Targeted inactivation of GPR26 leads to hyperphagia and adiposity by activating AMPK in the hypothalamus

G-protein coupled receptor 26 (GPR26) is a brain-specific orphan GPCR with high expression in the brain region that controls satiety. Depletion of GPR26 has been shown to increase fat storage in C. elegans, whereas GPR26 deficiency in the hypothalamus is associated with high genetic susceptibility to the onset of obesity in mice. However, the metabolic function of GPR26 in mammals remains elusive. Herein, we investigated a role of GPR26 in regulating energy homeostasis by generating mice with targeted deletion of the GPR26 gene. We show that GPR26 deficiency causes hyperphagia and hypometabolism, leading to early onset of diet-induced obesity. Accordingly, GPR26 deficiency also caused metabolic complications commonly associated with obesity, including glucose intolerance, hyperinsulinemia, and dyslipidemia. Moreover, consistent with hyperphagia in GPR26 null mice, GPR26 deficiency significantly increased hypothalamic activity of AMPK, a key signaling event that stimulates appetite. In further support of a regulatory role of GPR26 in satiety, GPR26 knockout mice also demonstrate hypersensitivity to treatment of rimonabant, an endocannabinoid receptor-1 antagonist commonly used to treat obesity by suppressing appetite in humans. Together, these findings identified a key role of GPR26 as a central regulator of energy homeostasis though modulation of hypothalamic AMPK activation.     

Differential DNA methylation in discrete developmental stages of the parasitic nematode Trichinella spiralis

Background

DNA methylation plays an essential role in regulating gene expression under a variety of conditions and it has therefore been hypothesized to underlie the transitions between life cycle stages in parasitic nematodes. So far, however, 5''-cytosine methylation has not been detected during any developmental stage of the nematode Caenorhabditis elegans. Given the new availability of high-resolution methylation detection methods, an investigation of life cycle methylation in a parasitic nematode can now be carried out.

Results

Here, using MethylC-seq, we present the first study to confirm the existence of DNA methylation in the parasitic nematode Trichinella spiralis, and we characterize the methylomes of the three life-cycle stages of this food-borne infectious human pathogen. We observe a drastic increase in DNA methylation during the transition from the new born to mature stage, and we further identify parasitism-related genes that show changes in DNA methylation status between life cycle stages.

Conclusions

Our data contribute to the understanding of the developmental changes that occur in an important human parasite, and raises the possibility that targeting DNA methylation processes may be a useful strategy in developing therapeutics to impede infection. In addition, our conclusion that DNA methylation is a mechanism for life cycle transition in T. spiralis prompts the question of whether this may also be the case in any other metazoans. Finally, our work constitutes the first report, to our knowledge, of DNA methylation in a nematode, prompting a re-evaluation of phyla in which this epigenetic mark was thought to be absent.     

3D characterization of bone strains in the rat tibia loading model

Bone strain is considered one of the factors inducing bone tissue response to loading. Nevertheless, where animal studies can provide detailed data on bone response, they only offer limited information on experimental bone strains. Including micro-CT-based finite element (micro FE) models in the analysis represents a potent methodology for quantifying strains in bone. Therefore, the main objective of this study was to develop and validate specimen-specific micro FE models for the assessment of bone strains in the rat tibia compression model. Eight rat limbs were subjected to axial compression loading; strain at the medio-proximal site of the tibiae was measured by means of strain gauges. Specimen-specific micro FE models were created and analyzed. Repeated measurements on each limb indicated that the effect of limb positioning was small (COV?= 6.45 ± 2.27 %). Instead, the difference in the measured strains between the animals was high (54.2%). The computational strains calculated at the strain gauge site highly correlated to the measured strains (R ²?=?0.95). Maximum peak strains calculated at exactly 25% of the tibia length for all specimens were equal to 435.11 ± 77.88 microstrains (COV?=?17.19%). In conclusion, we showed that strain gauge measurements are very sensitive to the exact strain gauge location on the bone; hence, the use of strain gauge data only is not recommended for studies that address at identifying reliable relationships between tissue response and local strains. Instead, specimen-specific micro FE models of rat tibiae provide accurate estimates of tissue-level strains.     

Ruminococcus bromii is a keystone species for the degradation of resistant starch in the human colon

The release of energy from particulate substrates such as dietary fiber and resistant starch (RS) in the human colon may depend on the presence of specialist primary degraders (or ‘keystone species'') within the microbial community. We have explored the roles of four dominant amylolytic bacteria found in the human colon in the degradation and utilization of resistant starches. Eubacterium rectale and Bacteroides thetaiotaomicron showed limited ability to utilize RS2- and RS3-resistant starches by comparison with Bifidobacterium adolescentis and Ruminococcus bromii. In co-culture, however, R. bromii proved unique in stimulating RS2 and RS3 utilization by the other three bacterial species, even in a medium that does not permit growth of R. bromii itself. Having previously demonstrated low RS3 fermentation in vivo in two individuals with undetectable populations of R. bromii-related bacteria, we show here that supplementation of mixed fecal bacteria from one of these volunteers with R. bromii, but not with the other three species, greatly enhanced the extent of RS3 fermentation in vitro. This argues strongly that R. bromii has a pivotal role in fermentation of RS3 in the human large intestine, and that variation in the occurrence of this species and its close relatives may be a primary cause of variable energy recovery from this important component of the diet. This work also indicates that R. bromii possesses an exceptional ability to colonize and degrade starch particles when compared with previously studied amylolytic bacteria from the human colon.     

Differences of ecological functions inside and outside the wetland nature reserves in Sanjiang Plain, China

Conservation effectiveness of wetland nature reserves is determined by both the management intensity inside the reserves and the hydrological status outside the reserves. Therefore, differences of ecological functions inside and outside the reserves are an integrated indictor for assessing conservation effectiveness. Based on the land use map created from Landsat-TM satellite image and 1:50000 Digital Elevation Model (DEM) data in the study area, the catchments that belong to the wetland reserves were determined as their hydrological sensitive zones by SWAT (Soil and Water Assessment Tool) hydrological model. The ecological function indices of wetland reserves and their corresponding hydrological sensitive zones were calculated through expert consultation and value assessment on wetland ecosystem service functions. The results showed that the ecological functions of national wetland reserves were better than those of local reserves in general. However, the wetland ecological functions of hydrological sensitive zones of the former were not always better than those of the latter. Meanwhile, clustering analysis showed that the wetland ecological functions of several adjacent reserves in Nongjiang-Bielahonghe watershed were similar. But correlation analysis found that there existed a remarkable positive correlation between the wetland ecological function indices of local reserves and their hydrological sensitive zones.     

有机肥对石灰性土壤肥力属性的长期影响

用常规化学分析和差热分析方法研究了长期不同施肥模式下有机肥对土壤生态肥力的影响。结果表明,长期施用有机肥(厩肥、高秸处理)可显著提高土壤有机碳含量,其水散性G0复合体减少;水稳性G1、G2复合体增加,3种胶散复合体的有机碳含量提高,重组复合体中活性强的松结合态腐殖质较多。施入有机肥不仅可提高土壤有机无机复合体的总能量水平,而且也能提高复合体中松结态、稳结态、紧结态腐殖质的能态。高秸、厩肥处理的原土、重组、稳紧态复合体、紧结态复合体和3种胶散复合体焓变值较高,具有较高能态。施用有机肥的土壤全氮、全磷、重组磷及C/N比均呈提高趋势,pH值降低,其原土和重组复合体的阳离子交换量较高。