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When isolated liver nuclei from methylchol-anthrene-treated rats are incubated with benzopyrene, covalent adducts are formed between DNA and the ultimate carcinogen, benzopyrene diol epoxide. Brief digestion with DNaseI, or micrococcal nuclease has been used to demonstrate that benzopyrene metabolites bind more readily to DNA in chromatin regions with a more open, active conformation than to inactive chromatin. 相似文献
3.
The Salmonella, Arizona, Shigella and Aeromonas contents of 39 snails (Achatina achatina) were investigated. Serotyping of the Salmonella isolates revealed the presence of S. manhattan, S. ndolo, S. reading, S. uppsala, and S. typhimurium. Six of 18 Shigella isolates were identified as Sh. sonnei while all the Aeromonas proved to be A. hydrophila. Fifty eight percent of these A. hydrophila isolates were enterotoxigenic, and their toxin was shown to be heat labile. All the A. hydrophila strains were both protease positive and haemolytic: 66.7% being both and haemolytic while 33.3% showed only haemolysis. 相似文献
4.
Anneleen Daemen Obi L Griffith Laura M Heiser Nicholas J Wang Oana M Enache Zachary Sanborn Francois Pepin Steffen Durinck James E Korkola Malachi Griffith Joe S Hur Nam Huh Jongsuk Chung Leslie Cope Mary Jo Fackler Christopher Umbricht Saraswati Sukumar Pankaj Seth Vikas P Sukhatme Lakshmi R Jakkula Yiling Lu Gordon B Mills Raymond J Cho Eric A Collisson Laura J van’t Veer Paul T Spellman Joe W Gray 《Genome biology》2013,14(10):R110
5.
You Li Hisato Yagi Ezenwa Obi Onuoha Rama Rao Damerla Richard Francis Yoshiyuki Furutani Muhammad Tariq Stephen M. King Gregory Hendricks Cheng Cui Manush Saydmohammed Dong Min Lee Maliha Zahid Iman Sami Linda Leatherbury Gregory J. Pazour Stephanie M. Ware Toshio Nakanishi Elizabeth Goldmuntz Michael Tsang Cecilia W. Lo 《PLoS genetics》2016,12(2)
Heterotaxy, a birth defect involving left-right patterning defects, and primary ciliary dyskinesia (PCD), a sinopulmonary disease with dyskinetic/immotile cilia in the airway are seemingly disparate diseases. However, they have an overlapping genetic etiology involving mutations in cilia genes, a reflection of the common requirement for motile cilia in left-right patterning and airway clearance. While PCD is a monogenic recessive disorder, heterotaxy has a more complex, largely non-monogenic etiology. In this study, we show mutations in the novel dynein gene DNAH6 can cause heterotaxy and ciliary dysfunction similar to PCD. We provide the first evidence that trans-heterozygous interactions between DNAH6 and other PCD genes potentially can cause heterotaxy. DNAH6 was initially identified as a candidate heterotaxy/PCD gene by filtering exome-sequencing data from 25 heterotaxy patients stratified by whether they have airway motile cilia defects. dnah6 morpholino knockdown in zebrafish disrupted motile cilia in Kupffer’s vesicle required for left-right patterning and caused heterotaxy with abnormal cardiac/gut looping. Similarly DNAH6 shRNA knockdown disrupted motile cilia in human and mouse respiratory epithelia. Notably a heterotaxy patient harboring heterozygous DNAH6 mutation was identified to also carry a rare heterozygous PCD-causing DNAI1 mutation, suggesting a DNAH6/DNAI1 trans-heterozygous interaction. Furthermore, sequencing of 149 additional heterotaxy patients showed 5 of 6 patients with heterozygous DNAH6 mutations also had heterozygous mutations in DNAH5 or other PCD genes. We functionally assayed for DNAH6/DNAH5 and DNAH6/DNAI1 trans-heterozygous interactions using subthreshold double-morpholino knockdown in zebrafish and showed this caused heterotaxy. Similarly, subthreshold siRNA knockdown of Dnah6 in heterozygous Dnah5 or Dnai1 mutant mouse respiratory epithelia disrupted motile cilia function. Together, these findings support an oligogenic disease model with broad relevance for further interrogating the genetic etiology of human ciliopathies. 相似文献
6.
