDa. Secondary structure prediction showed that C5orf12 contained 10 putative transmembrane helices, which has high identity with other family members. We performed RT-PCR to examine its expression pattern. The result showed that C5orf12 was highly expressed in placenta, skeletal muscle, spleen, thymus, testis and peripheral leukocyte while expressed weakly in heart and liver. C5orf12 has high identity with the rat TPO1, so we speculate that C5orf12 may also have a role in the brain development.

[Expression and Significance of Clusterin in Normal Prostate, Benign Prostate Hyperplasia and Prostate Cancer]

Zhonghua Wai Ke Za Zhi [Chinese Journal of Surgery]. Feb, 2003  |  Pubmed ID: 12783666

To investigate the expression and significance of Clusterin in normal prostate, benign prostate hyperplasia (BPH) and prostate cancer.

Identification of a Novel Human Doublecortin-domain-containing Gene (DCDC1) Expressed Mainly in Testis

Journal of Human Genetics. 2003  |  Pubmed ID: 12820024

Mutations in the X-linked gene doublecortex (DCX) result in lissencephaly in males or subcortical laminar heterotopia (double cortex) in females. Recently, an evolutionarily conserved doublecortin (DC) domain important for microtubule binding and microtubule polymerization was defined according to detailed sequence analysis of DCX and DCX-like proteins. Subsequently we cloned a novel human cDNA that contained a DC domain during large-scale DNA sequencing of the human fetal brain cDNA library, and termed it doublecortin-domain-containing 1 (DCDC1). According to a search against the human genome database, DCDC1 was mapped to 11p13. Expression analysis showed that DCDC1 was mainly expressed in adult testis. Furthermore, the expression level of DCDC1 in fetal brain was much higher than in adult brain.

Molecular Cloning and Characterization of a Novel Human Hydroxysteroid Dehydrogenase-like 2 (HSDL2) CDNA from Fetal Brain

Biochemical Genetics. Jun, 2003  |  Pubmed ID: 12834046

Hydroxysteroid dehydrogenases (HSDs) are responsible for the biosynthesis of steroid hormones and play a crucial role in mammalian physiology and development. By large-scale sequencing analysis of a human fetal brain cDNA library, we isolated a novel human hydroxysteroid dehydrogenase-like cDNA (HSDL2). This cDNA is 3211 bp in length, encoding a 418-amino-acid polypeptide, which contains a typical motif for NAD(P)+-binding (TGxxxGxG), an SDR active site motif (S-Y-K) and a sterol carrier protein domain. HSDL2 shows high similarity with the homologues in the mouse and fruit fly. The HSDL2 gene is mapped to chromosome 9q32 and contains 11 exons. RT-PCR analysis shows that the HSDL2 gene is widely expressed in human tissues and the expression levels in liver, kidney, prostate, testis, and ovary are relatively high.

Isolation and Characterization of a Human Putative Receptor Protein Kinase CDNA STYK1

Molecular Biology Reports. Jun, 2003  |  Pubmed ID: 12841579

Protein kinases (PKs) represent a well studied but most diverse protein superfamily. The covalent, reversible linkage of phosphate to serine, threonine, and tyrosine residues of substrate proteins by protein kinases is probably ubiquitous cellular mechanism for regulation of physiological processes. It is known to us that most signaling pathways impinge at some point on protein kinases. Here we report a human putative receptor protein kinase cDNA STYK1. The STYK1 cDNA is 2749 base pairs in length and contains an open reading frame encoding 422 amino acids. The STYK1 gene is mapped to human chromosome 12p13 and 11 exons were found. RT-PCR showed that STYK1 is widely expressed in human tissues.

[Effect of Different Methods for Postoperative Pain Management on Catecholamine Response to Abdominal Surgery]

Beijing Da Xue Xue Bao. Yi Xue Ban = Journal of Peking University. Health Sciences. Apr, 2003  |  Pubmed ID: 12920841

To observe the effect of different analgesic methods and the influence of catecholamine response to elective abdominal surgery.

Cloning and Sequence Analysis of the Human CDNA Encoding the Synaptoporin (delta), a Highly Conservative Synaptic Vesicle Protein

Molecular Biology Reports. Sep, 2003  |  Pubmed ID: 12974474

Synaptoporin is a membrane protein of synaptic vesicles, which belongs to the synaptophysin family. It was first isolated from rat brain. Here we report the cloning and characterization of the human cDNA that encodes the human homologue of synaptoporin. It has two splicing variants, which is in accordance with its ortholog in chicken. Its deduced amino acid sequence displays 97% and 81% identity with the synaptoporin of rat and chicken, respectively. This gene was mapped to the chromosome 3p14.3 by matching against the Human Genome Sequence Database. 16-tissue RT-PCR analysis shows that human synaptoporin is specifically expressed in the brain.

Development of New Multivalent-bispecific Agents for Pretargeting Tumor Localization and Therapy

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. Sep, 2003  |  Pubmed ID: 14506187

Two bispecific diabodies (BS1.5 and BS1.5H) and two bispecific trivalent proteins (BS6 and BS8) were produced and tested as potential agents for pretargeted delivery of radiolabeled bivalent haptens to tumors expressing carcinoembryonic antigen.

[Multivariate Analysis of Recurrence in T1 Bladder Transitional Cell Carcinoma]

Zhonghua Zhong Liu Za Zhi [Chinese Journal of Oncology]. Sep, 2003  |  Pubmed ID: 14575574

To investigate the prognostic value of some clinicopathologic indexes and biologic tumor markers in predicting recurrence in T1 transitional cell carcinoma (TCC) of the bladder.

[Impact of Short-term Neoadjuvant Hormonal Treatment on Neuroendocrine Differentiation in Prostate Carcinoma]

Zhonghua Zhong Liu Za Zhi [Chinese Journal of Oncology]. Sep, 2003  |  Pubmed ID: 14575578

To study the impact of short-term neoadjuvant hormonal treatment on neuroendocrine (NE) differentiation and the relation of NE differentiation and tumor regression.

[Application of Atomic Force Microscopy in the Study of Morphology of Double Minute Chromosomes]

Yi Chuan Xue Bao = Acta Genetica Sinica. Sep, 2003  |  Pubmed ID: 14577382

Atomic force microscopy (AFM) has many advantages in the study of biological samples, such as the convenient specimen preparation and the high resolution. In the present study, AFM was used to observe the double minute chromosomes (DMs) in mouse methotrexate-resistant cell line 3T3R500. AFM images were obtained by tapping mode, contact mode and later force mode of AFM. DMs were composed of two compact spheres connected with fibers. The number of DMs in the 3T3R500 cells increased with increasing levels of methotrexate (MTX) resistance. The data of the height and the underside diameter of the DMs were also obtained. The details of specimen preparation and scan mode selection of AFM were discussed. Our results show that AFM is a powerful method in the study of DMs.

Nogo-A at CNS Paranodes is a Ligand of Caspr: Possible Regulation of K(+) Channel Localization

The EMBO Journal. Nov, 2003  |  Pubmed ID: 14592966

We report Nogo-A as an oligodendroglial component congregating and interacting with the Caspr-F3 complex at paranodes. However, its receptor Nogo-66 receptor (NgR) does not segregate to specific axonal domains. CHO cells cotransfected with Caspr and F3, but not with F3 alone, bound specifically to substrates coated with Nogo-66 peptide and GST-Nogo-66. Binding persisted even after phosphatidylinositol- specific phospholipase C (PI-PLC) removal of GPI-linked F3 from the cell surface, suggesting a direct interaction between Nogo-66 and Caspr. Both Nogo-A and Caspr co-immunoprecipitated with Kv1.1 and Kv1.2, and the developmental expression pattern of both paralleled compared with Kv1.1, implicating a transient interaction between Nogo-A-Caspr and K(+) channels at early stages of myelination. In pathological models that display paranodal junctional defects (EAE rats, and Shiverer and CGT(-/-) mice), distances between the paired labeling of K(+) channels were shortened significantly and their localization shifted toward paranodes, while paranodal Nogo-A congregation was markedly reduced. Our results demonstrate that Nogo-A interacts in trans with axonal Caspr at CNS paranodes, an interaction that may have a role in modulating axon-glial junction architecture and possibly K(+)-channel localization during development.

Multiple Active Oxidants in Competitive Epoxidations Catalyzed by Porphyrins and Corroles

Chemical Communications (Cambridge, England). Dec, 2003  |  Pubmed ID: 14703814

We demonstrate the existence of multiple active oxygenating species in porphyrin and corrole-catalyzed competitive epoxidations of styrene and cis-cyclooctene.

Cloning and Characterization of Human Synaptotagmin 10 Gene

DNA Sequence : the Journal of DNA Sequencing and Mapping. Oct, 2003  |  Pubmed ID: 14756426

Synaptotagmin (Syt) is a membrane protein family of secretory vesicles, abundant in neural and some endocrine cells. All the members of this family contain one transmembrane region and two conserved C2 domains. Here we reported a new human Syt 10 gene isolated when screening a human fetal brain cDNA library. This cDNA clone is 3287 bp and contains an open reading frame from 299 to 1870 encoding a putative protein of 523 amino acids. It shares 94.6 and 94.8% homology to rat Syt 10 and mouse Syt 10 at protein level, respectively. RT-PCR result showed that it is expressed only in pancreas, lung and kidney.

Cloning and Identification of a Novel Human RNPC3 Gene That Encodes a Protein with Two RRM Domains and is Expressed in the Cell Nucleus

Biochemical Genetics. Oct, 2003  |  Pubmed ID: 14974681

The RNA recognition motifs (RRM) domain is one of the most common eukaryotic protein folds. Proteins containing RRM domains function in important steps of posttranscriptional regulation of gene expression and are involved in processing and transport of mRNA precursors. Here we describe the cloning and characterization of a novel human RNPC3 gene containing two RNA recognition motifs. The 1870 bp cDNA encodes a protein with 517 amino acids. It also contains two bipartite nuclear targeting sequences, which is important for nuclear targeting for proteins, especially those functioning in the cell nucleus. The GFP location of the RNPC3 gene product shows that this protein is located in the cell nucleus. RT-PCR reveals that it is abundantly expressed in kidney and pancreas.

Enhanced Stimulation of Chromosomal Translocations by Radiomimetic DNA Damaging Agents and Camptothecin in Saccharomyces Cerevisiae Rad9 Checkpoint Mutants

Mutation Research. Mar, 2004  |  Pubmed ID: 15013706

Saccharomyces cerevisiae rad9 checkpoint mutants exhibit pleiotropic phenotypes, including higher frequencies of chromosome loss, radiation sensitivity, and decreased induction of DNA damage-inducible genes. We had previously shown that rad9 mutants exhibit higher frequencies of DNA damage-associated translocations but lower frequencies of DNA damage-associated sister chromatid exchange (SCE), compared to wild type. Herein, we have shown that differences between the frequencies of DNA damage-associated recombination in the rad9 mutant and wild type depend on the identity and the concentration of the DNA damaging agent. Translocation and SCE frequencies were measured in strains containing truncated his3 fragments, located either on chromosomes II and IV, or located in tandem on chromosome IV, respectively. DNA damage-associated frequencies of translocations after exposure to hydrogen peroxide (H(2)O(2)), bleomycin, phleomycin, cisplatin, and camptothecin are higher in the rad9 diploid than in wild type. However, translocation frequencies after exposure to 4-nitroquinoline 1-oxide (4-NQO) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) are similar in rad9 and wild-type strains. We suggest that the deficiency in triggering G(2) arrest after exposure to specific DNA damaging agents results in the higher levels of DNA damage-associated translocations in rad9 mutants.

Apoptosis Incidence and Protein Expression of P53, TGF-beta Receptor II, P27Kip1, and Smad4 in Benign, Premalignant, and Malignant Human Prostate

Human Pathology. Mar, 2004  |  Pubmed ID: 15017584

Deregulation of apoptosis is involved in prostate cancer development and progression. This study involved an immunohistochemical "profiling" of prostate tissue specimens from patients who underwent prostatectomy for localized prostate cancer, to identify apoptosis-specific alterations associated with premalignant precursor lesions. Prostate tissue was pathologically evaluated, and areas of benign acini, high-grade prostate intraepithelial neoplasia (HGPIN), and prostate cancer were identified. Immunohistochemical analysis was performed to determine the expression of p27Kip1, a key cell cycle regulator, transforming growth factor (TGF)-beta receptor II (TbetaRII), a critical signaling effector of TGF-beta; Smad4, a downstream intracellular effector of TGF-beta signaling; p53, a key apoptosis regulator; and prostate-specific antigen (PSA), a clinical marker of prostate cancer. The apoptotic index of the same cell populations was determined using the transferase-mediated digoxigenin-tagged 16-desoxy-uridine-triphosphate nick end labeling assay. Our findings indicate a significant reduction in p27Kip1 immunoreactivity in HGPIN (P<0.0001) and prostate cancer (P<0.0001) compared with the benign tissue. A significant down-regulation was detected in TbetaRII expression in HGPIN and prostate cancer compared with benign prostatic hyperplasia (BPH)(P<0.001). A significant decrease was also observed in Smad4 levels in HGPIN and prostate cancer compared with BPH (P<0.001). Evaluation of the incidence of apoptosis revealed a significant decrease in the apoptotic index among the epithelial cell populations in HGPIN and a further decrease in prostate carcinoma (P<0.01). This reduced apoptotic index correlated with a significant increase in p53 immunoreactivity in the prostatic carcinoma foci. Prostate cancer cells exhibited strong nuclear staining for p53 compared with adjacent HGPIN (P<0.05) and the benign lesions of the same prostate specimens (P<0.05). A significant reduction in PSA immunostaining was detected in HGPIN and prostate carcinoma foci compared with the benign glandular epithelia (P<0.001). These results further define deregulation of TGF-beta signaling effectors as a molecular basis for loss of apoptotic control contributing to the development of prostate tumors. Identification of apoptotic regulators in precursor premalignant lesions may have prognostic significance in disease progression as well as therapeutic value for targeting prostate cancer.

