29 research outputs found

    MicroRNA mediated biological effects in response to bariatric surgery

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    Bariatric surgery offers sustained dramatic weight loss and remission of diabetes, yet the mechanisms of these health benefits are not clear. In the present study, I profiled circulating and colorectal miRNAome in response to bariatric surgery (Roux-en-Y gastric bypass). Indeed, the response of circulating and colorectal miRNA profiles to RYGB were striking and selective. Fourteen circulating microRNA and thirteen colorectal microRNA exhibited significantly alteration post RYGB. Interestingly, circulating miR-122 decreased dramatically (56 fold) post RYGB surgery. The expression of hepatic miR-122 and its metabolic targets were examined both in in vivo RYGB surgical model and in an in vitro mechanistic model. Manipulation of miRNA-122 cold induce changes of key enzymes involved in energy metabolism, glucose transport, glycolysis, TCA cycle, pentose phosphate shunt, fatty acid oxidation and gluconeogenesis, suggesting an overall increased energy expenditure status after RYGB. Furthermore, potential mechanisms involved in the control of hepatic miR-122 were investigated, with focus on metabolites (glucose, and fatty acids), hormones (glucocorticoid) and transcription factors (PPARs). Finally, by correlating the circulating miRNAome and metabolome data, we were able to generate a comprehensive landscape of the crosstalk between miRNAs and metabolic pathways. Follow-up studies will allow a detailed understanding of miRNAs responsible for regulating specific metabolic pathways, and conversely identifying metabolites capable of regulating the expression and activity of specific miRNAs.Open Acces

    INSIGHT: A population-scale COVID-19 testing strategy combining point-of-care diagnosis with centralized high-throughput sequencing.

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    We present INSIGHT [isothermal NASBA (nucleic acid sequence-based amplification) sequencing-based high-throughput test], a two-stage coronavirus disease 2019 testing strategy, using a barcoded isothermal NASBA reaction. It combines point-of-care diagnosis with next-generation sequencing, aiming to achieve population-scale testing. Stage 1 allows a quick decentralized readout for early isolation of presymptomatic or asymptomatic patients. It gives results within 1 to 2 hours, using either fluorescence detection or a lateral flow readout, while simultaneously incorporating sample-specific barcodes. The same reaction products from potentially hundreds of thousands of samples can then be pooled and used in a highly multiplexed sequencing-based assay in stage 2. This second stage confirms the near-patient testing results and facilitates centralized data collection. The 95% limit of detection is <50 copies of viral RNA per reaction. INSIGHT is suitable for further development into a rapid home-based, point-of-care assay and is potentially scalable to the population level

    Experimental Bariatric Surgery in Rats Generates a Cytotoxic Chemical Environment in the Gut Contents

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    Bariatric surgery, also known as metabolic surgery, is an effective treatment for morbid obesity, which also offers pronounced metabolic effects including the resolution of type 2 diabetes and a decrease in cardiovascular disease and long-term cancer risk. However, the mechanisms of surgical weight loss and the long-term consequences of bariatric surgery remain unclear. Bariatric surgery has been demonstrated to alter the composition of both the microbiome and the metabolic phenotype. We observed a marked shift toward Gammaproteobacteria, particularly Enterobacter hormaechei, following Roux-en-Y gastric bypass (RYGB) surgery in a rat model compared with sham-operated controls. Fecal water from RYGB surgery rats was highly cytotoxic to rodent cells (mouse lymphoma cell line). In contrast, fecal water from sham-operated animals showed no/very low cytotoxicity. This shift in the gross structure of the microbiome correlated with greatly increased cytotoxicity. Urinary phenylacetylglycine and indoxyl sulfate and fecal gamma-aminobutyric acid, putrescine, tyramine, and uracil were found to be inversely correlated with cell survival rate. This profound co-dependent response of mammalian and microbial metabolism to RYGB surgery and the impact on the cytotoxicity of the gut luminal environment suggests that RYGB exerts local and global metabolic effects which may have an influence on long-term cancer risk and cytotoxic load

    In situ functional dissection of RNA cis-regulatory elements by multiplex CRISPR-Cas9 genome engineering.

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    RNA regulatory elements (RREs) are an important yet relatively under-explored facet of gene regulation. Deciphering the prevalence and functional impact of this post-transcriptional control layer requires technologies for disrupting RREs without perturbing cellular homeostasis. Here we describe genome-engineering based evaluation of RNA regulatory element activity (GenERA), a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 platform for in situ high-content functional analysis of RREs. We use GenERA to survey the entire regulatory landscape of a 3'UTR, and apply it in a multiplex fashion to analyse combinatorial interactions between sets of miRNA response elements (MREs), providing strong evidence for cooperative activity. We also employ this technology to probe the functionality of an entire MRE network under cellular homeostasis, and show that high-resolution analysis of the GenERA dataset can be used to extract functional features of MREs. This study provides a genome editing-based multiplex strategy for direct functional interrogation of RNA cis-regulatory elements in a native cellular environment

    Vegetative Ecological Characteristics of Restored Reed (Phragmites australis) Wetlands in the Yellow River Delta, China

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    In this study, we compared ecological characteristics of wetland vegetation in a series of restoration projects that were carried out in the wetlands of Yellow River Delta. The investigated characteristics include plant composition structure, species diversity and community similarity in three kinds of Phragmites australis wetlands, i.e. restored P. australis wetlands (R1, R2, R3 and R4: restored in 2002, 2005, 2007 and 2009, respectively), natural P. australis wetland (N) and degraded P. australis wetland (D) to assess the process of wetlands restoration. The coverage of the R1 was 99%, which was similar to natural wetland. Among all studied wetlands, the highest and lowest stem density was observed in R1 and R2, respectively, Plant height and stem diameter show the same trend as N > R2 > R1 > R3 > D > R4. Species diversity of restored P. australis wetlands became closed to natural wetland. Both species richness and Shannon–Wiener index had similar tendency: increased first and then decreased with restored time. The highest species richness and species diversity were observed in R2, while the lowest values of those parameters were found in natural P. australis wetland. Similarity indexes between restored wetlands and natural wetland increased with the restoration time, but they were still less than 50%. The results indicate that the vegetation of P. australis wetlands has experienced a great improvement after several years’ restoration, and it is feasible to restored degraded P. australis wetlands by pouring fresh water into those wetlands in the Yellow River Delta. However, it is notable that costal degraded P. australis wetland in this region may take years to decades to reach the status of natural wetland

    Recent Glacier Mass Balance and Area Changes from DEMs and Landsat Images in Upper Reach of Shule River Basin, Northeastern Edge of Tibetan Plateau during 2000 to 2015

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    Glacier changes in the Upper Reach of the Shule River Basin (URSRB) serve as a good indicator of climate change in the western part of the Qilian Mountains, located on the northeastern edge of the Tibetan Plateau. However, information on recent glacier changes in the URSRB is limited. In this study, the changes in ice surface elevation were determined using geodetic methods based on digital elevation models (DEMs) derived from the Shuttle Radar Topography Mission (SRTM) (2000), and from pairs of Third Resources Satellite (ZY-3) of China (taken around 2013). In addition, glacier area changes from 2000&ndash;2015, were derived from Landsat TM/ETM+/OLI images. The results suggest that 478 glaciers with an area of 375.1 &plusmn; 2.68 km2 remained in the URSRB in 2015. Ice cover diminished by 57.5 &plusmn; 2.68 km2 (11.9 &plusmn; 0.60%), or 0.79 &plusmn; 0.04% a&minus;1 and 35 small glaciers disappeared from 2000 to 2015 in the URSRB. The most pronounced glacier shrinkage occurred during 2004 to 2009. The average ice surface elevation of the URSRB from 1999 to 2013 reduced by about 4.98 &plusmn; 0.6 m, which is equal to a mass loss of 0.383 &plusmn; 0.046 m&middot;a&minus;1. This reduction indicates that the ice storage loss has accelerated since 1999, compared to a mass loss of 0.21 &plusmn; 0.04 m&middot;a&minus;1 around Tuanjiefeng from 1966 to 1999, as reported by Xu et al. (2013)

    A Privacy-Preserving Personalized Service Framework through Bayesian Game in Social IoT

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    It is enormously challenging to achieve a satisfactory balance between quality of service (QoS) and users’ privacy protection along with measuring privacy disclosure in social Internet of Things (IoT). We propose a privacy-preserving personalized service framework (Persian) based on static Bayesian game to provide privacy protection according to users’ individual security requirements in social IoT. Our approach quantifies users’ individual privacy preferences and uses fuzzy uncertainty reasoning to classify users. These classification results facilitate trustworthy cloud service providers (CSPs) in providing users with corresponding levels of services. Furthermore, the CSP makes a strategic choice with the goal of maximizing reputation through playing a decision-making game with potential adversaries. Our approach uses Shannon information entropy to measure the degree of privacy disclosure according to the probability of game mixed strategy equilibrium. Experimental results show that Persian guarantees QoS and effectively protects user privacy despite the existence of adversaries
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