ALBERT

Description: We present a Radio Recombination Line (RRL) survey of the Galactic plane from the H i Parkes All-sky Survey and associated Zone of Avoidance survey, which mapped the region l  = 196°–0°–52° and | b | ≤ 5° at 1.4 GHz and 14.4 arcmin resolution. We combine three RRLs, H168α, H167α, and H166α to derive fully sampled maps of the diffuse ionized emission along the inner Galactic plane. The velocity information, at a resolution of 20 km s –1 , allows us to study the spatial distribution of the ionized gas and compare it with that of the molecular gas, as traced by CO. The longitude–velocity diagram shows that the RRL emission is mostly associated with CO gas from the molecular ring and is concentrated within the inner 30° of longitude. A map of the free–free emission in this region of the Galaxy is derived from the line-integrated RRL emission, assuming an electron temperature gradient with Galactocentric radius of 496 ± 100 K kpc –1 . Based on the thermal continuum map, we extracted a catalogue of 317 compact (15 arcmin) sources, with flux densities, sizes, and velocities. We report the first RRL observations of the southern ionized lobe in the Galactic Centre. The line profiles and velocities suggest that this degree-scale structure is in rotation. We also present new evidence of diffuse ionized gas in the 3-kpc arm. Helium and carbon RRLs are detected in this survey. The He line is mostly observed towards H ii regions, whereas the C line is also detected further away from the source of ionization. These data represent the first observations of diffuse C RRLs in the Galactic plane at a frequency of 1.4 GHz.

Description: : High-throughput genome-wide studies of alternatively spliced mRNA transcripts have become increasingly important in clinical research. Consequently, easy-to-use software tools are required to process data from these studies, for example, using exon and junction arrays. Here, we introduce JETTA, an integrated software package for the calculation of gene expression indices as well as the identification and visualization of alternative splicing events. We demonstrate the software using data of human liver and muscle samples hybridized on an exon–junction array. Availability: JETTA and its demonstrations are freely available at http://igenomed.stanford.edu/~junhee/JETTA/index.html Contacts: wxiao1@partners.org

Description: Motivation: Mass spectrometry (MS)-based high-throughput quantitative proteomics shows great potential in large-scale clinical biomarker studies, identifying and quantifying thousands of proteins in biological samples. However, there are unique challenges in analyzing the quantitative proteomics data. One issue is that the quantification of a given peptide is often missing in a subset of the experiments, especially for less abundant peptides. Another issue is that different MS experiments of the same study have significantly varying numbers of peptides quantified, which can result in more missing peptide abundances in an experiment that has a smaller total number of quantified peptides. To detect as many biomarker proteins as possible, it is necessary to develop bioinformatics methods that appropriately handle these challenges. Results: We propose a Significance Analysis for Large-scale Proteomics Studies (SALPS) that handles missing peptide intensity values caused by the two mechanisms mentioned above. Our model has a robust performance in both simulated data and proteomics data from a large clinical study. Because varying patients’ sample qualities and deviating instrument performances are not avoidable for clinical studies performed over the course of several years, we believe that our approach will be useful to analyze large-scale clinical proteomics data. Availability and Implementation: R codes for SALPS are available at http://www.stanford.edu/%7eclairesr/software.html . Contact: wenzhong.xiao@mgh.harvard.edu Supplementary information: Supplementary materials are available at Bioinformatics online.

Description: We present an analysis of the diffuse emission at 5 GHz in the first quadrant of the Galactic plane using two months of preliminary intensity data taken with the C-Band All-Sky Survey (C-BASS) northern instrument at the Owens Valley Radio Observatory, California. Combining C-BASS maps with ancillary data to make temperature–temperature plots, we find synchrotron spectral indices of β = –2.65 ± 0.05 between 0.408 and 5 GHz and β = –2.72 ± 0.09 between 1.420 and 5 GHz for –10° 〈 | b | 〈 –4°, 20° 〈  l  〈 40°. Through the subtraction of a radio recombination line free–free template, we determine the synchrotron spectral index in the Galactic plane (| b | 〈 4°) to be β = –2.56 ± 0.07 between 0.408 and 5 GHz, with a contribution of 53 ± 8 per cent from free–free emission at 5 GHz. These results are consistent with previous low-frequency measurements in the Galactic plane. By including C-BASS data in spectral fits, we demonstrate the presence of anomalous microwave emission (AME) associated with the H ii complexes W43, W44 and W47 near 30 GHz, at 4.4, 3.1 and 2.5, respectively. The CORNISH (Co-Ordinated Radio ‘N’ Infrared Survey for High mass star formation) VLA 5-GHz source catalogue rules out the possibility that the excess emission detected around 30 GHz may be due to ultracompact H ii regions. Diffuse AME was also identified at a 4 level within 30° 〈  l  〈 40°, –2° 〈  b  〈 2° between 5 and 22.8 GHz.

Description: Functional defects of the mitochondrial translation machinery, as a result of mutations in nuclear-encoded genes, have been associated with combined oxidative phosphorylation (OXPHOS) deficiencies. We report siblings with congenital sensorineural deafness and lactic acidemia in association with combined respiratory chain (RC) deficiencies of complexes I, III and IV observed in fibroblasts and liver. One of the siblings had a more severe phenotype showing progressive hepatic and renal failure. Whole-exome sequencing revealed a homozygous mutation in the gene encoding mitochondrial ribosomal protein S7 ( MRPS7 ), a c.550A〉G transition that encodes a substitution of valine for a highly conserved methionine (p.Met184Val) in both affected siblings. MRPS7 is a 12S ribosomal RNA-binding subunit of the small mitochondrial ribosomal subunit, and is required for the assembly of the small ribosomal subunit. Pulse labeling of mitochondrial protein synthesis products revealed impaired mitochondrial protein synthesis in patient fibroblasts. Exogenous expression of wild-type MRPS7 in patient fibroblasts rescued complexes I and IV activities, demonstrating the deleterious effect of the mutation on RC function. Moreover, reduced 12S rRNA transcript levels observed in the patient's fibroblasts were also restored to normal levels by exogenous expression of wild-type MRPS7. Our data demonstrate the pathogenicity of the identified MRPS7 mutation as a novel cause of mitochondrial RC dysfunction, congenital sensorineural deafness and progressive hepatic and renal failure.

Description: Herschel far-infrared continuum data obtained as part of the Hi-GAL survey have been used, together with the GLIMPSE 8 μm and MIPSGAL 24 μm data, to attempt the first 3D-decomposition of dust emission associated with atomic, molecular and ionized gas at 15 arcmin angular resolution. Our initial test case is a 2 2 square degrees region centred on ( l , b ) = (30°, 0°), a direction that encompasses the origin point of the Scutum–Crux Arm at the tip of the Galactic Bar. Coupling the IR maps with velocity maps specific for different gas phases (H i 21cm, 12 CO and 13 CO, and radio recombination lines), we estimate the properties of dust blended with each of the gas components and at different Galactocentric distances along the line of sight (LOS). A statistical Pearson's coefficients analysis is used to study the correlation between the column densities estimated for each gas component and the intensity of the IR emission. This analysis provides evidence that the 2 2 square degree field under consideration is characterized by the presence of a gas component not accounted for by the standard tracers, possibly associated with warm H 2 and cold H i . We demonstrate that the IR radiation in the range 8 〈  〈 500 μm is systematically dominated by emission originating within the Scutum–Crux Arm. By applying an inversion method, we recover the dust emissivities associated with atomic, molecular and ionized gas. Using the DustEM model, we fit the spectral energy distributions for each gas phase, and find average dust temperatures of T d,H i  = 18.82 ± 0.47 K, T d,H 2  = 18.84 ± 1.06 K and T d,H ii  = 22.56 ± 0.64 K, respectively. We also obtain an indication for polycyclic aromatic hydrocarbons depletion in the diffuse ionized gas. We demonstrate the importance of including the ionized component in 3D-decompositions of the total IR emission. However, the main goal of this work is to discuss the impact of the missing column density associated with the dark gas component on the accurate evaluation of the dust properties, and to shed light on the limitations of the inversion method approach when this is applied to a small section of the Galactic plane and when the working resolution allows sufficient de-blending of the gas components along the LOS.

