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Impaired Cellular Responses to Cytosolic DNA or Infection with Listeria monocytogenes and Vaccinia Virus in the Absence of the Murine LGP2 Protein
Darja Pollpeter,Akihiko Komuro,Glen N. Barber,Curt M. Horvath
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0018842
Abstract: Innate immune signaling is crucial for detection of and the initial response to microbial pathogens. Evidence is provided indicating that LGP2, a DEXH box domain protein related to the RNA recognition receptors RIG-I and MDA5, participates in the cellular response to cytosolic double-stranded DNA (dsDNA). Analysis of embryonic fibroblasts and macrophages from mice harboring targeted disruption in the LGP2 gene reveals that LGP2 can act as a positive regulator of type I IFN and anti-microbial gene expression in response to transfected dsDNA. Results indicate that infection of LGP2-deficient mice with an intracellular bacterial pathogen, Listeria monocytogenes, leads to reduced levels of type I IFN and IL12, and allows increased bacterial growth in infected animals, resulting in greater colonization of both spleen and liver. Responses to infection with vaccinia virus, a dsDNA virus, are also suppressed in cells lacking LGP2, reinforcing the ability of LGP2 to act as a positive regulator of antiviral signaling. In vitro mechanistic studies indicate that purified LGP2 protein does not bind DNA but instead mediates these responses indirectly. Data suggest that LGP2 may be acting downstream of the intracellular RNA polymerase III pathway to activate anti-microbial signaling. Together, these findings demonstrate a regulatory role for LGP2 in the response to cytosolic DNA, an intracellular bacterial pathogen, and a DNA virus, and provide a plausible mechanistic hypothesis as the basis for this activity.
Relationship between the Concentration of Impurity and Albedo in Snow Surface  [PDF]
Yuki Komuro, Toshitaka Suzuki
Atmospheric and Climate Sciences (ACS) , 2015, DOI: 10.4236/acs.2015.54034
Abstract: Recent decline of cryosphere typified by retreat of glaciers is often explained by temperature rise due to global warming. However, the existence of glaciers shrinking since before 1950s warming accelerated suggested that decline of cryosphere may be due to not only temperature rise, but also another possibility. As a possible cause of snow and ice melting, it has been pointed out that the surface albedo reduction due to increase of snow impurity, aeolian dust and anthropogenic pollutant, for example. To clarify the quantitative relationship between albedo and impurity in snow surface, we investigated the correlativity of turbidity and metal concentration in snow to the snow surface albedo from the simultaneous observations on the snow-covered area in Yamagata, Japan. The observed albedo shows a tendency of decrease with the turbidity increase in snow surface, we could find strong correlation between the albedo and the turbidity in 76% of contribution factor using logarithmic regression analysis. The relationship of albedo to total concentration of Fe and Al in snow surface shows the similar tendency to turbidity, we could model the relationship using logarithmic equation with high value of contribution ratio, 74% and 66%, respectively. The concentration ratio of Fe/Al is nearly constant with about 0.75, which is close to mean crustal ratio of both elements, therefore, it can be said there is a strong correlation between the albedo and the concentration of mineral particle in snow surface. We cannot find a significant correlation between the albedo and total concentration of Na in snow surface. It can be considered that Na existed as dissolved ion has not significant effect to the albedo in snow surface. These results indicate that the snow albedo correlates strongly with the particulate matter in snow surface, which is typified by mineral particle.
