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101.
Li J Coven DL Miller EJ Hu X Young ME Carling D Sinusas AJ Young LH 《American journal of physiology. Heart and circulatory physiology》2006,291(4):H1927-H1934
AMP-activated protein kinase (AMPK) plays a key role in modulating cellular metabolic processes. AMPK, a serine-threonine kinase, is a heterotrimeric complex of catalytic alpha-subunits and regulatory beta- and gamma-subunits with multiple isoforms. Mutations in the cardiac gamma(2)-isoform have been associated with hypertrophic cardiomyopathy and pre-excitation syndromes. However, physiological regulation of AMPK complexes containing different subunit isoforms is not well defined and is important for an understanding of the function of this signaling pathway in the intact heart. We evaluated the kinase activity associated with heart AMPK complexes containing specific alpha- and gamma-subunit isoforms of AMPK in an in vivo rat model of regional ischemia. Left coronary artery occlusion activated the immunoprecipitated alpha(1)-isoform (6-fold, P < 0.01) and alpha(2)-isoform (9-fold, P < 0.01) in the ischemic left ventricle compared with sham controls. The degree of alpha-subunit activation depended on the extent of ischemia and paralleled echocardiographic contractile dysfunction. The regulatory gamma(1)- and gamma(2)-isoforms were expressed in the heart. The gamma(1)- and gamma(2)-isoforms coimmunoprecipitated with alpha(1)- and alpha(2)-isoforms in proportion to alpha-subunit content. gamma(1)-Isoform immunocomplexes accounted for 70% of AMPK activity and AMPK phosphorylation (Thr(172)) in hearts. Ischemia similarly increased AMPK activity associated with the gamma(1)- and gamma(2)-isoform complexes threefold (P < 0.01 for each). Thus AMPK catalytic alpha(1)- and alpha(2)-isoforms are activated by regional ischemia in vivo in the heart, irrespective of the regulatory gamma(1)- or gamma(2)-isoforms to which they are complexed. Despite the pathophysiological importance of gamma(2)-isoform mutations, gamma(1)-isoform complexes account for most of the AMPK activity in the ischemic heart. 相似文献
102.
Maria das Graas C. Pereira Edward R. Atwill Melissa R. Crawford Rance B. Lefebvre 《Applied microbiology》1998,64(4):1584-1586
We evaluated whether nucleic acid amplification with primers specific for Cryptosporidium parvum followed by automated DNA sequence analysis of the PCR amplicons could differentiate between California isolates of C. parvum obtained from livestock, humans, and feral pigs. Almost complete sequence identity existed among the livestock isolates and between the livestock and human isolates. DNA sequences from feral pig isolates differed from those from livestock and humans by 1.0 to 1.2%. The reference sequence obtained by Laxer et al. (M. A. Laxer, B. K. Timblin, and R. J. Patel, Am. J. Trop. Med. Hyg. 45:688–694, 1991.) differed from California isolates of C. parvum by 1.8 to 3.2%. These data suggest that DNA sequence analysis of the amplicon of Laxer et al. does not allow for differentiation between various strains of C. parvum or that our collection of isolates obtained from various hosts from across California was limited to one strain of C. parvum. 相似文献
103.
104.
Peter J. Kerr Elodie Ghedin Jay V. DePasse Adam Fitch Isabella M. Cattadori Peter J. Hudson David C. Tscharke Andrew F. Read Edward C. Holmes 《PLoS pathogens》2012,8(10)
The attenuation of myxoma virus (MYXV) following its introduction as a biological control into the European rabbit populations of Australia and Europe is the canonical study of the evolution of virulence. However, the evolutionary genetics of this profound change in host-pathogen relationship is unknown. We describe the genome-scale evolution of MYXV covering a range of virulence grades sampled over 49 years from the parallel Australian and European epidemics, including the high-virulence progenitor strains released in the early 1950s. MYXV evolved rapidly over the sampling period, exhibiting one of the highest nucleotide substitution rates ever reported for a double-stranded DNA virus, and indicative of a relatively high mutation rate and/or a continually changing selective environment. Our comparative sequence data reveal that changes in virulence involved multiple genes, likely losses of gene function due to insertion-deletion events, and no mutations common to specific virulence grades. Hence, despite the similarity in selection pressures there are multiple genetic routes to attain either highly virulent or attenuated phenotypes in MYXV, resulting in convergence for phenotype but not genotype. 相似文献
105.
