3-D modeling and molecular dynamics simulation of interleukin-22 from the So-iny mullet, Liza haematocheila

Background: Interleukin-22 (IL-22) plays an important role in the regulation of immune responses. However, little is known about its function or structure in fish. Results: The IL-22 gene was first cloned from So-iny mullet ( Liza haematocheila ), one of commercially important fish species in China. Then, 3-D structure model of the mullet IL-22 was constructed by comparative modeling method using human IL-22 (1M4R) as template, and a 5 ns molecular dynamics (MD) was studied. The open reading frame (ORF) of mullet IL-22 cDNA was 555 bp, encoding 184 amino acids. The mullet IL-22 shared higher identities with the other fish IL-22 homologs and possessed a conserved IL-10 signature motif at its C-terminal. The mullet IL-22 model possessed six conserved helix structure. PROCHECK, SAVES and Molprobity server analysis confirmed that this model threaded well with human IL-22. Strikingly, analysis with CastP, cons-PPISP server suggested that the cysteines in mullet IL-22 might not be involved in the forming of disulfide bond for structural stabilization, but related to protein-protein interactions. Conclusions: The structure of IL-22 in So-iny mullet (Liza haematocheila) was constructed using comparative modeling method which provide more information for studying the function of fish IL-22

Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis.

Most BRCA1-associated breast tumours are basal-like yet originate from luminal progenitors. BRCA1 is best known for its functions in double-strand break repair and resolution of DNA replication stress. However, it is unclear whether loss of these ubiquitously important functions fully explains the cell lineage-specific tumorigenesis. In vitro studies implicate BRCA1 in elimination of R-loops, DNA-RNA hybrid structures involved in transcription and genetic instability. Here we show that R-loops accumulate preferentially in breast luminal epithelial cells, not in basal epithelial or stromal cells, of BRCA1 mutation carriers. Furthermore, R-loops are enriched at the 5' end of those genes with promoter-proximal RNA polymerase II (Pol II) pausing. Genetic ablation of Cobra1, which encodes a Pol II-pausing and BRCA1-binding protein, ameliorates R-loop accumulation and reduces tumorigenesis in Brca1-knockout mouse mammary epithelium. Our studies show that Pol II pausing is an important contributor to BRCA1-associated R-loop accumulation and breast cancer development

Mortality among People Living with HIV and AIDS in China: Implications for Enhancing Linkage.

To assess the patterns and predictors of AIDS-related mortality and identify its correlates among adult people living with HIV/AIDS (PLWHA) in China, a retrospective record-based cohort study was conducted among 18 years or older PLWHA, who had at least one follow up reported to the national database between January-1989 and June-2012. Cumulative Incidence Function was used to calculate AIDS-related mortality rate. Gray's test was used to determine the variation in cumulative incidence across strata. The Fine and Gray model was used to measure the burden of cumulative incidence of AIDS-related mortality and strength of its association with potential correlates. Among 375,629 patients, 107,634 died during study period, of which 54,759 (50.87%) deaths were AIDS-related. Cumulative mortality rates of AIDS-related death at one, two, five, 10 and 15 years post-diagnosis were 5.7%, 8.2%, 14.3%, 22.9% and 30.9%, respectively. Among PLWHA, male gender, ethnic minority and having AIDS were associated with significantly higher mortality. Further, homosexual transmission, being on ART and increasing CD4-testing frequency were associated with lower mortality. To reduce mortality among PLWHA, efficient interventions targeting males, ethnic minority, heterosexually infected and AIDS patients should be combined with immunologic monitoring, enhancement of coverage of HIV-testing and ART

Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis

Most BRCA1-associated breast tumours are basal-like yet originate from luminal progenitors. BRCA1 is best known for its functions in double-strand break repair and resolution of DNA replication stress. However, it is unclear whether loss of these ubiquitously important functions fully explains the cell lineage-specific tumorigenesis. In vitro studies implicate BRCA1 in elimination of R-loops, DNA-RNA hybrid structures involved in transcription and genetic instability. Here we show that R-loops accumulate preferentially in breast luminal epithelial cells, not in basal epithelial or stromal cells, of BRCA1 mutation carriers. Furthermore, R-loops are enriched at the 50 end of those genes with promoter-proximal RNA polymerase II (Pol II) pausing. Genetic ablation of Cobra1, which encodes a Pol II-pausing and BRCA1-binding protein, ameliorates R-loop accumulation and reduces tumorigenesis in Brca1-knockout mouse mammary epithelium. Our studies show that Pol II pausing is an important contributor to BRCA1-associated R-loop accumulation and breast cancer development

Machine learning versus classical electrocardiographic criteria for echocardiographic left ventricular hypertrophy in a pre-participation cohort

Background: Classical electrocardiographic (ECG) criteria for left ventricular hypertrophy (LVH) are well studied in older populations and patients with hypertension. Their utility in young pre-participation cohorts is unclear.Aims: We aimed to develop machine learning models for detection of echocardiogram-diagnosed LVH from ECG, and compare these models with classical criteria.Methods: Between November 2009 and December 2014, pre-participation screening ECG and subsequent echocardiographic data was collected from 17 310 males aged 16 to 23, who reported for medical screening prior to military conscription. A final diagnosis of LVH was made during echocardiography, defined by a left ventricular mass index >115 g/m2. The continuous and threshold forms of classical ECG criteria (Sokolow–Lyon, Romhilt–Estes, Modified Cornell, Cornell Product, and Cornell) were compared against machine learning models (Logistic Regression, GLMNet, Random Forests, Gradient Boosting Machines) using receiver-operating characteristics curve analysis. We also compared the important variables identified by machine learning models with the input variables of classical criteria.Results: Prevalence of echocardiographic LVH in this population was 0.82% (143/17310). Classical ECG criteria had poor performance in predicting LVH. Machine learning methods achieved superior performance: Logistic Regression (area under the curve [AUC], 0.811; 95% confidence interval [CI], 0.738–0.884), GLMNet (AUC, 0.873; 95% CI, 0.817–0.929), Random Forest (AUC, 0.824; 95% CI, 0.749–0.898), Gradient Boosting Machines (AUC, 0.800; 95% CI, 0.738–0.862).Conclusions: Machine learning methods are superior to classical ECG criteria in diagnosing echocardiographic LVH in the context of pre-participation screening

Electrogenerated Chemiluminescence Biosensor with a Tripod Probe for the Highly Sensitive Detection of MicroRNA

A novel probe for the highly sensitive detection of microRNA with enhanced helix accessibility and good assembling without backfilling was developed using a tripod structure fabricated by triplex DNA. A layer of triplex DNA assembled on electrodeposited reduced graphene oxide was used as the capture probe, and a subsequent hybridization chain reaction that promoted the efficient intercalation of the electrogenerated chemiluminescence (ECL) emitter [Ru(bpy)2(dppz)]2+ (bpy refers to 2,2′-bipyridine, and dppz refers to dipyrido[3,2-a:2′,3′-c]phenazine) was used as an analytical-signal amplifier. The fabricated biosensor was examined with an anodic ECL mode using tri-n-propyl amine as the coreactant. The construction of the biosensor was systematically characterized with various techniques including atomic-force microscopy, gel electrophoresis, cyclic voltammetry, and electrochemical-impedance spectroscopy, and its performance was optimized under a variety of experimental conditions, especially the concentration of each reagent as well as the incubation time. Under the optimal experimental conditions, the reported biosensor showed a very low limit of detection of 0.10 fM (S/N = 3) and a wide linear dynamic range covering 0.50 fM to 100 pM toward microRNA-155 with excellent specificity, stability, and reproducibility. Finally, the biosensor was successfully applied to the detection of microRNA-155 extracted from the colon-cancer cell line DLD1, demonstrating its potential application in the sensitive detection of biological samples in the early diagnosis of diseases

Spontaneous Phase Segregation Enabling Clogging Aversion in Continuous Flow Microfluidic Synthesis of Nanocrystals Supported on Reduced Graphene Oxide

Eliminating clogging in capillary tube reactors is critical but challenging for enabling continuous-flow microfluidic synthesis of nanoparticles. Creating immiscible segments in a microfluidic flow is a promising approach to maintaining a continuous flow in the microfluidic channel because the segments with low surface energy do not adsorb onto the internal wall of the microchannel. Herein we report the spontaneous self-agglomeration of reduced graphene oxide (rGO) nanosheets in polyol flow, which arises because the reduction of graphene oxide (GO) nanosheets by hot polyol changes the nanosheets from hydrophilic to hydrophobic. The agglomerated rGO nanosheets form immiscible solid segments in the polyol flow, realizing the liquid–solid segmented flow to enable clogging aversion in continuous-flow microfluidic synthesis. Simultaneous reduction of precursor species in hot polyol deposits nanocrystals uniformly dispersed on the rGO nanosheets even without surfactant. Cuprous oxide (Cu2O) nanocubes of varying edge lengths and ultrafine metal nanoparticles of platinum (Pt) and palladium (Pd) dispersed on rGO nanosheets have been continuously synthesized using the liquid–solid segmented flow microfluidic method, shedding light on the promise of microfluidic reactors in synthesizing functional nanomaterials

The Interactions of Oxygen with Small Gold Clusters on Nitrogen-Doped Graphene

By means of density functional theory, the adsorption properties of O2 molecule on both isolated and N-graphene supported gold clusters have been studied. The N-graphene is modeled by a C65NH22 cluster of finite size. The results indicate that the catalytic activity and the O2 adsorption energies of odd-numbered Au clusters are larger than those of adjacent even-numbered ones. The O2 molecule is in favor of bonding to the bridge sites of odd-numbered Au clusters, whereas for odd-numbered ones, the end-on adsorption mode is favored. The perpendicular adsorption orientation on N-graphene is preferred than the parallel one for Au2, Au3 and Au4 clusters, while for Au5, Au6 and Au7, the parallel ones are favored. When O2 is adsorbed on N-graphene supported Au clusters, the adsorption energies are largely increased compared with those on gas-phase ones. The increased adsorption energies would significantly facilitate the electron transfer from Au d-orbital to π* orbital of O2, which would further weakening the O–O bond and therefore enhancing the catalytic activity. The carbon atoms on N-graphene could anchor the clusters, which could make them more difficult to structural distortion, therefore enhance their stability

Ultrasensitive Detection of miRNA Based On Efficient Immobilization of Probe and Electrochemiluminescent Quenching of Ru(bpy)\u3csub\u3e3\u3c/sub\u3e\u3csup\u3e2+\u3c/sup\u3e

A high performance miRNA biosensor based on effective click chemistry assembly of a Ru(bpy)32+ labeled DNA probe and efficient electrochemiluminescence (ECL) quenching of the Ru(bpy)32+/BDEA (BDEA = N-butyldiethanolamine) system by surface-confined electroactive methylene blue (MB) dye is reported. When the target miRNA was present, the ECL signal instantly changed from “light off” to “light on” status. Using the specific miRNA let-7d as the target analyte, this biosensor provided sensitive detection over approximately six orders of magnitude (10 fM-10 nM), with a limit of detection of 10 fM (S/N = 3). Detailed study of the ECL quenching behavior of the Ru(bpy)32+/BDEA system by MB in solution suggested that the ECL quenching involves a combination of photoluminescence dynamic quenching and quenching processes directly associated with the redox reactions, as well as resonance energy transfer. A large binding constant of 4.7 × 1011 M−1 between let-7d and the DNA hairpin was estimated using an ECL-based extended Langmuir isotherm model, suggesting remarkably strong binding of the target to the probe. Furthermore, our biosensor exhibited excellent specificity and reproducibility. Using the developed system, the concentration of the target miRNA extracted from the A549 cell line could be obtained, demonstrating the potential application of the developed biosensor to practical biological sample analysis