Increase of GADD34 expression in skeletal muscle by ATRA

All-trans retinoic acid (ATRA) increases the sensitivity to unfolded protein response in differentiating leukemic blasts. The downstream transcriptional factor of PERK, a major arm of unfolded protein response, regulates muscle differentiation. However, the role of growth arrest and DNA damage-inducible protein 34 (GADD34), one of the downstream factors of PERK, and the effects of ATRA on GADD34 expression in muscle remain unclear. In this study, we identified ATRA increased the GADD34 expression independent of the PERK signal in the gastrocnemius muscle of mice. ATRA up-regulated GADD34 expression through the transcriptional activation of GADD34 gene via inhibiting the interaction of homeobox Six1 and transcription co-repressor TLE3 with the MEF3-binding site on the GADD34 gene promoter in skeletal muscle. ATRA also inhibited the interaction of TTP, which induces mRNA degradation, with AU-rich element on GADD34 mRNA via p-38 MAPK, resulting in the instability of GADD34 mRNA. Overexpressed GADD34 in C2C12 cells changes the type of myosin heavy chain in myotubes. These results suggest ATRA increases GADD34 expression via transcriptional and post-transcriptional regulation, which changes muscle fiber type

Group-theoretic spectrum analysis of hexagonal city distributions in Southern Germany and Eastern USA

Hexagonal distributions of cities of various sizes in Southern Germany are envisaged in central place theory. Yet scientific verification of this theory has been lacking. To scientifically support this theory, we propose a group-theoretic double Fourier spectrum analysis procedure that can detect geometrical patterns in population distributions of cities. In addition to hexagonal patterns in the theory, we propose megalopolis patterns. Using this procedure, strong power spectra for megalopolis patterns were detected for population data in Southern Germany. Moreover, a gigantic hexagonal distribution of cities in Eastern USA was found to be an assemblage of megalopolis and hexagonal patterns. The amazing geometrical regularity of this distribution manifests the existence of these patterns in the real world, thereby underpinning central place theory

Hexagonal distributions of cities in Southern Germany and Eastern USA: Group-theoretic spectrum analysis

Cities in Southern Germany are envisaged to form hexagonal distributions in central place theory; however, rigorous verification of this theory has been lacking over years. To support this theory, we introduce a group-theoretic Fourier spectrum analysis that can detect geometrical patterns of cities based on the statistical population data. In addition to hexagonal patterns in the theory, we propose a core--satellite pattern. Using this analysis, we detected a strong power spectrum for this pattern for population data in Southern Germany. Moreover, a gigantic hexagonal distribution of cities in Eastern USA was found to be an assemblage of the core--satellite and hexagonal patterns. The amazing geometrical regularity of this distribution implies the existence of such patterns in the real world, thereby underpinning the theory

Group-theoretic spectrum analysis of hexagonal city distributions in Southern Germany and Eastern USA

Hexagonal distributions of cities of various sizes in Southern Germany are envisaged in central place theory. Yet scientific verification of this theory has been lacking. To scientifically support this theory, we propose a group-theoretic double Fourier spectrum analysis procedure that can detect geometrical patterns in population distributions of cities. In addition to hexagonal patterns in the theory, we propose megalopolis patterns. Using this procedure, strong power spectra for megalopolis patterns were detected for population data in Southern Germany. Moreover, a gigantic hexagonal distribution of cities in Eastern USA was found to be an assemblage of megalopolis and hexagonal patterns. The amazing geometrical regularity of this distribution manifests the existence of these patterns in the real world, thereby underpinning central place theory

Effect of Beni-Koji on Blood Pressure and Learning Behavior in Spontaneously Hypertensive Rats

1)紅麹投与群は米粉を投与した対照群と比べ､体重増加に対しては有意な差は認められなかった｡ 2)紅麹投与群は対照群と比べ2週目より有意な血圧下降作用が認められた｡ 3)紅麹投与群は､対照群に比べ総エラー数および参照記憶エラー数の減少､すなわち学習獲得能が高いことが判明した｡ 4)以上の成績より､紅麹の投与により生じた血圧下降が二次的に学習獲得能を上昇させたのではないかと考えられる

Differenting Cushing’s disease from myasthenia gravis : A case report

The patient is a 77-year-old woman with a history of diabetes mellitus that was refractory to the medication and dietary restrictions. Four months prior to the admission, she developed a dropped head and ptosis that worsened in the evening. These symptoms were improved by the edrophonium test and the 3 Hz repetitive nerve stimulation testing was positive ; nevertheless, anti-acetylcholine and anti-muscle-specific tyrosine kinase antibodies were negative. Further examination demonstrated sustained hypokalemia and high levels of cortisol and ACTH. Moreover, CRH and high-dose dexamethasone suppression testings were positive and MRI demonstrated pituitary microadenoma. Based on these findings, she was subsequently diagnosed with Cushing’s disease. After the resection of the pituitary tumor, ptosis improved with an alleviation of systemic edema, suggesting that it was caused by an eyelid edema. This case uniquely illustrates that Cushing’s disease may mimic myasthenia gravis. Differentiation of the two disorders is crucial as treatment with steroids could compromise the interpretation of diagnostic testings for Cushing’s disease and might result in a disease exacerbation. In this case, the history of treatment-refractory diabetes mellitus was helpful cue to differentiate the two disorders

