Dramatic attenuation of hypusine formation on eukaryotic initiation factor 5A during senescence of IMR-90 human diploid fibroblasts

Deoxyhypusine synthase catalyzes the conversion of lysine to deoxyhypusine residue on the eukaryotic initiation factor 5A (eIF-5A) precursor using spermidine as the substrate. Subsequent hydroxylation of the deoxyhypusine residue completes hypusine formation on eIF-5A. Hypusine formation is one of the most specific polyamine-dependent biochemical events in eukaryotic cells. Although changes in polyamine metabolism have been demonstrated in human diploid fibroblasts during senescence (Chen and Chang, 1986, J. Cell. Physiol., 128:27–32.), it is unclear whether or not polyamine-dependent hypusine formation itself is an age-dependent biochemical event. In the present study, hypusine-forming activity was measured by a radiolabeling assay in cells whose polyamines have been depleted by prior treatment of α-difluoromethyl ornithine (DFMO). In addition, an in vitro cross-labeling assay was developed for simultaneous measurement of the deoxyhypusine synthase activity and protein substrate (eIF-5A precursor) amount. We showed that the hypusine-forming activity in low-passage presenescent IMR-90 cells [population doubling level (PDL) = 15–23, termed young cells] was prominently induced by serum whereas little or no hypusine-forming activity could be detected in late-passage senescent cells (PDL = 46–54, termed old cells). The striking difference in hypusine-forming activity between young and old cells was due to changes in both deoxyhypusine synthase activity and eIF-5A precursor amount in IMR-90 cells during senescence. However, Northern blot analysis showed no significant difference in the eIF-5A messenger RNA (mRNA) between young and old cells, suggesting that the age-dependent attenuation of eIF-5A precursor protein may be regulated at either translational or posttranslational level. J. Cell. Physiol. 170:248–254, 1997. © 1997 Wiley-Liss, Inc.     

一种简易繁殖潜蝇姬小蜂的方法

简要介绍了以蚕豆作为寄主作物,南美斑潜蝇作寄主,在自然条件下利用纱岗笼罩进行潜蝇姬小蜂Diglyphus isaea Walker的人工繁殖方法。     

High‐Performance and Stable Perovskite Solar Cells Based on Dopant‐Free Arylamine‐Substituted Copper(II) Phthalocyanine Hole‐Transporting Materials

A power conversion efficiency (PCE) as high as 19.7% is achieved using a novel, low‐cost, dopant‐free hole transport material (HTM) in mixed‐ion solution‐processed perovskite solar cells (PSCs). Following a rational molecular design strategy, arylamine‐substituted copper(II) phthalocyanine (CuPc) derivatives are selected as HTMs, reaching the highest PCE ever reported for PSCs employing dopant‐free HTMs. The intrinsic thermal and chemical properties of dopant‐free CuPcs result in PSCs with a long‐term stability outperforming that of the benchmark doped 2,2′,7,7′‐Tetrakis‐(N,N‐di‐p‐methoxyphenylamine)‐9,9′‐Spirobifluorene (Spiro‐OMeTAD)‐based devices. The combination of molecular modeling, synthesis, and full experimental characterization sheds light on the nanostructure and molecular aggregation of arylamine‐substituted CuPc compounds, providing a link between molecular structure and device properties. These results reveal the potential of engineering CuPc derivatives as dopant‐free HTMs to fabricate cost‐effective and highly efficient PSCs with long‐term stability, and pave the way to their commercial‐scale manufacturing. More generally, this case demonstrates how an integrated approach based on rational design and computational modeling can guide and anticipate the synthesis of new classes of materials to achieve specific functions in complex device structures.     

Affinity-based proteomics reveal cancer-specific networks coordinated by Hsp90

Most cancers are characterized by multiple molecular alterations, but identification of the key proteins involved in these signaling pathways is currently beyond reach. We show that the inhibitor PU-H71 preferentially targets tumor-enriched Hsp90 complexes and affinity captures Hsp90-dependent oncogenic client proteins. We have used PU-H71 affinity capture to design a proteomic approach that, when combined with bioinformatic pathway analysis, identifies dysregulated signaling networks and key oncoproteins in chronic myeloid leukemia. The identified interactome overlaps with the well-characterized altered proteome in this cancer, indicating that this method can provide global insights into the biology of individual tumors, including primary patient specimens. In addition, we show that this approach can be used to identify previously uncharacterized oncoproteins and mechanisms, potentially leading to new targeted therapies. We further show that the abundance of the PU-H71-enriched Hsp90 species, which is not dictated by Hsp90 expression alone, is predictive of the cell's sensitivity to Hsp90 inhibition.     

Copper-Mediated Mitochondrial Fission/Fusion Is Associated with Intrinsic Apoptosis and Autophagy in the Testis Tissues of Chicken

Biological Trace Element Research - The aim of this study is to investigate whether copper (Cu) could induce testicular poisoning and influence the mitochondrial dynamics, apoptosis, and autophagy...     

中国的脊棱齿象属(Stegolophodon)化石

剑齿象属 Stegodon 起源于脊棱齿象属 Stegolophodon,两者都是亚洲大陆晚新生代的特有动物,本文讨论两属中一些种的性质和分类位置问题,并记述了药铺脊棱齿象 Stegolophodon officinalis 的新材料.     

极低密度脂蛋白对巨噬细胞载脂蛋白E基因表达的调节

巨噬细胞（M）是动脉粥样硬化（AS）斑块中泡沫细胞的主要来源之一,它可通过其表面的多种脂蛋白受体介导摄取合APOB或APOE的脂蛋白,导致M的脂质增加．此外,M有较强的分泌ApOE的能力[1],这一现象虽已发现多年,但意义尚不清楚VLDL是一种含APOE的脂蛋白,它能通过M膜上识别APOE的受体进入M,从而促进Mg内脂质堆积,并与AS密切相关[2,3]．流行病学调查发现在我国的高脂血症中2／3为VLDL升高为主的高甘油三酯（HTG）血症．另外,Evans等报道HTG血症患者的血浆中以ApoE－poorVLDL升高为主,它们在血浆中清除的速率较Apo…     

Synthesis and investigation of novel 6-(1,2,3-triazol-4-yl)-4-aminoquinazolin derivatives possessing hydroxamic acid moiety for cancer therapy

By merging the critical pharmacophore of EGFR/HER2 and HDAC inhibitors into one compound, a novel series of EGFR, HER-2, and HDAC multitarget inhibitors were synthesized. Compounds 9a–l contained 4-anilinoquinazolines with C-6 triazole-linked long alkyl chains of hydroxamic acid and displayed excellent inhibition against these enzymes (compound 9d exhibited the best inhibitory potency on wild-type EGFR, HDAC1, and HDAC6 with IC₅₀ values 0.12 nM, 0.72 nM and 3.2 nM individually). Furthermore, compounds 9b and 9d potently inhibited proliferation of five human cancer cell lines (with IC₅₀ values between 0.49 and 8.76 μM). Further mechanistic study revealed that compound 9d also regulated the phosphorylation of EGFR and HER2 and histone H3 hyperacetylation on the cellular level and induced remarkable apoptosis in BT-474 cells. Therefore, our study suggested that a system network-based multi-target drug design strategy might provided an alternate drug design method, by taking into account the synergy effect of EGFR, HER-2 and HDAC.