Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate < 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched in patients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases.
Nanogenerators capable of converting energy from mechanical sources to electricity with high effective efficiency using low-cost, nonsemiconducting, organic nanomaterials are attractive for many applications, including energy harvesters. In this work, near-field electrospinning is used to direct-write poly(vinylidene fluoride) (PVDF) nanofibers with in situ mechanical stretch and electrical poling characteristics to produce piezoelectric properties. Under mechanical stretching, nanogenerators have shown repeatable and consistent electrical outputs with energy conversion efficiency an order of magnitude higher than those made of PVDF thin films. The early onset of the nonlinear domain wall motions behavior has been identified as one mechanism responsible for the apparent high piezoelectricity in nanofibers, rendering them potentially advantageous for sensing and actuation applications.
A universal but simple procedure for identifying the α, β and γ phases in PVDF using FTIR is proposed and validated. An integrated quantification methodology for individual β and γ phase in mixed systems is also proposed.
Toll-like receptor 3 (TLR3) recognizes double-stranded RNA (dsRNA), a molecular signature of most viruses, and triggers inflammatory responses that prevent viral spread. TLR3 ectodomains (ECDs) dimerize on oligonucleotides of at least 40 to 50 base pairs in length, the minimal length required for signal transduction. To establish the molecular basis for ligand binding and signaling, we determined the crystal structure of a complex between two mouse TLR3-ECDs and dsRNA at 3.4 angstrom resolution. Each TLR3-ECD binds dsRNA at two sites located at opposite ends of the TLR3 horseshoe, and an intermolecular contact between the two TLR3-ECD C-terminal domains coordinates and stabilizes the dimer. This juxtaposition could mediate downstream signaling by dimerizing the cytoplasmic Toll interleukin-1 receptor (TIR) domains. The overall shape of the TLR3-ECD does not change upon binding to dsRNA.
Cellular DNA damage causes stabilization and activation of the tumor suppressor and transcription factor p53, in part by promoting multiple covalent modifications of the p53 protein, including acetylation. We investigated the importance of acetylation in p53 function and the mechanism by which acetylation influences p53 activity. Acetylation site substitutions reduced p53-dependent transcriptional induction and G1 cell cycle arrest. Chromatin immunoprecipitation analysis of the endogenous p21 promoter showed increased association of p53, coactivators (CBP and TRRAP), and acetylated histones following cell irradiation. Results with acetylation-defective p53 demonstrate that the critical function of acetylation is not to increase the DNA binding affinity of p53 but rather to promote coactivator recruitment and histone acetylation. Therefore, we propose that an acetylation cascade consisting of p53 acetylation-dependent recruitment of coactivators/HATs is crucial for p53 function.
With fast development and wide applications of next-generation sequencing (NGS) technologies, genomic sequence information is within reach to aid the achievement of goals to decode life mysteries, make better crops, detect pathogens, and improve life qualities. NGS systems are typically represented by SOLiD/Ion Torrent PGM from Life Sciences, Genome Analyzer/HiSeq 2000/MiSeq from Illumina, and GS FLX Titanium/GS Junior from Roche. Beijing Genomics Institute (BGI), which possesses the world's biggest sequencing capacity, has multiple NGS systems including 137 HiSeq 2000, 27 SOLiD, one Ion Torrent PGM, one MiSeq, and one 454 sequencer. We have accumulated extensive experience in sample handling, sequencing, and bioinformatics analysis. In this paper, technologies of these systems are reviewed, and first-hand data from extensive experience is summarized and analyzed to discuss the advantages and specifics associated with each sequencing system. At last, applications of NGS are summarized.
BackgroundThe increase in childhood obesity is a serious public health concern. Several studies have indicated that breastfed children have a lower risk of childhood obesity than those who were not breastfed, while other studies have provided conflicting evidence. The objective of this meta-analysis was to investigate the association between breastfeeding and the risk of childhood obesity.MethodsThe PubMed, EMBASE and CINAHL Plus with Full Text databases were systematically searched from start date to 1st August 2014. Based on the meta-analysis, pooled adjusted odds ratio (AOR) and 95% confidence interval (CI) were calculated. I2 statistic was used to evaluate the between-study heterogeneity. Funnel plots and Fail-safe N were used to assess publication bias and reliability of results, and results from both Egger test and Begg test were reported.ResultsTwenty-five studies with a total of 226,508 participants were included in this meta-analysis. The studies’ publication dates ranged from 1997 to 2014, and they examined the population of 12 countries. Results showed that breastfeeding was associated with a significantly reduced risk of obesity in children (AOR = 0.78; 95% CI: 0.74, 0.81). Categorical analysis of 17 studies revealed a dose-response effect between breastfeeding duration and reduced risk of childhood obesity.ConclusionResults of our meta-analysis suggest that breastfeeding is a significant protective factor against obesity in children.
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