Identification of a bronze weapon based on an embedded fragment in a 3000-year-old skull.
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Adult↗
Biomedical subjects
Li Wang
Publications and source records attributed to Li Wang.
Association of the HTR6 polymorphism C267T with late-onset Alzheimer's disease in Chinese.
Serotonergic neurotransmitter system has been implicated in the pathogenesis of Alzheimer's disease (AD). 5-Hydroxytryptamine (5-HT)(6) receptor is mainly expressed in the brain areas involved in cognitive processes. And 5-HT(6) receptor gene (HTR6) variants may be a genetic risk factor for late-onset Alzheimer's disease (LOAD). To assess whether HTR6 increases the risk for LOAD, we carried out an association study between the HTR6 polymorphism C267T and sporadic LOAD in Mainland Chinese. An association of C/T genotype with LOAD (OR = 2.10, P = 0.014) was observed. And no statistical difference was found between cases and controls after stratification for APOE epsilon4 status. These data suggest that the HTR6 polymorphism C267T possibly involved in the susceptibility to LOAD as an APOE epsilon4-allele independent risk factor of LOAD.
Aged↗
[Effects of Smad7 gene silencing on cell proliferation].
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Bronchi↗
Role of soluble Fas ligand in autoimmune diseases.
AIM: To investigate the role of soluble Fas ligand in autoimmune diseases. METHODS: RT-PCR was performed to amplify sFasL cDNA from the total RNA extracted from activated human peripheral blood lymphocytes. DNA fragments were cloned into PCR vector. After sequenced, sFasL gene fragments were inserted into pQE-31 vector and expressed in E. Coli M15 respectively. Proteins were purified through affinity chromatography column with ligand of 6XHis tag and identified by SDS-PAGE and Western blot. Mice were immunized with sFasL protein and specific anti-serum was harvested 6 wk after immunization. Monoclonal anti-human FasL antibody was made from the immunized mice. Serum level of sFasL in different patients was detected using anti-FasL antibodies from the immunized mice. RESULTS: The protein expressed was 24 ku by SDS-PAGE electrophrosis. The protein was specially bound to anti-human FasL antibody by Western blot analysis. The sFasL protein could induce Jurket cell apoptosis in vitro. The concentration of serum sFasL in patients with autoimmune diseases was higher than that in normal individuals. sFasL could reduce arthritis in collagen induced arthritis (CIA) mice model by subcutaneous injection. CONCLUSION: sFasL may be involved in either induction of apoptosis or autoimmune diseases. Furthermore, sFasL may have potential application in treatment of autoimmune diseases.
Animals↗
Rpn4 is a physiological substrate of the Ubr2 ubiquitin ligase.
The homeostatic abundance of the proteasome in Saccharomyces cerevisiae is controlled by a feedback circuit in which transcriptional activator Rpn4 up-regulates the proteasome genes and is destroyed by the assembled, active proteasome. Remarkably, the degradation of Rpn4 can be mediated by two independent pathways. One pathway is independent of ubiquitin, whereas the other involves ubiquitination on internal lysines. In the present study, we investigated the mechanism underlying the ubiquitin-dependent degradation of Rpn4. We demonstrated, through in vivo and in vitro assays, that Rpn4 is a physiological substrate of the Ubr2 ubiquitin ligase, which was originally identified as a sequence homolog of Ubr1, the E3 component of the N-end rule pathway. The ubiquitin-conjugating enzyme Rad6, which directly interacts with Ubr2, is also required for the ubiquitin-dependent degradation of Rpn4. Furthermore, we showed that deletion of UBR2 exhibited a strong synthetic growth defect with a mutation in the Rpt1 proteasome subunit when Rpn4 was overexpressed. This study not only identified the ubiquitination apparatus for Rpn4 but also unveiled the first physiological substrate of Ubr2. The biological significance of Ubr2-mediated degradation of Rpn4 is also discussed.
Amino Acid Sequence↗
Association between a T/C polymorphism in intron 2 of cholesterol 24S-hydroxylase gene and Alzheimer's disease in Chinese.
