Different integration site structures between L1 protein-mediated retrotransposition in cis and retrotransposition in trans

Abstract Background Long interspersed nuclear element-1 (LINE-1 or L1) is a dominant repetitive sequence in the human genome. Besides mediating its own retrotransposition, L1 can mobilize Alu and messenger RNA (mRNA) in trans, and probably also SVA and non-coding RNA. The structures of L1 copies and trans-mobilized retrocopies are variable and can be classified into three categories: full-length; 5'-truncated; and 5'-inverted insertions. These structures may be generated by different 5' integration mechanisms. Results In this study, a method to correctly characterize insertions with short target site duplications (TSDs) is developed and extranucleotides, TSDs and microhomologies (MHs) at junctions were analysed for the three types of insertions. Only 5'-truncated L1 insertions were found to be associated with short TSDs. Both full-length and 5'-truncated retrotransposed sequences in trans, including Alu, SVA and mRNA retrocopies and also full-length and 5'-inverted L1, were not associated with short TSDs, indicating the difference of 5' attachment between retrotransposition in cis and retrotransposition in trans. Target sequence analysis suggested that short TSDs were generated in an L1 endonuclease-dependent manner. The MHs were longer for 5'-inverted L1 than for 5'-truncated L1, indicating less dependence on annealing in 5'-truncated L1 insertions. Conclusions The results suggest that insertions flanked by short TSDs occur more often coupled with the insertion of 5'-truncated L1 than with those of other types of insertions in vivo. The method used in this study can be used to characterize elements without any apparent boundary structures.</p

Crypton transposons: identification of new diverse families and ancient domestication events

<p>Abstract</p> <p>Background</p> <p>"Domestication" of transposable elements (TEs) led to evolutionary breakthroughs such as the origin of telomerase and the vertebrate adaptive immune system. These breakthroughs were accomplished by the adaptation of molecular functions essential for TEs, such as reverse transcription, DNA cutting and ligation or DNA binding. <it>Cryptons </it>represent a unique class of DNA transposons using tyrosine recombinase (YR) to cut and rejoin the recombining DNA molecules. <it>Cryptons </it>were originally identified in fungi and later in the sea anemone, sea urchin and insects.</p> <p>Results</p> <p>Herein we report new <it>Cryptons </it>from animals, fungi, oomycetes and diatom, as well as widely conserved genes derived from ancient <it>Crypton </it>domestication events. Phylogenetic analysis based on the YR sequences supports four deep divisions of <it>Crypton </it>elements. We found that the domain of unknown function 3504 (DUF3504) in eukaryotes is derived from <it>Crypton </it>YR. DUF3504 is similar to YR but lacks most of the residues of the catalytic tetrad (R-H-R-Y). Genes containing the DUF3504 domain are potassium channel tetramerization domain containing 1 (<it>KCTD1</it>), <it>KIAA1958</it>, zinc finger MYM type 2 (<it>ZMYM2</it>), <it>ZMYM3</it>, <it>ZMYM4</it>, glutamine-rich protein 1 (<it>QRICH1</it>) and "without children" (<it>WOC</it>). The <it>DUF3504 </it>genes are highly conserved and are found in almost all jawed vertebrates. The sequence, domain structure, intron positions and synteny blocks support the view that <it>ZMYM2</it>, <it>ZMYM3</it>, <it>ZMYM4</it>, and possibly <it>QRICH1</it>, were derived from <it>WOC </it>through two rounds of genome duplication in early vertebrate evolution. <it>WOC </it>is observed widely among bilaterians. There could be four independent events of <it>Crypton </it>domestication, and one of them, generating <it>WOC</it>/<it>ZMYM</it>, predated the birth of bilaterian animals. This is the third-oldest domestication event known to date, following the domestication generating telomerase reverse transcriptase (<it>TERT</it>) and <it>Prp8</it>. Many <it>Crypton</it>-derived genes are transcriptional regulators with additional DNA-binding domains, and the acquisition of the DUF3504 domain could have added new regulatory pathways via protein-DNA or protein-protein interactions.</p> <p>Conclusions</p> <p><it>Cryptons </it>have contributed to animal evolution through domestication of their YR sequences. The DUF3504 domains are domesticated YRs of animal <it>Crypton </it>elements.</p

Families of transposable elements, population structure and the origin of species

