Biology subjects

Ujihara, Y.

Publications and source records attributed to Ujihara, Y..

3 recordsLinked to original sources

bioRxiv2021

Novel method for clarifying faster interstitial flow in the intimal side of the aorta under intraluminal pressurization

Hypertension causes aortic thickening, especially on the intimal side. Although the production of the extracellular matrix is observed, the type of mechanical stress that produces this response remains unclear. In this study, we hypothesize that the interstitial flow causes the thickening. To validate this claim, we proposed a novel method to measure the velocity distribution in the radial direction in the aorta, which has been unclear. A fluorescent dye was introduced in the lumen of the mouse thoracic aorta ex vivo, intraluminal pressure was applied, and a time-lapse image in the radial-circumferential plane was acquired under a two-photon microscope. The flow of the fluorescent dye from the intimal to the adventitial sides in the aorta was successfully observed. The acquired image was converted to a radial-time image (i.e., kymograph), and the flow velocity was quantified by applying the one-dimensional advection-diffusion equation to the fluorescent images. The results revealed a higher interstitial flow velocity in the aortic walls under higher intraluminal pressure and a higher velocity on the more intimal side. Thus, the interstitial flow is a candidate for the mechanical stress causing hyperplasia of the aorta under hypertension.

biophysics↗

bioRxiv2021

Transient induction of cell cycle promoter Fam64a improves cardiac function through regulating Klf15-dependent cardiomyocyte differentiation in mice

The introduction of fetal or neonatal signatures such as cell cycle promoting genes into damaged adult hearts has been vigorously pursued as a promising strategy for stimulating proliferation and regeneration of adult cardiomyocytes, which normally cannot divide. However, cell division of cardiomyocytes requires preceding dedifferentiation with sarcomere disassembly and calcium dysregulation, which, in principle, compromises contractile function. To overcome this intrinsic dilemma, we explored the feasibility of optimizing the induction protocol of the cell cycle promoter in mice. As a model of this approach, we used Fam64a, a fetal-specific cardiomyocyte cell cycle promoter that we have recently identified. We first analyzed transgenic mice maintaining long-term cardiomyocyte-specific expression of Fam64a after birth, when endogenous expression was abolished. Despite having an enhanced proliferation of postnatal cardiomyocytes, these mice showed age-related cardiac dysfunction characterized by sustained cardiomyocyte dedifferentiation, which was reminiscent of the dilemma. Mechanistically, Fam64a inhibited glucocorticoid receptor-mediated transcriptional activation of Klf15, a key regulator that drives cardiomyocyte differentiation, thereby directing cardiomyocytes toward immature undifferentiated states. In contrast, transient induction of Fam64a in cryoinjured wildtype adult mice hearts improved functional recovery with augmented cell cycle activation of cardiomyocytes. These data indicate that optimizing the intensity and duration of the stimulant to avoid excessive cardiomyocyte dedifferentiation could pave the way toward developing efficient strategy for successful heart regeneration.

physiology↗

bioRxiv2020

Interceptive capturing in large-billed crows: Velocity-dependent weighing of prediction of future target location and visual feedback of current target location.

Interception of a moving target is a fundamental behaviour of predators and requires tight coupling between the sensory and motor systems. In the literature of foraging studies, feedback mechanisms based on current target position are frequently reported. However, there have also been recent reports of animals employing feedforward mechanisms, in which prediction of future target location plays an important role. In nature, coordination of these two mechanisms may contribute to intercepting evasive prey. However, how animals weigh these two mechanisms remain poorly understood. Here, we conducted a behavioural experiment involving crows (which show flexible sensorimotor coordination in various domains) capturing a moving target. We changed the velocity of the target to examine how the crows utilised prediction of the target location. The analysis of moment-to-moment head movements and computational simulations revealed that the crows used prediction of future target location when the target velocity was high. In contrast, their interception depended on the current momentary position of the target when the target velocity was slow. These results suggest that crows successfully intercept targets by weighing predictive and visual feedback mechanisms, depending on the target velocity.

animal behavior and cognition↗