Deciphering the metabolic response of Mycobacterium tuberculosis to nitrogen stress.

© 2015 John Wiley & Sons Ltd.A key component to the success of Mycobacterium tuberculosis as a pathogen is the ability to sense and adapt metabolically to the diverse range of conditions encountered in vivo, such as oxygen tension, environmental pH and nutrient availability. Although nitrogen is an essential nutrient for every organism, little is known about the genes and pathways responsible for nitrogen assimilation in M. tuberculosis. In this study we have used transcriptomics and chromatin immunoprecipitation and high-throughput sequencing to address this. In response to nitrogen starvation, a total of 185 genes were significantly differentially expressed (96 up-regulated and 89 down regulated; 5% genome) highlighting several significant areas of metabolic change during nitrogen limitation such as nitrate/nitrite metabolism, aspartate metabolism and changes in cell wall biosynthesis. We identify GlnR as a regulator involved in the nitrogen response, controlling the expression of at least 33 genes in response to nitrogen limitation. We identify a consensus GlnR binding site and relate its location to known transcriptional start sites. We also show that the GlnR response regulator plays a very different role in M. tuberculosis to that in non-pathogenic mycobacteria, controlling genes involved in nitric oxide detoxification and intracellular survival instead of genes involved in nitrogen scavenging

Deciphering the response of Mycobacterium smegmatis to nitrogen stress using bipartite active modules.

Background The ability to adapt to environments with fluctuating nutrient availability is vital for bacterial survival. Although essential for growth, few nitrogen metabolism genes have been identified or fully characterised in mycobacteria and nitrogen stress survival mechanisms are unknown. Results A global transcriptional analysis of the mycobacterial response to nitrogen stress, showed a significant change in the differential expression of 16% of the Mycobacterium smegmatis genome. Gene expression changes were mapped onto the metabolic network using Active Modules for Bipartite Networks (AMBIENT) to identify metabolic pathways showing coordinated transcriptional responses to the stress. AMBIENT revealed several key features of the metabolic response not identified by KEGG enrichment alone. Down regulated reactions were associated with the general reduction in cellular metabolism as a consequence of reduced growth rate. Up-regulated modules highlighted metabolic changes in nitrogen assimilation and scavenging, as well as reactions involved in hydrogen peroxide metabolism, carbon scavenging and energy generation. Conclusions Application of an Active Modules algorithm to transcriptomic data identified key metabolic reactions and pathways altered in response to nitrogen stress, which are central to survival under nitrogen limiting environments

Molecular gas in nearby powerful radio galaxies

We report the detection of CO(1-0) and CO(2-1) emission from the central region of nearby 3CR radio galaxies (z$<$ 0.03). Out of 21 galaxies, 8 have been detected in, at least, one of the two CO transitions. The total molecular gas content is below 10$^9$ \msun. Their individual CO emission exhibit, for 5 cases, a double-horned line profile that is characteristic of an inclined rotating disk with a central depression at the rising part of its rotation curve. The inferred disk or ring distributions of the molecular gas is consistent with the observed presence of dust disks or rings detected optically in the cores of the galaxies. We reason that if their gas originates from the mergers of two gas-rich disk galaxies, as has been invoked to explain the molecular gas in other radio galaxies, then these galaxies must have merged a long time ago (few Gyr or more) but their remnant elliptical galaxies only recently (last 10$^7$ years or less) become active radio galaxies. Instead, we argue the the cannibalism of gas-rich galaxies provide a simpler explanation for the origin of molecular gas in the elliptical hosts of radio galaxies (Lim et al. 2000). Given the transient nature of their observed disturbances, these galaxies probably become active in radio soon after the accretion event when sufficient molecular gas agglomerates in their nuclei.Comment: 6 pages, including 2 figures,in "QSO Hosts and Their Environments", ed. I. Marquez, in pres

The impact of solvent characteristics on performance and process stability of printed carbon resistive materials

