Cryptochrome and Period Proteins Are Regulated by the CLOCK/BMAL1 Gene: Crosstalk between the PPARs/RXRα-Regulated and CLOCK/BMAL1-Regulated Systems

Feeding and the circadian system regulate lipid absorption and metabolism, and the expression of enzymes involved in lipid metabolism is believed to be directly controlled by the clock system. To investigate the interaction between the lipid metabolism system and the circadian system, we analyzed the effect of a CLOCK/BMAL1 heterodimer on the transcriptional regulation of PPAR-controlled genes through PPAR response elements (PPREs). Transcription of acyl-CoA oxidase, cellular retinol binding protein II (CRBPII), and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase was altered by CLOCK/BMAL1, and transcriptional activity via PPRE by PPARs/RXRα was enhanced by CLOCK/BMAL1 and/or by PPARs ligand/activators. We also found that CLOCK/BMAL1-mediated transcription of period (PER) and cryptochrome (CRY) was modulated by PPARα/RXRα. These results suggest that there may be crosstalk between the PPARs/RXRα-regulated system and the CLOCK/BMAL1-regulated system

One-, Two-, and Three-dimensional Simulations of Oxygen Shell Burning Just Before the Core-Collapse of Massive Stars

We perform two- (2D) and three-dimensional (3D) hydrodynamics simulations of convective oxygen shell-burning that takes place deep inside a massive progenitor star of a core-collapse supernova. Using one dimensional (1D) stellar evolution code, we first calculate the evolution of massive stars with an initial mass of 9-40 $M_\odot$. Four different overshoot parameters are applied, and CO core mass trend similar to previous works is obtained in the 1D models. Selecting eleven 1D models that have a silicon and oxygen coexisting layer, we perform 2D hydrodynamics simulations of the evolution $\sim$100 s until the onset of core-collapse. We find that convection with large-scale eddies and the turbulent Mach number $\sim$0.1 is obtained in the models having a Si/O layer with a scale of 10$^8$ cm, whereas most models that have an extended O/Si layer up to a few $\times 10^9$ cm exhibit lower turbulent velocity. Our results indicate that the supernova progenitors that possess a thick Si/O layer could provide a preferable condition for perturbation-aided explosions. We perform 3D simulation of a 25 $M_\odot$ model, which exhibits large-scale convection in the 2D models. The 3D model develops large ($\ell = 2$) convection similar to the 2D model, however, the turbulent velocity is lower. By estimating the neutrino emission properties of the 3D model, we point out that a time modulation of the event rates, if observed in KamLAND and Hyper-Kamiokande, would provide an important information about structural changes in the presupernova convective layer.Comment: 25 pages, 17 figures, 2 tables. Accepted for publication in Ap

Three-dimensional Hydrodynamics Simulations of Precollapse Shell Burning in the Si- and O-rich Layers

We present 3D hydrodynamics simulations of shell burning in two progenitors with zero-age main-sequence masses of 22 and 27 $M_{\odot}$ for $\sim$65 and 200 s up to the onset of gravitational collapse, respectively. The 22 and 27 $M_{\odot}$ stars are selected from a suite of 1D progenitors. The former and the latter have an extended Si- and O-rich layer with a width of $\sim$10$^9$ cm and $\sim$5$\times 10^9$ cm, respectively. Our 3D results show that turbulent mixing occurs in both of the progenitors with the angle-averaged turbulent Mach number exceeding $\sim$0.1 at the maximum. We observe that an episodic burning of O and Ne, which takes place underneath the convection bases, enhances the turbulent mixing in the 22 and 27 $M_\odot$ models, respectively. The distribution of nucleosynthetic yields is significantly different from that in 1D simulations, namely, in 3D more homogeneous and inhomogeneous in the radial and angular direction, respectively. By performing a spectrum analysis, we investigate the growth of turbulence and its role of material mixing in the convective layers. We also present a scalar spherical harmonics mode analysis of the turbulent Mach number. This analytical formula would be helpful for supernova modelers to implement the precollapse perturbations in core-collapse supernova simulations. Based on the results, we discuss implications for the possible onset of the perturbation-aided neutrino-driven supernova explosion.Comment: 23 pages, 26 figures, 5 tables. Accepted for publication in Astrophys.

