设计及自组装六边形网格状DNA二维阵列

根据Watson-Crick DNA碱基互补配对原则,设计了不同黏性末端DNA序列,以两种三点星状为模块(three-point-star motif),运用DNA自组装技术,成功制备了六边形网格状DNA二维阵列.研究不同单链DNA的摩尔比例对三点星状模块结构组装的影响,以及不同起始退火温度对二维阵列自组装的影响,用凝胶电泳及原子力显微镜(AFM)对结构进行了表征.结果表明,当构成三点星状模块的3条单链摩尔比例为1:3:3时得到的模块结构更稳定,从50℃开始退火时得到的二维阵列更完整.自组装得到的二维阵列厚度约2nm,六边形边长约20nm.本研究为进一步探究三点星模块组装二维阵列的机理提供了新的思路.     

Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24

Using a multistage genetic association approach comprising 7,480 affected individuals and 7,779 controls, we identified markers in chromosomal region 8q24 associated with colorectal cancer. In stage 1, we genotyped 99,632 SNPs in 1,257 affected individuals and 1,336 controls from Ontario. In stages 2-4, we performed serial replication studies using 4,024 affected individuals and 4,042 controls from Seattle, Newfoundland and Scotland. We identified one locus on chromosome 8q24 and another on 9p24 having combined odds ratios (OR) for stages 1-4 of 1.18 (trend; P = 1.41 x 10(-8)) and 1.14 (trend; P = 1.32 x 10(-5)), respectively. Additional analyses in 2,199 affected individuals and 2,401 controls from France and Europe supported the association at the 8q24 locus (OR = 1.16, trend; 95% confidence interval (c.i.): 1.07-1.26; P = 5.05 x 10(-4)). A summary across all seven studies at the 8q24 locus was highly significant (OR = 1.17, c.i.: 1.12-1.23; P = 3.16 x 10(-11)). This locus has also been implicated in prostate cancer.     

Amygdala intercalated neurons are required for expression of fear extinction

Congruent findings from studies of fear learning in animals and humans indicate that research on the circuits mediating fear constitutes our best hope of understanding human anxiety disorders. In mammals, repeated presentations of a conditioned stimulus that was previously paired to a noxious stimulus leads to the gradual disappearance of conditioned fear responses. Although much evidence suggests that this extinction process depends on plastic events in the amygdala, the underlying mechanisms remain unclear. Intercalated (ITC) amygdala neurons constitute probable mediators of extinction because they receive information about the conditioned stimulus from the basolateral amygdala (BLA), and contribute inhibitory projections to the central nucleus (CEA), the main output station of the amygdala for conditioned fear responses. Thus, after extinction training, ITC cells could reduce the impact of conditioned-stimulus-related BLA inputs to the CEA by means of feed-forward inhibition. Here we test the hypothesis that ITC neurons mediate extinction by lesioning them with a toxin that selectively targets cells expressing micro-opioid receptors (microORs). Electron microscopic observations revealed that the incidence of microOR-immunoreactive synapses is much higher in ITC cell clusters than in the BLA or CEA and that microORs typically have a post-synaptic location in ITC cells. In keeping with this, bilateral infusions of the microOR agonist dermorphin conjugated to the toxin saporin in the vicinity of ITC neurons caused a 34% reduction in the number of ITC cells but no significant cell loss in surrounding nuclei. Moreover, ITC lesions caused a marked deficit in the expression of extinction that correlated negatively with the number of surviving ITC neurons but not CEA cells. Because ITC cells exhibit an unusual pattern of receptor expression, these findings open new avenues for the treatment of anxiety disorders.     