Gab Docking Proteins in Cardiovascular Disease, Cancer, and Inflammation
Yoshikazu Nakaoka,Issei Komuro
International Journal of Inflammation , 2013, DOI: 10.1155/2013/141068
Gab Docking Proteins in Cardiovascular Disease, Cancer, and Inflammation
Yoshikazu Nakaoka,Issei Komuro
International Journal of Inflammation , 2013, DOI: 10.1155/2013/141068
Abstract: The docking proteins of the Grb2-associated binder (Gab) family have emerged as crucial signaling compartments in metazoans. In mammals, the Gab proteins, consisting of Gab1, Gab2, and Gab3, are involved in the amplification and integration of signal transduction evoked by a variety of extracellular stimuli, including growth factors, cytokines, antigens, and other molecules. Gab proteins lack the enzymatic activity themselves; however, when phosphorylated on tyrosine residues, they provide binding sites for multiple Src homology-2 (SH2) domain-containing proteins, such as SH2-containing protein tyrosine phosphatase 2 (SHP2), phosphatidylinositol 3-kinase regulatory subunit p85, phospholipase Cγ, Crk, and GC-GAP. Through these interactions, the Gab proteins transduce signals from activated receptors into pathways with distinct biological functions, thereby contributing to signal diversification. They are known to play crucial roles in numerous physiological processes through their associations with SHP2 and p85. In addition, abnormal Gab protein signaling has been linked to human diseases including cancer, cardiovascular disease, and inflammatory disorders. In this paper, we provide an overview of the structure, effector functions, and regulation of the Gab docking proteins, with a special focus on their associations with cardiovascular disease, cancer, and inflammation. 1. Introduction The mammalian Grb2-associated binder (Gab) proteins are homologs of Drosophila DOS (Daughter Of Sevenless) and Caenorhabditis elegans SOC-1 (Suppressor Of Clear). These proteins define a family of docking proteins closely related to the insulin receptor substrate (IRS-1, IRS-2, IRS-3), fibroblast growth factor substrate (FRS2), linker of T cell (LAT), and downstream of kinase (Dok) families [1]. In contrast to adaptor proteins such as growth factor receptor bound protein 2 (Grb2) and Shc, which are usually smaller and often function as a molecular bridge between two proteins in the assembly of larger protein complexes, docking proteins contain a membrane-targeting region at the N-terminus, binding sites for src homology 3 (SH3) domain-containing proteins, and multiple tyrosine phosphorylation sites that, when phosphorylated, function as binding sites for the src homology 2 (SH2) domains of a variety of effectors. Consequently, the docking proteins are significantly larger than adaptor proteins. In addition, docking proteins usually contain one or more moieties that mediate their recruitment to plasma membranes through protein-protein or protein-lipid interactions. Their
Cyclosporin A inhibits the growth of neonatal MHC-expressing myotubes independent of NFATc1 and NFATc3 in the mechanically overloaded soleus muscle of mice  [PDF]
Kunihiro Sakuma, Akihiko Yamaguchi
American Journal of Molecular Biology (AJMB) , 2011, DOI: 10.4236/ajmb.2011.11002
Abstract: ABSTRACT The molecular signaling pathway linked to hyper-trophy of the anti-gravity/postural soleus muscle af-ter mechanical overloading has not been identified. Using Western blot and immunohistochemical analy-ses, we investigated whether the amounts of NFATc3, GSK-3?, NFATc1, and neonatal MHC change in the mechanically overloaded soleus muscle after cyc-losporine A (CsA) treatment. Adult male ICR mice were subjected to a surgical ablation of the gas-trocnemius muscle and treated with either CsA (25 mg/Kg) or vehicle once daily. They were sacrificed at 2, 4, 7, 10, and 14 days post-injury. Mechanical over-loading resulted in a significant increase in the wet weight and the cross-sectional area of slow and fast fibers of the soleus muscle in placebo-treated mice but not CsA-treated mice. After 4 days of mechanical overloading, we observed a similar co-localization of neonatal MHC and NFATc3 in several myotubes of both mice. The placebo-treated mice possessed larger myotubes with neonatal MHC than CsA-treated mice. At 7 days, mechanical overloading induced marked expression of neonatal MHC in myotubes and/or myofibers. Such neonatal MHC-positive fibers emerged less often in the hypertrophied soleus mus-cle subjected to treatment with CsA. CsA treatment did not significantly change the amount of GSK-3? protein in the soleus muscle. The modulation of growth in neonatal MHC-positive myofibers by CsA treatment may inhibit the hypertrophic process in the soleus muscle after mechanical overloading.
Selection of Suitable Safety Activities and Experience of Safety Condition Establishment  [PDF]
Akihiko Hidaka, Atsumi Miyake
Open Journal of Safety Science and Technology (OJSST) , 2015, DOI: 10.4236/ojsst.2015.51001
Abstract: In recent years, Japanese manufacturing firms have been building factories in the developing countries of Southeast Asia and employing local personnel. Using local employees who were basically people of the agricultural countries implies difficulties in both technical and safety terms. This study examines how quickly and effectively the companies going into the developing countries establish a standard of safety. The authors focus on Vietnam and Thailand as representative countries. To their surprise, the authors find that all 27 companies that answered their questionnaire had introduced “5S activities” at startup and were continuing to use them. In addition, nearly 80% of the companies began using “KY activities”, “Safety proposal activities”, and “Examinations of accidents” soon after startup. One of the authors Akihiko Hidaka, when serving as the president of the Thai subsidiary of a Japanese chemical company, developed safety activities to reduce work-related accidents. And he knew that the kinds of safety activities he developed were same as above 4 activities. So he evaluated these activities and judged them to be effective. The authors conclude that “5S activities”, “KY activities”, “Safety proposal activities”, and “Examinations of accidents” were the activities best able to improve safety effectively and quickly in developing countries. The authors describe the safety activities carried out at the Thai company and then describe the most important features of the methods used to establish safety conditions at the firm.
Toward Circumventing Collinearity Effect in Nonlinear Spectral Mixture Analysis by Using a Spectral Shape Measure  [PDF]
Wei Yang, Akihiko Kondoh
Advances in Remote Sensing (ARS) , 2016, DOI: 10.4236/ars.2016.53015
Abstract: Nonlinear spectral mixture analysis (NSMA) is a widely used unmixing algorithm. It can fit the mixed spectra adequately, but collinearity effect among true and virtual endmembers will decrease the retrieval accuracies of endmember fractions. Use of linear spectral mixture analysis (LSMA) can effectively reduce the degree of collinearity in the NSMA. However, the inadequate modeling of mixed spectra in the LSMA will also yield retrieval errors, especially for the cases where the multiple scattering is not ignorable. In this study, a generalized spectral unmixing scheme based on a spectral shape measure, i.e. spectral information divergence (SID), was applied to overcome the limitations of the conventional NSMA and LSMA. Two simulation experiments were undertaken to test the performances of the SID, LSMA and NSMA in the mixture cases of treesoil, tree-concrete and tree-grass. Results demonstrated that the SID yielded higher accuracies than the LSMA for almost all the mixture cases in this study. On the other hand, performances of the SID method were comparable with the NSMA for the tree-soil and tree-grass mixture cases, but significantly better than the NSMA for the tree-concrete mixture case. All the results indicate that the SID method is fairly effective to circumvent collinearity effect within the NSMA, and compensate the inadequate modeling of mixed spectra within the LSMA.
Risk Assessment of Land Subsidence in Kathmandu Valley, Nepal, Using Remote Sensing and GIS  [PDF]
Richa Bhattarai, Akihiko Kondoh
Advances in Remote Sensing (ARS) , 2017, DOI: 10.4236/ars.2017.62010
Abstract: Land subsidence is identified as a global problem and intensive studies are being conducted worldwide to detect and monitor risk of this problem. Risk assessment of land subsidence is simply an evaluation of the probability and frequency of occurrence of land subsidence, exposure of people and property to the subsidence and consequence of that exposure. Remote sensing technology was used to extract information of land subsidence in Kathmandu Valley, Nepal. Also, Disaster Risk Index method and Analytic Hierarchy Process (AHP) along with Geographic Information System (GIS) tools were used to assess risk of land subsidence in Kathmandu Valley, Nepal. Subsidence volume for locations Central Kathmandu, Chauni, Lalitpur, Imadol, Thimi, Madhyaour Thimi, New Baneshwor, Koteshwor and Gothatar was calculated using a simple mathematical formula. The subsidence depth for these locations was found to be in a range of 1 cm to 17 cm and the maximum subsidence velocity was found to be 4.8 cm/yr. This study revealed that the location where maximum subsidence was observed (i.e. Central Kathmandu and Lalitpur) was found to be at high risk of experiencing land subsidence induced damage. Other location where subsidence was observed was found to be at medium risk and the rest of the Kathmandu valley was found to be at low risk with current data situation. This study can be considered as the first step towards other comprehensive study relating to land subsidence risk assessment. The outcome of this research provides a basic understanding of the current situation that can further assist in developing prevention and risk management techniques.
