Ectopic beta-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis

The effect of high-density lipoprotein (HDL) in protecting against atherosclerosis is usually attributed to its role in 'reverse cholesterol transport'. In this process, HDL particles mediate the efflux and the transport of cholesterol from peripheral cells to the liver for further metabolism and bile excretion. Thus, cell-surface receptors for HDL on hepatocytes are chief partners in the regulation of cholesterol homeostasis. A high-affinity HDL receptor for apolipoprotein A-I (apoA-I) was previously identified on the surface of hepatocytes. Here we show that this receptor is identical to the beta-chain of ATP synthase, a principal protein complex of the mitochondrial inner membrane. Different experimental approaches confirm this ectopic localization of components of the ATP synthase complex and the presence of ATP hydrolase activity at the hepatocyte cell surface. Receptor stimulation by apoA-I triggers the endocytosis of holo-HDL particles (protein plus lipid) by a mechanism that depends strictly on the generation of ADP. We confirm this effect on endocytosis in perfused rat liver ex vivo by using a specific inhibitor of ATP synthase. Thus, membrane-bound ATP synthase has a previously unsuspected role in modulating the concentrations of extracellular ADP and is regulated by a principal plasma apolipoprotein.     

Diagrams and alien ways of thinking

The recent wave of data on exoplanets lends support to METI ventures (Messaging to Extra-Terrestrial Intelligence), insofar as the more exoplanets we find, the more likely it is that “exominds” await our messages. Yet, despite these astronomical advances, there are presently no well-confirmed tests against which to check the design of interstellar messages. In the meantime, the best we can do is distance ourselves from terracentric assumptions. There is no reason, for example, to assume that all inferential abilities are language-like. With that in mind, I argue that logical reasoning does not have to be couched in symbolic notation. In diagrammatic reasoning, inferences are underwritten, not by rules, but by transformations of self-same qualitative signs. I use the Existential Graphs of C. S. Peirce to show this. Since diagrams are less dependent on convention and might even be generalized to cover non-visual senses, I argue that METI researchers should add some form of diagrammatic representations to their repertoire. Doing so can shed light, not just on alien minds, but on the deepest structures of reasoning itself.     

The nucleotide receptor P2Y13 is a key regulator of hepatic High-Density Lipoprotein (HDL) endocytosis

Cell surface receptors for high-density lipoprotein (HDL) on hepatocytes are major partners in the regulation of cholesterol homeostasis. We recently identified a cell surface ATP synthase as a high-affinity receptor for HDL apolipoprotein A-I (apoA-I) on human hepatocytes. Stimulation of this ectopic ATP synthase by apoA-I triggered a low-affinity-receptor-dependent HDL endocytosis by a mechanism strictly related to the generation of ADP. This suggests that nucleotide G-protein- coupled receptors of the P2Y family are molecular components in this pathway. Only P2Y₁ and P2Y₁₃ are present on the membrane of hepatocytes. Using both a pharmacological approach and small interference RNA, we identified P2Y₁₃ as the main partner in hepatic HDL endocytosis, in cultured cells as well as in situ in perfused mouse livers. We also found a new important action of the antithrombotic agent AR-C69931MX as a strong activator of P2Y₁₃-mediated HDL endocytosis. Received 9 May 2005; received after revision 24 June 2005; accepted 1 September 2005     

