A model study of the morphogenesis of D. melanogaster mechanoreceptors: the central regulatory circuit.

Macrochaetes (large bristles) are sensor organs of the Drosophila peripheral nervous system with a function of mechanoreceptors. An adult mechanoreceptor comprises four specialized cells: shaft (trichogen), socket (tormogen), neuron, and glial cell (thecogen). All these cells originate from a single cell, the so-called sensor organ precursor (SOP) cell. Separation of the SOP cell from the encompassing cells of the imaginal disc initiates a multistage process of sensory organ development. A characteristic feature of the SOP cell is the highest amount of the proneural proteins AS-C as compared with the encompassing ectodermal cells. The accumulation of proneural proteins and maintenance of their amount in the SOP cell at a necessary level is provided by the gene network with the achaete-scute gene complex (AS-C) as its key component. The activity of this complex is controlled by the central regulatory circuit (CRC). The CRC comprises the genes hairy, senseless (sens), charlatan (chn), scratch (scrt), daughterless (da), extramacrochaete (emc), and groucho (gro), coding for the transcription factors involved in the system of direct links and feedbacks and implementation of activation-repression relationships between the CRC components. The gene phyllopod (phyl), involved in degradation of the AS-C proteins, is also associated with the CRC functioning. In this paper, we propose a mathematical model for the CRC functioning as a regulator of the amount of proneural AS-C proteins in the SOP cell taking into account their degradation. The modeling has demonstrated that a change in the amount of proneural proteins in the SOP cell is stepwise rather than strictly monotonic. This prediction can be tested experimentally.

Adult Opisthorchis felineus major protein fractions deduced from transcripts: comparison with liver flukes Opisthorchis viverrini and Clonorchis sinensis.

The epidemiologically important liver flukes Opisthorchis felineus, Opisthorchis viverrini, and Clonorchis sinensis are of interest to health professionals, epidemiologists, pharmacologists, and molecular biologists. Recently the transcriptomes of the latter two species were intensively investigated. However our knowledge on molecular biology of O. felineus is scarce. We report the first results of the O. felineus transcriptome analysis. We isolated and annotated a total of 2560 expressed sequence tag (EST) sequences from adult O. felineus (deposited within the database of expressed sequence tags (dbEST), under accession numbers GenBank: JK624271-JK626790, JK006511-JK006547, JK649790-JK649792). Clustering and analysis resulted in the detection of 267 contigs. Of the protein sequences deduced from these, 82% had homologs in the NCBI (nr) protein database and 63% contained conserved domains, allowing the functions to be interpreted using the Gene Ontology terms. Comprehensive analysis of Opisthorchiidae- and Trematoda-specific substitutions within amino acid sequences deduced for the proteins myoglobin, vitelline precursor protein, cathepsin F, and 28kDa glutathione transferase was carried out. The gene set of the 32 ribosomal proteins for the three Opisthorchiidae species with the addition of available Schistosoma and Fasciola orthologs was created and is provided in the supplementary. The orthologous gene set created was used for inferring phylogeny within the Trematoda with special attention to interrelations within the Opisthorchiidae. The phylogenetic analysis revealed a closer relationship between C. sinensis and O. viverrini and some divergence of O. felineus from either O. viverrini or C. sinensis.

Drosophila mechanoreceptors as a model for studying asymmetric cell division.

Asymmetric cell division (ACD) is one of the processes creating the overall diversity of cell types in multicellular organisms. The essence of this process is that the daughter cells exit from it being different from both the parental cell and one another in their ability to further differentiation and specialization. The large bristles (macrochaetae) that are regularly arranged on the surface of the Drosophila adult function as mechanoreceptors, and since their development requires ACD, they have been extensively used as a model system for studying the genetic control of this process. Each macrochaete is composed of four specialized cells, the progeny resulting from several ACDs from a single sensory organ precursor (SOP) cell, which differentiates from the ectodermal cells of the wing imaginal disc in the third-instar larva and pupa. In this paper we review the experimental data on the genes and their products controlling the ACDs of the SOP cell and its daughter cells, and their further specialization. We discuss the main mechanisms determining the time when the cell enters ACD, as well as the mechanisms providing for the structural characteristics of asymmetric division, namely, polar distribution of protein determinants (Numb and Neuralized), orientation of the division spindle relative to these determinants, and unequal segregation of the determinants specifying the direction of daughter cell development.

