Showing papers by "Sichuan University published in 2008"

Large recurrent microdeletions associated with schizophrenia

Abstract: Reduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations (CNVs) can be detected using genome-wide single nucleotide polymorphism arrays. This has led to the identification of CNVs associated with mental retardation and autism. In a genome-wide search for CNVs associating with schizophrenia, we used a population-based sample to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring. The 66 de novo CNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample (phase I) were followed up in a second sample of 3,285 cases and 7,951 controls (phase II). All three deletions significantly associate with schizophrenia and related psychoses in the combined sample. The identification of these rare, recurrent risk variants, having occurred independently in multiple founders and being subject to negative selection, is important in itself. CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia.

Using support vector machine combined with auto covariance to predict protein–protein interactions from protein sequences

Abstract: Compared to the available protein sequences of different organisms, the number of revealed protein– protein interactions (PPIs) is still very limited. So many computational methods have been developed to facilitate the identification of novel PPIs. However, the methods only using the information of protein sequences are more universal than those that depend on some additional information or predictions about the proteins. In this article, a sequence-based method is proposed by combining a new feature representation using auto covariance (AC) and support vector machine (SVM). AC accounts for the interactions between residues a certain distance apart in the sequence, so this method adequately takes the neighbouring effect into account. When performed on the PPI data of yeast Saccharomyces cerevisiae, the method achieved a very promising prediction result. An independent data set of 11 474 yeast PPIs was used to evaluate this prediction model and the prediction accuracy is 88.09%. The performance of this method is superior to those of the existing sequence-based methods, so it can be a useful supplementary tool for future proteomics studies. The prediction software and all data sets used in this article are freely available at http://www. scucic.cn/Predict_PPI/index.htm.

Toxicological effect of ZnO nanoparticles based on bacteria.

Abstract: Streptococcus agalactiae and Staphylococcus aureus are two pathogenetic agents of several infective diseases in humans. Biocidal effects and cellular internalization of ZnO nanoparticles (NPs) on two bacteria are reported, and ZnO NPs have a good bacteriostasis effect. ZnO NPs were synthesized in the EG aqueous system through the hydrolysis of ionic Zn2+ salts. Particle size and shape were controlled by the addition of the various surfactants. Bactericidal tests were performed in an ordinary broth medium on solid agar plates and in liquid systems with different concentrations of ZnO NPs. The biocidal action of ZnO materials was studied by transmission electron microscopy of bacteria ultrathin sections. The results confirmed that bactericidal cells were damaged after ZnO NPs contacted with them, showing both gram-negative membrane and gram-positive membrane disorganization. The surface modification of ZnO NPs causes an increase in membrane permeability and the cellular internalization of these NPs whereas there is a ZnO NP structure change inside the cells.

Tumor necrosis factor and cancer, buddies or foes?

Abstract: Tumor necrosis factor (TNF) is a multifunctional cytokine that plays important roles in diverse cellular events such as cell survival, proliferation, differentiation, and death. As a pro-inflammatory cytokine, TNF is secreted by inflammatory cells, which may be involved in inflammation-associated carcinogenesis. TNF exerts its biological functions through activating distinct signaling pathways such as nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK). NF-κB is a major cell survival signal that is anti-apoptotic, whereas sustained JNK activation contributes to cell death. The crosstalk between the NF-κB and JNK is involved in determining cellular outcomes in response to TNF. In regard to cancer, TNF is a double-dealer. On one hand, TNF could be an endogenous tumor promoter, because TNF stimulates the growth, proliferation, invasion and metastasis, and tumor angiogenesis of cancer cells. On the other hand, TNF could be a cancer killer. The property of TNF in inducing cancer cell death renders it a potential cancer therapeutic, although much work is needed to reduce its toxicity for systematic TNF administration. Recent studies have focused on sensitizing cancer cells to TNF-induced apoptosis through inhibiting survival signals such as NF-κB, by combined therapy. In this article we provide an overview of the roles of TNF-induced signaling pathways in cancer biology with specific emphasis on carcinogenesis and cancer therapy.

