Four R 1 R 2 Si(OMe) 2 type compounds were added as an external electron donor (De) in propylene polymerization with TiCl 4 /Di/MgCl 2 type supported Ziegler−Natta catalysts (Di = internal donor). Each polypropylene (PP) sample was fractionated into three parts (atactic, medium-isotactic and isotactic PP), and the number of active centers ([C*]/[Ti]) in each PP fraction was counted using 2-thiophenecarbonyl chloride as the quenching and tagging agent. The gradual decrease of [C*]/ [Ti] with De/Ti ratio is ascribed to competitive and reversible coordination of De on either central Ti of the active center or Mg adjacent to the central Ti. The former coordination leads to deactivation of C*, and the latter one leads to still living C*. The chain propagation rate constant (k p ) of the active centers producing atactic, medium-isotactic and isotactic PP change with De/ Ti in different ways. Only the k p of active centers producing isotactic PP was evidently increased by De. Enhancement in isotacticity of PP product is found to be a combined result of both deactivation of active centers by De and selective activation of the active centers that produce isotactic PP. Changing the alkyl groups of R 1 R 2 Si(OMe) 2 leads to an altered balance between the deactivation and activation effects of De.

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The protein serine/threonine phosphatase calcineurin (CN) is activated by calmodulin (CaM) in response to intracellular calcium mobilization. A widely accepted model for CN activation involves displacement of the CN autoinhibitory peptide (CN [467][468][469][470][471][472][473][474][475][476][477][478][479][480][481][482][483][484][485][486] ) from the active site upon binding of CaM. However, CN activation requires calcium binding both to the low affinity sites of CNB and to CaM, and previous studies did not dissect the individual contributions of CNB and CaM to displacement of the autoinhibitory peptide from the active site. In this work we have produced separate CN fragments corresponding to the CNA regulatory region (CNRR 381-521 , residues 381-521), the CNA catalytic domain truncated at residue 341, and the CNA-CNB heterodimer with CNA truncated at residue 380 immediately after the CNB binding helix. We show that the separately expressed regulatory region retains its ability to inhibit CN phosphatase activity of the truncated CN341 and CN380 and that the inhibition can be reversed by calcium/CaM binding. Tryptophan fluorescence quenching measurements further indicate that the isolated regulatory region inhibits CN activity by occluding the catalytic site and that CaM binding exposes the catalytic site. The results provide new support for a model in which calcium binding to CNB enables CaM binding to the CNA regulatory region, and CaM binding then instructs an activating conformational change of the regulatory region that does not depend further on CNB. Moreover, the secondary structural content of the CNRR 381-521 was tentatively addressed by Fourier transform infrared spectroscopy. The results indicate that the secondary structure of CNRR 381-521 fragment is predominantly random coil, but with significant amount of ␤-strand and ␣-helix structures. Calcineurin (CN),3 also called protein phosphatase 2B, is a calcium/CaM-dependent Ser/Thr protein phosphatase (1-3) and plays a critical role in the coupling of Ca 2ϩ signals to cellular responses (3-10). CN is stimulated by the multifunctional protein, calmodulin (CaM), which ensures the coordinated regulation of CN protein phosphatase activity, together with the activities of many other enzymes, including a large number of protein kinases under Ca 2ϩ and CaM control (7). CN has a wide range of physiological substrates (7). The complex regulation observed with CN is expected for an enzyme that is a major player in the regulation of many cellular processes. Various phosphoproteins such as inhibitor 1a, protein kinase A regulatory subunit RII, neurogranin, phosphorylase kinase a, neuromodulin, and small organic substrate p-nitrophenyl phosphate are all dephosphorylated by CN (7). Among CN substrates, the nuclear factor of activated T cells (NFAT) family of transcription factors is arguably the best understood (2, 9). NFAT is a phosphoprotein located in the cytoplasm of the resting cell. In response to physiological signals that elevate intracellular calcium, NFAT ...