CDNA Cloning and Expression Analysis of a Novel Human F-box Domain Containing Gene

Molecular Biology Reports. Mar, 2004  |  Pubmed ID: 15040455

F-box proteins are a large family of eukaryotic proteins that are characterized by an approximately 40 amino acid motif. Some F-box proteins are critical for the controlled degradation of cellular regulatory proteins. Here we report that a novel member of F-box proteins, FBXO35 gene, was cloned and identified during the large-scale sequencing analysis from a human fetal brain cDNA library. FBXO35 gene shares amino acid similarity with several putative mouse genes not only in F-box domain but also in the rest of the sequence, which indicates that FBXO35 might also contain some other unknown conserved domain. RT-PCR analysis indicated that FBXO35 gene had a ubiquitously low expression pattern in most human adult tissues. According to bioinformatics analysis, the FBXO35 gene was found located in chromosome 3p21.

Characterization of a Human Sec14-like Protein CDNA SEC14L3 Highly Homologous to Human SPF/TAP

Molecular Biology Reports. Mar, 2004  |  Pubmed ID: 15040456

Supernatant protein factor (SPF) and alpha-tocopherol-associated protein (TAP) both belong to a widespread lipid-binding Sec 14-like protein family. All the members of the family have the lipid-binding motif called CRAL_TRIO. SPF is showed to stimulate the conversion of squalene to lanosterol and enhance cholesterol biosynthesis. TAP is identified to be involved in the intracellular distribution of alpha-tocopherol. Recently TAP is identified as SPF though they have very different functions. Here we report a human SPF/TAP homology SEC14L3 with 2082 base pairs in length and contains an open reading frame encoding a 400 amino acids protein. Analysis shows that SEC14L3 is mapped to 22q12 and expresses only in the liver among the used sixteen tissues in the test.

Cloning and Expression of Human GTDC1 Gene (glycosyltransferase-like Domain Containing 1) from Human Fetal Library

DNA and Cell Biology. Mar, 2004  |  Pubmed ID: 15068588

The glycosyltransferases (GTs) catalyze the synthesis of the carbohydrate portions of glycoproteins, glycolipids, and proteoglycans. Here we report the cloning and characterization of a novel human GTDC1 (glycosyltransferase-like domain containing 1) gene, which locates on human chromosome 2q22. The GTDC1 cDNA is 2954 bp in length, encoding a putative protein of 458 amino acids. At protein level human GTDC1 has 75 and 37% identity with its homologous counterparts in the mouse and fruitfly, respectively. RT-PCR analysis revealed its relatively high expression level in the adult lung, spleen, testis, and peripheral blood leukocyte.

Donor Ligand Effect on the Nature of the Oxygenating Species in Mn(III)(salen)-catalyzed Epoxidation of Olefins: Experimental Evidence for Multiple Active Oxidants

Inorganic Chemistry. Apr, 2004  |  Pubmed ID: 15074985

The stereoselectivity of olefin epoxidation catalyzed by Mn(III)(salen)X (1a, X = Cl(-); 1b, X = BF(4)(-)) complexes is examined in the presence of neutral donor ligands, employing various iodosylarenes (ArIO: PhIO, C(6)F(5)IO, and MesIO) as the oxygen atom source. The cis/trans ratios of stilbene oxides and the enantiomeric excesses of styrene oxide and 1,2-dihydronaphthalene oxide are found to be strongly dependent on the nature of the iodosylarenes under certain conditions. In other cases, olefin epoxidation is shown to proceed with essentially identical diastereoselectivities or enantioselectivities, regardless of the oxygen atom source used. We propose that a Mn(V)(salen)-oxo intermediate and a complex between the catalyst and the terminal oxidant competitively effect the epoxidation when the stereoselectivities are markedly dependent on the oxygen atom source. A single Mn(V)(salen)-oxo species is considered to be the sole oxygenating intermediate when the terminal oxidants do not exert a notable influence on the product selectivities. Our results clearly demonstrate the existence of multiple oxidizing species and the conditions in which only a single oxygenating intermediate is involved. The axial donor ligands (both anionic ligands and neutral ligands) are shown to strongly influence both the identity and the reactivity of the oxygenating species.

[Report of a Case of Penile Epithelioid Sarcoma]

Zhonghua Nan Ke Xue = National Journal of Andrology. Mar, 2004  |  Pubmed ID: 15080069

To enhance the knowledge and the effect of the diagnosis and treatment of primary epithelioid sarcoma of the penis.

Isolation and Characterization of a Jerky and JRK/JH8 Like Gene, Tigger Transposable Element Derived 7, TIGD7

Biochemical Genetics. Aug, 2004  |  Pubmed ID: 15487591

Cloning and Characterization of a Human CDNA ACAD10 Mapped to Chromosome 12q24.1

Molecular Biology Reports. Sep, 2004  |  Pubmed ID: 15560374

Mitochondrial fatty acid beta-oxidation is an important energy resource for many mammal tissues. Acyl-CoA dehydrogenases (ACADs) are a family of flavoproteins that are involved in the beta-oxidation of the fatty acyl-CoA derivatives. Deficiency of these ACADs can cause metabolic disorders including muscle fatigue, hypoglycaemia, hepatic lipidosis and so on. By large scale sequencing, we identified a cDNA sequence of 3960 base pairs with a typical acyl-CoA dehydrogenase function domain. RT-PCR result shows that it is widely expressed in human tissues, especially high in liver, kidney, pancreas and spleen. It is hypothesized that this is a novel member of ACADs family.

CDNA Cloning, Gene Organization and Expression Analysis of Human Peptidylarginine Deiminase Type VI

Acta Biochimica Polonica. 2004  |  Pubmed ID: 15625577

Peptidylarginine deiminase (PAD) catalyzes the post-translational modification of protein through the conversion of arginine to citrulline in the presence of calcium ions. Human, similar to rodents, has four isoforms of PAD (type I, II, III and IV/V), each of which is distinct in substrate specificity and tissue specific expression. In our large-scale sequencing project, we identified a new human PAD cDNA from a human fetal brain cDNA library. The putative protein encoded by this cDNA is designated hPADVI. Expression analysis of hPADVI showed that it is mainly expressed in adult human ovary and peripheral blood leukocytes. We conclude that hPADVI may be orthologous to mouse ePAD, basing on sequence comparison, chromosome localization and exon-intron structure analysis. PAD-mediated deimination of epithelial cell keratin resulting in cytoskeletal remodeling suggests a possible role for hPADVI in cytoskeletal reorganization in the egg and in early embryo development. This study describes a new important member of the human PAD family.

[Effect of Heparin on Fetal Growth Restriction]

Zhonghua Fu Chan Ke Za Zhi. Dec, 2004  |  Pubmed ID: 15733401

To investigate the clinical effect and safety of heparin in treating fetal growth restriction (FGR).

Conditional Macrophage Ablation in Transgenic Mice Expressing a Fas-based Suicide Gene

Journal of Leukocyte Biology. Apr, 2004  |  Pubmed ID: 14726498

Transgenic mice expressing an inducible suicide gene, which allows systemic and reversible elimination of macrophages, were developed. A macrophage-specific c-fms promoter was used to express enhanced green fluorescent protein and a drug-inducible suicide gene that leads to Fas-mediated apoptosis in resting and cycling cells of the macrophage lineage. Transgenic mice were fertile, of normal weight, and showed no abnormal phenotype before drug exposure. The transgene was expressed constitutively in macrophages and dendritic cells (DC) but not significantly in T cells or B cells. Induction of the suicide gene led to depletion of 70-95% of macrophages and DC in nearly all tissues examined. Depletion reduced the ability to clear bacteria from the blood and led to increased bacterial growth in the liver. Depleted mice displayed several abnormalities, including splenomegaly, lymphadenopathy, thymic atrophy, extramedullary hematopoiesis, and development of peritoneal adhesions. This new, transgenic line will be useful in investigating the role of macrophages and DC.

[Methods of Modern Clinical Research Design]

Zhonghua Yi Xue Za Zhi. Feb, 2005  |  Pubmed ID: 15854498

Effect of Terazosin on Tissue Vascularity and Apoptosis in Transitional Cell Carcinoma of Bladder

Urology. May, 2005  |  Pubmed ID: 15882756

To present a pilot study to determine whether the alpha1-adrenoceptor antagonist terazosin can induce apoptosis in transitional cell carcinoma (TCC) of the bladder, similar to the effect seen with prostate cancer. The alpha1-adrenoceptor antagonist terazosin has recently been shown to induce apoptosis in prostate cancer cells both in vitro and in vivo and to reduce prostatic tissue vascularity by potentially affecting endothelial cell adhesion.

ERK Phosphorylates P66shcA on Ser36 and Subsequently Regulates P27kip1 Expression Via the Akt-FOXO3a Pathway: Implication of P27kip1 in Cell Response to Oxidative Stress

Molecular Biology of the Cell. Aug, 2005  |  Pubmed ID: 15930121

Mice deficient for p66shcA represent an animal model to link oxidative stress and aging. p66shcA is implicated in oxidative stress response and mitogenic signaling. Phosphorylation of p66shcA on Ser36 is critical for its function in oxidative stress response. Here we report the identification of ERK as the kinase phosphorylating p66shcA on Ser36. Activation of ERKs was necessary and sufficient for Ser36 phosphorylation. p66shcA interacted with ERK and was demonstrated to be a substrate for ERK, with Ser36 being the major phosphorylation site. Furthermore, in response to H2O2, inhibition of ERK activation repressed p66shcA-dependent phosphorylation of FOXO3a and the down-regulation of its target gene p27kip1. Down-regulation of p27 might promote cell survival, as p27 played a proapoptotic role in oxidative stress response. As a feedback regulation, Ser36 phosphorylated p66shcA attenuated H2O2-induced ERK activation, whereas p52/46shcA facilitated ERK activation, which required tyrosine phosphorylation of CH1 domain. p66shcA formed a complex with p52/46ShcA, which may provide a platform for efficient signal propagation. Taken together, the data suggest there exists an interplay between ERK and ShcA proteins, which modulates the expression of p27 and cell response to oxidative stress.

Identification of TopBP1 As a C-Abl-interacting Protein and a Repressor for C-Abl Expression

The Journal of Biological Chemistry. Aug, 2005  |  Pubmed ID: 15961388

Expression of BCR-ABL is the leading cause of chronic myelogenous leukemia. In chronic myelogenous leukemia cells, c-Abl expression is silenced by promoter methylation. In addition, the level of c-Abl needs to be tightly and constantly regulated due to its cytotoxicity and its rapid degradation after activation. Yet the regulation of c-Abl expression remains unclear. In an effort to gain better understanding of c-Abl function, we performed a glutathione S-transferase-Abl pull-down screen and identified TopBP1, a topoisomerase IIbeta-binding protein that contains Brca1 C-terminal motifs and has been implicated in DNA damage response. Their physical interaction was verified by in vitro and in vivo assays with TopBP1 found as a substrate of Abl proteins. TopBP1 could repress the expression of c-Abl at both mRNA and protein levels. Reporter assays indicate that TopBP1 directly repressed the promoter activity of c-Abl. Furthermore, TopBP1 repressed expression of c-Abl through a novel mechanism that involved histone deacetylation and DNA methylation. This transcriptional repression was inhibited by c-Abl in a kinase-dependent manner. The dual antagonistic interplay between c-Abl and TopBP1 may also provide a mechanism for fine-tuning of c-Abl levels.

Enhanced Stimulation of Chromosomal Translocations and Sister Chromatid Exchanges by Either HO-induced Double-strand Breaks or Ionizing Radiation in Saccharomyces Cerevisiae Yku70 Mutants

Mutation Research. Oct, 2005  |  Pubmed ID: 15990123

DNA double-strand break (DSB) repair occurs by homologous recombination (HR) or non-homologous endjoining (NHEJ). In Saccharomyces cerevisiae, expression of both MATa and MATalpha inhibits NHEJ and facilitates DSB-initiated HR. We previously observed that DSB-initiated recombination between two his3 fragments, his3-Delta5' and his3-Delta3'::HOcs is enhanced in haploids and diploids expressing both MATa and MATalpha genes, regardless of the position or orientation of the his3 fragments. Herein, we measured frequencies of DNA damage-associated translocations and sister chromatid exchanges (SCEs) in yku70 haploid mutants, defective in NHEJ. Translocation and SCE frequencies were measured in strains containing the same his3 fragments after DSBs were made directly at trp1::his3-Delta3'::HOcs. Wild type and yku70 cells were also exposed to ionizing radiation and radiomimetic agents methyl methanesulfonate (MMS), phleomycin, and 4-nitroquinolone-1-oxide (4-NQO). Frequencies of X-ray-associated and DSB-initiated translocations were five-fold higher in yku70 mutants compared to wild type; however, frequencies of phleomycin-associated translocations were lower in the yku70 haploid mutant. Frequencies of DSB-initiated SCEs were 1.8-fold higher in the yku70 mutant, compared to wild type. Thus, DSB-initiated HR between repeated sequences on non-homologous chromosomes and sister chromatids occurs at higher frequencies in yku70 haploid mutants; however, higher frequencies of DNA damage-associated HR in yku70 mutants depend on the DNA damaging agent.

