Multi-objective dynamic population shuffled frog-leaping biclustering of microarray data

<p>Abstract</p> <p>The structure of RiboNucleic Acid (RNA) has the potential to be altered by a Single Nucleotide Polymorphism (SNP). Disease-associated SNPs mapping to non-coding regions of the genome that are transcribed into RiboNucleic Acid (RNA) can potentially affect cellular regulation (and cause disease) by altering the structure of the transcript. We performed a large-scale meta-analysis of Selective 2'-Hydroxyl Acylation analyzed by Primer Extension (SHAPE) data, which probes the structure of RNA. We found that several single point mutations exist that significantly disrupt RNA secondary structure in the five transcripts we analyzed. Thus, every RNA that is transcribed has the potential to be a “RiboSNitch;” where a SNP causes a large conformational change that alters regulatory function. Predicting the SNPs that will have the largest effect on RNA structure remains a contemporary computational challenge. We therefore benchmarked the most popular RNA structure prediction algorithms for their ability to identify mutations that maximally affect structure. We also evaluated metrics for rank ordering the extent of the structural change. Although no single algorithm/metric combination dramatically outperformed the others, small differences in AUC (Area Under the Curve) values reveal that certain approaches do provide better agreement with experiment. The experimental data we analyzed nonetheless show that multiple single point mutations exist in all RNA transcripts that significantly disrupt structure in agreement with the predictions.</p

Dynamic biclustering of microarray data by multi-objective immune optimization

Abstract Background Newly microarray technologies yield large-scale datasets. The microarray datasets are usually presented in 2D matrices, where rows represent genes and columns represent experimental conditions. Systematic analysis of those datasets provides the increasing amount of information, which is urgently needed in the post-genomic era. Biclustering, which is a technique developed to allow simultaneous clustering of rows and columns of a dataset, might be useful to extract more accurate information from those datasets. Biclustering requires the optimization of two conflicting objectives (residue and volume), and a multi-objective artificial immune system capable of performing a multi-population search. As a heuristic search technique, artificial immune systems (AISs) can be considered a new computational paradigm inspired by the immunological system of vertebrates and designed to solve a wide range of optimization problems. During biclustering several objectives in conflict with each other have to be optimized simultaneously, so multi-objective optimization model is suitable for solving biclustering problem. Results Based on dynamic population, this paper proposes a novel dynamic multi-objective immune optimization biclustering (DMOIOB) algorithm to mine coherent patterns from microarray data. Experimental results on two common and public datasets of gene expression profiles show that our approach can effectively find significant localized structures related to sets of genes that show consistent expression patterns across subsets of experimental conditions. The mined patterns present a significant biological relevance in terms of related biological processes, components and molecular functions in a species-independent manner. Conclusions The proposed DMOIOB algorithm is an efficient tool to analyze large microarray datasets. It achieves a good diversity and rapid convergence

Characterization of a Novel blaKLUC Variant With Reduced β-Lactam Resistance From an IncA/C Group Plasmid in a Clinical Klebsiella pneumoniae Isolate

Similar to other CTX-M family enzymes, KLUC is a recently identified and emerging determinant of cefotaxime resistance that has been recovered from at least three Enterobacteriaceae species, including Kluyvera cryocrescens, Escherichia coli, and Enterobacter cloacae. Whether this extended-spectrum β-lactamase (ESBL) has been disseminated among commonly isolated Enterobacteriaceae is worthy of further investigation. In this study, we screened 739 nosocomial Enterobacteriaceae isolates (240 Klebsiella pneumoniae and 499 E. coli strains) and found that one K. pneumoniae and four E. coli isolates harbored the blaKLUC gene. Three blaKLUC determinants isolated from E. coli were entirely identical to a blaKLUC-3 gene previously recovered in the same hospital. PFGE of four blaKLUC-harboring E. coli strains showed that prevalence of these determinants was most likely mediated by horizontal gene transfer but not clonal dissemination. However, the variant isolated from K. pneumoniae belonged to a novel member of the KLUC enzyme group. This newly identified enzyme (KLUC-5) has an amino acid substitution compared with previously identified KLUC-1 (G18S) and KLUC-3 (G240D). Antimicrobial susceptibility tests showed that KLUC-5 significantly reduced resistance activity to almost all the selected antimicrobials compared to previously identified KLUC-3. Site-directed mutagenesis showed that blaKLUC-5-D240G and blaKLUC-5-S18G significantly enhanced the MIC against its best substrate. Conjugation and S1-PFGE indicated that blaKLUC-5 was located on a transferable plasmid, which was further decoded by single-molecule, real-time sequencing. Comparative genome analysis showed that its backbone exhibited genetic homology to the IncA/C incompatibility group plasmids. A transposable element, ISEcp1, was detected 256-bp upstream of the blaKLUC-5 gene; this location was inconsistent with the previously identified blaKLUC-1 but congruent with the variants recovered from E. coli in the same hospital. These data provide evidence of the increasingly emerging KLUC group of ESBLs in China