T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV

Many viruses, including retroviruses, are characterized by their specific cell tropism. Lymphadenopathy-associated virus (LAV) is a human lymphotropic retrovirus isolated from patients with acquired immune deficiency syndrome (AIDS) or related syndromes, that displays selective tropism for a subset of T lymphocytes defined by the expression of a surface glycoprotein of relative molecular mass 62,000 (62K) termed T4 (refs 6-8). This glycoprotein delineates a subset of T lymphocytes with mainly helper/inducer functions, while T lymphocytes of the reciprocal subset express a glycoprotein termed T8, have mainly cytotoxic/suppressor activities, and are unable to replicate LAV. Such a tropism may be controlled at the genomic level by regulatory sequences, as described for the human T-cell leukaemia viruses HTLV-I and -II (refs 2, 3). Alternatively or concomitantly, productive cell infection may be controlled at the membrane level, requiring the interaction of a specific cellular receptor with the virus envelope, as demonstrated recently for Epstein-Barr virus (EBV). Therefore, we have investigated whether the T4 molecule itself is related to the receptor for LAV. We report here that preincubation of T4+ lymphocytes with three individual monoclonal antibodies directed at the T4 glycoprotein blocked cell infection by LAV. This blocking effect was specific, as other monoclonal antibodies--such as antibody to histocompatibility locus antigen (HLA) class II or anti-T-cell natural killer (TNK) target--directed at other surface structures strongly expressed on activated cultured T4+ cells, did not prevent LAV infection. Direct virus neutralization by monoclonal antibodies was also ruled out. These results strongly support the view that a surface molecule directly involved in cellular functions acts as, or is related to, the receptor for a human retrovirus.     

利用光纤光栅实现压力和温度同时测量

结合光纤光栅弹簧管压力传感器的结构特点 ,在悬臂梁的上下两面分别粘贴两个应力和温度灵敏系数基本相同的光纤光栅 ,通过分别测量光纤光栅对的波长位移 ,实现了压力和温度的同时测量 ,压力和温度测量的分辨率分别为 0 .1 4 MPa和 0 .5℃ .     

Skewed maturation of memory HIV-specific CD8 T lymphocytes

Understanding the lineage differentiation of memory T cells is a central question in immunology. We investigated this issue by analysing the expression of the chemokine receptor CCR7, which defines distinct subsets of naive and memory T lymphocytes with different homing and effector capacities and antiviral immune responses to HIV and cytomegalovirus. Ex vivo analysis of the expression of CD45RA and CCR7 antigens, together with in vitro analysis of the cell-division capacity of different memory CD8+ T-cell populations, identified four subsets of HIV- and CMV-specific CD8+ T lymphocytes, and indicated the following lineage differentiation pattern: CD45RA+ CCR7+ --> CD45RA- CCR7+ --> CD45RA- CCR7- --> CD45RA+ CCR7-. Here we demonstrate through analysis of cell division (predominantly restricted to the CCR7+ CD8+ T-cell subsets) that the differentiation of antigen-specific CD8+ T cells is a two-step process characterized initially by a phase of proliferation largely restricted to the CCR7+ CD8+ cell subsets, followed by a phase of functional maturation encompassing the CCR7- CD8+ cell subsets. The distribution of these populations in HIV- and CMV-specific CD8+ T cells showed that the HIV-specific cell pool was predominantly (70%) composed of pre-terminally differentiated CD45RA- CCR7- cells, whereas the CMV-specific cell pool consisted mainly (50%) of the terminally differentiated CD45RA+ CCR7- cells. These results demonstrate a skewed maturation of HIV-specific memory CD8+ T cells during HIV infection.     

Photosensitization and feeding deterrence ofEuxoa messoria (Lepidoptera: Noctuiidae) by α-terthienyl,a naturally occurring thiophene from the Asteraceae

Summary Alpha-terthienyl, a phototoxic thiophene derivative from species in the Asteraceae reduced feeding and growth of the phytophagous lepidopteran,Euxoa messoria, when incorporated into artificial diets at a concentration of 100 ppm. The effects of this substance were substantially enhanced by including photosensitizing near-UV radiation in the trials. The results suggest that the phototoxic properties of this secondary substance provide significant protection to the plants containing it.This work was supported by NSERC and Agriculture Canada.     

一种新型叶绿体表达系统的构建

针对目前的叶绿体转基因技术存在载体构建步骤繁琐耗时的问题,建立了一种新型的不需自带启动子的叶绿体表达系统,选择模式植物烟草叶绿体中的假基因作为外源基因的插入位点.通过基因枪转化法获得4株独立的叶绿体转化植株.此新技术可实现叶绿体载体构建的时间、技术成本最小化,从而促进转基因叶绿体的应用.