A genetically humanized mouse model for hepatitis C virus infection

Hepatitis C virus (HCV) remains a major medical problem. Antiviral treatment is only partially effective and a vaccine does not exist. Development of more effective therapies has been hampered by the lack of a suitable small animal model. Although xenotransplantation of immunodeficient mice with human hepatocytes has shown promise, these models are subject to important challenges. Building on the previous observation that CD81 and occludin comprise the minimal human factors required to render mouse cells permissive to HCV entry in vitro, we attempted murine humanization via a genetic approach. Here we show that expression of two human genes is sufficient to allow HCV infection of fully immunocompetent inbred mice. We establish a precedent for applying mouse genetics to dissect viral entry and validate the role of scavenger receptor type B class I for HCV uptake. We demonstrate that HCV can be blocked by passive immunization, as well as showing that a recombinant vaccinia virus vector induces humoral immunity and confers partial protection against heterologous challenge. This system recapitulates a portion of the HCV life cycle in an immunocompetent rodent for the first time, opening opportunities for studying viral pathogenesis and immunity and comprising an effective platform for testing HCV entry inhibitors in vivo.     

The genome of the green anole lizard and a comparative analysis with birds and mammals

The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments. Among amniotes, genome sequences are available for mammals and birds, but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes. Also, A. carolinensis mobile elements are very young and diverse-more so than in any other sequenced amniote genome. The GC content of this lizard genome is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds. We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations.     

城乡规划类专业制图软件比较分析

提高学生实验应用技能是高等学校教学改革的重要内容之一。重点分析了AutoCAD、Photoshop、Corel draw、Mapin-fo、Arcgis等城乡规划类专业制图软件的优劣势。提出了制图课程教学改革的相关对策建议:加强师资队伍建设,及时进行制图课程教学改革,加大实验室建设投入,最终达到提高城乡规划类专业学生制图操作技能之目的。     

试论以合力论思想构建和谐社会

中国共产党提出了构建和谐社会的新理念,把和谐社会的建设同经济建设、政治建设、文化建设有力地结合起来,形成了构建和谐社会的合力论思想。构建社会主义和谐社会,必须坚持马克思主义关于历史发展的合力论思想,即“促正”、“纠反”,构建和谐社会,并构建由四大合力机制组成的合力机制体系。     

Interaction between adjacent left-lateral strike-slip faults and thrust faults: the 1976 Songpan earthquake sequence

Based on the published focal mechanisms we have built the fault model of the main shocks of the 1976 Songpan earthquake sequence and calculated the coseismic Coulomb stress changes in the region. The results show that most of the aftershocks had occurred in the region where the Coulomb stresses had been increased, indicating a triggering relationship between the main shocks and the aftershocks. We also show that the first main shock （Ms = 7.2）, which is a left-lateral slip event, had increased the Coulomb stresses by 5×10^5 Pa at the second main shock （a thrust event with Ms = 6.7）. Therefore, we conclude that the first main shock had triggered the second main shock. The third main shock is also a left-lateral event, however, the triggering relationship between the third main shock and the previous two events is less obvious. General model calculations show that there is a good triggering relationship between adjacent left-lateral slip fault and thrust fault, but triggering between parallel slip faults is rather weak.     

Science,truth and dictatorship: Wishful thinking or wishful speaking?

This paper argues for a novel way of addressing questions about the relationship between politics and science: in terms of norms of communication, rather than norms of cognition. The first half of the paper motivates this general shift through close study of the concept of "wishful speaking"; arguing that this vice - rather than the more familiar "wishful thinking" - better captures real-life cases, such as the Lysenko affair. The second half builds on the ethics of communication to develop an account of the proper role of non-epistemic values in justification in terms of "value-aptness".     

The Future of Life and What it Means for Humanity

Vidal’s (Found Sci, 2010) and Rottiers’s (Found Sci, 2010) commentaries on my (2010) paper raised a number of important issues about the possible future trajectory of evolution and its implications for humanity. My response emphasizes that despite the inherent uncertainty involved in extrapolating the trajectory of evolution into the far future, the possibilities it reveals nonetheless have significant strategic implications for what we do with our lives here and now, individually and collectively. One important implication is the replacement of postmodern scepticism and relativism with an evolutionary grand narrative that can guide humanity to participate successfully in the future evolution of life in the universe.     

The patterns and dynamics of genomic instability in metastatic pancreatic cancer

Pancreatic cancer is an aggressive malignancy with a five-year mortality of 97-98%, usually due to widespread metastatic disease. Previous studies indicate that this disease has a complex genomic landscape, with frequent copy number changes and point mutations, but genomic rearrangements have not been characterized in detail. Despite the clinical importance of metastasis, there remain fundamental questions about the clonal structures of metastatic tumours, including phylogenetic relationships among metastases, the scale of ongoing parallel evolution in metastatic and primary sites, and how the tumour disseminates. Here we harness advances in DNA sequencing to annotate genomic rearrangements in 13 patients with pancreatic cancer and explore clonal relationships among metastases. We find that pancreatic cancer acquires rearrangements indicative of telomere dysfunction and abnormal cell-cycle control, namely dysregulated G1-to-S-phase transition with intact G2-M checkpoint. These initiate amplification of cancer genes and occur predominantly in early cancer development rather than the later stages of the disease. Genomic instability frequently persists after cancer dissemination, resulting in ongoing, parallel and even convergent evolution among different metastases. We find evidence that there is genetic heterogeneity among metastasis-initiating cells, that seeding metastasis may require driver mutations beyond those required for primary tumours, and that phylogenetic trees across metastases show organ-specific branches. These data attest to the richness of genetic variation in cancer, brought about by the tandem forces of genomic instability and evolutionary selection.