International research ethics: progress, but not perfection

To the uninitiated researcher, bioethics can be a confusing and sometimes bureaucratic process. The recent debates in international research ethics have both increased understanding of contentious issues while extending confusion to the international arena. Here, we attempt to demystify bioethics, or more specifically international research ethics, by defining ethics in the context of morality, reviewing core Western ethical principles, and highlighting challenges in international research ethics.     

噬菌体：微小却不简单

噬菌体是专一感染细菌等微生物的病毒,是地球上多样性最高和最丰富的生物体,是生物学研究中重要的模式生物,同时是抗生素耐药菌的天然抗菌剂。噬菌体研究的相关成果极大地推动了生物学各个领域的发展。     

Bacteria are small but not stupid: cognition, natural genetic engineering and socio-bacteriology

Forty years' experience as a bacterial geneticist has taught me that bacteria possess many cognitive, computational and evolutionary capabilities unimaginable in the first six decades of the twentieth century. Analysis of cellular processes such as metabolism, regulation of protein synthesis, and DNA repair established that bacteria continually monitor their external and internal environments and compute functional outputs based on information provided by their sensory apparatus. Studies of genetic recombination, lysogeny, antibiotic resistance and my own work on transposable elements revealed multiple widespread bacterial systems for mobilizing and engineering DNA molecules. Examination of colony development and organization led me to appreciate how extensive multicellular collaboration is among the majority of bacterial species. Contemporary research in many laboratories on cell-cell signaling, symbiosis and pathogenesis show that bacteria utilise sophisticated mechanisms for intercellular communication and even have the ability to commandeer the basic cell biology of 'higher' plants and animals to meet their own needs. This remarkable series of observations requires us to revise basic ideas about biological information processing and recognise that even the smallest cells are sentient beings.     

细菌小RNA的研究

小RNA(smallRNA,sRNA)在基因表达调控和生长发育等方面发挥着重要作用。细菌sRNA多通过与靶mRNA配对,转录后水平影响目的mRNA翻译或(和)稳定性,对基因的表达进行调节,以影响细胞的多种生理功能。本文从细菌sRNA与真核生物微RNA(microRNA,miRNA)的比较,sRNA的分类,sRNA分子伴侣Hfq及sRNA鉴别方法等方面综述了sRNA的研究进展,指出目前sRNA研究仍然存在的问题。原核生物中sRNA的大量发现和深入研究,有可能使人们对生物进化和生命的发展过程有更为深入的认识与了解。     

Infection of XC cells by MLVs and Ebola virus is endosome-dependent but acidification-independent

Inhibitors of endosome acidification or cathepsin proteases attenuated infections mediated by envelope proteins of xenotropic murine leukemia virus-related virus (XMRV) and Ebola virus, as well as ecotropic, amphotropic, polytropic, and xenotropic murine leukemia viruses (MLVs), indicating that infections by these viruses occur through acidic endosomes and require cathepsin proteases in the susceptible cells such as TE671 cells. However, as previously shown, the endosome acidification inhibitors did not inhibit these viral infections in XC cells. It is generally accepted that the ecotropic MLV infection in XC cells occurs at the plasma membrane. Because cathepsin proteases are activated by low pH in acidic endosomes, the acidification inhibitors may inhibit the viral infections by suppressing cathepsin protease activation. The acidification inhibitors attenuated the activities of cathepsin proteases B and L in TE671 cells, but not in XC cells. Processing of cathepsin protease L was suppressed by the acidification inhibitor in NIH3T3 cells, but again not in XC cells. These results indicate that cathepsin proteases are activated without endosome acidification in XC cells. Treatment with an endocytosis inhibitor or knockdown of dynamin 2 expression by siRNAs suppressed MLV infections in all examined cells including XC cells. Furthermore, endosomal cathepsin proteases were required for these viral infections in XC cells as other susceptible cells. These results suggest that infections of XC cells by the MLVs and Ebola virus occur through endosomes and pH-independent cathepsin activation induces pH-independent infection in XC cells.     

Bupivacaine, but not lidocaine, disrupts cardiolipin-containing small biomimetic unilamellar liposomes

Inadvertent intravenous administration of bupivacaine, unlike that of lidocaine, is associated with significant cardiotoxicity. However, the mechanism(s) underlying this phenomenon is uncertain. High concentrations of cardiolipin, an anionic phospholipid, are found in the mitochondria membrane of cardiomyocytes. We hypothesized that bupivacaine, but not lidocaine, interacts avidly with cardiolipin in the mitochondria membrane of cardiomyocytes and alters its integrity thereby accounting, in part, for cardiotoxicity. Accordingly, the purpose of this study was to begin to address this issue by determining the effects of bupivacaine and lidocaine on permeability of cardiolipin-containing biomimetic small unilamellar liposomes. We found that bupivacaine, but not lidocaine, elicited a significant, concentration-dependent increase in carboxyfluorescein release from cardiolipin-containing small unilamellar liposomes (size, 165 nm) composed of egg yolk phosphatidylcholine and cholesterol (p < 0.05). Both drugs had no significant effects on carboxyfluorescein release from liposomes devoid of cardiolipin (p > 0.5). Collectively, these data indicate that bupivacaine, but not lidocaine, interacts avidly and selectively with biomimetic small unilamellar liposomes containing cardiolipin and disrupts their integrity. We suggest that these interactions underlie, in part, bupivacaine-induced cardiotoxicity.     

African trypanosomiasis research: 100 years of progress, but questions and problems still remain

Past and present progress in our understanding of African trypanosomiasis is briefly reviewed. Although tremendous scientific strides have been achieved, an epidemic of the disease is currently underway. Three areas of research which are believed necessary for the control of African trypanosomiasis are discussed. It is suggested that a better understanding of the host-parasite relationship is essential; more emphasis and a broader approach to drug development is required; and finally, further research into the socio-economic aspects of African trypanosomiasis is urgently needed before the human disease can again be controlled.     

The Ebola Virus Glycoprotein Contributes to but Is Not Sufficient for Virulence In Vivo

Among the Ebola viruses most species cause severe hemorrhagic fever in humans; however, Reston ebolavirus (REBOV) has not been associated with human disease despite numerous documented infections. While the molecular basis for this difference remains unclear, in vitro evidence has suggested a role for the glycoprotein (GP) as a major filovirus pathogenicity factor, but direct evidence for such a role in the context of virus infection has been notably lacking. In order to assess the role of GP in EBOV virulence, we have developed a novel reverse genetics system for REBOV, which we report here. Together with a previously published full-length clone for Zaire ebolavirus (ZEBOV), this provides a unique possibility to directly investigate the role of an entire filovirus protein in pathogenesis. To this end we have generated recombinant ZEBOV (rZEBOV) and REBOV (rREBOV), as well as chimeric viruses in which the glycoproteins from these two virus species have been exchanged (rZEBOV-RGP and rREBOV-ZGP). All of these viruses could be rescued and the chimeras replicated with kinetics similar to their parent virus in tissue culture, indicating that the exchange of GP in these chimeric viruses is well tolerated. However, in a mouse model of infection rZEBOV-RGP demonstrated markedly decreased lethality and prolonged time to death when compared to rZEBOV, confirming that GP does indeed contribute to the full expression of virulence by ZEBOV. In contrast, rREBOV-ZGP did not show any signs of virulence, and was in fact slightly attenuated compared to rREBOV, demonstrating that GP alone is not sufficient to confer a lethal phenotype or exacerbate disease in this model. Thus, while these findings provide direct evidence that GP contributes to filovirus virulence in vivo, they also clearly indicate that other factors are needed for the acquisition of full virulence.