Saccharomyces Cerevisiae RAD53 (CHK2) but Not CHK1 is Required for Double-strand Break-initiated SCE and DNA Damage-associated SCE After Exposure to X Rays and Chemical Agents

DNA Repair. Nov, 2005  |  Pubmed ID: 16039914

Saccharomyces cerevisiae RAD53 (CHK2) and CHK1 control two parallel branches of the RAD9-mediated pathway for DNA damage-induced G(2) arrest. Previous studies indicate that RAD9 is required for X-ray-associated sister chromatid exchange (SCE), suppresses homology-directed translocations, and is involved in pathways for double-strand break repair (DSB) repair that are different than those controlled by PDS1. We measured DNA damage-associated SCE in strains containing two tandem fragments of his3, his3-Delta5' and his3-Delta3'::HOcs, and rates of spontaneous translocations in diploids containing GAL1::his3-Delta5' and trp1::his3-Delta3'::HOcs. DNA damage-associated SCE was measured after log phase cells were exposed to methyl methanesulfonate (MMS), 4-nitroquinoline 1-oxide (4-NQO), UV, X rays and HO-induced DSBs. We observed that rad53 mutants were defective in MMS-, 4-NQO, X-ray-associated and HO-induced SCE but not in UV-associated SCE. Similar to rad9 pds1 double mutants, rad53 pds1 double mutants exhibited more X-ray sensitivity than the single mutants. rad53 sml1 diploid mutants exhibited a 10-fold higher rate of spontaneous translocations compared to the sml1 diploid mutants. chk1 mutants were not deficient in DNA damage-associated SCE after exposure to DNA damaging agents or after DSBs were generated at trp1::his3-Delta5'his3-Delta3'::HOcs. These data indicate that RAD53, not CHK1, is required for DSB-initiated SCE, and DNA damage-associated SCE after exposure to X-ray-mimetic and UV-mimetic chemicals.

The Saccharomyces Cerevisiae PDS1 and RAD9 Checkpoint Genes Control Different DNA Double-strand Break Repair Pathways

DNA Repair. Jan, 2005  |  Pubmed ID: 15533838

In response to DNA damage, the Saccharomyces cerevisiae securin Pds1 blocks anaphase promotion by inhibiting ESP1-dependent degradation of cohesins. PDS1 is positioned downstream of the MEC1- and RAD9-mediated DNA damage-induced signal transduction pathways. Because cohesins participate in postreplicative repair and the pds1 mutant is radiation sensitive, we identified DNA repair pathways that are PDS1-dependent. We compared the radiation sensitivities and recombination phenotypes of pds1, rad9, rad51 single and double mutants, and found that whereas pds1 rad9 double mutants were synergistically more radiation sensitive than single mutants, pds1 rad51 mutants were not. To determine the role of PDS1 in recombinational repair pathways, we measured spontaneous and DNA damage-associated sister chromatid exchanges (SCEs) after exposure to X rays, UV and methyl methanesulfonate (MMS) and after the initiation of an HO endonuclease-generated double-strand break (DSB). The rates of spontaneous SCE and frequencies of DNA damage-associated SCE were similar in wild type and pds1 strains, but the latter exhibited reduced viability after exposure to DNA damaging agents. To determine whether pds1 mutants were defective in other pathways for DSB repair, we measured both single-strand annealing (SSA) and non-homologous end joining (NHEJ) in pds1 mutants. We found that the pds1 mutant was defective in SSA but efficient at ligating cohesive ends present on a linear plasmid. We therefore suggest that checkpoint genes control different pathways for DSB repair, and PDS1 and RAD9 have different roles in recombinational repair.

[Expression of IRP2 MRNA, TfR MRNA and Fn MRNA in HL-60 Cells]

Zhongguo Shi Yan Xue Ye Xue Za Zhi / Zhongguo Bing Li Sheng Li Xue Hui = Journal of Experimental Hematology / Chinese Association of Pathophysiology. Aug, 2005  |  Pubmed ID: 16129039

To explore the mechanism of iron metabolism and its regulation as well as the roles of IRP(2) in ion metabolism of HL-60 cells, HL-60 cells were cultured in RPMI 1640 medium supplemented with 10% heat-inactivated fetal bovine serum, which was treated with ferric chloride (FeCl(3)) or deferoxamine (DFO). The cells were harvested at 12, 24 and 48 hours of proliferation, and total RNA was isolated; cDNA was synthesized by reverse transcription (RT), and relative expression levels of IRP(2) mRNA, Fn mRNA and TfR mRNA were determined by RT-PCR. The results showed at follows: (1) the level of IRP(2) mRNA remained constant in all cells, whether or not treated with DFO or FeCl(3). However, the expression of IRP(2) mRNA decreased when the time of cell culture was prolonged. There was no significant difference between groups (F(B-S) = 1.199, P > 0.05), but there was significant difference among the different time culture (F(W-S) = 43.418, P < 0.01). (2) Cells which treated neither with DFO nor ferri chloride showed significant difference from the control (F(W-S) = 7.184, F(B-S) = 113.926; P < 0.01). The level of TfR mRNA increased in the cells treated with DFO. Surprisingly, when cells treated with FeCl(3), there was not decline of TfR mRNA expression, but it increased lightly at 12 hours and peaked at 24 hours and declined drastically at 48 hours. (3) The level of Fn mRNA in the cells treated with FeCl(3) was approximately 2-fold as the control cells. In contrast with the control cells, there was significant difference (P < 0.05). The level of Fn mRNA of the cells treated with DFO had little change. As compared with the control cells, no significant difference was seen (P > 0.05). (4) There was not any significant correlation between IRP(2) mRNA and TfR mRNA or Fn mRNA in HL-60 cells (r = -0.005; r = 0.074; P > 0.05). It is concluded that (1) IRP(2) may regulate the iron metabolism in HL-60 cells by altering amounts of the IRP(2) 3.7- or 6.4-kb mRNA at the transcriptional level, or by IRP(2) degradation at the post transcriptional level. (2) Both of Fn mRNA and TfR mRNA participated, more or less, in the iron metabolism in HL-60 cells.

Neurological Monitoring and Off-pump Surgery in a Very High-risk Stroke Patient

The Annals of Thoracic Surgery. Dec, 2005  |  Pubmed ID: 16305918

Stroke remains a high risk of coronary artery bypass grafting. We present a patient with progressively symptomatic coronary disease and severe four-vessel cerebrovascular disease not amenable to revascularization. This patient underwent coronary revascularization without neurologic complication using off-pump coronary surgery to avoid aortic manipulation and intraoperative electroencephalographic monitoring of cerebral perfusion. This management strategy may reduce the stroke risk in similar patients.

Isolation and Characterization of Ubiquitin-activating Enzyme E1-domain Containing 1, UBE1DC1

Molecular Biology Reports. Dec, 2005  |  Pubmed ID: 16328888

Ubiquitin and other ubiquitin-like proteins play important roles in post-translational modification. They are phylogenetically well-conserved in eukaryotes. Activated by other proteins, ubiquitin and ubiquitin-like proteins can covalently modify target proteins. The enzymes responsible for the activation of this modification have been known to include UBA1, SAE2, UBA3, SAE1 and ULA1. Here we report a new ubiquitin activating enzyme like cDNA, named ubiquitin activating enzyme E1-domain containing 1 (UBE1DC1), whose cDNA is 2654 base pairs in length and contains an open reading frame encoding 404 amino acids. The UBE1DC1 gene consists of 12 exons and is located at human chromosome 3q22. The result of RT-PCR showed that UBE1DC1 is expressed in most of human tissues.

A Selective Turn-on Fluorescent Sensor for Imaging Copper in Living Cells

Journal of the American Chemical Society. Jan, 2006  |  Pubmed ID: 16390096

We present the synthesis, properties, and biological applications of Coppersensor-1 (CS1), a new water-soluble, turn-on fluorescent sensor for intracellular imaging of copper in living biological samples. CS1 utilizes a BODIPY reporter and thioether-rich receptor to provide high selectivity and sensitivity for Cu+ over other biologically relevant metal ions, including Cu2+, in aqueous solution. This BODIPY-based probe is the first Cu+-responsive sensor with visible excitation and emission profiles and gives a 10-fold turn-on response for detecting this ion. Confocal microscopy experiments further establish that CS1 is membrane-permeable and can successfully monitor intracellular Cu+ levels within living cells.

Asymmetric Localization of Numb in the Chick Somite and the Influence of Myogenic Signals

Developmental Dynamics : an Official Publication of the American Association of Anatomists. Mar, 2006  |  Pubmed ID: 16425215

Whereas Notch signaling is known to play an essential role in the formation of somites, its role during later stages of somite maturation is less well understood. Here, we examine the signals and transcription factors that control the expression of the Notch antagonist, Numb, during somite maturation in the chick embryo. Numb mRNA is present in the epithelial somite and is increased in expression in the forming myotome. Numb protein displays a very specific subcellular localization and dynamic expression during somite maturation. Numb protein is asymmetrically localized in a cortical crescent on the basal side of dividing cells in the dorsomedial lip of the dermomyotome and is subsequently uniformly distributed throughout differentiated myotomal cells. Treatment of somites with either the combination of Wnt-3a and Shh, or ectodermal signals plus noggin, both of which induce somitic myogenesis, did not significantly affect Numb transcript levels but did lead to a dramatic increase in the levels of Numb protein, which was uniformly distributed throughout the cytoplasm of the resultant myotubes. Forced expression of MyoD in somites similarly induced high levels of Numb protein throughout the cytoplasm, without affecting Numb mRNA levels. We also found that signals that promote somitic myogenesis or forced MyoD expression induced expression of the Notch ligand, Serrate-2. Our findings suggest that Notch signals are specifically repressed in the myotome and that asymmetric expression of Numb in dividing cells of the dorsomedial lip of the dermomyotome may modulate whether these cells continue to divide or differentiate into myotomal cells.

[Effects of N-linked Oligosaccharide Chains on Expression of Integrin Beta1 and Apoptosis in Glomerular Mesangial Cells]

Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition. Jan, 2006  |  Pubmed ID: 16475271

The effects of N-linked oligosaccharide chains (TM), an inhibitor of N-glycosylation of proteins, on the expression of beta1 integrin and the apoptosis of glomerular mesangial cells (GMC) were observed for exploring the role of inhibitors of N-linked oligosaccharide chains in cell apoptosis, proliferation, and expression of beta1 integrin and cyclin D1, and hence finding a new approach to the synteresis of proliferative nephropathy.

Novel 2-substituted Nitronyl Nitroxides As Free Radical Scavengers: Synthesis, Biological Evaluation and Structure-activity Relationship

Bioorganic & Medicinal Chemistry. Aug, 2006  |  Pubmed ID: 16650996

To develop more potent small molecules with enhanced free radical scavenger properties, we designed and synthesized a series of nitronyl nitroxide derivatives 4a-h. A lead compound 4f was discovered based on Ach-induced vascorelaxation assay. Further chemical modification based on this scaffold provided a new series of 2-substituted phenylnitronyl nitroxide derivatives 6a-s. The newly synthesized compounds 6a-s possess improved radical scavenger's activity based on PC12 cell survival assay. Compounds 6g,n,o, and s are some of the most potent compounds in terms of NO, H(2)O(2), and OH scavenging ability. 2-Substitued phenylnitronyl nitroxides had a higher radical scavenging activity with the electron-donating group (EDG). In contrast, the introduction of electron-withdrawing group (EWG) to the aromatic ring led to a dramatic decrease in its radical scavenging activity. These results suggest that the electron-donating group (EDG) of the aromatic ring may be an important factor influencing the radical scavenging behavior of these compounds, and the potency of free radical scavenging activity largely depended on the position and electronic properties of the phenyl ring substituents. The enhanced radical scavenging capacities of the novel 2-substituted nitronyl nitroxides may be potential drug leads against the deleterious action of ROS (reactive oxygen species)/RNS (reactive nitrogen species).

Cloning and Characterization of a Novel KRAB-domain-containing Zinc Finger Gene (ZNF284L)

Molecular Biology Reports. Jun, 2006  |  Pubmed ID: 16817023

The zinc finger gene (ZNF) family plays an important role in the regulation of transcription. This study reports the cloning and characterization of a novel human zinc finger protein cDNA (ZNF284L) from fetal brain cDNA library. The ZNF284L cDNA is 2223 bp in length encoding a 593-aa polypeptide. The protein contains a KRAB A+b box and eleven C2H2 type zinc finger motifs. ZNF284L gene is mapped to 19q13.2-19q13.3 with 5 exons, and the expression pattern of ZNF284L gene was also examined by reverse transcription polymerase chain reaction (RT-PCR). The transcripts were detected in the human lung, liver, pancreas, thymus, heart, placenta, spleen, prostate, ovary, small intestine and colon, but in human brain, skeletal muscle, kidney, testis and peripheral blood leukocyte, no expression was detected.

[Effects of Rosiglitazone on the Expression of Beta1, Integrin and ICAM-1 in High Glucose-induced Rat Glomerular Mesangial Cells]

Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition. Jul, 2006  |  Pubmed ID: 16909611

To observe the effects of PPARgamma activators thiazolidinediones (Rosiglitazone) on the expression of intercellular adhesion molecule-1 (ICAM-1) and beta1 integrin in high glucose-induced rat glomerular mesangial cells (GMC) in order to elucidate the relationship between PPARgamma and adhesion molecules.

[Pathological Changes in the Testes of the Rats with Hypospadia Induced by Dichlorvos]

Zhonghua Nan Ke Xue = National Journal of Andrology. Aug, 2006  |  Pubmed ID: 16970155

To study the mechanism of dichlorvos leading to hypospadia of rats.

