Histone 3 lysine 9 (H3K9) demethylase JMJD1A regulates β-adrenergic-induced systemic metabolism and body weight control. Here we show that JMJD1A is phosphorylated at S265 by protein kinase A (PKA), and this is pivotal to activate the β1-adrenergic receptor gene (Adrb1) and downstream targets including Ucp1 in brown adipocytes (BATs). Phosphorylation of JMJD1A by PKA increases its interaction with the SWI/SNF nucleosome remodelling complex and DNA-bound PPARγ. This complex confers β-adrenergic-induced rapid JMJD1A recruitment to target sites and facilitates long-range chromatin interactions and target gene activation. This rapid gene induction is dependent on S265 phosphorylation but not on demethylation activity. Our results show that JMJD1A has two important roles in regulating hormone-stimulated chromatin dynamics that modulate thermogenesis in BATs. In one role, JMJD1A is recruited to target sites and functions as a cAMP-responsive scaffold that facilitates long-range chromatin interactions, and in the second role, JMJD1A demethylates H3K9 di-methylation.

BackgroundThe transmission of malaria in Indonesia is highly heterogeneous spatially and seasonally. Anti-malaria antibody responses can help characterize this variation. In the present study antibody responses to Plasmodium falciparum MSP-1 and AMA-1 were measured to assess the transmission intensity in a hypo-endemic area of Purworejo and a meso-endemic area of Lampung during low and high transmission seasons.MethodsFilter-paper blood spot samples collected from Purworejo and Lampung by cross-sectional survey during high and low transmission season were stored at −20°C. Indirect ELISA assays were carried out using PfMSP1-19 and PfAMA1 antigens. A positivity threshold was determined by samples from local unexposed individuals, and the differences in seroprevalence, antibody level and correlation between antibody level and age in each site were statistically analysed.ResultsPrevalence of antibodies to either PfMSP1-19 or PfAMA1 was higher in Lampung than in Purworejo in both the low (51.3 vs 25.0%) and high transmission season (53.9 vs 37.5%). The magnitude of antibody responses was associated with increasing age in both sites and was higher in Lampung. Age-adjusted seroconversion rates showed an approximately ten-fold difference between Lampung and Purowejo. Two different seroconversion rates were estimated for Lampung suggesting behaviour-related differences in exposure. In both settings antibody responses to PfMSP1-19 were significantly lower in the low season compared to the high season.ConclusionSeasonal changes may be detectable by changes in antibody responses. This is particularly apparent in lower transmission settings and with less immunogenic antigens (in this case PfMSP1-19). Examination of antibody levels rather than seroprevalence is likely to be a more sensitive indicator of changes in transmission. These data suggest that sero-epidemiological analysis may have a role in assessing short-term changes in exposure especially in low or seasonal transmission settings.

Background NKX2-5 variant in atrial septal defect patients has been reported. However, it is not yet been described in the Southeast Asian population. Here, we screened the NKX2-5 variants in patients with atrial septal defect (ASD) in the Indonesian population. Method We recruited 97 patients with ASD for genetic screening of the NKX2-5 variant using Sanger sequencing. Results We identified three variants of NKX2-5: NM_004387.4:c.63A>G at exon 1, NM_004387.4:c.413G>A, and NM_004387.4:c.561G>C at exon 2. The first variant is commonly found (85.6%) and benign. The last two variants are heterozygous at the same locus. These variants are rare (3.1%) and novel. Interestingly, these variants were discovered in familial atrial septal defects with a spectrum of arrhythmia and severe pulmonary hypertension. Conclusion Our study is the first report of the NKX2-5 variant in ASD patients in the Southeast Asian population, including a novel heterozygous variant: NM_004387.4:c.413G>A and NM_004387.4:c.561G>C. These variants might contribute to familial ASD risk with arrhythmia and severe pulmonary hypertension. Functional studies are necessary to prove our findings.

BACKGROUND: Acute myocardial infarction (AMI) is the most common cause of death in the world. One preventive attempt to reduce AMI is early detection of blood lipid profile. A simple method of lipid profile assessment is the measurement of atherogenic index of plasma (AIP), meanwhile more accurate method of lipid profile assessment is the measurement of apolipoprotein B/apolipoprotien A-I (ApoB/ApoAI) ratio. However, whether both measurements are interchangeable is need to be investigated. This study aims to investigate the correlation between AIP value and ApoB/ApoAI ratio in patients with AMI.METHODS: The study design was cross-sectional study. The blood samples of consecutively enrolled AMI patients had been selected after inclusion and exclusion criteria. The blood samples were taken within 24 hours of patient admission to the hospital. The blood concentration of high-density lipoprotein (HDL) and triglycerides (TG) were measured using turbidimetric method. The AIP was calculated as logarithmic of TG/HDL ratio (log10.[TG:HDL]) The concentration of ApoB and ApoAI were measured using immunoturbidimetric method. The correlation between these measurements was analyzed with Pearson correlation test.RESULTS: The blood samples of 76 subjects were collected and analyzed. The subjects were dominated by male (n=67, 88%) and those whose age ≥55 years old (n=54, 71%). The mean ApoB value was 88.66 mg/dL and ApoAI was 97.39 mg/dL. The AIP value was 0.05. The Pearson correlation test between AIP and ApoB/ApoAI ratio showed a significant positive correlation with the strength of correlation was moderate (r=0.51, p-value<0.01).CONCLUSION: There was a significantly positive and moderate correlation between AIP value and ApoB/ApoAI ratio in acute myocardial infarction patients.KEYWORDS: atherogenic index of plasma, acute myocardial infarction, apolipoprotein B/apolipoprotein A-I ratio