Carbon conductive pastes deposited by screen printing are used in many commercial applications including sensors, PCB, batteries, and PV, and as such represent an important value-added coating. An experimental investigation was carried out into the role of the solvent on the drying characteristics, conductivity, and process consistency in screen printed carbon pastes. Four materials with solvent boiling points between 166 and 219°C were deposited at film thickness between 6 and 16 μm, and the sheet resistance and film thickness were measured after successive passes through an industrial dryer operating with an air temperature of 155°C. Sheet resistances of 14 Ω/sq. were obtained with the thicker films while thinner films produced a sheet resistance of 46 Ω/sq. Thinner films achieved a stable resistivity within a 2.5-min residence time, while the thicker films required a residence time in excess of 12.5 min to achieve a stable resistivity. As well as prolonging drying times, the higher boiling point increased the resistivity of the cured film. It is postulated that the lower resistance of the faster drying materials is a result of film stressing increasing inter particle contact. Process models indicate that multiple thin layers are a more efficient means of manufacture for the process parameters examined

Methods to study splicing from high-throughput RNA Sequencing data

The development of novel high-throughput sequencing (HTS) methods for RNA (RNA-Seq) has provided a very powerful mean to study splicing under multiple conditions at unprecedented depth. However, the complexity of the information to be analyzed has turned this into a challenging task. In the last few years, a plethora of tools have been developed, allowing researchers to process RNA-Seq data to study the expression of isoforms and splicing events, and their relative changes under different conditions. We provide an overview of the methods available to study splicing from short RNA-Seq data. We group the methods according to the different questions they address: 1) Assignment of the sequencing reads to their likely gene of origin. This is addressed by methods that map reads to the genome and/or to the available gene annotations. 2) Recovering the sequence of splicing events and isoforms. This is addressed by transcript reconstruction and de novo assembly methods. 3) Quantification of events and isoforms. Either after reconstructing transcripts or using an annotation, many methods estimate the expression level or the relative usage of isoforms and/or events. 4) Providing an isoform or event view of differential splicing or expression. These include methods that compare relative event/isoform abundance or isoform expression across two or more conditions. 5) Visualizing splicing regulation. Various tools facilitate the visualization of the RNA-Seq data in the context of alternative splicing. In this review, we do not describe the specific mathematical models behind each method. Our aim is rather to provide an overview that could serve as an entry point for users who need to decide on a suitable tool for a specific analysis. We also attempt to propose a classification of the tools according to the operations they do, to facilitate the comparison and choice of methods.Comment: 31 pages, 1 figure, 9 tables. Small corrections adde

TOI-3235 b: A Transiting Giant Planet around an M4 Dwarf Star

We present the discovery of TOI-3235 b, a short-period Jupiter orbiting an M dwarf with a stellar mass close to the critical mass at which stars transition from partially to fully convective. TOI-3235 b was first identified as a candidate from TESS photometry and confirmed with radial velocities from ESPRESSO and ground-based photometry from HATSouth, MEarth-South, TRAPPIST-South, LCOGT, and ExTrA. We find that the planet has a mass of 0.665 ± 0.025 M J and a radius of 1.017 ± 0.044 R J. It orbits close to its host star, with an orbital period of 2.5926 days but has an equilibrium temperature of ≈ 604 K, well below the expected threshold for radius inflation of hot Jupiters. The host star has a mass of 0.3939 ± 0.0030 M ☉, a radius of 0.3697 ± 0.0018 R ☉, an effective temperature of 3389 K, and a J-band magnitude of 11.706 ± 0.025. Current planet formation models do not predict the existence of gas giants such as TOI-3235 b around such low-mass stars. With a high transmission spectroscopy metric, TOI-3235 b is one of the best-suited giants orbiting M dwarfs for atmospheric characterization