Preparation and Use of Coppersensor-1, a Synthetic Fluorophore for Live-cell Copper Imaging

Nature Protocols. 2006  |  Pubmed ID: 17406313

Coppersensor-1 (CS1) is a small-molecule, membrane-permeable fluorescent dye for imaging labile copper pools in biological samples, including live cells. This probe, comprising a boron dipyrromethene (BODIPY) chromophore coupled to a thioether-rich receptor, has a picomolar affinity for Cu+ with high selectivity over competing cellular metal ions. CS1 fluorescence increases up to 10-fold on binding to Cu+. In this protocol we describe the synthesis of CS1 and how to use this chemical tool to investigate intracellular levels of labile copper in cultured cells. The preparation of CS1 is anticipated to take 4-5 d, and imaging assays can be performed in 1-2 d with cultured cells.

Voluntary Wheel Running Ameliorates Vascular Smooth Muscle Hyper-contractility in Type 2 Diabetic Db/db Mice

Applied Physiology, Nutrition, and Metabolism = Physiologie Appliquée, Nutrition Et Métabolisme. Aug, 2007  |  Pubmed ID: 17622286

Physical activity reduces cardiovascular disease related mortality in diabetic patients. However, it is unknown if the diabetic state reduces voluntary physical activity and, if so, if the voluntary physical activity at the reduced level is sufficient to improve cardiovascular risk factors. To address these two specific questions, we investigated voluntary wheel running performance in an obese and type 2 diabetic mouse model, the db/db mice. In addition, we determined the effects of running on body mass, blood glucose, insulin, plasma free fatty acids, cholesterol, and vascular smooth muscle hyper-contractility. Our results showed that daily running distance, time, and speed were significantly reduced in the db/db mice to about 23%, 32%, and 71%, respectively, of that in non-diabetic control mice. However, this low level of running was sufficient to induce a reduction in the vascular smooth muscle hyper-contractility, cholesterol, and some plasma free fatty acids, as well as to delay the decrease in blood insulin. These changes occurred in the absence of weight loss and a detectable decrease in blood glucose. Thus, the results of this study demonstrated that voluntary wheel running activity was dramatically reduced in db/db mice. However, the low levels of running were beneficial, in the absence of effects on obesity or blood glucose, with significant reductions in cardiovascular risk factors and potential delays in beta-cell dysfunction.

[Effects of ErbB Signal and Protein Kinase B on Monkey Cardiocyte Apoptosis Induced by Rapid Pacing]

Yao Xue Xue Bao = Acta Pharmaceutica Sinica. May, 2007  |  Pubmed ID: 17703766

This study is to investigate the roles of neuregulin receptor ErbB2 and protein kinase B (PKB) in pacing-induced heart failure of rhesus monkey. Rapid pacing was used to induce heart failure in rhesus monkey. Aorta intubatton was used to perform hemodynamic measurements, 17 days after pacing. N-Terminal pro-brain natriuretic peptide (BNP), one of the most important molecular marker of heart failure, was also measured by the method of electrochemical luminescence immunoassay. The mRNA expressions of ErbB2, PKB and Bcl-xl were detected in the left ventricular free walls by RT-PCR method. The expressions of phospho-PKB and Bcl-xl on protein level were also detected by Western blotting. The contractibility of cardiac muscle decreased significantly, which consisted with the increase of BNP. Compared with control group, the mRNA expressions of ErbB2, PKB and Bcl-xl were depressed, and similar results were also found in the protein expression analysis of phospho-PKB and Bcl-xl. The expressions of ErbB2, PKB and Bcl-xl were down-regulated during heart failure in rhesus monkey which suggested the important roles of ErbB2 receptor and PKB in the mechanism of heart failure.

[The Expression of TfR1 MRNA and IRP1 MRNA in the Placenta from Different Maternal Iron Status]

Zhonghua Xue Ye Xue Za Zhi = Zhonghua Xueyexue Zazhi. Apr, 2007  |  Pubmed ID: 17877204

To investigate the mRNA expression of transferrin receptor 1 (TfR1) and iron regulatory protein 1 (IRP1) in the full-term placenta from different maternal iron status, and explore the mechanism of placental iron transport and regulation.

[Effects of Recombined Human Neuregulin on the Contractibility of Cardiac Muscles of Rhesus Monkeys with Pacing-induced Heart Failure]

Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition. Jan, 2007  |  Pubmed ID: 17294740

To evaluate the effects of recombined human Neuregulin on the contractibility of cardiac muscles of Rhesus Monkeys with pacing-induced heart failure and to reveal the possible mechanisms involved.

A TAG1-APP Signalling Pathway Through Fe65 Negatively Modulates Neurogenesis

Nature Cell Biology. Mar, 2008  |  Pubmed ID: 18278038

The release of amyloid precursor protein (APP) intracellular domain (AICD) may be triggered by extracellular cues through gamma-secretase-dependent cleavage. AICD binds to Fe65, which may have a role in AICD-dependent signalling; however, the functional ligand has not been characterized. In this study, we have identified TAG1 as a functional ligand of APP. We found that, through an extracellular interaction with APP, TAG1 increased AICD release and triggered Fe65-dependent activity in a gamma-secretase-dependent manner. TAG1, APP and Fe65 colocalized in the neural stem cell niche of the fetal ventricular zone. Neural precursor cells from TAG1-/-, APP-/- and TAG1-/-;APP-/- mice had aberrantly enhanced neurogenesis, which was significantly reversed in TAG1-/- mice by TAG1 or AICD but not by AICD mutated at the Fe65 binding site. Notably, TAG1 reduced normal neurogenesis in Fe65+/+ mice. Abnormally enhanced neurogenesis also occurred in Fe65-/- mice but could not be reversed by TAG1. These results describe a TAG1-APP signalling pathway that negatively modulates neurogenesis through Fe65.

Fetal Meconium Peritonitis Complicated with Bacterial Infection

Journal of Clinical Ultrasound : JCU. Jun, 2008  |  Pubmed ID: 18386824

Fetal meconium peritonitis complicated by bacterial infection is extremely rare. We report a case of fetal ascites at 21 weeks of gestation with subsequent development of loculation, encapsulation, and calcification at 25 weeks. Paracentesis of loculated ascitic fluid at 28 weeks of gestation showed a purulent appearance with the presence of cocci bacteria, increase in white cell count, and a low glucose level, which were suggestive of bacterial infection. However, no sources of maternal infection could be identified. The total bilirubin level of the ascitic fluid was normal (21 micromol/L). A healthy baby was delivered at 37 weeks. CT scan revealed normal bowel without any sign of perforation. We postulate that when ascitic fluid becomes loculated, a normal bilirubin level on paracentesis indicates spontaneous closure of a previous bowel perforation.

Saturated Fatty Acids Modulate Cell Response to DNA Damage: Implication for Their Role in Tumorigenesis

PloS One. 2008  |  Pubmed ID: 18523653

DNA damage triggers a network of signaling events that leads to cell cycle arrest or apoptosis. This DNA damage response acts as a mechanism to prevent cancer development. It has been reported that fatty acids (FAs) synthesis is increased in many human tumors while inhibition of fatty acid synthase (FASN) could suppress tumor growth. Here we report that saturated fatty acids (SFAs) play a negative role in DNA damage response. Palmitic acid, as well as stearic acid and myristic acid, compromised the induction of p21 and Bax expression in response to double stranded breaks and ssDNA, while inhibition or knockdown of FASN enhanced these cellular events. SFAs appeared to regulate p21 and Bax expression via Atr-p53 dependent and independent pathways. These effects were only observed in primary mouse embryonic fibroblasts and osteoblasts, but not in immortalized murine NIH3T3, or transformed HCT116 and MCF-7 cell lines. Accordingly, SFAs showed some positive effects on proliferation of MEFs in response to DNA damage. These results suggest that SFAs, by negatively regulating the DNA damage response pathway, might promote cell transformation, and that increased synthesis of SFAs in precancer/cancer cells might contribute to tumor progression and drug resistance.

[Expression of Bcl-2 and Fas and Apoptosis of T Lymphocyte in the Peripheral Blood of Patients with End-stage Renal Diseases]

Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition. May, 2008  |  Pubmed ID: 18575326

To investigate the expression of Bcl-2 and Fas and the apoptosis of T lymphocyte in the peripheral blood of patients with end-stage renal diseases; and to test the impact of various dialysis membranes on the apoptosis of T lymphocyte.

Immobilization Stress Inhibits Intimal Fibromuscular Proliferation in the Process of Arterial Remodeling in Rats

Hypertension Research : Official Journal of the Japanese Society of Hypertension. May, 2008  |  Pubmed ID: 18712053

We investigated role of beta-endorphin (END), which is released by immobilization stress, on intimal fibromuscular proliferation in a rat model of arterial remodeling after intimal injury. The endothelium of the abdominal aorta of Wistar-Kyoto rats was denuded, and the rats were subjected to immobilization stress (6 h/d), which raised the serum concentration of END, and intraperitoneal administration of either END (20 ng/kg/d) or naltrexone (NAL: 4 mg/kg/d). The proliferative activity (PA) of medial smooth muscle cells (SMCs) and the intima/media area ratio (R) were determined at 3 and 14 d after denudation, respectively. PA and R were significantly reduced by immobilization (PA: 64.8%, R: 34.6%), and NAL treatment completely reversed the decreases in PA and R. On the other hand, END reduced both PA and R (PA: 21.7% and R: 24.9%), and NAL also reversed the decreases in PA and R. END (20 pg/mL) inhibited both the proliferation (79% at 96 h) and migration (26%) of SMCs cultured with 5% fetal bovine serum in vitro, and NAL (100 microg/mL) reversed the inhibition of both activities. Our results suggest that immobilization stress stimulates the release of endogenous END, which then prevents both proliferation and migration of medial SMCs after intimal injury.

A Gradient of Shh Establishes Mutually Repressing Somitic Cell Fates Induced by Nkx3.2 and Pax3

Developmental Biology. Nov, 2008  |  Pubmed ID: 18796301

Wnt and Sonic Hedgehog (Shh) signals are known to pattern the somite into dermomyotomal, myotomal and sclerotomal cell fates. By employing explants of presomitic mesoderm cultured with constant levels of Wnt3a conditioned medium and increasing levels of Shh, we found that differing levels of Shh signaling elicit differing responses from somitic cells: the lowest level of Shh signaling allows dermomyotomal gene expression, intermediate levels induce loss of dermomyotomal markers and activation of myogenic differentiation, and higher levels induce loss of myotomal markers and activation of sclerotomal gene expression. In addition, we have found that in the presence of high levels of Wnt signaling, instead of inducing sclerotomal markers, Shh signals act to maintain the expression of dermomyotomal and myotomal markers. One of the sclerotomal genes induced by high levels of Shh signaling is Nkx3.2. Forced expression of Nkx3.2 blocks somitic expression of the dermomyotomal marker Pax3 both in vitro and in vivo. Conversely, forced expression of Pax3 in somites can block Shh-mediated induction of sclerotomal gene expression and chondrocyte differentiation in vitro. Thus we propose that varying levels of Shh signaling act in a morphogen-like manner to elicit differing responses from somitic cells, and that Pax3 and Nkx3.2 set up mutually repressing cell fates that promote either dermomyotome/myotome or sclerotome differentiation, respectively.

Revealing Interaction Mode Between HIV-1 Reverse Transcriptase and Diaryltriazine Analog Inhibitor

Chemical Biology & Drug Design. Nov, 2008  |  Pubmed ID: 19012571

HIV-1 reverse transcriptase is a key enzyme playing an important role in the HIV-1 life cycle for the replication of the RNA genome into DNA form. Lys103Asn (K103N) mutant frequently is observed in HIV-1 reverse transcriptase. Therefore, a series of novel non-nucleoside reverse transcriptase inhibitors were designed and synthesized. In vitro experimental results show that diaryltriazine analogs have potent anti-HIV activity with moderate to high selectivity. In order to design anti-HIV drug, docking and molecular dynamics simulation were used to investigate the binding mode between ligand and HIV-1 reverse transcriptase. The results suggest that the analogs might have a similar interaction mechanism with HIV-1 reverse transcriptase. Then comparative molecular field analysis and comparative molecular similarity indices analysis were used to construct quantitative structure-activity models. These models were evaluated by eight test set compounds. These models are helpful in making quantitative prediction of their activity for new lead compounds before resorting in vitro and in vivo experimentation.

Cell Surface Sialylation and Fucosylation Are Regulated by L1 Via Phospholipase Cgamma and Cooperate to Modulate Neurite Outgrowth, Cell Survival and Migration

PloS One. 2008  |  Pubmed ID: 19048108

Cell surface glycosylation patterns are markers of cell type and status. However, the mechanisms regulating surface glycosylation patterns remain unknown.

[Polymorphisms of Human Papillomavirus Type 81 L1 Gene in Patients with Cervical Lesions in Guangdong]

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Dec, 2008  |  Pubmed ID: 19114360

To investigate the positivity rates and genetic polymorphism of human papillomavirus (HPV) type 81 (HPV81) L1 gene in patients with cervical cancer in Guangdong.

[Design of a Medical Equipment Purchasing System]

Zhongguo Yi Liao Qi Xie Za Zhi = Chinese Journal of Medical Instrumentation. Sep, 2008  |  Pubmed ID: 19119663

This paper introduces the network data dynamic exchange technology applied to the design of the medical equipment purchase system according to the process of the medical equipment purchasing. The new system adopts B/S structure based on .net technology, to realize the medical equipment purchasing information's dynamic management of network purchase application and verification, suppliers qualification examination and the contact file inquiry etc.

