Identification of a gonadotropin-releasing hormone receptor orthologue in Caenorhabditis elegans

BACKGROUND: The Caenorhabditis elegans genome is known to code for at least 1149 G protein-coupled receptors (GPCRs), but the GPCR(s) critical to the regulation of reproduction in this nematode are not yet known. This study examined whether GPCRs orthologous to human gonadotropin-releasing hormone receptor (GnRHR) exist in C. elegans. RESULTS: Our sequence analyses indicated the presence of two proteins in C. elegans, one of 401 amino acids [GenBank: NP_491453; WormBase: F54D7.3] and another of 379 amino acids [GenBank: NP_506566; WormBase: C15H11.2] with 46.9% and 44.7% nucleotide similarity to human GnRHR1 and GnRHR2, respectively. Like human GnRHR1, structural analysis of the C. elegans GnRHR1 orthologue (Ce-GnRHR) predicted a rhodopsin family member with 7 transmembrane domains, G protein coupling sites and phosphorylation sites for protein kinase C. Of the functionally important amino acids in human GnRHR1, 56% were conserved in the C. elegans orthologue. Ce-GnRHR was actively transcribed in adult worms and immunoanalyses using antibodies generated against both human and C. elegans GnRHR indicated the presence of a 46-kDa protein, the calculated molecular mass of the immature Ce-GnRHR. Ce-GnRHR staining was specifically localized to the germline, intestine and pharynx. In the germline and intestine, Ce-GnRHR was localized specifically to nuclei as revealed by colocalization with a DNA nuclear stain. However in the pharynx, Ce-GnRHR was localized to the myofilament lattice of the pharyngeal musculature, suggesting a functional role for Ce-GnRHR signaling in the coupling of food intake with reproduction. Phylogenetic analyses support an early evolutionary origin of GnRH-like receptors, as evidenced by the hypothesized grouping of Ce-GnRHR, vertebrate GnRHRs, a molluscan GnRHR, and the adipokinetic hormone receptors (AKHRs) and corazonin receptors of arthropods. CONCLUSION: This is the first report of a GnRHR orthologue in C. elegans, which shares significant similarity with insect AKHRs. In vertebrates, GnRHRs are central components of the reproductive endocrine system, and the identification of a GnRHR orthologue in C. elegans suggests the potential use of C. elegans as a model system to study reproductive endocrinology

The gas density around SN 1006

The density of the ambient medium where the supernova remnant evolves is a relevant parameter for its hydrodynamical evolution, for the mechanism of particle acceleration, and for the emission at TeV energies. Using XMM-Newton X-ray observations, we present a study of the ambient medium density of the historical supernova remnant SN 1006. We modelled the post-shock thermal emission to constrain the ambient medium density. Our study is focused on the North-West and the South-East rims of the remnant, where the thermal emission dominates. We used a plane-parallel shock plasma model plus another component for the ejecta that are not negligible in the regions of our study. The importance of the synchrotron component is also studied. In order to improve statistics, we combined several observations of the remnant. The density found in the South-East rim is low, roughly 0.05 cm-3, and seems to be representative of the rest of the remnant. However, in the North-West rim (close to the bright optical filament), the density is significantly higher (about 0.15-0.25 cm-3). This confirms a picture of SN 1006 evolving in a tenuous ambient medium, except in the North-West where the remnant has recently encountered a denser region. A density this low is compatible with the non-detection of the remnant by the HESS gamma-ray observatory. The lower density in the South-East implies a higher shock speed of 4900 km/s, higher than that of 2890 km/s measured in the North-West. This new estimate of the velocity could increase the maximum energy that accelerated particles can reach to energies of about 1 PeV.Comment: 8 pages, 4 figures, accepted for publication in A&A, Figure 3 correcte

Low-energy electron holographic imaging of individual tobacco mosaic virions

Modern structural biology relies on NMR, X-ray crystallography and cryo-electron microscopy for gaining information on biomolecules at nanometer, sub-nanometer or atomic resolution. All these methods, however, require averaging over a vast ensemble of entities and hence knowledge on the conformational landscape of an individual particle is lost. Unfortunately, there are now strong indications that even X-ray free electron lasers will not be able to image individual molecules but will require nanocrystal samples. Here, we show that non-destructive structural biology of single particles has now become possible by means of low-energy electron holography. As an example, individual tobacco mosaic virions deposited on ultraclean freestanding graphene are imaged at one nanometer resolution revealing structural details arising from the helical arrangement of the outer protein shell of the virus. Since low-energy electron holography is a lens-less technique and since electrons with a deBroglie wavelength of approximately 1 Angstrom do not impose radiation damage to biomolecules, the method has the potential for Angstrom resolution imaging of single biomolecules

Insights into the role of DNA methylation in diatoms by genome-wide profiling in Phaeodactylum tricornutum

DNA cytosine methylation is a widely conserved epigenetic mark in eukaryotes that appears to have critical roles in the regulation of genome structure and transcription. Genome-wide methylation maps have so far only been established from the supergroups Archaeplastida and Unikont. Here we report the first whole-genome methylome from a stramenopile, the marine model diatom Phaeodactylum tricornutum. Around 6% of the genome is intermittently methylated in a mosaic pattern. We find extensive methylation in transposable elements. We also detect methylation in over 320 genes. Extensive gene methylation correlates strongly with transcriptional silencing and differential expression under specific conditions. By contrast, we find that genes with partial methylation tend to be constitutively expressed. These patterns contrast with those found previously in other eukaryotes. By going beyond plants, animals and fungi, this stramenopile methylome adds significantly to our understanding of the evolution of DNA methylation in eukaryotes.Fil: Veluchamy, Alaguraj. Institut de Biologie de l'École Normale Supérieure; FranciaFil: Lin, Xin. Institut de Biologie de l'École Normale Supérieure; Francia. Xiamen University; ChinaFil: Maumus, Florian.Fil: Rivarola, Maximo Lisandro.Fil: Bhavsar, Jaysheel.Fil: Creasy, Todd.Fil: O'Brien, Kimberly.Fil: Sengamalay, Naomi A..Fil: Tallon, Luke J..Fil: Smith, Andrew D..Fil: Rayko, Edda.Fil: Ahmed, Ikhlak.Fil: Crom, Stéphane Le.Fil: Farrant, Gregory K..Fil: Sgro, Jean-Yves.Fil: Olson, Sue A..Fil: Bondurant, Sandra Splinter.Fil: Allen, Andrew.Fil: Rabinowicz, Pablo D..Fil: Sussman, Michael R..Fil: Bowler, Chris.Fil: Tirichine, Leïla

Energy, unemployment and trade

© 2018 Informa UK Limited, trading as Taylor & Francis Group. This article investigates the dynamic relationships among sectoral economic activities, macro expenditure patterns, renewable and non-renewable energy consumption and unemployment in 41 countries from 1980 to 2014. The state of the art econometric techniques, both linear and non-linear panel and time series estimation techniques are used. The results show that industrialization, services sector, government expenditure and trade openness play a positive role in reducing unemployment, while agriculture and renewable energy consumption increase unemployment. This might be, in part, due to recent technological advancements and large capital intensive investments in agriculture and renewable energy sectors. Therefore, dedicated social and labour market policies need to be adopted to complement greening economic policies

Waking up dormant tumor suppressor genes with zinc fingers, TALEs and the CRISPR/dCas9 system

The aberrant epigenetic silencing of tumor suppressor genes (TSGs) plays a major role during carcinogenesis and regaining these dormant functions by engineering of sequence-specific epigenome editing tools offers a unique opportunity for targeted therapies. However, effectively normalizing the expression and regaining tumor suppressive functions of silenced TSGs by artificial transcription factors (ATFs) still remains a major challenge. Herein we describe novel combinatorial strategies for the potent reactivation of two class II TSGs, MASPIN and REPRIMO, in cell lines with varying epigenetic states, using the CRISPR/dCas9 associated system linked to a panel of effector domains (VP64, p300, VPR and SAM complex), as well as with protein-based ATFs, Zinc Fingers and TALEs. We found that co-delivery of multiple effector domains using a combination of CRISPR/dCas9 and TALEs or SAM complex maximized activation in highly methylated promoters. In particular, CRISPR/dCas9 VPR with SAM upregulated MASPIN mRNA (22,145-fold change) in H157 lung cancer cells, with accompanying re-expression of MASPIN protein, which led to a concomitant inhibition of cell proliferation and induction of apoptotic cell death. Consistently, CRISPR/dCas9 VP64 with SAM upregulated REPRIMO (680-fold change), which led to phenotypic reprogramming in AGS gastric cancer cells. Altogether, our results outlined novel sequence-specific, combinatorial epigenome editing approaches to reactivate highly methylated TSGs as a promising therapy for cancer and other diseases

On possible interpretations of the high energy electron-positron spectrum measured by the Fermi Large Area Telescope

The Fermi-LAT experiment recently reported high precision measurements of the spectrum of cosmic-ray electrons-plus-positrons (CRE) between 20 GeV and 1 TeV. The spectrum shows no prominent spectral features, and is significantly harder than that inferred from several previous experiments. Here we discuss several interpretations of the Fermi results based either on a single large scale Galactic CRE component or by invoking additional electron-positron primary sources, e.g. nearby pulsars or particle Dark Matter annihilation. We show that while the reported Fermi-LAT data alone can be interpreted in terms of a single component scenario, when combined with other complementary experimental results, specifically the CRE spectrum measured by H.E.S.S. and especially the positron fraction reported by PAMELA between 1 and 100 GeV, that class of models fails to provide a consistent interpretation. Rather, we find that several combinations of parameters, involving both the pulsar and dark matter scenarios, allow a consistent description of those results. We also briefly discuss the possibility of discriminating between the pulsar and dark matter interpretations by looking for a possible anisotropy in the CRE flux.Comment: 29 pages, 12 figures. Final version accepted for publication in Astroparticle Physic