ALBERT

Description: Background: Herlyn-Werner-Wunderlich (HWW) syndrome is a very rare congenital anomaly of the urogenital tract involving Müllerian ducts and Wolffian structures, and it is characterized by the triad of didelphys uterus, obstructed hemivagina and ipsilateral renal agenesis. It generally occurs at puberty and exhibits non-specific and variable symptoms with acute or pelvic pain shortly following menarche, causing a delay in the diagnosis. Moreover, the diagnosis is complicated by the infrequency of this syndrome, because Müllerian duct anomalies (MDA) are infrequently encountered in a routine clinical setting.Cases presentationtwo cases of HWW syndrome in adolescents and a differential diagnosis for one case of a different MDA, and the impact of magnetic resonance (MR) imaging technology to achieve the correct diagnosis. Conclusions: MR imaging is a very suitable diagnostic tool in order to perform the correct diagnosis of HWW syndrome.

Description: Background: Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism of PCR products (PCR-RFLP) are extensively used molecular biology techniques. An exercise for the design and simulation of PCR and PCR-RFLP experiments will be a useful educational tool.FindingsAn online PCR and PCR-RFLP exercise has been create that requires users to find the target genes, compare them, design primers, search for restriction endonucleases, and finally to simulate the experiment. Each user of the service is randomly assigned a gene from Escherichia coli; to complete the exercise, users must design an experiment capable of distinguishing among E. coli strains. By applying the experimental procedure to all completely sequenced E. coli, a basic understanding of strain comparison and clustering can also be acquired. Comparison of results obtained in different experiments is also very instructive. Conclusion: The exercise is freely available at http://insilico.ehu.es/edu

Description: Background: Pseudomonas aeruginosa is an opportunistic pathogen with a high incidence of hospital infections that represents a threat to immune compromised patients. Genomic studies have shown that, in contrast to other pathogenic bacteria, clinical and environmental isolates do not show particular genomic differences. In addition, genetic variability of all the P. aeruginosa strains whose genomes have been sequenced is extremely low. This low genomic variability might be explained if clinical strains constitute a subpopulation of this bacterial species present in environments that are close to human populations, which preferentially produce virulence associated traits. Results: In this work, we sequenced the genomes and performed phenotypic descriptions for four non-human P. aeruginosa isolates collected from a plant, the ocean, a water-spring, and from a dolphin stomach. We show that the four strains are phenotypically diverse and that this is not reflected in genomic variability, since their genomes are almost identical. Furthermore, we performed a detailed comparative genomic analysis of all the seven previously completed P. aeruginosa genomes with the four strains studied in this work by means of describing its core and pan-genomes. Conclusions: Contrary to what has been described for other bacteria, we found that P. aeruginosa's core genome is constituted by a high proportion of genes and that its pan-genome is thus relatively small. Considering the high degree of genomic conservation between isolates of P. aeruginosa from diverse environments, including human tissues, some implications for the treatment of infections are discussed. This work also represents a methodological contribution for the genomic study of P. aeruginosa, since the pan-genome database of protein comparisons is provided.

Description: We have investigated the gas content of a sample of several hundred AGN host galaxies at z  〈 1 and compared it with a sample of inactive galaxies, matched in bins of stellar mass and redshift. Gas masses have been inferred from the dust masses, obtained by stacked Herschel far-IR and sub-mm data in the GOODS and COSMOS fields, under reasonable assumptions and metallicity scaling relations for the dust-to-gas ratio. We find that AGNs are on average hosted in galaxies much more gas rich than inactive galaxies. In the vast majority of stellar mass bins, the average gas content of AGN hosts is higher than that in inactive galaxies. The difference is up to a factor of 10 higher in low-stellar-mass galaxies, with a significance of 6.5. In almost half of the AGN sample, the gas content is three times higher than that in the control sample of inactive galaxies. Our result strongly suggests that the probability of having an AGN activated is simply driven by the amount of gas in the host galaxy; this can be explained in simple terms of statistical probability of having a gas cloud falling into the gravitational potential of the black hole. The increased probability of an AGN being hosted by a star-forming galaxy, identified by previous works, may be a consequence of the relationship between gas content and AGN activity, found in this paper, combined with the Schmidt–Kennicutt law for star formation.