Labelling and Family Resemblance in the discrimination of polymorphous categories by pigeons

publication-status: Acceptedtypes: Article© 2011 Springer Verlag. This is a post print version of the article published in Animal Cognition, 2011, 14 (1), pp 21-34. The final publication is available at link.springer.comTwo experiments examined whether pigeons discriminate polymorphous categories on the basis of a single highly predictive feature or overall similarity. In the first experiment, pigeons were trained to discriminate between categories of photographs of complex real objects. Within these pictures, single features had been manipulated to produce a highly salient texture cue. Either the picture or the texture provided a reliable cue for discrimination during training, but in probe tests, the picture and texture cues were put into conflict. Some pigeons showed a significant tendency to discriminate on the basis of the picture cue (overall similarity or family resemblance), whereas others appeared to rely on the manipulated texture cue. The second experiment used artificial polymorphous categories in which one dimension of the stimulus provided a completely reliable cue to category membership, whereas three other dimensions provided cues that were individually unreliable but collectively provided a completely reliable basis for discrimination. Most pigeons came under the control of the reliable cue rather than the unreliable cues. A minority, however, came under the control of single dimensions from the unreliable set. We conclude that cue salience can be more important than cue reliability in determining what features will control behavior when multiple cues are available

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Increased Expression of Integrin-Linked Kinase Improves Cardiac Function and Decreases Mortality in Dilated Cardiomyopathy Model of Rats

AIMS: Integrin-linked kinase (ILK) is a multifunctional kinase linking the extracellular matrix to intracellular signaling pathways, whose activation in the heart gives rise to a number of functional consequences. The aim of this study is to demonstrate the therapeutic and survival benefit of cardiac ILK overexpression in a rat model of dilated cardiomyopathy. METHODS AND RESULTS: The dilated cardiomyopathy model was generated in rats by intraperitoneal administration of six equal doses of doxorubicin over a 2 week period. Five weeks after the first injection, echocardiographic analysis demonstrated impaired cardiac function and, at that point, recombinant adenoviral vector harboring ILK cDNA or vehicle was injected into the myocardium, and the rats re-studied 4 weeks later. Compared with vehicle injection, ILK treatment ameliorated inflammatory cell infiltration and cardiomyocyte degeneration, as well as left ventricular dilation and dysfunction. ILK treatment was also associated with a reduction in apoptosis and an increase in proliferation of cardiomyocytes, as well as decreased oxidative stress and autophagic vacuole accumulation. Importantly, mortality was lower in rats following ILK treatment than in those following vehicle injection. In cultured neonatal rat cardiomyocytes, we also found that ILK overexpression protected against doxorubicin-induced apoptosis, giving rise to an increase in their proliferation. CONCLUSIONS: These data demonstrate for the first time that ILK gene therapy improves cardiac function and survival in a model of dilated cardiomyopathy, and this may be mediated through suppression of inflammation, prevention of ventricular remodeling, inhibition of cardiomyocyte apoptosis and autophagy, and stimulation of cardiomyocyte proliferation

Predation by Bears Drives Senescence in Natural Populations of Salmon

Classic evolutionary theory predicts that populations experiencing higher rates of environmentally caused (“extrinsic”) mortality should senesce more rapidly, but this theory usually neglects plausible relationships between an individual's senescent condition and its susceptibility to extrinsic mortality. We tested for the evolutionary importance of this condition dependence by comparing senescence rates among natural populations of sockeye salmon (Oncorhynchus nerka) subject to varying degrees of predation by brown bears (Ursus arctos). We related senescence rates in six populations to (1) the overall rate of extrinsic mortality, and (2) the degree of condition dependence in this mortality. Senescence rates were determined by modeling the mortality of individually-tagged breeding salmon at each site. The overall rate of extrinsic mortality was estimated as the long-term average of the annual percentage of salmon killed by bears. The degree of condition dependence was estimated as the extent to which bears killed salmon that exhibited varying degrees of senescence. We found that the degree of condition dependence in extrinsic mortality was very important in driving senescence: populations where bears selectively killed fish showing advanced senescence were those that senesced least rapidly. The overall rate of extrinsic mortality also contributed to among-population variation in senescence-but to a lesser extent. Condition-dependent susceptibility to extrinsic mortality should be incorporated more often into theoretical models and should be explicitly tested in natural populations