Effects of the DNA state fluctuation on single-cell dynamics of self-regulating gene

A dynamical mean-field theory is developed to analyze stochastic single-cell dynamics of gene expression. By explicitly taking account of nonequilibrium and nonadiabatic features of the DNA state fluctuation, two-time correlation functions and response functions of single-cell dynamics are derived. The method is applied to a self-regulating gene to predict a rich variety of dynamical phenomena such as anomalous increase of relaxation time and oscillatory decay of correlations. Effective "temperature" defined as the ratio of the correlation to the response in the protein number is small when the DNA state change is frequent, while it grows large when the DNA state change is infrequent, indicating the strong enhancement of noise in the latter case.Comment: 18 pages, 5 figure

マウスにおける動脈硬化性急性大動脈症候群の発症に対するケルセチンの予防効果

Atherosclerosis-related acute aortic syndromes, such as aortic aneurysms or aortic dissection are life-threatening diseases. Since they develop suddenly and progress rapidly, the establishment of preventive strategies is urgently needed. Quercetin, a flavonoid abundant in various vegetables and fruits, is suggested to reduce the risk of cardiovascular disease. Therefore, in this study, the preventive effect of quercetin was evaluated using a mouse model of aortic aneurysm and dissection. The model was established by administering angiotensin II (Ang II) and β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, to mice to induce hypertension and degeneration of the elastic lamina, which would eventually result in the onset of an aortic aneurysm. Ang II, BAPN, and a nitric oxide synthase inhibitor was administered to induce aortic dissection via endothelial dysfunction. Quercetin (60 mg/kg/day) was administered 2 weeks before inducing aortic diseases by the end of the experiments (8 weeks in the aneurysm model, 6 weeks in the dissection model). It was found to reduce the incidence of aneurysm (from 72 to 45%), dissection (from 17 to 10%), and rupture (from 33 to 15%) in mice. Elastin degradation was ameliorated in the quercetin-treated mice compared to that in the mice without quercetin treatment (degradation score 2.9 ± 0.3 vs 2.2 ± 0.2). Furthermore, quercetin suppressed the expression of vascular cell adhesion molecule-1, macrophage infiltration, and pro-matrix metalloproteinase-9 activity. Our results suggest that quercetin might prevent the onset of atherosclerosis-related acute aortic syndromes through its anti-inflammatory and endothelial cell-protective effects

Preventive Effects of Quercetin against the Onset of Atherosclerosis-Related Acute Aortic Syndromes in Mice

Atherosclerosis-related acute aortic syndromes, such as aortic aneurysms or aortic dissection are life-threatening diseases. Since they develop suddenly and progress rapidly, the establishment of preventive strategies is urgently needed. Quercetin, a flavonoid abundant in various vegetables and fruits, is suggested to reduce the risk of cardiovascular disease. Therefore, in this study, the preventive effect of quercetin was evaluated using a mouse model of aortic aneurysm and dissection. The model was established by administering angiotensin II (Ang II) and β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, to mice to induce hypertension and degeneration of the elastic lamina, which would eventually result in the onset of an aortic aneurysm. Ang II, BAPN, and a nitric oxide synthase inhibitor was administered to induce aortic dissection via endothelial dysfunction. Quercetin (60 mg/kg/day) was administered 2 weeks before inducing aortic diseases by the end of the experiments (8 weeks in the aneurysm model, 6 weeks in the dissection model). It was found to reduce the incidence of aneurysm (from 72 to 45%), dissection (from 17 to 10%), and rupture (from 33 to 15%) in mice. Elastin degradation was ameliorated in the quercetin-treated mice compared to that in the mice without quercetin treatment (degradation score 2.9 ± 0.3 vs 2.2 ± 0.2). Furthermore, quercetin suppressed the expression of vascular cell adhesion molecule-1, macrophage infiltration, and pro-matrix metalloproteinase-9 activity. Our results suggest that quercetin might prevent the onset of atherosclerosis-related acute aortic syndromes through its anti-inflammatory and endothelial cell-protective effects

Optical development in the murine eye lens of accelerated senescence-prone SAMP8 and senescence-resistant SAMR1 strains

The eye lens is responsible for focusing objects at various distances onto the retina and its refractive power is determined by its surface curvature as well as its internal gradient refractive index (GRIN). The lens continues to grow with age resulting in changes to the shape and to the GRIN profile. The present study aims to investigate how the ageing process may influence lens optical development. Murine lenses of accelerated senescence-prone strain (SAMP8) aged from 4 to 50 weeks; senescence-resistant strain (SAMR1) aged from 5 to 52 weeks as well as AKR strain (served as control) aged from 6 to 70 weeks were measured using the X-ray interferometer at the SPring-8 synchrotron Japan within three consecutive years from 2020 to 2022. Three dimensional distributions of the lens GRIN were reconstructed using the measured data and the lens shapes were determined using image segmentation in MatLab. Variations in the parameters describing the lens shape and the GRIN profile with age were compared amongst three mouse strains. With advancing age, both the lens anterior and posterior surface flattens and the lens sagittal thickness increase in all three mouse strains (Anterior radius of curvature increase at 0.008 mm/week, 0.007 mm/week and 0.002 mm/week while posterior radius of curvature increase at 0.002 mm/week, 0.007 mm/week and 0.003 mm/week respectively in AKR, SAMP8 and SAMR1 lenses). Compared with the AKR strain, the SAMP8 samples demonstrate a higher rate of increase in the posterior curvature radius (0.007 mm/week) and the thickness (0.015 mm/week), whilst the SAMR1 samples show slower increases in the anterior curvature radius (0.002 mm/week) and its thickness (0.013 mm/week). There are similar age-related trends in GRIN shape in the radial direction (in all three types of murine lenses nr2 and nr6 increase with age while nr4 decrease with age consistently) but not in the axial direction amongst three mouse strains (nz1 of AKR lens decrease while of SAMP8 and SAMR1 increase with age; nz2 of all three models increase with age; nz3 of AKR lens increase while of SAMP8 and SAMR1 decrease with age). The ageing process can influence the speed of lens shape change and affect the GRIN profile mainly in the axial direction, contributing to an accelerated decline rate of the optical power in the senescence-prone strain (3.5 D/week compared to 2.3 D/week in the AKR control model) but a retardatory decrease in the senescence-resistant strain (2.1 D/week compared to the 2.3D/week in the AKR control model).</p