The Digenea parasite Opisthorchis felineus: a target for the discovery and development of novel drugs.

Opisthorchosis is a helminthiasis affecting mainly the hepatobiliary system and pancreas; its most dramatic complication is malignization of the organs infected by the parasites. The causative agents of opisthorchosis are two species of liver flukes, the trematodes belonging to the family Opisthorchiidae--Opisthorchis felineus and O. viverrini. The Chinese liver fluke, Clonorchis sinensis, also member of the family Opisthorchiidae, causes clonorchosis, a disease very close in symptomatology. According to different estimations, up to 40 million people are currently infected with these liver flukes and up to 600-750 million people in Eurasian countries constitute the risk group. These parasites colonize ever-increasing new areas in Eurasia where this disease has never been previously reported. Opisthorchiases are gradually transforming from a local problem of individual geographic regions to a widespead problem; in particular, O. viverrini is now referred to as "an underestimated parasite." As we see it, O. felineus has all the reasons to share this status. First and foremost, the observed expansion is likely to be connected with the ever-increasing intensity of traffic flows and migration of the infection carriers between cities, regions, and countries. This review briefs the characteristics of O. felineus and the other liver flukes persisting in various countries of Eurasia, clinical manifestations of opisthorchosis, the drugs for chemotherapy of trematodiasis, and the strategy for discovery of new antihelminthic drugs.

Promoters of the genes encoding the transcription factors regulating the cytokine gene expression in macrophages contain putative binding sites for aryl hydrocarbon receptor.

The computer system SITECON was used to study the regulatory regions in the transcription factor genes expressed in the activated macrophage and the genes of the proteins mediating the macrophage involvement in the immune response. Dioxin responsive elements (DREs), the specific sites responsible for expression regulation of the genes involved in the cell response to dioxin, were found in these gene regions. Thus, the role of dioxin in activity regulation of the genes involved in development of the immune response can be regulated both directly, by the transcription complex containing dioxin as a ligand, and indirectly, via intrinsic transcription factors.The double regulation, via DRE and the binding sites for the corresponding transcription factors in the promoter regions of macrophage genes, and the interregulation of the genes providing for the immune response allow the system to rapidly respond to a provocative agent (xenobiotic) and finely tune its function.

The gene network determining development of Drosophila melanogaster mechanoreceptors.

Macrochaetes (large bristles), functioning as mechanoreceptors, are located in an orderly fashion on the drosophila head and body forming a species-specific bristle pattern. A simple organization of each bristle organ, comprising only four specialized cells, and conservation of bristle pattern make macrochaetes a convenient model for studying the development patterns of spatial structures with a fixed number of elements at certain positions and the mechanisms of cell differentiation. In this work, we systematize the experimental data on the main genes and their products that are involved in the control of proneural clusters in the ectoderm of imaginal discs and determination of the sensory organ precursor (SOP) cell within the proneural clusters. The computer system GeneNet was used to reconstruct the gene network controlling these stages of macrochaete development, which are critical for the formation of a correct bristle pattern. The role of achaete-scute complex and EGFR and Notch signaling pathways and the regulatory mechanisms acting in this gene network are discussed.

NPRD: Nucleosome Positioning Region Database.

Nucleosome Positioning Region Database (NPRD), which is compiling the available experimental data on locations and characteristics of nucleosome formation sites (NFSs), is the first curated NFS-oriented database. The object of the database is a single NFS described in an individual entry. When annotating results of NFS experimental mapping, we pay special attention to several important functional characteristics, such as the relationship between type of gene activity and nucleosome positioning, the influence of non-histone proteins on nucleosome formation, type of the variant of nucleosome positioning (translational or rotational), indication of tissue types and states of cell activity, description of experimental methods used and accuracy of nucleosome position determination, and the results of applying theoretical and computer methods to the analysis of contextual and conformational DNA properties. At present, the NPRD database contains 438 entries and integrates the data described in 124 original papers. The database URL: http://srs6.bionet.nsc.ru/srs6/. Then click the button 'Databank' and open the link NUCLEOSOME.