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Bin Yu

Publications and source records attributed to Bin Yu.

At least 37 records · Page 2Linked to original sources
PubMed2005

Cyclophilin A-deficient mice are resistant to immunosuppression by cyclosporine.

Cyclosporine is an immunosuppressive drug that is widely used to prevent organ transplant rejection. Known intracellular ligands for cyclosporine include the cyclophilins, a large family of phylogenetically conserved proteins that potentially regulate protein folding in cells. Immunosuppression by cyclosporine is thought to result from the formation of a drug-cyclophilin complex that binds to and inhibits calcineurin, a serine/threonine phosphatase that is activated by TCR engagement. Amino acids within the cyclophilins that are critical for binding to cyclosporine have been identified. Most of these residues are highly conserved within the 15 mammalian cyclophilins, suggesting that many are potential targets for the drug. We examined the effects of cyclosporine on immune cells and mice lacking Ppia, the gene encoding the prototypical cyclophilin protein cyclophilin A. TCR-induced proliferation and signal transduction by Ppia(-/-) CD4(+) T cells were resistant to cyclosporine, an effect that was attributable to diminished calcineurin inhibition. Immunosuppressive doses of cyclosporine failed to block the responses of Ppia(-/-) mice to allogeneic challenge. Rag2(-/-) mice reconstituted with Ppia(-/-) splenocytes were also cyclosporine resistant, indicating that this property is intrinsic to Ppia(-/-) immune cells. Thus, among multiple potential ligands, CypA is the primary mediator of immunosuppression by cyclosporine.

Animals↗
PubMed2005

Stat3 regulates genes common to both wound healing and cancer.

Wound healing and cancer are both characterized by cell proliferation, remodeling of extracellular matrix, cell invasion and migration, new blood vessel formation, and modulation of blood coagulation. The mechanisms that link wound healing and cancer are poorly understood. We report here that Stat3, a common signaling mechanism involved in oncogenesis and tissue injury, regulates a common set of genes involved in wound healing and cancer. Using oligonucleotide gene arrays and quantitative real-time PCR, we evaluated changes in global gene expression resulting from expression of Stat3 in lung epithelial cells. We report here previously uncharacterized genes induced by Stat3 implicated in signaling pathways common to both wound healing and cancer including cell invasion and migration, angiogenesis, modulation of coagulation, and repression of interferon-inducible genes. Consistent with these results, we found increased Stat3 activity associated with wound healing in chronically inflamed mouse lungs and increased Stat3 activity was identified at the leading edge of lung tumors invading adjacent nontumor stroma. These findings provide a molecular basis for understanding cancer as a deregulation of normal wound healing processes.

Acute-Phase Proteins↗
PubMed2005

[Comparison of instrumented posterior fusion with instrumented circumferential lumbar fusion in the treatment of lumbar stenosis with low degree lumbar spondylolisthesis].

OBJECTIVE: To compare and evaluate instrumented posterior fusion with instrumented circumferential lumbar fusion in the treatment of lumbar stenosis with low degree lumbar spondylolisthesis. METHODS: From April 1998 to April 2003, 45 patients who suffered from lumbar stenosis with low degree lumbar spondylolisthesis were divided into 2 groups (A and B) at random. The patients in group A (n = 24, average age 54 years old) were performed decompressive laminectomy, intertransverse process arthrodesis with bone grafting and transpedicle instrumentation of solid connection (SOCON) system. The patients in group B (n = 21, average age 53 years old) were performed the same procedure as group A except adding posterior lumbar interbody fusion (PROSPACE). The main levels of lumbar spondylolisthesis in 2 groups was L(4 - 5) or L(5)-S(1). All cases were classified as degree 1 to degree 2. All patients in the two groups received preoperative myelography or CTM, and were diagnosed lateral recess stenosis and(or) central lumbar canal stenosis. RESULTS: All the patients were followed up from 12 to 72 months. In group A, the results showed that the preoperative clinical symptoms disappeared completely in 12 of 24 patients, pain relief was seen in 91.7% (22/24), anatomical reduction rate was 91.7%. No infection or neurologic complication occurred in this series. In group B, the results showed that the preoperative clinical symptoms disappeared completely in 13 of 21 patients, pain relief was seen in 90.5% (19/21), anatomical reduction rate was 95.2%. Four cases of infection or neurologic complication occurred in this series. Two groups had no significant difference in follow-up clinical outcome and anatomical reduction rate. But group A had better intraoperative circumstances and postoperative outcome than group B, group B had better postoperative parameters in X-ray of angle of slipping and disc index than group A. CONCLUSIONS: The best surgical treatment method of lumbar stenosis with low degree lumbar spondylolisthesis is complete intraoperative decompressive laminectomy, reduction with excellent transpedicle system instrumentation and solid fusion after bone grafting. The use of cage should be conformed to strict indications.

