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71.
TRIAD3/RNF216 mutations associated with Gordon Holmes syndrome lead to synaptic and cognitive impairments via Arc misregulation 下载免费PDF全文
Nilofer Husain Qiang Yuan Yi‐Chun Yen Olga Pletnikova Dong Qianying Sally Paul Worley Zoë Bichler H. Shawn Je 《Aging cell》2017,16(2):281-292
Multiple loss‐of‐function mutations in TRIAD3 (a.k.a. RNF216) have recently been identified in patients suffering from Gordon Holmes syndrome (GHS), characterized by cognitive decline, dementia, and movement disorders. TRIAD3A is an E3 ubiquitin ligase that recognizes and facilitates the ubiquitination of its target for degradation by the ubiquitin‐proteasome system (UPS). Here, we demonstrate that two of these missense substitutions in TRIAD3 (R660C and R694C) could not regulate the degradation of their neuronal target, activity‐regulated cytoskeletal‐associated protein (Arc/Arg 3.1), whose expression is critical for synaptic plasticity and memory. The synaptic deficits due to the loss of endogenous TRIAD3A could not be rescued by TRIAD3A harboring GHS‐associated missense mutations. Moreover, we demonstrate that the loss of endogenous TRIAD3A in the mouse hippocampal CA1 region led to deficits in spatial learning and memory. Finally, we show that these missense mutations abolished the interaction of TRIAD3A with Arc, disrupting Arc ubiquitination, and consequently Arc degradation. Our current findings of Arc misregulation by TRIAD3A variants suggest that loss‐of‐function mutations in TRIAD3A may contribute to dementia observed in patients with GHS driven by dysfunctional UPS components, leading to cognitive impairments through the synaptic protein Arc. 相似文献
72.
Background
Acinetobacter baumannii is a nosocomial pathogen of increasing importance, but the pathogenic mechanism of this microorganism has not been fully explored. This study investigated the potential of A. baumannii to invade epithelial cells and determined the role of A. baumannii outer membrane protein A (AbOmpA) in interactions with epithelial cells. 相似文献73.
Jae Su Kim Jae Young Choi Joo Hyun Lee Jong Bin Park Zhenli Fu Qin Liu Xueying Tao Byung Rae Jin Margaret Skinner Bruce L. Parker Yeon Ho Je 《PloS one》2013,8(4)
Insect-killing (entomopathogenic) fungi have high potential for controlling agriculturally harmful pests. However, their pathogenicity is slow, and this is one reason for their poor acceptance as a fungal insecticide. The expression of bumblebee, Bombus ignitus, venom serine protease (VSP) by Beauveria bassiana (ERL1170) induced melanization of yellow spotted longicorn beetles (Psacothea hilaris) as an over-reactive immune response, and caused substantially earlier mortality in beet armyworm (Spodopetra exigua) larvae when compared to the wild type. No fungal outgrowth or sporulation was observed on the melanized insects, thus suggesting a self-restriction of the dispersal of the genetically modified fungus in the environment. The research is the first use of a multi-functional bumblebee VSP to significantly increase the speed of fungal pathogenicity, while minimizing the dispersal of the fungal transformant in the environment. 相似文献
74.
Bong Cho Kim Hyung Chul Lee Je‐Jung Lee Chang‐Min Choi Dong‐Kwan Kim Jae Cheol Lee Young‐Gyu Ko Jae‐Seon Lee 《The EMBO journal》2012,31(22):4289-4303
Premature senescence, a key strategy used to suppress carcinogenesis, can be driven by p53/p21 proteins in response to various stresses. Here, we demonstrate that Wig1 plays a critical role in this process through regulation of p21 mRNA stability. Wig1 controls the association of Argonaute2 (Ago2), a central component of the RNA‐induced silencing complex (RISC), with target p21 mRNA via binding of the stem‐loop structure near the microRNA (miRNA) target site. Depletion of Wig1 prohibited miRNA‐mediated p21 mRNA decay and resulted in premature senescence. Wig1 plays an essential role in cell proliferation, as demonstrated in tumour xenografts in mice, and Wig1 and p21 mRNA levels are inversely correlated in human normal and cancer tissues. Together, our data indicate a novel role of Wig1 in RISC target accessibility, which is a key step in RNA‐mediated gene silencing. In addition, these findings indicate that fine‐tuning of p21 levels by Wig1 is essential for the prevention of cellular senescence. 相似文献
75.