A polymorphism (T/C) in intron 2 of the cholesterol 24-hydroxylase (CYP46) gene has recently been reported to be associated with the risk for late-onset Alzheimer's disease (LOAD). To investigate possible involvement of the CYP46 gene and apolipoprotein E (APOE) gene polymorphisms in the manifestation of LOAD, we analyzed 99 sporadic LOAD patients and 113 healthy controls of China. We found an obvious association between CYP46 TT genotype and LOAD (OR = 2.98, 95% CI 1.64-5.44, P < 0.001). A clear increase of the risk to develop LOAD was also observed in subjects carrying both the CYP46 TT genotype and the APOE epsilon4-allele (OR = 12.94, 95% CI 4.26-39.32, P < 0.001). Our data reveal that the polymorphism of CYP46 intron 2 is implicated in the susceptibility to LOAD and a strong synergistic interaction between CYP46 TT homozoygots and APOE epsilon4 carrier status on the risk of LOAD.
Aged↗
Gi-independent macrophage chemotaxis to lysophosphatidylcholine via the immunoregulatory GPCR G2A.
G2A is a G-protein-coupled receptor (GPCR) involved in immune regulation. Previous studies have shown that lysophosphatidylcholine (LPC), a bioactive lipid associated with atherosclerosis and autoimmunity, acts through G2A to induce diverse biologic effects. Production of LPC during cell apoptosis serves as a chemotactic signal for macrophage recruitment. Here we demonstrate that macrophage chemotaxis to LPC is dependent on G2A function. Wild-type but not G2A-deficient mouse peritoneal macrophages migrated toward LPC. RNAi-mediated knockdown of G2A in J774A.1 macrophages abolished LPC-induced chemotaxis, whereas overexpression of G2A significantly enhanced this process. Mutation of the conserved DRY motif of G2A resulted in loss of chemotaxis to LPC, suggesting a requirement for G-protein signaling. Unlike most GPCRs, including the chemokine receptors, coupling to G(i) is not required for LPC/G2A-mediated chemotaxis, but coupling to G(q/11) and G(12/13) is necessary as judged by inhibition with dominant negative forms of these alpha subunits or with regulators of G-protein signaling (RGS) constructs. Collectively, these data establish that pertussis toxin-insensitive G2A signaling regulates macrophage chemotaxis to LPC. Defects in this signaling pathway may be related to the pathogenesis of systemic autoimmune disease.
Animals↗
tPatternHunter: gapped, fast and sensitive translated homology search.
UNLABELLED: New ideas, spaced seeds and gapped alignment before 6-frame translation are implemented for translated homology search in tPatternHunter. The new software compares favorably with tBLASTx. AVAILABILITY: The software is free to academics at http://www.bioinformaticssolutions.com/downloads/ph-academic/ CONTACT: bma@csd.uwo.ca.
Algorithms↗
[A prospective study of the anterior cruciate ligament reconstruction: allograft versus autograft].
OBJECTIVE: To compare the clinical outcomes and differences of arthroscopic anterior cruciate ligament (ACL) reconstruction by using allografts and autografts. METHODS: Fifty-three patients with grade III ACL injuries were divided randomly into 2 groups. Twenty-five cases of group A with autografts of patellar bone-tendon-bone (B-PT-B;n = 15) and 4 strands of semitendinosus/gracilis (n = 10); 28 patients of group B with allografts of B-PT-B (n = 18), 4 strands of semitendinosus/2 strands of gracilis tendons (n = 6) and double tibialis posterior (n = 4) as well as Achilles bone-tendon (n = 2). All procedures were performed endoscopically by some surgeons. All patients were followed up for 12 to 31 months, average 19 months. RESULTS: There were statistically significant differences revealed in physical examination. IKDC and Lysholm-Tegner Score as well as KT-2000 testing was used preoperation and postoperation for both group, but there were no significant differences between the two groups except that group B had less time in operation and longer time in postoperative fever comparing with group A. (2-sample t test, P < 0.05). The KT-2000 side to side difference less than 3 mm were 88% and 86% and more than 5 mm were 4% and 7.1% respectively. The infection rates were 0% and 3.5% for the two groups. CONCLUSION: The clinical outcomes of the allografts and autografts in ACL reconstruction is almost the same. Allografts are a reasonably alternative choice for ACL reconstruction in patients over middle ages and for multiple ligament surgery as well as revision procedures.
Adult↗
Human acyl-coenzyme A:cholesterol acyltransferase 1 (acat1) sequences located in two different chromosomes (7 and 1) are required to produce a novel ACAT1 isoenzyme with additional sequence at the N terminus.
