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1.
Qian Jiang Stacey Arnold Tiffany Heanue Krishna?Praneeth Kilambi Betty Doan Ashish Kapoor Albee?Yun Ling Maria?X. Sosa Moltu Guy Qingguang Jiang Grzegorz Burzynski Kristen West Seneca Bessling Paola Griseri Jeanne Amiel Raquel?M. Fernandez Joke?B.G.M. Verheij Robert?M.W. Hofstra Salud Borrego Stanislas Lyonnet Isabella Ceccherini Jeffrey?J. Gray Vassilis Pachnis Andrew?S. McCallion Aravinda Chakravarti 《American journal of human genetics》2015,96(4):581-596
Innervation of the gut is segmentally lost in Hirschsprung disease (HSCR), a consequence of cell-autonomous and non-autonomous defects in enteric neuronal cell differentiation, proliferation, migration, or survival. Rare, high-penetrance coding variants and common, low-penetrance non-coding variants in 13 genes are known to underlie HSCR risk, with the most frequent variants in the ret proto-oncogene (RET). We used a genome-wide association (220 trios) and replication (429 trios) study to reveal a second non-coding variant distal to RET and a non-coding allele on chromosome 7 within the class 3 Semaphorin gene cluster. Analysis in Ret wild-type and Ret-null mice demonstrates specific expression of Sema3a, Sema3c, and Sema3d in the enteric nervous system (ENS). In zebrafish embryos, sema3 knockdowns show reduction of migratory ENS precursors with complete ablation under conjoint ret loss of function. Seven candidate receptors of Sema3 proteins are also expressed within the mouse ENS and their expression is also lost in the ENS of Ret-null embryos. Sequencing of SEMA3A, SEMA3C, and SEMA3D in 254 HSCR-affected subjects followed by in silico protein structure modeling and functional analyses identified five disease-associated alleles with loss-of-function defects in semaphorin dimerization and binding to their cognate neuropilin and plexin receptors. Thus, semaphorin 3C/3D signaling is an evolutionarily conserved regulator of ENS development whose dys-regulation is a cause of enteric aganglionosis. 相似文献
2.
Phylogeny of the M superhaplogroup inferred from complete mitochondrial genome sequence of Indian specific lineages 下载免费PDF全文
Revathi Rajkumar Jheelam Banerjee Hima Bindu Gunturi R Trivedi VK Kashyap 《Genome biology》2004,6(2):P3
Background
Phylogenetic analysis of human complete mitochondrial DNA sequences has largely contributed to resolving phylogenies and antiquity of different lineages belonging to the majorhaplogroups L, N and M (East-Asian lineages). In the absence of whole mtDNA sequence information of M lineages reported in India that exhibits highest diversity within the sub-continent, the present study was undertaken to provide a detailed analysis of this haplogroup to precisely characterize the lineages and unravel their intricate phylogeny. 相似文献3.
P. Diana Subramanian Saravanakumar D. Sivaganesh V. Sivakumar Yang Li S. Sebastian Ji-Man Kim Padmanathan Karthick Kannan L. Sangeetha Vijayendran K. K. Praneeth 《Luminescence》2023,38(5):625-636
The present investigation deals with the effect of calcination temperature on the structural and thermoluminescent (TL) properties of Zn2SiO4 materials. For this study, Zn2SiO4 was prepared via a simple hydrothermal route and calcinated at temperatures from 700°C to 1100°C in an air atmosphere. TL data of all Zn2SiO4 samples showed two peaks at around 240°C and 330°C due to the formation of the luminescence centre during X-ray irradiation. More interestingly, the Zn2SiO4 sample calcinated at 900°C exhibited a shift in the TL peak (282°C and 354°C) with an optimal TL intensity attributed to its good crystallinity with a well-defined hexagonal plate-like morphology. X-ray-irradiated Zn2SiO4 samples calcinated at 900°C exhibited a high-temperature TL glow curve peak, suggesting that the present material could be used for high-temperature dosimetry applications. 相似文献
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Kastrati I Edirisinghe PD Hemachandra LP Chandrasena ER Choi J Wang YT Bolton JL Thatcher GR 《PloS one》2011,6(11):e27876
There is association between exposure to estrogens and the development and progression of hormone-dependent gynecological cancers. Chemical carcinogenesis by catechol estrogens derived from oxidative metabolism is thought to contribute to breast cancer, yet exact mechanisms remain elusive. Malignant transformation was studied in MCF-10A human mammary epithelial cells, since estrogens are not proliferative in this cell line. The human and equine estrogen components of estrogen replacement therapy (ERT) and their catechol metabolites were studied, along with the influence of co-administration of selective estrogen receptor modulators (SERMs), raloxifene and desmethyl-arzoxifene (DMA), and histone deacetylase inhibitors. Transformation was induced by human estrogens, and selectively by the 4-OH catechol metabolite, and to a lesser extent by an equine estrogen metabolite. The observed estrogen-induced upregulation of CYP450 1B1 in estrogen receptor negative MCF-10A cells, was compatible with a causal role for 4-OH catechol estrogens, as was attenuated transformation by CYP450 inhibitors. Estrogen-induced malignant transformation was blocked by SERMs correlating with a reduction in formation of nucleobase catechol estrogen (NCE) adducts and formation of 8-oxo-dG. NCE adducts can be formed consequent to DNA abasic site formation, but NCE adducts were also observed on incubation of estrogen quinones with free nucleotides. These results suggest that NCE adducts may be a biomarker for cellular electrophilic stress, which together with 8-oxo-dG as a biomarker of oxidative stress correlate with malignant transformation induced by estrogen oxidative metabolites. The observed attenuation of transformation by SERMs correlated with these biomarkers and may also be of clinical significance in breast cancer chemoprevention. 相似文献
6.
Hye-Yeong Kim Johann Sohn Gihani T. Wijewickrama Praneeth Edirisinghe Teshome Gherezghiher Madhubani Hemachandra Pei-Yi Lu R. Esala Chandrasena Mary Ellen Molloy Debra A. Tonetti Gregory R.J. Thatcher 《Bioorganic & medicinal chemistry》2010,18(2):809-821
Cyclodextrin (CD) is a well known drug carrier and excipient for enhancing aqueous solubility. CDs themselves are anticipated to have low membrane permeability because of relatively high hydrophilicity and molecular weight. CD derivatization with 17-beta estradiol (E2) was explored extensively using a number of different click chemistries and the cell membrane permeability of synthetic CD–E2 conjugate was explored by cell reporter assays and confocal fluorescence microscopy. In simile with reported dendrimer–E2 conjugates, CD–E2 was found to be a stable, extranuclear receptor selective estrogen that penetrated into the cytoplasm. 相似文献
7.
A Puri R Sethi B Singh SK Dwivedi VS Narain RK Saran VK Puri 《Indian pacing and electrophysiology journal》2009,9(3):186-189
A 25-year-old previously asymptomatic pregnant woman at 36 weeks'' gestation was noticed to have repetitive monomorphic ventricular tachycardia. A dilated left ventricle with moderately reduced systolic function was found on echocardiographic examination. This is a very rare presentation of peripartum cardiomyopathy (PPCMP) presenting with repetitive monomorphic ventricular tachycardia. 相似文献
8.
Processing of viral envelope glycoprotein by the endomannosidase pathway: evaluation of host cell specificity 总被引:2,自引:2,他引:2
Endo-alpha-D-mannosidase is an enzyme involved in N-linked oligosaccharide
processing which through its capacity to cleave the internal linkage
between the glucose-substituted mannose and the remainder of the
polymannose carbohydrate unit can provide an alternate pathway for
achieving deglucosylation and thereby make possible the continued formation
of complex oligosaccharides during a glucosidase blockade. In view of the
important role which has been attributed to glucose on nascent
glycoproteins as a regulator of a number of biological events, we chose to
further define the in vivo action of endomannosidase by focusing on the
well characterized VSV envelope glycoprotein (G protein) which can be
formed by the large array of cell lines susceptible to infection by this
pathogen. Through an assessment of the extent to which the G protein was
converted to an endo-beta-N- acetylglucosaminidase (endo H)-resistant form
during a castanospermine imposed glucosidase blockade, we found that
utilization of the endomannosidase-mediated deglucosylation route was
clearly host cell specific, ranging from greater than 90% in HepG2 and PtK1
cells to complete absence in CHO, MDCK, and MDBK cells, with intermediate
values in BHK, BW5147.3, LLC-PK1, BRL, and NRK cell lines. In some of the
latter group the electrophoretic pattern after endo H treatment suggested
that only one of the two N-linked oligosaccharides of the G protein was
processed by endomannosidase. In the presence of the specific
endomannosidase inhibitor, Glcalpha1-->3(1- deoxy)mannojirimycin, the
conversion of the G protein into an endo H- resistant form was completely
arrested. While the lack of G protein processing by CHO cells was
consistent with the absence of in vitro measured endomannosidase activity
in this cell line, the failure of MDBK and MDCK cells to convert the G
protein into an endo H-resistant form was surprising since these cell lines
have substantial levels of the enzyme. Similarly, we observed that
influenza virus hemagglutinin was not processed in castanospermine-treated
MDCK cells. Our findings suggest that studies which rely on glucosidase
inhibition to explore the function of glucose in controlling such critical
biological phenomena as intracellular movement or quality control should be
carried out in cell lines in which the glycoprotein under study is not a
substrate for endomannosidase action.
