Abstract We investigated the role of nuclear factor (NF)-κB on tumor necrosis factor (TNF)-α-induced regulated upon activation, normal T-cell expressed and secreted (RANTES) expression in fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA). Using cultured human fibroblast-like synoviocytes from patients with RA, semiquantitative reverse transcriptase-polymerase chain reaction, electrophoretic mobility shift assay, and Western blot were performed for RANTES expression, NF-κB activation, and degradation of IκB, respectively. In addition, the transcriptional effect of TNF-α on RANTES gene expression was analyzed by reporter gene assay. We found that TNF-α clearly induced RANTES protein production and expression of RANTES mRNA in a time-dependent manner. Furthermore, TNF-α persistently induced NF-κB activation caused by IκBα and IκBβ1 degradation. Supershift analysis revealed that TNF-α-induced DNA-binding complexes were composed principally of the p65 and p50 Rel family members. Moreover, transcriptional activation of the RANTES promoter by TNF-α was dependent on specific NF-κB response elements that were regulated by NF-κB. Results herein indicate that NF-κB activation caused by degradation of IκBα and IκBβ1 by TNF-α increased RANTES gene expression in fibroblast-like synoviocytes, suggesting that NF-κB plays an important role in the migration of inflammatory cells by RANTES to the synovium in patients with rheumatoid arthritis.
In an agricultural field, plant phenotyping using object detection models is gaining attention. However, collecting the training data necessary to create generic and high-precision models is extremely challenging due to the difficulty of annotation and the diversity of domains. Furthermore, it is difficult to transfer training data across different crops, and although machine learning models effective for specific environments, conditions, or crops have been developed, they cannot be widely applied in actual fields. In this study, we propose a generative data augmentation method (D4) for vineyard shoot detection. D4 uses a pre-trained text-guided diffusion model based on a large number of original images culled from video data collected by unmanned ground vehicles or other means, and a small number of annotated datasets. The proposed method generates new annotated images with background information adapted to the target domain while retaining annotation information necessary for object detection. In addition, D4 overcomes the lack of training data in agriculture, including the difficulty of annotation and diversity of domains. We confirmed that this generative data augmentation method improved the mean average precision by up to 28.65% for the BBox detection task and the average precision by up to 13.73% for the keypoint detection task for vineyard shoot detection. Our generative data augmentation method D4 is expected to simultaneously solve the cost and domain diversity issues of training data generation in agriculture and improve the generalization performance of detection models.
Abstract U6 snRNA undergoes post-transcriptional 3′ end modification prior to incorporation into the active site of spliceosomes. The responsible exoribonuclease is Usb1, which removes nucleotides from the 3′ end of U6 and, in humans, leaves a 2′,3′ cyclic phosphate that is recognized by the Lsm2–8 complex. Saccharomycescerevisiae Usb1 has additional 2′,3′ cyclic phosphodiesterase (CPDase) activity, which converts the cyclic phosphate into a 3′ phosphate group. Here we investigate the molecular basis for the evolution of Usb1 CPDase activity. We examine the structure and function of Usb1 from Kluyveromyces marxianus, which shares 25 and 19% sequence identity to the S. cerevisiae and Homo sapiens orthologs of Usb1, respectively. We show that K. marxianus Usb1 enzyme has CPDase activity and determined its structure, free and bound to the substrate analog uridine 5′-monophosphate. We find that the origin of CPDase activity is related to a loop structure that is conserved in yeast and forms a distinct penultimate (n – 1) nucleotide binding site. These data provide structural and mechanistic insight into the evolutionary divergence of Usb1 catalysis.
Objective: The ages at onset of myasthenia gravis (MG) in Japan show two peaks, the highest in the young children around 3 year-old followed by usual peak in young adulthood. This presentation covers the clinical characteristics and treatment of the childhood MG.
At least two separate enzymes, an endonuclease and a ligase, are thought to be involved in the tRNA splicing pathway. The yeast and archaeal endonucleases acting in the first step of tRNA splicing commonly produce 2′, 3′-cyclic phosphate and 5′ hydroxy group at the exon-intron borders. Despite this similarity in the first step of tRNA splicing, the subsequent mechanism of archaeal splicing pathway has not been elucidated yet. We have been searching for the archaeal ligase activitiy from Methanosarcina acetivorans. Here, we report the distinct activity of a splicing endonuclease detected in its cell extract.
