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91.
Yoshida Y Chiba T Tokunaga F Kawasaki H Iwai K Suzuki T Ito Y Matsuoka K Yoshida M Tanaka K Tai T 《Nature》2002,418(6896):438-442
N-glycosylation of proteins in the endoplasmic reticulum (ER) has a central role in protein quality control. Here we report that N-glycan serves as a signal for degradation by the Skp1-Cullin1-Fbx2-Roc1 (SCF(Fbx2)) ubiquitin ligase complex. The F-box protein Fbx2 (ref. 4) binds specifically to proteins attached to N-linked high-mannose oligosaccharides and subsequently contributes to ubiquitination of N-glycosylated proteins. Pre-integrin beta 1 is a target of Fbx2; these two proteins interact in the cytosol after inhibition of the proteasome. In addition, expression of the mutant Fbx2 Delta F, which lacks the F-box domain that is essential for forming the SCF complex, appreciably blocks degradation of typical substrates of the ER-associated degradation pathway. Our results indicate that SCF(Fbx2) ubiquitinates N-glycosylated proteins that are translocated from the ER to the cytosol by the quality control mechanism. 相似文献
92.
Qiuli?Li Shuguang?LiEmail author Hongying?Zhou Huimin?Li Ji’an?Hong Qingchen?Wang H.?J.?Massonne 《科学通报(英文版)》2002,47(1):62-65
The U-Pb isotope compositions of rutile, omphacite and garnet in the eclogite from the Jinheqiao area in the Southern Dabie ultrahigh-pressure metamorphic zone were analyzed. The consistent high precision U-Pb age (218 ± 1.2) Ma of rutile in eclogite from the Dabie Mountains was obtained by two ways of isochron and common Pb correction based on the composition of omphacite. This proves that the omphacite in eclogite has a U/Pb ratio (m = 2.8) low enough to be used for common Pb correction in the analyses of rutile. Under the rapid cooling condition (40℃/Ma) the closure temperature for U-Pb diffusion in rutile is about 470℃. Thus, this U-Pb age of rutile proves that 218 Ma should be the cooling age of eclogite at 470℃ instead of the peak metamorphic age. 相似文献
93.
Kapfhamer D Valladares O Sun Y Nolan PM Rux JJ Arnold SE Veasey SC Bućan M 《Nature genetics》2002,32(2):290-295
Rab3a is the most abundant Rab (ras-associated binding) protein in the brain and has a regulatory role in synaptic vesicle trafficking. Mice with a targeted loss-of-function mutation in Rab3a have defects in Ca(2+)-dependent synaptic transmission: the number of vesicles released in response to an action potential is greater than in wildtype mice, resulting in greater synaptic depression and the abolishment of CA3 mossy-fiber long term potentiation. The effect of these changes on behavior is unknown. In a screen for mouse mutants with abnormal rest-activity and sleep patterns, we identified a semidominant mutation, called earlybird, that shortens the circadian period of locomotor activity. Sequence analysis of Rab3a identified a point mutation in the conserved amino acid (Asp77Gly) within the GTP-binding domain of this protein in earlybird mutants, resulting in significantly reduced levels of Rab3a protein. Phenotypic assessment of earlybird mice and a null allele of Rab3a revealed anomalies in circadian period and sleep homeostasis, providing evidence that Rab3a-mediated synaptic transmission is involved in these behaviors. 相似文献
94.
基于MATLAB软件的信号与系统实验平台,弥补了教学中的不足,通过实验,加强学生对信号与系统课程的理解和掌握。 相似文献
95.
cDNA cloning and functional analysis of 4-coumarate --CoA: ligase (4CL) gene in Chinese white aspen 总被引:5,自引:0,他引:5
cDNA encoding 4-coumarate: CoA ligase (4CL) was isolated from the secondary developing xylem of Chinese white aspen (Populus tomentosa) by RT-PCR for the first time, which was 1619 bp in length. The coding sequence and putative amino acid sequence showed 97.53% and 97.00% identity to that of Pt4CL1 in quaking aspen (P. tremuloids), respectively. Molecular analysis indicated that 4CL was encoded by multiple genes in P.tomentosa, its mRNA was highly accumulated in xylem and the expression of 4CL revealed a biphasic pattern in one growing season, almost in phase with the expression of other related enzymes in lignin biosynthesis. Transgenic research showed that expression of antisense 4CL cDNA led to the decreasing of lignin content in transgenic tobaccos, among which the average reduction was 10.3% and the highest could be up to 18.9%. These data suggested that 4CL gene was a potential gene used in altering lignin biosynthesis by biotechnology for producing new materials of papermaking. 相似文献
96.
Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector 总被引:24,自引:0,他引:24
Kay MA Manno CS Ragni MV Larson PJ Couto LB McClelland A Glader B Chew AJ Tai SJ Herzog RW Arruda V Johnson F Scallan C Skarsgard E Flake AW High KA 《Nature genetics》2000,24(3):257-261
Pre-clinical studies in mice and haemophilic dogs have shown that introduction of an adeno-associated viral (AAV) vector encoding blood coagulation factor IX (FIX) into skeletal muscle results in sustained expression of F.IX at levels sufficient to correct the haemophilic phenotype. On the basis of these data and additional pre-clinical studies demonstrating an absence of vector-related toxicity, we initiated a clinical study of intramuscular injection of an AAV vector expressing human F.IX in adults with severe haemophilia B. The study has a dose-escalation design, and all patients have now been enrolled in the initial dose cohort (2 x 10(11) vg/kg). Assessment in the first three patients of safety and gene transfer and expression show no evidence of germline transmission of vector sequences or formation of inhibitory antibodies against F.IX. We found that the vector sequences are present in muscle by PCR and Southern-blot analyses of muscle biopsies and we demonstrated expression of F.IX by immunohistochemistry. We observed modest changes in clinical endpoints including circulating levels of F.IX and frequency of FIX protein infusion. The evidence of gene expression at low doses of vector suggests that dose calculations based on animal data may have overestimated the amount of vector required to achieve therapeutic levels in humans, and that the approach offers the possibility of converting severe haemophilia B to a milder form of the disease. 相似文献
97.
以对羟基苯甲醛和丙二酸为原料,经Knoevenagel缩合反应,酯化、仿生氧化偶联、DDQ脱氢、还原和水解等反应步骤,合成了6种未见文献报道的苯并二氢呋喃新木脂素和苯并呋喃新木脂素类化合物(1~6).其中两分子对羟基苯丙烯酸甲酯仿生氧化偶联为它的二聚体(1)和DDQ脱氢反应是整个合成路线的关键步骤.DDQ脱氢反应可成功实现由苯二氢呋喃向苯并呋喃环转化,这为合成苯并呋喃新木脂素类化合物提供了一种新方法. 相似文献
98.
1998-2000年通过室内溶液培养和田间调查分析,对甜菜缺素症状与田间诊断进行了研究。结果表明,甜菜缺乏必须营养元素会表现出其特有的缺素症状,但甜菜营养生理性病害的田间诊断不仅要通过缺素症状进行形态诊断,还应结合化学诊断来综合判断其发生原因。 相似文献
99.
The mechanism of discontinuity behavior has important significance in the study of thermal science, such as fire, combustion,
explosion and heat transfer. This sort of discontinuity behavior and the catastrophe caused by system nonlinearity may be
equivalently classified according to the catastrophe model promulgated by catastrophe theory. Under the conditions of uniform
temperature and thermal isolation, the self-ignition behavior of a Semenov System can be viewed as a result of the fold catastrophe
of the system. 相似文献
100.
本文应用透射电镜技术对平原移居高原(海拔3900米)实验家兔骨髓内各级红系细胞电镜照片的费莱特直径(Feret)进行了研究,实验分平原对照组,高原给药及高原对照三个组,实验结果:高原给药组骨髓原红,早、中,晚幼红细胞Feret直径均低于高原对照组,差别有显著性,结果提示白花夏枯草可降低由低氧引起的各级幼红细胞胸体增大,从而降低血液的粘滞性,改善血循环。 相似文献