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101.
Valerie?A. Arboleda Hane Lee Naghmeh Dorrani Neda Zadeh Mary Willis Colleen?Forsyth Macmurdo Melanie?A. Manning Andrea Kwan Louanne Hudgins Florian Barthelemy M.?Carrie Miceli Fabiola Quintero-Rivera Sibel Kantarci Samuel?P. Strom Joshua?L. Deignan UCLA Clinical Genomics Center Wayne?W. Grody Eric Vilain Stanley?F. Nelson 《American journal of human genetics》2015,96(3):498-506
Chromatin remodeling through histone acetyltransferase (HAT) and histone deactylase (HDAC) enzymes affects fundamental cellular processes including the cell-cycle, cell differentiation, metabolism, and apoptosis. Nonsense mutations in genes that are involved in histone acetylation and deacetylation result in multiple congenital anomalies with most individuals displaying significant developmental delay, microcephaly and dysmorphism. Here, we report a syndrome caused by de novo heterozygous nonsense mutations in KAT6A (a.k.a., MOZ, MYST3) identified by clinical exome sequencing (CES) in four independent families. The same de novo nonsense mutation (c.3385C>T [p.Arg1129∗]) was observed in three individuals, and the fourth individual had a nearby de novo nonsense mutation (c.3070C>T [p.Arg1024∗]). Neither of these variants was present in 1,815 in-house exomes or in public databases. Common features among all four probands include primary microcephaly, global developmental delay including profound speech delay, and craniofacial dysmorphism, as well as more varied features such as feeding difficulties, cardiac defects, and ocular anomalies. We further demonstrate that KAT6A mutations result in dysregulation of H3K9 and H3K18 acetylation and altered P53 signaling. Through histone and non-histone acetylation, KAT6A affects multiple cellular processes and illustrates the complex role of acetylation in regulating development and disease. 相似文献
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103.
Mustafa Akker Sibel Güldiken Tammam Sipahi Orkide Palabıyık Ayhan Tosunoğlu Özlem Çelik Nermin Tunçbilek Atakan Sezer Necdet Süt 《Molecular biology reports》2014,41(5):3541-3547
We aimed to investigate insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), insulin-like growth factor binding protein-3 (IGFBP-3) genotypes, which are thought to be involved in the pathogenesis of many solid tumors and have thus far not been studied in patients with differentiated thyroid cancer (DTC). The study consisted of 93 patients diagnosed with DTC (79 females, 14 males) and 111 healthy control subjects (63 females, 48 males). The anthropometric measurements, lipid profiles, thyroid function tests and homeostatic model assessment (HOMA) as an indicator of insulin resistance (IR) of all patients were recorded. In addition IRS-1, IRS-2 and IGFBP-3 gene polymorphisms were determined by using polymerase chain reaction and restriction fragment length polymorphism. Hardy–Weinberg equilibrium was tested for each gene polymorphisms, and genetic effects were evaluated by the Chi Square test and multiple logistic regression. Homeostasis model assessment of insulin resistance (HOMA-IR), body mass index, waist circumference and serum total cholesterol levels were significantly higher in patients with DTC than in the control group. There was no difference between the two groups with respect to IRS-1, IRS-2 and IGFBP-3 gene polymorphisms. In addition, these gene polymorphisms were found to have no effect on lymph node metastases or tumor staging. While, obesity and increased HOMA-IR may be risk factors in DTC development, we suggest that IRS-1, IRS-2 and IGFBP-3 gene polymorphisms do not play an important role in pathogenesis of DTC. 相似文献
104.
Hakan Erdem Zeliha Kocak-Tufan Omer Yilmaz Zuhal Karakurt Aykut Cilli Hulya Turkan Ozlem Yazicioglu-Mocin Nalan Adıguzel Gokay Gungor Canturk Taşcı Gulden Yilmaz Oral Oncul Aygul Dogan-Celik Ozcan Erdemli Nefise Oztoprak Yakup Tomak Asuman Inan Demet Tok Sibel Temur Hafize Oksuz Ozgur Senturk Unase Buyukkocak Fatma Yilmaz-Karadag Derya Ozturk-Engin Dilek Ozcengiz Ahmet Karakas Hayati Bilgic Hakan Leblebicioglu 《Annals of clinical microbiology and antimicrobials》2014,13(1):1-5
Background
Burkholderia cepacia complex (BCC) bacteria are highly virulent, typically multidrug-resistant, opportunistic pathogens in cystic fibrosis (CF) patients and other immunocompromised individuals. B. vietnamiensis is more often susceptible to aminoglycosides than other BCC species, and strains acquire aminoglycoside resistance during chronic CF infection and under tobramycin and azithromycin exposure in vitro, apparently from gain of antimicrobial efflux as determined through pump inhibition. The aims of the present study were to determine if oxidative stress could also induce aminoglycoside resistance and provide further observations in support of a role for antimicrobial efflux in aminoglycoside resistance in B. vietnamiensis.Findings
Here we identified hydrogen peroxide as an additional aminoglycoside resistance inducing agent in B. vietnamiensis. After antibiotic and hydrogen peroxide exposure, isolates accumulated significantly less [3H] gentamicin than the susceptible isolate from which they were derived. Strains that acquired aminoglycoside resistance during infection and after exposure to tobramycin or azithromycin overexpressed a putative resistance-nodulation-division (RND) transporter gene, amrB. Missense mutations in the repressor of amrB, amrR, were identified in isolates that acquired resistance during infection, and not in those generated in vitro.Conclusions
These data identify oxidative stress as an inducer of aminoglycoside resistance in B. vietnamiensis and further suggest that active efflux via a RND efflux system impairs aminoglycoside accumulation in clinical B. vietnamiensis strains that have acquired aminoglycoside resistance, and in those exposed to tobramycin and azithromycin, but not hydrogen peroxide, in vitro. Furthermore, the repressor AmrR is likely just one regulator of the putative AmrAB-OprM efflux system in B. vietnamiensis. 相似文献105.