相似文献
9.
The green tea compound, (-)-epigallocatechin-3-gallate downregulates N-cadherin and suppresses migration of bladder carcinoma cells 总被引:1,自引:0,他引:1
Rieger-Christ KM Hanley R Lodowsky C Bernier T Vemulapalli P Roth M Kim J Yee AS Le SM Marie PJ Libertino JA Summerhayes IC 《Journal of cellular biochemistry》2007,102(2):377-388
Green tea has been reported as potential dietary protection against numerous cancers and has been shown to have activity in bladder tumor inhibition in different animal models. The goal of this study was to examine the effects of (-)-epigallocatechin gallate (EGCG-the major phytochemical in green tea) on growth inhibition and behavior of human bladder carcinoma cells and to identify the altered signaling pathway(s) underlying the response to EGCG exposure. EGCG inhibited the in vitro growth of invasive bladder carcinoma cells with an IC(50) range of 70-87 microM. At a concentration of 20 microM, EGCG decreased the migratory potential of bladder carcinoma cells with concomitant activation of p42/44 MAPK and STAT3 and inactivation of Akt. Using biochemical inhibitors of MAPK/ERK, and siRNA to knockdown STAT3 and Akt, inhibition of migration was recorded associated with Akt but not MAPK/ERK or STAT3 signaling in bladder cells. In addition, EGCG downregulated N-cadherin in a dose-dependent manner where reduction in N-cadherin expression paralleled declining migratory potential. Continuous feeding of EGCG to mice prior to and during the establishment of bladder carcinoma xenografts in vivo revealed >50% reduction in mean final tumor volume (P = 0.05) with no detectable toxicity. EGCG inhibited bladder carcinoma cell growth and suppressed the in vitro migration capacity of cells via downregulation of N-cadherin and inactivation of Akt signaling. Continuous administration of EGCG to mice revealed significant inhibition of tumor growth in vivo indicating a possible preventative role for green tea in bladder cancer. 相似文献
10.
The interaction of the Fe(II)-porphyrin NO model complex [Fe(TPP)(NO)] (1, TPP=tetraphenylporphyrin) with thiophenolate ligands and tetrahydrothiophene is explored both computationally and experimentally. Complex 1 is reacted with substituted thiophenolates and the obtained six-coordinate adducts of type [Fe(TPP)(SR)(NO)](-) are investigated in solution using electron paramagnetic resonance (EPR) spectroscopy. From the obtained g values and (14)N hyperfine pattern of the NO ligand it is concluded that the interaction of the thiophenolates with the Fe(II) center is weak in comparison to the corresponding 1-methylimidazole adduct. The strength of the Fe-S bond is increased when alkylthiolates are used as evidenced by comparison with the published EPR spectra of ferrous NO adducts in cytochromes P450 and P450nor, which have an axial cysteinate ligand. These results are further evaluated by density functional (DFT) calculations. The six-coordinate model complex [Fe(P)(SMe)(NO)](-) (1-SMe; P=porphine ligand used for the calculations) has an interesting electronic structure where NO acts as a medium strong sigma donor and pi acceptor ligand. Compared to the N-donor adducts with 1-methylimidazole (1-MeIm), etc., donation from the pi(h)( *) orbital of NO to Fe(II) is reduced due to the stronger trans effect of the alkylthiolate ligand. This is reflected by the predicted longer Fe-NO bond length and smaller Fe-NO force constant for 1-SMe compared to the 1-MeIm adduct. Therefore, the Fe(II)-porphyrin NO adducts with trans alkylthiolate coordination have to be described as Fe(II)-NO(radical) systems. The N-O stretching frequency of these complexes is predicted below 1600cm(-1) in agreement with the available experimental data. In addition, 1-SMe has a unique spin density distribution where Fe has a negative spin density of -0.26 from the calculations. The implications of this unusual electronic structure for the reactivity of the Fe(II)-NO alkylthiolate adducts as they occur in cytochrome P450nor are discussed. 相似文献