Neuronal inputs and outputs of aging and longevity.

An animal's survival strongly depends on its ability to maintain homeostasis in response to the changing quality of its external and internal environment. This is achieved through intracellular and intercellular communication within and among different tissues. One of the organ systems that plays a major role in this communication and the maintenance of homeostasis is the nervous system. Here we highlight different aspects of the neuronal inputs and outputs of pathways that affect aging and longevity. Accordingly, we discuss how sensory inputs influence homeostasis and lifespan through the modulation of different types of neuronal signals, which reflects the complexity of the environmental cues that affect physiology. We also describe feedback, compensatory, and feed-forward mechanisms in these longevity-modulating pathways that are necessary for homeostasis. Finally, we consider the temporal requirements for these neuronal processes and the potential role of natural genetic variation in shaping the neurobiology of aging

Endonuclease domain of the Drosophila melanogaster R2 non-LTR retrotransposon and related retroelements: a new model for transposition

The molecular mechanisms of the transposition of non-long terminal repeat (non-LTR) retrotransposons are not well understood; the key questions of how the 3′-ends of cDNA copies integrate and how site-specific integration occurs remain unresolved. Integration depends on properties of the endonuclease (EN) domain of retrotransposons. Using the EN domain of the Drosophila R2 retrotransposon as a model for other, closely related non-LTR retrotransposons, we investigated the EN domain and found that it resembles archaeal Holliday-junction resolvases. We suggest that these non-LTR retrotransposons are co-transcribed with the host transcript. Combined with the proposed resolvase activity of the EN domain, this model yields a novel mechanism for site-specific retrotransposition within this class of retrotransposons, with resolution proceeding via a Holliday junction intermediate

Neuronal inputs and outputs of aging and longevity

An animal’s survival strongly depends on its ability to maintain homeostasis in response to the changing quality of its external and internal environment. This is achieved through intracellular and intercellular communication within and among different tissues. One of the organ systems that plays a major role in this communication and the maintenance of homeostasis is the nervous system. Here we highlight different aspects of the neuronal inputs and outputs of pathways that affect aging and longevity. Accordingly, we discuss how sensory inputs influence homeostasis and lifespan through the modulation of different types of neuronal signals, which reflects the complexity of the environmental cues that affect physiology. We also describe feedback, compensatory and feed-forward mechanisms in these longevity-modulating pathways that are necessary for homeostasis. Finally, we consider the temporal requirements for these neuronal processes and the potential role of natural genetic variation in shaping the neurobiology of aging

Multiple Quantitative Trait Loci Influence the Shape of a Male-Specific Genital Structure in Drosophila melanogaster

The observation that male genitalia diverge more rapidly than other morphological traits during evolution is taxonomically widespread and likely due to some form of sexual selection. One way to elucidate the evolutionary forces acting on these traits is to detail the genetic architecture of variation both within and between species, a program of research that is considerably more tractable in a model system. Drosophila melanogaster and its sibling species, D. simulans, D. mauritiana, and D. sechellia, are morphologically distinguishable only by the shape of the posterior lobe, a male-specific elaboration of the genital arch. We extend earlier studies identifying quantitative trait loci (QTL) responsible for lobe divergence across species and report the first genetic dissection of lobe shape variation within a species. Using an advanced intercross mapping design, we identify three autosomal QTL contributing to the difference in lobe shape between a pair of D. melanogaster inbred lines. The QTL each contribute 4.6–10.7% to shape variation, and two show a significant epistatic interaction. Interestingly, these intraspecific QTL map to the same locations as interspecific lobe QTL, implying some shared genetic control of the trait within and between species. As a first step toward a mechanistic understanding of natural lobe shape variation, we find an association between our QTL data and a set of genes that show sex-biased expression in the developing genital imaginal disc (the precursor of the adult genitalia). These genes are good candidates to harbor naturally segregating polymorphisms contributing to posterior lobe shape

TranspoGene and microTranspoGene: transposed elements influence on the transcriptome of seven vertebrates and invertebrates

Transposed elements (TEs) are mobile genetic sequences. During the evolution of eukaryotes TEs were inserted into active protein-coding genes, affecting gene structure, expression and splicing patterns, and protein sequences. Genomic insertions of TEs also led to creation and expression of new functional non-coding RNAs such as micro- RNAs. We have constructed the TranspoGene database, which covers TEs located inside proteincoding genes of seven species: human, mouse, chicken, zebrafish, fruit fly, nematode and sea squirt. TEs were classified according to location within the gene: proximal promoter TEs, exonized TEs (insertion within an intron that led to exon creation), exonic TEs (insertion into an existing exon) or intronic TEs. TranspoGene contains information regarding specific type and family of the TEs, genomic and mRNA location, sequence, supporting transcript accession and alignment to the TE consensus sequence. The database also contains host gene specific data: gene name, genomic location, Swiss-Prot and RefSeq accessions, diseases associated with the gene and splicing pattern. In addition, we created microTranspoGene: a database of human, mouse, zebrafish and nematode TEderived microRNAs. The TranspoGene and micro- TranspoGene databases can be used by researchers interested in the effect of TE insertion on the eukaryotic transcriptome

IMPROVEMENT OF SPECIFIC CHOLERA PREVENTION USING IMMUNOMODULATORS

It is known that the combined use of vaccines, cytokines and various immunomodulatory drugs contributes to the development of a full-fledged immune response. This approach makes it possible to enhance the immunogenicity of modern vaccines and to direct the development of immune responses according to the humoral or cellular type, depending on the properties of the pathogen of a particular disease. The improvement of preventive drugs due to their combined use with cytokines and immunomodulators increases the intensity of immunity, increases the level of production of specific immunoglobulins, the protectivity of antigens, and also reduces the manifestation of adverse reactions leading to post-vaccination complications.Immunomodulators are already successfully used in drugs intended for the treatment and prevention of chronic herpes infections and influenza vaccines. Numerous experimental and clinical data indicate a positive effect of the use of immunomodulatory drugs in the vaccination of various viral and bacterial infections, including particularly dangerous ones.Improving the specific prevention of cholera can be achieved through immunomodulatory agents that can stimulate the formation of a local and systemic immune response.We conducted a comparative assessment of the feasibility of the combined use of the cholera bivalent chemical vaccine (the Federal Government Health Institution Antiplague Research Institute “Microbe”) and immunomodulators in order to increase the effectiveness of cholera vaccination.Since the cholera vaccine causes the activation of the humoral immune response, the production of specific immunoglobulins in the body of vaccinated experimental animals and the effect of immunomodulators on this process at different times of the post-vaccination period were evaluated.The ability of immunomodulators to increase the protective activity of the cholera vaccine was studied by infecting animals with a virulent strain of cholera one month and seven months after vaccination.It was found that immunomodulators increase the immunogenicity and protectivity of antigens that are part of the anti-cholera vaccine. The use of all immunopreparations increases the production of specific immunoglobulins in the serum of vaccinated experimental animals. It was shown that in the first month after vaccination, polyoxidonium most effectively stimulated the formation of antibodies, but lycopide contributed to a longer retention of anti-cholera immunoglobulins in the serum of vaccinated rabbits. The combined use of the vaccine and lycopide prevented the development of cholera in all animals taken in the experiment, including those vaccinated with a reduced dose. In the long-term post-vaccination period, this immunomodulator increased the protectiveness of the anti-cholera vaccine by three times. Polyoxidonium and derinate also increased the protective effect of the cholera vaccine, but were slightly inferior to lycopide. The combined use of cholera vaccine and immunomodulators, especially lycopide, can be used to improve specific cholera prevention