Coordinated regulation of hepatic and adipose tissue transcriptomes by the oral administration of an amino acid mixture simulating the larval saliva of Vespa species

Genes mapped on Fig. 3. (XLSX 13 kb

The dipeptide Phe-Phe amide attenuates signs of hyperalgesia, allodynia and nociception in diabetic mice using a mechanism involving the sigma receptor system

<p>Abstract</p> <p>Background</p> <p>Previous studies have demonstrated that intrathecal administration of the substance P amino-terminal metabolite substance P_1-7(SP_1-7) and its C-terminal amidated congener induced antihyperalgesic effects in diabetic mice. In this study, we studied a small synthetic dipeptide related to SP_1-7and endomorphin-2, i.e. Phe-Phe amide, using the tail-flick test and von Frey filament test in diabetic and non-diabetic mice.</p> <p>Results</p> <p>Intrathecal treatment with the dipeptide increased the tail-flick latency in both diabetic and non-diabetic mice. This effect of Phe-Phe amide was significantly greater in diabetic mice than non-diabetic mice. The Phe-Phe amide-induced antinociceptive effect in both diabetic and non-diabetic mice was reversed by the σ₁receptor agonist (+)-pentazocine. Moreover, Phe-Phe amide attenuated mechanical allodynia in diabetic mice, which was reversible by (+)-pentazocine. The expression of spinal σ1 receptor mRNA and protein did not differ between diabetic mice and non-diabetic mice. On the other hand, the expression of phosphorylated extracellular signal-regulated protein kinase 1 (ERK1) and ERK2 proteins was enhanced in diabetic mice. (+)-Pentazocine caused phosphorylation of ERK1 and ERK2 proteins in non-diabetic mice, but not in diabetic mice.</p> <p>Conclusions</p> <p>These results suggest that the spinal σ₁receptor system might contribute to diabetic mechanical allodynia and thermal hyperalgesia, which could be potently attenuated by Phe-Phe amide.</p

Decreased activity in the reward network of chronic insomnia patients

In modern society, many people have insomnia. Chronic insomnia has been noted as a risk factor for depression. However, there are few functional imaging studies of the brain on affective functions in chronic insomnia. This study aimed to investigate brain activities induced by emotional stimuli in chronic insomnia patients. Fifteen patients with primary insomnia and 30 age and gender matched healthy controls participated in this study. Both groups were presented images of fearful, happy, and neutral expressions consciously and non-consciously while undergoing MRI to compare the activity in regions of the brain responsible for emotions. Conscious presentation of the Happy-Neutral contrast showed significantly lower activation in the right orbitofrontal cortex of patients compared to healthy controls. The Happy-Neutral contrast presented in a non-conscious manner resulted in significantly lower activation of the ventral striatum, right insula, putamen, orbitofrontal cortex and ventral tegmental area in patients compared to healthy controls. Our findings revealed that responsiveness to positive emotional stimuli were decreased in insomniac patients. Specifically, brain networks associated with rewards and processing positive emotions showed decreased responsiveness to happy emotions especially for non-conscious image. The magnitude of activity in these areas also correlated with severity of insomnia, even after controlling for depression scale scores. These findings suggest that insomnia induces an affective functional disorder through an underlying mechanism of decreased sensitivity in the regions of the brain responsible for emotions and rewards to positive emotional stimuli

MafB is a critical regulator of complement component C1q

The transcription factor MafB is expressed by monocytes and macrophages. Efferocytosis (apoptotic cell uptake) by macrophages is important for inhibiting the development of autoimmune diseases, and is greatly reduced in Mafb-deficient macrophages. Here, we show the expression of the first protein in the classical complement pathway C1q is important for mediating efferocytosis and is reduced in Mafb-deficient macrophages. The efferocytosis defect in Mafb-deficient macrophages can be rescued by adding serum from wild-type mice, but not by adding serum from C1q-deficient mice. By hemolysis assay we also show that activation of the classical complement pathway is decreased in Mafb-deficient mice. In addition, MafB overexpression induces C1q-dependent gene expression and signals that induce C1q genes are less effective in the absence of MafB. We also show that Mafb-deficiency can increase glomerular autoimmunity, including anti-nuclear antibody deposition. These results show that MafB is an important regulator of C1q