Evx2-Hoxd13 Intergenic Region Restricts Enhancer Association to Hoxd13 Promoter

Expression of Hox genes is tightly regulated in spatial and temporal domains. Evx2 is located next to Hoxd13 within 8 kb on the opposite DNA strand. Early in development, the pattern of Hoxd13 expression resembles that of Evx2 in limb and genital buds. After 10 dpc, however, Evx2 begins to be expressed in CNS as well. We analyzed the region responsible for these differences using ES cell techniques, and found that the intergenic region between Evx2 and Hoxd13 behaves as a boundary element that functions differentially in space and time, specifically in the development of limbs, genital bud, and brain. This boundary element comprises a large sequence spanning several kilobases that can be divided into at least two units: a constitutive boundary element, which blocks transcription regulatory influences from the chromosomal environment, and a regulatory element, which controls the function of the constitutive boundary element in time and space

Methylglyoxal reduces molecular responsiveness to 4 weeks of endurance exercise in mouse plantaris muscle

Endurance exercise triggers skeletal muscle adaptations, including enhanced insulin signaling, glucose metabolism, and mitochondrial biogenesis. However, exercise-induced skeletal muscle adaptations may not occur in some cases, a condition known as exercise-resistance. Methylglyoxal (MG) is a highly reactive dicarbonyl metabolite and has detrimental effects on the body such as causing diabetic complications, mitochondrial dysfunction, and inflammation. This study aimed to clarify the effect of methylglyoxal on skeletal muscle molecular adaptations following endurance exercise. Mice were randomly divided into 4 groups (n = 12 per group): sedentary control group, voluntary exercise group, MG-treated group, and MG-treated with voluntary exercise group. Mice in the voluntary exercise group were housed in a cage with a running wheel, while mice in the MG-treated groups received drinking water containing 1% MG. Four weeks of voluntary exercise induced several molecular adaptations in the plantaris muscle, including increased expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α), mitochondria complex proteins, toll-like receptor 4 (TLR4), 72-kDa heat shock protein (HSP72), hexokinase II, and glyoxalase 1; this also enhanced insulin-stimulated Akt Ser473 phosphorylation and citrate synthase activity. However, these adaptations were suppressed with MG treatment. In the soleus muscle, the exercise-induced increases in the expression of TLR4, HSP72, and advanced glycation end products receptor 1 were inhibited with MG treatment. These findings suggest that MG is a factor that inhibits endurance exercise-induced molecular responses including mitochondrial adaptations, insulin signaling activation, and the upregulation of several proteins related to mitochondrial biogenesis, glucose handling, and glycation in primarily fast-twitch skeletal muscle

Glycative stress and skeletal muscle dysfunctions: as an inducer of "Exercise-Resistance."

Skeletal muscle, the largest tissue in the body, is often overlooked for its role as a locomotor organ, however over the past few decades it has been revealed that it also has an important role as a metabolic organ. In recent years, its role as an endocrine organ that controls the homeostatic functions of organs throughout the body mediated by myokine secretion has come under close scrutiny. Skeletal muscle is indispensable for our daily life activities, and in order to maintain its function, it is necessary to understand the factors that deteriorate muscle function and establish a countermeasure. Glycative stress has recently received attention as a factor that impairs skeletal muscle function. Accumulation of advanced glycation end products (AGEs) in skeletal muscle impairs contractile function and myogenic potential. Furthermore, AGEs in the blood elicit inflammatory signals through binding to RAGE (Receptor for AGEs) expressed on muscle cells, resulting in muscle proteolysis. Habitual exercise is important to mitigate the negative effects of such glycative stress on skeletal muscle. On the other hand, it is known that the beneficial effects of exercise vary among individuals. The state in which the effects of exercise are difficult to obtain is called "exercise-resistance, " and we hypothesize that glycative stress may be one of the causes of exercise-resistance. In this paper, we will discuss the possibility of glycative stress as an inducer of exercise resistance and summarize its impacts on skeletal muscle

Menaquinone-4 enhances testosterone production in rats and testis-derived tumor cells

<p>Abstract</p> <p>Background</p> <p>Vitamin K is essential for the posttranslational modification of various Gla proteins. Although it is widespread in several organs, including the testis, the function of vitamin K in these organs is not well characterized. In this study, we investigated the function of vitamin K in the testis and analyzed its role in steroidogenesis.</p> <p>Methods</p> <p>Eight-week-old male Wistar rats were fed a diet supplemented with menaquinone-4 (MK-4, 75 mg/kg diet), one of the predominant K₂vitamins present in the testis, for 5 weeks. <it>In vivo </it>testosterone levels of the rats' plasma and testes were measured by enzyme-linked immunosorbent assay, and <it>in vitro </it>testosterone levels of testis-derived tumor cells (I-10 cells) maintained in Ham's F-10 medium with 10% fetal bovine serum were measured following treatment with MK-4 (0 to 100 μM) at several time points. Testosterone and cellular protein levels were analyzed with respect to their effects on steroidogenesis.</p> <p>Results</p> <p>Testosterone levels in the plasma and testes of MK-4-fed rats were significantly increased compared to those of control rats, with no obvious differences in plasma luteinizing hormone levels. Secreted testosterone levels from I-10 cells were elevated by MK-4, but not by vitamin K₁, in a dose-dependent manner independent of cAMP treatment. Western blot analysis revealed that expression of CYP11A, the rate-limiting enzyme in steroidogenesis, and phosphorylation levels of protein kinase A (PKA) and the cAMP response element-binding protein were all stimulated by the presence of MK-4. Enhancement of testosterone production was inhibited by H89, a specific inhibitor of PKA, but not by warfarin, an inhibitor of γ-glutamylcarboxylation.</p> <p>Conclusions</p> <p>MK-4 stimulates testosterone production in rats and testis-derived tumor cells via activation of PKA. MK-4 may be involved in steroidogenesis in the testis, and its supplementation could reverse the downregulation of testosterone production in elders.</p

