Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10⁻⁸–1.2×10⁻⁴³). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10⁻⁴). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10⁻³, n = 22,044), increased triglycerides (p = 2.6×10⁻¹⁴, n = 93,440), increased waist-to-hip ratio (p = 1.8×10⁻⁵, n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10⁻³, n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10⁻¹³, n = 96,748) and decreased BMI (p = 1.4×10⁻⁴, n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.     

Id-1 induces proteasome-dependent degradation of the HBX protein

Id-1 is a member of the HLH protein family that regulates a wide range of cellular processes such as cell proliferation, apoptosis, senescence and overexpression of Id-1 was recently suggested to play roles in the development and progression of different cancers. Previously, Id-1 was shown to physically interact with the viral protein E1A. Meanwhile, Id-1 expression was found to be regulated by several of the virus-encoded proteins, suggesting that Id-1 may be a common cellular target of the viral proteins. Here, we report that Id-1 interacts with the Hepatitis-B virus (HBV)-encoded protein HBX and regulates its stability in hepatocellular carcinoma (HCC) cells. We found that in HCC cells, ectopic Id-1 expression significantly decreased the half-life of the HBX protein, indicating that HBX is destabilized by Id-1. Meanwhile, the Id-1-induced HBX degradation was found to be inhibited by treatment with proteasome inhibitor, suggesting that this process is mediated through the proteasome pathway. Interestingly, while Id-1 did not induce HBX-ubiquitination, we found that removal of all the lysine residues of the HBX protein protects it from the effect of Id-1, indicating that ubiquitination is still required for the Id-1-mediated HBX degradation. Meanwhile, we found that Id-1 binds to the proteasome subunit C8 and facilitates its interaction with the HBX protein and disruption of this interaction completely abolishes the negative effect of Id-1 on HBX protein stability. Taken together, our results demonstrated a novel function of Id-1 in regulating HBX protein stability through interaction with the proteasome.     

MORPHOLOGICAL AND GENETIC VARIATION IN THE POPULATIONS OF SARGASSUM HEMIPHYLLUM (PHAEOPHYCEAE) IN THE NORTHWESTERN PACIFIC1

Difficulty in species identification of Sargassum (Sargassaceae, Fucales) is partly attributed to the high polymorphism among its individuals and populations. This study aimed at assessing morphological and genetic variations in two varieties, var. hemiphyllum J. Agardh and var. chinense J. Agardh, of Sargassum hemiphyllum (Turner) C. Agardh, a widely distributed species in the northwestern Pacific. We investigated 26 measurable, five numerical, and 33 categorical morphological parameters associated with different branching levels of specimens from each of six localities within its distribution range using cluster analysis (CA) and principal coordinate analysis (PCoA). Leaf size of the primary and secondary branching levels and the vesicle size of the secondary branches of the specimens examined were determined to be the most important morphological parameters that were significantly different among populations. Change in leaf and vesicle length of individuals among the six populations followed a latitudinal gradient, with smaller leaves and vesicles associated with northern populations and larger ones in the southern populations. The possible influence of the gradual change in sea surface temperatures (SSTs) along this gradient in the northwestern Pacific on leaf and vesicle morphologies of this species was suggested. PCR‐RFLP analysis of the RUBISCO spacer in the chloroplast genome revealed two distinct and highly homogenous clades, a China clade and a Japan‐Korea clade, which corresponded to var. chinense and var. hemiphyllum, respectively. The formation of refugia along the “Paleo‐coast” in the East China Sea during glacial periods is suggested to have led to the vicariance of ancestral populations of S. hemiphyllum and thus to have promoted genetic differentiation. The massive freshwater outflow of the Yellow and Yangtze rivers may continue to act as a barrier, prolonging the allopatric distribution of the two varieties.     

Occurrence and molecular differentiation of environmental mycobacteria in surface waters

To investigate the occurrence and species diversity of mycobacteria in waters, surface water samples were collected monthly from the Han River and tap water samples at the terminal sites of the distribution system. Mycobacteria in each water sample were isolated by decontamination using cetylpyridinium chloride (CPC) and cultivation on Middlebrook 7H10 agar, and then identified by polymerase chain reaction-restriction fragment length polymorphism analysis (PRA) and sequencing of the 65-kDa heat-shock protein gene (hsp65 gene). Mycobacteria were detected in 59% of the surface water samples and 26% of the tap water samples. Over half of the 158 isolates could not be identified by hsp65 PRA and gene sequencing, and several identification discrepancies were observed between the two methods. The most frequently isolated species was Mycobacterium gordonae in surface water and M. lentiflavum in tap water. M. avium complex (MAC), the most important pathogen among environmental mycobacteria, was detected in the surface water samples but not found in the tap water samples. The result demonstrated that water is an important environmental source of mycobacteria and the combined application of hsp65 PRA and sequencing was more reliable than hsp65 PRA alone to accurately identify mycobacteria present in water.     