Cell Surface Sialylation and Fucosylation Are Regulated by the Cell Recognition Molecule L1 Via PLCgamma and Cooperate to Modulate Embryonic Stem Cell Survival and Proliferation

FEBS Letters. Feb, 2009  |  Pubmed ID: 19166842

Cell surface glycosylation patterns are markers of cell type and status. However, the mechanisms regulating surface glycosylation patterns remain unknown. Using a panel of carbohydrate markers, we have shown that cell surface sialylation and fucosylation are upregulated in L1-transfected embryonic stem cells (L1-ESCs). Consistently, the mRNA levels of sialyltransferase ST6Gal1 and ST3Gal4, and fucosyltransferase FUT9 were significantly increased in L1-transfected ESCs. Activation of L1 signaling promoted cell survival and inhibited cell proliferation. ShRNAs knocking down FUT9, ST6Gal1 and ST3Gal4 blocked these effects. A phospholipase Cgamma (PLCgamma) inhibitor and shRNA reduced ST6Gal1, ST3Gal4 and FUT9 mRNA levels in the L1-ESCs. Thus, embryonic stem cell surface sialylation and fucosylation are regulated via PLCgamma by L1, with which they cooperate to modulate cell survival and proliferation.

[Effect of High Glucose Exposure on Connective Tissue Growth Factor Expression in Cultured Human Renal Tubular Epithelial Cells and the Role of P38MAPK Pathway]

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Jan, 2009  |  Pubmed ID: 19218111

To observe the effect of high glucose exposure on connective tissue growth factor (CTGF) expression in cultured human renal tubular epithelial cells and investigate the role of p38MAPK pathway in this process.

Silent Information Regulator, Sirtuin 1, and Age-related Diseases

Geriatrics & Gerontology International. Mar, 2009  |  Pubmed ID: 19260974

Sirtuin 1 (SIRT1), a member of the silent information regulator 2 in mammals, has recently been found to be involved in age-related diseases, such as cancer, metabolic diseases, cardiovascular disease, neurodegenerative diseases, osteoporosis and chronic obstructive pulmonary disease (COPD), mainly through deacetylation of substrates such as p53, forkhead box class O, peroxisome proliferator activated receptor gamma co-activator 1alpha, and nuclear factor-kappaB. It is widely reported that SIRT1 can promote not only carcinogenesis but also metastasis and insulin resistance, andhave beneficial effects in metabolic diseases, mediate high-density lipoprotein synthesis and regulate endothelial nitric oxide to protect against cardiovascular disease, have a cardioprotective role in heart failure, protect against neurodegenerative pathological changes, promote osteoblast differentiation, and also play a pivotal role as an anti-inflammatory mediator in COPD. However, there are controversial results suggesting that SIRT1 has an effect in protecting against DNA damage and accumulation of mutations, and preventing tumorigenesis. In addition, a high level of SIRT1 can induce cardiomyopathy and even heart failure. This article reviews recent developments relating to these issues.

Gender and Metabolic Differences of Gallstone Diseases

World Journal of Gastroenterology : WJG. Apr, 2009  |  Pubmed ID: 19370788

To investigate the risk factors for gallstone disease in the general population of Chengdu, China.

[Pollution Characteristics of Antimony, Arsenic and Mercury in Human Hair at Xikuangshan Antimony Mining Area and Guiyang City, China]

Huan Jing Ke Xue= Huanjing Kexue / [bian Ji, Zhongguo Ke Xue Yuan Huan Jing Ke Xue Wei Yuan Hui "Huan Jing Ke Xue" Bian Ji Wei Yuan Hui.]. Mar, 2009  |  Pubmed ID: 19432349

The concentration levels of antimony, arsenic and mercury in human hair collected from Xikuangshan antimony mining area and Guiyang City were determined by hydride generation-atomic fluorescence spectrometry after having been digested by nitric acid and perchloric acid. The contents of Sb, As and Hg are 15.9, 4.21, 1.79 microg/g in the samples from Xikuangshan antimony mining area and 0.532, 0.280, 0.338 microg/g in the samples from Guiyang City respectively. The contents of Sb, As and Hg in human hair of Xikuangshan antimony area are much higher than those of Guiyang City. The independent-samples t-test shows that there are no marked differences in the contents of Sb and As between male and female hair samples from both Xikuangshan antimony mining area and Guiyang City (p > 0.05), while Hg contents in male hair are apparently higher than those in female hair from Guiyang City (p < or = 0.05). There is positive correlation observed between As and Sb, as well as between As and Hg, while Sb is weakly correlated with Hg (p < or = 0.01). These results show that the heavy metals (Sb, As and Hg) in antimony mining area may significantly affect human health than in the un-mining areas.

[Extraction Process and Content Determination of Total Organic Acids from Pothos Chinensis]

Zhong Yao Cai = Zhongyaocai = Journal of Chinese Medicinal Materials. Jan, 2009  |  Pubmed ID: 19445138

To study the optimum extracting process of total organic acids from Pothos chinensis and establish a determination method for total organic acids.

A Comparison of Prediction Equations for Estimating Glomerular Filtration Rate in Chinese Potential Living Kidney Donors

Clinical Transplantation. Aug-Sep, 2009  |  Pubmed ID: 19573086

Accurate measurement of donor renal function has important long-term implications for both donors and recipients. In clinical practice, renal function may be estimated by using 24-h urinary creatinine clearance (urine-CrCl) and various specifically derived prediction equations. We assessed the suitability of urine-CrCl and prediction equations for evaluating Chinese kidney donors.

Prevalence and Risk Factors of Fatty Liver Disease in Chengdu, Southwest China

Hepatobiliary & Pancreatic Diseases International : HBPD INT. Aug, 2009  |  Pubmed ID: 19666406

Fatty liver disease (FLD) is increasingly recognized as one of the most common chronic liver diseases in China. This study aimed to investigate the prevalence and risk factors of FLD in Chengdu, Southwest China, and to provide a relevant basis for the prevention and intervention of FLD.

[Effects of Small Interfering RNA Targeting Connective Tissue Growth Factor on High Glucose-induced Human Tubular Epithelial Hypertrophy]

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Oct, 2009  |  Pubmed ID: 19861250

To observe the effect of transfection with small interfering RNA (siRNA) targeting connective tissue growth factor (CTGF) on human tubular epithelial hypertrophy induced by high glucose.

Parallel SART Algorithm of Linear Scan Cone-beam CT for Fixed Pipeline

Journal of X-ray Science and Technology. 2009  |  Pubmed ID: 19893214

Linear scan cone-beam Computed Tomography (CT) is useful to fixed pipeline inspection. We extend Simultaneous Algebraic Reconstruction Technique (SART) to linear scan cone-beam CT and focus on reducing its reconstruction time through cluster computing. In order to reduce communication overhead, we investigate a trapeziform image space decomposition scheme and a subsets-reduce communication technique. The performance of proposed parallel algorithm is analyzed theoretically and verified through experiment. The results show that the proposed parallel algorithm can generate approving CT images and its performance is mainly influenced by load imbalance and network bandwidth.

Dual Helical Cone-beam CT for Inspecting Large Object

Journal of X-ray Science and Technology. 2009  |  Pubmed ID: 19893215

In cone beam industrial computed tomography (ICT), it is often required to inspect the large object using flat detector. If traditional helical scanning is used, the field of view (FOV) is limited due to the size of flat detector. As an alternative, a dual helical cone-beam scanning is proposed in this paper. Before each helical scanning, x-ray source and flat detector are horizontally translated a given distance, and part of the object is covered by x-ray at each view angle. Then the object function is reconstructed by use of the improved helical FDK algorithm, which does not rebin projection data. Simulations validate that the images, which are reconstructed by proposed scanning mode and improved algorithm with small flat detector, are similar to those from the conventional helical scanning and FDK algorithm with large flat detector. The improved FDK algorithm is not sensitive to translation step. Furthermore, the proposed scanning mode can extend the radius of FOV up to at least 1.7 times.

Antiproliferative and Pro-apoptotic Effects of Uncaria Tomentosa in Human Medullary Thyroid Carcinoma Cells

Anticancer Research. Nov, 2009  |  Pubmed ID: 20032400

Medullary thyroid carcinoma (MTC), a rare calcitonin-producing tumor, is derived from parafollicular C-cells of the thyroid and is characterized by constitutive Bcl-2 overexpression. The tumor is relatively insensitive to radiation therapy as well as conventional chemotherapy. To date, the only curative treatment is the early and complete surgical removal of all neoplastic tissue. In this study, the antiproliferative and pro-apoptotic effects of fractions obtained from Uncaria tomentosa (Willd.) DC, commonly known as uña de gato or cat's claw were investigated. Cell growth of MTC cells as well as enzymatic activity of mitochondrial dehydrogenase was markedly inhibited after treatment with different fractions of the plant. Furthermore, there was an increase in the expressions of caspase-3 and -7 and poly(ADP-ribose) polymerase (PARP) fraction, while bcl-2 overexpression remained constant. In particular, the alkaloids isopterpodine and pteropodine of U. tomentosa exhibited a significant pro-apoptotic effect on MTC cells, whereas the alkaloid-poor fraction inhibited cell proliferation but did not show any pro-apoptotic effects. These promising results indicate the growth-restraining and apoptotic potential of plant extracts against neuroendocrine tumors, which may add to existing therapies for cancer.

[Identification and Genotyping of Oncogenic Type of Human Papillomavirus in Paraffin-embedded Cervical Cancer Samples in Guangzhou]

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Dec, 2009  |  Pubmed ID: 20034908

To investigate human papillomavirus (HPV) infection and genotyping in patients with cervical cancer in Guangzhou in the last 3 decades.

[In Utero Exposure to Dichlorvos Induces Apoptosis of Leydig Cells in Rats]

Zhonghua Nan Ke Xue = National Journal of Andrology. Nov, 2009  |  Pubmed ID: 20218312

To observe the influence of the organophosphate insecticide dichlorvos on the apoptosis of Leydig cells in the male offspring of the SD rats exposed to dichlorvos, and to investigate the role of the changes of Leydig cells in genitourinary malformation.

Evaluation of Living Related Kidney Donors in China: Policies and Practices in a Transplant Center

Clinical Transplantation. Sep-Oct, 2010  |  Pubmed ID: 20236131

Rigorous donor evaluation is essential for living related donor kidney transplantation (LRDKT). However, guidelines for living kidney donor evaluation are absent in China. The aim of this study is to describe the initial experience in the living kidney donor evaluation process in a single transplant center in China.

Computational Study of CCR5 Antagonist with Support Vector Machines and Three Dimensional Quantitative Structure Activity Relationship Methods

Chemical Biology & Drug Design. Mar, 2010  |  Pubmed ID: 20331647

CCR5 is the key receptor of HIV-1 virus entry into host cells and it becomes an attractive target for antiretroviral drug design. To date, six types of CCR5 antagonist were synthesized and evaluated. To search more potent bio-active compounds, non-linear support vector machine was used to construct the relationship models for 103 oximino-piperidino-piperidine CCR5 antagonists. Then, comparative molecular field analysis and comparative molecular similarity indices analysis models were constructed after alignment with their common substructure. Twenty-one structural diverse compounds, which were not included in the support vector machine, comparative molecular field analysis, and comparative molecular similarity indices analysis models, validated these models. The results show that these models possess good predictive ability. When comparing between support vector machine and 3D-quantitative structure activity relationship models, the results obtained from these two methods are compatible. However, 3D-quantitative structure activity relationship model is significantly better than support vector machine model and previous reported pharmacophore model. These models can help us to make quantitative prediction of their bio-activities before in vitro and in vivo stages.

Removal of Methyl Violet from Aqueous Solutions Using Poly (acrylic Acid-co-acrylamide)/attapulgite Composite

Journal of Environmental Sciences (China). 2010  |  Pubmed ID: 20397381

The adsorption of Methyl Violet (MV) cationic dye from aqueous solution was carried out by using crosslinked poly (acrylic acid-coacrylamide)/attapulgite (Poly(AA-co-AM)/ATP) composite as adsorbent. The factors influencing adsorption capacity of the composite such as pH, concentration of the dye, temperature, contact time, adsorbent dosage, ionic strength and surfactant were systematically investigated. The equilibrium data fitted very well to the Langmuir isotherm and the maximum adsorption capacity reached 1194 mg/g at 30 degrees C. The thermodynamic parameters including deltaG0, deltaH0 and deltaS0 for the adsorption processes of MV on the composite were also calculated, and the negative deltaH0 and deltaG0 confirmed that the adsorption process was exothermic and spontaneous. The kinetic studies showed that the adsorption process was consistent with the pseudo second-order kinetic model and the desorption studies revealed that the regeneration of the composite adsorbent can be easily achieved.

Turning off Transcription of the Bcl-2 Gene by Stabilizing the Bcl-2 Promoter Quadruplex with Quindoline Derivatives

Journal of Medicinal Chemistry. Jun, 2010  |  Pubmed ID: 20481493

Human bcl-2 gene is an apoptosis-related oncogene containing a GC-rich sequence which is located upstream from P1 promoter and has the potential to form G-quadruplex structures. However, the regulatory role of the quadruplex and the effect of its ligands on bcl-2 have not been clarified. Here, we demonstrated that the G-quadruplex structure was disrupted when partial mutation of G --> A was made, resulting in a 2-fold increase in basal transcriptional activity of bcl-2 promoter. Quindoline derivatives, the highly active G-quadruplex ligands developed by our group, could significantly suppress bcl-2 transcriptional activation but had less effect on mutated bcl-2 transcription. These results provided direct evidence that G-quadruplex structure formed in bcl-2 promoter region could function as a transcriptional repressor element, and G-quadruplex specific ligands could regulate the transcription of bcl-2 through stabilization of quadruplex structure. The results further indicated that quindoline derivatives could induce apoptosis of HL-60 tumor cells.

