62 research outputs found

    Shaking Table Test on Effects of Combination of Soil and Building Properties on Seismic Response of Building

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    To clarify seismic force to buildings and foundations, an effect of dynamic soil and structure interaction is very important. The seismic force to buildings and foundations is influenced by characteristics of both soil deposits and buildings. To investigate the effects of vibration of soil deposits and buildings, a scaled model of building, foundation, and soil deposit is set up on a shaking table. Through analyzing difference between response of foundation without buildings, and surface grounds under the steady state excitation, the horizontal response of foundation is less that of ground surface. This tendency is large with frequency. As one of parameters, there are three kinds of buildings that are 8, 11 and 15 stories models. Under combinations of soil deposits and building properties, seismic forces are compared. The building response is very large when a resonant frequency of building is near to that of soil deposit. The bending moment of piles are affected by not only a base shear of buildings but a displacement of surface ground

    Insulin resistance and white adipose tissue inflammation are uncoupled in energetically challenged Fsp27-deficient mice.

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    Fsp27 is a lipid droplet-associated protein almost exclusively expressed in adipocytes where it facilitates unilocular lipid droplet formation. In mice, Fsp27 deficiency is associated with increased basal lipolysis, 'browning' of white fat and a healthy metabolic profile, whereas a patient with congenital CIDEC deficiency manifested an adverse lipodystrophic phenotype. Here we reconcile these data by showing that exposing Fsp27-null mice to a substantial energetic stress by crossing them with ob/ob mice or BATless mice, or feeding them a high-fat diet, results in hepatic steatosis and insulin resistance. We also observe a striking reduction in adipose inflammation and increase in adiponectin levels in all three models. This appears to reflect reduced activation of the inflammasome and less adipocyte death. These findings highlight the importance of Fsp27 in facilitating optimal energy storage in adipocytes and represent a rare example where adipose inflammation and hepatic insulin resistance are disassociated.This work was supported by grants from the National Basic Research Program (2013CB530602 and 2011CB910801 to P.L.), from the National Natural Science Foundation of China (31430040, 31321003 and 31030038), from the China Postdoctoral Science Foundation (2012M520249 and 2013T60103 to L.Z.) and from the Wellcome Trust (091551 to D.S.). This work was also supported by the Bio and Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2013M3A9D5072563 to C.C.) and Korea Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Korea (A102060 to C.C.).This is the final published version. It first appeared at http://www.nature.com/ncomms/2015/150107/ncomms6949/full/ncomms6949.html?WT.ec_id=NCOMMS-20150114

    FSP27 Promotes Lipid Droplet Clustering and Then Fusion to Regulate Triglyceride Accumulation

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    Fat Specific Protein 27 (FSP27), a lipid droplet (LD) associated protein in adipocytes, regulates triglyceride (TG) storage. In the present study we demonstrate that FSP27 plays a key role in LD morphology to accumulate TGs. We show here that FSP27 promotes clustering of the LDs which is followed by their fusion into fewer and enlarged droplets. To map the domains of FSP27 responsible for these events, we generated GFP-fusion constructs of deletion mutants of FSP27. Microscopic analysis revealed that amino acids 173–220 of FSP27 are necessary and sufficient for both the targeting of FSP27 to LDs and the initial clustering of the droplets. Amino acids 120–140 are essential but not sufficient for LD enlargement, whereas amino acids 120–210 are necessary and sufficient for both clustering and fusion of LDs to form enlarged droplets. In addition, we found that FSP27-mediated enlargement of LDs, but not their clustering, is associated with triglyceride accumulation. These results suggest a model in which FSP27 facilitates LD clustering and then promotes their fusion to form enlarged droplets in two discrete, sequential steps, and a subsequent triglyceride accumulation

    Genome-Wide Association Study Confirming Association of HLA-DP with Protection against Chronic Hepatitis B and Viral Clearance in Japanese and Korean

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    Hepatitis B virus (HBV) infection can lead to serious liver diseases, including liver cirrhosis (LC) and hepatocellular carcinoma (HCC); however, about 85–90% of infected individuals become inactive carriers with sustained biochemical remission and very low risk of LC or HCC. To identify host genetic factors contributing to HBV clearance, we conducted genome-wide association studies (GWAS) and replication analysis using samples from HBV carriers and spontaneously HBV-resolved Japanese and Korean individuals. Association analysis in the Japanese and Korean data identified the HLA-DPA1 and HLA-DPB1 genes with Pmeta = 1.89×10−12 for rs3077 and Pmeta = 9.69×10−10 for rs9277542. We also found that the HLA-DPA1 and HLA-DPB1 genes were significantly associated with protective effects against chronic hepatitis B (CHB) in Japanese, Korean and other Asian populations, including Chinese and Thai individuals (Pmeta = 4.40×10−19 for rs3077 and Pmeta = 1.28×10−15 for rs9277542). These results suggest that the associations between the HLA-DP locus and the protective effects against persistent HBV infection and with clearance of HBV were replicated widely in East Asian populations; however, there are no reports of GWAS in Caucasian or African populations. Based on the GWAS in this study, there were no significant SNPs associated with HCC development. To clarify the pathogenesis of CHB and the mechanisms of HBV clearance, further studies are necessary, including functional analyses of the HLA-DP molecule

    Sex difference in the association of obesity with personal or social background among urban residents in Japan

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    The development of obesity is influenced by genetic and environmental factors and is associated with a variety of health problems. To gain insight into environmental factors that contribute to obesity, we analyzed the relation of personal or social background to obesity in men and women separately with the use of data from a community-based questionnaire survey of 5425 residents aged 20 to 64 years of Kobe, a representative large city in Japan. Obesity and normal weight were defined as a body mass index (BMI) of ≥25 and of ≥ 18.5 and < 25 kg/m(2), respectively, according to the diagnostic criteria of the Japan Society for the Study of Obesity. The personal or social background factors examined included marital status, family structure, employment, household income, residence type, welfare enrollment, economic conditions of current life, educational level, extracurricular activity in school, living conditions at 15 years of age, and childhood adversity. We found that the prevalence of obesity was 27.2% and 10.6% in men and women, respectively. Among women, unmarried status, a low household income, welfare enrollment, difficult current economic conditions, a low educational level, and childhood adversity were associated with obesity, whereas none of the personal or social background factors examined were associated with obesity in men. Our results suggest that the development of obesity in women is strongly influenced by personal or social background, and such factors should be taken into consideration in the management of this condition in women

    Insulin-stimulated Fusion of GLUT4 Vesicles to Plasma Membrane is Dependent on Wortmannin-sensitive Insulin Signaling Pathway in 3T3-L1 Adipocytes

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    It is established that wortmannin which completely inhibits class IA PI 3-kinaseactivation abrogated the insulin-dependent translocation of GLUT4 to the plasmamembrane in adipocytes and skeletal muscle. However, it was not clear which stepswortmannin inhibited during the whole translocation process of GLUT4. We have nowdissected the each steps of the GLUT4 trafficking in 3T3-L1 adipocytes usingexogenously-expressed GLUT4 reporter in combination with plasma membrane lawnassay. We showed that 100 nM wortmannin inhibited the fusion of GLUT4 vesicles tothe plasma membrane without affecting the movement and the subsequenttethering/docking event of GLUT4 vesicles to the membrane in 3T3-L1 adipocytes.These results suggest that wortmannin-sensitive insulin signaling pathway plays acrucial role in the fusion step of GLUT4 vesicles to the plasma membrane in 3T3-L1adipocytes
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