Cacina C Bulgurcuoglu-Kuran S Iyibozkurt AC Yaylim-Eraltan I Cakmakoglu B 《Molecular biology reports》2012,39(2):1225-1229
In this study, we aimed to investigate a possible association between the Stromal cell-derived factor-1 (SDF-1) and CXCR4 polymorphisms and the risk of developing endometrial carcinoma. SDF-1 3??A and CXCR4 gene polymorphisms was performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism in 139 healthy individuals and 113 patients with endometrial carcinoma. In our study groups SDF-1 3??A AA genotype frequency was higher in patients that of controls and individuals who had AA genotype showed a 2.6-fold increased risk for endometrial cancer. The carriers of CXCR4 T allele were higher in patients compared with controls and individuals who had TT genotype had a 2.5-fold high risk for endometrial carcinoma. Our finding suggest that there was no significant association between the (SDF-1) and CXCR4 polymorphisms and endometrium cancer risk. Further studies in a larger population are needed to better elucidate the role of (SDF-1) and CXCR4 gene polymorphisms in the risk of endometrial carcinogenesis. To the best of our knowledge, this is the first study to show such an association. 相似文献
106.
Melatonin (MLT) is a hormone produced in the brain by the pineal gland, from the amino acid tryptophan. It is also an antioxidant hormone with a particular role in the protection of nuclear and mitochondrial DNA. In recent years, many physiological properties of MLT have been described resulting in much attention in the development of synthetic compounds possessing the indole ring. Sixteen MLT analogue indole hydrazide/hydrazone derivatives were synthesized and in vitro antioxidant activity was investigated. Most of the compounds showed significantly higher activity than MLT at 10(-3) M and 10(-4) M concentrations. 相似文献
107.
The more the mold species isolated on a culture medium, the more the sampling environment is represented accurately. According to the sampling purpose, it is crucial to use the best culture medium for mold. However, no study is available regarding the comparison of dichloran rose bengal chloramphenicol (DRBC) and Sabouraud dextrose agar with cycloheximide and chloramphenicol (SDA-CHX-CHL) culture media in terms of their application for airborne sampling, isolation, and identification of fungi. Airborne mold samples were impacted onto both DRBC and SDA-CHX-CHL, simultaneously using single-stage Andersen sampler. The limit of detection (LOD) value for airborne mold count was 7 CFU m?3 (1 colony growth on the Petri dish). The total mold counts (TMC) ranged between <7 and 504 CFU m?3 (med 56 CFU m?3) and <7 and 1218 CFU m?3 (med 259 CFU m?3), collected on SDA-CHX-CHL and DRBC, respectively. Significantly higher TMC were observed on DRBC than on SDA regardless of the sampling environment (i.e, indoor or outdoor) (p < 0.05). Among the most predominant mold genera, observation frequencies of Penicillium spp. and Aspergillus spp. on both culture media were found to be more than 70%. Observation frequencies of Cladosporium spp., Alternaria spp., and yeast were found to be higher in samples collected on DRBC than those on SDA-CHX-CHL. Finally, DRBC was found to be superior to SDA in terms of both number of colonies and number of genera isolated from the air. 相似文献
108.
109.
Yesim Ozarda Ilcol M Sibel Gurun Yavuz Taga Ismail H Ulus 《European journal of biochemistry》2003,270(5):991-999
Intraperitoneal injection of choline (30-90 mg.kg-1) produced a dose-dependent increase in serum insulin, glucose and choline levels in rats. The increase in serum insulin induced by choline (90 mg.kg-1) was blocked by pretreatment with the muscarinic acetylcholine receptor antagonists, atropine (2 mg.kg-1), pirenzepine (2 mg.kg-1) and 4-diphenylacetoxy-N-methylpiperidine (2 mg.kg-1) or the ganglionic nicotinic receptor antagonist, hexamethonium (15 mg.kg-1). The effect of choline on serum insulin and glucose was enhanced by oral glucose administration (3 g.kg-1). Choline administration was associated with a significant (P < 0.001) increase in the acetylcholine content of pancreatic tissue. Choline (10-130 microm) increased basal and stimulated acetylcholine release but failed to evoke insulin release from the minced pancreas at considerably higher concentrations (0.1-10 mm). Hemicholium-3, a choline uptake inhibitor, attenuated the increase in acetylcholine release induced by choline augmentation. Choline (1-32 mm) inhibited [3H]quinuclidinyl benzilate binding to the muscarinic receptors in the pancreatic homogenates. These data show that choline, a precursor of the neurotransmitter acetylcholine, increases serum insulin by indirectly stimulating peripheral acetylcholine receptors through the enhancement of acetylcholine synthesis and release. 相似文献
110.