Molecular analysis of bacterial community structures in paddy soils for environmental risk assessment with two varieties of genetically modified rice, Iksan 483 and Milyang 204

The impacts of planted transgenic rice varieties on bacterial communities in paddy soils were monitored using both cultivation and molecular methods. The rice field plot consisted of eighteen subplots planted with two genetically modified (GM) rice and four non-GM rice plants in three replicates. Analysis with denaturing gradient gel electrophoresis (DGGE) of PCR-amplified 16S rRNA genes revealed that the bacterial community structures were quite similar to each other in a given month, suggesting that there were no significant differences in bacterial communities between GM and non- GM rice soils. The bacterial community structures appeared to be generally stable with the seasons, as shown by a slight variation of microbial population levels and DGGE banding patterns over the year. Comparison analysis of 16S rDNA clone libraries constructed from soil bacterial DNA showed that there were no significant differences between GM and non-GM soil libraries but revealed seasonal differences of phyla distribution between August and December. The composition profile of phospholipid fatty acids (PLFA) between GM and non-GM soils also was not significantly different to each other. When soil DNAs were analyzed with PCR by using primers for the bar gene, which was introduced into GM rice, positive DNA bands were found in October and December soils. However, no bar gene sequence was detected in PCR analysis with DNAs extracted from both cultured and uncultured soil bacterial fractions. The result of this study suggested that, in spite of seasonal variations of bacterial communities and persistence of the bar gene, the bacterial communities of the experimental rice field were not significantly affected by cultivation of GM rice varieties.     

Thermoimaging as a tool for studying light-induced heating of leaves: Correlation of heat dissipation with the efficiency of photosystem II photochemistry and non-photochemical quenching

Thermoimaging – a highly sensitive and non-invasive method of temperature measurement – was applied to explore the role of changing photosynthetic efficiency in light-induced heating of tobacco (Nicotiana tabacum cv. Samsun) leaves. In the absence of evaporative cooling through the stomata, which was achieved by covering leaves with Vaseline, illumination with 50–1400 μM photons m^?2 s^?1 intensity of photosynthetically active radiation resulted in ≈1–5 °C leaf temperature increase in about 2 min. The heating effect showed a non-linear correlation with the extent of non-photochemical quenching (NPQ) resulting in higher leaf temperatures at higher NPQ values. When leaves were adapted to excessive irradiance (1300 μM photons m^?2 s^?1 for 6 h), which resulted in reduction of photosynthetic efficiency and amplification of NPQ the light-induced heating effect was enhanced. The experimental results have been explained on the basis of a simple theoretical model characterizing the balance of energy fluxes in leaves in relation to the efficiency of photosystem II photochemistry and non-photochemical quenching. The role of alternative energy dissipation pathways outside of PSII in the phenomenon of light-induced leaf heating is also discussed.     

Molecular Evidence for the Hybrid Origin of Bauhinia blakeana （Caesalpinioideae）

Bauhinia blakeana Dunn is the Hong Kong Special Administrative Region emblem and a popular horticultural species in many Asian countries. It was first described as a new species from Hong Kong almost a century ago. This plant is sterile and has long been considered a hybrid, possibly from two related species, B. purpurea and B. variegata. However, not much evidence based on molecular methods was available to support this hypothesis. In this study, sequences of internal transcribed spacer I （ITS1）, rbcL and atpB-rbcL intergenic spacer for five Bauhinia species and two varieties of one of the species were determined and compared. There were two types of ITS1 sequences in B. blakeana, one indistinguishable from that of B. purpurea and the other one identical to that of B. variegata. This confirmed that B. blakeana was a hybrid of these two species. Chloroplast atpB-rbcL intergenic spacer sequence of B. blakeana was identical to that of B. purpurea, indicating that B. purpurea was the female parent. The hybridization event seemed to occur only recently and was a rare incident. Its occurrence was likely facilitated by interspecific pollen competition. It appeared that human efforts played a crucial role in the preservation and ubiquity of B. blakeana.     

Association of monosodium glutamate intake with overweight in Chinese adults: the INTERMAP Study

Animal studies indicate that monosodium glutamate (MSG) can induce hypothalamic lesions and leptin resistance, possibly influencing energy balance, leading to overweight. This study examines the association between MSG intake and overweight in humans. We conducted a cross-sectional study involving 752 healthy Chinese (48.7% women), aged 40-59 years, randomly sampled from three rural villages in north and south China. The great majority of participants prepared their foods at home, without use of commercially processed foods. Diet was assessed with four in-depth multipass 24-h recalls. Participants were asked to demonstrate MSG amounts added in food preparation. Amounts shaken out were weighed by trained interviewers. Overweight was defined as BMI > or =25.0 or > or =23.0 kg/m(2)(based on World Health Organization recommendations for Asian populations). Eighty-two percent of participants were MSG users. Average intake was 0.33 g/day (s.d. = 0.40). With adjustment for potential confounders including physical activity and total energy intake, MSG intake was positively related to BMI. Prevalence of overweight was significantly higher in MSG users than nonusers. For users in the highest tertile of MSG intake compared to nonusers, the multivariable-adjusted odds ratios of overweight (BMI > or =23.0 and > or =25.0) were 2.10 (95% confidence interval, 1.13-3.90, P for trend across four MSG categories = 0.03) and 2.75 (95% confidence interval, 1.28-5.95, P = 0.04). This research provides data that MSG intake may be associated with increased risk of overweight independent of physical activity and total energy intake in humans.