A fourth HI 21-cm absorption system in the sight-line of MG J0414+0534: a record for intervening absorbers

We report the detection of a strong HI 21-cm absorption system at z=0.5344, as well as a candidate system at z=0.3389, in the sight-line towards the z=2.64 quasar MG J0414+0534. This, in addition to the absorption at the host redshift and the other two intervening absorbers, takes the total to four (possibly five). The previous maximum number of 21-cm absorbers detected along a single sight-line is two and so we suspect that this number of gas-rich absorbers is in some way related to the very red colour of the background source. Despite this, no molecular gas (through OH absorption) has yet been detected at any of the 21-cm redshifts, although, from the population of 21-cm absorbers as a whole, there is evidence for a weak correlation between the atomic line strength and the optical--near-infrared colour. In either case, the fact that so many gas-rich galaxies (likely to be damped Lyman-alpha absorption systems) have been found along a single sight-line towards a highly obscured source may have far reaching implications for the population of faint galaxies not detected in optical surveys, a possibility which could be addressed through future wide-field absorption line surveys with the Square Kilometre Array.Comment: Accepted by ApJ Letter

HI and OH absorption in the lensing galaxy of MG J0414+0534

We report the detection of \HI 21-cm absorption in the $z=0.96$ early-type lensing galaxy towards MG J0414+0534 with the Green Bank Telescope. The absorption, with total $N_{\rm HI}=1.6 \times 10^{18} (T_{\rm s}/f) {\rm cm}^{-2}$, is resolved into two strong components, probably due to the two strongest lens components, which are separated by 0.4\arcsec. Unlike the other three lenses which have been detected in \HI, J0414+0534 does not exhibit strong OH absorption, giving a OH/\HI column density ratio of N_{\rm OH}/N_{\rm HI}\lapp10^{-6} (for $T_{\rm s}=100$ K, $T_{\rm x}=10$ K and $f_{\rm HI}=f_{\rm OH}=1$). This underabundance of molecular gas may indicate that the extreme optical--near-IR colour ($V-K=10.26$) along the line-of-sight is not due to the lens. We therefore suggest that despite the strong upper limits on molecular absorption at the quasar redshift, as traced by millimetre lines, the extinction occurs primarily in the quasar host galaxy.Comment: Accepted by MNRAS Letters, 5 (and a bit) pages, 5 figure

Modeling the evolution space of breakage fusion bridge cycles with a stochastic folding process

Breakage-Fusion-Bridge cycles in cancer arise when a broken segment of DNA is duplicated and an end from each copy joined together. This structure then 'unfolds' into a new piece of palindromic DNA. This is one mechanism responsible for the localised amplicons observed in cancer genome data. The process has parallels with paper folding sequences that arise when a piece of paper is folded several times and then unfolded. Here we adapt such methods to study the breakage-fusion-bridge structures in detail. We firstly consider discrete representations of this space with 2-d trees to demonstrate that there are 2^(n(n-1)/2) qualitatively distinct evolutions involving n breakage-fusion-bridge cycles. Secondly we consider the stochastic nature of the fold positions, to determine evolution likelihoods, and also describe how amplicons become localised. Finally we highlight these methods by inferring the evolution of breakage-fusion-bridge cycles with data from primary tissue cancer samples

Lysosomal membrane stability in mussels

In 2012, the ICES Study Group on Integrated Monitoring of Chemicals and their Effects provided a framework for integrated monitoring to the OSLO-Paris Commission. UNEP/MAP and HELCOM expert groups have also developed guidelines on integrated monitoring of chemicals and their effects for the Mediterranean and Baltic Sea. This document provides the technical information for one of the biological effects measurements, the lysosomal membrane stability (LMS), which is a part of the above mentioned integrated monitoring approaches. Lysosomes are cytoplasmic, single membrane organelles whose condition is sensitive to stress whether it be due to environmental conditions or exposure to a wide array of contaminants. Two different methodologies have been developed to assess LMS in mussels: an enzyme cytochemical method using cryostatic sections of digestive gland tissue, and an in vivo cytochemical method (using haemolymph cells). In this document, different aspects of the operational procedures have been standardized and harmonized, with particular reference to the in vivo cytochemical method. New graphical material has been added to clarify criteria of interpretation and new external quality assurance programmes for measurements of lysosomal membrane stability have been proposed. Background (BAC) and environmental (EAC) assessment criteria to assess the LMS data are provided. Additionally, a new scoring procedure to enhance the sensitivity of the LMS measurements using the in vivo assay is provided.Versión del edito

