Revisiting the evolution of mouse LINE-1 in the genomic era

Background LINE-1 (L1) is the dominant category of transposable elements in placental mammals. L1 has significantly affected the size and structure of all mammalian genomes and understanding the nature of the interactions between L1 and its mammalian host remains a question of crucial importance in comparative genomics. For this reason, much attention has been dedicated to the evolution of L1. Among the most studied elements is the mouse L1 which has been the subject of a number of studies in the 1980s and 1990s. These seminal studies, performed in the pre-genomic era when only a limited number of L1 sequences were available, have significantly improved our understanding of L1 evolution. Yet, no comprehensive study on the evolution of L1 in mouse has been performed since the completion of this genome sequence. Results Using the Genome Parsing Suite we performed the first evolutionary analysis of mouse L1 over the entire length of the element. This analysis indicates that the mouse L1 has recruited novel 5’UTR sequences more frequently than previously thought and that the simultaneous activity of non-homologous promoters seems to be one of the conditions for the co-existence of multiple L1 families or lineages. In addition the exchange of genetic information between L1 families is not limited to the 5’UTR as evidence of inter-family recombination was observed in ORF1, ORF2, and the 3’UTR. In contrast to the human L1, there was little evidence of rapid amino-acid replacement in the coiled-coil of ORF1, although this region is structurally unstable. We propose that the structural instability of the coiled-coil domain might be adaptive and that structural changes in this region are selectively equivalent to the rapid evolution at the amino-acid level reported in the human lineage. Conclusions The pattern of evolution of L1 in mouse shows some similarity with human suggesting that the nature of the interactions between L1 and its host might be similar in these two species. Yet, some notable differences, particularly in the evolution of ORF1, suggest that the molecular mechanisms involved in host-L1 interactions might be different in these two species

Development of a real-time PCR assay for the specific detection and identification of Streptococcus pseudopneumoniae using the recA gene

AbstractWe sequenced the evolutionarily conserved genes 16S rRNA, atpD, tuf, and recA from Streptococcus pseudopneumoniae, Streptococcus pneumoniae, Streptococcus mitis, and Streptococcus oralis. Phylogenetic analysis revealed that recA provided good resolution between these species, including discrimination of the novel species S. pseudopneumoniae. By contrast, the more conserved 16S rRNA, tuf and atpD are not sufficiently discriminatory. Therefore, recA sequences were used to develop a real-time PCR assay with a locked nucleic acid-mediated TaqMan probe for the specific detection and identification of S. pseudopneumoniae. The PCR assay showed excellent specificity and a detection limit of <10 genome copies for the detection and identification of S. pseudopneumoniae strains, which makes it a promising tool for molecular identification and epidemiological studies. In conclusion, this article describes for the first time a PCR assay for the specific identification of S. pseudopneumoniae

Cytokines as biomarkers in rheumatoid arthritis

RA is a complex disease that develops as a series of events often referred to as disease continuum. RA would benefit from novel biomarker development for diagnosis where new biomarkers are still needed (even if progresses have been made with the inclusion of ACPA into the ACR/EULAR 2010 diagnostic criteria) and for prognostic notably in at risk of evolution patients with autoantibody-positive arthralgia. Risk biomarkers for rapid evolution or cardiovascular complications are also highly desirable. Monitoring biomarkers would be useful in predicting relapse. Finally, predictive biomarkers for therapy outcome would allow tailoring therapy to the individual. Increasing numbers of cytokines have been involved in RA pathology. Many have the potential as biomarkers in RA especially as their clinical utility is already established in other diseases and could be easily transferable to rheumatology. We will review the current knowledge’s relation to cytokine used as biomarker in RA. However, given the complexity and heterogeneous nature of RA, it is unlikely that a single cytokine may provide sufficient discrimination; therefore multiple biomarker signatures may represent more realistic approach for the future of personalised medicine in RA

Crossing the Rift valley: using complete mitogenomes to infer the diversification and biogeographic history of ethiopian highlands Ptychadena (anura: Ptychadenidae)