A rare form of human ACAT1 mRNA, containing the optional long 5'-untranslated region, is produced as a 4.3-kelonucleotide chimeric mRNA through a novel interchromosomal trans-splicing of two discontinuous RNAs transcribed from chromosomes 1 and 7. To investigate its function, we express the chimeric ACAT1 mRNA in Chinese hamster ovary cells and show that it can produce a larger ACAT1 protein, with an apparent molecular mass of 56 kDa on SDS-PAGE, in addition to the normal, 50-kDa ACAT1 protein, which is produced from the ACAT1 mRNAs without the optional long 5'-untranslated repeat. To produce the 56-kDa ACAT1, acat1 sequences located at both chromosomes 7 and 1 are required. The 56-kDa ACAT1 can be recognized by specific antibodies prepared against the predicted additional amino acid sequence located upstream of the N-terminal of the ACAT1(ORF). The translation initiation codon for the 56-kDa protein is GGC, which encodes for glycine, as deduced by mutation analysis and mass spectrometry. Similar to the 50-kDa protein, when expressed alone, the 56-kDa ACAT1 is located in the endoplasmic reticulum and is enzymatically active. The 56-kDa ACAT1 is present in native human cells, including human monocyte-derived macrophages. Our current results show that the function of the chimeric ACAT1 mRNA is to increase the ACAT enzyme diversity by producing a novel isoenzyme. To our knowledge, our result provides the first mammalian example that a trans-spliced mRNA produces a functional protein.
Amino Acid Sequence↗
Homeostatic regulation of the proteasome via an Rpn4-dependent feedback circuit.
The 26S proteasome is a complex protease consisting of at least 32 different subunits. Early studies showed that Rpn4 (also named Son1 and Ufd5) is a transcriptional activator of the Saccharomyces cerevisiae proteasome genes, and that Rpn4 is rapidly degraded by the 26S proteasome. These observations suggested that in vivo proteasome abundance may be regulated by an Rpn4-dependent feedback circuit. Here, we present direct evidence to support the Rpn4-proteasome feedback model. We show that proteasome expression is increased when proteasome activity is impaired, and that this increase is Rpn4-dependent. Moreover, we demonstrate that expression of a stable form of Rpn4 leads to elevation of proteasome expression. Our data also reveal that the Rpn4-proteasome feedback circuit is critical for cell growth when proteasome activity is compromised, and plays an important role in response to DNA damage. This study provides important insights into the mechanism underlying proteasome homeostasis.
DNA-Binding Proteins↗
Prophylactic vaccination with phage-displayed epitope of C. albicans elicits protective immune responses against systemic candidiasis in C57BL/6 mice.
Epitope LKVIRK on 47 kDa of heat shock protein (Hsp) 90 of Candida albicans, corresponding to residues 386-391 of the Hsp90, is recognized by patients recovering from invasive candidiasis. The efficacy of hybrid phage displaying epitope LKVIRK in the N-terminal region of the major coat protein (pVIII) in inducing anti-invasive candidiasis immune response was studied in C57BL/6 mice. Indirect phage-ELISA results demonstrated that the mice immunized with hybrid phage had significantly higher titers of epitope LKVIRK-specific serum IgG as compared to those immunized with heat-killed C. albicans (HK-CA). C57BL/6 mice immunized either with hybrid phage or with wild-type phage also developed significant levels of delayed-type hypersensitivity (DTH) response and splenocyte proliferation, as well as with HK-CA. In addition, high levels of IFN-gamma in the CD4(+) splenocytes from phage-immunized mice were detected as well during 1 week post-inoculation. Furthermore, mice immunized with hybrid phage acquired a resistance to systemic C. albicans infection as confirmed by fewer C. albicans cells in the kidneys, and had a longer lifespan compared to control groups following intravenous challenge with C. albicans. These results indicate that hybrid phage displaying epitope LKVIRK may serve as a potential vaccine conferring a resistance to systemic candidiasis.
Animals↗
Visualization of regulated exocytosis with a granule-membrane probe using total internal reflection microscopy.