Molecular characterization of florfenicol and oxazolidinone resistance in Enterococcus isolates from animals in China

Florfenicol is widely used for the treatment of bacterial infections in domestic animals. The aim of this study was to analyze the molecular mechanisms of florfenicol and oxazolidinone resistance in Enterococcus isolates from anal feces of domestic animals. The minimum inhibitory concentration (MIC) levels were determined by the agar dilution method. Polymerase chain reaction (PCR) was performed to analyze the distribution of the resistance genes. Whole-genome sequencing and comparative plasmid analysis was conducted to analyze the resistance gene environment. A total of 351 non-duplicated enteric strains were obtained. Among these isolates, 22 Enterococcus isolates, including 19 Enterococcus. faecium and 3 Enterococcus. faecalis, were further studied. 31 florfenicol resistance genes (13 fexA, 3 fexB, 12 optrA, and 3 poxtA genes) were identified in 15 of the 19 E. faecium isolates, and no florfenicol or oxazolidinone resistance genes were identified in 3 E. faecalis isolates. Whole-genome sequencing of E. faecium P47, which had all four florfenicol and oxazolidinone resistance genes and high MIC levels for both florfenicol (256 mg/L) and linezolid (8 mg/L), revealed that it contained a chromosome and 3 plasmids (pP47-27, pP47-61, and pP47-180). The four florfenicol and oxazolidinone resistance genes were all related to the insertion sequences IS1216 and located on two smaller plasmids. The genes fexB and poxtA encoded in pP47-27, while fexA and optrA encoded in the conjugative plasmid pP47-61. Comparative analysis of homologous plasmids revealed that the sequences with high identities were plasmid sequences from various Enterococcus species except for the Tn6349 sequence from a Staphylococcus aureus chromosome (MH746818.1). The current study revealed that florfenicol and oxazolidinone resistance genes (fexA, fexB, poxtA, and optrA) were widely distributed in Enterococcus isolates from animal in China. The mobile genetic elements, including the insertion sequences and conjugative plasmid, played an important role in the horizontal transfer of florfenicol and oxazolidinone resistance

Identification of floR Variants Associated With a Novel Tn4371-Like Integrative and Conjugative Element in Clinical Pseudomonas aeruginosa Isolates

Florfenicol is widely used to control respiratory diseases and intestinal infections in food animals. However, there are increasing reports about florfenicol resistance of various clinical pathogens. floR is a key resistance gene that mediates resistance to florfenicol and could spread among different bacteria. Here, we investigated the prevalence of floR in 430 Pseudomonas aeruginosa isolates from human clinical samples and identified three types of floR genes (designated floR, floR-T1 and floR-T2) in these isolates, with floR-T1 the most prevalent (5.3%, 23/430). FloR-T2 was a novel floR variant identified in this study, and exhibited less identity with other FloR proteins than FloRv. Moreover, floR-T1 and floR-T2 identified in P. aeruginosa strain TL1285 were functionally active and located on multi-drug resistance region of a novel incomplete Tn4371-like integrative and conjugative elements (ICE) in the chromosome. The expression of the two floR variants could be induced by florfenicol or chloramphenicol. These results indicated that the two floR variants played an essential role in the host’s resistance to amphenicol and the spreading of these floR variants might be related with the Tn4371 family ICE

Effects of Crystalline Anisotropy and Indenter Size on Nanoindentation by Multiscale Simulation

