Olfactory receptor (OR) genes are the largest multi-gene family in the mammalian genome, with 874 in human and 1483 loci in mouse (including pseudogenes). The expansion of the OR gene repertoire has ...occurred through numerous duplication events followed by diversification, resulting in a large number of highly similar paralogous genes. These characteristics have made the annotation of the complete OR gene repertoire a complex task. Most OR genes have been predicted in silico and are typically annotated as intronless coding sequences.
Here we have developed an expert curation pipeline to analyse and annotate every OR gene in the human and mouse reference genomes. By combining evidence from structural features, evolutionary conservation and experimental data, we have unified the annotation of these gene families, and have systematically determined the protein-coding potential of each locus. We have defined the non-coding regions of many OR genes, enabling us to generate full-length transcript models. We found that 13 human and 41 mouse OR loci have coding sequences that are split across two exons. These split OR genes are conserved across mammals, and are expressed at the same level as protein-coding OR genes with an intronless coding region. Our findings challenge the long-standing and widespread notion that the coding region of a vertebrate OR gene is contained within a single exon.
This work provides the most comprehensive curation effort of the human and mouse OR gene repertoires to date. The complete annotation has been integrated into the GENCODE reference gene set, for immediate availability to the research community.
The design, construction, and commissioning of the ALICE Time-Projection Chamber (TPC) is described. It is the main device for pattern recognition, tracking, and identification of charged particles ...in the ALICE experiment at the CERN LHC. The TPC is cylindrical in shape with a volume close to 90m3 and is operated in a 0.5T solenoidal magnetic field parallel to its axis.
In this paper we describe in detail the design considerations for this detector for operation in the extreme multiplicity environment of central Pb–Pb collisions at LHC energy. The implementation of the resulting requirements into hardware (field cage, read-out chambers, electronics), infrastructure (gas and cooling system, laser-calibration system), and software led to many technical innovations which are described along with a presentation of all the major components of the detector, as currently realized. We also report on the performance achieved after completion of the first round of stand-alone calibration runs and demonstrate results close to those specified in the TPC Technical Design Report.
SorCS2 is a member of the Vps10p-domain receptor gene family receptors with critical roles in the control of neuronal viability and function. Several genetic studies have suggested SORCS2 to confer ...risk of bipolar disorder, schizophrenia and attention deficit-hyperactivity disorder. Here we report that hippocampal N-methyl-d-aspartate receptor-dependent synaptic plasticity is eliminated in SorCS2-deficient mice. This defect was traced to the ability of SorCS2 to form complexes with the neurotrophin receptor p75
, required for pro-brain-derived neurotrophic factor (BDNF) to induce long-term depression, and with the BDNF receptor tyrosine kinase TrkB to elicit long-term potentiation. Although the interaction with p75
was static, SorCS2 bound to TrkB in an activity-dependent manner to facilitate its translocation to postsynaptic densities for synaptic tagging and maintenance of synaptic potentiation. Neurons lacking SorCS2 failed to respond to BDNF by TrkB autophosphorylation, and activation of downstream signaling cascades, impacting neurite outgrowth and spine formation. Accordingly, Sorcs2
mice displayed impaired formation of long-term memory, increased risk taking and stimulus seeking behavior, enhanced susceptibility to stress and impaired prepulse inhibition. Our results identify SorCS2 as an indispensable coreceptor for p75
and TrkB in hippocampal neurons and suggest SORCS2 as the link between proBDNF/BDNF signaling and mental disorders.
Metastasis remains the leading cause of cancer mortality, and reactive oxygen species (ROS) signaling promotes the metastatic cascade. However, the molecular pathways that control ROS signaling ...relevant to metastasis are little studied. Here, we identify SIRT3, a mitochondrial deacetylase, as a regulator of cell migration via its control of ROS signaling. We find that, although mitochondria are present at the leading edge of migrating cells, SIRT3 expression is down-regulated during migration, resulting in elevated ROS levels. This SIRT3-mediated control of ROS represses Src oxidation and attenuates focal adhesion kinase (FAK) activation. SIRT3 overexpression inhibits migration and metastasis in breast cancer cells. Finally, in human breast cancers, SIRT3 expression is inversely correlated with metastatic outcome and Src/FAK signaling. Our results reveal a role for SIRT3 in cell migration, with important implications for breast cancer progression.
