A cellular mechanism for multi-robot construction via evolutionary multi-objective optimization of a gene regulatory network

A major research challenge of multi-robot systems is to predict the emerging behaviors from the local interactions of the individual agents. Biological systems can generate robust and complex behaviors through relatively simple local interactions in a world characterized by rapid changes, high uncertainty, infinite richness, and limited availability of information. Gene Regulatory Networks (GRNs) play a central role in understanding natural evolution and development of biological organisms from cells. In this paper, inspired by biological organisms, we propose a distributed GRN-based algorithm for a multi-robot construction task. Through this algorithm, multiple robots can self-organize autonomously into different predefined shapes, and self-reorganize adaptively under dynamic environments. This developmental process is evolved using a multi-objective optimization algorithm to achieve a shorter travel distance and less convergence time. Furthermore, a theoretical proof of the system's convergence is also provided. Various case studies have been conducted in the simulation, and the results show the efficiency and convergence of the proposed method.     

Phenotypic expression of ADH regulatory genes inDrosophila melanogaster: a comparative study between a paleartic and a tropical population

In vitro ADH activity was studied inD. melanogaster males from two sets of third chromosome substitution lines, one from a paleartic population (Gigean, France), the other from a tropical population (Brazzaville, Congo). As a linear model with raw ADH activity dependent on fresh weight was significant in both sets of lines, the raw activity was adjusted by regression on weight. Two main results were found: (a) the well-known substantial intrapopulation variability; and (b) third chromosome geographical origin did not affect the mean ADH activity. Unlike the structuralAdh gene polymorphism which allows the two populations to be distinguished, the polymorphism of the third chromosome ADH regulatory genes (or more exactly their phenotypic expression) does not allow to discriminate between them. These results are discussed in the context of the adaptation ofD. melanogaster to the alcoholic substrates in light of a model proposed by Hedrick and McDonald (1980) in order to interpret variations in both structural and regulatory gene polymorphisms.     

Evolutionary pattern of the regulatory network for flower development:Insights gained from a comparison of two Arabidopsis species

Previous studies on Arabidopsis thaliana and other model plants have indicated that the development of a flower is controlled by a regulatory network composed of genes and the interactions among them.Studies on the evolution of this network will therefore help understand the genetic basis that underlies flower evolution.In this study,by reviewing the most recent published work,we added 31 genes into the previously proposed regulatory network for flower development.Thus,the number of genes reached 60.We then compared the composition,structure,and evolutionary rate of these genes between A.thaliana and one of its allies,A.lyrata.We found that two genes (FLC and MAF2) show 1∶ 2 and 2∶ 2 relationships between the two species,suggesting that they have experienced independent,post-speciation duplications.Of the remaining 58 genes,35 (60.3％) have diverged in exon-intron structure and,consequently,code for proteins with different sequence features and functions.Molecular evolutionary analyses further revealed that,although most floral genes have evolved under strong purifying selection,some have evolved under relaxed or changed constraints,as evidenced by the elevation of nonsynonymous substitution rates and/or the presence of positively selected sites.Taken together,these results suggest that the regulatory network for flower development has evolved rather rapidly,with changes in the composition,structure,and functional constraint of genes,as well as the interactions among them,being the most important contributors.     

Gene regulatory network from microarray data of colon cancer patients using TSK-type recurrent neural fuzzy network

In this work we applied a TSK-type recurrent neural fuzzy approach to extract regulatory relationship among genes and reconstruct gene regulatory network from microarray data. The identified signature has captured the regulatory relationship among 27 differentially expressed genes from microarray dataset. We applied three different methods viz., feed forward neural fuzzy, modified genetic algorithm and recurrent neural fuzzy, on the same data set for the inference of GRNs and the results obtained are almost comparable. In all tested cases, TRNFN identified more biologically meaningful relations. We found that 87.8% of the total interactions extracted by TRNFN are correct in accordance with the biological knowledge. Our analysis resulted in 2 major outcomes. First, upregulated genes are regulated by more genes than downregulated genes. Second, tumor activators activate other tumor activators and suppress tumor suppressers strongly in the disease environment. These findings will help to elucidate the common molecular mechanism of colon cancer, and provide new insights into cancer diagnostics, prognostics and therapy.     