Expression of 2 Transcripts of NGX6 Gene in Colorectal Cancer and the Correlation with Carcinoembryonic Antigen

Zhong Nan Da Xue Xue Bao. Yi Xue Ban = Journal of Central South University. Medical Sciences. May, 2010  |  Pubmed ID: 20543461

To investigate the expression and function of NGX6-S (short transcript) and NGX6-L (long transcript) in colorectal cancer.

Comparison of Single High-dose Streptozotocin with Partial Pancreatectomy Combined with Low-dose Streptozotocin for Diabetes Induction in Rhesus Monkeys

Experimental Biology and Medicine (Maywood, N.J.). Jul, 2010  |  Pubmed ID: 20558842

Monkeys with insulin-dependent diabetes are important experimental models for islet xenotransplantation. However, with regard to diabetes induction, total pancreatectomy is a difficult operation with a high complication rate, while streptozotocin (STZ) administration may cause serious toxic effects and individual difference in metabolism. We compared two strategies involving pancreatectomy and STZ to successfully and safely induce diabetes in rhesus monkeys. Thirteen rhesus monkeys were divided into two groups: single high-dose STZ administration (80, 100 and 120 mg/kg, n = 3 for each dose) (group 1) and partial pancreatectomy (70-75%) combined with low-dose STZ (15 mg/kg, n = 4) (group 2). Induction of diabetes was evaluated by blood glucose, insulin, C-peptide, intravenous glucose tolerance test (IVGTT) and arginine stimulation test (AST). Detection of hematological and serum biochemical parameters and biopsies of pancreas, liver and kidney were periodically performed. In our study, animals in both groups developed diabetes. Serum C-peptide levels in groups 1 and 2 decreased to 0.08 +/- 0.07 and 0.35 +/- 0.06 nmol/L, respectively. IVGTT and AST indicated severely impaired glucose tolerance. Immunohistochemistry demonstrated that rare insulin-positive cells remained in the pancreas. In terms of STZ toxicity, four monkeys died 8-14 days after STZ administration (3 with 120 mg/kg STZ and 1 with 100 mg/kg STZ). Group 1 animals developed liver and kidney injury evidenced by increased alanine aminotransferase, aspartate aminotransferase, total cholesterol, LDL, triglyceride and blood urea nitrogen for one month, and histological abnormality including hepatic steatosis, renal glomerulus and tubular injury. Nevertheless, moderate histological injuries were seen in animals with 80 mg/kg STZ, with subsequent recovery. In contrast, group 2 animals displayed normal biochemical parameters and histology, with generally less risk of postoperative complications. We conclude that injection of 80 mg/kg STZ could induce diabetes with moderate injuries. Partial pancreatectomy with low-dose STZ is a safer and more reproducible method for inducing diabetes in rhesus monkeys.

[Plasma Fibroblast Growth Factor-21 and Abdominal Obesity]

Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition. May, 2010  |  Pubmed ID: 20629328

To investigate the association of plasma fibroblast growth factor-21 (FGF-21) with abdominal obesity and other metabolic indicators.

Clinical Risk Factors in Regional Brain Ischemia Using Single Photon Emission Computed Tomography

Journal of the American Geriatrics Society. Jul, 2010  |  Pubmed ID: 20649703

S6K1 is a Multifaceted Regulator of Mdm2 That Connects Nutrient Status and DNA Damage Response

The EMBO Journal. Sep, 2010  |  Pubmed ID: 20657550

p53 mediates DNA damage-induced cell-cycle arrest, apoptosis, or senescence, and it is controlled by Mdm2, which mainly ubiquitinates p53 in the nucleus and promotes p53 nuclear export and degradation. By searching for the kinases responsible for Mdm2 S163 phosphorylation under genotoxic stress, we identified S6K1 as a multifaceted regulator of Mdm2. DNA damage activates mTOR-S6K1 through p38alpha MAPK. The activated S6K1 forms a tighter complex with Mdm2, inhibits Mdm2-mediated p53 ubiquitination, and promotes p53 induction, in addition to phosphorylating Mdm2 on S163. Deactivation of mTOR-S6K1 signalling leads to Mdm2 nuclear translocation, which is facilitated by S163 phosphorylation, a reduction in p53 induction, and an alteration in p53-dependent cell death. These findings thus establish mTOR-S6K1 as a novel regulator of p53 in DNA damage response and likely in tumorigenesis. S6K1-Mdm2 interaction presents a route for cells to incorporate the metabolic/energy cues into DNA damage response and links the aging-controlling Mdm2-p53 and mTOR-S6K pathways.

A New Iterative Reconstruction Algorithm for 2D Exterior Fan-beam CT

Journal of X-ray Science and Technology. 2010  |  Pubmed ID: 20714085

The exterior computed tomography (CT) problem is one kind of truncation problem. It is very ill-posed, so that accurate reconstruction of the attenuation function is hardly possible from real data. Based on projection onto convex sets (POCS) algorithm, total variation minimization (TVM) methods, and C-V model, we develop and investigate a new iterative reconstruction algorithm, which is referred to as subregion-averaged-TVM-POCS (SA-TVM-POCS). Numerical simulations are presented to illustrate the efficiency of the algorithm. The results of this paper can be easily applied to other x-ray CT reconstruction problems.

Investigation on Fragmentation Pathways of Rutaecarpine and Its Two Derivatives Using Electrospray Ionization Ion-trap Time-of-flight Tandem Mass Spectrometry

Rapid Communications in Mass Spectrometry : RCM. Sep, 2010  |  Pubmed ID: 20814986

Katsevich-type Reconstruction for Dual Helical Cone-beam CT

Journal of X-ray Science and Technology. 2010  |  Pubmed ID: 21045273

This paper is about inspecting large and long object using dual helical cone-beam computed tomography (CT) and Katsevich-type reconstruction algorithm. Conventional cone-beam helical industrial CT imaging is based on the assumption that the entire cross-section of an object is illuminated with x-rays at each view angle. The field of view is limited by the width of planar detector. As an alternative, this paper developed a dual-helical scanning. When scanning at each helix, part of cross-section is covered by x-ray at each view angle. During reconstruction, Katsevich-type algorithm is applied, which does not rebin projection data. The algorithm is approximate, as it applies Hilbert transform on truncated projection. The reconstruction result is better than extended FDK algorithm, especially for large helical pitch.

Mesenchymal Stem Cells Protect Islets from Hypoxia/reoxygenation-induced Injury

Cell Biochemistry and Function. Dec, 2010  |  Pubmed ID: 21061411

Hypoxia/reoxygenation (H/R)-induced injury is the key factor associated with islet graft dysfunction. This study aims to examine the effect of mesenchymal stem cells (MSCs) on islet survival and insulin secretion under H/R conditions. Islets from rats were isolated, purified, cultured with or without MSCs, and exposed to hypoxia (O(2) ≤ 1%) for 8 h and reoxygenation for 24 and 48 h, respectively. Islet function was evaluated by measuring basal and glucose-stimulated insulin secretion (GSIS). Apoptotic islet cells were quantified using Annexin V-FITC. Anti-apoptotic effects were confirmed by mRNA expression analysis of hypoxia-resistant molecules, HIF-1α, HO-1, and COX-2, using semi-quantitative retrieval polymerase chain reaction (RT-PCR). Insulin expression in the implanted islets was detected by immunohistological analysis. The main results show that the stimulation index (SI) of GSIS was maintained at higher levels in islets co-cultured with MSCs. The MSCs protected the islets from H/R-induced injury by decreasing the apoptotic cell ratio and increasing HIF-1α, HO-1, and COX-2 mRNA expression. Seven days after islet transplantation, insulin expression in the MSC-islets group significantly differed from that of the islets-alone group. We proposed that MSCs could promote anti-apoptotic gene expression by enhancing their resistance to H/R-induced apoptosis and dysfunction. This study provides an experimental basis for therapeutic strategies based on enhancing islet function.

(E)-N'-(3-Nitro-benzyl-idene)-4-(8-quinol-yloxy)butano-hydrazide

Acta Crystallographica. Section E, Structure Reports Online. 2010  |  Pubmed ID: 21587886

In the title Schiff base compound, C(20)H(18)N(4)O(4), the conformation along the bond sequence linking the benzene and quinoline rings is trans-(+)gauche-trans-trans-(+)gauche-trans-trans. The dihedral angle between the aromatic ring systems is 80.3 (6)°. In the crystal, a pair of inter-molecular N-H⋯N hydrogen bonds link the mol-ecules into centrosymmetric R(2) (2)(20) dimers, which are aggregated via π-π inter-actions into sheets [quinoline-benzene ring centroid-centroid separation = 3.572 (2)-3.773 (3) Å].

Psychosocial Evaluation of Chinese Living Related Kidney Donors

Clinical Transplantation. Nov, 2010  |  Pubmed ID: 20041909

Although living kidney transplantation has numerous advantages over cadaveric transplantation, donor apprehension remains a problem. This study investigated psychosocial features and quality of life in Chinese living kidney donors after transplantation procedures.

Muscle Cells Enhance Resistance to Pro-inflammatory Cytokine-induced Cartilage Destruction

Biochemical and Biophysical Research Communications. Jan, 2010  |  Pubmed ID: 20043873

Pro-inflammatory cytokines IL-1beta and TNFalpha play important roles in the manifestation of arthritis by disrupting the anabolic and catabolic activities of the chondrocytes. We observed a novel mechanism of cartilage regulation by which muscle cells diminish the response of chondrocytes to IL-1beta and TNFalpha. We found that chondrocytes cocultured with muscle cells or cultured in muscle cell-conditioned medium significantly enhanced the expression of cartilage matrix proteins (collagen II and collagen IX) and resisted IL-1beta and TNFalpha-induced cartilage damage. Our data suggest that this effect is achieved by inhibiting the expression of key components of the signaling pathways of pro-inflammatory cytokines (including NFkappaB, ESE-1, Cox-2, and GADD45beta), leading to attenuated expression of cartilage-degrading enzymes (MMPs and ADAMTS4). Therefore, our work unveils a potential role of muscle in regulating cartilage homeostasis and response to pro-inflammatory stimuli, and provides insights on designing treatment strategies for joint degenerative diseases such as arthritis.

Visualizing Ascorbate-triggered Release of Labile Copper Within Living Cells Using a Ratiometric Fluorescent Sensor

Journal of the American Chemical Society. Feb, 2010  |  Pubmed ID: 20052977

We present the synthesis, properties, and biological applications of Ratio-Coppersensor-1 (RCS1), a new water-soluble fluorescent sensor for ratiometric imaging of copper in living cells. RCS1 combines an asymmetric BODIPY reporter and thioether-based ligand receptor to provide high selectivity and sensitivity for Cu(+) over other biologically relevant metal ions, including Cu(2+) and Zn(2+), a ca. 20-fold fluorescence ratio change upon Cu(+) binding, and visible excitation and emission profiles compatible with standard fluorescence microscopy filter sets. Live-cell confocal microscopy experiments show that RCS1 is membrane-permeable and can sense changes in the levels of labile Cu(+) pools within living cells by ratiometric imaging, including expansion of endogenous stores of exchangeable intracellular Cu(+) triggered by ascorbate stimulation in kidney and brain cells.

IL-10 Promotes Resistance to Apoptosis and Metastatic Potential in Lung Tumor Cell Lines

Cytokine. Mar, 2010  |  Pubmed ID: 20034810

Treatment of non-small cell lung carcinoma (NSCLC) remains at a disappointingly low success rate. Not only is metastatic spread common in NSCLC, but therapeutic success decreases dramatically once metastases are present. Understanding factors which contribute to poor prognosis in NSCLC is critical for development of more successful therapeutic approaches. Interleukin-10 (IL-10) expression has been shown in several studies to correlate with a poorer prognosis in NSCLC; however, the mechanisms by which IL-10 affects lung tumor growth and metastases are unclear. The goal of this study was to evaluate the effects of tumor-derived IL-10 on the growth and metastasis of lung cancer cells in a murine model. Lewis lung carcinoma cells were stably transfected with the chicken ovalbumin gene (cOVA) as a model tumor antigen (LL43 tumor cells) and subsequently transfected with the murine IL-10 gene (LL43-10 tumor cells). Subcutaneous growth of the LL43 tumor cells was not affected by expression of IL-10. However, LL43-10 tumors had a fourfold increase in tumor microvessel density, as indicated by CD31 staining. Metastatic potential was also increased in IL-10-expressing lung tumor cells, leading to a greater number of tumor cells in lymph nodes draining the primary tumor site. Finally, exposure of Lewis lung tumor cells in vitro to exogenous IL-10 dramatically increased their resistance to UV-induced apoptosis. These results indicate that a primary effect of IL-10 on lung cancer cells may be to increase their metastatic potential by promoting angiogenesis and resistance to apoptosis.