<p>Abstract</p> <p>Background</p> <p>Eukaryotic genomes harbor diverse families of repetitive DNA derived from transposable elements (TEs) that are able to replicate and insert into genomic DNA. The biological role of TEs remains unclear, although they have profound mutagenic impact on eukaryotic genomes and the origin of repetitive families often correlates with speciation events. We present a new hypothesis to explain the observed correlations based on classical concepts of population genetics.</p> <p>Presentation of the hypothesis</p> <p>The main thesis presented in this paper is that the TE-derived repetitive families originate primarily by genetic drift in small populations derived mostly by subdivisions of large populations into subpopulations. We outline the potential impact of the emerging repetitive families on genetic diversification of different subpopulations, and discuss implications of such diversification for the origin of new species.</p> <p>Testing the hypothesis</p> <p>Several testable predictions of the hypothesis are examined. First, we focus on the prediction that the number of diverse families of TEs fixed in a representative genome of a particular species positively correlates with the cumulative number of subpopulations (demes) in the historical metapopulation from which the species has emerged. Furthermore, we present evidence indicating that human AluYa5 and AluYb8 families might have originated in separate proto-human subpopulations. We also revisit prior evidence linking the origin of repetitive families to mammalian phylogeny and present additional evidence linking repetitive families to speciation based on mammalian taxonomy. Finally, we discuss evidence that mammalian orders represented by the largest numbers of species may be subject to relatively recent population subdivisions and speciation events.</p> <p>Implications of the hypothesis</p> <p>The hypothesis implies that subdivision of a population into small subpopulations is the major step in the origin of new families of TEs as well as of new species. The origin of new subpopulations is likely to be driven by the availability of new biological niches, consistent with the hypothesis of punctuated equilibria. The hypothesis also has implications for the ongoing debate on the role of genetic drift in genome evolution.</p> <p>Reviewers</p> <p>This article was reviewed by Eugene Koonin, Juergen Brosius and I. King Jordan.</p

SILVERRUSH. VII. Subaru/HSC Identifications of 42 Protocluster Candidates at z~6-7 with the Spectroscopic Redshifts up to z=6.574: Implications for Cosmic Reionization

We report fourteen and twenty-eight protocluster candidates at z=5.7 and 6.6 over 14 and 19 deg^2 areas, respectively, selected from 2,230 (259) Lya emitters (LAEs) photometrically (spectroscopically) identified with Subaru/Hyper Suprime-Cam (HSC) deep images (Keck, Subaru, and Magellan spectra and the literature data). Six out of the 42 protocluster candidates include 1-12 spectroscopically confirmed LAEs at redshifts up to z=6.574. By the comparisons with the cosmological Lya radiative transfer (RT) model reproducing LAEs with the reionization effects, we find that more than a half of these protocluster candidates are progenitors of the present-day clusters with a mass of > 10^14 M_sun. We then investigate the correlation between LAE overdensity delta and Lya rest-frame equivalent width EW_Lya^rest, because the cosmological Lya RT model suggests that a slope of EW_Lya^rest-delta relation is steepened towards the epoch of cosmic reionization (EoR), due to the existence of the ionized bubbles around galaxy overdensities easing the escape of Lya emission from the partly neutral intergalactic medium (IGM). The available HSC data suggest that the slope of the EW_Lya^rest-delta correlation does not evolve from the post-reionization epoch z=5.7 to the EoR z=6.6 beyond the moderately large statistical errors. There is a possibility that we would detect the evolution of the EW_Lya^rest - delta relation from z=5.7 to 7.3 by the upcoming HSC observations providing large samples of LAEs at z=6.6-7.3

Detection of Progeny Immune Responses after Intravenous Administration of DNA Vaccine to Pregnant Mice

A number of factors influence the development of tolerance, including the nature, concentration and mode of antigen presentation to the immune system, as well as the age of the host. The studies were conducted to determine whether immunizing pregnant mice with liposome-encapsulated DNA vaccines had an effect on the immune status of their offspring. Two different plasmids (encoding antigens from HIV-1 and influenza virus) were administered intravenously to pregnant mice. At 9.5 days post conception with cationic liposomes, injected plasmid was present in the tissues of the fetus, consistent with trans-placental transfer. When the offspring of vaccinated dams were immunized with DNA vaccine, they mounted stronger antigen-specific immune responses than controls and were protected against challenge by homologous influenza virus after vaccination. Moreover, such immune responses were strong in the offspring of mothers injected with DNA plasmid 9.5 days after coitus. These results suggest that DNA vaccinated mothers confer the antigen-specific immunity to their progeny. Here we describe the methods in detail as they relate to our previously published work

NGCPV: a new generation of concentrator photovoltaic cells, modules and systems

Starting on June 2011, NGCPV is the first project funded jointly between the European Commission (EC) and the New Energy and Industrial Technology Development Organization (NEDO) of Japan to research on new generation concentration photovoltaics (CPV). The Project, through a collaborative research between seven European and nine Japanese leading research centers in the field of CPV, aims at lowering the cost of the CPVproduced photovoltaic kWh down to 5 ?cents. The main objective of the project is to improve the present concentrator cell, module and system efficiency, as well as developing advanced characterization tools for CPV components and systems. As particular targets, the project aims at achieving a cell efficiency of at least 45% and a CPV module with an efficiency greater than 35%. This paper describes the R&D activities that are being carried out within the NGCPV project and summarizes some of the most relevant results that have already been attained, for instance: the manufacturing of a 44.4% world record efficiency triple junction solar cell (by Sharp Corp.) and the installation of a 50 kWp experimental CPV plant in Spain, which will be used to obtain accurate forecasts of the energy produced at system level