Adolescent↗
PubMed2005

Potentiometric sensor for dipicolinic acid.

A potentiometric chemosensor for selective determination of dipicolinic acid (2,6-pyridinedicarboxylic acid, DPA) was developed based on the surface imprinting technique coupled with a nanoscale transducer: an indium tin oxide (ITO)-coated glass plate. The sensor fabrication conditions, optimal recognition condition, as well as selectivity, sensitivity, and stability of the DPA sensor have been investigated. The DPA sensor could recognize DPA from 3,5-pyridinedicarboxylic acid. Potentiometric measurements demonstrated selective detection of DPA in a concentration range of 1.5 x 10(-6) to 0.0194 M. The response time of DPA sensor for 4 x 10(-4) M DPA was 25 s. The potentiometric response of the DPA sensor to DPA is at 90% of its initial magnitude after 550 times measurement. The viability of such a modified ITO electrode in the presence of other inorganic, organic, and biological materials was probed.

Bacillus anthracis↗
PubMed2005

Methylation as a crucial step in plant microRNA biogenesis.

Methylation on the base or the ribose is prevalent in eukaryotic ribosomal RNAs (rRNAs) and is thought to be crucial for ribosome biogenesis and function. Artificially introduced 2'-O-methyl groups in small interfering RNAs (siRNAs) can stabilize siRNAs in serum without affecting their activities in RNA interference in mammalian cells. Here, we show that plant microRNAs (miRNAs) have a naturally occurring methyl group on the ribose of the last nucleotide. Whereas methylation of rRNAs depends on guide RNAs, the methyltransferase protein HEN1 is sufficient to methylate miRNA/miRNA* duplexes. Our studies uncover a new and crucial step in plant miRNA biogenesis and have profound implications in the function of miRNAs.

Arabidopsis↗
PubMed2005

Chimeras of the agouti-related protein: insights into agonist and antagonist selectivity of melanocortin receptors.

The specific melanocortin receptors, MC3R and MC4R, are directly linked to metabolism and body weight control. These receptors are activated by the peptide hormone alpha-MSH and antagonized by the agouti-related protein (AGRP). Whereas alpha-MSH acts broadly on most members of the MCR family (with the exception of MC2R), AGRP is highly specific for only MC3R and MC4R. AGRP is a complex ligand of approximately 100 amino acids. Within AGRP, MCR recognition and antagonism is localized to a 34 residue, cysteine-rich domain that adopts an inhibitor cystine knot (ICK) fold. An oxidatively folded peptide corresponding to this domain, referred to as mini-AGRP, exhibits full antagonist function and selectivity for MC3R and MC4R. Here we investigate a series of chimera proteins based on the mini-AGRP scaffold. Amino acid sequences derived from peptide agonists are grafted into the mini-AGRP active loop, implicated in receptor recognition, with the goal of producing ICK based agonists specific for MC3R and MC4R. Several constructs indeed exhibited potent agonist activity; however, with all chimeras, receptor selectivity is significantly altered. Pharmacologic data indicate that the chimeras do not interact with MC receptors through native AGRP like contacts. A model to explain the data suggest that there is only partial overlap of the agonist versus antagonist binding surfaces within MC receptors. Moreover, accessibility to the binding pocket is highly receptor specific with MC3R being the least tolerant of ligand alterations.

Agouti-Related Protein↗
PubMed2004

Invadolysin: a novel, conserved metalloprotease links mitotic structural rearrangements with cell migration.

The cell cycle is widely known to be regulated by networks of phosphorylation and ubiquitin-directed proteolysis. Here, we describe IX-14/invadolysin, a novel metalloprotease present only in metazoa, whose activity appears to be essential for mitotic progression. Mitotic neuroblasts of Drosophila melanogaster IX-14 mutant larvae exhibit increased levels of nuclear envelope proteins, monopolar and asymmetric spindles, and chromosomes that appear hypercondensed in length with a surrounding halo of loosely condensed chromatin. Zymography reveals that a protease activity, present in wild-type larval brains, is missing from homozygous tissue, and we show that IX-14/invadolysin cleaves lamin in vitro. The IX-14/invadolysin protein is predominantly found in cytoplasmic structures resembling invadopodia in fly and human cells, but is dramatically relocalized to the leading edge of migrating cells. Strikingly, we find that the directed migration of germ cells is affected in Drosophila IX-14 mutant embryos. Thus, invadolysin identifies a new family of conserved metalloproteases whose activity appears to be essential for the coordination of mitotic progression, but which also plays an unexpected role in cell migration.