Description: Chandra data in the COSMOS, AEGIS-XD and 4 Ms Chandra Deep Field South are combined with multiwavelength photometry available in those fields to determine the rest-frame U  –  V versus V  –  J colours of X-ray AGN hosts in the redshift intervals 0.1 〈  z  〈 0.6 (mean $\overline{z}=0.40$ ) and 0.6 〈  z  〈 1.2 (mean $\overline{z}=0.85$ ). This combination of colours provides an effective and least model-dependent means of separating quiescent from star-forming, including dust reddened, galaxies. Morphological information emphasizes differences between AGN populations split by their U  –  V versus V  –  J colours. AGN in quiescent galaxies consist almost exclusively of bulges, while star-forming hosts are equally split between early- and late-type hosts. The position of AGN hosts on the U  –  V versus V  –  J diagram is then used to set limits on the accretion density of the Universe associated with evolved and star-forming systems independent of dust induced biases. It is found that most of the black hole growth at z 0.40 and 0.85 is associated with star-forming hosts. Nevertheless, a non-negligible fraction of the X-ray luminosity density, about 15–20 per cent, at both $\overline{z}=0.40$ and 0.85, is taking place in galaxies in the quiescent region of the U  –  V versus V  –  J diagram. For the low-redshift sub-sample, 0.1 〈  z  〈 0.6, we also find tentative evidence, significant at the 2 level, that AGN split by their U  –  V and V  –  J colours have different Eddington ratio distributions. AGN in blue star-forming hosts dominate at relatively high Eddington ratios. In contrast, AGN in red quiescent hosts become increasingly important as a fraction of the total population towards low Eddington ratios. At higher redshift, z  〉 0.6, such differences are significant at the 2 level only for sources with Eddington ratios 10 – 3 . These findings are consistent with scenarios in which diverse accretion modes are responsible for the build-up of supermassive black holes at the centres of galaxies. We compare these results with the predictions of the galform semi-analytic model for the cosmological evolution of AGN and galaxies. This model postulates two black hole fuelling modes, the first is linked to star formation events and the second takes place in passive galaxies. galform predicts that a substantial fraction of the black hole growth at z  〈 1 is associated with quiescent galaxies, in apparent conflict with the observations. Relaxing the strong assumption of the model that passive AGN hosts have zero star formation rate could bring those predictions in better agreement with the data.

Description: We present X-shooter at Very Large Telescope observations of a sample of 10 luminous, X-ray obscured quasi-stellar objects (QSOs) at z  ~ 1.5 from the XMM -COSMOS survey, expected to be caught in the transitioning phase from starburst to active galactic nucleus (AGN)-dominated systems. The main selection criterion is X-ray detection at bright fluxes ( L X   10 44  erg s –1 ) coupled to red optical-to-near-infrared-to-mid-infrared colours. Thanks to its large wavelength coverage, X-shooter allowed us to determine accurate redshifts from the presence of multiple emission lines for five out of six targets for which we had only a photometric redshift estimate, with an 80 per cent success rate, significantly larger than what is observed in similar programs of spectroscopic follow-up of red QSOs. We report the detection of broad and shifted components in the [O iii ] 5007, 4959 complexes for six out of eight sources with these lines observable in regions free from strong atmospheric absorptions. The full width at half-maximum (FWHM) associated with the broad components are in the range FWHM ~ 900–1600 km s –1 , larger than the average value observed in Sloan Digital Sky Survey type 2 AGN samples at similar observed [O iii ] luminosity, but comparable to those observed for QSO/ultraluminous infrared galaxies systems for which the presence of kpc scale outflows has been revealed through integral field unit spectroscopy. Although the total outflow energetics (inferred under reasonable assumptions) may be consistent with winds accelerated by stellar processes, we favour an AGN origin for the outflows given the high outflow velocities observed ( v  〉 1000 km s –1 ) and the presence of strong winds also in objects undetected in the far-infrared.

Description: Background: Common approaches to pathway analysis treat pathways merely as lists of genes disregarding their topological structures, that is, ignoring the genes' interactions on which a pathway's cellular function depends. In contrast, PathWave has been developed for the analysis of high-throughput gene expression data that explicitly takes the topology of networks into account to identify both global dysregulation of and localized (switch-like) regulatory shifts within metabolic and signaling pathways. For this purpose, it applies adjusted wavelet transforms on optimized 2D grid representations of curated pathway maps. Results: Here, we present the new version of PathWave with several substantial improvements including a new method for optimally mapping pathway networks unto compact 2D lattice grids, a more flexible and user-friendly interface, and pre-arranged 2D grid representations. These pathway representations are assembled for several species now comprising H. sapiens, M. musculus, D. melanogaster, D. rerio, C. elegans, and E. coli. We show that PathWave is more sensitive than common approaches and apply it to RNA-seq expression data, identifying crucial metabolic pathways in lung adenocarcinoma, as well as microarray expression data, identifying pathways involved in longevity of Drosophila. Conclusions: PathWave is a generic method for pathway analysis complementing established tools like GSEA, and the update comprises efficient new features. In contrast to the tested commonly applied approaches which do not take network topology into account, PathWave enables identifying pathways that are either known be involved in or very likely associated with such diverse conditions as human lung cancer or aging of D. melanogaster. The PathWave R package is freely available at http://www.ichip.de/software/pathwave.html.

