A wide field-of-view low-resolution spectrometer at APEX: Instrument design and scientific forecast

Context. Characterising the large-scale structure in the Universe from present times to the high redshift epoch of reionisation is essential to constraining the cosmology, the history of star formation, and reionisation, to measuring the gas content of the Universe, and to obtaining a better understanding of the physical processes that drive galaxy formation and evolution. Using the integrated emission from unresolved galaxies or gas clouds, line intensity mapping (LIM) provides a new observational window to measure the larger properties of structures. This very promising technique motivates the community to plan for LIM experiments. Aims. We describe the development of a large field-of-view instrument, named CONCERTO (for CarbON CII line in post-rEionisation and ReionisaTiOn epoch), operating in the range 130-310 GHz from the APEX 12-m telescope (5100 m above sea level). CONCERTO is a low-resolution spectrometer based on the lumped element kinetic inductance detectors (LEKID) technology. Spectra are obtained using a fast Fourier transform spectrometer (FTS), coupled to a dilution cryostat with a base temperature of 0.1 K. Two two kilo-pixel arrays of LEKID are mounted inside the cryostat that also contains the cold optics and the front-end electronics. Methods. We present, in detail, the technological choices leading to the instrumental concept, together with the design and fabrication of the instrument and preliminary laboratory tests on the detectors. We also give our best estimates for CONCERTO sensitivity and give predictions for two of the main scientific goals of CONCERTO, that is, a [CII]-intensity mapping survey and observations of galaxy clusters. Results. We provide a detailed description of the instrument design. Based on realistic comparisons with existing instruments developed by our group (NIKA, NIKA2, and KISS), and on the laboratory characterisation of our detectors, we provide an estimate for CONCERTO sensitivity on the sky. Finally, we describe, in detail, two of the main scientific goals offered by CONCERTO at APEX

Translation of the FMR1 mRNA is not influenced by AGG interruptions

The fragile X mental retardation 1 (FMR1) gene contains a CGG-repeat element within its 5′ untranslated region (5′UTR) which, for alleles with more than ∼40 repeats, increasingly affects both transcription (up-regulation) and translation (inhibition) of the repeat-containing RNA with increasing CGG-repeat length. Translational inhibition is thought to be due to impaired ribosomal scanning through the CGG-repeat region, which is postulated to form highly stable secondary/tertiary structure. One striking difference between alleles in the premutation range (55–200 CGG repeats) and those in the normal range (<∼40 repeats) is the reduced number/absence of ‘expansion stabilizing’ AGG interruptions in the larger alleles. Such interruptions, which generally occur every 9–11 repeats in normal alleles, are thought to disrupt the extended CGG-repeat hairpin structure, thus facilitating translational initiation. To test this hypothesis, we have measured the translational efficiency of CGG-repeat mRNAs with 0–2 AGG interruptions, both in vitro (rabbit reticulocyte lysates) and in cell culture (HEK-293 cells). We demonstrate that the AGG interruptions have no detectable influence on translational efficiency in either a cell-free system or cell culture, indicating that any AGG-repeat-induced alterations in secondary/tertiary structure, if present, do not involve the rate-limiting step(s) in translational initiation

DOR/Tp53inp2 and Tp53inp1 Constitute a Metazoan Gene Family Encoding Dual Regulators of Autophagy and Transcription

