Administration of the antitumor drug mitoguazone protects normal thymocytes against spontaneous and etoposide-induced apoptosis

The suggestion has been made that polyamines may be involved in the control of cell death, since exceedingly high or low levels induce apoptosis in different cell systems. For a deeper insight into the relationship between apoptosis and polyamine metabolism, we investigated in vitro the effect on rat thymocytes of mitoguazone (MGBG, which inhibits S-adenosylmethionine decarboxylase, i.e. a key enzyme in the polyamine biosynthetic pathway). Thymocytes were selected as an especially suitable model system, since they undergo spontaneous apoptosis in vivo and can be easily induced to apoptose in vitro by etoposide, used here as an apoptogenic agent. MGBG protected thymocytes from both spontaneous and drug-induced apoptosis, and this protective effect was associated with a decrease in polyamine oxidase activity and total polyamine levels.Received 7 July 2004; received after revision 2 September 2004; accepted 9 September 2004     

Novel aspects of glypican glycobiology

Mutations in glypican genes cause dysmorphic and overgrowth syndromes in men and mice, abnormal development in flies and worms, and defective gastrulation in zebrafish and ascidians. All glypican core proteins share a characteristic pattern of 14 conserved cysteine residues. Upstream from the C-terminal membrane anchorage are 3–4 heparan sulfate attachment sites. Cysteines in glypican-1 can become nitrosylated by nitric oxide in a copper-dependent reaction. When glypican-1 is exposed to ascorbate, nitric oxide is released and participates in deaminative cleavage of heparan sulfate at sites where the glucosamines have a free amino group. This process takes place while glypican-1 recycles via a nonclassical, caveolin-1-associated route. Glypicans are involved in growth factor signalling and transport, e.g. of polyamines. Cargo can be unloaded from heparan sulfate by nitric oxide-dependent degradation. How glypican and its degradation products and the cargo exit from the recycling route is an enigma.Received 27 November 2003; received after revision 8 January 2004; accepted 13 January 2004     

Angiogenesis and signal transduction in endothelial cells

Endothelial cells receive multiple information from their environment that eventually leads them to progress along all the stages of the process of formation of new vessels. Angiogenic signals promote endothelial cell proliferation, increased resistance to apoptosis, changes in proteolytic balance, cytoskeletal reorganization, migration and, finally, differentiation and formation of a new vascular lumen. We aim to review herein the main signaling cascades that become activated in angiogenic endothelial cells as well as the opportunities of modulating angiogenesis through pharmacological interference with these signaling mechanisms. We will deal mainly with the mitogen-activated protein kinases pathway, which is very important in the transduction of proliferation signals; the phosphatidylinositol-3-kinase/protein kinase B signaling system, particularly essential for the survival of the angiogenic endothelium; the small GTPases involved in cytoskeletal reorganization and migration; and the kinases associated to focal adhesions which contribute to integrate the pathways from the two main sources of angiogenic signals, i.e. growth factors and the extracellular matrix.Received 13 February 2004; received after revision 25 March 2004; accepted 19 April 2004     

Requirement of Src kinases Lyn, Hck and Fgr for BCR-ABL1-induced B-lymphoblastic leukemia but not chronic myeloid leukemia

The Abl kinase inhibitor imatinib mesylate is the preferred treatment for Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia (CML) in chronic phase but is much less effective in CML blast crisis or Ph(+) B-cell acute lymphoblastic leukemia (B-ALL). Here, we show that Bcr-Abl activated the Src kinases Lyn, Hck and Fgr in B-lymphoid cells. BCR-ABL1 retrovirus-transduced marrow from mice lacking all three Src kinases efficiently induced CML but not B-ALL in recipients. The kinase inhibitor CGP76030 impaired the proliferation of B-lymphoid cells expressing Bcr-Abl in vitro and prolonged survival of mice with B-ALL but not CML. The combination of CGP76030 and imatinib was superior to imatinib alone in this regard. The biochemical target of CGP76030 in leukemia cells was Src kinases, not Bcr-Abl. These results implicate Src family kinases as therapeutic targets in Ph(+) B-ALL and suggest that simultaneous inhibition of Src and Bcr-Abl kinases may benefit individuals with Ph(+) acute leukemia.     

Genesis of zircon and its constraints on interpretation of U-Pb age

Zircon U-Pb dating is the most commonly used method for isotopic geochronology. However, it has been a difficult issue when relating zircon U-Pb ages to metamorphic conditions in complex metamorphic rocks. Much progress has been made in the past decade with respect to the genesis of zircon and its constraints on interpretation of U-Pb age. Three methods have been proposed to link zircon U-Pb age to metamorphic conditions: ( i ) internal structure; ( ii ) trace element feature; (iii) mineral inclusion composition. Magmatic zircon shows typical oscillatory zoning and/or sector zoning, whereas metamorphic zircon has internal structures such as no zoned, weakly zoned, cloudy zoned, sector zoned, planar zoned, and patched zoned ones. Zircons formed in different geological environments generally have characteristic internal structures. Magmatic zircons from different rock types have variable trace element abundances, with a general trend of increasing trace element abundances in zircons from ultramafic through mafic to granitic rocks. Zircons formed under different metamorphic conditions have different trace element characteristics that can be used to relate their formation to metamorphic conditions. It is an effective way to relate zircon growth to certain P-T conditions by studying the trace element partitioning between coexisting metamorphic zircon and garnet in high-grade metamorphic rocks containing both zircon and garnet. Primary mineral inclusions in zircon can also provide unambiguous constraints on its formation conditions. Therefore, interpretation of zircon U-Pb ages can be constrained by its internal structure, trace element composition, mineral inclusion and so on.     