Secretory granules labeled with Vamp-green fluorescent protein (GFP) showed distinct signatures upon exocytosis when viewed by total internal reflection fluorescence microscopy. In approximately 90% of fusion events, we observed a large increase in fluorescence intensity coupled with a transition from a small punctate appearance to a larger, spreading cloud with free diffusion of the Vamp-GFP into the plasma membrane. Quantitation suggests that these events reflect the progression of an initially fused and spherical granule flattening into the plane of the plasma membrane as the Vamp-GFP simultaneously diffuses through the fusion junction. Approximately 10% of the events showed a transition from puncta to ring-like structures coupled with little or no spreading. The ring-like images correspond quantitatively to granules fusing and retaining concavity (recess of approximately 200 nm). A majority of fusion events involved granules that were present in the evanescent field for at least 12 s. However, approximately 20% of the events involved granules that were present in the evanescent field for no more than 0.3 s, indicating that the interaction of the granule with the plasma membrane that leads to exocytosis can occur within that time. In addition, approximately 10% of the exocytotic sites were much more likely to occur within a granule diameter of a previous event than can be accounted for by chance, suggestive of sequential (piggy-back) exocytosis that has been observed in other cells. Overall granule behavior before and during fusion is strikingly similar to exocytosis previously described in the constitutive secretory pathway.
Animals↗
[Advanced glycation end products accelerate atherosclerosis via enhancement of oxidative stress].
OBJECTIVE: To investigate the effect of advanced glycation end products (AGE) on atheromatous plaque formation and its possible mechanisms. METHODS: Fifty rabbits were randomly divided into five groups of 10 rabbits: group A, fed with hypercholesterolemic diet and injected intravenously with AGE modified rabbit serum albumin (AGE-RSA); group B, fed with hypercholesterolemic diet and injected with unmodified RSA; group C, fed with hypercholesterolemic diet; group D, fed with normal diet alone: and group E, fed with normal diet and injected with AGE-RSA. Ten weeks after the rabbits were killed. Their aortas were taken out and stained with Sudan red IV. The extent of atheromatous plaques in the aortas en face was evaluated by computer-assisted morphometry and by histologic examination. Photoshop system was used to measure the percentage of atheromatous plaques in the area of tunica intima. The depositions of AGE, malondialdehyde modified low-density lipoprotein (MDA-LDL), oxidized low-density lipoprotein (ox-LDL) and expression of receptor of AGE (RAGE) in aortic tissue were detected by using immunohistological staining. The circulating AGE, blood lipids, serum selenium glutathione peroxydase (SeGSHPx) activity, malonyldialdehyde (MDA), and oxidized LDL (ox-LDL) were detected before the experiment and after the rabbits were killed. RESULTS: (1) The relative plaque area was significantly increased in group A (50% +/- 8%) compared with in group B (21% +/- 7%) and group C (29% +/- 6%). No plaque could be found in animals fed with normal diet (group D) even in those receiving repeated injections of AGE-RSA (group E). Depositions of ox-LDL, MDA-LDL and AGE in atherosclerotic lesions increased and RAGE expression were upregulated in the rabbits fed with hypercholesterolemic diet and injected with AGE-RSA (group A) compared with the other four groups. (2) All hypercholesterolemic rabbits showed comparable serum levels of triglyceride and cholesterol. However, the serum levels of AGE, ox-LDL and MDA were significantly higher and the serum level of SeGSHPx was relatively lower in group A compared with those in the other four groups. (3) The serum level of AGE was directly correlated with the serum ox-LDL (r = 0.459, P < 0.01) or serum MDA concentration (r = 0.423, P < 0.05), and inversely correlated with the serum level of SeGSHPx (r = - 0.448, P < 0.01). A close correlation was found between the serum level of AGE and endothelium RAGE expression (r = 0.384, P < 0.05) and deposition area of AGE (r = 0.468, P < 0.05) in aorta. CONCLUSION: AGE accelerates the atheromatous plaque formation through induction of oxidative stress and upregulation of RAGE.
Animals↗
Complete genome sequence of Yersinia pestis strain 91001, an isolate avirulent to humans.
