Role of Transcription Factor Modifications in the Pathogenesis of Insulin Resistance

Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver not due to alcohol abuse. NAFLD is accompanied by variety of symptoms related to metabolic syndrome. Although the metabolic link between NAFLD and insulin resistance is not fully understood, it is clear that NAFLD is one of the main cause of insulin resistance. NAFLD is shown to affect the functions of other organs, including pancreas, adipose tissue, muscle and inflammatory systems. Currently efforts are being made to understand molecular mechanism of interrelationship between NAFLD and insulin resistance at the transcriptional level with specific focus on post-translational modification (PTM) of transcription factors. PTM of transcription factors plays a key role in controlling numerous biological events, including cellular energy metabolism, cell-cycle progression, and organ development. Cell type- and tissue-specific reversible modifications include lysine acetylation, methylation, ubiquitination, and SUMOylation. Moreover, phosphorylation and O-GlcNAcylation on serine and threonine residues have been shown to affect protein stability, subcellular distribution, DNA-binding affinity, and transcriptional activity. PTMs of transcription factors involved in insulin-sensitive tissues confer specific adaptive mechanisms in response to internal or external stimuli. Our understanding of the interplay between these modifications and their effects on transcriptional regulation is growing. Here, we summarize the diverse roles of PTMs in insulin-sensitive tissues and their involvement in the pathogenesis of insulin resistance

Active site phosphoryl groups in the biphosphorylated phosphotransferase complex reveal dynamics in a millisecond time scale

AbstractThe N-terminal domain of Enzyme I (EIN) and phosphocarrier HPr can form a biphosphorylated complex when they are both phosphorylated by excess cellular phosphoenolpyruvate. Here we show that the electrostatic repulsion between the phosphoryl groups in the biphosphorylated complex results in characteristic dynamics at the active site in a millisecond time scale. The dynamics is localized to phospho-His15 and the stabilizing backbone amide groups of HPr, and does not impact on the phospho-His189 of EIN. The dynamics occurs with the kex of ∼500s−1 which compares to the phosphoryl transfer rate of ∼850s−1 between EIN and HPr. The conformational dynamics in HPr may be important for its phosphotransfer reactions with multiple partner proteins.Structured summary of protein interactionsEIN and HPr bind by nuclear magnetic resonance (View Interaction)

Electrically Small Loop Antenna for UHF Band RFID Tag

UHF band RFID tag antenna which has a similar radiation pattern of the electrically small loop antenna is presented. The structure of the proposed tag antenna is a small circular dipole array on the xy-plane, and the antenna is fed by inductively coupled loop to flow a uniform amplitude and in phased current along its circumference. Since its radiation pattern has an omnidirectional pattern in the xy-plane, the proposed tag antenna can reduce the interference among adjacent tag antennas arranged parallel to xy-plane

AKT1 Gene Polymorphisms and Obstetric Complications in the Patients with Schizophrenia

ObjectiveaaWe performed a genetic association study with schizophrenic patients to investigate whether the V-akt murine thymoma viral oncogene homolog 1 (AKT1) gene plays a role in obstetric complications. MethodsaaOne-hundred-eighty patients with schizophrenia (male, 113; female, 67) were included. All patients fulfilled DSM-IV criteria for schizophrenia. Obstetric complications were measured by the Lewis scale. Prenatal and perinatal information was retrospectively collected from the patients ’ mothers. We selected six single nucleotide polymorphisms (SNPs) for the AKT1 gene: SNP1 (rs3803300), SNP2 (rs1130214), SNP3 (rs3730358), SNP4 (rs 1130233), SNP5 (rs2494732), and SNPA (rs2498804). The genotype data were analyzed for an association with the Lewis total score in terms of allele, genotype, and haplotype distribution. ResultsaaThe mean total Lewis scores were 1.30±1.61 for males and 1.54±1.87 for females. Higher total score tended to be correlated with an earlier age of onset of schizophrenia in females. In the total sample, no SNP was associated with obstetric complications. However, the additional analyses for male and female subgroups found a significant associatio

Maintained Seroprevalence of Toxoplasmosis among the Residents of Jeju Island, Korea

Seroepidemiological status of toxoplasmosis among the residents of Jeju island was surveyed and evaluated by ELISA with crude extract of Toxoplasma gondii. The sera of 2,348 residents (male 1,157 and female 1,191) were collected and checked for the IgG antibody titers, which showed 13.2% positive rate (309 sera). The positive rates were increasing gradually according to the age from 4.3% in teenage to 20.6% in seventies. The positive rates were significantly different between the sex by 16.2% for male and 10.2% for female (P<0.05). This positive rate of toxoplasmosis in Jeju island residents is regarded relatively higher than any other regions of Korea. And the high positive rate may be maintained continuously among Jeju island residents without any clear reasons until now but due to some parts peculiar socio-cultural tradition of Jeju island. Therefore, it is necessary to study further the epidemiology of toxoplasmosis of Jeju island

No Association of Functional Polymorphisms in Methlylenetetrahydrofolate Reductase and the Risk and Minor Physical Anomalies of Schizophrenia in Korean Population

Methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate metabolism, plays an important role in DNA methylation. It has been suggested that abnormal DNA methylation contributes to the pathogenesis of schizophrenia and congenital anomalies. The previous findings regarding the genetic relationship between MTHFR and schizophrenia are controversial. This study investigated the association of the two functional polymorphisms of MTHFR, C677T and A1298C, with the risk for schizophrenia. Furthermore, we conducted an updated meta-analysis on the two polymorphisms. In addition, we investigated the relationship between the polymorphisms and minor physical anomaly (MPA), which may represent neurodevelopmental aberrations in 201 schizophrenia patients and 350 normal control subjects. There was no significant association between either of the two polymorphisms and the risk of schizophrenia (chi-square = 0.001, df = 1, P = 0.971 for C677T; chi-square = 1.319, df = 1, P = 0.251 for A1298C). However, in meta-analysis, the C677T polymorphism showed a significant association in the combined and Asian populations (OR = 1.13, P = 0.005; OR = 1.21, P = 0.011, respectively) but not in the Korean and Caucasian populations alone. Neither polymorphism was associated with MPAs measured by the Waldrop scale (chi-square = 2.513, df = 2, P = 0.285). In conclusion, the present findings suggest that in the Korean population, the MTHFR polymorphisms are unlikely to be associated with the risk for schizophrenia and neurodevelopmental abnormalities related to schizophrenia