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951.
The objective of this study was to analyze the clinical manifestation, imaging characteristics, genotype, and the relationship
between the three aforementioned parameters in two pedigrees suffering from spinocerebellar ataxia. To evaluate the clinical
manifestation of the two pedigrees and to compare the characteristics, we performed the MRI analysis of some patients from
both pedigrees, while 2 ml of the peripheral blood sample was collected for gene analysis. The gene analysis data showed that
pedigree 1 was certified spinocerebellar ataxia type-2 (SCA2); the CAG repeats in the proband, proband’s mother, and proband’s
brother were 44, 36, and 38, respectively. The MRI revealed brainstem cerebellar atrophy and “cross sign” and “ordinate sign”
of pons. Pedigree 2 was certified SCA1; the CAG repeats of the proband, proband’s aunt, and proband’s asymptomatic cousin
were 60, 51, and 52, respectively. The MRI revealed cerebellar atrophy in these individuals. We, therefore, concluded that
it was difficult to diagnose the SCA subset solely through the clinical manifestation. The imaging characteristics analysis
and final diagnosis depended basically on gene analysis data. 相似文献
952.
Tyrosine phosphorylation of mitochondrial pyruvate dehydrogenase kinase 1 is important for cancer metabolism 总被引:1,自引:0,他引:1
Hitosugi T Fan J Chung TW Lythgoe K Wang X Xie J Ge Q Gu TL Polakiewicz RD Roesel JL Chen GZ Boggon TJ Lonial S Fu H Khuri FR Kang S Chen J 《Molecular cell》2011,44(6):864-877
Many tumor cells rely on aerobic glycolysis instead of oxidative phosphorylation for their continued proliferation and survival. Myc and HIF-1 are believed to promote such a metabolic switch by, in part, upregulating gene expression of pyruvate dehydrogenase (PDH) kinase 1 (PDHK1), which phosphorylates and inactivates mitochondrial PDH and consequently pyruvate dehydrogenase complex (PDC). Here we report that tyrosine phosphorylation enhances PDHK1 kinase activity by promoting ATP and PDC binding. Functional PDC can form in mitochondria outside of the matrix in some cancer cells and PDHK1 is commonly tyrosine phosphorylated in human cancers by diverse oncogenic tyrosine kinases localized to different mitochondrial compartments. Expression of phosphorylation-deficient, catalytic hypomorph PDHK1 mutants in cancer cells leads to decreased cell proliferation under hypoxia and increased oxidative phosphorylation with enhanced mitochondrial utilization of pyruvate and reduced tumor growth in xenograft nude mice. Together, tyrosine phosphorylation activates PDHK1 to promote the Warburg effect and tumor growth. 相似文献
953.
Kim SG Jung BW Kim H 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2011,159(2):103-108
Phenoloxidase (PO) activity is a major component of the innate immune response in arthropods. In this study, we characterized PO activity from the hair crab Erimacrus isenbeckii, which inhabits very cold regions (2.4-3.4°C) of the Bering Sea. Hemocyte lysate supernatant (HLS) prepared from E. isenbeckii was inactive HLS until activated by nonspecific agents such as sodium dodecyl sulfate and trypsin, and elicitors such as lipopolysaccharide and lipoteichoic acid from the cell wall constituent of bacteria. The PO activity was maximal at 4°C, decreased slightly at temperatures up to 60°C, and fell rapidly at 80°C. Both L-DOPA and catechol were efficient substrates for the PO (EC 1.10.3.1), with K(m) values of 0.96 and 1.15mM, respectively, whereas tyrosine and hydroquinone were not. We isolated a protein fraction from HLS as a hexamer of 75kDa units with 216.7-fold higher PO activity than that of the HLS. The N-terminal amino acid analysis of an isolated protein revealed 80% sequence identity to hemocyanins from other crabs. These results suggest that cold-adapted hemocyanin-derived PO activity is important to the survival of these crabs. This is the first report of a crab PO activity with broad temperature stability extending into the cold environment. 相似文献
954.