David Freeman Rudy Cedillos Samantha Choyke Zana Lukic Kathleen McGuire Shauna Marvin Andrew M. Burrage Stacey Sudholt Ajay Rana Christopher O'Connor Christopher M. Wiethoff Edward M. Campbell 《PloS one》2013,8(4)
α-synuclein dysregulation is a critical aspect of Parkinson''s disease pathology. Recent studies have observed that α-synuclein aggregates are cytotoxic to cells in culture and that this toxicity can be spread between cells. However, the molecular mechanisms governing this cytotoxicity and spread are poorly characterized. Recent studies of viruses and bacteria, which achieve their cytoplasmic entry by rupturing intracellular vesicles, have utilized the redistribution of galectin proteins as a tool to measure vesicle rupture by these organisms. Using this approach, we demonstrate that α-synuclein aggregates can induce the rupture of lysosomes following their endocytosis in neuronal cell lines. This rupture can be induced by the addition of α-synuclein aggregates directly into cells as well as by cell-to-cell transfer of α-synuclein. We also observe that lysosomal rupture by α-synuclein induces a cathepsin B dependent increase in reactive oxygen species (ROS) in target cells. Finally, we observe that α-synuclein aggregates can induce inflammasome activation in THP-1 cells. Lysosomal rupture is known to induce mitochondrial dysfunction and inflammation, both of which are well established aspects of Parkinson''s disease, thus connecting these aspects of Parkinson''s disease to the propagation of α-synuclein pathology in cells. 相似文献
106.
Summary The ultrastructure of chicken and frog cardiac muscle are compared and then contrasted with the ultrastructure of mammalian cardiac muscle. Both chicken and frog cardiac muscle have no transverse tubules, remarkably few nexuses and no prominent M-lines. M-fibers of both animals are small (2–5 ) in diameter and contain dense granules. Chicken cardiac muscle like mammalian cardiac muscle has very well developed sarcoplasmic reticulum and couplings. The latter do not occur in frog cardiac muscle and the former is poorly developed in that muscle. Morphologic evidence is presented in the frog and chicken heart that would tend to attribute to the sarcoplasmic reticulum a transport function for electron-dense material (presumably proteinaceous) the possible significance of which is discussed. Purkinje fibers were identified in the form of a network on the endocardial surface of both atria and ventricles of chicken hearts. The topography of these fibers corresponds to that of a population of fibers in small mammalian hearts that, and unlike ventricular fibers in those animals, does not have transverse tubules.This investigation was presented, in part, at the 2nd Annual Summer Workshop of the Council on Basic Science of the American Heart Association in Mountain View, California, August 5–8, 1968; at the Gordon Conference on Myocardial Contractility in Holderness, New Hampshire, August 12–16, 1968; and at the 8th Annual Meeting of the American Society for Cell Biology in Boston, Massachusetts, November 11–13, 1968. This research was supported by grant No. 66737 from the American Heart Association, Inc. and by grant No. HE 08620 from the NIH. 相似文献
107.