Dietary effect of selenium-fortified Chlorella vulgaris on reproduction of Brachionus plicatilis species complex (Rotifera: Monogononta)

We investigated the effects of fortifying a diet of Chlorella vulgaris with Selenium (Se) on sexual and asexual reproduction of rotifers in the Brachionus plicatilis species complex: i.e. two strains of B. plicatilis sensu stricto and one of Brachionus rotundiformis. These rotifers were cultured for 8?10 days on one of three different diets that were adjusted to provide the same dry weight of food: non-fortified Chlorella, Se-fortified Chlorella, and Nannochloropsis oculata. B. plicatilis (Makishima strain), which is obligatorily asexual, showed no difference in population growth rate among the three different diets (r?=?0.55?0.61). On the other hand, B. plicatilis (NH17L strain), which reproduces by cyclical parthenogenesis, showed higher population growth (r?=?0.25) and also higher rates of fertilization (35.9%) and absolute resting egg production (2803.9?eggs/g food) with the Se-fortified Chlorella diet than with other foods. Although B. rotundiformis (Kochi strain), which also exhibits cyclical parthenogenesis, showed no differences in population growth among the three different diets (r?=?0.42?0.48), sexual reproduction parameters were different depending on the feeding regime. The highest mixis (26.2%), fertilization (72.6%), and resting egg production (3489.9?eggs/g food) were observed with the Se-fortified Chlorella diet. We posit that the effect of Se-fortified diet was greater on the resting egg production by enhancing male fertility than on population growth

A three-dimensional hydrodynamics simulation of oxygen-shell burning in the final evolution of a fast-rotating massive star

We perform for the first time a 3D hydrodynamics simulation of the evolution of the last minutes pre-collapse of the oxygen shell of a fast-rotating massive star. This star has an initial mass of 38 M$_\odot$, a metallicity of $\sim$1/50 Z$_\odot$, an initial rotational velocity of 600 km s$^{-1}$, and experiences chemically homogeneous evolution. It has a silicon- and oxygen-rich (Si/O) convective layer at (4.7-17)$\times 10^{8}$ cm, where oxygen-shell burning takes place. The power spectrum analysis of the turbulent velocity indicates the dominance of the large-scale mode ($\ell \sim 3$), which has also been seen in non-rotating stars that have a wide Si/O layer. Spiral arm structures of density and silicon-enriched material produced by oxygen-shell burning appear in the equatorial plane of the Si/O shell. Non-axisymmetric, large-scale ($m \le 3$) modes are dominant in these structures. The spiral arm structures have not been identified in previous non-rotating 3D pre-supernova models. Governed by such a convection pattern, the angle-averaged specific angular momentum becomes constant in the Si/O convective layer, which is not considered in spherically symmetrical stellar evolution models. Such spiral arms and constant specific angular momentum might affect the ensuing explosion or implosion of the star.Comment: 6 pages, 6 figures, accepted for publication in MNRAS Letter

Health improvement framework for actionable treatment planning using a surrogate Bayesian model

効果的な健康改善プランを提案するAIを開発 --個別化医療における健康介入への活用に期待--. 京都大学プレスリリース. 2021-05-28.Clinical decision-making regarding treatments based on personal characteristics leads to effective health improvements. Machine learning (ML) has been the primary concern of diagnosis support according to comprehensive patient information. A prominent issue is the development of objective treatment processes in clinical situations. This study proposes a framework to plan treatment processes in a data-driven manner. A key point of the framework is the evaluation of the actionability for personal health improvements by using a surrogate Bayesian model in addition to a high-performance nonlinear ML model. We first evaluate the framework from the viewpoint of its methodology using a synthetic dataset. Subsequently, the framework is applied to an actual health checkup dataset comprising data from 3132 participants, to lower systolic blood pressure and risk of chronic kidney disease at the individual level. We confirm that the computed treatment processes are actionable and consistent with clinical knowledge for improving these values. We also show that the improvement processes presented by the framework can be clinically informative. These results demonstrate that our framework can contribute toward decision-making in the medical field, providing clinicians with deeper insights

Neuroprotective effects of Si-based hydrogen-producing agent on 6-hydroxydopamine-induced neurotoxicity in juvenile mouse model