ABSTRACT
Intracluster light is thought to originate from stars that were ripped away from their parent galaxies by gravitational tides and galaxy interactions during the build up of the cluster. The ...stars from such interactions will accumulate over time, so semi-analytic models suggest that the abundance of intracluster stars is negligible in young proto-clusters at z∼ 2 and grows to around a quarter of the stellar mass in the oldest, most mature clusters. In contrast to these theoretical expectations, we report on the detection of intracluster light within two proto-clusters at z= 2 using deep HST images. We use the colour of the intracluster light to estimate its mass-to-light ratio in annuli around the brightest cluster galaxies (BCG), up to a radius of 100 kpc. We find that 54 ± 5 per cent and 71 ± 3 per cent of the stellar mass in these regions is located more than 10 kpc away from the BCGs in the two proto-clusters. This low concentration is similar to BCGs in lower redshift clusters, and distinct from other massive proto-cluster galaxies. This suggests that intracluster stars are already present within the core 100 kpc of proto-clusters. We compare these observations to the Hydrangea hydrodynamical galaxy cluster simulations and find that intracluster stars are predicted to be a generic feature of group-sized haloes at z= 2. These intracluster stars will gradually move further away from the BCG as the proto-cluster assembles into a cluster.
Distant powerful radio-loud active galactic nuclei (RLAGN) tend to reside in dense environments and are commonly found in protoclusters at z > 1.3. We examine whether this occurs because RLAGN are ...hosted by massive galaxies, which preferentially reside in rich environments. We compare the environments of powerful RLAGN at 1.3 < z < 3.2 from the Clusters Around Radio-Loud AGN survey to a sample of radio-quiet galaxies matched in mass and redshift. We find that the environments of RLAGN are significantly denser than those of radio-quiet galaxies, implying that not more than 50 per cent of massive galaxies in this epoch can host powerful radio-loud jets. This is not an observational selection effect as we find no evidence to suggest that it is easier to observe the radio emission when the galaxy resides in a dense environment. We therefore suggest that the dense Mpc-scale environment fosters the formation of a radio jet from an AGN. We show that the number density of potential RLAGN host galaxies is consistent with every >1014 M⊙ cluster having experienced powerful radio-loud feedback of duration ∼60 Myr during 1.3 < z < 3.2. This feedback could heat the intracluster medium to the extent of 0.5–1 keV per gas particle, which could limit the amount of gas available for further star formation in the protocluster galaxies.
ABSTRACT The South Pole Telescope has discovered 100 gravitationally lensed, high-redshift, dusty, star-forming galaxies (DSFGs). We present 0 5 resolution 870 Atacama Large Millimeter/submillimeter ...Array imaging of a sample of 47 DSFGs spanning , and construct gravitational lens models of these sources. Our visibility-based lens modeling incorporates several sources of residual interferometric calibration uncertainty, allowing us to properly account for noise in the observations. At least 70% of the sources are strongly lensed by foreground galaxies ( ), with a median magnification of , extending to . We compare the intrinsic size distribution of the strongly lensed sources to a similar number of unlensed DSFGs and find no significant differences in spite of a bias between the magnification and intrinsic source size. This may indicate that the true size distribution of DSFGs is relatively narrow. We use the source sizes to constrain the wavelength at which the dust optical depth is unity and find this wavelength to be correlated with the dust temperature. This correlation leads to discrepancies in dust mass estimates of a factor of two compared to estimates using a single value for this wavelength. We investigate the relationship between the C ii line and the far-infrared luminosity and find that the same correlation between the C ii/ ratio and found for low-redshift star-forming galaxies applies to high-redshift galaxies and extends at least two orders of magnitude higher in . This lends further credence to the claim that the compactness of the IR-emitting region is the controlling parameter in establishing the "C ii deficit."
Large vessel vasculitis (LVV) is defined as a disease mainly affecting the large arteries, with two major variants, Takayasu arteritis (TA) and giant cell arteritis (GCA). GCA often coexists with ...polymyalgia rheumatica (PMR) in the same patient, since both belong to the same disease spectrum. FDG-PET/CT is a functional imaging technique which is an established tool in oncology, and has also demonstrated a role in the field of inflammatory diseases. Functional FDG-PET combined with anatomical CT angiography, FDG-PET/CT(A), may be of synergistic value for optimal diagnosis, monitoring of disease activity, and evaluating damage progression in LVV. There are currently no guidelines regarding PET imaging acquisition for LVV and PMR, even though standardization is of the utmost importance in order to facilitate clinical studies and for daily clinical practice. This work constitutes a joint procedural recommendation on FDG-PET/CT(A) imaging in large vessel vasculitis (LVV) and PMR from the Cardiovascular and Inflammation & Infection Committees of the European Association of Nuclear Medicine (EANM), the Cardiovascular Council of the Society of Nuclear Medicine and Molecular Imaging (SNMMI), and the PET Interest Group (PIG), and endorsed by the American Society of Nuclear Cardiology (ASNC). The aim of this joint paper is to provide recommendations and statements, based on the available evidence in the literature and consensus of experts in the field, for patient preparation, and FDG-PET/CT(A) acquisition and interpretation for the diagnosis and follow-up of patients with suspected or diagnosed LVV and/or PMR. This position paper aims to set an internationally accepted standard for FDG-PET/CT(A) imaging and reporting of LVV and PMR.
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