The Ethiopian Highlands are considered a biodiversity hotspot, harboring a high number of endemic species. Some of the endemic species probably diversified in situ; this is, for example, the case of a monophyletic clade containing 12 known species of grass frogs of the genus Ptychadena. The different species occur at elevations ranging from 1,500 to above 3,400 m and constitute excellent models to study the process of diversification in the highlands as well as adaptations to high elevations. In this study, we sampled 294 specimens across the distribution of this clade and used complete mitogenomes and genome-wide SNP data to better understand how landscape features influenced the population structure and dispersal of these grass frogs across time and space. Using phylogenetic inference, population structure analyses, and biogeographic reconstructions, we found that the species complex probably first diversified on the south-east side of the Great Rift Valley. Later on, species dispersed to the north-west side, where more recent diversification occurred. We further demonstrate that Ptychadena species have dispersed across the Great Rift Valley at different times. Our analyses allowed for a more complete understanding of the contribution of geological events, biogeographic barriers and climatic changes as drivers of species diversification and adaptation in this important biogeographic region

Toward Automatic Label-Free Whispering Gallery Modes Biodetection with a Quantum Dot-Coated Microsphere Population

We explore a new calibration-free approach to biodetection based on whispering gallery modes (WGMs) without a reference measure and relative shifts. Thus, the requirement to keep track of the sensor position is removed, and a freely moving population of fluorophore-doped polystyrene microspheres can now fulfill this role of sensing resonator. Breaking free from fixed surface-based biosensing promotes adhesion between the microsphere sensors and the analytes since both can now be thoroughly mixed. The 70-nm-wide spectrum of green fluorescent microbeads allows us to monitor over 20 WGMs simultaneously without needing evanescent light coupling into the microspheres, hence enabling remote sensing. Since the exact radius of each microsphere is unknown a priori, it requires algorithmic analyses to obtain a reliable result for the refractive index of a solution. We first test our approach with different solutions of alcohol in water obtaining 3 × 10−4 precision on the refractive index at lower concentrations. Then, the solutions of bacterial spores in water yield clear evidence of biodetection in the statistical analysis of WGMs from 50 microspheres. To extend the fluorescence spectral range of our WGM sensors, we present preliminary results on coating microspheres with CdSe/ZnS quantum dots

First spectroscopy of 66^{66}Se and 65^{65}As: Investigating shape coexistence beyond the N = Z line

The experiment was performed at the National Superconducting Cyclotron Laboratory (NSCL), at Michigan State University (USA).We report on the first γ spectroscopy of 66Se and 65As from two-neutron removal at intermediate beam energies. The deduced excitation energies for the first-excited states in 66Se and 65As are compared to mean-field-based predictions within a collective Hamiltonian formalism using the Gogny D1S effective interaction and to state-of-the-art shell-model calculations restricted to the pf5/2 g9/2 valence space. The obtained Coulomb-energy differences for the first excited states in 66Se and 65As are discussed within the shell-model formalism to assess the shape-coexistence picture for both nuclei. Our results support a favored oblate ground-state deformation in 66Se and 65As. A shape transition for the ground state of even-odd As isotopes from oblate in 65As to prolate in 67,69,71As is suggested

Autoantibodies to posttranslational modifications in rheumatoid arthritis

Autoantibodies have been associated with human pathologies for a long time, particularly with autoimmune diseases (AIDs). Rheumatoid factor (RF) is known since the late 1930s to be associated with rheumatoid arthritis (RA). The discovery of anticitrullinated protein antibodies in the last century has changed this and other posttranslational modifications (PTM) relevant to RA have since been described. Such PTM introduce neoepitopes in proteins that can generate novel autoantibody specificities. The recent recognition of these novel specificities in RA provides a unique opportunity to understand human B-cell development in vivo. In this paper, we will review the three of the main classes of PTMs already associated with RA: citrullination, carbamylation, and oxidation. With the advancement of research methodologies it should be expected that other autoantibodies against PTM proteins could be discovered in patients with autoimmune diseases. Many of such autoantibodies may provide significant biomarker potential

Intermediate-energy Coulomb excitation of 104 Sn: Moderate E2 strength decrease approaching 100 Sn

International audienceThe reduced transition probability B(E2)↑ of the first excited 2 + state in the nucleus 104 Sn was measured via Coulomb excitation in inverse kinematics at intermediate energies. A value of 0.173(28) e 2 b 2 was extracted from the absolute cross section on a Pb target. Feeding contributions in 104 Sn from higher lying states were estimated by a reference measurement of the stable 112 Sn. Corresponding only to a moderate decrease of excitation strength relative to the almost constant values observed in the proton-rich, even-A 106−114 Sn isotopes, present state-of-the-art shell-model predictions, which include proton and neutron excitations across the N = Z = 50 shell closures as well as standard polarization charges, underestimate the experimental findings

Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma