Physical environment, man-made pollution, nutrition and their mutual interactions can be major causes of human diseases. These disease determinants have distinct spatial distributions across geographical units, so that their adequate study involves the investigation of the associated geographical strata. We propose four geographical detectors based on spatial variation analysis of the geographical strata to assess the environmental risks of health: the risk detector indicates where the risk areas are; the factor detector identifies factors that are responsible for the risk; the ecological detector discloses relative importance between the factors; and the interaction detector reveals whether the risk factors interact or lead to disease independently. In a real-world study, the primary physical environment (watershed, lithozone and soil) was found to strongly control the neural tube defects (NTD) occurrences in the Heshun region (China). Basic nutrition (food) was found to be more important than man-made pollution (chemical fertilizer) in the control of the spatial NTD pattern. Ancient materials released from geological faults and subsequently spread along slopes dramatically increase the NTD risk. These findings constitute valuable input to disease intervention strategies in the region of interest.
Recent studies reveal that circular RNAs (circRNAs) are a novel class of abundant, stable and ubiquitous noncoding RNA molecules in animals. Comprehensive detection of circRNAs from high-throughput transcriptome data is an initial and crucial step to study their biogenesis and function. Here, we present a novel chiastic clipping signal-based algorithm, CIRI, to unbiasedly and accurately detect circRNAs from transcriptome data by employing multiple filtration strategies. By applying CIRI to ENCODE RNA-seq data, we for the first time identify and experimentally validate the prevalence of intronic/intergenic circRNAs as well as fragments specific to them in the human transcriptome.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-014-0571-3) contains supplementary material, which is available to authorized users.
a b s t r a c tSpatial stratified heterogeneity, referring to the within-strata variance less than the between stratavariance, is ubiquitous in ecological phenomena, such as ecological zones and many ecological variables. Spatial stratified heterogeneity reflects the essence of nature, implies potential distinct mechanisms by strata, suggests possible determinants of the observed process, allows the representativeness of observations of the earth, and enforces the applicability of statistical inferences. In this paper, we propose a q-statistic method to measure the degree of spatial stratified heterogeneity and to test its significance. The q value is within [0,1] (0 if a spatial stratification of heterogeneity is not significant, and 1 if there is a perfect spatial stratification of heterogeneity). The exact probability density function is derived. The q-statistic is illustrated by two examples, wherein we assess the spatial stratified heterogeneities of a hand map and the distribution of the annual NDVI in China.
ObjectiveThe initial colonisation of the human microbiota and the impact of maternal health on neonatal microbiota at birth remain largely unknown. The aim of our study is to investigate the possible dysbiosis of maternal and neonatal microbiota associated with gestational diabetes mellitus (GDM) and to estimate the potential risks of the microbial shift to neonates.DesignPregnant women and neonates suffering from GDM were enrolled and 581 maternal (oral, intestinal and vaginal) and 248 neonatal (oral, pharyngeal, meconium and amniotic fluid) samples were collected. To avoid vaginal bacteria contaminations, the included neonates were predominantly delivered by C-section, with their samples collected within seconds of delivery.ResultsNumerous and diverse bacterial taxa were identified from the neonatal samples, and the samples from different neonatal body sites were grouped into distinct clusters. The microbiota of pregnant women and neonates was remarkably altered in GDM, with a strong correlation between certain discriminatory bacteria and the oral glucose tolerance test. Microbes varying by the same trend across the maternal and neonatal microbiota were observed, revealing the intergenerational concordance of microbial variation associated with GDM. Furthermore, lower evenness but more depletion of KEGG orthologues and higher abundance of some viruses (eg, herpesvirus and mastadenovirus) were observed in the meconium microbiota of neonates associated with GDM.ConclusionGDM can alter the microbiota of both pregnant women and neonates at birth, which sheds light on another form of inheritance and highlights the importance of understanding the formation of early-life microbiome.
