Introduction of new genetic material into pluripotent haematopoietic stem cells of the mouse

An infectious retrovirus vector has been used to transfer a bacterial gene encoding resistance to the neomycin analogue G418 into pluripotent haematopoietic stem cells present in explanted murine bone marrow tissue. Subsequent transplantation of the cells into lethally irradiated mice results in engraftment of the animals with donor haematopoietic tissue containing the bacterial gene. This approach affords an efficient and rapid means of re-introducing genetically modified tissue into intact organisms and provides a system whereby the expression and regulation of cloned genes can be followed within the context of a well characterized developmental programme.     

运动导体感应涡电流分布的解析计算与仿真验证

在电磁应用中,分析导体在电磁场激励作用下感应涡电流的分布有利于深入理解导体与激励源之间的相互作用。因其复杂性,运动导体在电磁场作用下涡电流分布的规律尚未得到充分研究。采用二维傅里叶变换方法,推导出圆形通电激励线圈作用下导电平板涡电流分布的积分形式表达式;该表达式与线圈的激励频率、导体的材料特性、形状及运动速度等参数有关。计算并分析了在相同线圈激励条件下,导体以不同速度运动时,表面涡电流密度分布特点,总结了导体运动速度对涡电流分布的影响规律;并用有限元方法对解析计算结果进行了验证。所采用的解析方法具有方便、快速的优点,该方法也可以用于其他涡电流问题的分析计算。     

RNA molecules stimulate prion protein conversion

Much evidence supports the hypothesis that the infectious agents of prion diseases are devoid of nucleic acid, and instead are composed of a specific infectious protein. This protein, PrP(Sc), seems to be generated by template-induced conformational change of a normally expressed glycoprotein, PrP(C) (ref. 2). Although numerous studies have established the conversion of PrP(C) to PrP(Sc) as the central pathogenic event of prion disease, it is unknown whether cellular factors other than PrP(C) might be required to stimulate efficient PrP(Sc) production. We investigated the biochemical amplification of protease-resistant PrP(Sc)-like protein (PrPres) using a modified version of the protein-misfolding cyclic amplification method. Here we report that stoichiometric transformation of PrP(C) to PrPres in vitro requires specific RNA molecules. Notably, whereas mammalian RNA preparations stimulate in vitro amplification of PrPres, RNA preparations from invertebrate species do not. Our findings suggest that host-encoded stimulatory RNA molecules may have a role in the pathogenesis of prion disease. They also provide a practical approach to improve the sensitivity of diagnostic techniques based on PrPres amplification.     

Points of control in inflammation

Inflammation is a complex set of interactions among soluble factors and cells that can arise in any tissue in response to traumatic, infectious, post-ischaemic, toxic or autoimmune injury. The process normally leads to recovery from infection and to healing, However, if targeted destruction and assisted repair are not properly phased, inflammation can lead to persistent tissue damage by leukocytes, lymphocytes or collagen. Inflammation may be considered in terms of its checkpoints, where binary or higher-order signals drive each commitment to escalate, go signals trigger stop signals, and molecules responsible for mediating the inflammatory response also suppress it, depending on timing and context. The non-inflammatory state does not arise passively from an absence of inflammatory stimuli; rather, maintenance of health requires the positive actions of specific gene products to suppress reactions to potentially inflammatory stimuli that do not warrant a full response.     

An endocannabinoid mechanism for stress-induced analgesia

Acute stress suppresses pain by activating brain pathways that engage opioid or non-opioid mechanisms. Here we show that an opioid-independent form of this phenomenon, termed stress-induced analgesia, is mediated by the release of endogenous marijuana-like (cannabinoid) compounds in the brain. Blockade of cannabinoid CB(1) receptors in the periaqueductal grey matter of the midbrain prevents non-opioid stress-induced analgesia. In this region, stress elicits the rapid formation of two endogenous cannabinoids, the lipids 2-arachidonoylglycerol (2-AG) and anandamide. A newly developed inhibitor of the 2-AG-deactivating enzyme, monoacylglycerol lipase, selectively increases 2-AG concentrations and, when injected into the periaqueductal grey matter, enhances stress-induced analgesia in a CB1-dependent manner. Inhibitors of the anandamide-deactivating enzyme fatty-acid amide hydrolase, which selectively elevate anandamide concentrations, exert similar effects. Our results indicate that the coordinated release of 2-AG and anandamide in the periaqueductal grey matter might mediate opioid-independent stress-induced analgesia. These studies also identify monoacylglycerol lipase as a previously unrecognized therapeutic target.     

The MLH1 D132H variant is associated with susceptibility to sporadic colorectal cancer

Most susceptibility to colorectal cancer (CRC) is not accounted for by known risk factors. Because MLH1, MSH2 and MSH6 mutations underlie high-penetrance CRC susceptibility in hereditary nonpolyposis colon cancer (HNPCC), we hypothesized that attenuated alleles might also underlie susceptibility to sporadic CRC. We looked for gene variants associated with HNPCC in Israeli probands with familial CRC unstratified with respect to the microsatellite instability (MSI) phenotype. Association studies identified a new MLH1 variant (415G-->C, resulting in the amino acid substitution D132H) in approximately 1.3% of Israeli individuals with CRC self-described as Jewish, Christian and Muslim. MLH1 415C confers clinically significant susceptibility to CRC. In contrast to classic HNPCC, CRCs associated with MLH1 415C usually do not have the MSI defect, which is important for clinical mutation screening. Structural and functional analyses showed that the normal ATPase function of MLH1 is attenuated, but not eliminated, by the MLH1 415G-->C mutation. The new MLH1 variant confers a high risk of CRC and identifies a previously unrecognized mechanism in microsatellite-stable tumors. These studies suggest that variants of mismatch repair proteins with attenuated function may account for a higher proportion of susceptibility to sporadic microsatellite-stable CRC than previously assumed.     

Science Is Not Always “Self-Correcting”

Some prominent scientists and philosophers have stated openly that moral and political considerations should influence whether we accept or promulgate scientific theories. This widespread view has significantly influenced the development, and public perception, of intelligence research. Theories related to group differences in intelligence are often rejected a priori on explicitly moral grounds. Thus the idea, frequently expressed by commentators on science, that science is “self-correcting”—that hypotheses are simply abandoned when they are undermined by empirical evidence—may not be correct in all contexts. In this paper, documentation spanning from the early 1970s to the present is collected, which reveals the influence of scientists’ moral and political commitments on the study of intelligence. It is suggested that misrepresenting findings in science to achieve desirable social goals will ultimately harm both science and society.     

“文化簇”与中国科学技术史研究——北京大学“科学文化史”讨论班述要

劳埃德和席文合著的《道与名》一书中提出的"文化簇"概念,其意义不同于此前人文学者们使用的同样短语,是一个研究科学史的新工具,它超越了科学智识史、建制史和社会史之间的分野,对于中国科学史的研究尤有意义。北京大学任定成讨论班成员已经将其用于宋代医学知识扩散、秋石史、斗蟋史、针刺镇痛机理研究史、中国现代制碱技术史、中国科学化运动史和中宣部科学处历史的研究。