Togawa S., Usui N., Doi M., et al. Neuroprotective effects of Si-based hydrogen-producing agent on 6-hydroxydopamine-induced neurotoxicity in juvenile mouse model. Behavioural Brain Research 468, 115040 (2024); https://doi.org/10.1016/j.bbr.2024.115040.Neurotoxins have been extensively investigated, particularly in the field of neuroscience. They induce toxic damage, oxidative stress, and inflammation on neurons, triggering neuronal dysfunction and neurodegenerative diseases. Here we demonstrate the neuroprotective effect of a silicon (Si)-based hydrogen-producing agent (Si-based agent) in a juvenile neurotoxic mouse model induced by 6-hydroxydopamine (6-OHDA). The Si-based agent produces hydrogen in bowels and functions as an antioxidant and anti-inflammatory agent. However, the effects of the Si-based agent on neural degeneration in areas other than the lesion and behavioral alterations caused by it are largely unknown. Moreover, the neuroprotective effects of Si-based agent in the context of lactation and use during infancy have not been explored in prior studies. In this study, we show the neuroprotective effect of the Si-based agent on 6-OHDA during lactation period and infancy using the mouse model. The Si-based agent safeguards against the degradation and neuronal cell death of dopaminergic neurons and loss of dopaminergic fibers in the striatum (STR) and ventral tegmental area (VTA) caused by 6-OHDA. Furthermore, the Si-based agent exhibits a neuroprotective effect on the length of axon initial segment (AIS) in the layer 2/3 (L2/3) neurons of the medial prefrontal cortex (mPFC). As a result, the Si-based agent mitigates hyperactive behavior in a juvenile neurotoxic mouse model induced by 6-OHDA. These results suggest that the Si-based agent serves as an effective neuroprotectant and antioxidant against neurotoxic effects in the brain, offering the possibility of the Si-based agent as a neuroprotectant for nervous system diseases

Protective role of vascular endothelial growth factor in endotoxin-induced acute lung injury in mice

<p>Abstract</p> <p>Background</p> <p>Vascular endothelial growth factor (VEGF), a substance that stimulates new blood vessel formation, is an important survival factor for endothelial cells. Although overexpressed VEGF in the lung induces pulmonary edema with increased lung vascular permeability, the role of VEGF in the development of acute lung injury remains to be determined.</p> <p>Methods</p> <p>To evaluate the role of VEGF in the pathogenesis of acute lung injury, we first evaluated the effects of exogenous VEGF and VEGF blockade using monoclonal antibody on LPS-induced lung injury in mice. Using the lung specimens, we performed TUNEL staining to detect apoptotic cells and immunostaining to evaluate the expression of apoptosis-associated molecules, including caspase-3, Bax, apoptosis inducing factor (AIF), and cytochrome C. As a parameter of endothelial permeability, we measured the albumin transferred across human pulmonary artery endothelial cell (HPAEC) monolayers cultured on porous filters with various concentrations of VEGF. The effect of VEGF on apoptosis HPAECs was also examined by TUNEL staining and active caspase-3 immunoassay.</p> <p>Results</p> <p>Exogenous VEGF significantly decreased LPS-induced extravascular albumin leakage and edema formation. Treatment with anti-VEGF antibody significantly enhanced lung edema formation and neutrophil emigration after intratracheal LPS administration, whereas extravascular albumin leakage was not significantly changed by VEGF blockade. In lung pathology, pretreatment with VEGF significantly decreased the numbers of TUNEL positive cells and those with positive immunostaining of the pro-apoptotic molecules examined. VEGF attenuated the increases in the permeability of the HPAEC monolayer and the apoptosis of HPAECs induced by TNF-α and LPS. In addition, VEGF significantly reduced the levels of TNF-α- and LPS-induced active caspase-3 in HPAEC lysates.</p> <p>Conclusion</p> <p>These results suggest that VEGF suppresses the apoptosis induced by inflammatory stimuli and functions as a protective factor against acute lung injury.</p

Analysis of comorbid factors that increase the COPD assessment test scores

Background: The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) is a concise health status measure for COPD. COPD patients have a variety of comorbidities, but little is known about their impact on quality of life. This study was designed to investigate comorbid factors that may contribute to high CAT scores. Methods: An observational study at Keio University and affiliated hospitals enrolled 336 COPD patients and 67 non-COPD subjects. Health status was assessed by the CAT, the St. Georges Respiratory Questionnaire (SGRQ), and all components of the Medical Outcomes Study Short-Form 36-Item (SF-36) version 2, which is a generic measure of health. Comorbidities were identified based on patients’ reports, physicians’ records, and questionnaires, including the Frequency Scale for the Symptoms of Gastro-esophageal reflux disease (GERD) and the Hospital Anxiety and Depression Scale. Dual X-ray absorptiometry measurements of bone mineral density were performed. Results: The CAT showed moderate-good correlations with the SGRQ and all components of the SF-36. The presence of GERD, depression, arrhythmia, and anxiety was significantly associated with a high CAT score in the COPD patients. Conclusions: Symptomatic COPD patients have a high prevalence of comorbidities. A high CAT score should alert the clinician to a higher likelihood of certain comorbidities such as GERD and depression, because these diseases may co-exist unrecognize