Association of neuregulin 1 with schizophrenia confirmed in a Scottish population

Recently, we identified neuregulin 1 (NRG1) as a susceptibility gene for schizophrenia in the Icelandic population, by a combined linkage and association approach. Here, we report the first study evaluating the relevance of NRG1 to schizophrenia in a population outside Iceland. Markers representing a core at-risk haplotype found in Icelanders at the 5' end of the NRG1 gene were genotyped in 609 unrelated Scottish patients and 618 unrelated Scottish control individuals. This haplotype consisted of five SNP markers and two microsatellites, which all appear to be in strong linkage disequilibrium. For the Scottish patients and control subjects, haplotype frequencies were estimated by maximum likelihood, using the expectation-maximization algorithm. The frequency of the seven-marker haplotype among the Scottish patients was significantly greater than that among the control subjects (10.2% vs. 5.9%, P=.00031). The estimated risk ratio was 1.8, which is in keeping with our report of unrelated Icelandic patients (2.1). Three of the seven markers in the haplotype gave single-point P values ranging from .000064 to .0021 for the allele contributing to the at-risk haplotype. This direct replication of haplotype association in a second population further implicates NRG1 as a factor that contributes to the etiology of schizophrenia.     

Enhancing Specific-Antibody Production to the ragB Vaccine with GITRL That Expand Tfh,IFN-γ+ T Cells and Attenuates Porphyromonas gingivalis Infection in Mice

The outer membrane protein RagB is one of the major virulence factors of the periodontal pathogen Porphyromonas gingivalis (P. gingivalis). In order to induce protective immune response against P. gingivalis infection, an mGITRL gene-linked ragB DNA vaccine (pIRES-ragB-mGITRL ) was constructed. Six-week-old female BALB/c mice were immunized with pIRES-ragB-mGITRL through intramuscular injection and then challenged by subcutaneous injection in the abdomen with P. gingivalis. RagB-specific antibody-forming cells were evaluated by an Enzyme-linked immunosorbent spot, and specific antibody was determined by enzyme-linked immunosorbent assay. In addition, the frequencies of Tfh and IFN-γ⁺ T cells in spleen were measured using flow cytometer, and the levels of IL-21 and IFN-γ mRNA or proteins were detected by real time RT-PCR or ELISA. The data showed that the mGITRL-linked ragB DNA vaccine induced higher levels of RagB-specific IgG in serum and RagB-specific antibody-forming cells in spleen. The frequencies of Tfh and IFN-γ⁺ T cells were obviously expanded in mice immunized by pIRES-ragB-mGITRL compared with other groups (pIRES or pIRES-ragB ). The levels of Tfh and IFN-γ⁺ T cells associated cytokines were also significantly increased in pIRES-ragB-mGITRL group. Therefore, the mice immunized with ragB plus mGITRL showed the stronger resistant to P. gingivalis infection and a significant reduction of the lesion size caused by P. gingivalis infection comparing with other groups. Taken together, our findings demonstrated that intramuscular injection of DNA vaccine ragB together with mGITRL induced protective immune response dramatically by increasing Tfh and IFN-γ⁺ T cells and antibody production to P. gingivalis.     

奇异果甜蛋白及其基因工程

奇异果甜蛋白(thaumatin)是迄今为止最甜的物质之一,对其研究具有很重要的意义。奇异果甜蛋白的生化性质基本清楚,基因序列和氨基酸序列都已测定。它的甜味可能是由奇异果甜蛋白上特定基团和受体结合引起的。对奇异果甜蛋白的生理功能知之甚少。近二十年来,在奇异果甜蛋白的基因工程上取得了一定进展,但仍然存在许多困难。 Abstract:Thaumatin is one of the sweetest substances known to date,it is important to study the thaumatin.The biochemical properties of thaumatin have been clarified clearly.Thaumatin had been isolated and sequenced.The mechanism of the sweetness of thaumatin may be due to the combination of some special groups and the receptors.The exact function of thaumatin is still not clear.Although gene engineering of thaumatin has been carried out for 20 years,there are still some difficulties to be solved for using in the market.     

Inhibition of CLIC4 enhances autophagy and triggers mitochondrial and ER stress-induced apoptosis in human glioma U251 cells under starvation

CLIC4/mtCLIC, a chloride intracellular channel protein, localizes to mitochondria, endoplasmic reticulum (ER), nucleus and cytoplasm, and participates in the apoptotic response to stress. Apoptosis and autophagy, the main types of the programmed cell death, seem interconnected under certain stress conditions. However, the role of CLIC4 in autophagy regulation has yet to be determined. In this study, we demonstrate upregulation and nuclear translocation of the CLIC4 protein following starvation in U251 cells. CLIC4 siRNA transfection enhanced autophagy with increased LC3-II protein and puncta accumulation in U251 cells under starvation conditions. In that condition, the interaction of the 14-3-3 epsilon isoform with CLIC4 was abolished and resulted in Beclin 1 overactivation, which further activated autophagy. Moreover, inhibiting the expression of CLIC4 triggered both mitochondrial apoptosis involved in Bax/Bcl-2 and cytochrome c release under starvation and endoplasmic reticulum stress-induced apoptosis with CHOP and caspase-4 upregulation. These results demonstrate that CLIC4 nuclear translocation is an integral part of the cellular response to starvation. Inhibiting the expression of CLIC4 enhances autophagy and contributes to mitochondrial and ER stress-induced apoptosis under starvation.     

