Measurement of social net benefit of climate stabilization policy

To evaluate the social welfare of climate stabilization policy from perspectives of cost–benefit analysis in a optimal economic growth framework based on macroeconomic theory, the purposes of this study are to show theoretically that the equivalent variation is divisible into a public-welfare effect, an income-change effect, and changes in investment in consideration of non-market effects of temperature change on utility. Then each effect of climate stabilization policy must be measured using simulation analysis. Consequently, it is concluded that the framework that this study has adopted is theoretically consistent with traditional cost-benefit framework and can measure each effect of climate stabilization policy.equivalent welfare measure, cost-benefit analysis, climate stabilization policy, macroeconomic model

Computational cell model based on autonomous cell movement regulated by cell-cell signalling successfully recapitulates the "inside and outside" pattern of cell sorting

<p>Abstract</p> <p>Background</p> <p>Development of multicellular organisms proceeds from a single fertilized egg as the combined effect of countless numbers of cellular interactions among highly dynamic cells. Since at least a reminiscent pattern of morphogenesis can be recapitulated in a reproducible manner in reaggregation cultures of dissociated embryonic cells, which is known as cell sorting, the cells themselves must possess some autonomous cell behaviors that assure specific and reproducible self-organization. Understanding of this self-organized dynamics of heterogeneous cell population seems to require some novel approaches so that the approaches bridge a gap between molecular events and morphogenesis in developmental and cell biology. A conceptual cell model in a computer may answer that purpose. We constructed a dynamical cell model based on autonomous cell behaviors, including cell shape, growth, division, adhesion, transformation, and motility as well as cell-cell signaling. The model gives some insights about what cellular behaviors make an appropriate global pattern of the cell population.</p> <p>Results</p> <p>We applied the model to "inside and outside" pattern of cell-sorting, in which two different embryonic cell types within a randomly mixed aggregate are sorted so that one cell type tends to gather in the central region of the aggregate and the other cell type surrounds the first cell type. Our model can modify the above cell behaviors by varying parameters related to them. We explored various parameter sets with which the "inside and outside" pattern could be achieved. The simulation results suggested that direction of cell movement responding to its neighborhood and the cell's mobility are important for this specific rearrangement.</p> <p>Conclusion</p> <p>We constructed an <it>in silico </it>cell model that mimics autonomous cell behaviors and applied it to cell sorting, which is a simple and appropriate phenomenon exhibiting self-organization of cell population. The model could predict directional cell movement and its mobility are important in the "inside and outside" pattern of cell sorting. Those behaviors are altered by signal molecules and consequently affect the global pattern of the cell sorting. Our model is also applicable to other developmental processes beyond cell sorting.</p

Development of engineered chromatic acclimation sensor with strict and reverse response to light signal, and application to optogenetic control in cyanobacteria

Genetic regulation and metabolic engineering enabled cyanobacteria to produce renewable chemical compounds from carbon dioxide via photosynthesis. Optogenetic control enables to precisely regulate the timing and level of gene expression without chemical inducer which is environment-hazardous. We recently developed a green-light regulated gene expression system in a model cyanobacterial strain Synechocystis sp. PCC6803 (hereafter PCC6803) [1] and a fast-growing marine cyanobacterial strain Synechococcus sp. NKBG15041c (hereafter NKBG15041c) [2] using a PCC6803-derived chromatic acclimation sensor, CcaS/CcaR two-component system [3]. However, the regulation of gene expression by CcaS is not strictly controllable and the background expression level under non-inductive condition is not negligible. Furthermore, altering the direction of gene expression, that is induction under red-light and repression under green-light, may expand its flexibility as one of the genetic tools. To obtain stricter and versatile system, we fabricated engineered CcaSs focusing on its domain structure using Escherichia coli expression system. One of the engineered CcaSs, CcaS#11, showed reverse response to light signal, i.e. inducible under red-light and strictly repressible under green-light [4]. To investigate the potential application and versatility of CcaS#11 as the red-light regulated gene expression system in cyanobacteria, we next introduced CcaS#11/CcaR two-component system and GFPuv as a probe of gene expression into PCC6803 after knocking out genomic CcaS/CcaR two-component system to exclude the interference. In this strain, the gene expression was induced under red-light and strictly repressed under green-light as we expected. Then, we applied this system to NKBG15041c. Similarly, red-light inducible gene expression with 2-fold higher ON/OFF ratio compared with the original system was successfully observed in NKBG15041c. Remarkably, there was no leaky expression under green-light, indicating that this system enables strict regulation of gene expression by light signal. In conclusion, we successfully constructed the engineered CcaS, CcaS#11, with strict and reverse response to light signal. Then we also confirmed its versatility and applicability as the red-light regulated gene expression system with strict regulation in cyanobacteria. Further development of the light regulated bioprocess will be expected using cyanobacterial hosts with this system, as a cell factory for the renewable chemical compounds production. [1] K. Abe et al., ‘Engineering of a Green-light Inducible Gene Expression System in Synechocystis sp. PCC 6803’, Microb. Biotechnol. 7 (2014) 177-183 [2] A. Badary et al., ‘The Development and Characterization of an Exogenous Green-light-regulated Gene Expression System in Marine Cyanobacteria’, Mar. Biotechnol. 17 (2015) 245-251 [3] Y. Hirose et al., ‘Cyanobacteriochrome CcaS is the Green Light Receptor That Induces the Expression of Phycobilisome Linker Protein’, Proc. Natl. Acad. Sci. USA 105 (2008) 9528-9533 [4] M. Nakajima et al., ‘Construction of a Miniaturized Chromatic Acclimation Sensor from Cyanobacteria with Reversed Response to a Light Signal’, Sci. Rep. 6 (2016) 3759

