International Reserves for Emerging Economies: A Liquidity Approach.

The massive stocks of foreign exchange reserves, mostly held in the form of U.S. T-Bonds by emerging economies, are still an important puzzle. Why do emerging economies continue to willingly loan to the United States despite the low rates of return? We propose that a dynamic general equilibrium model incorporating international capital markets, characterized by a non-centralized trading mechanism and U.S. T-Bonds as facilitators of trade, can provide an answer to this question. Declining financial frictions in these over-the-counter (OTC) markets would generate rising liquidity premiums on U.S. T-Bonds. Meanwhile, the higher liquidity properties of the U.S. T-Bonds would induce recipients of foreign investments, namely emerging economies, to hold more liquidity, that is U.S. T-Bonds, in equilibrium. The prediction of our model is confirmed by an empirical simultaneous equations approach considering an endogenous relationship between OTC capital inflows and reserves holdings

International Reserves for Emerging Economies: A Liquidity Approach.

The massive stocks of foreign exchange reserves, mostly held in the form of U.S. T-Bonds by emerging economies, are still an important puzzle. Why do emerging economies continue to willingly loan to the United States despite the low rates of return? We propose that a dynamic general equilibrium model incorporating international capital markets, characterized by a non-centralized trading mechanism and U.S. T-Bonds as facilitators of trade, can provide an answer to this question. Declining financial frictions in these over-the-counter (OTC) markets would generate rising liquidity premiums on U.S. T-Bonds. Meanwhile, the higher liquidity properties of the U.S. T-Bonds would induce recipients of foreign investments, namely emerging economies, to hold more liquidity, that is U.S. T-Bonds, in equilibrium. The prediction of our model is confirmed by an empirical simultaneous equations approach considering an endogenous relationship between OTC capital inflows and reserves holdings

Cellular energy stress induces AMPK-mediated regulation of YAP and the Hippo pathway.

YAP (Yes-associated protein) is a transcription co-activator in the Hippo tumour suppressor pathway and controls cell growth, tissue homeostasis and organ size. YAP is inhibited by the kinase Lats, which phosphorylates YAP to induce its cytoplasmic localization and proteasomal degradation. YAP induces gene expression by binding to the TEAD family transcription factors. Dysregulation of the Hippo-YAP pathway is frequently observed in human cancers. Here we show that cellular energy stress induces YAP phosphorylation, in part due to AMPK-dependent Lats activation, thereby inhibiting YAP activity. Moreover, AMPK directly phosphorylates YAP Ser 94, a residue essential for the interaction with TEAD, thus disrupting the YAP-TEAD interaction. AMPK-induced YAP inhibition can suppress oncogenic transformation of Lats-null cells with high YAP activity. Our study establishes a molecular mechanism and functional significance of AMPK in linking cellular energy status to the Hippo-YAP pathway

Angiomyofibroblastoma-Like Tumor of the Scrotum

Various tumors can occur in the scrotum. Of them, angiomyofibroblastoma-like tumors are very rare mesenchymal tumors. Angiomyofibroblastoma-like tumors cannot be easily differentially diagnosed from other malignant tumors invading the male genital tract on the basis of clinical characteristics and imaging study. Therefore, surgical removal and a histopathologic diagnosis must also be performed

Rag GTPases are cardioprotective by regulating lysosomal function.

The Rag family proteins are Ras-like small GTPases that have a critical role in amino-acid-stimulated mTORC1 activation by recruiting mTORC1 to lysosome. Despite progress in the mechanistic understanding of Rag GTPases in mTORC1 activation, little is known about the physiological function of Rag GTPases in vivo. Here we show that loss of RagA and RagB (RagA/B) in cardiomyocytes results in hypertrophic cardiomyopathy and phenocopies lysosomal storage diseases, although mTORC1 activity is not substantially impaired in vivo. We demonstrate that despite upregulation of lysosomal protein expression by constitutive activation of the transcription factor EB (TFEB) in RagA/B knockout mouse embryonic fibroblasts, lysosomal acidification is compromised owing to decreased v-ATPase level in the lysosome fraction. Our study uncovers RagA/B GTPases as key regulators of lysosomal function and cardiac protection

