CD39 and control of cellular immune responses

CD39 is the cell surface-located prototypic member of the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) family. Biological actions of CD39 are a consequence (at least in part) of the regulated phosphohydrolytic activity on extracellular nucleotides. This ecto-enzymatic cascade in tandem with CD73 (ecto-5–nucleotidase) also generates adenosine and has major effects on both P2 and adenosine receptor signalling. Despite the early recognition of CD39 as a B lymphocyte activation marker, little is known of the role of CD39 in humoral or cellular immune responses. There is preliminary evidence to suggest that CD39 may impact upon antibody affinity maturation. Pericellular nucleotide/nucleoside fluxes caused by dendritic cell expressed CD39 are also involved in the recruitment, activation and polarization of naïve T cells. We have recently explored the patterns of CD39 expression and the functional role of this ecto-nucleotidase within quiescent and activated T cell subsets. Our data indicate that CD39, together with CD73, efficiently distinguishes T regulatory cells (Treg) from other resting or activated T cells in mice (and humans). Furthermore, CD39 serves as an integral component of the suppressive machinery of Treg, acting, at least in part, through the modulation of pericellular levels of adenosine. We have also shown that the coordinated regulation of CD39/CD73 expression and of the adenosine receptor A2A activates an immunoinhibitory loop that differentially regulates Th1 and Th2 responses. The in vivo relevance of this network is manifest in the phenotype of Cd39-null mice that spontaneously develop features of autoimmune diseases associated with Th1 immune deviation. These data indicate the potential of CD39 and modulated purinergic signalling in the co-ordination of immunoregulatory functions of dendritic and Treg cells. Our findings also suggest novel therapeutic strategies for immune-mediated diseases.     

Signal sequence is still required in genes downstream of “autocleaving” 2A peptide for secretary or membrane-anchored expression

2A Peptide sequences are now being widely used to construct multicistronic expression vectors. It is suggested that when only the first 2A-linked protein bears a signal sequence, the signal-less protein(s) downstream of 2A can also be translocated into the mammalian endoplasmic reticulum system through a “slipstreaming” mechanism. By using flow cytometry and cell surface CD90 as a localization indicator, we show here that slipstreaming translocation does not occur in mammalian cells; that is, the second protein downstream of 2A still requires signal sequence for secretary or membrane-anchored expression.     

Interleukin-6 is required for parasite specific response and host resistance to Trypanosoma cruzi.

Infection with Trypanosoma cruzi, the agent of Chagas' disease, results in elevated levels of interleukin-6 (IL-6) in serum and infected tissues. However, it remains unknown whether IL-6 plays a role in host defence against T. cruzi. To determine whether IL-6 underlies disease progression, we followed the time course of T. cruzi-infected mice bearing IL-6 +/+ and minus sign/minus sign genotypes, respectively. We found that IL-6 minus sign/minus sign mice were more susceptible to T. cruzi infection as they exhibited about 3-fold higher parasitaemia and died earlier than wild-type animals. Unlike what might be expected, T. cruzi-infected IL-6 minus sign/minus sign mice did not show at peak infection a decrease in the secretion of IFN-gamma, a Th1 cytokine crucial for controlling the parasite. Instead, they exhibited a much reduced splenocyte recall response to T. cruzi antigens. Our results suggest that IL-6 mediates anti-parasite protective responses against T. cruzi.     

Structure of plant photosystem I−light harvesting complex I supercomplex at 2.4 Å resolution

Photosystem I (PSI) is one of the two photosystems in photosynthesis, and performs a series of electron transfer reactions leading to the reduction of ferredoxin. In higher plants, PSI is surrounded by four light-harvesting complex I (LHCI) subunits, which harvest and transfer energy efficiently to the PSI core. The crystal structure of PSI-LHCI supercomplex has been analyzed up to 2.6 Å resolution, providing much information on the arrangement of proteins and cofactors in this complicated supercomplex. Here we have optimized crystallization conditions, and analyzed the crystal structure of PSI-LHCI at 2.4 Å resolution. Our structure showed some shift of the LHCI, especially the Lhca4 subunit, away from the PSI core, suggesting the indirect connection and inefficiency of energy transfer from this Lhca subunit to the PSI core. We identified five new lipids in the structure, most of them are located in the gap region between the Lhca subunits and the PSI core. These lipid molecules may play important roles in binding of the Lhca subunits to the core, as well as in the assembly of the supercomplex. The present results thus provide novel information for the elucidation of the mechanisms for the light-energy harvesting, transfer and assembly of this supercomplex.     

Effects of environmental factors on genetic diversity of Caragana microphylla in Horqin Sandy Land,northeast China

Caragana microphylla (Leguminosae) is a dominant climax semishrub species in northern China. We evaluated genetic variation within and among populations sampled from three different environmental gradients in Horqin Sandy Land in northern China using intersimple sequence repeats markers and investigated the possible existence of relationships between genetic diversity and environmental factors. The results showed that C. microphylla have high genetic diversity, and environmental gradients affected genetic diversity of C. microphylla populations. Genetic diversity of all populations was affected by many environmental factors and as well correlated with warm index and soil Olsen phosphorus (SOP) concentration. These results have important implications for restoration and management of these degraded ecosystems in arid and semi‐arid areas.     

Effects of mutations of D1-R323, D1-N322, D1-D319, D1-H304 on the functioning of photosystem II in Thermosynechococcus vulcanus

Photosynthesis Research - Photosystem II (PSII) has a number of hydrogen-bonding networks connecting the manganese cluster with the lumenal bulk solution. The structure of PSII from...     

Differing Epidemiological Dynamics of Influenza B Virus Lineages in Guangzhou,Southern China, 2009-2010

The epidemiological and evolutionary dynamics of the two cocirculating lineages of influenza B virus, Victoria and Yamagata, are poorly understood, especially in tropical or subtropical areas of Southeast Asia. We performed a phylogenetic analysis of the hemagglutinin (HA) and neuraminidase (NA) sequences of influenza B viruses isolated in Guangzhou, a southern Chinese city, during 2009 to 2010 and compared the demographic and clinical features of infected patients. We identified multiple viral introductions of Victoria strains from both Chinese and international sources, which formed two phylogenetically and antigenically distinct clades (Victoria 1 and 2), some of which persisted between seasons. We identified one dominant Yamagata introduction from outside China during 2009. Our phylogenetic analysis reveals the occurrence of reassortment events among the Victoria and Yamagata lineages and also within the Victoria lineage. We found no significant difference in clinical severity by influenza B lineage, with the exceptions that (i) the Yamagata lineage infected older people than either Victoria lineage and (ii) fewer upper respiratory tract infections were caused by the Victoria 2 than the Victoria 1 clade. Overall, our study reveals the complex epidemiological dynamics of different influenza B lineages within a single geographic locality and has implications for vaccination policy in southern China.     

培养基除菌过滤在百日咳菌苗生产中的应用

经一系列试验证实百日咳菌大罐培养浓度的下降与培养基中不耐热营养因子不足有关,将培养基的高压灭菌方式改为除菌过滤,保留热不稳定营养因子,可以提高百日咳菌大罐培养浓度;优化酸沉淀条件后,提高了菌苗回收率,从而节省了大量培养基,缩短了生产时间,获得了良好的经济效益。