Suzuki A Obi K Urabe T Hayakawa H Yamada M Kaneko S Onodera M Mizuno Y Mochizuki H 《Journal of neurochemistry》2002,82(4):953-960
Neuronal progenitor cells (NPC) are particularly suited as the target population for genetic and cellular therapy of neurological disorders such as Parkinson's disease or stroke. However, genetic modification of these cells using retroviral vectors remains a great challenge because of the low transduction rate and the need for fetal calf serum (FCS) during the transduction process that induces the cell differentiation to mature neurons. To overcome these problems, we developed a new retrovirus production system in which the simplified retroviral vector GCDNsap engineered to be resistant to denovo methylation was packaged in the vesicular stomatitis virus G protein (VSV-G), concentrated by centrifugation, and resuspended in serum-free medium (StemPro-34 SFM). In transduction experiments using enhanced green fluorescent protein (EGFP) as a marker, the concentrated FCS-free virus supernatant infected NPC at a high rate, while maintaining the ability of these cells to self-renew and differentiate in vitro. When such cells were grafted into mouse brains, EGFP-expressing NPC were detected in the region around the injection site at 8 weeks post transplantation. These findings suggest that the gene transfer system described here may provide a useful tool to genetically modify NPC for treatments of neurological disorders. 相似文献
7.
The clinical use of doxorubicin, an antineoplasmic agent, is limited by its extensive cardiotoxicity which is mediated by the mobilization of intracellular Ca2+ from SR. In order to elucidate the mechanism of Ca2+ release, we analyzed the binding sites of doxorubicin on rabbit cardiac SR (sarcoplasmic reticulum). One of the binding sites was identified as cardiac-type ryanodine receptor (RyR2) which was purified by immunoprecipitation from solubilized cardiac SR in the presence of DTT. Ligand blot analysis revealed the direct binding of doxorubicin to RyR2. The binding of doxorubicin to RyR2 was specific and displaced by caffeine. Both doxorubicin and caffeine enhanced [3H]-ryanodine binding to RyR2 in a Ca2+ dependent manner. These results suggest that there is a doxorubicin binding site on RyR2. 相似文献
8.
Murata Yoshiyuki; Fujita Masashi; Nakatani Takuya; Obi Ichiro; Kakutani Tadaaki 《Plant & cell physiology》1998,39(4):452-457
Characteristics of Ca2+-binding on the plasma membrane of barleymesophyll cells were studied by a microelec-trophoretic method.The results indicated that Na+ ions could cause nonspecificreduction but not specific reduction in the total amount ofCa2+ bound to the plasma membrane of (salt-tolerant) barleymesophyll cells. (Received October 13, 1997; Accepted January 23, 1998) 相似文献
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10.
Krig SR Frietze S Simion C Miller JK Fry WH Rafidi H Kotelawala L Qi L Griffith OL Gray JW Carraway KL Sweeney C 《Molecular cancer research : MCR》2011,9(10):1406-1417
Lrig1 is the founding member of the Lrig family and has been implicated in the negative regulation of several oncogenic receptor tyrosine kinases including ErbB2. Lrig1 is expressed at low levels in several cancer types but is overexpressed in some prostate and colorectal tumors. Given this heterogeneity, whether Lrig1 functions to suppress or promote tumor growth remains a critical question. Previously, we found that Lrig1 was poorly expressed in ErbB2-positive breast cancer, suggesting that Lrig1 has a growth-inhibitory role in this tumor type. However, breast cancer is a complex disease, with ErbB2-positive tumors accounting for just 25% of all breast cancers. To gain a better understanding of the role of Lrig1 in breast cancer, we examined its expression in estrogen receptor α (ERα)-positive disease which accounts for the majority of breast cancers. We find that Lrig1 is expressed at significantly higher levels in ERα-positive disease than in ERα-negative disease. Our study provides a molecular rationale for Lrig1 enrichment in ERα-positive disease by showing that Lrig1 is a target of ERα. Estrogen stimulates Lrig1 accumulation and disruption of this induction enhances estrogen-dependent tumor cell growth, suggesting that Lrig1 functions as an estrogen-regulated growth suppressor. In addition, we find that Lrig1 expression correlates with prolonged relapse-free survival in ERα-positive breast cancer, identifying Lrig1 as a new prognostic marker in this setting. Finally, we show that ErbB2 activation antagonizes ERα-driven Lrig1 expression, providing a mechanistic explanation for Lrig1 loss in ErbB2-positive breast cancer. This work provides strong evidence for a growth-inhibitory role for Lrig1 in breast cancer. 相似文献