Liang Zhang Zhongyang Ding Peng Xu Yuhong Wang Zhenghua Gu Zhu Qian Guiyang Shi Kechang Zhang 《Biotechnology and Bioprocess Engineering》2011,16(3):457-461
Tyrosinase is a key enzyme in the biosynthesis of melanin, and the use of inhibitors against tyrosinase can prevent hyperpigmentation
by inhibiting enzymatic oxidation. However, the current use of tyrosine inhibitors is limited by their low activities and
high toxicities. The aim of the present research was to develop novel whitening agents, or tyrosinase-targeted medicine, from
a submerged culture of the fungus Ganoderma lucidum. Methyl lucidenate F was isolated from the ethanol-soluble-acidic components (ESACs) of G. lucidum, with the structure of ESACs elucidated via UV, LC-MS, and 13C-NMR spectral analysis. The tyrosinase inhibitory activity was measured using catechol as a substrate. Methyl lucidenate
F displayed uncompetitive inhibition of the potato tyrosinase activity, for which Lineweaver-Burk plots revealed a maximum
reaction rate (V
max) of 0.4367/min, Michaelis constant (K
m) of 6.765 mM and uncompetitive inhibition constant (K
i) of 19.22 μM. Meanwhile, methyl lucidenate F (tetra cyclic triterpenoid) exhibited high tyrosinase inhibitory activity, with
an IC50 of 32.23 μM. These results suggest that methyl lucidenate F may serve as a potential candidate for skin-whitening agents. 相似文献
955.
956.
The Wood-Ljungdahl pathway is responsible for acetyl-CoA biosynthesis and used as a major mean of generating energy for growth in some anaerobic microbes. Series of genes, from the anaerobic human pathogen Clostridium difficile, have been identified that show striking similarity to the genes involved in this pathway including methyltetrahydrofolate- and corrinoid-dependent methyltransferase. This methyltransferase plays a central role in this pathway that transfers the methyl group from methyltetrahydrofolate to a cob(I)amide center in the corrinoid iron-sulfur protein. In this study, we developed two efficient expression and purification methods for methyltransferase from C. difficile for the first time with two expression vectors MBPHT-mCherry2 and pETDuet-1, respectively. Using the latter vector, more than 50mg MeTr was produced per liter Luria-Bertani broth media. The recombinant methyltransferase was well characterized by SDS-PAGE, gel filtration chromatography, enzyme assay and far-UV circular dichroism (CD). Furthermore, a highly effective approach was established for determining the methyl transfer activity of the methyltetrahydrofolate- and cobalamin-dependent methyltransferase using exogenous cobalamin as a substrate by stopped-flow method. These results will provide a solid basis for further study of the methyltransferase and the Wood-Ljungdahl pathway. 相似文献
957.
Malaria continues to be one of the most devastating global health problems due to the high morbidity and mortality it causes in endemic regions. The search for new antimalarial targets is of high priority because of the increasing prevalence of drug resistance in malaria parasites. Malarial proteases constitute a class of promising therapeutic targets as they play important roles in the parasite life cycle and it is possible to design and screen for specific protease inhibitors. In this mini-review, we provide a phylogenomic overview of malarial proteases. An evolutionary perspective on the origin and divergence of these proteases will provide insights into the adaptive mechanisms of parasite growth, development, infection, and pathogenesis.B. 相似文献
958.
959.
Aimin Wang Yan Wang Zhifeng Gu Sifa Li Yaohua Shi Ximing Guo 《Marine biotechnology (New York, N.Y.)》2011,13(2):275-283
The pearl oyster, Pinctada martensii, is the primary species used for the aquaculture production of marine pearls in China and Japan. Genetic tools and resources
are needed to study the genome of this species and to understand the molecular basis of development, growth, host defense,
pearl formation, and other important traits. In this study, we developed a set of expressed sequence tags (ESTs) for P. martensii. We constructed cDNA libraries from adult tissues and sequenced 7,128 ESTs. Clustering analysis identified 788 contigs (covering
5,769 ESTs) and 1,351 singletons, yielding a total of 2,139 unique genes. Of these unique genes, only 935 had significant
(E-value ≤ 0.005) hits in GenBank, and the remaining 1,204 (56.3%) were novel. Most of the known genes are related to cellular
structure, protein binding, and metabolic processes. Putative host-defense genes (86) were identified including C-type lectin,
ferritin, polyubiquitin, proteases, protease inhibitors, scavenger receptors, heat shock proteins, and RAS oncogenes. The
EST sequences developed in this study provide a valuable resource for future efforts on gene identification, marker development,
and studies on molecular mechanism of host defense in pearl oysters. 相似文献
960.
The purpose of this study was to assess if there was trophic niche overlap of silver carp (Hypophthalmichthys molitrix) and bighead carp (H. nobilis) in four large freshwater ecosystems from southern China using stable carbon and nitrogen isotopes (δ13C and δ15N). Multivariate analysis of variance (MANOVA) on the δ13C and δ15N values measured from muscle tissue indicates trophic niche overlap in one unproductive and one highly productive large system
and trophic niche segregation in two systems with moderate watershed size and productivity. For these two coexisting planktivorous
fish, which were hitherto believed to occupy different trophic niches, this study demonstrated that the degree of their trophic
niche overlap varied according to ecosystem properties. 相似文献