Human DOR/TP53INP2 displays a unique bifunctional role as a modulator of autophagy and gene transcription. However, the domains or regions of DOR that participate in those functions have not been identified. Here we have performed structure/function analyses of DOR guided by identification of conserved regions in the DOR gene family by phylogenetic reconstructions. We show that DOR is present in metazoan species. Invertebrates harbor only one gene, DOR/Tp53inp2, and in the common ancestor of vertebrates Tp53inp1 may have arisen by gene duplication. In keeping with these data, we show that human TP53INP1 regulates autophagy and that different DOR/TP53INP2 and TP53INP1 proteins display transcriptional activity. The use of molecular evolutionary information has been instrumental to determine the regions that participate in DOR functions. DOR and TP53INP1 proteins share two highly conserved regions (region 1, aa residues 28–42; region 2, 66–112 in human DOR). Mutation of conserved hydrophobic residues in region 1 of DOR (that are part of a nuclear export signal, NES) reduces transcriptional activity, and blocks nuclear exit and autophagic activity under autophagy-activated conditions. We also identify a functional and conserved LC3-interacting motif (LIR) in region 1 of DOR and TP53INP1 proteins. Mutation of conserved acidic residues in region 2 of DOR reduces transcriptional activity, impairs nuclear exit in response to autophagy activation, and disrupts autophagy. Taken together, our data reveal DOR and TP53INP1 as dual regulators of transcription and autophagy, and identify two conserved regions in the DOR family that concentrate multiple functions crucial for autophagy and transcription

Hospital emergency department utilisation rates among the immigrant population in Barcelona, Spain

<p>Abstract</p> <p>Background</p> <p>The recent increase in the number of immigrants of Barcelona represents a challenge for the public healthcare system, the emergency department being the most used healthcare service by this group. However, utilisation rates in our environment have not yet been studied. We aimed to compare emergency department utilisation rates between Spanish-born and foreign-born residents in a public hospital of Barcelona.</p> <p>Methods</p> <p>The <it>s</it>tudy population included all adults residing in the area of study and visiting the emergency department of Hospital del Mar in 2004. The emergency care episodes were selected from the Emergency Department register, and the population figures from the Statistics Department of Barcelona. Emergency care episodes were classified into five large clinical categories. Adjusted rate ratios (RR) of utilisation among foreign-born vs. Spanish-born residents were assessed through negative binomial regression.</p> <p>Results</p> <p>The overall utilisation rate was 382 emergency contacts per 1,000 persons-years. The RR for foreign-born versus Spanish-born residents was 0.62 (95% CI: 0.52; 0.74%). The RR was also significantly below one in surgery (0.51, 95% CI: 0.42; 0.63), traumatology (0.47, 95% CI: 0.38; 0.59), medicine (0.48, 95% CI: 0.38; 0.59) and psychiatry (0.42, 95% CI: 0.18; 0.97). No differences were found in utilisation of gynaecology and minor emergency services.</p> <p>Conclusion</p> <p>The overall lower utilisation rates obtained for foreign-born residents is consistent with previous studies and is probably due to the "healthy immigrant effect". Thus, the population increase due to immigration does not translate directly into a corresponding increase in the number of emergency contacts. The lack of differences in minor and gynaecological emergency care supports the hypothesis that immigrants overcome certain barriers by using the emergency department to access to health services. The issue of healthcare barriers should therefore be addressed, especially among immigrants.</p

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

Identification of Maize Genes Associated with Host Plant Resistance or Susceptibility to Aspergillus flavus Infection and Aflatoxin Accumulation

infection and aflatoxin accumulation. inoculation were compared in two resistant maize inbred lines (Mp313E and Mp04∶86) in contrast to two susceptible maize inbred lines (Va35 and B73) by microarray analysis. Principal component analysis (PCA) was used to find genes contributing to the larger variances associated with the resistant or susceptible maize inbred lines. The significance levels of gene expression were determined by using SAS and LIMMA programs. Fifty candidate genes were selected and further investigated by quantitative RT-PCR (qRT-PCR) in a time-course study on Mp313E and Va35. Sixteen of the candidate genes were found to be highly expressed in Mp313E and fifteen in Va35. Out of the 31 highly expressed genes, eight were mapped to seven previously identified quantitative trait locus (QTL) regions. A gene encoding glycine-rich RNA binding protein 2 was found to be associated with the host hypersensitivity and susceptibility in Va35. A nuclear pore complex protein YUP85-like gene was found to be involved in the host resistance in Mp313E. infection and aflatoxin accumulation. These findings will be important in identification of DNA markers for breeding maize lines resistant to aflatoxin accumulation

Interdigital cell death in the embryonic limb is associated with depletion of Reelin in the extracellular matrix

