Intercellular protein-protein interactions at synapses

Chemical synapses are asymmetric intercellular junctions through which neurons send nerve impulses to communicate with other neurons or excitable cells. The appropriate formation of synapses, both spatially and temporally, is essential for brain function and depends on the intercellular protein-protein interactions of cell adhesion molecules (CAMs) at synaptic clefts. The CAM proteins link pre- and post-synaptic sites, and play essential roles in promoting synapse formation and maturation, maintaining synapse number and type, accumulating neurotransmitter receptors and ion channels, controlling neuronal differentiation, and even regulating synaptic plasticity directly. Alteration of the interactions of CAMs leads to structural and functional impairments, which results in many neurological disorders, such as autism, Alzheimer’s disease and schizophrenia. Therefore, it is crucial to understand the functions of CAMs during development and in the mature neural system, as well as in the pathogenesis of some neurological disorders. Here, we review the function of the major classes of CAMs, and how dysfunction of CAMs relates to several neurological disorders.     

A new unconventional HLA-A2-restricted epitope from HBV core protein elicits antiviral cytotoxic T lymphocytes

Cytotoxic T cells (CTLs) play a key role in the control of Hepatitis B virus (HBV) infection and viral clearance. However, most of identified CTL epitopes are derived from HBV of genotypes A and D, and few have been defined in virus of genotypes B and C which are more prevalent in Asia. As HBV core protein (HBc) is the most conservative and immunogenic component, in this study we used an overlapping 9-mer peptide pool covering HBc to screen and identify specific CTL epitopes. An unconventional HLA-A2-restricted epitope HBc141–149 was discovered and structurally characterized by crystallization analysis. The immunogenicity and anti-HBV activity were further determined in HBV and HLAA2 transgenic mice. Finally, we show that mutations in HBc141–149 epitope are associated with viral parameters and disease progression in HBV infected patients. Our data therefore provide insights into the structure characteristics of this unconventional epitope binding to MHC-I molecules, as well as epitope specific CTL activity that orchestrate T cell response and immune evasion in HBV infected patients.     

中国南方喀斯特荔波世界自然遗产地翼手目物种多样性与保护现状

为了解荔波世界自然遗产地翼手目动物的物种多样性和生存现状, 作者于2010年10月至2011年10月, 对中国南方喀斯特荔波世界自然遗产地区域内6个镇(乡)69个洞穴的翼手目动物进行了考察, 发现60个洞穴有翼手目动物栖息痕迹, 其中可以确定具体栖息物种的洞穴有37个。本次调查观察记录到翼手目动物10万余只, 隶属5科15种, 结合文献记载及贵州师范大学动物标本室保存的翼手目动物标本, 确认该地区共有翼手目动物7科24种。11种翼手目动物在荔波世界自然遗产地为首次记录, 其中狭耳鼠耳蝠(Myotis blythii)、果树蹄蝠(Hipposideros pomona)2种为贵州省翼手目新记录。该地区一些洞穴已被开发为旅游景点, 严重影响了洞穴内翼手目动物的生存, 翼手目动物保护状况令人担忧, 建议对翼手目动物栖息的洞穴采取必要的保护措施。     

Association of matrix metalloproteinases-9 gene polymorphisms with genetic susceptibility to esophageal squamous cell carcinoma

Matrix metalloproteinases-9 (MMP-9) plays important roles in tumor invasion and metastasis by degrading extracellular matrix components. Variations in the DNA sequence in the MMP-9 gene may lead to altered MMP-9 production and/or activity, and so this may modulate an individual's susceptibility to esophageal squamous cell carcinoma (ESCC). To test this hypothesis, we investigated the association of the MMP-9 polymorphisms and their haplotypes with the risk of ESCC in a Chinese population. There were significant differences in the genotype and allele distribution of P574R polymorphism of the MMP-9 gene among cases and controls. The P574R GG genotypes were associated with a significantly increased risk of ESCC as compared with the CC genotypes (odds ratio [OR] = 4.08; 95% confidence interval [CI]: 1.58-10.52; p = 0.00). Compared with 279R-574P haplotype, 279R-574R (OR = 3.52; 95% CI: 1.99-6.25) and 279Q-574P (OR = 2.16; 95% CI: 1.07-4.35) haplotypes can increase the onset risk of ESCC statistically, but the role of 279R-574R haplotype is more obvious. MMP-9 P574R polymorphisms and P574R-R279Q haplotype are significantly associated with the risk of ESCC. Our study shows for the first time that MMP-9 gene P574R polymorphism may contribute to a genetic risk factor for ESCC in a Chinese population.     

