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AAA-ATPase p97/Cdc48p, a Cytosolic Chaperone Required for Endoplasmic Reticulum-Associated Protein Degradation 下载免费PDF全文
Efrat Rabinovich Anat Kerem Kai-Uwe Frhlich Noam Diamant Shoshana Bar-Nun 《Molecular and cellular biology》2002,22(2):626-634
Endoplasmic reticulum-associated degradation (ERAD) disposes of aberrant proteins in the secretory pathway. Protein substrates of ERAD are dislocated via the Sec61p translocon from the endoplasmic reticulum to the cytosol, where they are ubiquitinated and degraded by the proteasome. Since the Sec61p channel is also responsible for import of nascent proteins, this bidirectional passage should be coordinated, probably by molecular chaperones. Here we implicate the cytosolic chaperone AAA-ATPase p97/Cdc48p in ERAD. We show the association of mammalian p97 and its yeast homologue Cdc48p in complexes with two respective ERAD substrates, secretory immunoglobulin M in B lymphocytes and 6myc-Hmg2p in yeast. The membrane 6myc-Hmg2p as well as soluble lumenal CPY*, two short-lived ERAD substrates, are markedly stabilized in conditional cdc48 yeast mutants. The involvement of Cdc48p in dislocation is underscored by the accumulation of ERAD substrates in the endoplasmic reticulum when Cdc48p fails to function, as monitored by activation of the unfolded protein response. We propose that the role of p97/Cdc48p in ERAD, provided by its potential unfoldase activity and multiubiquitin binding capacity, is to act at the cytosolic face of the endoplasmic reticulum and to chaperone dislocation of ERAD substrates and present them to the proteasome. 相似文献
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Rena Pollack Noam Koch Haggi Mazeh Avivit Cahn Lilach Katz Liat Appelbaum 《Endocrine practice》2022,28(8):754-759
ObjectiveIn our country, thyroid nodules are sonographically evaluated in health maintenance organization (HMO) imaging centers, and patients are referred to tertiary hospitals for ultrasound-guided fine-needle aspiration (FNA) biopsy when indicated. We evaluated the concordance in Thyroid Imaging Reporting and Data System (TI-RADS) classification reporting between these sites.MethodsWe conducted a retrospective cohort study reviewing the sonographic features of thyroid nodules evaluated both at the HMO and a large tertiary center between January 2018 and December 2019. The primary outcome was concordance between the TI-RADS classification at both sites. Additional endpoints included correlation of TI-RADS to the Bethesda category following FNA and correlation of TI-RADS with malignancy on final pathology at each site.ResultsThe records of 336 patients with 370 nodules were reviewed. The level of concordance was poor (19.8%), with 277 (74.8%) nodules demonstrating higher TI-RADS and 20 (5.4%) lower TI-RADS at the HMO compared to the hospital (P < .001; weighted κ = 0.120). FNA results were available for 236 (63.8%) nodules. The Bethesda category strongly correlated with the hospital TI-RADS (P < .001), yet not with HMO TI-RADS (P = .123). In the surgically removed 57 nodules, a strong correlation was identified between the malignancy on final pathology and TI-RADS documented at the hospital (P < .001), yet not at the HMO (P = .259).ConclusionsThere is poor agreement between TI-RADS classification on ultrasound performed in the HMO compared to a tertiary hospital. The hospital’s TI-RADS strongly correlated with the Bethesda category and the final risk of malignancy, unlike the HMO. 相似文献
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The Multi-Dimensional Voice Program (MDVP) and Praat are computer programs commonly used for acoustic analysis of voice in clinical and research settings. Both softwares extract a set of acoustic parameters, many of which are defined similarly. The purpose of this study was to compare results obtained by both programs, and examine whether they can clinically distinguish among pathological groups differently. Fifty-eight women participated in the study. Of these women, 28 were diagnosed with functional dysphonia and 30 were diagnosed with benign mass-lesions (10 nodules, ten polyps and 10 cysts). Six productions of the vowels /a/ and /i/, were analyzed using MDVP and Praat. Results show similar mean fundamental-frequency (mF0) values for both programs (P > 0.05). However, values of jitter, shimmer, noise-to-harmonic ratio (NHR) and degree of unvoiced (DUV) segment were significantly lower using Praat, in comparison with MDVP. Jitter values obtained using MDVP, for the vowel /i/, revealed a significant group difference between the nodule and cyst groups (P < 0.05). This group contrast was not observed using Praat. Results demonstrate that although high correlations are found between values obtained by both programs, individual numerical values vary greatly. Therefore, combining results from both programs are not advisable. In addition, there are indications that linear transformation for the results from one program to the other might lead to erroneous conclusions, and should be carried out with caution. 相似文献