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排序方式: 共有188条查询结果,搜索用时 15 毫秒
181.
Pepsin is formed as the zymogen, pepsinogen, which includes an additional 44 residue prosegment (PS) on the N-terminus. Upon acidification (pH <3) the PS is removed, yielding active pepsin. The PS is critical to such processes as the initiation of correct folding and protein stability. In the present study, the NMR assignments of the 34.6 kDa native porcine pepsin and porcine pepsin complexed with pepstatin are reported in order to obtain structural information regarding PS-catalyzed protein folding. Such information would contribute to a better understanding of the nature of folding/unfolding energy barrier of pepsin and other aspartic proteases. 相似文献
182.
Masato Moteki Naho Horimoto Riou Nagaiwa Kazuo Amakasu Takashi Ishimaru Yukuya Yamaguchi 《Polar Biology》2009,32(10):1461-1472
The horizontal and vertical distributions of fish were examined off Lützow-Holm Bay in the Indian Ocean sector of the Southern
Ocean during midnight sun in January 2005. Fish were sampled from six discrete depth layers (0–2,000 m). The most abundant
fish in layers from the surface to 200 m were larval stages of Electrona antarctica and Notolepis coatsi. In layers from 200 to 2,000 m, fish assemblages were relatively uniform among all stations and were dominated by E. antarctica (juvenile–subadult), Cyclothone microdon, and Bathylagus antarcticus. Cluster analysis revealed three epipelagic communities related to water temperature and salinity. An ontogenetic habitat
shift to deeper layers was apparent for E. antarctica, N. coatsi, and B. antarcticus. Preferences for warm waters were observed in E. antarctica (larvae) and N. coatsi (preflexion to flexion larvae), although they were distributed across a broad range of temperature and salinity in epipelagic
zones. 相似文献
183.
Susan L. Makris Howard M. Solomon Ruth Clark Kohei Shiota Stephane Barbellion Jochen Buschmann Makoto Ema Michio Fujiwara Konstanze Grote Keith P. Hazelden Kok Wah Hew Masao Horimoto Yojiro Ooshima Meg Parkinson L. David Wise 《Birth defects research. Part B, Developmental and reproductive toxicology》2011,92(6):575-575
184.
185.
Takumi Itoh Ryo Hatano Yoshiya Horimoto Taketo Yamada Dan Song Haruna Otsuka Yuki Shirakawa Shuji Mastuoka Noriaki Iwao Thomas M. Aune Nam H. Dang Yutaro Kaneko Ko Okumura Chikao Morimoto Kei Ohnuma 《Cell death & disease》2021,12(6)
Triple-negative breast cancer (TNBC) has a poor prognosis compared to other breast cancer subtypes. Although epidermal growth factor receptor (EGFR) is overexpressed in TNBC, clinical trials with EGFR inhibitors including tyrosine kinase inhibitors (EGFR-TKI) in TNBC have heretofore been unsuccessful. To develop effective EGFR-targeted therapy for TNBC, the precise mechanisms of EGFR-TKI resistance in TNBC need to be elucidated. In this study, to understand the molecular mechanisms involved in the differences in EGFR-TKI efficacy on TNBC between human and mouse, we focused on the effect of IL-26, which is absent in mice. In vitro analysis showed that IL-26 activated AKT and JNK signaling of bypass pathway of EGFR-TKI in both murine and human TNBC cells. We next investigated the mechanisms involved in IL-26-mediated EGFR-TKI resistance in TNBC. We identified EphA3 as a novel functional receptor for IL-26 in TNBC. IL-26 induced dephosphorylation and downmodulation of EphA3 in TNBC, which resulted in increased phosphorylation of AKT and JNK against EGFR-TKI-induced endoplasmic reticulum (ER) stress, leading to tumor growth. Meanwhile, the blockade of IL-26 overcame EGFR-TKI resistance in TNBC. Since the gene encoding IL-26 is absent in mice, we utilized human IL-26 transgenic (hIL-26Tg) mice as a tumor-bearing murine model to characterize the role of IL-26 in the differential effect of EGFR-TKI in human and mice and to confirm our in vitro findings. Our findings indicate that IL-26 activates the bypass pathway of EGFR-TKI, while blockade of IL-26 overcomes EGFR-TKI resistance in TNBC via enhancement of ER stress signaling. Our work provides novel insights into the mechanisms of EGFR-TKI resistance in TNBC via interaction of IL-26 with its newly identified receptor EphA3, while also suggesting IL-26 as a possible therapeutic target in TNBC.Subject terms: Stress signalling, Cell death and immune response, Breast cancer 相似文献
186.
Ayumu Yamashita Yuki Sakai Takashi Yamada Noriaki Yahata Akira Kunimatsu Naohiro Okada Takashi Itahashi Ryuichiro Hashimoto Hiroto Mizuta Naho Ichikawa Masahiro Takamura Go Okada Hirotaka Yamagata Kenichiro Harada Koji Matsuo Saori C. Tanaka Mitsuo Kawato Kiyoto Kasai Nobumasa Kato Hidehiko Takahashi Yasumasa Okamoto Okito Yamashita Hiroshi Imamizu 《PLoS biology》2020,18(12)
Many studies have highlighted the difficulty inherent to the clinical application of fundamental neuroscience knowledge based on machine learning techniques. It is difficult to generalize machine learning brain markers to the data acquired from independent imaging sites, mainly due to large site differences in functional magnetic resonance imaging. We address the difficulty of finding a generalizable marker of major depressive disorder (MDD) that would distinguish patients from healthy controls based on resting-state functional connectivity patterns. For the discovery dataset with 713 participants from 4 imaging sites, we removed site differences using our recently developed harmonization method and developed a machine learning MDD classifier. The classifier achieved an approximately 70% generalization accuracy for an independent validation dataset with 521 participants from 5 different imaging sites. The successful generalization to a perfectly independent dataset acquired from multiple imaging sites is novel and ensures scientific reproducibility and clinical applicability.Biomarkers for psychiatric disorders based on neuroimaging data have yet to be put to practical use. This study overcomes the problems of inter-site differences in fMRI data by using a novel harmonization method, thereby successfully constructing a generalizable brain network marker of major depressive disorder across multiple imaging sites. 相似文献
187.
188.
Derek R. Dee Shaun Filonowicz Yasumi Horimoto Rickey Y. Yada 《Biochimica et Biophysica Acta - Proteins and Proteomics》2009,1794(12):1795-1801
Porcine pepsin A, a gastric aspartic peptidase, is initially produced as the zymogen pepsinogen that contains an N-terminal, 44 residue prosegment (PS) domain. In the absence of the PS, native pepsin (Np) is irreversibly denatured and when placed under refolding conditions, folds to a thermodynamically stable denatured state. This denatured, refolded pepsin (Rp) state can be converted to Np by the exogenous addition of the PS, which catalyzes the folding of Rp to Np. In order to thoroughly study the mechanism by which the PS catalyzes pepsin folding, a soluble protein expression system was developed to produce recombinant PS peptide in a highly pure form. Using this system, the wild-type and three-mutant PS forms, in which single residue substitutions were made (V4A, R8A and K36A), were expressed and purified. These PS peptides were characterized for their ability to inhibit Np enzymatic activity and to catalyze the folding of Rp to Np. The V4A, R8A and K36A mutant PS peptides were found to have nanomolar inhibition constants, Ki, of 82.4, 58.3 and 95.6 nM, respectively, approximately a two-fold increase from that of the wild-type PS (36.2 nM). All three-mutant PS peptides were found to catalyze Np folding with a rate constant of 0.06 min? 1, five-fold lower than that of the wild-type. The observation that the mutant PS peptides retained their inhibition and folding-catalyst functionality suggests a high level of resilience to mutations of the pepsin PS. 相似文献