The Role of Muscle Cells in Regulating Cartilage Matrix Production

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society. Apr, 2010  |  Pubmed ID: 19813241

Muscle is one of the tissues located in close proximity to cartilage tissue. Although it has been suggested that muscle could influence skeletal development through generating mechanical forces by means of contraction, very little is known regarding whether muscle cells release biochemical signals to regulate cartilage gene expression. We tested the hypothesis that muscle cells directly regulate cartilage matrix production by analyzing chondrocytes cocultured with muscle cells in 2D or 3D conditions. We found that chondrocytes cultured with C2C12 muscle cells exhibited enhanced alcian blue staining and elevated expression of collagen II and collagen IX proteins. Although nonmuscle cells did not promote cartilage matrix production, converting them into muscle cells enhanced their pro-chondrogenic activity. Furthermore, muscle cell-conditioned medium led to increased cartilage matrix production, suggesting that muscle cells secrete pro-chondrogenic factors. Taken together, our study suggests that muscle cells may play an important role in regulating cartilage gene expression. This result may ultimately lead to the discovery of novel factors that regulate cartilage formation and homeostasis, and provide insights into improving the strategies for regenerating cartilage.

Isolation and Functional Characterization of DgZFP: a Gene Encoding a Cys2/His2-type Zinc Finger Protein in Chrysanthemum

Molecular Biology Reports. Feb, 2010  |  Pubmed ID: 19821150

A Cys2/His2-type zinc finger protein gene, DgZFP, was isolated from chrysanthemum by rapid amplification of cDNA ends (RACE) approach. The DgZFP encodes a protein of 211 amino acids residues with a calculated molecular mass of 22.9 kDa and theoretical isoelectric point is 8.59. DgZFP contains two Cys2/His2-type zinc finger motifs, one nuclear localization domain, one Leu-rich domain, and one ethylene-responsive element-binding factor (ERF)-associated amphiphilic repression (EAR) domain. The transcript of DgZFP was enriched in flowers than in roots, stems, and leaves of the adult chrysanthemum plants. The gene expression was strongly induced by NaCl, drought and cold treatment, and weakly by ABA treatment in the seedlings. Subcellular localization revealed that DgZFP was localized preferentially distributed to nucleus. Overexpression of DgZFP improved salt tolerance and resulted in growth suppression in transgenic tobacco. We argued that DgZFP is a new member of the Cys2/His2-type zinc finger protein genes, and it maybe function as a regulator in response to salt stress in plants.

[Effects of Chinese Herbal Compound on Monoamine and Neuronal Amino Acids in Rat's Telencephalon in the Course of Exhaustion and Recovery Process]

Zhongguo Ying Yong Sheng Li Xue Za Zhi = Zhongguo Yingyong Shenglixue Zazhi = Chinese Journal of Applied Physiology. Nov, 2011  |  Pubmed ID: 22295520

To observe the effect of Chinese herbal compound on variance of neurotransmitters in rat telencephalon and to further discuss the mechanism underlying Chinese herbal compound in improving exercise capacity and promoting recovery from exercise-induced fatigue.

Outcome of a Solitary Kidney Transplant into Adult Recipients from Pediatric Donors After Controlled Circulatory Death

Experimental and Clinical Transplantation : Official Journal of the Middle East Society for Organ Transplantation. Jun, 2011  |  Pubmed ID: 21649563

We sought to evaluate the outcomes of a single kidney transplant from pediatric donors into adult recipients after controlled circulatory death.

Revealing the Drug-resistant Mechanism for Diarylpyrimidine Analogue Inhibitors of HIV-1 Reverse Transcriptase

Chemical Biology & Drug Design. Sep, 2011  |  Pubmed ID: 21696545

Diaryltriazine (DATA) and diarylpyrimidine (DAPY) were two category inhibitors with highly potent activity for wild type (wt) and four principal mutant types (L100I, K103N, Y181C and Y188L) of HIV-1 reverse transcriptase (RT). We had revealed the drug-resistant mechanism of DATA analogue inhibitors with molecular dynamics simulation and three-dimensional quantitative structure-activity relationship (3D-QSAR) methods. In this work, we investigated the drug-resistant mechanism of DAPY analogue inhibitors. It was found that DAPY analogue inhibitors form more hydrogen bonds and hydrophobic contacts with wild type and mutants of HIV-1 RT than DATA inhibitors. This could explain that DAPY analogue inhibitors are more potent than DATA for the wild type and mutants of HIV-1 RT. Then, 3D-QSAR models were constructed for these inhibitors of wild type and four principal mutant types HIV-1 RT and evaluated by test set compounds. These combined models can be used to design new chemical entities and make quantitative prediction of the bioactivities for HIV-1 RT inhibitors before resorting to in vitro and in vivo experiment.

[Hospital Integrated Maintenance Management System Design and Application]

Zhongguo Yi Liao Qi Xie Za Zhi = Chinese Journal of Medical Instrumentation. Mar, 2011  |  Pubmed ID: 21706796

According to hospital medical equipment, information equipment and water, electricity and other equipment maintenance procedures, this paper planned and developed a comprehensive maintenance management system for hospitals. The system implements equipment maintenance, maintenance applications, maintenance registration, preventive maintenance, data quantitative analysis and other functions.

Epigenetic Changes in Osteosarcoma

Bulletin Du Cancer. Jul, 2011  |  Pubmed ID: 21708514

Osteosarcoma is one of the most prevalent primary bone tumors. The pathogenesis and molecular development of this tumor remains elusive. The prognosis is unfavorable due to lack of effective treatment methods. Recent advances in the epigenetics have brought a profound impact on the understanding of molecular mechanisms that lead to osteosarcoma. In this review, we summarized the current literature on epigenetic changes that are thought to contribute to the carcinogenesis of osteosarcoma, and discussed the potential diagnostic and therapeutic applications as well as future areas of research.

Inhibition of Cell Proliferation by Quindoline Derivative (SYUIQ-05) Through Its Preferential Interaction with C-myc Promoter G-quadruplex

Journal of Medicinal Chemistry. Aug, 2011  |  Pubmed ID: 21774525

G-Quadruplex is a special DNA secondary structure and present in many important regulatory regions in human genome, such as the telomeric end and the promoters of some oncogenes. Specially, different forms of G-quadruplexes exist in telomeric DNA and c-myc promoter and play important roles in the pathway of cell proliferation and senescence. The effects of G-quadruplex ligands for either telomeric or c-myc G-quadruplex in vitro have been widely studied, but the specificity of these effects in vivo is still unknown. In the present research, various experiments were carried out to study the effect of G-quadruplex ligand SYUIQ-05 on tumor cell lines and the mechanism of this effect. Our results showed that it preferred to bind with G-quadruplex in c-myc and had rather insignificant effect on G-quadruplex in telomere. Therefore, it is possible that this compound had its antitumor activity for cancer cells mainly through its interaction with c-myc quadruplex.

Subcellular Resolution Mapping of Endogenous Cytokine Secretion by Nano-plasmonic-resonator Sensor Array

Nano Letters. Aug, 2011  |  Pubmed ID: 21780816

Local extracellular signaling is central for cellular interactions and organizations. We report a novel sensing technique to interrogate extracellular signaling at the subcellular level. We developed an in situ immunoassay based on giant optical enhancement of a tunable nano-plasmonic-resonator array fabricated by nanoimprint lithography. Our nanoplasmonic device significantly increases the signal-to-noise ratio to enable the first time submicrometer resolution quantitative mapping of endogenous cytokine secretion. Our study shows a markedly high local interleukin-2 (IL-2) concentration within the immediate vicinity of the cell which finally validates a decades-old hypothesis on autocrine physiological concentration and spatial range. This general sensing technique can be applied for a broad range of cellular communication studies to improve our understanding of subcellular signaling and function.

[The Inhibition Effect of DFO Alone and in Combination with ATO on Xenograft Tumor Growth of HL-60 Cells in Nude Mice and Its Possible Mechanism]

Zhonghua Xue Ye Xue Za Zhi = Zhonghua Xueyexue Zazhi. Jun, 2011  |  Pubmed ID: 21781490

To investigate the effect of deferoxamine (DFO) and DFO in combination with arsenic trioxide (ATO) on inhibition of HL-60 cells xenograft tumor growth in nude mice and its mechanism.

Induction of Diabetes with Signs of Autoimmunity in Primates by the Injection of Multiple-low-dose Streptozotocin

Biochemical and Biophysical Research Communications. Aug, 2011  |  Pubmed ID: 21821007

To develop a preclinical large animal model of autoimmune diabetes to facilitate the translational research of autoimmune diabetes in human.

Protective Effects of Muscone on Ischemia-reperfusion Injury in Cardiac Myocytes

Journal of Ethnopharmacology. Oct, 2011  |  Pubmed ID: 21856397

Musk has been traditionally used in Chinese medicine as the main ingredient of many formulations for the treatment of chest pain and angina pectoris.

An Improved Half-covered Helical Cone-beam CT Reconstruction Algorithm Based on Localized Reconstruction Filter

Journal of X-ray Science and Technology. 2011  |  Pubmed ID: 21876280

Traditional helical cone-beam Computed Tomography (CT) is based on the assumption that the entire cross-section of the scanned object is covered by x-rays at each view angle. Because of the size limitation of planar detector, the traditional helical cone-beam CT scanning is restricted when the cross-section of the object is larger than the field of view (FOV) of the CT system. The helical cone-beam CT scanning based on FOV half-covered can almost double the FOV, whose mechanism is simple and the scanning efficiency is the same as that of traditional helical cone-beam CT. During reconstruction, the extended helical cone-beam FDK algorithm (called half-covered helical FDK for short) is developed, and the computational efficiency of this algorithm is high. But the reconstruction image has truncation error. Regarding this problem, this paper extends the idea of 2D local reconstruction to 3D half-covered helical cone-beam CT, and develops an improved half-covered helical cone-beam CT reconstruction algorithm based on localized reconstruction filter. Experimental results indicate that the presented algorithm well solves the truncation error of the half-covered helical FDK algorithm, improves the quality of the reconstruction image. And for the noise projection data, the presented algorithm can suppress noise and get better results. Moreover, the reconstruction time is much less.

Image Reconstruction from Limited Angle Projections Collected by Multisource Interior X-ray Imaging Systems

Physics in Medicine and Biology. Oct, 2011  |  Pubmed ID: 21908905

A multisource x-ray interior imaging system with limited angle scanning is investigated to study the possibility of building an ultrafast micro-CT for dynamic small animal imaging, and two methods are employed to perform interior reconstruction from a limited number of projections collected by the multisource interior x-ray system. The first is total variation minimization with the steepest descent search (TVM-SD) and the second is total difference minimization with soft-threshold filtering (TDM-STF). Comprehensive numerical simulations and animal studies are performed to validate the associated reconstructed methods and demonstrate the feasibility and application of the proposed system configuration. The image reconstruction results show that both of the two reconstruction methods can significantly improve the image quality and the TDM-SFT is slightly superior to the TVM-SD. Finally, quantitative image analysis shows that it is possible to make an ultrafast micro-CT using a multisource interior x-ray system scheme combined with the state-of-the-art interior tomography.

Effect of Electromagnetic Pulses (EMP) on Associative Learning in Mice and a Preliminary Study of Mechanism

International Journal of Radiation Biology. Dec, 2011  |  Pubmed ID: 21929296

To investigate the effects of electromagnetic pulses (EMP) on associative learning in mice and test a preliminary mechanism for these effects.

Evaluation of the Interaction Between Sitagliptin and Cyclodextrin Derivatives by Capillary Electrophoresis and Nuclear Magnetic Resonance Spectroscopy

Electrophoresis. Oct, 2011  |  Pubmed ID: 21983816

An aqueous capillary electrophoretic method was developed for chiral analysis of the novel anti-diabetic drug, sitagliptin. The acid-base profiling of the analyte was carried out using both capillary electrophoresis and nuclear magnetic resonance pH titrations. The apparent complex stability and chiral separation properties were investigated with 30 different cyclodextrins under acidic conditions. The effect of concentration and pH of the BGE, temperature of the capillary, and the type and concentration of the chiral selector on the enantiomer resolution were thoroughly investigated. The effects of dual cyclodextrin systems on separation were also extensively studied. Complete separation of racemic sitagliptin with good resolution (R(S)=2.24) was achieved within a short time (15 min) with optimized parameters (10°C, pH=4.4, 40 mM phosphate buffer) of a sulfobutylether-β-cyclodextrin (averaged degree of substitution ~4) and native β-cyclodextrin dual system. The averaged stoichiometry of the inclusion complex was determined using the Job plot method with both (1)H and (19)F NMR experiments and resulted in a 1:1 complex. The structure of the inclusion complex was elucidated using 2-D ROESY NMR experiments.

Associations of Fibroblast Growth Factor 21 Gene 3' Untranslated Region Single-Nucleotide Polymorphisms with Metabolic Syndrome, Obesity, and Diabetes in a Han Chinese Population

DNA and Cell Biology. Oct, 2011  |  Pubmed ID: 21988350

Fibroblast growth factor 21 (FGF-21) is a novel regulator for metabolic syndrome (MetS), diabetes, and obesity. However, no study has been performed on the association of these diseases with FGF-21 gene polymorphism. The aim of the study was to investigate the association of 3' untranslated region (UTR) single-nucleotide polymorphisms (SNPs) in the FGF-21 gene with MetS, obesity, and diabetes in the Han Chinese population. A total of 291 subjects were recruited from the Han Chinese population in Sichuan province. The genotypes of FGF-21 were determined by polymerase chain reaction-restriction fragment length polymorphism. The genotypes were confirmed by sequencing. No polymorphisms were found in rs11665841 (1 of 291) and rs3745706 (2 of 291). We did not find an association between genotype frequencies of SNP rs11665896 and lipid concentration, glucose concentration, or blood pressure. The TG/GG genotype relative to the TT genotype had an age- and sex-adjusted odds ratio of 1.41 for MetS (p=0.149), 1.84 (p=0.016) for obesity (body mass index ≥25 kg/m(2)), and 1.19 (p=0.492) for diabetes. Genetic variation of the 3' UTR of the FGF-21 gene was associated with obesity, however, not with MetS or diabetes.

