Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death

Mitochondria play an important role in energy production, Ca2+ homeostasis and cell death. In recent years, the role of the mitochondria in apoptotic and necrotic cell death has attracted much attention. In apoptosis and necrosis, the mitochondrial permeability transition (mPT), which leads to disruption of the mitochondrial membranes and mitochondrial dysfunction, is considered to be one of the key events, although its exact role in cell death remains elusive. We therefore created mice lacking cyclophilin D (CypD), a protein considered to be involved in the mPT, to analyse its role in cell death. CypD-deficient mice were developmentally normal and showed no apparent anomalies, but CypD-deficient mitochondria did not undergo the cyclosporin A-sensitive mPT. CypD-deficient cells died normally in response to various apoptotic stimuli, but showed resistance to necrotic cell death induced by reactive oxygen species and Ca2+ overload. In addition, CypD-deficient mice showed a high level of resistance to ischaemia/reperfusion-induced cardiac injury. Our results indicate that the CypD-dependent mPT regulates some forms of necrotic death, but not apoptotic death.     

Spin-torque diode effect in magnetic tunnel junctions

There is currently much interest in the development of 'spintronic' devices, in which harnessing the spins of electrons (rather than just their charges) is anticipated to provide new functionalities that go beyond those possible with conventional electronic devices. One widely studied example of an effect that has its roots in the electron's spin degree of freedom is the torque exerted by a spin-polarized electric current on the spin moment of a nanometre-scale magnet. This torque causes the magnetic moment to rotate at potentially useful frequencies. Here we report a very different phenomenon that is also based on the interplay between spin dynamics and spin-dependent transport, and which arises from unusual diode behaviour. We show that the application of a small radio-frequency alternating current to a nanometre-scale magnetic tunnel junction can generate a measurable direct-current (d.c.) voltage across the device when the frequency is resonant with the spin oscillations that arise from the spin-torque effect: at resonance (which can be tuned by an external magnetic field), the structure exhibits different resistance states depending on the direction of the current. This behaviour is markedly different from that of a conventional semiconductor diode, and could form the basis of a nanometre-scale radio-frequency detector in telecommunication circuits.     

Enhancement of the analgesic effect of morphine by sodium diethyldithiocarbamate in rats

Zusammenfassung Nach DDC-Vorbehandlung wurde bei männlichen Ratten eine deutliche Potenzierung der Morphinanalgesie beobachtet. Es konnte nachgewiesen werden, dass dieses Phänomen nicht durch die nach DDC-Gabe auftretende Veränderung des CA-Gehaltes im Gehirn bedingt ist.     

Enzymatic catalysis of anti-Baldwin ring closure in polyether biosynthesis

Polycyclic polyether natural products have fascinated chemists and biologists alike owing to their useful biological activity, highly complex structure and intriguing biosynthetic mechanisms. Following the original proposal for the polyepoxide origin of lasalocid and isolasalocid and the experimental determination of the origins of the oxygen and carbon atoms of both lasalocid and monensin, a unified stereochemical model for the biosynthesis of polyether ionophore antibiotics was proposed. The model was based on a cascade of nucleophilic ring closures of postulated polyepoxide substrates generated by stereospecific oxidation of all-trans polyene polyketide intermediates. Shortly thereafter, a related model was proposed for the biogenesis of marine ladder toxins, involving a series of nominally disfavoured anti-Baldwin, endo-tet epoxide-ring-opening reactions. Recently, we identified Lsd19 from the Streptomyces lasaliensis gene cluster as the epoxide hydrolase responsible for the epoxide-opening cyclization of bisepoxyprelasalocid A to form lasalocid A. Here we report the X-ray crystal structure of Lsd19 in complex with its substrate and product analogue to provide the first atomic structure-to our knowledge-of a natural enzyme capable of catalysing the disfavoured epoxide-opening cyclic ether formation. On the basis of our structural and computational studies, we propose a general mechanism for the enzymatic catalysis of polyether natural product biosynthesis.     

Planning method of infrastructure project in China

<正>Different planning methods have been applied in private and public infrastructure projects,which resulted in different approval procedures and querry about impartiality.However,planning methods of infrastructure projects are seldom investigated up to now.The authors propose a proper project planning method which is applicable to all kinds of infrastructure projects with various fund origins.The project planning method includes a comprehensive planning framework and a six-step planning process.The financial indicator,i.e.,self-reimbursement ratio is introduced for the proper division of financial obligation between government and project company.     

Glial cells express N-CAM/D2-CAM-like polypeptides in vitro

The joining together of neurites to form fascicles and the growth of axons along glial surfaces during early development suggest that neurone-neurone and neurone-glial adhesion interactions are of considerable importance for defining nerve tracts. In vitro studies have indicated that adhesion between neurones involves a glycoprotein that has been independently studied under the names of N-CAM (for neural cell adhesion molecule), D2-CAM and BSP-2 (refs 10, 11). As N-CAM/D2-CAM appears to be a homophilic ligand that binds to N-CAM/D2-CAM polypeptide on adjacent cells, this glycoprotein is potentially important in adhesion interactions between any two N-CAM/D2-CAM-expressing cells. While it has been suggested that neurone-glial adhesion involves molecules other than N-CAM/D2-CAM, it is known that N-CAM/D2-CAM antigenic determinants are expressed by glial cells in vivo and that injection of anti-N-CAM antibodies into the eye-cup of chick embryos disrupts normal patterns of neuritic apposition to glial endfeet in the developing optic stalk. Do the molecules expressed by glia share restricted antigenic determinants, or binding domains, with N-CAM/D2-CAM, or are N-CAM/D2-CAM polypeptides expressed by glia? Here we present immunocytochemical evidence which suggests that all classes of macroglia express N-CAM/D2-CAM antigenic determinants on their surfaces and immunochemical analyses which indicate that the molecules expressed by purified astrocytes are closely similar, or identical, to at least some forms of N-CAM/D2-CAM obtained from whole brain or purified neurones. However, our results also suggest that different N-CAM/D2-CAM polypeptides may be separately expressed by neurones and astrocytes.     

Important amino acid in the hemagglutinin glycoprotein of measles virus (MV) that governs hemadsorption

Two strains of measles virus IMA and SMD that were isolated using B95a cell line show hemadsorption negative. After adaptation to Vero cells, these strains gain the ability to agglutinate AGM-RBC and show hemadsorption positive. Sequence analysis of these two kinds of virus reveals that the two strains all have a Ser (HAD negative) to Gly (HAD positive) mutation at position 546 in the H protein. Site-directed mutagenesis and expression in COS cells were used to confirm that the mutation Ser→Gly is responsible for hemadsorption alteration. Then the monoclonal antibody against CD46 was used to identify that this mutation also governs the binding function of MV H protein to CD46 receptor. The data provide a new important amino acid of MV H protein that governs the hemadsorption and binding to CD46 receptor.