The Effect of Glycation Stress on Skeletal Muscle

Glycation stress (glycative stress) is a general concept of biological stress caused by a series of non-enzymatic glycation reactions, including advanced glycation end products (AGEs) formation, AGEs accumulation, glycation-associated dysfunction of proteins and cellular signaling, inflammation, oxidation, and/or tissue damage. There has been increasing evidence supporting a profound effect of AGEs on human diseases such as type 2 diabetes, cardiovascular disease, cancer, Alzheimer’s disease, osteoporosis, and dementia, as well as aging process itself. In addition, dietary AGEs intake has also been suggested to contribute to tissue dysfunction and development of the diseases. Skeletal muscle is the largest organ in the human body and important responsibility for maintaining our health as not only locomotor system but also metabolic and endocrine systems. Especially in past decades, numerous studies have suggested the contribution of glycation stress to skeletal muscle dysfunctions (e.g. muscle atrophy, reducing contractile property, and insulin resistance). In this chapter, we provide current evidence on the potential role of glycation stress in the impairment of skeletal muscle functions

Hard X-ray nanofocusing using adaptive focusing optics based on piezoelectric deformable mirrors

An adaptive Kirkpatrick-Baez mirror focusing optics based on piezoelectric deformable mirrors was constructed at SPring-8 and its focusing performance characteristics were demonstrated. By adjusting the voltages applied to the deformable mirrors, the shape errors (compared to a target elliptical shape) were finely corrected on the basis of the mirror shape determined using the pencil-beam method, which is a type of at-wavelength figure metrology in the X-ray region. The mirror shapes were controlled with a peak-to-valley height accuracy of 2.5 nm. A focused beam with an intensity profile having a full width at half maximum of 110 × 65 nm (V × H) was achieved at an X-ray energy of 10 keV.Takumi Goto, Hiroki Nakamori, Takashi Kimura, Yasuhisa Sano, Yoshiki Kohmura, Kenji Tamasaku, Makina Yabashi, Tetsuya Ishikawa, Kazuto Yamauchi, and Satoshi Matsuyama, "Hard X-ray nanofocusing using adaptive focusing optics based on piezoelectric deformable mirrors", Review of Scientific Instruments 86, 043102 (2015) https://doi.org/10.1063/1.4916617

Prevention of Pemetrexed-Induced Rash Using Low-Dose Corticosteroids : A Phase II Study

Background: Rash eruptions are a common side-effect of pemetrexed, for which the administration of 8 mg/day of dexamethasone for 3 days from the day preceding pemetrexed administration is recommended. This study aimed to prospectively assess the effectiveness of prophylactic administration of low-dose dexamethasone for pemetrexed-induced rashes. Methods: This single-arm, phase II study recruited patients with non-squamous non–small cell lung cancer and malignant pleural mesothelioma scheduled to receive chemotherapy including pemetrexed. Patients received 2 mg of dexamethasone daily from days 2 to 6 after chemotherapy with pemetrexed. The primary endpoint was the 3-week incidence of rash eruptions. Results: Twenty-five patients were enrolled between September 2017 and May 2019. The incidence of rash after 3 weeks was 16.7%. Rashes erupted mainly on the upper half of the body, such as the chest and neck, and were of grades 1 and 2 in 2 patients each. No rashes of grade 3 or higher were observed, and there were no adverse events associated with additional corticosteroids. Conclusion: Prophylactic administration of low-dose dexamethasone for 5 days from the day after pemetrexed administration resulted in a milder incidence and severity of rash. These findings may provide a standard preventative strategy for pemetrexed-induced rashes. (Trial identifier: UMIN000025666)

Development of precision Wolter mirrors for future solar x-ray observations

Taro Sakao, Satoshi Matsuyama, Ayumi Kime, Takumi Goto, Akihiko Nishihara, Hiroki Nakamori, Kazuto Yamauchi, Yoshiki Kohmura, Akira Miyake, Hirokazu Hashizume, Tadakazu Maezawa, Yoshinori Suematsu, and Noriyuki Narukage "Development of precision Wolter mirrors for future solar x-ray observations", Proc. SPIE 9603, Optics for EUV, X-Ray, and Gamma-Ray Astronomy VII, 96030U (4 September 2015); https://doi.org/10.1117/12.2188905

Development of precision Wolter mirrors for solar x-ray observations

Taro Sakao, Satoshi Matsuyama, Takumi Goto, Jumpei Yamada, Shuhei Yasuda, Kazuto Yamauchi, Yoshiki Kohmura, Ayumi Kime, Akira Miyake, Tadakazu Maezawa, Hirokazu Hashizume, Yoshinori Suematsu, Noriyuki Narukage, and Shin-nosuke Ishikawa "Development of precision Wolter mirrors for solar x-ray observations", Proc. SPIE 10386, Advances in X-Ray/EUV Optics and Components XII, 103860E (23 August 2017); https://doi.org/10.1117/12.2273507

Effects of Pin-up Oxygen on [60]Fullerene for Enhanced Antioxidant Activity

The introduction of pin-up oxygen on C60, such as in the oxidized fullerenes C60O and C60On, induced noticeable increase in the antioxidant activity as compared to pristine C60. The water-soluble inclusion complexes of fullerenes C60O and C60Onreacted with linoleic acid peroxyl radical 1.7 and 2.4 times faster, respectively