An improved sensitivity non-enzymatic glucose sensor based on a CuO nanowire modified Cu electrode

Abstract: CuO nanowires have been prepared and applied for the fabrication of glucose sensors with highly enhanced sensitivity. Cu(OH)(2) nanowires were initially synthesised by a simple and fast procedure, CuO nanowires were then formed simply by removing the water through heat treatment. The structures and morphologies of Cu(OH)(2) and CuO nanowires were characterised by X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, and transmission electron microscopy. The direct electrocatalytic oxidation of glucose in alkaline medium at CuO nanowire modified electrodes has been investigated in detail. Compared to a bare Cu electrode, a substantial decrease in the overvoltage of the glucose oxidation was observed at the CuO nanowire electrodes with oxidation starting at ca. 0.10 V vs. Ag/AgCl (saturated KCl). At an applied potential of 0.33 V, CuO nanowire electrodes produce high and reproducible sensitivity to glucose with 0.49 microA/micromol dm(-3). Linear responses were obtained over a concentration range from 0.40 micromol dm(-3) to 2.0 mmol dm(-3) with a detection limit of 49 nmol dm(-3) (S/N = 3). The CuO nanowire modified electrode allows highly sensitive, low working potential, stable, and fast amperometric sensing of glucose, thus is promising for the future development of non-enzymatic glucose sensors.

Genome-wide association identifies a common variant in the reelin gene that increases the risk of schizophrenia only in women

Abstract: Schizophrenia is a complex mental disease, which includes symptoms of delusions, hallucinations, disorganized speech, aberrant behavior, lack of emotional expression, diminished motivation, and social withdrawal. The cause of schizophrenia is unknown, but there is extensive evidence that genetics play a significant role in its aetiology. We studied the genetic basis of schizophrenia by analyzing around 500,000 genetic variants distributed across the whole human genome in DNA from schizophrenic patients and controls. We analyzed separately the DNA from men and women, and identified a genetic variant that increases the risk of developing schizophrenia in women only. The genetic variant is estimated to increase the risk of schizophrenia for women carrying the risk variant by 1.4-fold. The genetic variant is in a gene called reelin, which is known to play a part in brain development. However, it is still unclear how this genetic variant predisposes to schizophrenia nor why it is specific to women only.

Simvastatin-mediated upregulation of VEGF and BDNF, activation of the PI3K/Akt pathway, and increase of neurogenesis are associated with therapeutic improvement after traumatic brain injury.

Abstract: This study was undertaken to evaluate the effect of simvastatin, a cholesterol-lowering agent, on the Akt-mediated signaling pathway and neurogenesis in the dentate gyrus (DG) of the hippocampus in rats after traumatic brain injury (TBI). Adult male Wistar rats were divided into three groups: (1) sham group (n = 8); (2) saline control group (n = 40); and (3) simvastatin-treated group (n = 40). Controlled cortical impact (CCI) injury was performed over the left parietal lobe. Simvastatin was administered orally at a dose of 1 mg/kg starting at day 1 after TBI and then daily for 14 days. Bromodeoxyuridine (BrdU) was injected intraperitoneally into rats. A modified Morris Water Maze (WM) task was performed between 31 and 35 days after treatment to test spatial memory (n = 8/group). Animals were sacrificed at 1, 3, 7, 14, and 35 days after treatment (n = 8/group/time point). Western blot was utilized to investigate the changes in the Akt-mediated signaling pathway. Enzyme-linked immunosorbent assay (...