Fractal-like Distributions over the Rational Numbers in High-throughput Biological and Clinical Data

Recent developments in extracting and processing biological and clinical data are allowing quantitative approaches to studying living systems. High-throughput sequencing, expression profiles, proteomics, and electronic health records are some examples of such technologies. Extracting meaningful information from those technologies requires careful analysis of the large volumes of data they produce. In this note, we present a set of distributions that commonly appear in the analysis of such data. These distributions present some interesting features: they are discontinuous in the rational numbers, but continuous in the irrational numbers, and possess a certain self-similar (fractal-like) structure. The first set of examples which we present here are drawn from a high-throughput sequencing experiment. Here, the self-similar distributions appear as part of the evaluation of the error rate of the sequencing technology and the identification of tumorogenic genomic alterations. The other examples are obtained from risk factor evaluation and analysis of relative disease prevalence and co-mordbidity as these appear in electronic clinical data. The distributions are also relevant to identification of subclonal populations in tumors and the study of the evolution of infectious diseases, and more precisely the study of quasi-species and intrahost diversity of viral populations

A novel compartment, the 'subqpical stem' of the aerial hyphae, is the location of a sigN-dependent, developmentally distinct transcription in Streptomyces coelicolor.

Streptomyces coelicolor has nine SigB-like RNA polymerase sigma factors, several of them implicated in morphological differentiation and/or responses to different stresses. One of the nine, SigN, is the focus of this article. A constructed sigN null mutant was delayed in development and exhibited a bald phenotype when grown on minimal medium containing glucose as carbon source. One of two distinct sigN promoters, sigNP1, was active only during growth on solid medium, when its activation coincided with aerial hyphae formation. Transcription from sigNP1 was readily detected in several whi mutants (interrupted in morphogenesis of aerial mycelium into spores), but was absent from all bld mutants tested, suggesting that sigNP1 activity was restricted to the aerial hyphae. It also depended on sigN, thus sigN was autoregulated. Mutational and transcription studies revealed no functional significance to the location of sigN next to sigF, encoding another SigB-like sigma factor. We identified another potential SigN target, nepA, encoding a putative small secreted protein. Transcription of nepA originated from a single, aerial hyphae-specific and sigN-dependent promoter. While in vitro run-off transcription using purified SigN on the Bacillus subtilis ctc promoter confirmed that SigN is an RNA polymerase sigma factor, SigN failed to initiate transcription from sigNP1 and from the nepA promoter in vitro. Additional in vivo data indicated that further nepA upstream sequences, which are likely to bind a potential activator, are required for successful transcription. Using a nepA–egfp transcriptional fusion we located nepA transcription to a novel compartment, the ‘subapical stem’ of the aerial hyphae. We suggest that this newly recognized compartment defines an interface between the aerial and vegetative parts of the Streptomyces colony and might also be involved in communication between these two compartments

CYLD negatively regulates cell-cycle progression by inactivating HDAC6 and increasing the levels of acetylated tubulin

CYLD is a tumour-suppressor gene that is mutated in a benign skin tumour syndrome called cylindromatosis. The CYLD gene product is a deubiquitinating enzyme that was shown to regulate cell proliferation, cell survival and inflammatory responses, mainly through inhibiting NF-κB signalling. Here we show that CYLD controls cell growth and division at the G1/S-phase as well as cytokinesis by associating with α-tubulin and microtubules through its CAP-Gly domains. Translocation of activated CYLD to the perinuclear region of the cell is achieved by an inhibitory interaction of CYLD with histone deacetylase-6 (HDAC6) leading to an increase in the levels of acetylated α-tubulin around the nucleus. This facilitates the interaction of CYLD with Bcl-3, leading to a significant delay in the G1-to-S-phase transition. Finally, CYLD also interacts with HDAC6 in the midbody where it regulates the rate of cytokinesis in a deubiquitinase-independent manner. Altogether these results identify a mechanism by which CYLD regulates cell proliferation at distinct cell-cycle phases

The pH-responsive PacC transcription factor of Aspergillus fumigatus governs epithelial entry and tissue invasion during pulmonary aspergillosis

Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. Raw data have been deposited in the Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/) under accession number GSE54810. Funding: This work was supported in part by grants to EMB from the MRC (G0501164) and BBSRC (BB/G009619/1), to EMB and NDR from the Wellcome Trust (WT093596MA), to MB from Imperial College London (Division of Investigative Sciences PhD Studentship), to HH from the ERA-NET PathoGenoMics project TRANSPAT, Austrian Science Foundation (FWF I282-B09), to SGF from the National Institutes of Health, USA (R01AI073829). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD