Mining for the antibody-antigen interacting associations that predict the B cell epitopes

Background. Predicting B-cell epitopes is very important for designing vaccines and drugs to fight against the infectious agents. However, due to the high complexity of this problem, previous prediction methods that focus on linear and conformational epitope prediction are both unsatisfactory. In addition, antigen interacting with antibody is context dependent and the coarse binary classification of antigen residues into epitope and non-epitope without the corresponding antibody may not reveal the biological reality. Therefore, we take a novel way to identify epitopes by using associations between antibodies and antigens. Results. Given a pair of antibody-antigen sequences, the epitope residues can be identified by two types of associations: paratope-epitope interacting biclique and cooccurrent pattern of interacting residue pairs. As the association itself does not include the neighborhood information on the primary sequence, residues' cooperativity and relative composition are then used to enhance our method. Evaluation carried out on a benchmark data set shows that the proposed method produces very good performance in terms of accuracy. After compared with other two structure-based B-cell epitope prediction methods, results show that the proposed method is competitive to, sometimes even better than, the structure-based methods which have much smaller applicability scope. Conclusions. The proposed method leads to a new way of identifying B-cell epitopes. Besides, this antibody-specified epitope prediction can provide more precise and helpful information for wet-lab experiments. © 2010 Li and Zhao; licensee BioMed Central Ltd

RTeQTL: Real-Time Online Engine for Expression Quantitative Trait Loci Analyses

Our database tool, called Real-Time Engine for Expression Quantitative Trait Loci Analyses (RTeQTL), can efficiently provide eQTL association results that are not available in existing eQTL databases browsers. These functions include (i) single SNP (single-nucleotide polymorphism) and (ii) two-SNP conditional eQTL effects on gene expression regardless of the magnitude of P-values. The database is based on lymphoblastoid cell lines from >900 samples with global gene expression and genome-wide genotyped and imputed SNP data. The detailed result for any pairs of gene and SNPs can be efficiently computed and browsed online, as well as downloaded in batch mode. This is the only tool that can assess the independent effect of a disease- or trait-associated SNP on gene expression conditioning on other SNPs of interest, such as the top eQTL of the same gene. It is also useful to identify eQTLs for candidate genes, which are often missed in existing eQTL browsers, which only store results with genome-wide significant P-value. Additional analyses stratifying by gender can also be easily achieved by this tool. Database URL: http://eqtl.rc.fas.harvard.edu

Identification and Characterization of microRNAs from Peanut (Arachis hypogaea L.) by High-Throughput Sequencing

BACKGROUND: MicroRNAs (miRNAs) are noncoding RNAs of approximately 21 nt that regulate gene expression in plants post-transcriptionally by endonucleolytic cleavage or translational inhibition. miRNAs play essential roles in numerous developmental and physiological processes and many of them are conserved across species. Extensive studies of miRNAs have been done in a few model plants; however, less is known about the diversity of these regulatory RNAs in peanut (Arachis hypogaea L.), one of the most important oilseed crops cultivated worldwide. RESULTS: A library of small RNA from peanut was constructed for deep sequencing. In addition to 126 known miRNAs from 33 families, 25 novel peanut miRNAs were identified. The miRNA* sequences of four novel miRNAs were discovered, providing additional evidence for the existence of miRNAs. Twenty of the novel miRNAs were considered to be species-specific because no homolog has been found for other plant species. qRT-PCR was used to analyze the expression of seven miRNAs in different tissues and in seed at different developmental stages and some showed tissue- and/or growth stage-specific expression. Furthermore, potential targets of these putative miRNAs were predicted on the basis of the sequence homology search. CONCLUSIONS: We have identified large numbers of miRNAs and their related target genes through deep sequencing of a small RNA library. This study of the identification and characterization of miRNAs in peanut can initiate further study on peanut miRNA regulation mechanisms, and help toward a greater understanding of the important roles of miRNAs in peanut

Construction and validation of a predictive risk model for nosocomial infections with MDRO in NICUs: a multicenter observational study

ObjectivesThis study aimed to construct and validate a predictive risk model (PRM) for nosocomial infections with multi-drug resistant organism (MDRO) in neonatal intensive care units (NICUs), in order to provide a scientific and reliable prediction tool, and to provide reference for clinical prevention and control of MDRO infections in NICUs.MethodsThis multicenter observational study was conducted at NICUs of two tertiary children’s hospitals in Hangzhou, Zhejiang Province. Using cluster sampling, eligible neonates admitted to NICUs of research hospitals from January 2018 to December 2020 (modeling group) or from July 2021 to June 2022 (validation group) were included in this study. Univariate analysis and binary logistic regression analysis were used to construct the PRM. H-L tests, calibration curves, ROC curves and decision curve analysis were used to validate the PRM.ResultsFour hundred and thirty-five and one hundred fourteen neonates were enrolled in the modeling group and validation group, including 89 and 17 neonates infected with MDRO, respectively. Four independent risk factors were obtained and the PRM was constructed, namely: P = 1/ (1+ e−X), X = −4.126 + 1.089× (low birth weight) +1.435× (maternal age ≥ 35 years) +1.498× (use of antibiotics >7 days) + 0.790× (MDRO colonization). A nomogram was drawn to visualize the PRM. Through internal and external validation, the PRM had good fitting degree, calibration, discrimination and certain clinical validity. The prediction accuracy of the PRM was 77.19%.ConclusionPrevention and control strategies for each independent risk factor can be developed in NICUs. Moreover, clinical staff can use the PRM to early identification of neonates at high risk, and do targeted prevention to reduce MDRO infections in NICUs

Characterization of gene expression profiles in HBV-related liver fibrosis patients and identification of ITGBL1 as a key regulator of fibrogenesis

Although hepatitis B virus (HBV) infection is the leading cause of liver fibrosis (LF), the mechanisms underlying liver fibrotic progression remain unclear. Here, we investigated the gene expression profiles of HBV-related LF patients. Whole genome expression arrays were used to detect gene expression in liver biopsy samples from chronically HBV infected patients. Through integrative data analysis, we identified several pathways and key genes involved in the initiation and exacerbation of liver fibrosis. Weight gene co-expression analysis revealed that integrin subunit β-like 1 (ITGBL1) was a key regulator of fibrogenesis. Functional experiments demonstrated that ITGBL1 was an upstream regulator of LF via interactions with transforming growth factor β1. In summary, we investigated the gene expression profiles of HBV-related LF patients and identified a key regulator ITGBL1. Our findings provide a foundation for future studies of gene functions and promote the development of novel antifibrotic therapies

Response surface methodology used for statistical optimization of jiean-peptide production by Bacillus subtilise

Response surface methodology (RSM) was used for statistical optimization of jiean-peptide (JAA) production by Bacillus subtilise ZK8 cells adsorbed on wood chips to form a novel fermentation system. The Plackett-Burman design was used in the first step to evaluate the effects of eight factors, including six fermentation medium components and two cell adsorption conditions. Among the variables screened, soybean meal hydrolysate (SMH) and MgSO4\ub77H2O in the fermentation medium had significant effects on JAA production. In the second step, the concentrations of SMH and MgSO4\ub77H2O were further optimized using central composite designs and response surface analysis. The optimized concentration of SMH and MgSO4\ub77H2O was 24% (v/v) and 0.38% (w/v), respectively, which increased the production of JAA in a shake flask system by 41% relative to optimization of a single variable component of the culture medium

Increased intraocular inflammation in retinal vein occlusion is independent of circulating immune mediators and is involved in retinal oedema

We aim to understand the link between systemic and intraocular levels of inflammatory mediators in treatment-naïve retinal vein occlusion (RVO) patients, and the relationship between inflammatory mediators and retinal pathologies. Twenty inflammatory mediators were measured in this study, including IL-17E, Flt-3 L, IL-3, IL-8, IL-33, MIP-3β, MIP-1α, GRO β, PD-L1, CD40L, IFN-β, G-CSF, Granzyme B, TRAIL, EGF, PDGF-AA, PDGF-AB/BB, TGF-α, VEGF, and FGFβ. RVO patients had significantly higher levels of Flt-3 L, IL-8, MIP-3β, GROβ, and VEGF, but lower levels of EGF in the aqueous humor than cataract controls. The levels of Flt-3 L, IL-3, IL-33, MIP-1α, PD-L1, CD40 L, G-CSF, TRAIL, PDGF-AB/BB, TGF-α, and VEGF were significantly higher in CRVO than in BRVO. KEGG pathway enrichment revealed that these mediators affected the PI3K-Akt, Ras, MAPK, and Jak/STAT signaling pathways. Protein–Protein Interaction (PPI) analysis showed that VEGF is the upstream cytokine that influences IL-8, G-CSF, and IL-33 in RVO. In the plasma, the level of GROβ was lower in RVO than in controls and no alterations were observed in other mediators. Retinal thickness [including central retinal thickness (CRT) and inner limiting membrane to inner plexiform layer (ILM-IPL)] positively correlated with the intraocular levels of Flt-3 L, IL-33, GROβ, PD-L1, G-CSF, and TGF-α. The size of the foveal avascular zone positively correlated with systemic factors, including the plasma levels of IL-17E, IL-33, INF-β, GROβ, Granzyme B, and FGFβ and circulating high/low-density lipids and total cholesterols. Our results suggest that intraocular inflammation in RVO is driven primarily by local factors but not circulating immune mediators. Intraocular inflammation may promote macular oedema through the PI3K-Akt, Ras, MAPK, and Jak/STAT signaling pathways in RVO. Systemic factors, including cytokines and lipid levels may be involved in retinal microvascular remodeling

Novel integrated techniques of drilling-slotting-separation-sealing for enhanced coal bed methane recovery in underground coal mines

Coal bed Methane (CBM), a primary component of natural gas, is a relatively clean source of energy. Nevertheless, the impact of considerable coal mine methane emission on climate change in China has gained an increasing attention as coal production has powered the country's economic development. It is well-known that coal bed methane is a typical greenhouse gas, the greenhouse effect index of which is 30 times larger than that of carbon dioxide. Besides, gas disasters such as gas explosive and outburst, etc. pose a great threat to the safety of miners. Therefore, measures must be taken to capture coal mine methane before mining. This helps to enhance safety during mining and extract an environmentally friendly gas as well. However, as a majority of coal seams in China have low-permeability, it is difficult to achieve efficient methane drainage. Enhancing coal permeability is a good choice for high-efficiency drainage of coal mine methane. In this paper, a modified coal-methane co-exploitation model was established and a combination of drilling–slotting-separation–sealing was proposed to enhance coal permeability and CBM recovery. Firstly, rapid drilling assisted by water-jet and significant permeability enhancement via pressure relief were investigated, guiding the fracture network formation around borehole for high efficient gas flow. Secondly, based on the principle of swirl separation, the coal–water–gas separation instrument was developed to eliminate the risk of gas accumulation during slotting and reduce the gas emission from the ventilation air. Thirdly, to improve the performance of sealing material, we developed a novel cement-based composite sealing material based on the microcapsule technique. Additionally, a novel sealing–isolation combination technique was also proposed. Results of field test indicate that gas concentration in slotted boreholes is 1.05–1.91 times higher than that in conventional boreholes. Thus, the proposed novel integrated techniques achieve the goal of high-efficiency coal bed methane recovery

Fried food consumption, genetic risk, and body mass index: gene-diet interaction analysis in three US cohort studies

Objective: To examine the interactions between genetic predisposition and consumption of fried food in relation to body mass index (BMI) and obesity. Design: Prospective cohort study. Setting: Health professionals in the United States. Participants: 9623 women from the Nurses’ Health Study, 6379 men from the Health Professionals Follow-up Study, and a replication cohort of 21 421 women from the Women’s Genome Health Study. Main outcome measure Repeated measurement of BMI over follow-up. Results: There was an interaction between fried food consumption and a genetic risk score based on 32 BMI-associated variants on BMI in both the Nurses’ Health Study and Health Professionals Follow-up Study (P≤0.001 for interaction). Among participants in the highest third of the genetic risk score, the differences in BMI between individuals who consumed fried foods four or more times a week and those who consumed fried foods less than once a week amounted to 1.0 (SE 0.2) in women and 0.7 (SE 0.2) in men, whereas the corresponding differences were 0.5 (SE 0.2) and 0.4 (SE 0.2) in the lowest third of the genetic risk score. The gene-diet interaction was replicated in the Women’s Genome Health Study (P<0.001 for interaction). Viewed differently, the genetic association with adiposity was strengthened with higher consumption of fried foods. In the combined three cohorts, the differences in BMI per 10 risk alleles were 1.1 (SE 0.2), 1.6 (SE 0.3), and 2.2 (SE 0.6) for fried food consumption less than once, one to three times, and four or more times a week (P<0.001 for interaction); and the odds ratios (95% confidence intervals) for obesity per 10 risk alleles were 1.61 (1.40 to 1.87), 2.12 (1.73 to 2.59), and 2.72 (2.12 to 3.48) across the three categories of consumption (P=0.002 for interaction). In addition, the variants in or near genes highly expressed or known to act in the central nervous system showed significant interactions with fried food consumption, with the FTO (fat mass and obesity associated) variant showing the strongest result (P<0.001 for interaction). Conclusion: Our findings suggest that consumption of fried food could interact with genetic background in relation to obesity, highlighting the particular importance of reducing fried food consumption in individuals genetically predisposed to obesity