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41.
While K-ras is essential for mouse development, expression of the K-ras 4A splice variant is dispensable 下载免费PDF全文
Plowman SJ Williamson DJ O'Sullivan MJ Doig J Ritchie AM Harrison DJ Melton DW Arends MJ Hooper ML Patek CE 《Molecular and cellular biology》2003,23(24):9245-9250
In mammals, the three classical ras genes encode four highly homologous proteins, N-Ras, H-Ras, and the isoforms K-Ras 4A and 4B. Previous studies have shown that K-ras is essential for mouse development and that while K-ras 4A and 4B are expressed during development, K-ras 4A expression is regulated temporally and spatially and occurs in adult kidney, intestine, stomach, and liver. In the present study, the pattern of K-ras 4A expression was examined in a wide range of wild-type adult mouse tissues, and gene targeting was used to generate K-ras 4A-deficient mice to examine its role in development. It was found that K-ras 4A is also expressed in uterus, lung, pancreas, salivary glands, seminal vesicles, bone marrow cells, and cecum, where it was the major K-Ras isoform expressed. Mating between K-ras(tmDelta4A/+) mice produced viable K-ras(tmDelta4A/tmDelta4A) offspring with the expected Mendelian ratios of inheritance, and these mice expressed the K-ras 4B splice variant only. K-ras(tmDelta4A/tmDelta4A) mice were fertile and showed no histopathological abnormalities on inbred (129/Ola) or crossbred (129/Ola x C57BL/6) genetic backgrounds. The results demonstrate that K-Ras 4A, like H- and N-Ras, is dispensable for normal mouse development, at least in the presence of functional K-Ras 4B. 相似文献
42.
Michael M. Weil F. Andrew Ray Paula C. Genik Yongjia Yu Maureen McCarthy Christina M. Fallgren Robert L. Ullrich 《PloS one》2014,9(8)
Estimates of cancer risks posed to space-flight crews by exposure to high atomic number, high-energy (HZE) ions are subject to considerable uncertainty because epidemiological data do not exist for human populations exposed to similar radiation qualities. We assessed the carcinogenic effects of 300 MeV/n 28Si or 600 MeV/n 56Fe ions in a mouse model for radiation-induced acute myeloid leukemia and hepatocellular carcinoma. C3H/HeNCrl mice were irradiated with 0.1, 0.2, 0.4, or 1 Gy of 300 MeV/n 28Si ions, 600 MeV/n 56Fe ions or 1 or 2 Gy of protons simulating the 1972 solar particle event (1972SPE) at the NASA Space Radiation Laboratory. Additional mice were irradiated with 137Cs gamma rays at doses of 1, 2, or 3 Gy. All groups were followed until they were moribund or reached 800 days of age. We found that 28Si or 56Fe ions do not appear to be substantially more effective than gamma rays for the induction of acute myeloid leukemia. However, 28Si or 56Fe ion irradiated mice had a much higher incidence of hepatocellular carcinoma than gamma ray irradiated or proton irradiated mice. These data demonstrate a clear difference in the effects of these HZE ions on the induction of leukemia compared to solid tumors, suggesting potentially different mechanisms of tumorigenesis. Also seen in this study was an increase in metastatic hepatocellular carcinoma in the 28Si and 56Fe ion irradiated mice compared with those exposed to gamma rays or 1972SPE protons, a finding with important implications for setting radiation exposure limits for space-flight crew members. 相似文献
43.
Raphael Saginur Stephen S. Silver Richard Bonin Maureen Carlier Manuel Orizaga 《CMAJ》1985,133(12):1228-1230
44.