Government Expenditure Financing in the Money-in-the-Production-Function Model  [PDF]
Akihiko Kaneko, Daisuke Matsuzaki
Theoretical Economics Letters (TEL) , 2018, DOI: 10.4236/tel.2018.82008
Abstract: In this study, we consider a scenario in which the government resorts to an income and inflation tax to finance its expenditures in the money-in-the-production-function model. We show that a financing shift from the inflation tax to the income tax increases the real money holdings-to-capital ratio because the accumulation of capital is less favorable than holding money. We also find that a country’s economic growth rate is maximized if all government expenditures are financed through an income tax. For welfare maximization, the government should set the income tax rate higher than the growth maximizing tax rate and reimburse the excess revenue using money contraction.
Therapeutic Implications of PPAR in Cardiovascular Diseases
Hiroshi Hasegawa,Hiroyuki Takano,Issei Komuro
PPAR Research , 2010, DOI: 10.1155/2010/876049
Abstract: Peroxisome proliferator-activated receptor- (PPAR ) is the members of the nuclear receptor superfamily as a master transcriptional factor that promotes differentiation of preadipocytes by activating adipose-specific gene expression. Although PPAR is expressed predominantly in adipose tissue and associated with adipocyte differentiation and glucose homeostasis, PPAR is also present in a variety of cell types including vascular cells and cardiomyocytes. Activation of PPAR suppresses production of inflammatory cytokines, and there is accumulating data that PPAR ligands exert antihypertrophy of cardiomyocytes and anti-inflammatory, antioxidative, and antiproliferative effects on vascular wall cells and cardiomyocytes. In addition, activation of PPAR is implicated in the regulation of endothelial function, proliferation and migration of vascular smooth muscle cells, and activation of macrophages. Many studies suggest that PPAR ligands not only ameliorate insulin sensitivity, but also have pleiotropic effects on the pathophysiology of atherosclerosis, cardiac hypertrophy, ischemic heart, and myocarditis. 1. Introduction Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the western world. Major risk factors for CVD is hypertension, dyslipidemia, and hyperglycemia including insulin resistance [1]. Many antihypertensive drugs are widely used to normalize blood pressure, and its evidence of CVD preventive effect has been clarified [2]. Moreover, several classes of drugs for dyslipidemia, including bile acid sequestrants, fibrates, and statins, have been used historically to reduce cholesterol levels and reduced the morbidity and mortality of CVD [3]. Meanwhile, insulin has been used to improve hyperglycemia as a pivotal controller of basic glucose metabolism. Since the insulin self-injection of every day is intolerable [4], other agents that are used to help control elevated glucose concentrations in diabetes have been developed. These agents can decrease glucose production by the liver (metformin), stimulate insulin secretion (sulfonylureas and meglitinides), retard glucose absorption from the gastrointestinal tract (-glycosidase inhibitors), slow intestinal motility (amylin), reduce insulin resistance (thiazolidinediones (TZDs)), or replace gastrointestinal peptides known to be active in glucose metabolism (GLP-1 analogs or dipeptidyl peptase IV inhibitors). TZDs are a class of glucose-lowering oral medications which improve glycemic control and improve insulin sensitivity in muscle and liver [5]. TZDs exert their hypoglycemic
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