Genetic approaches to the investigation of serotonergic neuron functions in animals

The serotonergic system is one of the most important neurotransmitter systems that take part in the regulation of vital CNS functions. The understanding of its mechanisms will help scientists create new therapeutic approaches to the treatment of mental and neurodegenerative diseases and find out how this neurotransmitter system interacts with other parts of the brain and regulates their activity. Since the serotonergic system anatomy and functionality are heterogeneous and complex, the best tools for studying them are based on manipulation of individual types of neurons without affecting neurons of other neurotransmitter systems. The selective cell control is possible due to the genetic determinism of their functions. Proteins that determine the uniqueness of the cell type are expressed under the regulation of cell-specific promoters. By using promoters that are specific for genes of the serotonin system, one can control the expression of a gene of interest in serotonergic neurons. Here we review approaches based on such promoters. The genetic models to be discussed in the article have already shed the light on the role of the serotonergic system in modulating behavior and processing sensory information. In particular, genetic knockouts of serotonin genes sert, pet1, and tph2 promoted the determination of their contribution to the development and functioning of the brain. In addition, the review describes inducible models that allow gene expression to be controlled at various developmental stages. Finally, the application of these genetic approaches in optogenetics and chemogenetics provided a new resource for studying the functions, discharge activity, and signal transduction of serotonergic neurons. Nevertheless, the advantages and limitations of the discussed genetic approaches should be taken into consideration in the course of creating models of pathological conditions and developing pharmacological treatments for their correction

Induction and migration of cryptic/defective Salmonella enterica prophages as a consequence of infection with lytic phages is an additional factor in stability of a coevolutionary vector

The influence of infection of natural isolates of Salmonella enterica with lytic (nonlysogenic) phages on the expression of resident cryptic or defective prophages in host bacteria was studied. The induction of defective/cryptic phages after infection with nonlysogenic phages and packaging of bacterial chromosomal fragments in capsids of defective phages is demonstrated. This may lead to migration and wide distribution of both the genomes of defective phages per se and various fragments of the bacterial chromosome (including pathogenic islands) in new bacterial strains with concomitant change of their properties, the acquired new features of pathogenicity among them.This work was supported by EC PhageVet-P (contract no. FOOD-CT-2005-007224) and by the Russian Foundation for Basic Research (grant no. 08-04-00162-a). We gratefully acknowledge the support of organizations presenting the grants.info:eu-repo/semantics/publishedVersio

The T7-Related Pseudomonas putida Phage ϕ15 Displays Virion-Associated Biofilm Degradation Properties

Formation of a protected biofilm environment is recognized as one of the major causes of the increasing antibiotic resistance development and emphasizes the need to develop alternative antibacterial strategies, like phage therapy. This study investigates the in vitro degradation of single-species Pseudomonas putida biofilms, PpG1 and RD5PR2, by the novel phage ϕ15, a ‘T7-like virus’ with a virion-associated exopolysaccharide (EPS) depolymerase. Phage ϕ15 forms plaques surrounded by growing opaque halo zones, indicative for EPS degradation, on seven out of 53 P. putida strains. The absence of haloes on infection resistant strains suggests that the EPS probably act as a primary bacterial receptor for phage infection. Independent of bacterial strain or biofilm age, a time and dose dependent response of ϕ15-mediated biofilm degradation was observed with generally a maximum biofilm degradation 8 h after addition of the higher phage doses (104 and 106 pfu) and resistance development after 24 h. Biofilm age, an in vivo very variable parameter, reduced markedly phage-mediated degradation of PpG1 biofilms, while degradation of RD5PR2 biofilms and ϕ15 amplification were unaffected. Killing of the planktonic culture occurred in parallel with but was always more pronounced than biofilm degradation, accentuating the need for evaluating phages for therapeutic purposes in biofilm conditions. EPS degrading activity of recombinantly expressed viral tail spike was confirmed by capsule staining. These data suggests that the addition of high initial titers of specifically selected phages with a proper EPS depolymerase are crucial criteria in the development of phage therapy

SOME OUTCOMES IN STUDYING NANOTHEMATIC DOCUMENTARY FLOW IN SIBERIAN BRANCH OF THE RUSSIAN ACADEMY OF SCIENCES BASED ON INSPEC BD DATA

Based on the Inspec's data, the results of information search carried out using specialized terms, after studying the dynamics of their use for 2000-2011 years of publications, were diagnosed; analyses of publishing interactions among SB RAS scientific centers are shown.DOI: http://dx.doi.org/10.12731/2227-930X-2012-1-1

Genome Instability of Pseudomonas aeruginosa phages of the EL species: examination of virulent mutants

The article continues a study of pseudolysogeny in Pseudominas aeruginosa infected with phiKZ-like phages of the EL species. Analysis was performed for several newly isolated vir mutants of EL phages (EL and RU) that were virulent (capable of causing lysis of bacteria infected with the wild-type phage) and a lower extent of opalescence of negative colonies (NCs). Wile-type recombinants were detected in crosses of virulent mutants of phages EL and RU to confirm the polygenic control of virulence. Since a deletion mutation was found in one of the virulent EL mutants and high genetic instability was characteristic of another mutant, a mobile genetic element was assumed to play a role in mutagenesis. Pseudolysogeny of bacteria provides for horizontal gene transfer between different bacterial strains. Hence, sequencing of the phage genome and demonstration of the lack of toxic gene products are insufficient for the phage to be included into a therapeutic mixture. To use live phages, it is essential to study in detail the possible consequences of their interaction with host bacteria. © 2011 Pleiades Publishing, Ltd.status: publishe

Complete Genome Sequence of the Giant Virus OBP and Comparitive Genome Analysis of the Diverse {varphi}KZ-Related Phages

The 283,757 bp dsDNA genome of Pseudomonas fluorescens phage OBP shares a general genomic organization with Pseudomonas aeruginosa phage EL. Comparison of this genomic organization assembled in syntenic genomic blocks interspersed with hyperplastic regions of the ϕKZ-related phages, supports the proposed division in the "EL-like viruses", and the "phiKZ-like viruses" within a larger subfamily. Identification of putative early transcription promoters scattered throughout the hyperplastic regions, explains several features of the ϕKZ-related genome organization (existence of genomic islands) and evolution (multi-inversion in hyperplastic regions). Using Hidden Markov modeling typical conserved core genes could be identified including the portal protein, the injection needle, and two polypeptides with respective similarity to the 3' -5' exonuclease domain and the polymerase domain of the T4 DNA polymerase. While the N-terminal domains of the tail fiber module and peptidoglycan degrading proteins are conserved, the observation of C-terminal catalytic domains typical for the different genera supports the further subdivision of the ϕKZ-related phages.status: publishe