Animals↗
PubMed2004

Potentiometric sensing of chemical warfare agents: surface imprinted polymer integrated with an indium tin oxide electrode.

Rapid and specific recognition of methylphosphonic acid (MPA), the degradation product of nerve agents sarin, soman, VX, etc., was achieved with potentiometric measurements using a chemical sensor fabricated by a surface imprinting technique coupled with a nanoscale transducer, indium tin oxide (ITO). An octadecylsiloxane thin layer was covalently bound to the ITO-coated glass surface in the presence of MPA. After extraction of MPA, potentiometric measurements showed selective detection of MPA. The selectivity of the sensor has been tested on other alkylphosphonic acids, such as ethylphosphonic acid and propylphosphonic acid, as well as tert-butylphosphonic acid. The viability of the sensor in the presence of other chemical analogues, such as organophosphorus pesticides and herbicides, was investigated.

Journal Article↗
PubMed2004

Enhanced transfection efficiency of a systemically delivered tumor-targeting immunolipoplex by inclusion of a pH-sensitive histidylated oligolysine peptide.

Successful cancer gene therapy depends on the development of non-toxic, efficient, tumor cell- specific systemic gene delivery systems. Our laboratory has developed a systemically administered, ligand-liposome complex that can effectively and preferentially deliver its therapeutic payload to both primary and metastatic tumors. To further improve the transfection efficiency of this targeting complex, a synthetic pH-sensitive histidylated oligolysine K[K(H)KKK]5-K(H)KKC (HoKC), designed to aid in endosomal escape and condensation of DNA, was included in the complex. The presence of HoKC increased the in vitro transfection efficiency over that of the original complex. Moreover, no increase in cytotoxicity was observed due to the presence of the HoKC peptide. In a DU145 human prostate cancer xenograft tumor model in athymic nude mice, inclusion of the HoKC peptide did not interfere with the tumor targeting specificity of the i.v. administered ligand/liposome/DNA complex. Most importantly, the level of transgene expression was significantly elevated in the tumors, but not in the normal tissue in those animals receiving the complex incorporating HoKC. The in vivo enhancement of transfection efficiency by this modified gene delivery vehicle could lead to a reduction in the number of administrations required for antitumor efficacy.

Animals↗
PubMed2004

[Selective thoracic fusion in adolescent idiopathic scoliosis].

OBJECTIVE: To define the criteria of selective thoracic fusion in adolescent idiopathic scoliosis patients. METHODS: By reviewing the roentgenograms of adolescent idiopathic scoliosis patients undergoing selective thoracic fusion, the curve type, Cobb angle, apical rotation and translation, trunk shift, and thoracolumbar kyphosis were measured and analyzed. RESULTS: There were 12 King type II patients (PUMC type: IIb1 9, IIc3 3). The coronal Cobb angle of thoracic curve before and after surgery were 54.0 degrees and 19.0 degrees respectively, and the average correction rate was 62.7%. The coronal Cobb angle of lumbar curve before and after surgery were 34.6 degrees and 12.5 degrees respectively, and the average spontaneous correction rate was 64.7%. At the final follow-up, the coronal Cobb angle of thoracic and lumbar curve was 18.8 degrees and 15.9 degrees respectively. There was no significant change in the coronal Cobb angle, apical vertebral translation and rotation compared with that after surgery. 1 patient had 12 degrees of thoracolumbar kyphosis after surgery, no progression was noted at the final follow-up. There was no trunk decompensation or deterioration of the lumbar curve. In this group, 3.5 levels were saved compared with fusing both the thoracic and lumbar curves. CONCLUSION: Selective thoracic fusion can be safely and effectively performed in patients with a moderate and flexible lumbar curves, which can save more mobile segments to maintain a good coronal and sagittal balance.

Adolescent↗
PubMed2004

[The effect of anterior spinal release on severe adolescent idiopathic scoliosis].

