Bank Lending in Japan: its Determinants and Macroeconomic Implications.

We examine the role of bank loans in the Japanese economy by analyzing the lending behavior of banking firms and the investment behavior of non-financial firms.BANKS ; LENDING ; ESTIMATOR

The acceleration of reproductive aging in Nrg1flox/flox;Cyp19-Cre female mice

Irregular menstrual cycles, reduced responses to exogenous hormonal treatments, and altered endocrine profiles (high FSH/high LH/low AMH) are observed in women with increasing age before menopause. In this study, because the granulosa cell-specific Nrg1 knockout mice (gcNrg1KO) presented ovarian and endocrine phenotypes similar to older women, we sought to understand the mechanisms of ovarian aging and to develop anewstrategy for improving fertility in older women prior to menopause. In the ovary of 6-month-old gcNrg1KO mice, follicular development was blocked in bilayer secondary follicles and heterogeneous cells accumulated in ovarian stroma. The heterogeneous cells in ovarian stroma were distinguished as two different types: (i) the LH receptor-positive endocrine cells and (ii) actin-rich fibrotic cells expressing collagen. Both the endocrine and fibrotic cells disappeared following long-term treatment with a GnRH antagonist, indicating that the high levels of serum LH induced the survival of both cell types and the abnormal endocrine profile to reduce fertility. Moreover, follicular development to the antral stages was observed with reduced LH and the disappearance of the abnormal stromal cells. Mice treated with the GnRH antagonist regained normal, recurrent estrous cycles and continuously delivered pups for at least for 3 months. We conclude that endocrine and matrix alternations occur within the ovarian stroma with increasing age and that abolishing these alternations resets the cyclical release of LH. Thus, GnRH antagonist treatments might provide a new, noninvasive strategy for improving fertility in a subset of aging women before menopause.This work was supported in part by The Japan Society for the Promotion of Science (JSPS) KAKENHI, JP24688028, JP 16H05017 (to MS) and JP15J05331 (to TU), by Japan Agency for Medical Research and Development (AMED) 16gk0110015 h0001 (to MS), and by National Institute of Health (NIH)-HD-076980 (to JSR)

A numerical analysis of the monetary aspects of the Japanese economy: the cash-in-advance approach

This paper analyses the monetary aspects of the Japanese economy based on the cash-in-advance (CIA) model. The Svensson (1985) model and the Lucas and Stokey (1987) model are examined by calibration. The Euler equations obtained from the representative agent's optimization behaviour stand for a non-linear relationship including some random variables. We approximate a generating process of exogenous variables using the quadrature-based method developed by Tauchen and Hussey (1991) and apply the numerical method proposed in Hodrick et al. (1991) to the results. Several moments of monetary variables are calculated to satisfy the theoretical consistency of the CIA model. Comparing the theoretical values with actual sample statistics, we examine the validity of the CIA model in Japan. The numerical results show that theoretical moments generated by the Lucas and Stokey model are consistent with sample moments in the 1980s.

Proceedings of the Fifth International Workshop on Pulmonary Image Analysis

International audienc

Inductions of granulosa cell luteinization and cumulus expansion are dependent on the fibronectin-integrin pathway during ovulation process in mice

<div><p>It has been known that EGF-like factor secreted from LH-stimulated granuloma cells acts on granulosa cells and cumulus cells to induce ovulation process. Granulosa cells are changed the morphology with differentiating cell functions to produce progesterone. Cumulus cells are detached to make a space between the cells to accumulate hyaluronan rich matrix. LH also changes extracellular matrix (ECM) components including fibronectin in the follicular walls and granulosa cell layers. EGF like factor and fibronectin synergistically play important roles in numerous cell functions, especially cancer cell migration, estimating that fibronectin would impact on granulosa cells and cumulus cells. To clear this hypothesis, the localizations of fibronectin and its receptor integrin were observed by immunofluorescence technique. The functions were monitored by the detection of downstream signaling pathway, focal adhesion kinase (FAK). The pharmacological approach in both <i>in vivo</i> and <i>in vitro</i> were used for analyzing the physiological roles of FAK during ovulation process. The immunofluorescence staining revealed that fibronectin and integrin were observed in granulosa cells, cumulus cells and the space between cumulus cells and oocyte at 4 and 8 h after hCG injection. Concomitantly with the changes of fibronectin-integrin localization, FAK was phosphorylated in periovulatory follicles. The injection of FAK inhibitor suppressed not only ovulation but also luteinization of granulosa cells and cumulus expansion. In cultured-granulosa cells, fibronectin-integrin synergistically activated FAK with amphiregulin (AREG). Such cooperative stimulations induced a morphological change in granulosa cells, which resulted in the maximum level of progesterone production via the induction of <i>Hsd3b</i>. When cumulus-oocyte complexes (COCs) were cultured with AREG in the presence of serum, the maximum level of cumulus expansion was observed. The AREG-induced cumulus expansion was also suppressed by FAK inhibitor. Thus, it is concluded that fibronectin and AREG synergistically activate FAK not only in granulosa cells and cumulus cells to induce successful ovulation process.</p></div

Effects of FAK inhibitor Y15 during ovulation <i>in vivo</i>.

<p>(A): Ovarian morphology of mice treated with hCG for 8 or 16 h was observed by hematoxylin-eosin staining (n = 3 ovaries in each group at each time point). Y15: eCG-primed mice co-injected with hCG and Y15 (30 mg/kg). Scale bar is 100 μm. (B): Effect of Y15 on cumulus expansion (surface area of COCs in periovulatory follicles of the ovary). Ovaries were collected at 0, 8, and 10 h after hCG injection with or without Y15 (30 mg/kg). The ovarian tissue was stained with hematoxylin-eosin, and individual areas of COCs were measured in periovulatory follicles in sections containing an oocyte with a nucleus. C (control): eCG-primed mice injected with hCG; Y15: eCG-primed mice co-injected with hCG and Y15 (30 mg/kg). *; Treatment with Y15 significantly decreased the mean surface area of COCs compared with the control at each time point (p<0.05). Values are the mean ± SEM of five COCs each in three sections. (C): The number of ovulated oocytes when mice were co-administered with hCG and Y15. Ovulated oocytes were collected from oviducts and counted at 16 h after hCG injection. Values are the mean ± SEM of five mice. *; Significant differences were observed compared with the control (p<0.05). C (control): Immature female mice treated with eCG followed by hCG stimulation; Y15: mice co-injected with hCG and Y15 (30 mg/kg) at 48 h after eCG injection. (D): Expression of genes involved in progesterone production and hyaluronic acid synthesis in the ovary of mice treated with hCG and Y15 (30 mg/kg). Three mice were used for sampling granulosa cells in each treatment group at each time point. The mRNA levels of <i>Star</i>, <i>Cyp11a1</i>, <i>Hsd3b1</i>, <i>Ptgs2</i> and <i>Has2</i> were analyzed by real-time PCR and normalized to that of <i>L19</i>. Values are the mean ± SEM of three replicates. *; Y15 treatment significantly suppressed the expression of each gene compared with the control at each time point (p<0.05).</p

Expression of fibronectin and integrins in the mouse ovary during ovulation.

<p>Localization of fibronectin and integrin α5 in the mouse ovary was detected by immunofluorescence staining (n = 3 mice in each time point). Proteins were visualized with Cy3 (fibronectin) and FITC (integrin α5). The nucleus was counterstained with DAPI. Scale bar is 100 μm.</p