Projecting population distribution under depopulation conditions in Japan: scenario analysis for future socio-ecological systems.

This study develops a projection model of future population distribution on the basis of Japan's current depopulation trend and applies this model to scenario analyses that assume population compactification and dispersion. The model enables a description of population migration at two levels. First, municipal populations are projected using the cohort-component method, and second, the spatial distribution of populations within municipalities is projected at a 500 m grid resolution with the use of the gravity model. Based on the Japanese depopulation context and the country's National Spatial Strategy, the compact scenario predicts the formation of medium-scale regional urban areas (population centers located across Japan) and the concentration of people on high-density population areas within municipalities. Meanwhile, the dispersed scenario predicts the formation of more but smaller regional urban areas and the dispersion of the population to low-density areas. The simulated population distribution for 2050 reveals spatial change in population density and age structure, as well as an abundance of areas that were inhabited in 2015 but will be zero population areas by 2050. Overlay analysis of future land use maps and the simulated population distribution maps can contribute toward identifying areas where natural capital such as farmland and forest plantation should be managed but where there will be significant population loss by 2050.

Hypertrophic Pisiform: A Case of Osteoid Osteoma.

We treated an extremely rare case of osteoid osteoma of the pisiform. Pisiform hypertrophy caused persistent pain and ulnar nerve irritation at Guyon's canal after the initial trauma. The re-enlargement of the pisiform attracted our attention allowing us to ultimately diagnose the condition as osteoid osteoma and treat the patient with a successful clinical result.

Allogeneic Neural Stem/Progenitor Cells Derived From Embryonic Stem Cells Promote Functional Recovery After Transplantation Into Injured Spinal Cord of Nonhuman Primates.

UNLABELLED: : Previous studies have demonstrated that neural stem/progenitor cells (NS/PCs) promote functional recovery in rodent animal models of spinal cord injury (SCI). Because distinct differences exist in the neuroanatomy and immunological responses between rodents and primates, it is critical to determine the effectiveness and safety of allografted embryonic stem cell (ESC)-derived NS/PCs (ESC-NS/PCs) in a nonhuman primate SCI model. In the present study, common marmoset ESC-NS/PCs were grafted into the lesion epicenter 14 days after contusive SCI in adult marmosets (transplantation group). In the control group, phosphate-buffered saline was injected instead of cells. In the presence of a low-dose of tacrolimus, several grafted cells survived without tumorigenicity and differentiated into neurons, astrocytes, or oligodendrocytes. Significant differences were found in the transverse areas of luxol fast blue-positive myelin sheaths, neurofilament-positive axons, corticospinal tract fibers, and platelet endothelial cell adhesion molecule-1-positive vessels at the lesion epicenter between the transplantation and control groups. Immunoelectron microscopic examination demonstrated that the grafted ESC-NS/PC-derived oligodendrocytes contributed to the remyelination of demyelinated axons. In addition, some grafted neurons formed synaptic connections with host cells, and some transplanted neurons were myelinated by host cells. Eventually, motor functional recovery significantly improved in the transplantation group compared with the control group. In addition, a mixed lymphocyte reaction assay indicated that ESC-NS/PCs modulated the allogeneic immune rejection. Taken together, our results indicate that allogeneic transplantation of ESC-NS/PCs from a nonhuman primate promoted functional recovery after SCI without tumorigenicity. SIGNIFICANCE: This study demonstrates that allogeneic embryonic stem cell (ESC)-derived neural stem/progenitor cells (NS/PCs) promoted functional recovery after transplantation into the injured spinal cord in nonhuman primates. ESC-NS/PCs were chosen because ESC-NS/PCs are one of the controls for induced pluripotent stem cell-derived NS/PCs and because ESC derivatives are possible candidates for clinical use. This translational research using an allograft model of a nonhuman primate is critical for clinical application of grafting NS/PCs derived from various allogeneic pluripotent stem cells, especially induced pluripotent stem cells, into injured spinal cord at the subacute phase.

Involvement of afadin in barrier function and homeostasis of mouse intestinal epithelia.

Afadin interacts with the cytoplasmic region of nectins, which are immunoglobulin-like cell adhesion molecules at adherens junctions, and links them to the actin cytoskeleton. Afadin regulates activities of cells in culture such as directional motility, proliferation and survival. We used Cre-loxP technology to generate mice conditionally lacking afadin specifically in the intestinal epithelia after birth. The loss of afadin caused increased paracellular permeability in the intestinal mucosa and enhanced susceptibility to the tissue destruction induced by dextran sulfate sodium. The junctional architecture of the intestinal epithelia appeared to be preserved, whereas the deficiency of afadin caused the mislocalization of nectin-2 and nectin-3 from adherens junctions to basolateral membrane domains but not that of other components of apical junctions. By contrast, such phenotypic changes were undetected in mice lacking nectin-2, nectin-3 or both. These findings suggest that afadin plays crucial roles, independently of the role as the nectin-afadin module, in barrier function and homeostasis of the intestinal epithelia once the epithelial structure has been established.

Decreased expression of LMO7 and its clinicopathological significance in human lung adenocarcinoma.