Studies of genetic adaptation, a central focus of evolutionary biology, most often focus on the host's genome and only rarely on its co-evolved microbiome. The Qinghai-Tibetan Plateau (QTP) offers one of the most extreme environments for the survival of human and other mammalian species. Yaks (Bos grunniens) and Tibetan sheep (T-sheep) (Ovis aries) have adaptations for living in this harsh high-altitude environment, where nomadic Tibetan people keep them primarily for food and livelihood [1]. Adaptive evolution affects energy-metabolism-related genes in a way that helps these ruminants live at high altitude [2, 3]. Herein, we report convergent evolution of rumen microbiomes for energy harvesting persistence in two typical high-altitude ruminants, yaks and T-sheep. Both ruminants yield significantly lower levels of methane and higher yields of volatile fatty acids (VFAs) than their low-altitude relatives, cattle (Bos taurus) and ordinary sheep (Ovis aries). Ultra-deep metagenomic sequencing reveals significant enrichment in VFA-yielding pathways of rumen microbial genes in high-altitude ruminants, whereas methanogenesis pathways show enrichment in the cattle metagenome. Analyses of RNA transcriptomes reveal significant upregulation in 36 genes associated with VFA transport and absorption in the ruminal epithelium of high-altitude ruminants. Our study provides novel insights into the contributions of microbiomes to adaptive evolution in mammals and sheds light on the biological control of greenhouse gas emissions from livestock enteric fermentation.
Afterglow imaging that detects photons after cessation of optical excitation avoids tissue autofluorescence and thus possesses higher sensitivity than traditional fluorescence imaging. Purely organic molecules with room‐temperature phosphorescence (RTP) have emerged as a new library of benign afterglow agents. However, most RTP luminogens only emit visible light with shallow tissue penetration, constraining their in vivo applications. This study presents an organic RTP nanoprobe (mTPA‐N) with emission in the NIR range for in vivo afterglow imaging. Such a probe is composed of RTP molecule (mTPA) as the phosphorescent generator and an NIR‐fluorescent dye as the energy acceptor to enable room‐temperature phosphorescence resonance energy transfer (RT‐PRET), ultimately resulting in redshifted phosphorescent emission at 780 nm. Because of the elimination of background noise and redshifted afterglow luminescence in a biologically transparent window, mTPA‐N permits imaging of lymph nodes in living mice with a high signal‐to‐noise ratio. This study thus opens up a universal approach to develop organic RTP luminogens into NIR afterglow imaging agents via construction of RT‐PRET.
Seaweeds are essential for marine ecosystems and have immense economic value. Here we present a comprehensive analysis of the draft genome of Saccharina japonica, one of the most economically important seaweeds. The 537-Mb assembled genomic sequence covered 98.5% of the estimated genome, and 18,733 protein-coding genes are predicted and annotated. Gene families related to cell wall synthesis, halogen concentration, development and defence systems were expanded. Functional diversification of the mannuronan C-5-epimerase and haloperoxidase gene families provides insight into the evolutionary adaptation of polysaccharide biosynthesis and iodine antioxidation. Additional sequencing of seven cultivars and nine wild individuals reveal that the genetic diversity within wild populations is greater than among cultivars. All of the cultivars are descendants of a wild S. japonica accession showing limited admixture with S. longissima. This study represents an important advance toward improving yields and economic traits in Saccharina and provides an invaluable resource for plant genome studies.
Although previous studies demonstrated circular RNAs (circRNAs) does not exclusively comprise mRNA exons, no study has extensively explored their internal structure. By combining an algorithm with long-read sequencing data and experimental validation, we, for the first time, comprehensively investigate internal components of circRNAs in 10 human cell lines and 62 fruit fly samples, and reveal the prevalence of alternative splicing (AS) events within circRNAs. Significantly, a large proportion of circRNA AS exons can hardly be detected in mRNAs and are enriched with binding sites of distinct splicing factors from those enriched in mRNA exons. We find that AS events in circRNAs have a preference towards nucleus localization and exhibit tissue- and developmental stage-specific expression patterns. This study suggests an independent regulation on the biogenesis or decay of AS events in circRNAs and the identified circular AS isoforms provide targets for future studies on circRNA formation and function.
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