Genomics provides an unprecedented opportunity to probe in minute detail into the genomes of the world's most deadly pathogenic bacteria- Yersinia pestis. Here we report the complete genome sequence of Y. pestis strain 91001, a human-avirulent strain isolated from the rodent Brandt's vole-Microtus brandti. The genome of strain 91001 consists of one chromosome and four plasmids (pPCP1, pCD1, pMT1 and pCRY). The 9609-bp pPCP1 plasmid of strain 91001 is almost identical to the counterparts from reference strains (CO92 and KIM). There are 98 genes in the 70,159-bp range of plasmid pCD1. The 106,642-bp plasmid pMT1 has slightly different architecture compared with the reference ones. pCRY is a novel plasmid discovered in this work. It is 21,742 bp long and harbors a cryptic type IV secretory system. The chromosome of 91001 is 4,595,065 bp in length. Among the 4037 predicted genes, 141 are possible pseudo-genes. Due to the rearrangements mediated by insertion elements, the structure of the 91001 chromosome shows dramatic differences compared with CO92 and KIM. Based on the analysis of plasmids and chromosome architectures, pseudogene distribution, nitrate reduction negative mechanism and gene comparison, we conclude that strain 91001 and other strains isolated from M. brandti might have evolved from ancestral Y. pestis in a different lineage. The large genome fragment deletions in the 91001 chromosome and some pseudogenes may contribute to its unique nonpathogenicity to humans and host-specificity.
Carbohydrate Metabolism↗
[Integrins mediate the increase of concentration of intracellular free calcium in mouse eggs].
For studying the effect of integrin on the [Ca(2+)](i) of mouse eggs and its transmembrane signaling mechanism, zona-free mouse eggs were loaded with calcium probe Fluo-3/AM and the intensity of fluorescence of the eggs treated with different factors was measured through laser confocal microscopy. The results showed that the [Ca(2+)](i) of zona-free mouse eggs was increased when the eggs were treated with RGD peptide, fibronectin (Fn) and anti-mouse integrin subunit alpha(6) and beta(1) monoclonal antibodies, respectively. The [Ca(2+)](i) of the mouse eggs was also increased when the eggs were placed in calcium-free medium and treated with RGD peptide or Fn. The changes in the mouse egg [Ca(2+)](i) caused by RGD and Fn were similar to those caused by sperm. However, the concentration of Ca(2+) of the zona-free mouse eggs pretreated with tyrosine kinase inhibitor was not increased when the eggs were treated in the same way, and, neither was the intracellular calcium increased in those eggs pretreated with PKC inhibitor when the eggs were treated with RGD peptide. It is therefore suggested that the occupancy of integrins on the membrane of mouse eggs by their ligands mediates the release of Ca(2+) and then the increase in the [Ca(2+)](i) of eggs, which is one of the early events of egg activation. The tyrosine kinase signaling pathway and PKC are involved in this process as well.
Animals↗
Synthesis and characterization of ultrathin multilayer films based on molybdenum polyoxometalate (Mo(54)).
The crown-shaped molybdenum polyoxometalate cluster Na(26)[[Na(H(2)O)(2)](6)[(micro(3) -OH)(4) (Mo(20)(V)), (Mo(34)(VI)(O)(164) (micro-CH(3)COO(4)) x 120H(2)O(Mo(54)) was synthesized and first used as a bulk modifier to fabricate a three-dimensional modified WIGE electrode by the layer-by-layer method. The (Mo(54))/PAH)(n) multilayer films have been characterized by X-ray photoelectron spectra (XPS) and atomic force microscopy (AFM). UV-vis measurements reveal regular film growth with each Mo(54) adsorption. The electrochemical method was used to characterize the modified WIGE electrode, which is important for practical applications.
Journal Article↗
Characterization of an ultraviolet B-induced lipase in Arabidopsis.
An Arabidopsis expressed sequence tag clone, 221D24, encoding a lipase has been characterized using an antisense approach. The lipase gene is expressed during normal growth and development of Arabidopsis rosette leaves but is down-regulated as the leaves senesce. When plants are exposed to sublethal levels of UV-B radiation, expression of the lipase is strongly up-regulated. The lipase protein is localized in the cell cytosol and is present in all organs of Arabidopsis plants. Recombinant lipase protein produced in Escherichia coli preferentially hydrolyzed phospholipids, indicating that the gene encodes a phospholipase. Transgenic plants in which lipase expression is suppressed showed enhanced tolerance to UV-B stress but not osmotic stress and were unable to up-regulate PR-1 expression when irradiated with UV-B. The observations collectively indicate that the lipase is capable of deesterifying membrane phospholipids and is up-regulated in response to UV-B irradiation.
Amino Acid Sequence↗