Interdigital cell death is a physiological regression process responsible for sculpturing the digits in the embryonic vertebrate limb. Changes in the intensity of this degenerative process account for the different patterns of interdigital webbing among vertebrate species. Here, we show that Reelin is present in the extracellular matrix of the interdigital mesoderm of chick and mouse embryos during the developmental stages of digit formation. Reelin is a large extracellular glycoprotein which has important functions in the developing nervous system, including neuronal survival; however, the significance of Reelin in other systems has received very little attention. We show that reelin expression becomes intensely downregulated in both the chick and mouse interdigits preceding the establishment of the areas of interdigital cell death. Furthermore, fibroblast growth factors, which are cell survival signals for the interdigital mesoderm, intensely upregulated reelin expression, while BMPs, which are proapototic signals, downregulate its expression in the interdigit. Gene silencing experiments of reelin gene or its intracellular effector Dab-1 confirmed the implication of Reelin signaling as a survival factor for the limb undifferentiated mesoderm. We found that Reelin activates canonical survival pathways in the limb mesoderm involving protein kinase B and focal adhesion kinase. Our findings support that Reelin plays a role in interdigital cell death, and suggests that anoikis (apoptosis secondary to loss of cell adhesion) may be involved in this process

Fluid Shifts

NASA is focusing on long-duration missions on the International Space Station (ISS) and future exploration-class missions beyond low-Earth orbit. Visual acuity changes observed after short-duration missions were largely transient, but more than 50% of ISS astronauts experienced more profound, chronic changes with objective structural and functional findings such as papilledema and choroidal folds. Globe flattening, optic nerve sheath dilation, and optic nerve tortuosity also are apparent. This pattern is referred to as the visual impairment and intracranial pressure (VIIP) syndrome. VIIP signs and symptoms, as well as postflight lumbar puncture data, suggest that elevated intracranial pressure (ICP) may be associated with the spaceflight-induced cephalad fluid shifts, but this hypothesis has not been tested. The purpose of this study is to characterize fluid distribution and compartmentalization associated with long-duration spaceflight, and to correlate these findings with vision changes and other elements of the VIIP syndrome. We also seek to determine whether the magnitude of fluid shifts during spaceflight, as well as the VIIP-related effects of those shifts, is predicted by the crewmember's preflight conditions and responses to acute hemodynamic manipulations (such as head-down tilt). Lastly, we will evaluate the patterns of fluid distribution in ISS astronauts during acute reversal of fluid shifts through application of lower body negative pressure (LBNP) interventions to characterize and explain general and individual responses. METHODS: We will examine a variety of physiologic variables in 10 long-duration ISS crewmembers using the test conditions and timeline presented in the Figure below. Measures include: (1) fluid compartmentalization (total body water by D2O, extracellular fluid by NaBr, intracellular fluid by calculation, plasma volume by CO rebreathe, interstitial fluid by calculation); (2) forehead/eyelids, tibia, calcaneus tissue thickness (by ultrasound); (3) vascular dimensions by ultrasound (jugular veins, cerebral and carotid arteries, vertebral arteries and veins, portal vein); (4) vascular dynamics by MRI (head/neck blood flow, cerebrospinal fluid pulsatility); (5) ocular measures (optical coherence tomography, intraocular pressure, 2-dimensional ultrasound including optic nerve sheath diameter, globe flattening, and retina-choroid thickness, Doppler ultrasound of ophthalmic and retinal arteries, and veins); (6) cardiac variables by ultrasound (inferior vena cava, tricuspid flow and tissue Doppler, pulmonic valve, stroke volume, right heart dimensions and function, four-chamber views); and (7) ICP measures (tympanic membrane displacement, distortion-product otoacoustic emissions, and ICP calculated by MRI). On the ground, acute head-down tilt will induce cephalad fluid shifts, whereas LBNP will oppose these shifts. Controlled Mueller maneuvers will manipulate cardiovascular variables. Through interventions applied before, during, and after flight, we intend to fully evaluate the relationship between fluid shifts and the VIIP syndrome