ABSTRACT
Obesity is characterized by the excessive accumulation of the white adipose tissue (WAT), but healthy expansion of WAT via adipocyte hyperplasia can offset the negative metabolic effects of obesity. Thus, identification of novel adipogenesis regulators that promote hyperplasia may lead to effective therapies for obesity-induced metabolic disorders. Using transcriptomic approaches, we identified transmembrane BAX inhibitor motif-containing 1 (TMBIM1) as an inhibitor of adipogenesis. Gain or loss of function of TMBIM1 in preadipocytes inhibited or promoted adipogenesis, respectively. In vivo, in response to caloric excess, adipocyte precursor (AP)-specific Tmbim1 knockout (KO) mice displayed WAT hyperplasia and improved systemic metabolic health, while overexpression of Tmbim1 in transgenic mice showed the opposite effects. Moreover, mature adipocyte-specific Tmbim1 KO did not affect WAT cellularity or nutrient homeostasis. Mechanistically, TMBIM1 binds to and promotes the autoubiquitination and degradation of NEDD4, which is an E3 ligase that stabilizes PPARγ. Our data show that TMBIM1 is a potent repressor of adipogenesis and a potential therapeutic target for obesity-related metabolic disease.
Subject(s)
Adipogenesis , Metabolic Diseases , Adipocytes, White/metabolism , Adipose Tissue, White/metabolism , Animals , Hyperplasia/metabolism , Membrane Proteins , Metabolic Diseases/metabolism , Mice , Mice, Inbred C57BL , Nerve Tissue Proteins , Obesity/metabolismABSTRACT
OBJECTIVE: To investigate the epidemiological characteristics of influenza B viruses and explore the genetic evolution characteristics of the hemagglutinin(HA) and neuraminidase(NA) genes of local isolated strains in Ningbo, Southeast China, during 2010 to 2012. METHODS: Respiratory specimens from 3440 cases of patients with influenza-like illness(ILI) during 2010 to 2012 were collected in for virus isolation. And the 628 sera samples were collected in 2010 from the healthy community population to detect the HI antibody level against the local isolated virus.For phylogenetic analysis, the fragments of HA and NA genes were amplified and sequenced from strains isolated in different years. The association between evolution of HA and epidemiological characteristics were analyzed. RESULTS: A total of 109 strains of influenza B virus were isolated, including 102 (93.6%) Victoria-lineage strains and 7 (6.4%) Yamagata-lineage strains. Positive rates of HI antibody against Victoria-lineage strains and Yamagata-lineage strains were 51.1% (321) and 47.8% (300), respectively (χ(2) = 1.405, P > 0.05) among the 628 sera samples. The phylogenetic analysis showed that all HA fragments of isolated strains clustered the same branch with Malaysia/2506/2004 while the NA genes formed different branches. Compared with Brisbane/60/2008 strain, there were 1 to 5 Amino acid mutations in HA domain, and more mutations were detected in NA domain, ranged from 6 to 16 sites. The genetic evolution of NA in Victoria-lineage strains were faster compared with HA. CONCLUSION: The genetic evolution rates of NA genes were faster than that of HA genes in the local circulated Victoria-lineage viruses during 2010 to 2012;The comprehensive analysis of HA and NA fragments were more reliable and sensitive on surveillance of genetic evolution of influenza B viruses.
Subject(s)
Hemagglutinin Glycoproteins, Influenza Virus/genetics , Influenza B virus/genetics , Influenza, Human/virology , Neuraminidase/genetics , China/epidemiology , Genetic Variation , Humans , Influenza B virus/classification , Influenza B virus/isolation & purification , Influenza, Human/epidemiology , Phylogeny , RNA, ViralABSTRACT
110 children who were given the complete course of the inactivated hepatitis A vaccine (Havrix) were followed up 10 years later. Age-matched healthy children who were not inoculated served as controls. One month after two primary injections, all children were positive for serum antibody. After 10 years, 99.09% of inoculated children remained positive for serum anti-HAV antibody, with a geometric mean concentration (GMC) of 61.59mIU/mL. GMC values following a secondary immunization in children with antibody levels <20mIU/mL were significantly elevated (567.9mIU/mL), compared with the primary injection alone. Havrix appears to induce persistent immunity and potent immune memory.
Subject(s)
Hepatitis A Vaccines/immunology , Hepatitis A/immunology , Hepatitis A/prevention & control , Antibodies, Viral/analysis , Child , Child, Preschool , China/epidemiology , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , Hepatitis A Antibodies/analysis , Hepatitis A Antibodies/immunology , Humans , Immunologic Memory , Infant , Male , Models, Statistical , Vaccination/statistics & numerical data , Vaccines, Attenuated , Vaccines, InactivatedABSTRACT
OBJECTIVE: To understand the status of infants infected with influenza viruses after switch over of dominant strain in the summer of 2006. METHODS: Two groups of infants serum were collected and to be detected the antibodies of influenza viruses which the infants experienced two peaks of influenza A H1N1 circulation in the age of 3-4 and 10-11 months old and the infants only experience one circulation in 5-6 months old. RESULTS: The antibody of influenza A H1N1 viruses was 31.47% in the infants who experience two circulations in 3-4 months and 10-11 months old and was 26.42% which only experience circulation in the 5-6 months old. There were no significant difference between 2 groups (chi2 = 1.207, P > 0.05). CONCLUSION: The group of 13 months age of infants were rarely infected influenza virus in the first time exposure at the age of < or =4 months due to maternal antibodies protection. Whenas, the group of 8 months age who were exposed at the age of > or =5 months, were more easier infected the influenza virus than the group of 13 months age in the first time exposure at the age of < or =4 months.