The Expression of Matrix Metalloprotease 20 is Stimulated by Wild Type but not by 4 bp- or 2 bp- Deletion Mutant DLX3

Mutations in DLX3 are associated with both autosomal dominant hypoplastic hypomaturation amelogenesis imperfecta (ADHHAI) and tricho-dento-osseous (TDO) syndrome. ADHHAI is caused by a c.561_562delCT (2bpdel DLX3) mutation whereas TDO syndrome is associated with a c.571_574delGGGG (4bp-del DLX3) mutation. However, although the causal relationships between DLX3 and an enamel phenotype have been established, the pathophysiological role of DLX3 mutations in enamel development has not yet been clarified. In our current study, we prepared expression vectors for wild type and deletion mutant DLX3 products (4bp-del DLX3, 2bp-del DLX3) and examined the effects of their overexpression on the expression of the enamel matrix proteins and proteases. Wild type DLX3 enhanced the expression of matrix metalloprotease 20 (MMP20) mRNA and protein in murine ameloblast-like cells. However, neither a 4bp-del nor 2bpdel DLX3 increased MMP20 expression. Wild type DLX3, but not the above DLX3 mutants, also increased the activity of reporters containing 1.5 kb or 0.5 kb of the MMP20 promoter. An examination of protein stability showed that the half-life of wild type DLX3 protein was less than 12 h whilst that of both deletion mutants was longer than 24 h. Endogenous Dlx3 was also found to be continuously expressed during ameloblast differentiation. Since inactivating mutations in the gene encoding MMP20 are associated with amelogenesis imperfecta, the inability of 4bp-del or 2bp-del DLX3 to induce MMP20 expression suggests a possible involvement of such mutations in the enamel phenotype associated with TDO syndrome or ADHHAI

Fully immersive virtual reality exergames with dual-task components for patients with Parkinsons disease: a feasibility study

Abstract Background Dual-task training in Parkinsons disease (PD) improves spatiotemporal gait parameters, cognition, and quality of life. Virtual reality (VR) has been used as a therapeutic tool for patients to participate in activities in a safe environment, engage in multisensory experiences, and improve motivation and interest in rehabilitation. This study aimed to investigate the feasibility of fully immersive VR exergames with dual-task components in patients with PD. Methods We developed VR exergames (go/no-go punch game, go/no-go stepping game, and number punch game) to improve habitual behavior control using motor–cognitive dual-task performance in patients with PD. The participants underwent 10 sessions 2–3 times a week, consisting of 30min per session. The Unified Parkinsons Disease Rating Scale, Timed Up and Go test (TUG) under single- and dual-task (cognitive and physical) conditions, Berg balance scale (BBS), Stroop test, trail-making test, and digit span were evaluated before and after intervention. The Simulator Sickness Questionnaire (SSQ) was used to assess VR cybersickness. Usability was assessed using a self-reported questionnaire. Results Twelve patients were enrolled and completed the entire training session. The mean age of participants was 73.83 ± 6.09years; mean disease duration was 128.83 ± 76.96months. The Hoehn and Yahr stages were 2.5 in seven patients and 3 in five patients. A significant improvement was observed in BBS and Stroop color–word test (p = 0.047 and p = 0.003, respectively). TUG time and dual-task interferences showed positive changes, but these changes were not statistically significant. The median SSQ total score was 28.05 (IQR: 29.92), 13.09 (IQR: 11.22), and 35.53 (IQR: 52.36) before, after the first session, and after the final session, respectively; the differences were not significant. Overall satisfaction with the intervention was 6.0 (IQR: 1.25) on a 7-point Likert-type scale. Conclusions Fully immersive VR exergames combined with physical and cognitive tasks may be used for rehabilitation of patients with PD without causing serious adverse effects. Furthermore, the exergames using dual-task components improved executive function and balance. Further development of VR training content may be needed to improve motor and dual-task performances. Trial registration NCT04787549 (https://clinicaltrials.gov/ct2/show/NCT04787549)This study was supported by Grant no. 03-2020-2020 from the Seoul National University Hospital Research Fund