DNA Immunization with Fusion of CTLA-4 to Hepatitis B Virus (HBV) Core Protein Enhanced Th2 Type Responses and Cleared HBV with an Accelerated Kinetic

BACKGROUND: Typically, DNA immunization via the intramuscular route induces specific, Th1-dominant immune responses. However, plasmids expressing viral proteins fused to cytotoxic T lymphocyte antigen 4 (CTLA-4) primed Th2-biased responses and were able to induced effective protection against viral challenge in the woodchuck model. Thus, we addressed the question in the mouse model how the Th1/Th2 bias of primed immune responses by a DNA vaccine influences hepatitis B virus (HBV) clearance. PRINCIPAL FINDINGS: Plasmids expressing HBV core protein (HBcAg) or HBV e antigen and HBcAg fused to the extracellular domain of CTLA-4 (pCTLA-4-HBc), CD27, and full length CD40L were constructed. Immunizations of these DNA plasmids induced HBcAg-specific antibody and cytotoxic T-cell responses in mice, but with different characteristics regarding the titers and subtypes of specific antibodies and intensity of T-cell responses. The plasmid pHBc expressing HBcAg induced an IgG2a-dominant response while immunizations of pCTLA-4-HBc induced a balanced IgG1/IgG2a response. To assess the protective values of the immune responses of different characteristics, mice were pre-immunized with pCTLA-4-HBc and pHBc, and challenged by hydrodynamic injection (HI) of pAAV/HBV1.2. HBV surface antigen (HBsAg) and DNA in peripheral blood and HBcAg in liver tissue were cleared with significantly accelerated kinetics in both groups. The clearance of HBsAg was completed within 16 days in immunized mice while more than 50% of the control mice are still positive for HBsAg on day 22. Stronger HBcAg-specific T-cell responses were primed by pHBc correlating with a more rapid decline of HBcAg expression in liver tissue, while anti-HBs antibody response developed rapidly in the mice immunized with pCTLA-4-HBc, indicating that the Th1/Th2 bias of vaccine-primed immune responses influences the mode of viral clearance. CONCLUSION: Viral clearance could be efficiently achieved by Th1/Th2-balanced immune response, with a small but significant shift in T-cell and B-cell immune responses

Regulation of High-Temperature Stress Response by Small RNAs

Temperature extremes constitute one of the most common environmental stresses that adversely affect the growth and development of plants. Transcriptional regulation of temperature stress responses, particularly involving protein-coding gene networks, has been intensively studied in recent years. High-throughput sequencing technologies enabled the detection of a great number of small RNAs that have been found to change during and following temperature stress. The precise molecular action of some of these has been elucidated in detail. In the present chapter, we summarize the current understanding of small RNA-mediated modulation of high- temperature stress-regulatory pathways including basal stress responses, acclimation, and thermo-memory. We gather evidence that suggests that small RNA network changes, involving multiple upregulated and downregulated small RNAs, balance the trade-off between growth/development and stress responses, in order to ensure successful adaptation. We highlight specific characteristics of small RNA-based tem- perature stress regulation in crop plants. Finally, we explore the perspectives of the use of small RNAs in breeding to improve stress tolerance, which may be relevant for agriculture in the near future

Identification of a Marine Bacillus Strain C5 and Parathion-Methyl Degradation Characteristics of the Extracellular Esterase B1

A bacterial strain C5 that can produce new type of marine esterase was isolated and screened from marine sludge. According to 16S rRNA sequence analysis and physiological and biochemical experiments, the strain was identified as Bacillus subtilis. A single isozyme with a molecular weight of 86 kDa was observed by SDS-PAGE and native-PAGE. On this basis, the mechanism of esterase B1 secreted by strain C5 degrading parathion-methyl was explored, and the effects of temperature and pH on the degradation rate were investigated. From the results, p-nitrophenol was one of the degradation products of B1 degrading parathion-methyl, and the best degradation effect could be achieved at the temperature of 40°C and the neutral pH value

Learning Causal Biological Networks with Parallel Ant Colony Optimization Algorithm

A wealth of causal relationships exists in biological systems, both causal brain networks and causal protein signaling networks are very classical causal biological networks (CBNs). Learning CBNs from biological signal data reliably is a critical problem today. However, most of the existing methods are not excellent enough in terms of accuracy and time performance, and tend to fall into local optima because they do not take full advantage of global information. In this paper, we propose a parallel ant colony optimization algorithm to learn causal biological networks from biological signal data, called PACO. Specifically, PACO first maps the construction of CBNs to ants, then searches for CBNs in parallel by simulating multiple groups of ants foraging, and finally obtains the optimal CBN through pheromone fusion and CBNs fusion between different ant colonies. Extensive experimental results on simulation data sets as well as two real-world data sets, the fMRI signal data set and the Single-cell data set, show that PACO can accurately and efficiently learn CBNs from biological signal data

An Entropy-Based Multiobjective Evolutionary Algorithm with an Enhanced Elite Mechanism