LIM-domain only protein 7 (LMO7) has been suggested to act as a tumor suppressor for murine lung adenocarcinoma, while its splice variant p100 LMO7/#16 is associated with invasion and metastasis of rat AH130W1 cells. However, the importance of LMO7 in human lung cancer is unknown. We investigated LMO7 protein expression by immunohistochemistry in tumor tissues obtained from 57 patients with adenocarcinoma of the lung using a rabbit anti-LMO7 antibody. Signals for LMO7 were localized to the apical surface of the bronchial epithelium and to the cell membranes of pneumocytes in non-cancerous pulmonary tissues, but were noted circumferentially around the plasma membrane of cancer cells in all 57 patients with adenocarcinoma. The LMO7-positive group (24 patients, 42%) showed equivocal to strong expression of LMO7 in more than 50% cancer cells, while the remaining 33 patients (58%) showed LMO7 expression in less than 50% of their cancer cells. The latter group had significantly more advanced disease than the LMO7-positive group with regard to T factor (p=0.011), nodal involvement (p=0.026) and p-stage (p=0.010; χ(2) test). Multivariate analysis using a logistic regression model showed that LMO7 expression was independently associated with the T factor (p=0.041). Kaplan-Meier analysis showed that a poor prognosis was associated with low expression of LMO7 (p=0.036; log-rank test). Our findings are consistent with earlier observations and demonstrate that LMO7 is inversely correlated with the development and prognosis of human lung adenocarcinoma.

Can a solitary avian species use collective detection? An assay in semi-natural conditions.

Collective detection (e.g., enhanced predator detection through the vigilance of conspecifics) is expected to have evolved particularly in social species. However, we assessed the degree to which an avian territorial species (California towhee Pipilo crissalis) would use social cues about predation in a semi-natural assay. We also exposed a social species (house finch Carpodacus mexicanus) to similar conditions. California towhees increased scanning rates when foraging with conspecifics, whereas house finches increased scanning rates when foraging solitarily, suggesting that vigilance in these species is regulated mostly through interference competition and through predation risk, respectively. California towhees did not show early detection, and actually the last detector in the group delayed detection in relation to solitary individuals. House finches benefited from early detection, but the second and last detectors maintained detection at the level of solitary individuals. California towhees increased the chances of fleeing when in groups in relation to solitary conditions, but this effect was less pronounced in the last detector. House finches always fled across conditions. Overall, an asocial avian species may use collective detection, but limited to certain types of cues: responses were more pronounced to overt (conspecifics walking or fleeing) rather than subtle (conspecifics becoming alert or crouching) social cues.

Increased susceptibility to spontaneous lung cancer in mice lacking LIM-domain only 7.

LIM-domain only (LMO) 7 is a multifunctional protein that is predicted to regulate the actin cytoskeleton, assembly of adherens junctions in epithelial cells, and gene expression. LMO7 was highly expressed in the mouse lung and predominantly localized to the apical membrane domain of bronchiolar epithelial cells. Although mice lacking LMO7 were viable and fertile in specific pathogen-free conditions, they developed protruding epithelial lesions in the terminal and respiratory bronchioles and alveolar ducts at 14-15 weeks of age. Furthermore, they tended to develop spontaneous adenocarcinoma in the lung at over 90 weeks of age. The cumulative incidence ratios of lung cancer were 22% in LMO7(-/-) mice and 13% in LMO7(+/-) mice whereas no primary lung cancer was observed in wild-type mice. Ex vivo analyses of the cancer cells showed numerical chromosome abnormalities and tumorigenicity in nude mice. These results suggest that LMO7 can act as a tumor suppressor whose deficiency confers a genetic predisposition to naturally occurring lung cancer.

Defective chemokine-directed lymphocyte migration and development in the absence of Rho guanosine diphosphate-dissociation inhibitors alpha and beta.

Rho family small GTP-binding proteins, including Rho, Rac, and Cdc42, are key determinants of cell movement and actin-dependent cytoskeletal morphogenesis. Rho GDP-dissociation inhibitor (GDI) alpha and Rho GDIbeta (or D4/Ly-GDI), closely related regulators for Rho proteins, are both expressed in hemopoietic cell lineages. Nevertheless, the functional contributions of Rho GDIs remain poorly understood in vivo. In this study, we report that combined disruption of both the Rho GDIalpha and Rho GDIbeta genes in mice resulted in reduction of marginal zone B cells in the spleen, retention of mature T cells in the thymic medulla, and a marked increase in eosinophil numbers. Furthermore, these mice showed lower CD3 expression and impaired CD3-mediated proliferation of T cells. While B cells showed slightly enhanced chemotactic migration in response to CXCL12, peripheral T cells showed markedly reduced chemotactic migration in response to CCL21 and CCL19 associated with decreased receptor levels of CCR7. Overall, Rho protein levels were reduced in the bone marrow, spleen, and thymus but sustained activation of the residual part of RhoA, Rac1, and Cdc42 was detected mainly in the bone marrow and spleen. Rho GDIalpha and Rho GDIbeta thus play synergistic roles in lymphocyte migration and development by modulating activation cycle of the Rho proteins in a lymphoid organ-specific manner.