一类生态系统的持续生存和全局稳定性

讨论了一类具有连续时滞和功能性反应的两种群两缀块的一类生态系统的动力学行为。两种群之一能在两缀块中迁移,另一种群限制在一个缀块中,应用微分方程定性和稳定性的方法,证明了系统在一定条件下是持续生存的。进一步,得到了系统为全局稳定的充分条件     

抗汉坦病毒单链抗体双元载体的构建

利用PCR方法,从含有1A8 scFv基因的重组质粒中扩增出抗体基因,并使基因两端携带合适的限制性酶切位点。经多步连接将其克隆入植物表达载体pBI121或pCAMBIA1305．2。酶切结果证明1A8 scFv基因被成功克隆入植物表达载体pBI121及pCAMBIA1305．2,构建获得1A8 scFv-p BI121及1A8 scFv pCAMBI A1305．2重组质粒,并将其转入农杆菌GV3101。抗汉坦病毒mAb 1A 8scFv植物双元表达载体的获得,为进一步在植物中表达该抗体片段奠定了基础。     

Structure/function analysis of a critical disulfide bond in the active site of l-xylulose reductase

l-Xylulose reductase (XR) is involved in water re-absorption and cellular osmoregulation. The crystal structure of human XR complemented with site-directed mutagenesis (Cys138Ala) indicated that the disulfide bond in the active site between Cys138 and Cys150 is unstable and may affect the reactivity of the enzyme. The effects of reducing agents on the activities of the wild-type and mutant enzymes indicated the reversibility of disulfide-bond formation, which resulted in three-fold decrease in catalytic efficiency. Furthermore, the addition of cysteine (>2 mM) inactivated human XR and was accompanied by a 10-fold decrease in catalytic efficiency. TOF-MS analysis of the inactivated enzyme showed the S-cysteinylation of Cys138 in the wild-type and Cys150 in the mutant enzymes. Thus, the action of human XR may be regulated by cellular redox conditions through reversible disulfide-bond formation and by S-cysteinylation. Received 25 January 2009; received after revision 12 February 2009; accepted 16 February 2009 H.-T. Zhao, S. Endo: These two authors contribute equally to this work.     

Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21

In a genome-wide association study to identify loci associated with colorectal cancer (CRC) risk, we genotyped 555,510 SNPs in 1,012 early-onset Scottish CRC cases and 1,012 controls (phase 1). In phase 2, we genotyped the 15,008 highest-ranked SNPs in 2,057 Scottish cases and 2,111 controls. We then genotyped the five highest-ranked SNPs from the joint phase 1 and 2 analysis in 14,500 cases and 13,294 controls from seven populations, and identified a previously unreported association, rs3802842 on 11q23 (OR = 1.1; P = 5.8 x 10(-10)), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6 x 10(-26)) and 18q21 (rs4939827; OR = 1.2; P = 7.8 x 10(-28)). Risk was greater for rectal than for colon cancer for rs3802842 (P < 0.008) and rs4939827 (P < 0.009). Carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75-3.89) for CRC. These findings extend our understanding of the role of common genetic variation in CRC etiology.     

Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease

Several risk factors for Crohn's disease have been identified in recent genome-wide association studies. To advance gene discovery further, we combined data from three studies on Crohn's disease (a total of 3,230 cases and 4,829 controls) and carried out replication in 3,664 independent cases with a mixture of population-based and family-based controls. The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1. The expanded molecular understanding of the basis of this disease offers promise for informed therapeutic development.     

Extended and bent conformations of the mannose receptor family

In mammals, the mannose receptor family consists of four members, Endo180, DEC-205, phospholipase A₂ receptor and the mannose receptor. The extracellular domains of all these receptors contain a similar arrangement of domains in which an Nterminal cysteine-rich domain is followed by a single fibronectin type II domain and eight or ten C-type lectin-like domains. This review focuses on the threedimensional structure of the receptors in the mannose receptor family and its functional implication. Recent research has revealed that several members of this family can exist in at least two configurations: an extended conformation with the N-terminal cysteinerich domain pointing outwards from the cell membrane and a bent conformation where the N-terminal domains fold back to interact with C-type lectin-like domains at the middle of the structure. Conformational transitions between these two states seem to regulate the interaction of these receptors with ligands and their oligomerization. Received 25 October 2007; received after revision 23 November 2007; accepted 7 December 2007