Purification of aquarium water by PVA gel-immobilized photosynthetic bacteria during goldfish rearing

This study was conducted to evaluate the ability of a PVA-gel beads filtration (PVA) system using photosynthetic bacteria to purify water. To accomplish this, duplicate long-term goldfish rearing experiments were conducted using four different types of aquarium systems (COF, PSB, EMC, and PVA). The results revealed that the concentrations of NH₄ ⁺-N on the day of a goldfish’s death were significantly higher than the concentrations on other days for all the aquarium systems. In addition, the mean concentration of NH₄ ⁺-N during goldfish rearing occurred in the following order: COF system > EMC system > PSB system > PVA system. Furthermore, the mean values of all other ion concentrations (NO₃ ⁻-N, NO₂ ⁻-N, and PO₄ ²⁻-P) were found to be lowest in the PVA system. As a result, there was more prominent decomposition of organic matter in the aquarium tank containing the PVA system, as well as less turbid aquarium water and more active goldfish. Additionally, the PVA-gel beads resulted in almost complete denitrification, even after six-months of goldfish rearing. To our knowledge, this is the first study to report that PVA gel-immobilized photosynthetic bacteria have the ability to purify water. Overall, the results of this study indicate that this immobilized photosynthetic bacteria system has the potential for use as a component in circulating filtration systems.     

Strategy for allosteric analysis based on protein-patterned stationary phase in microfluidic chip

An effective method is presented for the on-chip analysis of chiral interactions with a successful depression of nonspecific adsorption. The alumina gel-derived protein network on poly(methyl methacrylate) (PMMA) microchannel was explored to form a protein-stationary phase and then used to carry out electrophoresis for fast enantioseparation coupled with electrochemical detection. On the basis of the chemical modification of a synthesized copolymer containing silane-functionalized scaffold, alumina sol-gel could react readily with the silane groups and form steady microstructure on the chip surface achieving the encapsulation of functional biomolecules. Compared with the native PMMA microchannels, the modified surfaces exhibited much better wettability, more stable and enhanced electroosmotic mobility, and less nonspecific adsorption. The water contact angle and EOF of alumina-gel-derived PMMA substrate were 22 degrees and 4.3 x 10(-4) cm(2) V(-1) s(-1), compared to those of 73 degrees and 1.9 x 10(-4) cm(2) V(-1) s(-1) from the untreated one, respectively. Bovine serum albumin, acting as a target protein, could be stably and homogeneously immobilized in the modified PMMA microchannel to fabricate a protein-stationary phase. Under a mild condition, D- and L-tryptophan were efficiently separated with a resolution of 1.57. The as-prepared microchip can perform chiral separations within short time, indicating that the general protocol has the potential to provide a platform for high throughput screening of enantiomer candidates such as those biochemical drugs with protein targets and the research of receptor interactions.     

The role of HIV replicative fitness in perinatal transmission of HIV

Perinatal transmission of Human immunodeficiency virus(HIV),also called mother-to-child transmission(MTCT),accounts for 90% of infections in infants worldwide and occurs in 30%-45% of children born to untreated HIV-1 infected mothers.Among HIV-1 infected mothers,some viruses are transmitted from mothers to their infants while others are not.The relationship between virologic properties and the pathogenesis caused by HIV-1 remains unclear.Previous studies have demonstrated that one obvious source of selective pressure in the perinatal transmission of HIV-1 is maternal neutralizing antibodies.Recent studies have shown that viruses which are successfully transmitted to the child have growth advantages over those not transmitted,when those two viruses are grown together.Furthermore,the higher fitness is determined by the gp120 protein of the virus envelope.This suggests that the selective transmission of viruses with higher fitness occurred exclusively,regardless of transmission routes.There are many factors contributing to the selective transmission and HIV replicative fitness is an important one that should not be neglected.This review summarizes current knowledge of the role of HIV replicative fitness in HIV MTCT transmission and the determinants of viral fitness upon MTCT.     

Miscellaneous terpenoid constituents of Abies nephrolepis and their moderate cytotoxic activities

Three monoterpenoids and two triterpenoids were isolated from Abiesnephrolepis together with 53 known terpenoids. The structures of the compounds were established by 1D and 2D NMR spectroscopy. The absolute configuration of 3-hydroxycamphane-2-carboxylic acid was established as (1S,2R,3S,4R) by Cu-Kα X-ray crystallography. All 58 isolates were tested for cytotoxic activity against four tumor cells viz. A549 (human lung adenocarcinoma), Colo205 (colon adenocarcinoma), QGY-7703 (human hepatoma) and THP-1 (human monocytic leukemia). α-Cadinol exhibited the best effects on A549, Colo205 and QGY-7703 with IC₅₀ values of 8.6, 8.1 and 4.6 μg/mL, respectively.