T2* and FSE MRI distinguishes four subtypes of neurodegeneration with brain iron accumulation

Abstract: Iron accumulates within the basal ganglia and dentate nuclei during normal aging.1 More intense iron deposition has been demonstrated within the substantia nigra in Parkinson disease, and structures affected by β amyloid plaques in Alzheimer disease, implicating iron deposition in the pathogenesis of common neurodegenerative diseases, possibly through increased oxidative stress.2,3 Direct evidence supporting a causal role for iron deposition in neurodegenerative conditions comes from a group of genetic disorders termed neurodegeneration with brain iron accumulation (NBIA), in which a variety of genetic defects in iron metabolism lead to brain iron accumulation with neuronal death in the affected brain regions.4 Four subtypes of NBIA have been defined at the molecular genetic level. Pantothenate kinase associated neurodegeneration (PKAN, NBIA type one, MIM 234200), formerly known as Hallervorden-Spatz syndrome, is caused by mutation of the pantothenate kinase 2 gene (PANK2).5 Infantile neuroaxonal dystrophy (INAD, MIM 256600) is a recessive disorder with psychomotor regression due to mutations in PLA2G6.6 Mutations of the ferritin light chain gene (FTL1) cause the adult onset autosomal dominant movement disorder neuroferritinopathy (FTL, NBIA type two, hereditary ferritinopathy, MIM 606159).7 A further form of NBIA is aceruloplasminemia (aCp, MIM 604290), an autosomal recessive ceruloplasmin deficiency which results in iron deposition in the reticuloendothelial system and brain, presenting with diabetes and an extrapyramidal movement disorder in adult life.8 Extensive phenotypic overlap presents a major challenge in the clinical diagnosis of different subtypes of NBIA, particularly in the early stages. Although molecular genetic testing can provide the definitive diagnosis, comprehensive testing is only available on a research basis, and the genetic defect remains undefined in a large subgroup of patients with so-called NBIA of unknown cause. A reliable clinical investigation capable of predicting the genetic diagnosis would be useful to inform genetic counseling, predict the disease course, and ensure appropriate enrollment in clinical trials of new treatments. Dramatic evidence of focal brain iron accumulation on brain imaging is usually the first indication of NBIA, but the features distinguishing the different subtypes have yet to be defined.

Membranes and membrane processes for chiral resolution

Abstract: This critical review is devoted to an active field of research on chiral separation, membrane-based enantioseparation technique, which has potential for large-scale production of single-enantiomer compounds. Adsorption-type enantioselective membranes and membrane-assisted resolution systems with non-enantioselective solid membranes have attracted much attention recently. The principles and recent developments of both enantioselective liquid and solid membranes and membrane-assisted processes for chiral resolution will be summarized comprehensively in this review, in which the contents are of interest to a wide range of readers in a variety of fields from analytical, organic and medicinal chemistry, to pharmaceutics and materials, to process engineering for fabricating pharmaceuticals, agrochemicals, fragrances and foods, and so on (148 references).

Inductively Coupled Plasma Optical Emission Spectrometry

Abstract: Inductively coupled plasma optical emission spectrometry (ICP OES) is a powerful tool for the determination of many elements in a variety of different sample matrices. With this method, liquid samples are injected into a radiofrequency (RF)-induced argon plasma using one of a variety of nebulizers or sample introduction techniques. The sample mist reaching the plasma is quickly dried, vaporized, and energized through collisional excitation at high temperature. The atomic emission emanating from the plasma is viewed in either a radial or axial configuration, collected with a lens or mirror, and imaged onto the entrance slit of a wavelength selection device. Single-element measurements can be performed cost-effectively with a simple monochromator–photomultiplier tube (PMT) combination, and simultaneous multielement determinations are performed for up to 70 elements with the combination of a polychromator and an array detector. The analytical performance of such systems is competitive with most other inorganic analysis techniques, especially with regard to sample throughput and sensitivity. Keywords: atomic spectrometry; instrumental analysis; argon plasma; nebulizers; gratings; charge-coupled device; multielement determination; trace element analysis; internal standard additions; standard dilution analysis

Fabrication of monodisperse thermosensitive microgels and gel capsules in microfluidic devices

Abstract: We use droplet-based microfluidic techniques to produce monodisperse poly(N-isopropylacrylamide) gel particles in the size range of 10–1000 µm. Our techniques offer exquisite control over both outer dimensions and inner morphology of the particles. We demonstrate this control by fabricating conventional microgels, microgels with embedded materials and voids, and gel microcapsules with single- and multi-phase cores. These techniques should be applicable for the synthesis of particles and capsules of a variety of chemical compositions and for the generation of higher order “supraparticles” by directed assembly of colloidal particles in droplets.