Schnute ME McReynolds MD Kasten T Yates M Jerome G Rains JW Hall T Chrencik J Kraus M Cronin CN Saabye M Highkin MK Broadus R Ogawa S Cukyne K Zawadzke LE Peterkin V Iyanar K Scholten JA Wendling J Fujiwara H Nemirovskiy O Wittwer AJ Nagiec MM 《The Biochemical journal》2012,444(1):79-88
SphK (sphingosine kinase) is the major source of the bioactive lipid and GPCR (G-protein-coupled receptor) agonist S1P (sphingosine 1-phosphate). S1P promotes cell growth, survival and migration, and is a key regulator of lymphocyte trafficking. Inhibition of S1P signalling has been proposed as a strategy for treatment of inflammatory diseases and cancer. In the present paper we describe the discovery and characterization of PF-543, a novel cell-permeant inhibitor of SphK1. PF-543 inhibits SphK1 with a K(i) of 3.6 nM, is sphingosine-competitive and is more than 100-fold selective for SphK1 over the SphK2 isoform. In 1483 head and neck carcinoma cells, which are characterized by high levels of SphK1 expression and an unusually high rate of S1P production, PF-543 decreased the level of endogenous S1P 10-fold with a proportional increase in the level of sphingosine. In contrast with past reports that show that the growth of many cancer cell lines is SphK1-dependent, specific inhibition of SphK1 had no effect on the proliferation and survival of 1483 cells, despite a dramatic change in the cellular S1P/sphingosine ratio. PF-543 was effective as a potent inhibitor of S1P formation in whole blood, indicating that the SphK1 isoform of sphingosine kinase is the major source of S1P in human blood. PF-543 is the most potent inhibitor of SphK1 described to date and it will be useful for dissecting specific roles of SphK1-driven S1P signalling. 相似文献
45.
Dave JK Halldorsdottir VG Eisenbrey JR Raichlen JS Liu JB McDonald ME Dickie K Wang S Leung C Forsberg F 《American journal of physiology. Heart and circulatory physiology》2012,303(1):H126-H132
Right heart catheterization is often required to monitor intra-cardiac pressures in a number of disease states. Ultrasound contrast agents can produce pressure modulated subharmonic emissions that may be used to estimate right ventricular (RV) pressures. A technique based on subharmonic acoustic emissions from ultrasound contrast agents to track RV pressures noninvasively has been developed and its clinical potential evaluated. The subharmonic signals were obtained from the aorta, RV, and right atrium (RA) of five anesthetized closed-chest mongrel dogs using a SonixRP ultrasound scanner and PA4-2 phased array. Simultaneous pressure measurements were obtained using a 5-French solid state micromanometer tipped catheter. Initially, aortic subharmonic signals and systemic blood pressures were used to obtain a calibration factor in units of millimeters of mercury per decibel. This factor was combined with RA pressures (that can be obtained noninvasively) and the acoustic data from the RV to obtain RV pressure values. The individual calibration factors ranged from -2.0 to -4.0 mmHg/dB. The subharmonic signals tracked transient changes in the RV pressures within an error of 0.6 mmHg. Relative to the catheter pressures, the mean errors in estimating RV peak systolic and minimum diastolic pressures, and RV relaxation [isovolumic negative derivative of change in pressure over time (-dP/dt)] by use of the subharmonic signals, were -2.3 mmHg, -0.8 mmHg, and 2.9 mmHg/s, respectively. Overall, acoustic estimates of RV peak systolic and minimum diastolic pressures and RV relaxation were within 3.4 mmHg, 1.8 mmHg, and 5.9 mmHg/s, respectively, of the measured pressures. This pilot study demonstrates that subharmonic emissions from ultrasound contrast agents have the potential to noninvasively track in vivo RV pressures with errors below 3.5 mmHg. 相似文献
46.
The effects of the Fanconi anemia zinc finger (FAZF) on cell cycle, apoptosis, and proliferation are differentiation stage-specific 总被引:5,自引:0,他引:5
Dai MS Chevallier N Stone S Heinrich MC McConnell M Reuter T Broxmeyer HE Licht JD Lu L Hoatlin ME 《The Journal of biological chemistry》2002,277(29):26327-26334
47.