Effectiveness of Domain-Based Intervention for Language Development in Japanese Hearing-Impaired Children: A Multicenter Study

Objective: Decreasing language delay in hearing-impaired children is a key issue in the maintenance of their quality of life. Language training has been presented mainly by experience-based training; effective intervention programs are crucially important for their future. The aim of this study was to confirm the efficacy of 6-month domain-based language training of school-age, severe-to-profound hearing-impaired children. Methods: We conducted a controlled before-after study involving 728 severe-to-profound prelingual hearing-impaired children, including an intervention group (n = 60), control group (n = 30), and baseline study group (n = 638). Language scores of the participants and questionnaires to the caregivers/therapists were compared before and after the intervention. Average monthly increase in each language score of the control group and baseline study group were compared with those of the intervention group. Results: Language scores and the results of the questionnaire of the intervention group showed a significant improvement (P < .05). The average monthly language growth of the intervention group was twice that of the control group and 3 to 4 times that of the baseline study group (P < .05). The effect size was largest in communication (1.914), followed by syntax (0.931). Conclusion: Domain-based language training improved the language development and daily communication of hearing-impaired children without any adverse effects

Downregulation of functional Reelin receptors in projection neurons implies that primary Reelin action occurs at early/premigratory stages

Reelin signaling is essential for correct development of the mammalian brain. Reelin binds to apolipoprotein E receptor 2 and very low-density lipoprotein receptor and induces phosphorylation of Dab1. However, when and where these reactions occur is essentially unknown, and the primary function(s) of Reelin remain unclear. Here, we used alkaline phosphatase fusion of the receptor-binding region of Reelin to quantitatively investigate the localization of functional Reelin receptors (i.e., those on the plasma membrane as mature forms) in the developing brain. In the wild-type cerebral cortex, they are mainly present in the intermediate and subventricular zones, as well as in radial fibers, but much less in the cell bodies of the cortical plate. Functional Reelin receptors are much more abundant in the Reelin-deficient cortical plate, indicating that Reelin induces their downregulation and that it begins before the neurons migrate out of the intermediate zone. In the wild-type cerebellum, functional Reelin receptors are mainly present in the cerebellar ventricular zone but scarcely expressed by Purkinje cells that have migrated out of it. It is thus strongly suggested that Reelin exerts critical actions on migrating projection neurons at their early/premigratory stages en route to their final destinations, in the developing cerebral cortex and cerebellum. Copyright © 2009 Society for Neuroscience.This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture (M.H., A.B.), Ono Medical Research Foundation, and Kanae Foundation for the Promotion of Medical Science (M.H.). T.H. is a Research Fellow of Japan Society for the Promotion of Science. J.M.L. is a Ramón y Cajal Research Fellow funded by Grant SAF2004-07685 and Fundación Mutua Madrileña.Peer Reviewe

SUMOylation of DISC1: a potential role in neural progenitor proliferation in the developing cortex

DISC1 is a multifunctional, intracellular scaffold protein. At the cellular level, DISC1 plays a pivotal role in neural progenitor proliferation, migration, and synaptic maturation. Perturbation of the biological pathways involving DISC1 is known to lead to behavioral changes in rodents, which supports a clinical report of a Scottish pedigree in which the majority of family members with disruption of the DISC1 gene manifest depression, schizophrenia, and related mental conditions. The discrepancy between modest evidence in genetics and strong biological support for the role of DISC1 in mental conditions suggests a working hypothesis that regulation of DISC1 at the protein level, such as posttranslational modification, may play a role in the pathology of mental conditions. In this study, we report on the SUMOylation of DISC1. This posttranslational modification occurs on lysine residues where the small ubiquitin-related modifier (SUMO) and its homologs are conjugated to a large number of cellular proteins, which in turn regulates their subcellular distribution and protein stability. By using in silico, biochemical, and cell-biological approaches, we now demonstrate that human DISC1 is SUMOylated at one specific lysine 643 (K643). We also show that this residue is crucial for proper neural progenitor proliferation in the developing cortex