Preconditioning with Physiological Levels of Ethanol Protect Kidney Against Ischemia/reperfusion Injury by Modulating Oxidative Stress

PloS One. 2011  |  Pubmed ID: 22022451

Oxidative stress due to excessive production of reactive oxygen species (ROS) and subsequent lipid peroxidation plays a critical role in renal ischemia/reperfusion (IR) injury. The purpose of current study is to demonstrate the effect of antecedent ethanol exposure on IR-induced renal injury by modulation of oxidative stress.

Protein Aggregation of SERCA2 Mutants Associated with Darier Disease Elicits ER Stress and Apoptosis in Keratinocytes

Journal of Cell Science. Nov, 2011  |  Pubmed ID: 22045735

Mutations in sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) underlie Darier disease (DD), a dominantly inherited skin disorder characterized by loss of keratinocyte adhesion (acantholysis) and abnormal keratinization (dyskeratosis) resulting in characteristic mucocutaneous abnormalities. However, the molecular pathogenic mechanism by which these changes influence keratinocyte adhesion and viability remains unknown. We show here that SERCA2 protein is extremely sensitive to endoplasmic reticulum (ER) stress, which typically results in aggregation and insolubility of the protein. Depletion of ER calcium stores is not necessary for the aggregation but accelerates the progression. Systematic analysis of diverse mutants identical to those found in DD patients demonstrated that the ER stress initiator is the SERCA2 mutant protein itself. These SERCA2 proteins were found to be less soluble, to aggregate and to be more polyubiquitinylated. After transduction into primary human epidermal keratinocytes, mutant SERCA2 aggregates elicited ER stress, caused increased numbers of cells to round up and detach from the culture plate, and induced apoptosis. These mutant induced events were exaggerated by increased ER stress. Furthermore, knockdown SERCA2 in keratinocytes rendered the cells resistant to apoptosis induction. These features of SERCA2 and its mutants establish a mechanistic base to further elucidate the molecular pathogenesis underlying acantholysis and dyskeratosis in DD.

Drug Resistant Mechanism of Diaryltriazine Analog Inhibitors of HIV-1 Reverse Transcriptase Using Molecular Dynamics Simulation and 3D-QSAR

Chemical Biology & Drug Design. Jan, 2011  |  Pubmed ID: 21134218

Diaryltriazine inhibitors have highly potent and effective bioactivities for the wild type of HIV-1 reverse transcription. To design new drug of antimutant HIV-1 reverse transcriptase, the mechanism of drug resistance for four types of mutants was revealed. Molecular dynamics simulations suggest that Lys101, Leu100, Lys103, Tyr181, and Tyr188 are key residues. Different mutants of key residues may have different interaction modes and lead to different drug resistances. Then, CoMFA and CoMSIA methods were employed to construct 3D quantitative structure-activity relationship models. These models were evaluated by test set compounds. These models can be used to make quantitative prediction of their bioactivities for lead compounds before resorting to in vitro and in vivo experimentation.

Association Between Human Metapneumovirus Seroprevalence and Hypertension in Elderly Subjects in a Long-term Care Facility

Hypertension Research : Official Journal of the Japanese Society of Hypertension. Apr, 2011  |  Pubmed ID: 21248755

Recently, relations between hypertension and infections caused by several pathogens have been reported. However, few studies have examined the relationship between human metapneumovirus (hMPV) and hypertension in elderly inpatients. To assess the association between anti-hMPV-immunoglobulin G (IgG) titer and the prevalence of hypertension, we conducted a case-control study in a Japanese long-term care facility (LTCF). The participants included 84 hypertensive patients aged 65 years, and 84 age- and sex-matched normotensive controls (38 males and 46 females in each group; cases, 79.9±8.4 (s.d.) years; controls, 80.1±8.3 years). Data on underling chronic clinical conditions were collected. Titers were measured using an immunofluorescence assay kit. The significance of risk factor differences was analyzed using univariate and multivariate comparisons of cases and controls. All serum samples were positive for hMPV, and IgG titers ranged from 40-fold to more than 5120-fold. There were no significant sex- or age-related differences in log(2) (anti-hMPV-IgG titer/10) among the subjects. Compared with normotensive subjects, hypertensive patients presented significantly higher log(2) (anti-hMPV-IgG titer/10) values (P<0.001). After adjustment with multiple logistic analysis, the odds ratio for log(2) (anti-hMPV-IgG titer/10) was 1.42 (95% confidence interval 1.16-1.75, P=0.001) relative to normotensive subjects. In all subjects, stepwise multiple regression analysis revealed that both hypertension and a poor nutritional state independently contributed to increased log(2) (anti-hMPV-IgG titer/10). These observations suggest that an increased anti-hMPV-IgG titer was closely related to hypertension in elderly subjects in a Japanese LTCF.

Treatment and Risk Factor Analysis of Hypoglycemia in Diabetic Rhesus Monkeys

Experimental Biology and Medicine (Maywood, N.J.). Feb, 2011  |  Pubmed ID: 21321318

In order to anticipate and promptly treat hypoglycemia in diabetic monkeys treated with insulin or other glucose-lowering drugs, the relationships between the incidence and symptoms of hypoglycemia in these animals, and many factors involved in model development and sustainment were analyzed. Different procedures were performed on 22 monkeys for the induction of diabetes. The monkey models were evaluated by blood glucose, insulin, C-peptide levels and intravenous glucose tolerance tests. A glucose treatment program for the diabetic monkeys was administered and laboratory tests were regularly performed. A standard procedure of hypoglycemia treatment was established and the risk factors of hypoglycemia were analyzed by a logistic regression model. Furthermore, the relationships between the four methods of diabetes induction, renal function, glycemic control and hypoglycemia were studied using one-way analysis of variance and t-test. We found that the hypoglycemic conditions of diabetic monkeys were improved rapidly by our treatment. The statistical analysis suggested that the modeling methods, renal function and glycemic control were related to the incidence of hypoglycemia. In detail, the progress of diabetes, effects of glycemic control and, particularly, the severity of the hypoglycemia differed according to the induction strategy used. The models induced by partial pancreatectomy with low-dose streptozotocin were not prone to hypoglycemia and their glycemic controls were stable. However, the models induced by total pancreatectomy were more vulnerable to severe hypoglycemia and their glycemic controls were the most unstable. Moreover, the levels of blood creatinine and triglyceride increased after the development of diabetes, which was related to the occurrence of hypoglycemia. In conclusion, we suggested that total pancreatectomy and renal impairment are two important risk factors for hypoglycemia in diabetic monkeys. More attention should be paid to daily care of diabetic monkeys, particularly monitoring and protecting their renal function.

Crack Surface Extraction of Industrial CT Volume Data Using FPIT and Planelet

Journal of X-ray Science and Technology. 2011  |  Pubmed ID: 21422585

As an advanced nondestructive testing (NDT) technology, industrial computed tomography (ICT) has been widely applied to diversified areas. In modern industry, ICT is especially useful for analyzing inner defects of complex and close work pieces. The common defects of work pieces include gas cavities, slag inclusions, cracks and shrinking cavities. Only cracks are often caused by fatigue usage. Precisely extracting a crack is important to estimate the remaining secure service time of the work piece. This paper presents a crack surface extraction method of ICT volume data based on finite plane integral transform (FPIT) and planelet. FPIT and planelet, as new methods of multiscale geometric analysis (MGA), have distinct discrimination for different plane singularities. Within the paper, firstly the definitions of FPIT and planelet are introduced. Secondly, after analyzing the components and relationship of planelet at monoscale, a fast performance of planelet transform is designed. Thirdly, the steps of the proposed crack surface extraction method are described. In numeric experiment, compared with the method of 3D facet model, C-V model and 3D wavelet respectively, the proposed method can extract the crack surface full and continuously, which,is robust to noise.

[Agreement and Repeatability of Central Corneal Thickness Measurement Using the Pentacam and Ultrasound Pachymetry]

[Zhonghua Yan Ke Za Zhi] Chinese Journal of Ophthalmology. Feb, 2011  |  Pubmed ID: 21426844

To compare the agreement and repeatability of the OCULUS Pentacam (a new Scheimpflug-based imaging system) with ultrasound pachymetry in the measurement of central corneal thickness (CCT).

Mixed Outer Synchronization of Coupled Complex Networks with Time-varying Coupling Delay

Chaos (Woodbury, N.Y.). Mar, 2011  |  Pubmed ID: 21456835

In this paper, the problem of outer synchronization between two complex networks with the same topological structure and time-varying coupling delay is investigated. In particular, we introduce a new type of outer synchronization behavior, i.e., mixed outer synchronization (MOS), in which different state variables of the corresponding nodes can evolve into complete synchronization, antisynchronization, and even amplitude death simultaneously for an appropriate choice of the scaling matrix. A novel nonfragile linear state feedback controller is designed to realize the MOS between two networks and proved analytically by using Lyapunov-Krasovskii stability theory. Finally, numerical simulations are provided to demonstrate the feasibility and efficacy of our proposed control approach.

In Vitro Effects of Polyethylene Glycol in University of Wisconsin Preservation Solution on Human Red Blood Cell Aggregation and Hemorheology

Clinical Hemorheology and Microcirculation. 2011  |  Pubmed ID: 21498897

Addition of hydroxyethyl starch (HES) to UW (University of Wisconsin) solution increases viscosity of the solution and red blood cell (RBC) aggregation. Recently, it was suggested that HES could be replaced by a new colloid, polyethylene glycol (PEG), in UW solution. The aim of this study was to see whether and how PEG affected RBC aggregation, and whether RBC aggregation parameters had any correlation with the molecular weight and concentration of PEG. After giving informed consent and signing consent documents, 12 healthy volunteers were enrolled in the study. Blood samples obtained from these volunteers were mixed with the test solutions with blood/solutions ratios of 5:1 and 1:1. Human RBC aggregation was investigated with an automatic hemorheological analyzer. Blood viscosity was measured with a cone-plate viscometer. Morphological characters of RBC aggregates were evaluated by light microscopy. It was found that viscosity was not affected by the Colloid-free UW solution. PEG20kDa (1 and 10 g/L) and PEG35kDa (1 g/L) had little effect on RBC aggregation, while PEG20kDa (30 g/L) and PEG35kDa (10 and 30 g/L) had a significant hyperaggregating effect on RBC. In conclusion, PEGs had a potential hyperaggregating effect on human RBC. This effect is correlated with PEG molecular weight and concentration. The use of large molecular weight and high concentration PEG in UW solution accounts for extended and accelerated aggregation of erythrocytes. The use of low concentration PEG35kDa (1 g/L) would be the optimal choice.

[The Role of DNA Double Strains Damage Repairing Mechanisms in High Glucose-induced Endothelial Senescence]

Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition. Mar, 2011  |  Pubmed ID: 21500551

To investigate the roles of DNA double stains damage repairing mechanisms in high glucose-induced cellular senescence.

Disubstituted Quinazoline Derivatives As a New Type of Highly Selective Ligands for Telomeric G-quadruplex DNA

European Journal of Medicinal Chemistry. Jan, 2012  |  Pubmed ID: 22104971

A series of 2,4-disubstituted quinazoline derivatives found to be a new type of highly selective ligand to bind with telomeric G-quadruplex DNA, and their biological properties were reported for the first time.Their interactions with telomeric G-quadruplex DNA were evaluated by using fluorescence resonance energy transfer (FRET) melting assay, circular dichroism (CD) spectroscopy, surface plasmon resonance (SPR), nuclear magnetic resonance (NMR), and molecular modeling. Our results showed that these derivatives could well recognize G-quadruplex and have high selectivity toward G-quadruplex over duplex DNA. The structure-activity relationships (SARs) study revealed that the disubstitution of quinazoline and the length of the amide side chain were important for its interaction with the G-quadruplex. Furthermore, telomerase inhibition of the quinazoline derivatives and their cellular effects were studied.

A Structural Basis for Antigen Presentation by the MHC Class Ib Molecule, Qa-1b

Journal of Immunology (Baltimore, Md. : 1950). Jan, 2012  |  Pubmed ID: 22131332

The primary function of the monomorphic MHC class Ib molecule Qa-1(b) is to present peptides derived from the leader sequences of other MHC class I molecules for recognition by the CD94-NKG2 receptors expressed by NK and T cells. Whereas the mode of peptide presentation by its ortholog HLA-E, and subsequent recognition by CD94-NKG2A, is known, the molecular basis of Qa-1(b) function is unclear. We have assessed the interaction between Qa-1(b) and CD94-NKG2A and shown that they interact with an affinity of 17 μM. Furthermore, we have determined the structure of Qa-1(b) bound to the leader sequence peptide, Qdm (AMAPRTLLL), to a resolution of 1.9 Å and compared it with that of HLA-E. The crystal structure provided a basis for understanding the restricted peptide repertoire of Qa-1(b). Whereas the Qa-1(b-AMAPRTLLL) complex was similar to that of HLA-E, significant sequence and structural differences were observed between the respective Ag-binding clefts. However, the conformation of the Qdm peptide bound by Qa-1(b) was very similar to that of peptide bound to HLA-E. Although a number of conserved innate receptors can recognize heterologous ligands from other species, the structural differences between Qa-1(b) and HLA-E manifested in CD94-NKG2A ligand recognition being species specific despite similarities in peptide sequence and conformation. Collectively, our data illustrate the structural homology between Qa-1(b) and HLA-E and provide a structural basis for understanding peptide repertoire selection and the specificity of the interaction of Qa-1(b) with CD94-NKG2 receptors.