Edward L. Kean 《Glycoconjugate journal》1996,13(4):675-680
Mannosyl-P-dolichol (man-P-dol) has been shown to stimulate the early reactions of the dolichol pathway, specifically, the biosynthesis of GlcNAc-P-P-dol and GlcNAc-GlcNAc-P-P-dol, and thus may play a regulatory role in glycoprotein biosynthesis. The site of action of man-P-dol has previously been suggested to be the GlcNAc-transferase concerned with the formation of the monoglucosaminyl derivative. Since the concentration of the chitobiosyl compound also increases as a result of the presence of man-P-dol, the immediate site of the activation was reexamined. The effect of man-P-dol on the formation of GlcNAc-GlcNAc-P-P-dol using GlcNAc-P-P-dol synthesizedin situ or added exogenously as the substrate was investigated. In addition, the distribution of radioactivity in the glucosaminyl constituents of the products under the stimulatory conditions was determined. The results of these studies supported the conclusion that the stimulation of GlcNAc-lipid synthesis by man-P-dol is due to the enhanced synthesis of GlcNAc-P-P-dol. It is not a result of the activation of the GlcNAc-transferase catalyzing the attachment of the second GlcNAc residue for the biosynthesis of the chitobiosyl derivative.Abbreviations GlcNAc-P-P-dol
N-acetylglucosaminylpyrophosphoryldolichol
- GlcNAc-GlcNAc-P-P-dol
N-acetylglucosaminyl-N-acetylglucosaminylpyrophosphoryldolichol;
- chito
N-N-diacetylchitobiose
- man-P-dol
mannosylphosphoryldolichol
- TX-100
triton X-100
- Tes
2-{[tris-(hydroxymethyl)-methyl]-amino}-ethanesulfonic acid 相似文献
108.
Gardens with nectar sources and larval host plants have been proposed to stem the decline in butterfly abundance caused by habitat loss. However, no study has provided evidence that gardens benefit butterflies. We examined the use of natural sites and gardens in the San Francisco bay area by the butterfly, Battus philenor. We found that natural sites were more likely to attract adult B. philenor, received more oviposition, and had higher juvenile survival than gardens sites. Butterflies were more likely to be present in gardens with established populations of the host plant, Aristolochia californica, growing in the sun. Battus philenor are unlikely to visit gardens with host plants planted within the past 7 years. Gardens between the ages of 8–40 years received oviposition, but did not always support completion of larval development of B. philenor. In gardens with host plants over 40 years of age, B. philenor consistently survived from egg to the adult stage. Natural enemy induced mortality of eggs did not differ between garden and natural sites, but overall egg survival was lower in gardens than at natural sites. It is unlikely that gardens serve as 'refugia' for B. philenor in years when populations in natural sites experience low survival or low fecundity. Even in gardens capable of supporting larvae to maturity, the density of eggs and survival rates were lower than in natural populations of the host plant suggesting that gardens were not optimal habitats. Therefore, without evidence that juvenile abundance and survival rates in gardens matches or exceeds that in natural sites, it is most likely that gardens act as population sinks for B. philenor. 相似文献
109.
110.
Lisa N. Meihls Vinzenz Handrick Gaetan Glauser Hugues Barbier Harleen Kaur Meena M. Haribal Alexander E. Lipka Jonathan Gershenzon Edward S. Buckler Matthias Erb Tobias G. K?llner Georg Jander 《The Plant cell》2013,25(6):2341-2355
Plants differ greatly in their susceptibility to insect herbivory, suggesting both local adaptation and resistance tradeoffs. We used maize (Zea mays) recombinant inbred lines to map a quantitative trait locus (QTL) for the maize leaf aphid (Rhopalosiphum maidis) susceptibility to maize Chromosome 1. Phytochemical analysis revealed that the same locus was also associated with high levels of 2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one glucoside (HDMBOA-Glc) and low levels of 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one glucoside (DIMBOA-Glc). In vitro enzyme assays with candidate genes from the region of the QTL identified three O-methyltransferases (Bx10a-c) that convert DIMBOA-Glc to HDMBOA-Glc. Variation in HDMBOA-Glc production was attributed to a natural CACTA family transposon insertion that inactivates Bx10c in maize lines with low HDMBOA-Glc accumulation. When tested with a population of 26 diverse maize inbred lines, R. maidis produced more progeny on those with high HDMBOA-Glc and low DIMBOA-Glc. Although HDMBOA-Glc was more toxic to R. maidis than DIMBOA-Glc in vitro, BX10c activity and the resulting decline of DIMBOA-Glc upon methylation to HDMBOA-Glc were associated with reduced callose deposition as an aphid defense response in vivo. Thus, a natural transposon insertion appears to mediate an ecologically relevant trade-off between the direct toxicity and defense-inducing properties of maize benzoxazinoids. 相似文献