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51.
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Seo-Jung Han Jae Eun Jung Do Hee Oh Minsup Kim Jae-Min Kim Kyung-Sook Chung Hee-Soo Han Jeong-Hun Lee Kyung-Tae Lee Hee Jin Jeong In Ho Park Eunkyeong Jeon Jeon-Soo Shin Dongkeun Hwang Art E. Cho Duck-Hyung Lee Taebo Sim 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1257
Identification of highly selective type II kinase inhibitors is described. Two different chiral peptidomimetic scaffolds were introduced on the tail region of non-selective type II kinase inhibitor GNF-7 to enhance the selectivity. Kinome-wide selectivity profiling analysis showed that type II kinase inhibitor 7a potently inhibited Lck kinase with great selectivity (IC50 of 23.0 nM). It was found that 7a and its derivatives possessed high selectivity for Lck over even structurally conserved all Src family kinases. We also observed that 7a inhibited Lck activation in Jurkat T cells. Moreover, 7a was found to alleviate clinical symptoms in DSS-induced colitis mice. This study provides a novel insight into the design of selective type II kinase inhibitors by adopting chiral peptidomimetic moieties on the tail region. 相似文献
53.
G Henderson A Duncan M Kromberg J Roberts F Sim G Vafidis 《BMJ (Clinical research ed.)》1990,300(6731):1076
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Acetylation changes tau interactome to degrade tau in Alzheimer’s disease animal and organoid models
Heesun Choi Haeng Jun Kim Jinhee Yang Sehyun Chae Wonik Lee Sunwoo Chung Jisoo Kim Hyunjung Choi Hyeseung Song Chang Kon Lee Jae Hyun Jun Yong Jae Lee Kyunghyeon Lee Semi Kim Hye‐ri Sim Young Il Choi Keun Ho Ryu Jong‐Chan Park Dongjoon Lee Sun‐Ho Han Daehee Hwang Jangbeen Kyung Inhee Mook‐Jung 《Aging cell》2020,19(1)
Alzheimer's disease (AD) is an age‐related neurodegenerative disease. The most common pathological hallmarks are amyloid plaques and neurofibrillary tangles in the brain. In the brains of patients with AD, pathological tau is abnormally accumulated causing neuronal loss, synaptic dysfunction, and cognitive decline. We found a histone deacetylase 6 (HDAC6) inhibitor, CKD‐504, changed the tau interactome dramatically to degrade pathological tau not only in AD animal model (ADLPAPT) brains containing both amyloid plaques and neurofibrillary tangles but also in AD patient‐derived brain organoids. Acetylated tau recruited chaperone proteins such as Hsp40, Hsp70, and Hsp110, and this complex bound to novel tau E3 ligases including UBE2O and RNF14. This complex degraded pathological tau through proteasomal pathway. We also identified the responsible acetylation sites on tau. These dramatic tau‐interactome changes may result in tau degradation, leading to the recovery of synaptic pathology and cognitive decline in the ADLPAPT mice. 相似文献
56.
Mikovski Andréia Izabel da Silva Nayara Tayane Silva Lázara Aline Simões Machado Mariana de Souza Barbosa Lília Cristina Reis Aryane Campos de Matos Elyabe Monteiro Viccini Lyderson Facio da Silva Souza Claudinei Machado Marcelo Dias Otoni Wagner Campos de Carvalho Ilio Fealho Rocha Diego Ismael da Silva Maurecilne Lemes 《Plant Cell, Tissue and Organ Culture》2021,145(2):239-259
Plant Cell, Tissue and Organ Culture (PCTOC) - Somaclonal variation during in vitro culture is often an undesirable phenomenon but may also be a source of genetic variation useful for breeders. The... 相似文献
57.
Iago Vinicios Geller Diego Azevedo Zoccal Garcia Alan Deivid Pereira Armando Cesar Rodrigues Casimiro Crislaine Cochak Jean Ricardo Simões Vitule Mário Luís Orsi 《Zeitschrift fur angewandte Ichthyologie》2021,37(5):779-785
The combination of highly equipped smartphones, with the increased use of social media, has offered a wide database. Given this, citizen science can be used to record and monitor non-native fish fauna, target new samples and collaborate with monitoring occurrences in new areas. We aimed to demonstrate the efficiency of social media in citizen science as a tool to cooperate with monitoring studies of non-native species. Consequently, we determined the occurrence points of S. brasiliensis in the Iguaçu River basin, indicating sites of greatest occurrence and analyzing the impact of the invasion on the native fauna of the basin. Files and information available on the YouTube® and Facebook® media platforms were used as data, was carried out from April 2019 to April 2020. The results were 40 records, 22 videos obtained from Youtube, and seven videos and 11 photos from Facebook, the oldest record was from April 2013, while the largest number of posts was in 2016. Fish records available from online platforms can reveal the occurrence and progressive dispersion of species, in the context of biological invasions, these tools can be of great value in studies that aim to follow the progress of introduced species, contributing by helping to direct new sampling programs and corroborating the occurrence of species in new areas in conjunction with standard monitoring programs. Based on citizen science records, it was possible to update the range of occurrence of the non-native S. brasiliensis in the Iguaçu River basin, cooperating with scientific knowledge. Innovative monitoring and control measures are necessary to deal with invasive species, with citizen science proving to be competent for determining the occurrence of species and showing promise in the entire field of ichthyology. 相似文献
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Ng Chu Xin Le Cheng Foh Tor Yin Sim Lee Sau Har 《International journal of peptide research and therapeutics》2021,27(4):2757-2775
International Journal of Peptide Research and Therapeutics - Bioactive peptides have emerged as promising therapeutic alternatives in pharmaceutical industry, especially to fight cancer. Here we... 相似文献
60.
Joseana Vieira Flávia Cristina de Paula Freitas Alexandre Santos Cristino Daniel Guariz Pinheiro Luiz Roberto Aguiar Marcela Aparecida Framartino Bezerra Laure Lívia Maria Rosatto Moda Zilá Luz Paulino Simões Angel Roberto Barchuk 《Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms》2021,1864(9):194732
Brain differential morphogenesis in females is one of the major phenotypic manifestations of caste development in honey bees. Brain diphenism appears at the fourth larval phase as a result of the differential feeding regime developing females are submitted during early phases of larval development. Here, we used a forward genetics approach to test the early brain molecular response to differential feeding leading to the brain diphenism observed at later developmental phases. Using RNA sequencing analysis, we identified 53 differentially expressed genes (DEGs) between the brains of queens and workers at the third larval phase. Since miRNAs have been suggested to play a role in caste differentiation after horizontal and vertical transmission, we tested their potential participation in regulating the DEGs. The miRNA-mRNA interaction network, including the DEGs and the royal- and worker-jelly enriched miRNA populations, revealed a subset of miRNAs potentially involved in regulating the expression of DEGs. The interaction of miR-34, miR-210, and miR-317 with Takeout, Neurotrophin-1, Forked, and Masquerade genes was experimentally confirmed using a luciferase reporter system. Taken together, our results reconstruct the regulatory network that governs the development of the early brain diphenism in honey bees. 相似文献