Evidence of the recombinant origin of a bat severe acute respiratory syndrome (SARS)-like coronavirus and its implications on the direct ancestor of SARS coronavirus.

Abstract: Bats have been identified as the natural reservoir of severe acute respiratory syndrome (SARS)-like and SARS coronaviruses (SLCoV and SCoV). However, previous studies suggested that none of the currently sampled bat SLCoVs is the descendant of the direct ancestor of SCoV, based on their relatively distant phylogenetic relationship. In this study, evidence of the recombinant origin of the genome of a bat SLCoV is demonstrated. We identified a potential recombination breakpoint immediately after the consensus intergenic sequence between open reading frame 1 and the S coding region, suggesting the replication intermediates may participate in the recombination event, as previously speculated for other CoVs. Phylogenetic analysis of its parental regions suggests the presence of an uncharacterized SLCoV lineage that is phylogenetically closer to SCoVs than any of the currently sampled bat SLCoVs. Using various Bayesian molecular-clock models, interspecies transfer of this SLCoV lineage from bats to the amplifying host (e.g., civets) was estimated to have happened a median of 4.08 years before the SARS outbreak. Based on this relatively short window period, we speculate that this uncharacterized SLCoV lineage may contain the direct ancestor of SCoV. This study sheds light on the possible host bat species of the direct ancestor of SCoV, providing valuable information on the scope and focus of surveillance for the origin of SCoV.

The growth inhibitory effect of mesenchymal stem cells on tumor cells in vitro and in vivo.

Abstract: Mesenchymal stem cells (MSCs) play an important role in the development and growth of tumor cells. The purpose of this study is to confirm the effect of MSCs on tumor cell growth in vitro and in vivo and to elucidate the mechanism. MSCs were isolated from mouse bone marrow and cocultured with murine hepatoma H22, lymphoma (YAC-1 and EL-4) and rat insulinoma INS-1 cell lines. The growth inhibitory effect of MSCs on tumor cells was tested through MTT and 3H-TdR incorporation assay. The apoptosis induction effect of MSCs on tumor cells was assessed with flow cytometry (FCM) and RT-PCR assay. MSCs were inoculated into BALB/c mice alone or coinoculated with ascitogenous hepatoma cells intraperitonealy, respectively. The tumor growth inhibition of MSCs was investigaed through the incidence and volume of ascites formation, and the immunosuppression effect was studied with splenocyte response to ConA stimulation test and T cell subsets analysis (FCM). The results showed that MSCs exhibited a number-dependent growth inhibitory effect on murine tumor cell lines in vitro and inhibited the growth of ascitogenous hepatoma cells in vivo without host immunosuppression. MSCs could upregulate tumor cells mRNA expression of cell cycle negative regulator p21 and apoptosis associated protease caspase 3. The findings of this experimental study demonstrated that MSCs had potential inhibitory effects on tumor cell growth in vitro and in vivo without host immunosuppression, by inducing apoptotic cell death and G(0)/G(1) phase arrest of cancer cells.

Supported CaO Catalysts Used in the Transesterification of Rapeseed Oil for the Purpose of Biodiesel Production

Abstract: Supported CaO/MgO catalysts were used as the catalyst of the transesterification of rapeseed oil with methanol The supported catalyst showed a higher activity than pure CaO and was easily separated from the product mixture The results of comparative experiments and catalyst characterization, such as XRD, CO2-TPD, BET, and AAS, showed that the activity of CaO catalysts is associated with their alkalinity The preparation method of this catalyst was optimized, and furthermore, the reaction parameters were investigated With the CaO/MgO catalyst so obtained, the conversion of rapeseed oil reached 92% at 645 °C The supported basic catalyst was found to be easily contaminated by the gaseous poisons in air, such as O2, CO2, and H2O, and as a result, a thermal treatment was required before the reaction to activate the catalyst