Alessandro Pintar Meike Hensmann Kornelia Jumel Maureen Pitkeathly Stephen E. Harding Iain D. Campbell 《European biophysics journal : EBJ》1996,24(6):371-380
The SH2 domain from Fyn tyrosine kinase, corresponding to residues 155–270 of the human enzyme, was expressed as a GST-fusion protein in a pGEX-E. coli system. After thrombin cleavage and removal of GST, the protein was studied by heteronuclear NMR. Two different phosphotyrosyl-peptides were synthesized and added to the SH2 domain. One peptide corresponded to the regulatory C-terminal tail region of Fyn. Sequence-specific assignment of NMR spectra was achieved using a combination of1H-15N-correlated 2D HSQC,15N-edited 3D TOCSY-HMQC, and15N-edited 3D NOESY-HMQC spectra. By analysis of the -proton chemical shifts and NOE intensities, the positions of secondary structural elements were determined and found to correspond closely to that seen in the crystal structure of the, homologous, Src-SH2 domain.To investigate the internal dynamics of the protein backbone, T1 and T2 relaxation parameters were measured on the free protein, as well as on both peptide complexes. Analytical ultracentrifugation and dynamic light scattering were employed to measure the effect of concentration and peptide-binding on self-association. The results suggest that, at NMR-sample concentrations, the free protein is present in at least dimeric form. Phosphopeptide binding and lower concentration significantly, but not completely, shift the equilibrium towards monomers. The possible role of this protein association in the regulation of the Src-family tyrosine kinases is discussed.Abbreviations SH
Src homology
- GST
glutathione-S-transferase
- IPTG
isopropyl--D-galactopyranoside
- DTT
dithiothreitol
- PMSF
phenyl-methyl-sulphonyl-fluoride
- TBS
50 mM Tris, 150 mM NaCl, 5 mM DTT, pH 8.0
- MWCO
molecular weight cut off
- NMR
nuclear magnetic resonance
- HSQC
heteronuclear single-quantum correlation
- NOESY
nuclear Overhauser effect spectroscopy 相似文献
48.
49.
Stable transformation of papaya via microprojectile bombardment 总被引:27,自引:0,他引:27
Maureen M. M. Fitch Richard M. Manshardt Dennis Gonsalves Jerry L. Slightom John C. Sanford 《Plant cell reports》1990,9(4):189-194
Summary Stable transformation of papaya (Carica papaya L.) has been achieved following DNA delivery via high velocity microprojectiles. Three types of embryogenic tissues, including immature zygotic embryos, freshly explanted hypocotyl sections, and somatic embryos derived from both, were bombarded with tungsten particles carrying chimeric NPTII and GUS genes. All tissue types were cultured prior to and following bombardment on half-strength MS medium supplemented with 10 mg 1–1 2,4-D, 400 mg 1–1 glutamine, and 6% sucrose. Upon transfer to 2,4-D-free medium containing 150 mg 1–1 kanamycin sulfate, ten putative transgenic isolates produced somatic embryos and five regenerated leafy shoots. Leafy shoots were produced six to nine months following bombardment. Tissues from 13 of these isolates were assayed for NPTII activity, and 10 were positive. Six out of 15 isolates assayed for GUS expression were positive. Three isolates were positive for both NPTII and GUS,Abbreviations 2,4-D
2,4-dichlorophenoxyacetic acid
- GUS
-glucuronidase
- X-gluc
5-Br-4-Cl-3-indolyl--D-glucuronic acid
- CaMV
cauliflower mosaic virus
- NOS
nopaline synthase
- NPTII
neomycin phosphotransferase II
Journal Series no. 3448 of the Hawaii Institute of Tropical Agriculture and Human Resources 相似文献
50.
A. Justin Nowakowski James I. Watling Michelle E. Thompson George A. Brusch IV Alessandro Catenazzi Steven M. Whitfield David J. Kurz Ángela Suárez‐Mayorga Andrés Aponte‐Gutiérrez Maureen A. Donnelly Brian D. Todd 《Ecology letters》2018,21(3):345-355
Human activities often replace native forests with warmer, modified habitats that represent novel thermal environments for biodiversity. Reducing biodiversity loss hinges upon identifying which species are most sensitive to the environmental conditions that result from habitat modification. Drawing on case studies and a meta‐analysis, we examined whether observed and modelled thermal traits, including heat tolerances, variation in body temperatures, and evaporative water loss, explained variation in sensitivity of ectotherms to habitat modification. Low heat tolerances of lizards and amphibians and high evaporative water loss of amphibians were associated with increased sensitivity to habitat modification, often explaining more variation than non‐thermal traits. Heat tolerances alone explained 24–66% (mean = 38%) of the variation in species responses, and these trends were largely consistent across geographic locations and spatial scales. As habitat modification alters local microclimates, the thermal biology of species will likely play a key role in the reassembly of terrestrial communities. 相似文献