Nanoindentation processes in single crystal Ag thin film under different crystallographic orientations and various indenter widths are simulated by the quasicontinuum method. The nanoindentation deformation processes under influences of crystalline anisotropy and indenter size are investigated about hardness, load distribution, critical load for first dislocation emission and strain energy under the indenter. The simulation results are compared with previous experimental results and Rice-Thomson (R-T) dislocation model solution. It is shown that entirely different dislocation activities are presented under the effect of crystalline anisotropy during nanoindentation. The sharp load drops in the load–displacement curves are caused by the different dislocation activities. Both crystalline anisotropy and indenter size are found to have distinct effect on hardness, contact stress distribution, critical load for first dislocation emission and strain energy under the indenter. The above quantities are decreased at the indenter into Ag thin film along the crystal orientation with more favorable slip directions that easy trigger slip systems; whereas those will increase at the indenter into Ag thin film along the crystal orientation with less or without favorable slip directions that hard trigger slip systems. The results are shown to be in good agreement with experimental results and R-T dislocation model solution

Inhibitory Effects of Appropriate Addition of Zero-Valent Iron on NH₃ and H₂S Emissions during Sewage Sludge Composting

Large amounts of NH3 and H2S are emitted during sewage sludge composting, resulting in odor pollution. This composting experiment was carried out using sewage sludge mixed with sawdust, and different amounts of zero-valent iron (ZVI) were added to investigate the effect on volatile gases, such as NH3 and H2S, and to analyze the effect on the available sulfur, total sulfur, moisture content, and germination index of the compost. The results showed that the addition of ZVI during the composting process had noticeable effects on the emission of NH3 and H2S. ZVI could also increase the heating rate and peak temperature of the pile, reduce the available sulfur loss, and promote the dewatering and decomposition of the compost pile. The addition of 3% ZVI had the best effect on NH3 emissions; it reduced the peak concentration of NH3 release during composting by 21.0% compared to the blank group. However, the addition of 2% ZVI was the most effective for H2S emissions; it reduced the peak release concentration of H2S by 20.0%. A higher addition of ZVI was more effective in reducing the moisture content and increasing the germination index of the compost

Inhibitory Effects of the Addition of KNO₃ on Volatile Sulfur Compound Emissions during Sewage Sludge Composting

Odor released from the sewage sludge composting process often has a negative impact on the sewage sludge treatment facility and becomes a hindrance to promoting compost technology. This study investigated the effect of adding KNO3 on the emissions of volatile sulfur compounds, such as hydrogen sulfide (H2S), dimethyl sulfide (DMS), and carbon disulfide (CS2), during sewage sludge composting and on the physicochemical properties of compost products, such as arylsulfatase activity, available sulfur, total sulfur, moisture content, and germination index. The results showed that the addition of KNO3 could inhibit the emissions of volatile sulfur compounds during composting. KNO3 can also increase the heating rate and peak temperature of the compost pile and reduce the available sulfur loss. The addition of 4% and 8% KNO3 had the best effect on H2S emissions, and it reduced the emissions of H2S during composting by 19.5% and 20.0%, respectively. The addition of 4% KNO3 had the best effect on DMS and CS2 emissions, and it reduced the emissions of DMS and CS2 by 75.8% and 63.0%, respectively. Furthermore, adding 4% KNO3 had the best effect from the perspective of improving the germination index of the compost

Quantifying the impact of strong ties in international scientific research collaboration.

Tie strength has been examined as an antecedent of creativity. Although it has been discovered that international collaboration affects scientific performance, the effect of tie strength in the international collaboration network has been largely neglected. Based on international publications of 72 countries/regions published from 1993 to 2013, we combine descriptive and panel regression methods to examine how the bonding of strong collaboration ties contributes to countries' international scientific performance. Strong ties occur at an average rate of 1 in 4 collaborators, whereas countries/regions share on average 84% of articles with their strong-tie collaborators. Our quantitative results provide an explanation for this phenomenon in international collaboration: the establishment of a strong tie relationship contributes to above-average productivity and citation frequency for countries/regions. To further explore which types of strong ties tend to have stronger citation impact, we analyse the relationship between persistent and stable collaboration and publication citation impact. Experimental results show that international collaborations with greater persistence and moderate stability tend to produce high impact publications. It is noteworthy that when the collaboration period is divided into different time intervals, similar findings can be found after the same analysis procedure is carried out. This indicates that our conclusions are robust. Overall, this study provides quantitative insights into the added value of long-term commitment and social trust associated with strong collaborative partnerships in international collaboration