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31.
Kalay E Yigit G Aslan Y Brown KE Pohl E Bicknell LS Kayserili H Li Y Tüysüz B Nürnberg G Kiess W Koegl M Baessmann I Buruk K Toraman B Kayipmaz S Kul S Ikbal M Turner DJ Taylor MS Aerts J Scott C Milstein K Dollfus H Wieczorek D Brunner HG Hurles M Jackson AP Rauch A Nürnberg P Karagüzel A Wollnik B 《Nature genetics》2011,43(1):23-26
Functional impairment of DNA damage response pathways leads to increased genomic instability. Here we describe the centrosomal protein CEP152 as a new regulator of genomic integrity and cellular response to DNA damage. Using homozygosity mapping and exome sequencing, we identified CEP152 mutations in Seckel syndrome and showed that impaired CEP152 function leads to accumulation of genomic defects resulting from replicative stress through enhanced activation of ATM signaling and increased H2AX phosphorylation. 相似文献
32.
Chasman DI Schürks M Anttila V de Vries B Schminke U Launer LJ Terwindt GM van den Maagdenberg AM Fendrich K Völzke H Ernst F Griffiths LR Buring JE Kallela M Freilinger T Kubisch C Ridker PM Palotie A Ferrari MD Hoffmann W Zee RY Kurth T 《Nature genetics》2011,43(7):695-698
Migraine is a common, heterogeneous and heritable neurological disorder. Its pathophysiology is incompletely understood, and its genetic influences at the population level are unknown. In a population-based genome-wide analysis including 5,122 migraineurs and 18,108 non-migraineurs, rs2651899 (1p36.32, PRDM16), rs10166942 (2q37.1, TRPM8) and rs11172113 (12q13.3, LRP1) were among the top seven associations (P < 5 × 10(-6)) with migraine. These SNPs were significant in a meta-analysis among three replication cohorts and met genome-wide significance in a meta-analysis combining the discovery and replication cohorts (rs2651899, odds ratio (OR) = 1.11, P = 3.8 × 10(-9); rs10166942, OR = 0.85, P = 5.5 × 10(-12); and rs11172113, OR = 0.90, P = 4.3 × 10(-9)). The associations at rs2651899 and rs10166942 were specific for migraine compared with non-migraine headache. None of the three SNP associations was preferential for migraine with aura or without aura, nor were any associations specific for migraine features. TRPM8 has been the focus of neuropathic pain models, whereas LRP1 modulates neuronal glutamate signaling, plausibly linking both genes to migraine pathophysiology. 相似文献
33.
Terhi Vihervaara Riikka-Liisa Uronen Gerd Wohlfahrt Ingemar Björkhem Elina Ikonen Vesa M. Olkkonen 《Cellular and molecular life sciences : CMLS》2011,68(3):537-551
ORP1L is an oxysterol binding homologue that regulates late endosome (LE) positioning. We show that ORP1L binds several oxysterols
and cholesterol, and characterize a mutant, ORP1L Δ560–563, defective in oxysterol binding. While wild-type ORP1L clusters
LE, ORP1L Δ560–563 induces LE scattering, which is reversed by disruption of the endoplasmic reticulum (ER) targeting FFAT
motif, suggesting that it is due to enhanced LE–ER interactions. Endosome motility is reduced upon overexpression of ORP1L.
Both wild-type ORP1L and the Δ560–563 mutant induce the recruitment of both dynactin and kinesin-2 on LE. Most of the LE decorated
by overexpressed ORP1L fail to accept endocytosed dextran or EGF, and the transfected cells display defective degradation
of internalized EGF. ORP1L silencing in macrophage foam cells enhances endosome motility and results in inhibition of [3H]cholesterol efflux to apolipoprotein A-I. These data demonstrate that LE motility and functions in both protein and lipid
transport are regulated by ORP1L. 相似文献
34.
Zircon isotopic ages from magnetite quartzites of the Jianping metamorphic complex, western Liaoning Province 总被引:1,自引:0,他引:1
ö 《科学通报(英文版)》2000,45(6):547-551
Using the zircon Pb evaporation method and high precise ion microprobe analyses, zircon isotopic ages in supracrustal magnetite
quartzites from Jianping metamorphic complex have been obtained. The results show that the deposition of the supracrustal
rocks occurred around 2 552–2 520 Ma and the peak of granulite facies metamorphism reached at about 2 487 Ma; about (1 806±16)
Ma, i.e. Mid-Proterozoic, the other possible metamorphic event with relatively low intensity happened in the study area. It
is speculated that a likely tectonic setting where the Jianping metamorphic complex formed is an active continental margin
that is involved in continental collision and crustal thickening shortly after its formation. 相似文献
35.
J. v. Schönfeld M. Rünzi H. Goebell M. K. Müller 《Cellular and molecular life sciences : CMLS》1995,51(6):556-560
It is well known that oral administration of camostate induces hyperplasia and hypertrophy of the rat pancreas. It is not clear, however, whether pancreatic hormone and enzyme secretion are affected by camostate treatment.In rats, daily administration of 200 mg camostate/kg b. wt for 14 days significantly increased pancreatic weight and pancreatic content of DNA, protein, amylase, lipase, trypsin and chymotrypsin, as well as the amount of insulin, glucagon and somatostatin. In the intact animal, blood glucose levels and serum concentrations of insulin and glucagon in response to an oral glucose load were not impaired after camostate treatment. In the isolated perfused pancreas, however, insulin and glucagon secretions were reduced, whereas somatostatin release was not affected. The volume of pancreatic juice produced by the unstimulated isolated perfused organ, as well as protein and enzyme secretion, were increased after camostate treatment. Likewise, the isolated perfused pancreas from camostate-treated rats secreted a larger volume of pancreatic juice and more protein in response to cholecystokinin (CCK), while enzyme secretion was affected in a non-parallel manner: amylase release was markedly reduced, lipase release was unchanged, and release of trypsin and chymotrypsin was increased. 相似文献
36.
37.
Viable metacyclic forms of T. cruzi, Y strain, treated with an adequate dose of actinomycin D (50 micrograms Act-D/ml/10(7) parasites/ml for 72 h at 28 degrees C) showed the following properties: 1) they lost their ability to replicate in culture medium, in blood and in tissues of normal mice and were no longer able to incorporate tritiated thymidine; 2) they could not penetrate into Vero cells and could not replicate inside normal macrophages; 3) they retained their immunogenicity and the ability to protect mice against a virulent infection; 4) they did not induce histological lesions as described in chronic experimental Chagas' disease. 相似文献
38.
Summary Stimulation of aminopyrine demethylation induced in rats by oral or i.p. administration of phenobarbital was partially inhibited in animals receiving daily treatments of 2×200 mg/kg gum Arabic p.o. 相似文献
39.
Summary The relationship between the pH of urine and the measured activity of ULDH, UAP and UAA was investigated in vivo and in vitro. The activity of ULDH and UAP is only half as much, or less, in acid urine (pH 4.8–5.1) as it is in alkaline urine (pH 7.0–8.1). The UAA activity, however, does not change in the pH range measured. The isoenzymes ULDH 2–4, present in alkaline urine of normal adults, does not appear in acid urine. 相似文献
40.
Summary In the isolated guinea-pig heart, it has been found that the amount of adenosine which slows the heart rate is about 100 times greater than the amount which increases coronary flow. 相似文献