Distribution of repetitious DNA in human chromosomes

Zusammenfassung Studien von in situ DNS/RNS-Hybriden (oder Mischflüssigkeiten) zwischen RNS und verschiedenen Fraktionen von DNS und Metaphase-Chromosomen des Menschen ergaben, dass hauptsächlich die wiederholt vorkommende DNS-Fraktion C _o t = 0 0.005 sich in der centromeren und telomeren Region befindet.

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Supported in part by grants No. G-267 and No. G-373 from the Robert A. Welch Foundation, and grants No. DRG-269 and No. 1061 from the Damon Runyon Memorial Fund for Cancer Research     

Imbalance between pSmad3 and Notch induces CDK inhibitors in old muscle stem cells

Adult skeletal muscle robustly regenerates throughout an organism's life, but as the muscle ages, its ability to repair diminishes and eventually fails. Previous work suggests that the regenerative potential of muscle stem cells (satellite cells) is not triggered in the old muscle because of a decline in Notch activation, and that it can be rejuvenated by forced local activation of Notch. Here we report that, in addition to the loss of Notch activation, old muscle produces excessive transforming growth factor (TGF)-beta (but not myostatin), which induces unusually high levels of TGF-beta pSmad3 in resident satellite cells and interferes with their regenerative capacity. Importantly, endogenous Notch and pSmad3 antagonize each other in the control of satellite-cell proliferation, such that activation of Notch blocks the TGF-beta-dependent upregulation of the cyclin-dependent kinase (CDK) inhibitors p15, p16, p21 and p27, whereas inhibition of Notch induces them. Furthermore, in muscle stem cells, Notch activity determines the binding of pSmad3 to the promoters of these negative regulators of cell-cycle progression. Attenuation of TGF-beta/pSmad3 in old, injured muscle restores regeneration to satellite cells in vivo. Thus a balance between endogenous pSmad3 and active Notch controls the regenerative competence of muscle stem cells, and deregulation of this balance in the old muscle microniche interferes with regeneration.     

Progesterone inhibits human endothelial cell proliferation through a p53-dependent pathway

Previous studies have shown that progesterone inhibits endothelial cell proliferation through a nuclear receptor-mediated mechanism. Here, we further demonstrate that progesterone at physiologic levels (5 – 500 nM) dose- and time-dependently inhibited DNA synthesis of cultured human umbilical vein endothelial cells (HUVEC). The mRNA and protein levels of p21, p27, and p53 in HUVEC were increased by progesterone. The formation of CDK2-p21 and CDK2-p27 were increased and the CDK2 activity was decreased in the progesterone-treated HUVEC. The progesterone-inhibited [3H]thymidine incorporation was completely blocked when the expressions of p21 and p27 were knocked-down together. Transfection of HUVEC with dominant negative p53 cDNA prevented the progesterone-induced increases in p21 and p27 promoter activity and protein level, decreases in thymidine incorporation, and capillary-like tube formation. Matrigel angiogenesis assay in mice demonstrated the antiangiogenic effect of progesterone in vivo. These findings demonstrate for the first time that progesterone inhibited endothelial cell proliferation through a p53-dependent pathway. Received 28 July 2008; received after revision 25 September 2008; accepted 26 September 2008     

Error-prone replication of oxidatively damaged DNA by a high-fidelity DNA polymerase

Aerobic respiration generates reactive oxygen species that can damage guanine residues and lead to the production of 8-oxoguanine (8oxoG), the major mutagenic oxidative lesion in the genome. Oxidative damage is implicated in ageing and cancer, and its prevalence presents a constant challenge to DNA polymerases that ensure accurate transmission of genomic information. When these polymerases encounter 8oxoG, they frequently catalyse misincorporation of adenine in preference to accurate incorporation of cytosine. This results in the propagation of G to T transversions, which are commonly observed somatic mutations associated with human cancers. Here, we present sequential snapshots of a high-fidelity DNA polymerase during both accurate and mutagenic replication of 8oxoG. Comparison of these crystal structures reveals that 8oxoG induces an inversion of the mismatch recognition mechanisms that normally proofread DNA, such that the 8oxoG.adenine mismatch mimics a cognate base pair whereas the 8oxoG.cytosine base pair behaves as a mismatch. These studies reveal a fundamental mechanism of error-prone replication and show how 8oxoG, and DNA lesions in general, can form mismatches that evade polymerase error-detection mechanisms, potentially leading to the stable incorporation of lethal mutations.     

The pattern of esterase variation in the Mimulus glabratus complex (Scrophulariaceae)

Disc gel electrophoretic assays of Mimulus plants showed young stems to contain at least 15 esterase bands. The 6 bands in the center of the gels were highly reproducible. Eighty-one populations representative of all the cytotaxonomic groups and of the Western Hemisphere geographic range of the Mimulus glabratus complex were assayed for those 6 bands. There was no apparent correlation between the distribution of the esterase bands and important environmental parameters such as elevation and latitude. Hence, their distribution did not appear to reflect environmental adaptive values. Each population was monophonic for its particular combination and intensity of esterase bands which is consistent with our previous suggestion that genetic drift is a strong component of the evolutionary pattern of the complex.     

Zebrafish rgs4 is essential for motility and axonogenesis mediated by Akt signaling

The schizophrenia susceptibility gene, Rgs4, is one of the most intensively studied regulators of G-protein signaling members, well known to be fundamental in regulating neurotransmission. However, little is known about its role in the developing nervous system. We have isolated zebrafish rgs4 and shown that it is transcribed in the developing nervous system. Rgs4 knockdown did not affect neuron number and patterning but resulted in locomotion defects and aberrant development of axons. This was confirmed using a selective Rgs4 inhibitor, CCG-4986. Rgs4 knockdown also attenuated the level of phosphorylated-Akt1, and injection of constitutively-activated AKT1 rescued the motility defects and axonal phenotypes in the spinal cord but not in the hindbrain and trigeminal neurons. Our in vivo analysis reveals a novel role for Rgs4 in regulating axonogenesis during embryogenesis, which is mediated by another schizophrenia-associated gene, Akt1, in a region-specific manner.     

Evaluation of the going-concern status for companies: An ensemble framework-based model

Issuing a going-concern opinion is a difficult and complex task for auditors. The auditors have to take into account different critical factors in order to make the right decision based on information obtained from the auditing process. This study adopts the so-called “random forest” approach (based on the ensemble method) to assist auditors in making such a decision. To investigate the corresponding effect of the proposed approach, we conduct a series of experiments and a performance comparison. The results show that the random forest method outperforms the baseline methods in terms of the accuracy rate, ROC area, kappa value, type II error, precision, and recall rate. The proposed approach is proven to be more accurate and stable than previous methods.     

Immobilization of cross-linked In-doped Mo(O,S)2 on cellulose nanofiber for effective organic-compound degradation under visible light illumination

Relatively small amounts of In-doped Mo(O,S)₂(IMS) catalysts(10%, 20%, and 30%) were deposited on cellulose nanofiber(CNF) by cross-linking them with functional groups of siloxane and epoxy to form CNF-IMS hybrid composites. The as-prepared hybrid composites were characterized and tested their performances toward the photo degradations of cationic(MB and Rh B) and anionic(MO) dyes. As indium was doped into Mo(O,S)₂ lattice to form solid-solution, the charge transfer and pho...     

用间羧基偶氮氯膦─树脂相分光光度法测定钪

本文研究了间羧基偶氮氯膦（ＣＰＡｍＫ）在树脂相中与钪的显色条件。在盐酸介质中，以阴离子交换树脂吸附Ｓｃ－ＣＰＡｍＫ络阴离子。钪与试剂在０．０６ｍｏｌ／Ｌ盐酸介质中生成１：２的螯合物，在波长６７５ｎｍ处有最大吸收，表观摩尔吸光系数ε＝１４０×１０５Ｌ·ｍｏｌ－１·ｃｍ－１。在５０ｍｌ溶液中，１－７μｇＳｃ／５０ｍｌ符合比耳定律，应用于合金中钪的直接测定，结果良好。