OBJECTIVE: To explore the effect of anterior spinal release on severe scoliosis. METHODS: Twenty-six cases of severe scoliosis were retrospectively reviewed from January 1998 to December 2001. There were 7 males and 19 females with an average age of 15 years (ranging from 10 to 21 years). Twenty-four cases were classified according to King classification for adolescent idiopathic scoliosis, including King type I 4 cases, type II 9 cases, type III 5 cases, King IV 4 cases, King V 2 cases; another two cases were thoracolumbar curve. The major curves were averaged respectively 89.8 degrees, 66.5 degrees, 67.7 degrees, 61.2 degrees on standing, traction, bending and fulcrum film before operation. The distance of apex vertebrae deviated from sacral midline was 39.7 mm before operation. RESULTS: Six cases received anterior spinal release with posterior correction by one stage, 20 cases by two stages. The cases with two stage operation increased the spinal flexibility about 17.8 degrees after anterior release. The major curve was 52.6 degrees on average, and the distance of apex vertebrae deviated from sacral midline was 9.9 mm after operation. The major curve was 54.9 degrees on average, loss the correction 6.4% during follow-up. There was no complication related to the operation in this group. CONCLUSIONS: The anterior spinal release alone has little effect on severe scoliosis with flexibility less than 20% preoperation. The curve can be corrected to a great degree by anterior osteotomy for spine.

Adolescent↗
PubMed2004

EST-analysis of the thermo-acidophilic red microalga Galdieria sulphuraria reveals potential for lipid A biosynthesis and unveils the pathway of carbon export from rhodoplasts.

When we think of extremophiles, organisms adapted to extreme environments, prokaryotes come to mind first. However, the unicellular red micro-alga Galdieria sulphuraria (Cyanidiales) is a eukaryote that can represent up to 90% of the biomass in extreme habitats such as hot sulfur springs with pH values of 0-4 and temperatures of up to 56 degrees C. This red alga thrives autotrophically as well as heterotrophically on more than 50 different carbon sources, including a number of rare sugars and sugar alcohols. This biochemical versatility suggests a large repertoire of metabolic enzymes, rivaled by few organisms and a potentially rich source of thermo-stable enzymes for biotechnology. The temperatures under which this organism carries out photosynthesis are at the high end of the range for this process, making G. sulphuraria a valuable model for physical studies on the photosynthetic apparatus. In addition, the gene sequences of this living fossil reveal much about the evolution of modern eukaryotes. Finally, the alga tolerates high concentrations of toxic metal ions such as cadmium, mercury, aluminum, and nickel, suggesting potential application in bioremediation. To begin to explore the unique biology of G. sulphuraria , 5270 expressed sequence tags from two different cDNA libraries have been sequenced and annotated. Particular emphasis has been placed on the reconstruction of metabolic pathways present in this organism. For example, we provide evidence for (i) a complete pathway for lipid A biosynthesis; (ii) export of triose-phosphates from rhodoplasts; (iii) and absence of eukaryotic hexokinases. Sequence data and additional information are available at http://genomics.msu.edu/galdieria.

Algal Proteins↗
PubMed2004

Cyclophilin A regulates TCR signal strength in CD4+ T cells via a proline-directed conformational switch in Itk.

Cyclophilin A (CypA/Ppia) is a peptidyl-prolyl isomerase (PPIase) that binds the immunosuppressive drug cyclosporine. The resulting complex blocks T cell function by inhibiting the calcium-dependent phosphatase calcineurin. To identify the native function of CypA, long suspected of regulating signal transduction, we generated mice lacking the Ppia gene. These animals develop allergic disease, with elevated IgE and tissue infiltration by mast cells and eosinophils, that is driven by CD4+ T helper type II (Th2) cytokines. Ppia(-/-) Th2 cells were hypersensitive to TCR stimulation, a phenotype consistent with increased activity of Itk, a Tec family tyrosine kinase crucial for Th2 responses. CypA bound Itk via the PPIase active site. Mutation of a conformationally heterogeneous proline in the SH2 domain of Itk disrupted interaction with CypA and specifically increased Th2 cytokine production from wild-type CD4+ T cells. Thus, CypA inhibits CD4+ T cell signal transduction in the absence of cyclosporine via a regulatory proline residue in Itk.

Animals↗
PubMed2004

Reciprocal regulation of thymus and activation-regulated chemokine/macrophage-derived chemokine production by interleukin (IL)-4/IL-13 and interferon-gamma in HaCaT keratinocytes is mediated by alternations in E-cadherin distribution.

Keratinocytes produce many cytochemokines that are involved in the pathogenesis of skin disorders. In particular, the CC chemokines thymus and activation-regulated chemokine (TARC)/macrophage-derived chemokine (MDC) play an important role in the infiltration of Th2 cells. This study was undertaken to examine the regulatory effects of interleukin (IL)-4, IL-13, and interferon (IFN)-gamma on TARC/MDC production in the human keratinocyte cell line HaCaT. HaCaT cells spontaneously secrete TARC and MDC. The production of TARC/MDC was downregulated by IL-4/IL-13, whereas it was upregulated by IFN-gamma. To explore these regulatory mechanisms, we investigated the capacity of cytokines to regulate expression of several adhesion molecules that may affect TARC/MDC production. Of the adhesion molecules examined, the constitutive surface expression of E-cadherin was downregulated by IL-4/IL-13, but was upregulated by IFN-gamma. Moreover, disruption of the homophilic adherence of E-cadherin by anti-E-cadherin antibody or calcium chelation abolished the production of TARC/MDC. We further examined the distribution of the adherens junction complex composed of E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin. IL-4/IL-13 decreased the levels of membrane staining for adherens junction proteins, whereas IFN-gamma increased membrane staining. Taken together, these results suggest that IL-4/IL-13 and IFN-gamma induce alternations in the distribution of adherens junctions in a different fashion and thereby contribute to the reciprocal regulation of TARC/MDC production.

Adherens Junctions↗
PubMed2004

Loss of plastidic lysophosphatidic acid acyltransferase causes embryo-lethality in Arabidopsis.

Phosphatidic acid is a key intermediate for chloroplast membrane lipid biosynthesis. De novo phosphatidic acid biosynthesis in plants occurs in two steps: first the acylation of the sn-1 position of glycerol-3-phosphate giving rise to lysophosphatidic acid; second, the acylation of the sn-2 position of lysophosphatidic acid to form phosphatidic acid. The second step is catalyzed by a lysophosphatidic acid acyltransferase (LPAAT). Here we describe the identification of the ATS2 gene of Arabidopsis encoding the plastidic isoform of this enzyme. Introduction of the ATS2 cDNA into E. coli JC 201, which is temperature-sensitive and carries a mutation in its LPAAT gene plsC, restored this mutant to nearly wild type growth at high temperature. A green-fluorescent protein fusion with ATS2 localized to the chloroplast. Disruption of the ATS2 gene of Arabidopsis by T-DNA insertion caused embryo lethality. The development of the embryos was arrested at the globular stage concomitant with a transient increase in ATS2 gene expression. Apparently, plastidic LPAAT is essential for embryo development in Arabidopsis during the transition from the globular to the heart stage when chloroplasts begin to form.

Acyltransferases↗
PubMed2004

[Individual prefabricated titanium implant for the reconstruction of the skull bone defect].

OBJECTIVE: This paper presents a new method of individual prefabricated titanium implant for the reconstruction of the skull bone defect. METHOD: A computer-based 3D model of the cranial bone defect is created from helical CT-data and serves as the basis for the computer aided design and manufacturing (CAD/CAM) of the individual prefabricated titanium implant for the cranial bone defect reconstruction. RESULT: Since 2001, a total of nine patients suffering from the cranial bone defect have been operated on by this method with satisfied result. The fallow-up is 3 to 12 months. CONCLUSION: These individual prefabricated titanium implants have won a high precision, a good biomechanics and a excellent biocompatibility. It is a quite ideal and very simple method with much less complication for the surgical treatment of the cranial bone defect.

Adolescent↗
PubMed2004

[Comparative study on the enteral and parenteral nutrition during early postburn stage in burn patients].

OBJECTIVE: To investigate the influence of early enteral nutrition on the nutritional indices of the burn patients. METHODS: Thirty-seven burn patients were enrolled in the study and were randomly divided into early enteral nutrition (EN) and parenteral nutrition (PN) groups. The body weight, serum levels of prealbumin and transferrin, the incidence of burn sepsis, and the hospital stay days were surveyed respectively and compared between these two groups. RESULTS: The percentage of body weight loss in EN group was obviously lower than that in PN group on the 7th and 14th post burn day (PBD) (P < 0.05). The serum contents of prealbumin and transferrin in EN group were significantly higher than that in PN group on the 4th, 8th and 14th PBD (P < 0.05 or 0.01). The incidence of burn sepsis in EN group was lower than that in PN group (5.56% vs 31.58%, P < 0.05). The hospital stay days in EN group were less than that in PN group (40.39 +/- 10.81 d vs 54.89 +/- 11.26 d, P < 0.01). CONCLUSION: Early enteral nutrition is beneficial to the improving of nutrition state of the burn patients, and to the reduction of the incidence of burn sepsis and the hospitalization time.

Adult↗