Description: Proper modelling of astronomical receivers is vital: it describes the systematic errors in the raw data, guides the receiver design process, and assists data calibration. In this paper, we describe a method of analytically modelling the full signal and noise behaviour of arbitrarily complex radio receivers. We use electrical scattering matrices to describe the signal behaviour of individual components in the receiver, and noise correlation matrices to describe their noise behaviour. These are combined to produce the full receiver model. We apply this approach to a specified receiver architecture: a hybrid of a continuous comparison radiometer and correlation polarimeter designed for the C-Band All-Sky Survey. We produce analytic descriptions of the receiver Mueller matrix and noise temperature, and discuss how imperfections in crucial components affect the raw data. Many of the conclusions drawn are generally applicable to correlation polarimeters and continuous comparison radiometers.

Description: Approximately 36 000 cases of simplex and familial retinitis pigmentosa (RP) worldwide are caused by a loss in phosphodiesterase (PDE6) function. In the preclinical Pde6α nmf363 mouse model of this disease, defects in the α-subunit of PDE6 result in a progressive loss of photoreceptors and neuronal function. We hypothesized that increasing PDE6α levels using an AAV2/8 gene therapy vector could improve photoreceptor survival and retinal function. We utilized a vector with the cell-type-specific rhodopsin (RHO) promoter: AAV2/8(Y733F)- Rho - Pde6α , to transduce Pde6α nmf363 retinas and monitored its effects over a 6-month period (a quarter of the mouse lifespan). We found that a single injection enhanced survival of photoreceptors and improved retinal function. At 6 months of age, the treated eyes retained photoreceptor cell bodies, while there were no detectable photoreceptors remaining in the untreated eyes. More importantly, the treated eyes demonstrated functional visual responses even after the untreated eyes had lost all vision. Despite focal rescue of the retinal structure adjacent to the injection site, global functional rescue of the entire retina was observed. These results suggest that RP due to PDE6α deficiency in humans, in addition to PDE6β deficiency, is also likely to be treatable by gene therapy.

Description: The C-Band All-Sky Survey is a project to map the full sky in total intensity and linear polarization at 5 GHz. The northern component of the survey uses a broad-band single-frequency analogue receiver fitted to a 6.1-m telescope at the Owens Valley Radio Observatory in California, USA. The receiver architecture combines a continuous-comparison radiometer and a correlation polarimeter in a single receiver for stable simultaneous measurement of both total intensity and linear polarization, using custom-designed analogue receiver components. The continuous-comparison radiometer measures the temperature difference between the sky and temperature-stabilized cold electrical reference loads. A cryogenic front-end is used to minimize receiver noise, with a system temperature of 30 K in both linear polarization and total intensity. Custom cryogenic notch filters are used to counteract man-made radio frequency interference. The radiometer 1/ f noise is dominated by atmospheric fluctuations, while the polarimeter achieves a 1/ f noise knee frequency of 10 mHz, similar to the telescope azimuthal scan frequency.

Description: It was recently reported that the sizes of many mRNAs change when budding yeast cells exit mitosis and enter the meiotic differentiation pathway. These differences were attributed to length variations of their untranslated regions. The function of UTRs in protein translation is well established. However, the mechanism controlling the expression of distinct transcript isoforms during mitotic growth and meiotic development is unknown. In this study, we order developmentally regulated transcript isoforms according to their expression at specific stages during meiosis and gametogenesis, as compared to vegetative growth and starvation. We employ regulatory motif prediction, in vivo protein-DNA binding assays, genetic analyses and monitoring of epigenetic amino acid modification patterns to identify a novel role for Rpd3 and Ume6, two components of a histone deacetylase complex already known to repress early meiosis-specific genes in dividing cells, in mitotic repression of meiosis-specific transcript isoforms. Our findings classify developmental stage-specific early, middle and late meiotic transcript isoforms, and they point to a novel HDAC-dependent control mechanism for flexible transcript architecture during cell growth and differentiation. Since Rpd3 is highly conserved and ubiquitously expressed in many tissues, our results are likely relevant for development and disease in higher eukaryotes.