Transplantation of a polyembryonic wasp embryo: a technique for transferring endoparasitic embryo into the host egg

Concealed development of many animal embryos prevents examination of development and limits the application of embryo manipulation techniques aimed at understanding developmental processes. In embryos developing in utero, such as in mammals, it is necessary to dissect embryos from the mother and, upon manipulative intervention, to implant them back into the recipient. Parasitic wasps present a promising system for understanding the evolution of early developmental processes. In basal ectoparasitic species that lay eggs on the surface of the host, it is possible to adapt embryo manipulation techniques developed in Drosophila. However, their derived endoparasitic relatives, which exhibit various modifications of developmental programs, undergo concealed development within the host body. For example, the parasitic polyembryonic wasp Copidosoma floridanum oviposits an egg into the egg of the host moth Trichoplusia ni. The host larva emerges and the parasite undergoes development within the host body, preventing embryo manipulation as a means of examining developmental regulation. Here we present a protocol for embryo transfer that allows the transplantation of C. floridanum egg into the host egg. This approach opens a new avenue in the application of various embryo manipulation techniques aimed at understanding the evolution of embryogenesis in endoparasitic Hymenoptera. In addition, this approach has potential for the development of other tools in C. floridanum, such as transgenesis and reverse genetics, which can also be extended to other endoparasitic species.     

Simultaneous expression of glutaryl-7-aminocephalosporanic acid acylase gene and lysis genes of phage λ in a recombinant E. coli

Glutaryl-7-aminocephalosporanic acid acylase (GLA), recommended for use in the form of immobilized-enzyme, is one of the two key enzymes in the two-step synthesis of 7-aminocephalosporanic acid. For simplifying the process of cell disruption and immobilization, the lysis genes of phage λ (S⁻RRz) with the S amber mutation were designed to introduce into the over-expression system of GLA. A novel recombinant strain, E. coli TB1/pMKC-AS, simultaneously containing the maltose binding protein gene (malE), the lysis genes (S⁻RRz) and the target GLA gene (Acy) in a same operon, was successfully constructed. Under neutral pH conditions, cell growth and GLA activity of TB1/pMKC-AS was not affected by the presence of the lysis genes, however, autolysis phenomenon was observed under weak alkaline conditions. Through pH control and fed-batch culture, the GLA activity of TB1/pMKC-AS reached as high as 6810 U/L with 24.8 g/L dry cell density (OD₆₀₀ = 67.9) in a 5 L fermentor. In contrast to the cells of E. coli TB1/pMKC-Acy without the lysis genes, the mild EDTA/Tris buffer (pH 8.0) can cause the lysis of the cells of TB1/pMKC-AS containing the lysis genes. Correspondingly, a mild pH 9.0/42 °C incubation method was developed for conveniently degrading the recombinant cells of TB1/pMKC-AS, based on the expression of the lysis genes. Further experiments showed that the cell lysate after the mild incubation disruption can be directly immobilized by 10% polyacrylamide to make the immobilized enzymes. In comparison with the immobilized GLA from TB1/pMKC-Acy, the immobilized cell lysate of TB1/pMKC-AS has the similar characteristics of catalysis stability, implying a great potential for industrial application of the lysis genes-assisted cell disruption.     

Regulation of interlocking gene regulatory network subcircuits by a small molecule inhibitor of retinoblastoma protein (RB) phosphorylation: Cancer cell expression of HLA-DR

The induction of the major histocompatibility (MHC), antigen-presenting class II molecules by interferon-gamma, in solid tumor cells, requires the retinoblastoma tumor suppressor protein (Rb). In the absence of Rb, a repressosome blocks the access of positive-acting, promoter binding proteins to the MHC class II promoter. However, a complete molecular linkage between Rb expression and the disassembly of the MHC class II repressosome has been lacking. By treating A549 lung carcinoma cells with a novel small molecule that prevents phosphorylation-mediated, Rb inactivation, we demonstrate that Rb represses the synthesis of an MHC class II repressosome component, YY1. The reduction in YY1 synthesis correlates with the advent of MHC class II inducibility; with loss of YY1 binding to the promoter of the HLA–DRA gene, the canonical human MHC class II gene; and with increased Rb binding to the YY1 promoter. These results support the concept that the Rb gene regulatory network (GRN) subcircuit that regulates cell proliferation is linked to a GRN subcircuit regulating a tumor cell immune function.     

Expression of Rhizobium meliloti genes for nitrogen fixation in Escherichia coli minicells: Mapping of the subunit of the nitrogenase reductase

An EcoRI fragment of Rhizobium meliloti M2011 which shows homology to Klebsiella pneumoniae DNA carrying nifH and nifD was cloned in both orientations into the Cm gene of plasmid pACYC184 and expressed in Escherichia coli minicells. Fragment specific polypeptides of M_r 12 500, 21 000, 30 000, and 31 000 could be identified. By transposon mutagenesis it was shown that two of them (M_r 12 500 and 21 000) are fusion products with parts of the chloramphenicol acetyltransferase. The other two polypeptides are specified by one coding region which could be mapped by transposon mutagenesis. There are several reasons (homology to Klebsiella nifH, sequence data and molecular weight of the gene products) to assume that this coding region represents the R. meliloti nifH gene (gene for the subunit of the R. meliloti nitrogenase reductase, RmII).     

Association of dystrobrevin and regulatory subunit of protein kinase A: a new role for dystrobrevin as a scaffold for signaling proteins

The dystrophin-related and -associated protein dystrobrevin is a component of the dystrophin-associated protein complex, which directly links the cytoskeleton to the extracellular matrix. It is now thought that this complex also serves as a dynamic scaffold for signaling proteins, and dystrobrevin may play a role in this context. Since dystrobrevin involvement in signaling pathways seems to be dependent on its interaction with other proteins, we sought new insights and performed a two-hybrid screen of a mouse brain cDNA library using beta-dystrobrevin, the isoform expressed in non-muscle tissues, as bait. Among the positive clones characterized after the screen, one encodes the regulatory subunit RIalpha of the cAMP-dependent protein kinase A (PKA). We confirmed the interaction by in vitro and in vivo association assays, and mapped the binding site of beta-dystrobrevin on RIalpha to the amino-terminal region encompassing the dimerization/docking domain of PKA regulatory subunit. We also found that the domain of interaction for RIalpha is contained in the amino-terminal region of beta-dystrobrevin. We obtained evidence that beta-dystrobrevin also interacts directly with RIIbeta, and that not only beta-dystrobrevin but also alpha-dystrobrevin interacts with PKA regulatory subunits. We show that both alpha and beta-dystrobrevin are specific phosphorylation substrates for PKA and that protein phosphatase 2A (PP2A) is associated with dystrobrevins. Our results suggest a new role for dystrobrevin as a scaffold protein that may play a role in different cellular processes involving PKA signaling.     

Identification of susceptibility modules for coronary artery disease using a genome wide integrated network analysis

Although recent genome-wide association studies (GWAS) have identified a handful of variants with best significance for coronary artery disease (CAD), it remains a challenge to summarize the underlying biological information from the abundant genotyping data. Here, we propose an integrated network analysis that effectively combines GWAS genotyping dataset, protein–protein interaction (PPI) database, literature and pathway annotation information. This three-step approach was illustrated for a comprehensive network analysis of CAD as the following. First, a network was constructed from PPI database and CAD seed genes mined from the available literatures. Then, susceptibility network modules were captured from the results of gene-based association tests. Finally, susceptibility modules were annotated with potential mechanisms for CAD via the KEGG pathway database. Our network analysis identified four susceptibility modules for CAD including a complex module that consisted of 15 functional inter-connected sub-modules, AGPAT3–AGPAT4–PPAP2B module, ITGA11–ITGB1 module and EMCN–SELL module. MAPK10 and COL4A2 among the top-scored focal adhesion pathway related module were the most significant genes (MAPK10: OR = 32.5, P = 3.5 × 10^− 11; COL4A2: OR = 2.7, P = 2.8 × 10^− 10). The significance of the two genes were further validated by other two gene-based association tests (MAPK10: P = 0.009 and 0.007; COL4A2: P = 0.001 and 0.023) and another independent GWAS dataset (MAPK10: P = 0.001; COL4A2: P = 0.0004). Furthermore, 34 out of 44 previously reported CAD susceptibility genes were captured by our CAD PPI network and 17 of them were also significant genes. The susceptibility modules identified in our study might provide novel clues for the clarification of CAD pathogenesis in the future.