Multiobjective optimization problem (MOP) is an important and challenging topic in the fields of industrial design and scientific research. Multi-objective evolutionary algorithm (MOEA) has proved to be one of the most efficient algorithms solving the multi-objective optimization. In this paper, we propose an entropy-based multi-objective evolutionary algorithm with an enhanced elite mechanism (E-MOEA), which improves the convergence and diversity of solution set in MOPs effectively. In this algorithm, an enhanced elite mechanism is applied to guide the direction of the evolution of the population. Specifically, it accelerates the population to approach the true Pareto front at the early stage of the evolution process. A strategy based on entropy is used to maintain the diversity of population when the population is near to the Pareto front. The proposed algorithm is executed on widely used test problems, and the simulated results show that the algorithm has better or comparative performances in convergence and diversity of solutions compared with two state-of-the-art evolutionary algorithms: NSGA-II, SPEA2 and the MOSADE

Genome-Wide Identification and Characterization of Cysteine-Rich Receptor-Like Protein Kinase Genes in Tomato and Their Expression Profile in Response to Heat Stress

During plant growth, development and stress adaption, receptor-like protein kinases (RLKs) are essential components in perceiving and integrating extracellular stimuli and transmitting the signals to activate the downstream signaling pathways. Cysteine-rich receptor-like protein kinases (CRKs) are a large subfamily of RLKs and their roles in modulating plant disease resistance are well elucidated. However, the roles of CRKs in plant abiotic stress responses, especially heat stress, are largely unknown. In this study, 35 SlCRK genes were identified in tomato (Solanum lycopersicum) based on the multiple sequence alignment and phylogenetic relationships. SlCRK genes are tandemly distributed on seven chromosomes and have similar exon–intron organization and common conserved motifs. Various phytohormone responsive, stress responsive cis-regulatory elements and heat shock elements are predicted in the promoter regions of SlCRK genes. Transcriptome analysis of tomato fruits under heat stress revealed that most SlCRK genes were downregulated upon heat treatment. GO enrichment analyses of genes that were co-expressed with SlCRK members have identified various stress responses related and proteasomal protein catabolic process related genes, which may be involved in heat stress signaling. Overall, our results provide valuable information for further research on the roles of SlCRKs in response to abiotic stress, especially heat stress

Cloning, Overexpression and Characterization of a Catalase from a Marine Acinetobacter Bacterium

Objective: The marine catalase YS0810CAT gene was cloned and overexpressed from Acinetobacter sp. YS0810, and high stability of the recombinant enzyme was validated, which made it important for potential applications in the elimination of hydrogen peroxide from industrial process-generated streams. Methods: The gene was cloned by PCR and overexpressed in Escherichia coli. Evolutionary analyses of this enzyme were conducted with the MEGA software. Anion exchange was applied to purify the recombinant enzyme. The effects of pH and temperature on the activity and stability of YS0810CAT were measured. Results: The gene consists of 1,518 bp and belongs to Clade 3 of monofunctional catalases. The maximum protein production was obtained with 0.8 mM IPTG, a post-induction temperature of 37°C, and a post-induction time of 8 h. The recombinant protein was most active at 60°C and pH 11. Conclusion: The effects of pH and temperature on the activity and stability of the wild type and recombinant YS0810CAT are similar. The protocol for the preparation of recombinant YS0810CAT could aid enzyme crystallization; moreover, improvement in its properties may be possible through protein engineering

Artificial Bee Colony Algorithm Merged with Pheromone Communication Mechanism for the 0-1 Multidimensional Knapsack Problem

Given a set of n objects, the objective of the 0-1 multidimensional knapsack problem (MKP_01) is to find a subset of the object set that maximizes the total profit of the objects in the subset while satisfying m knapsack constraints. In this paper, we have proposed a new artificial bee colony (ABC) algorithm for the MKP_01. The new ABC algorithm introduces a novel communication mechanism among bees, which bases on the updating and diffusion of inductive pheromone produced by bees. In a number of experiments and comparisons, our approach obtains better quality solutions in shorter time than the ABC algorithm without the mechanism. We have also compared the solution performance of our approach against some stochastic approaches recently reported in the literature. Computational results demonstrate the superiority of the new ABC approach over all the other approaches

Test Investigation and Rule Analysis of Bearing Fault Diagnosis in Induction Motors

In this paper, a series of tests were conducted on the bearings of induction motors to investigate vibration signal analysis-based diagnosis of bearing faults, and a thorough analysis was also conducted. In the engineering field, the kurtosis coefficient of vibration acceleration and the root mean square of vibration velocity, as well as resonant demodulated spectrum analysis of vibration acceleration, have been widely used for bearing fault diagnosis. These are integrated in almost any commercially available device for diagnosing bearing faults. However, the unsuitable use of these devices results in many false diagnoses. In light of this, they were selected as research objects and were investigated experimentally. In three induction motors, faults of different severity in the bearing outer race and cage were modeled for tests, and the corresponding results were used to evaluate the performance of the selected diagnosis methods. Some vague information in engineering was clarified, and some instructive rules were outlined to improve the bearing fault diagnosis performance. Taking the kurtosis coefficient of vibration acceleration (Ku) as an example, in engineering, Ku = 4 is generally taken as the diagnostic threshold of bearing faults. This means the following rule applies: if Ku ≤ 4, the bearing is healthy; otherwise, the bearing is faulty. However, the test results in this paper show that even if Ku ≤ 4, the bearing might be faulty; if Ku > 4, the bearing is indeed faulty. Therefore, the diagnostic rule should be improved as follows: if Ku > 4, the bearing is faulty (which can be assured), and if Ku ≤ 4, the status of the bearing is still undetermined. Thus, this paper can be helpful for researchers to gain an experimental understanding of the selected diagnosis methods and provides some improved rules on their use for reducing false diagnoses