Multimodal imaging that aims to advance imaging by strategically combining existing technologies with uniquely designed probes has attracted great interest in recent years. Here, Gd 3+ -functionalized gold nanoclusters (Gd-AuNCs) were synthesized for dual model (fluorescence/magnetic resonance) imaging. We designed a cyclodecapeptide that contained one tyrosine and two cysteines for the synthesis, and it biomineralized gold nanoclusters and chelated Gd 3+ ions at the same time. The Gd-AuNC probes emit an intense red fluorescence under UV light, while exhibiting a high longitudinal relaxivity of 41.5 AE 2.5 mM À1 s À1 and a low r 2 /r 1 ratio of 1.2 at 0.55 T. The versatility of the probes for dual model imaging has been demonstrated by means of cellular imaging and in vivo T 1 -weighted MRI. Thanks to the optimal size of the nanocluster, it can freely circulate in the blood pool without significant accumulation in the liver and spleen, but with a long circulation half-life (t 1/2 ) of $128 min. Moreover, the nanoclusters can be noticeably excreted from the body within a period of 24 h through renal clearance, making it attractive for in vivo multimodal imaging.

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Inorganic nanoparticle-based T 1 contrast agents with high longitudinal relaxivity (r 1 ) and low r 2 /r 1 ratio have attracted great interest in recent years. However, the r 1 relaxivity of inorganic nanoparticles reported to date is relatively low. In this work, 2.3 AE 0.1 nm paramagnetic gadolinium hydrated carbonate nanoparticles (GHC-1) with a high r 1 relaxivity of 34.8 mM À1 s À1 and low r 2 /r 1 ratio of 1.17 are synthesized using a one-pot hydrothermal process. The r 1 of GHC-1 is 9.4 times higher than that of Gd-DTPA at 0.55 T. The synthetic procedure is simple, cost effective, and easy to scale up. The nanoparticles have a small core size, an amorphous phase, and are well-coated by poly(acrylic acid). Due to the hydrophilic polymer coating, the particles are highly dispersible and stable in aqueous solution.No significant cellular or in vivo toxicity are observed for the nanoparticles, which guarantees the in vivo application of this material. Finally, we apply the nanoparticles to in vivo magnetic resonance imaging and study the biodistribution in organs. This study reveals GHC-1 as a potential candidate for a T 1 contrast agent with extraordinary ability to enhance MR images.

Risk estimates for low-dose radiation (LDR) remain controversial. The possible involvement of DNA repair-related genes in long-term low-dose-rate neutron-gamma radiation exposure is poorly understood. In this study, 60 rats were divided into control groups and irradiated groups, which were exposed to low-dose-rate n-γ combined radiation (LDCR) for 15, 30, or 60 days. The effects of different cumulative radiation doses on peripheral blood cell (PBC), subsets of T cells of peripheral blood lymphocytes (PBL) and DNA damage repair were investigated. Real-time PCR and immunoblot analyses were used to detect expression of DNA DSB-repair-related genes involved in the NHEJ pathway, such as Ku70 and Ku80, in PBL. The mRNA level of H2AX and the expression level of γ-H2AX were detected by real-time PCR, immunoblot, and flow cytometry. White blood cells (WBC) and platelets (PLT) of all ionizing radiation (IR) groups decreased significantly, while no difference was seen between the 30 day and 60 day exposure groups. The numbers of CD3(+), CD4(+) T cells and CD4(+)/CD8(+) in the PBL of IR groups were lower than in the control group. In the 30 day and 60 day exposure groups, CD8(+) T cells decreased significantly. Real-time PCR and immunoblot results showed no significant difference in the mRNA and protein expression of Ku70 and Ku80 between the control groups and IR groups. However, the mRNA of H2AX increased significantly, and there was a positive correlation with dose. There was no difference in the protein expression of γ-H2AX between 30 day and 60 day groups, which may help to explain the damage to PBL. In conclusion, PBL damage increased with cumulative dose, suggesting that γ-H2AX, but neither Ku70 nor Ku80, plays an important role in PBL impairment induced by LDCR.