Immunogenicity of recombinant fowl-pox virus co-expressing structural protein precursor P1-2A and proteinase 3C of FMDV

Two recombinant plasmids, pUTA2P1 and pUTAL3CP1, were constructed by inserting structural protein precursor P1-2A and proteinase 3C of foot-and-mouth disease virus (FMDV) into fowl-pox virus (FPV) recombinant vectors pUTA-2 and pUTA-16-LacZ respectively, and two recombinant FPVs (vUTA2P1 and vUTAL3CP1) screened by the RT-PCR, IFA assay and Western blotting assay were obtained successfully. Mice injected respectively with rFPVs were induced high level specific anti-FMDV antibodies, increasing of T subtypes, and higher cytotoxicities of splenocytes than those of control groups. These results indicated that a new method was used to construct a potential candidate vaccine of FMDV.     

AC2 and AC4 proteins of <Emphasis Type="Italic">Tomato yellow leaf curl China virus</Emphasis> and <Emphasis Type="Italic">Tobacco curly shoot virus</Emphasis> mediate suppression of RNA silencing

Tomato yellow leaf curl China virus Y10 isolate (TYLCCNV-Y10) alone could systemically infect host plants such as Nicotiana benthamiana without symptoms. In contrast, Tobacco curly shoot virus Y35 isolate (TbCSV-Y35) alone induces leaf curl symptoms in N. benthamiana. When inoculated into transgenic N. benthamiana plants expressing GFP gene (line 16c), TYLCCNV-Y10 neither reverses the established GFP silencing nor blocks the onset of GFP silencing. In contrast, TbCSV-Y35 can partially reverse the established GFP silencing and block the onset of GFP silencing in new leaves. In the patch co-infiltration assays, the AC2 and AC4 proteins of TYLCCNV-Y10 and TbCSV-Y35 could suppress local GFP silencing and delay systemic GFP silencing, suggesting that they are suppressors of RNA silencing. Comparison of the accumulation levels of GFP mRNA in the co-infiltration patches showed that Y10 AC2 and Y35 AC2 proteins had similar efficiency for suppression of RNA silencing. However, Y35 AC4 protein functioned as a stronger suppressor of RNA silencing than Y10 AC4 protein. There-fore, the pathogenicity difference between TbCSV-Y35 and TYLCCNV-Y10 may be related to the functional difference in their AC4 proteins.     

Self-assembled structure of alkyloxy substituted benzoic acid methyl ester on HOPG：An STM study

Self-assembled structures of 3,4,5-tris-dodecy-loxy benzoic acid methyl ester (E12), 3,4,5-tris-tetradecy-loxy-benzoic acid methyl ester (E14) and their mixture (E12/E14) have been studied on HOPG by scanning tunneling microscopy (STM). Dimer-like patterns induced by dipole-dipole interaction are observed in E12 and E14 monolayers. The molecules form close-packed rows and interdigitate with the alkyl chains in adjacent molecules. The structural differences are proposed to be from the different length of substituted alkyl chains. Owing to similar adsorption energy, phase separation is observed in the E12 and E14 mixed adlayer with different domains.     

Special IR properties of palladium nanoparticles and their aggregations in CO molecular probe infrared spectroscopy

Dispersed Pd nanoparticles (Pdn) have been synthesized by reducing H2PdCI4 with ethanol, and stabilized using poly(vinylpyrrolidone) (PVP). The Pdn is applied to the glassy carbon substrate to form a thin film, and then the potential cyclic scanning at 50 mV.s^-1 from -0.25 to 1.25 V was carried out for about 30 min to form the aggregations of Pdn (Pdn^ag). FTIR spectroscopy of both transmission and reflection modes was employed to study CO adsorption on Pdn and Pdn^ag in both solidlliquid and solidlgas interfaces. It has been revealed that CO adsorption on Pdn film yields two IRbands near 1964 and 1906 cm-1, which are assigned to IR absorption of CO bonded on asymmetric and symmetric bridge sites, respectively. In contrast to the IR properties of CO adsorbed on Pdn, only species of CO bonded on asymmetric bridge sites was determined on Pdn^ag, and the direction of the IR band near 1963 cm^-1 is completely inverted. The full width at half-maximum (FWHM) of the COB^as band near 1964 cm^-1 is measured to be 14 cm^-1 on Pdn film, while it is 24 cm^-1 on Pdn^ag film. The results of the present study demonstrated that the inverting of the IR band direction is a general phenomenon that is closely related to the interaction between nanoparticles in aggregation of Pdn.