Description: Background: Plant ALDH10 enzymes are aminoaldehyde dehydrogenases (AMADHs) that oxidize different omega-amino or trimethylammonium aldehydes, but only some of them have betaine aldehyde dehydrogenase (BADH) activity and produce the osmoprotectant glycine betaine (GB). The latter enzymes possess alanine or cysteine at position 441 (numbering of the spinach enzyme, SoBADH), while those ALDH10s that cannot oxidize betaine aldehyde (BAL) have isoleucine at this position. Only the plants that contain A441- or C441-type ALDH10 isoenzymes accumulate GB in response to osmotic stress. In this work we explored the evolutionary history of the acquisition of BAL specificity by plant ALDH10s. Results: We performed extensive phylogenetic analyses and constructed and characterized, kinetically and structurally, four SoBADH variants that simulate the parsimonious intermediates in the evolutionary pathway from I441-type to A441- or C441-type enzymes. All mutants had a correct folding, average thermal stabilities and similar activity with aminopropionaldehyde, but whereas A441S and A441T exhibited significant activity with BAL, A441V and A441F did not. The kinetics of the mutants were consistent with their predicted structural features obtained by modeling, and confirmed the importance of position 441 for BAL specificity. The acquisition of BADH activity could have happened through any of these intermediates without detriment of the original function or protein stability. Phylogenetic studies showed that this event occurred independently several times during angiosperms evolution when an ALDH10 gene duplicate changed the critical Ile residue for Ala or Cys in two consecutive single mutations. ALDH10 isoenzymes frequently group in two clades within a plant family: one includes peroxisomal I441-type, the other peroxisomal and non-peroxisomal I441-, A441- or C441-type. Interestingly, high GB-accumulators plants have non-peroxisomal A441- or C441-type isoenzymes, while low-GB accumulators have the peroxisomal C441-type, suggesting some limitations in the peroxisomal GB synthesis. Conclusion: Our findings shed light on the evolution of the synthesis of GB in plants, a metabolic trait of most ecological and physiological relevance for their tolerance to drought, hypersaline soils and cold. Together, our results are consistent with smooth evolutionary pathways for the acquisition of the BADH function from ancestral I441-type AMADHs, thus explaining the relatively high occurrence of this event.

Description: The processes that trigger active galactic nuclei (AGN) remain poorly understood. While lower luminosity AGN may be triggered by minor disturbances to the host galaxy, stronger disturbances are likely required to trigger luminous AGN. Major wet mergers of galaxies are ideal environments for AGN triggering since they provide large gas supplies and galaxy scale torques. There is however little observational evidence for a strong connection between AGN and major mergers. We analyse the morphological properties of AGN host galaxies as a function of AGN and host galaxy luminosity and compare them to a carefully matched sample of control galaxies. AGN are X-ray selected in the redshift range 0.5 〈  z  〈 0.8 and have luminosities 41  log ( L X  [erg s –1 ])  44.5. ‘Fake AGN’ are simulated in the control galaxies by adding point sources with the magnitude of the matched AGN. We find that AGN host and control galaxies have comparable asymmetries, Sérsic indices and ellipticities at rest frame ~950 nm. AGN host galaxies show neither higher average asymmetries nor higher fractions of very disturbed objects. There is no increase in the prevalence of merger signatures with AGN luminosity. At 95 per cent confidence we find that major mergers are responsible for 〈6 per cent of all AGN in our sample as well as 〈40 per cent of the highest luminosity AGN (log ( L X [erg s –1 ]) ~ 43.5). Major mergers therefore either play only a very minor role in the triggering of AGN in the luminosity range studied or time delays are too long for merger features to remain visible.

Description: We present the most complete study to date of the X-ray emission from star formation in high-redshift (median z  = 0.7; z  〈 1.5), IR-luminous ( L IR  = 10 10 –10 13  L ) galaxies detected by Herschel 's PACS and SPIRE instruments. For our purpose, we take advantage of the deepest X-ray data to date, the Chandra Deep Fields (North and South). Sources which host AGN are removed from our analysis by means of multiple AGN indicators. We find an AGN fraction of 18 ± 2 per cent amongst our sample and note that AGN entirely dominate at values of log [ L X / L IR ] 〉 –3 in both hard and soft X-ray bands. From the sources which are star formation dominated, only a small fraction are individually X-ray detected and for the bulk of the sample we calculate average X-ray luminosities through stacking. We find an average soft X-ray to infrared ratio of log 〈 L SX / L IR 〉 = –4.3 and an average hard X-ray to infrared ratio of log 〈 L HX / L IR 〉 = –3.8. We report that the X-ray/IR correlation is approximately linear through the entire range of L IR and z probed and, although broadly consistent with the local ( z  〈 0.1) one, it does display some discrepancies. We suggest that these discrepancies are unlikely to be physical, i.e. due to an intrinsic change in the X-ray properties of star-forming galaxies with cosmic time, as there is no significant evidence for evolution of the L X / L IR ratio with redshift. Instead, they are possibly due to selection effects and remaining AGN contamination. We also examine whether dust obscuration in the galaxy plays a role in attenuating X-rays from star formation, by investigating changes in the L X / L IR ratio as a function of the average dust temperature. We conclude that X-rays do not suffer any measurable attenuation in the host galaxy.