Atomic resolution structure of cucurmosin, a novel type 1 ribosome-inactivating protein from the sarcocarp of Cucurbita moschata

A novel type 1 ribosome-inactivating protein (RIP) designated cucurmosin was isolated from the sarcocarp of Cucurbita moschata (pumpkin). Besides rRNA N-glycosidase activity, cucurmosin exhibits strong cytotoxicities to three cancer cell lines of both human and murine origins, but low toxicity to normal cells. Plant genomic DNA extracted from the tender leaves was amplified by PCR between primers based on the N-terminal sequence and X-ray sequence of the C-terminal. The complete mature protein sequence was obtained from N-terminal protein sequencing and partial DNA sequencing, confirmed by high resolution crystal structure analysis. The crystal structure of cucurmosin has been determined at 1.04A, a resolution that has never been achieved before for any RIP. The structure contains two domains: a large N-terminal domain composed of seven alpha-helices and eight beta-strands, and a smaller C-terminal domain consisting of three alpha-helices and two beta-strands. The high resolution structure established a glycosylation pattern of GlcNAc(2)Man(3)Xyl. Asn225 was identified as a glycosylation site. Residues Tyr70, Tyr109, Glu158 and Arg161 define the active site of cucurmosin as an RNA N-glycosidase. The structural basis of cytotoxicity difference between cucurmosin and trichosanthin is discussed.     

Transdifferentiation of mesenchymal stem cells derived from human fetal lung to hepatocyte-like cells

The great shortage of human hepatic cells makes it desirable to generate extrahepatic stem or precursor cells. In recent years, it has been reported that human multipotential mesenchymal stem cells (hMSCs) differentiate into hepatocyte-like cells. The fetal lung is one of the largest organs containing many MSCs that can be easily obtained. Whether MSCs from fetal lung can differentiate into hepatocytes or bile duct cells is an important issue in basic medicine and clinical application. We isolated fetal lung cells, and expanded and analyzed them. At passage 4, their morphologic, immunophenotyping and cytokine secretions were similar to adult bone marrow-derived MSCs. We conclude that these cells from fetal lung are MSCs, indicating that human fetal lung is an ideal source of hMSCs. hMSCs from fetal lung induced in special differentiation medium showed homogeneous and small polygonal endothelial-like morphology, expressing weak mRNA, as well as Alb and AFP. This implies that hMSCs from fetal lung can differentiate into hepatocyte-like cells.     

Screening for antiviral inhibitors of the HIV integrase-LEDGF/p75 interaction using the AlphaScreen luminescent proximity assay

Small-molecule inhibitors of HIV integrase (HIV IN) have emerged as a promising new class of antivirals for the treatment of HIV/AIDS. The compounds currently approved or in clinical development specifically target HIV DNA integration and were identified using strand-transfer assays targeting the HIV IN/viral DNA complex. The authors have developed a second biochemical assay for identification of HIV integrase inhibitors, targeting the interaction between HIV IN and the cellular cofactor LEDGF/p75. They developed a luminescent proximity assay (AlphaScreen) designed to measure the association of the 80-amino-acid integrase binding domain of LEDGF/p75 with the 163-amino-acid catalytic core domain of HIV IN. This assay proved to be quite robust (with a Z' factor of 0.84 in screening libraries arrayed as orthogonal mixtures) and successfully identified several compounds specific for this protein-protein interaction.     

Development of a biochip using antibody-coated gold nanoparticles to detect specific bioparticles

This study developed a method of detecting bioparticles such as Salmonella that exist in the biological samples. The method employed a substrate with interlaced comb-like electrodes into which the mixtures of biological samples and antibody-coated gold nanoparticles were added. The alternative signals with appropriate frequency bands were then conducted into the comb-like electrodes to change the dielectrophoresis force. The gold-modified Salmonella can be adsorbed on the edges of the electrodes and isolated from various biological samples. The impedance of the adsorbed Salmonella on the edges of the electrodes was measured and comparison of the impedance between the electrodes with and without Salmonella can quantify the amount of the adsorbed Salmonella.