Ghrelin Treatment of Cachectic Patients with Chronic Obstructive Pulmonary Disease: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

BACKGROUND: Pulmonary cachexia is common in advanced chronic obstructive pulmonary disease (COPD), culminating in exercise intolerance and a poor prognosis. Ghrelin is a novel growth hormone (GH)-releasing peptide with GH-independent effects. The efficacy and safety of adding ghrelin to pulmonary rehabilitation (PR) in cachectic COPD patients were investigated. METHODOLOGY/PRINCIPAL FINDINGS: In a multicenter, randomized, double-blind, placebo-controlled trial, 33 cachectic COPD patients were randomly assigned PR with intravenous ghrelin (2 µg/kg) or placebo twice daily for 3 weeks in hospital. The primary outcomes were changes in 6-min walk distance (6-MWD) and the St. George Respiratory Questionnaire (SGRQ) score. Secondary outcomes included changes in the Medical Research Council (MRC) scale, and respiratory muscle strength. At pre-treatment, serum GH levels were increased from baseline levels by a single dose of ghrelin (mean change, +46.5 ng/ml; between-group p<0.0001), the effect of which continued during the 3-week treatment. In the ghrelin group, the mean change from pre-treatment in 6-MWD was improved at Week 3 (+40 m, within-group p = 0.033) and was maintained at Week 7 (+47 m, within-group p = 0.017), although the difference between ghrelin and placebo was not significant. At Week 7, the mean changes in SGRQ symptoms (between-group p = 0.026), in MRC (between-group p = 0.030), and in maximal expiratory pressure (MEP; between-group p = 0.015) were better in the ghrelin group than in the placebo group. Additionally, repeated-measures analysis of variance (ANOVA) indicated significant time course effects of ghrelin versus placebo in SGRQ symptoms (p = 0.049) and MEP (p = 0.021). Ghrelin treatment was well tolerated. CONCLUSIONS/SIGNIFICANCE: In cachectic COPD patients, with the safety profile, ghrelin administration provided improvements in symptoms and respiratory strength, despite the lack of a significant between-group difference in 6-MWD. TRIAL REGISTRATION: UMIN Clinical Trial Registry C000000061

Stable Operation of a 300-m Laser Interferometer with Sufficient Sensitivity to Detect Gravitational-Wave Events within our Galaxy

TAMA300, an interferometric gravitational-wave detector with 300-m baseline length, has been developed and operated with sufficient sensitivity to detect gravitational-wave events within our galaxy and sufficient stability for observations; the interferometer was operated for over 10 hours stably and continuously. With a strain-equivalent noise level of $h\sim 5 \times 10^{-21} /\sqrt{\rm Hz}$, a signal-to-noise ratio (SNR) of 30 is expected for gravitational waves generated by a coalescence of 1.4 $M_\odot$-1.4 $M_\odot$ binary neutron stars at 10 kpc distance. %In addition, almost all noise sources which limit the sensitivity and which %disturb the stable operation have been identified. We evaluated the stability of the detector sensitivity with a 2-week data-taking run, collecting 160 hours of data to be analyzed in the search for gravitational waves.Comment: 5 pages, 4 figure

Lifespan-Extending Effects of Royal Jelly and Its Related Substances on the Nematode Caenorhabditis elegans

One of the most important challenges in the study of aging is to discover compounds with longevity-promoting activities and to unravel their underlying mechanisms. Royal jelly (RJ) has been reported to possess diverse beneficial properties. Furthermore, protease-treated RJ (pRJ) has additional pharmacological activities. Exactly how RJ and pRJ exert these effects and which of their components are responsible for these effects are largely unknown. The evolutionarily conserved mechanisms that control longevity have been indicated. The purpose of the present study was to determine whether RJ and its related substances exert a lifespan-extending function in the nematode Caenorhabditis elegans and to gain insights into the active agents in RJ and their mechanism of action.We found that both RJ and pRJ extended the lifespan of C. elegans. The lifespan-extending activity of pRJ was enhanced by Octadecyl-silica column chromatography (pRJ-Fraction 5). pRJ-Fr.5 increased the animals' lifespan in part by acting through the FOXO transcription factor DAF-16, the activation of which is known to promote longevity in C. elegans by reducing insulin/IGF-1 signaling (IIS). pRJ-Fr.5 reduced the expression of ins-9, one of the insulin-like peptide genes. Moreover, pRJ-Fr.5 and reduced IIS shared some common features in terms of their effects on gene expression, such as the up-regulation of dod-3 and the down-regulation of dod-19, dao-4 and fkb-4. 10-Hydroxy-2-decenoic acid (10-HDA), which was present at high concentrations in pRJ-Fr.5, increased lifespan independently of DAF-16 activity.These results demonstrate that RJ and its related substances extend lifespan in C. elegans, suggesting that RJ may contain longevity-promoting factors. Further analysis and characterization of the lifespan-extending agents in RJ and pRJ may broaden our understanding of the gene network involved in longevity regulation in diverse species and may lead to the development of nutraceutical interventions in the aging process