Miscanthus sinensis is a promising species for biomass production. Influences of genetic and nongenetic factors on androgenesis induction efficiency
were investigated. This is the first report on successful induction of pollen-derived callus inM. sinensis. The callus yield was strongly affected by genotype. A beneficial influence of cold pretreatment of spikes on androgenesis
induction was observed. The highest yield of calli was obtained in cultures on a modified C17 medium. The results suggest
that the high callus yield might be caused by the late culture initiation. The beginning of anther culture at the end of the
flowering season caused a 17-fold increase in callus yield, in comparison to culture initiated at the height of the flowering
season (August). It is likely, however, that the efficiency of androgenesis induction in the case ofM. sinensis anther culture beginning in October could be related to a positive influence of growing donor plants in conditions of cooler
and shorter day, i.e. 11-h day with temperature around 11°C and 13-h night with temperature around 5°C. Results of this study
can significantly support the development of effective methods ofM. sinensis haploidization, which could be used in crop improvement by breeding. 相似文献
76.
Lee HS Kang IM Lee HW Seo JH Ryu JH Choi SJ Lee MJ Jeong SY Cho YW Lee KT 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2008,863(1):158-162
A simple and specific method using a one-step liquid-liquid extraction (LLE) with butyl acetate followed by high performance liquid chromatography (HPLC) coupled with positive ion electrospray ionization tandem mass spectrometry (ESI-MS/MS) detection was developed for the determination of etodolac in human plasma, using indomethacin as an internal standard (IS). Chromatographic separation was performed isocratically using a Capcellpak MGII C(18) column with 65% acetonitrile and 35% water containing 10mM ammonium formate (adjusted to pH 3.5 with formic acid). Acquisition was performed in multiple reaction monitoring (MRM) mode by monitoring the transitions: m/z 287.99>172.23 for etodolac and m/z 357.92>139.01 for IS. The method was validated to determine its selectivity, linearity, sensitivity, precision, accuracy, recovery and stability. The limit of quantitation (LLOQ) was 0.1microg/mL with a relative standard deviation of less than 15%. The devised method provides an accurate, precise and sensitive tool for determining etodolac levels in plasma. 相似文献
77.
Hypertext atlas of fetal and neonatal pathology is a free resource for pregraduate students of medicine, pathologists and other health professionals dealing with prenatal medicine. The atlas can be found at http://www.muni.cz/atlases. The access is restricted to registered users. Concise texts summarize the gross and microscopic pathology, etiology, and clinical signs of both common and rare fetal and neonatal conditions. The texts are illustrated with over 300 images that are accompanied by short comments. The atlas offers histological pictures of high quality. Virtual microscope interface is used to access the high-resolution histological images. Fetal ultrasound video clips are included. Case studies integrate clinical history, prenatal ultrasonographic examination, gross pathology and histological features. The atlas is available in English (and Czech) and equipped with an active index. The atlas is suitable both for medical students and pathologists as a teaching and reference tool. The atlas is going to be further expanded while keeping the high quality of the images. 相似文献
78.
Choong Je Ma Won Joo Jung Ki Yong Lee Young Choong Kim 《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):676-679
The n-butanol (n-BuOH) fraction of Orostachys japonicus A. Berger (Crassulaceae) significantly inhibited calpain activity. Through the activity-guided isolation from the n-BuOH fraction, herbacetin 8-O-α-D-ribopyranoside (1), kaempferol (2), quercetin (3), afzelin (4), astragalin (5), isoquercetin (6) and quercitrin (7) were obtained. Their structures were determined by spectroscopic techniques. Among them, compound 3 and 5 had significant calpain inhibitory activities. 相似文献
79.
Yi SS Hwang IK Kim DW Shin JH Nam SM Choi JH Lee CH Won MH Seong JK Yoon YS 《Neurochemical research》2011,36(1):117-128
Because it appears that oxidative stress and inflammation are implicated with disease pathogenesis in the diabetic brain,
many researchers have used streptozotocin (STZ)-induced diabetic animals to study superoxide production and the effects of
superoxide scavengers like Cu,Zn-superoxide dismutase (SOD1). However, many studies have been conducted without considering
temporal changes after STZ injection. Interestingly, though SOD activities were not significantly different among the groups,
SOD1 and 4-hydroxy-2-nonenal (4-HNE) immunoreactivities were significantly enhanced at 3 weeks after an STZ injection (STZ3w)
versus only marginal levels in sham controls, whereas microglial activity was remarkably reduced in injected rats at this
time. However, SOD1 immunoreactivity and microglial activities were only at the sham level at STZ4w. The present study provides
important information concerning cell damage by ROS generated by STZ. Microglial response was found to be inactivated at STZ3w
and neuronal cells (NeuN) showed a non-significant tendency to be reduced in number at STZ4w except in the dentate gyrus.
We speculated that the above oxidative stress-related events should be accomplished at STZ3w in the brains of STZ-induced
diabetes animal models. Therefore, the aim of the present study was to investigate chronological changes in SOD1 immunoreactivity
associated with lipid peroxidation and inflammatory responses in the hippocampi of STZ-induced type I diabetic rats. 相似文献
80.