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CYP24A1 is a multifunctional, P450 mitochondrial enzyme that catabolizes the vitamin D hormone (calcitriol, 1,25(OH)2D3), its precursor (calcifediol, 25(OH)D3), and numerous vitamin D metabolites. In the kidney, Cyp24a1 is induced by 1,25(OH)2D3 and fibroblast growth factor 23 (FGF23) and potently suppressed by PTH to control the circulating levels of 1,25(OH)2D3. Cyp24a1 is controlled by a pair of promoter proximal (PRO) vitamin D response elements (VDREs) that are aided by distal, downstream (DS) enhancers. The downstream 1 region of Cyp24a1 (DS1) enhancer is kidney-specific and responsible for PTH and FGF23 actions, and the downstream 2 region of Cyp24a1 enhancer responds to 1,25(OH)2D3 in all tissues. Despite this knowledge, in vivo contributions of the PRO VDREs to basal expression, FGF23 activation, and PTH suppression of Cyp24a1 remain unknown. In this study, we selectively mutated the PRO VDREs in the mouse to address these questions. We found mutation of the VDREs leads to a dramatic loss of VDR occupancy, a reduction of 1,25(OH)D3-induced kidney Cyp24a1 expression, and near elimination of intestinal Cyp24a1 induction. FGF23 induction of Cyp24a1 was reduced but not eliminated and still showed a synergistic increase with 1,25(OH)2D3. PTH suppression of Cyp24a1 was unchanged, despite minor reductions in total for phosphorylated cAMP-response element binding protein occupancy. Finally, VDR recruitment was dramatically reduced across the DS enhancers in the Cyp24a1 locus. Taken together, our data suggest a cooperative relationship between the DS and PRO enhancers in the regulation of Cyp24a1 by 1,25(OH)2D3 and FGF23 and points to the DS1 region as a crucial basal switch for Cyp24a1 activity that further defines the interconnected genomic control in vitamin D catabolism. [ABSTRACT FROM AUTHOR]

Benign prostatic hyperplasia (BPH) is the non-malignant enlargement of the prostate, associated with lower urinary tract symptoms (LUTSs). Taraxaci Herba (TH), commonly known as dandelion, has traditionally been utilized in East Asia to treat symptoms related to LUTSs. Based on this traditional use, our study aimed to explore the inhibitory effects of TH on BPH progression using a testosterone propionate-induced rat model. To induce BPH, male Sprague Dawley rats were castrated and injected subcutaneously with testosterone propionate (3 mg/kg/day) for 28 days. Concurrently, TH extract was administered orally at doses of 100 and 300 mg/kg/day throughout the four-week period of testosterone propionate injections. The TH extract significantly reduced both the absolute and relative weights of the prostate, along with histopathological changes in the gland. Moreover, it lowered serum levels of testosterone and dihydrotestosterone and reduced the expression of the androgen receptor in the prostate. Additionally, the TH extract modulated the protein expressions of Bax and Bcl-2, which are key regulators of apoptosis in prostate cells. Collectively, our findings suggest that TH inhibits BPH development partially by modulating androgen signaling and inducing apoptosis within the prostate. [ABSTRACT FROM AUTHOR]

Corynebacterium glutamicum is a gram-positive and non-pathogenic microorganism that has traditionally been used as a major host for amino acid production. With the rapid increase in demand for high-value bioindustrial and pharmaceutically-relevant proteins, C. glutamicum has also gained significant interest as an attractive host for the production of recombinant proteins owing to several advantages over other microbial hosts, including Escherichia coli. As an emerging technology, various synthetic biology tools have been developed and successfully used to design and engineer C. glutamicum cells, making this microorganism a promising cell factory in the bioindustry field. In this review, we first summarize the synthetic biology tools for genome editing, synthetic parts for gene expression and regulation (i.e., promoters, ribosome binding sites, and bicistronic system), plasmids, and chassis, which have been intensively used for designing optimal expression constructs for C. glutamicum. Subsequently, as applications of synthetic biology tools, we discuss the extensive engineering of C. glutamicum as a potential platform for the secretory production of recombinant proteins. [ABSTRACT FROM AUTHOR]

This article presents to develop a robust control system of spherical motion platform (SMP) capable of controlling six-degree-of-freedom motion, particularly unlimited rotational motion for better virtual reality. The SMP is the new design of a motion manipulator/simulator driven by the frictional force between a set of spherical wheels and cockpit sphere. However, it has intrinsic difficulties in control due to numerous uncertainties, including slipping motion between spherical wheels and cockpit sphere. Inaccurate motion control may degrade human perception as well as tracking performance. In this article, sliding mode control based on a disturbance observer is developed for the SMP to achieve precise motion tracking performance and provide a more realistic environment regardless of kinematic and dynamic uncertainties. Numerical simulation and experimental results with proportional–integral–differential and the robust controllers are compared for step and sinusoidal inputs to demonstrate the feasibility of motion control and tracking performance in spite of uncertainties. Finally, the SMP is operated using two representative flight maneuvers as a flight simulator. The results show that the SMP with the control system can be utilized to provide motion cue for a human on board for virtual reality. [ABSTRACT FROM AUTHOR]

Our recent genomic studies identified a complex kidney‐specific enhancer module located within the introns of adjacent Mettl1 (M1) and Mettl21b (M21) genes that mediate basal and PTH induction of Cyp27b1, as well as suppression by FGF23 and 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3]. The tissue specificity for this regulatory module appears to be localized exclusively to renal proximal tubules. Gross deletion of these segments in mice has severe consequences on skeletal health, and directly affects Cyp27b1 expression in the kidney. Deletion of both the M1 and M21 submodules together almost completely eliminates basal Cyp27b1 expression in the kidney, creating a renal specific pseudo‐null mouse, resulting in a systemic and skeletal phenotype similar to that of the Cyp27b1‐KO mouse caused by high levels of both 25‐hydroxyvitamin D3 [25(OH)D3] and PTH and depletion of 1,25(OH)2D3. Cyp24a1 levels in the double KO mouse also decrease because of compensatory downregulation of the gene by elevated PTH and reduced FGF23 that is mediated by an intergenic module located downstream of the Cyp24a1 gene. Outside of the kidney in nonrenal target cells (NRTCs), expression of Cyp27b1 in these mutant mice was unaffected. Dietary normalization of calcium, phosphate, PTH, and FGF23 rescues the aberrant phenotype of this mouse and normalizes the skeleton. In addition, both the high levels of 25(OH)D3 were reduced and the low levels of 1,25(OH)2D3 were fully eliminated in these mutant mice as a result of the rescue‐induced normalization of renal Cyp24a1. Thus, these hormone‐regulated enhancers for both Cyp27b1 and Cyp24a1 in the kidney are responsible for the circulating levels of 1,25(OH)2D3 in the blood. The retention of Cyp27b1 and Cyp24a1 expression in NRTCs of these endocrine 1,25(OH)2D3‐deficient mice suggests that this Cyp27b1 pseudo‐null mouse will provide a model for the future exploration of the role of NRTC‐produced 1,25(OH)2D3 in the hormone's diverse noncalcemic actions in both health and disease. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

In this paper, a six-degree-of-freedom (DOF) motion platform based on spherical wheels is presented to improve design and motion control from the earlier design. The motion platform developed here is capable of 3-DOFs unlimited rotation and 3-DOFs translation, which has large workspace of linear motion with better stability and high rigidity. In particular, the new design offers better motion control, uniformity, and safety in motion range by additional actuators providing better motion capability for virtual reality. Kinematic analysis of the platform is investigated to provide a basis for motion controllability. In particular, the rotational motion can be independently controlled from the translation by the active driving control. The design and motion analysis are demonstrated from both numerical simulation and experiment using a prototype in an open-loop control. Slipping motion and friction as a main driving torque are experimentally evaluated for a nonslip condition. The comparison results prove the design feasibility and motion control capability. [ABSTRACT FROM AUTHOR]

This paper presents a new concept and design of a multidegree-of-freedom (DOF) motion platform capable of controlling three DOFs rotation and three DOFs translation to provide unlimited rotational range of motion for virtual reality (VR) based on spherical wheels. Multi-DOF motion platforms have been developed for various applications such as motion simulators and game industry. In addition, motion recognition is one of main features for VR with visual display. However, existing motion platforms have critical limits of range of motion in motion realization due to mechanical linkages and their actuating mechanisms. In addition, unnatural motion control causes mismatch in the VR environment. The motion platform developed in this paper can provide six DOFs motion, and in particular, unlimited range of rotation without motion singularity. The design is compact and lightweight offering fast speed of response. Kinematic and dynamic analysis of the platform are investigated to provide a basis of motion control in an open loop. Performance of motion control is demonstrated in real scale size (ride on platform). The experimental results show that the platform is successfully capable of multi-DOF motion control and can be utilized for various applications in future demands. [ABSTRACT FROM PUBLISHER]

In this paper, we investigate dynamic walking as a convergence to the system's own limit cycles, not to artificially generated trajectories, which is one of the lessons in the concept of passive dynamic walking. For flexible walking, gait transitions can be performed by moving from one limit cycle to another one, and thus, the flexibility depends on the range in which limit cycles exist. To design a bipedal walker based on this approach, we explore period-1 passive limit cycles formed by natural dynamics and analyze them. We use a biped model with knees and point feet to perform numerical simulations by changing the center of mass locations of the legs. As a result, we obtain mass distributions for the maximum flexibility, which can be attained from very limited location sets. We discuss the effect of parameter variations on passive dynamic walking and how to improve robot design by analyzing walking performance. Finally, we present a practical application to a real bipedal walker, designed to exhibit more flexible walking based on this study. [ABSTRACT FROM PUBLISHER]