Environmental and energy gains from using molten magnesium–sodium–potassium chlorides for electro-metallisation of refractory metal oxides

The molten eutectic mixture of magnesium,sodium and potassium chlorides(Mg Cl2–Na Cl–KCl) has inappreciable solubility for oxide ions,and can help disengage a carbon anode from the oxide ions generated at a metal oxide cathode,and effectively avoid carbon dioxide formation.This "disengaging strategy" was successfully demonstrated in electro-reduction of solid oxides of zirconium and tantalum.It has led to significantly higher current efficiency(93%),and lower energy consumption(1.4 k W h kg 1) in electrolysis of tantalum oxide to tantalum metal compared to the conventional electrolysis in molten calcium chloride(e.g.78% and 2.4 k W h/kg-Ta).     

Human immunodeficiency viruses: SIV infection in wild gorillas

Chimpanzees (Pan troglodytes troglodytes) from west central Africa are recognized as the reservoir of simian immunodeficiency viruses (SIVcpzPtt) that have crossed at least twice to humans: this resulted in the AIDS pandemic (from human immunodeficiency virus HIV-1 group M) in one instance and infection of just a few individuals in Cameroon (by HIV-1 group N) in another. A third HIV-1 lineage (group O) from west central Africa also falls within the SIVcpzPtt radiation, but the primate reservoir of this virus has not been identified. Here we report the discovery of HIV-1 group O-like viruses in wild gorillas.     

Stoichiometry and turnover in single, functioning membrane protein complexes

Many essential cellular processes are carried out by complex biological machines located in the cell membrane. The bacterial flagellar motor is a large membrane-spanning protein complex that functions as an ion-driven rotary motor to propel cells through liquid media. Within the motor, MotB is a component of the stator that couples ion flow to torque generation and anchors the stator to the cell wall. Here we have investigated the protein stoichiometry, dynamics and turnover of MotB with single-molecule precision in functioning bacterial flagellar motors in Escherichia coli. We monitored motor function by rotation of a tethered cell body, and simultaneously measured the number and dynamics of MotB molecules labelled with green fluorescent protein (GFP-MotB) in the motor by total internal reflection fluorescence microscopy. Counting fluorophores by the stepwise photobleaching of single GFP molecules showed that each motor contains approximately 22 copies of GFP-MotB, consistent with approximately 11 stators each containing two MotB molecules. We also observed a membrane pool of approximately 200 GFP-MotB molecules diffusing at approximately 0.008 microm2 s(-1). Fluorescence recovery after photobleaching and fluorescence loss in photobleaching showed turnover of GFP-MotB between the membrane pool and motor with a rate constant of the order of 0.04 s(-1): the dwell time of a given stator in the motor is only approximately 0.5 min. This is the first direct measurement of the number and rapid turnover of protein subunits within a functioning molecular machine.     

The origins and the future of microfluidics

The manipulation of fluids in channels with dimensions of tens of micrometres--microfluidics--has emerged as a distinct new field. Microfluidics has the potential to influence subject areas from chemical synthesis and biological analysis to optics and information technology. But the field is still at an early stage of development. Even as the basic science and technological demonstrations develop, other problems must be addressed: choosing and focusing on initial applications, and developing strategies to complete the cycle of development, including commercialization. The solutions to these problems will require imagination and ingenuity.     

The DNA sequence, annotation and analysis of human chromosome 3

After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion.     

Analysis of Freemium Business Model Considering Network Externalities and Consumer Uncertainty

An emerging business model increasingly used by companies in the online software market is to provide both a free basic version and a paid premium version for a service or a product to customers. Such a setting is often called freemium model. The existence of the free version can reduce the customer uncertainty regarding the evaluation of the commercial software and make use of network effect to improve the firm’s profit. However, the freemium model may also have the cannibalization effect which can hurt the profit. Hence, the firm needs to determine the optimal content for the free version and the optimal price for the premium version to maximize its profit. In this paper, first, we obtain the optimal decisions of the freemium model and their properties. Second, we compare the freemium model with the traditional charge-for-everything model that all content of the product need to be charged in terms of the profit, customer welfare, and social welfare. The results show that when customer underestimates the value of the software significantly and the true value of the software is high enough, the freemium model can generate higher profit, higher customer welfare, and higher social welfare. Otherwise, the freemium model may not deliver the desired results.