Regulation of the mitochondrial dynamin-like protein Opa1 by proteolytic cleavage

The dynamin-related protein Opa1 is localized to the mitochondrial intermembrane space, where it facilitates fusion between mitochondria. Apoptosis causes Opa1 release into the cytosol and causes mitochondria to fragment. Loss of mitochondrial membrane potential also causes mitochondrial fragmentation but not Opa1 release into the cytosol. Both conditions induce the proteolytic cleavage of Opa1, suggesting that mitochondrial fragmentation is triggered by Opa1 inactivation. The opposite effect was observed with knockdown of the mitochondrial intermembrane space protease Yme1. Knockdown of Yme1 prevents the constitutive cleavage of a subset of Opa1 splice variants but does not affect carbonyl cyanide m-chlorophenyl hydrazone or apoptosis-induced cleavage. Knockdown of Yme1 also increases mitochondrial connectivity, but this effect is independent of Opa1 because it also occurs in Opa1 knockdown cells. We conclude that Yme1 constitutively regulates a subset of Opa1 isoforms and an unknown mitochondrial morphology protein, whereas the loss of membrane potential induces the further proteolysis of Opa1

Tensile strain increases expression of CCN2 and COL2A1 by activating TGF-beta-Smad2/3 pathway in chondrocytic cells

Physiologic mechanical stress stimulates expression of chondrogenic genes, such as multifunctional growth factor CYR61/CTGF/NOV (CCN) 2 and alpha 1(II) collagen (COL2A1), and maintains cartilage home-ostasis. In our previous studies, cyclic tensile strain (CTS) induces nuclear translocation of transforming growth factor (TGF)-beta receptor-regulated Smad2/3 and the master chondrogenic transcription factor Srytype HMG box (SOX) 9. However, the precise mechanism of stretch-mediated Smad activation remains unclear in transcriptional regulation of CCN2 and COL2A1. Here we hypothesized that CTS may induce TGF-beta 1 release and stimulate Smad-dependent chondrogenic gene expression in human chondrocytic SW1353 cells. Uni-axial CTS (0.5 Hz, 5% strain) stimulated gene expression of CCN2 and COL2A1 in SW1353 cells, and induced TGF-beta 1 secretion. CCN2 synthesis and nuclear translocalization of Smad2/3 and SOX9 were stimulated by CTS. In addition, CTS increased the complex formation between phosphorylated Smad2/3 and SOX9. The CCN2 promoter activity was cooperatively enhanced by CIS and Smad3 in luciferase reporter assay. Chromatin immunoprecipitation revealed that CTS increased Smad2/3 interaction with the CCN2 promoter and the COL2A1 enhancer. Our results suggest that CTS epigenetically stimulates CCN2 transcription via TGF-beta 1 release associated with Smad2/3 activation and enhances COL2A1 expression through the complex formation between SOX9 and Smad2/3

Control of peroxyoxalate chemiluminescence by nitrogen-containing ligand quenching: turning off and on by ligand-metal ion host-guest interactions

ArticleTETRAHEDRON. 67(36):6927-6933 (2011)journal articl

Association between Mammographic Breast Density and Lifestyle in Japanese Women

A high mammographic breast density is considered to be a risk factor for breast cancer. However, only a small number of studies on the association between breast density and lifestyle have been performed. A cross-sectional study was performed using a survey with 29 questions on life history and lifestyle. The breast density on mammography was classified into 4 categories following the BI-RADS criteria. The subjects were 522 women with no medical history of breast cancer. The mean age was 53.3 years old. On multivariate analysis, only BMI was a significant factor determining breast density in premenopausal women (parameter estimate, －0.403;p value, 0.0005), and the density decreased as BMI rose. In postmenopausal women, BMI (parameter estimate, －0.196;p value, 0.0143) and number of deliveries (parameter estimate, －0.388;p value, 0.0186) were significant factors determining breast density;breast density decreased as BMI and number of deliveries increased. Only BMI and number of deliveries were identified as factors significantly influencing breast density. BMI was inversely correlated with breast density before and after menopause, whereas the influence of number of deliveries on breast density was significant only in postmenopausal women in their 50 and 60s

Zerobot®: A Remote-controlled Robot for Needle Insertion in CT-guided Interventional Radiology Developed at Okayama University

Since 2012, we have been developing a remote-controlled robotic system (Zerobot®) for needle insertion during computed tomography (CT)-guided interventional procedures, such as ablation, biopsy, and drainage. The system was designed via a collaboration between the medical and engineering departments at Okayama University, including various risk control features. It consists of a robot with 6 degrees of freedom that is manipulated using an operation interface to perform needle insertions under CT-guidance. The procedure includes robot positioning, needle targeting, and needle insertion. Phantom experiments have indicated that robotic insertion is equivalent in accuracy to manual insertion, without physician radiation exposure. Animal experiments have revealed that robotic insertion of biopsy introducer needles and various ablation needles is safe and accurate in vivo. The first in vivo human trial, therefore, began in April 2018. After its completion, a larger clinical study will be conducted for commercialization of the robot. This robotic procedure has many potential advantages over a manual procedure: 1) decreased physician fatigue; 2) stable and accurate needle posture without tremor; 3) procedure automation; 4) less experience required for proficiency in needle insertion skills; 5) decreased variance in technical skills among physicians; and 6) increased likelihood of performing the procedure at remote hospitals (i.e., telemedicine)

Novel anti‐tumor mechanism of galanin receptor type 2 in head and neck squamous cell carcinoma cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102710/1/cas12315.pd