Mosaic DNA imports with interspersions of recipient sequence after natural transformation of Helicobacter pylori

Helicobacter pylori colonizes the gastric mucosa of half of the human population, causing gastritis, ulcers, and cancer. H. pylori is naturally competent for transformation by exogenous DNA, and recombination during mixed infections of one stomach with multiple H. pylori strains generates extensive allelic diversity. We developed an in vitro transformation protocol to study genomic imports after natural transformation of H. pylori. The mean length of imported fragments was dependent on the combination of donor and recipient strain and varied between 1294 bp and 3853 bp. In about 10% of recombinant clones, the imported fragments of donor DNA were interrupted by short interspersed sequences of the recipient (ISR) with a mean length of 82 bp. 18 candidate genes were inactivated in order to identify genes involved in the control of import length and generation of ISR. Inactivation of the antimutator glycosylase MutY increased the length of imports, but did not have a significant effect on ISR frequency. Overexpression of mutY strongly increased the frequency of ISR, indicating that MutY, while not indispensable for ISR formation, is part of at least one ISR-generating pathway. The formation of ISR in H. pylori increases allelic diversity, and contributes to the uniquely low linkage disequilibrium characteristic of this pathogen

Predictions for the X-ray circumgalactic medium of edge-on discs and spheroids

We investigate how the X-ray circumgalactic medium (CGM) of present-day galaxies depends on galaxy morphology and azimuthal angle using mock observations generated from the EAGLE cosmological hydrodynamic simulation. By creating mock stacks of eROSITA-observed galaxies oriented to be edge-on, we make several observationally-testable predictions for galaxies in the stellar mass range M⋆ = 1010.7 − 11.2 M⊙. The soft X-ray CGM of disc galaxies is between 60 and 100% brighter along the semi-major axis compared to the semi-minor axis, between 10-30 kpc. This azimuthal dependence is a consequence of the hot (T > 106 K) CGM being non-spherical: specifically it is flattened along the minor axis such that denser and more luminous gas resides in the disc plane and co-rotates with the galaxy. Outflows enrich and heat the CGM preferentially perpendicular to the disc, but we do not find an observationally-detectable signature along the semi-minor axis. Spheroidal galaxies have hotter CGMs than disc galaxies related to spheroids residing at higher halos masses, which may be measurable through hardness ratios spanning the 0.2 − 1.5 keV band. While spheroids appear to have brighter CGMs than discs for the selected fixed M⋆ bin, this owes to spheroids having higher stellar and halo masses within that M⋆ bin, and obscures the fact that both simulated populations have similar total CGM luminosities at the exact same M⋆. Discs have brighter emission inside 20 kpc and more steeply declining profiles with radius than spheroids. We predict that the eROSITA 4-year all-sky survey should detect many of the signatures we predict here, although targeted follow-up observations of highly inclined nearby discs after the survey may be necessary to observe some of our azimuthally-dependent predictions

Presence and Persistence of Ebola or Marburg Virus in Patients and Survivors: A Rapid Systematic Review

Background: The 2013-15 Ebola outbreak was unprecedented due to sustainedtransmission within urban environments and thousands of survivors. In 2014 the World Health Organization stated that there was insufficient evidence to give definitive guidance about which body fluids are infectious and when they pose a risk to humans. We report a rapid systematic review of published evidence on the presence of filoviruses in body fluids of infected people and survivors. Methods: Scientific articles were screened for information about filovirus in human body fluids. The aim was to find primary data that suggested high likelihood of actively infectious filovirus in human body fluids (viral RNA). Eligible infections were from Marburg virus (MARV or RAVV) and Zaire, Sudan, Taï Forest and Bundibugyo species of Ebola. [1] Cause of infection had to be laboratory confirmed (in practice either tissue culture or RT-PCR tests), or evidenced by compatible clinical history with subsequent positivity for filovirus antibodies or inflammatory factors. Data were extracted and summarized narratively. Results: 6831 unique articles were found, and after screening, 33 studies were eligible. For most body fluid types there were insufficient patients to draw strong conclusions, and prevalence of positivity was highly variable. Body fluids taken >16 days after onset were usually negative. In the six studies that used both assay methods RT-PCR tests for filovirus RNA gave positive results about 4 times more often than tissue culture. Conclusions: Filovirus was reported in most types of body fluid, but not in every sample from every otherwise confirmed patient. Apart from semen, most non-blood, RT-PCR positive samples are likely to be culture negative and so possibly of low infectious risk. Nevertheless, it is not apparent how relatively infectious many body fluids are during or after illness, even when culture-positive, not least because most test results come from more severe cases. Contact with blood and blood-stained body fluids remains the major risk for disease transmission because of the known high viral loads in blood

EAGLE and Illustris-TNG Predictions for Resolved eROSITA X-Ray Observations of the Circumgalactic Medium around Normal Galaxies

We simulate stacked observations of nearby hot X-ray coronae associated with galaxies in the EAGLE and Illustris-TNG hydrodynamic simulations. A forward modeling pipeline is developed to predict 4-year eROSITA observations and stacked image analysis, including the effects of instrumental and astrophysical backgrounds. We propose an experiment to stack z~0.01 galaxies separated by specific star-formation rate (sSFR) to examine how the hot (T>=10^6 K) circumgalactic medium (CGM) differs for high- and low-sSFR galaxies. The simulations indicate that the hot CGM of low-mass (M_*~10^{10.5} Msol), high-sSFR (defined as the top one-third ranked by sSFR) central galaxies will be detectable to a galactocentric radius r~30-50 kpc. Both simulations predict lower luminosities at fixed stellar mass for the low-sSFR galaxies (the lower third of sSFR) with Illustris-TNG predicting 3x brighter coronae around high-sSFR galaxies than EAGLE. Both simulations predict detectable emission out to r~150-200 kpc for stacks centered on high-mass (M_*~10^{11.0} Msol) galaxies, with EAGLE predicting brighter X-ray halos. The extended soft X-ray luminosity correlates strongly and positively with the mass of circumgalactic gas within the virial radius (f_{CGM}). Prior analyses of both simulations have established that f_{CGM} is reduced by expulsive feedback driven mainly by black hole growth, which quenches galaxy growth by inhibiting replenishment of the ISM. Both simulations predict that eROSITA stacks should not only conclusively detect and resolve the hot CGM around L^* galaxies for the first time, but provide a powerful probe of how the baryon cycle operates, for which there remains an absence of consensus between state-of-the-art simulations

Imprint of Drivers of Galaxy Formation in the Circumgalactic Medium

The majority of baryons reside beyond the optical extent of a galaxy in the circumgalactic and intergalactic media (CGM/IGM). Gaseous halos are inextricably linked to the appearance of their host galaxies through a complex story of accretion, feedback, and continual recycling. The energetic processes, which define the state of gas in the CGM, are the same ones that 1) regulate stellar growth so that it is not over-efficient, and 2) create the diversity of today's galaxy colors, SFRs, and morphologies spanning Hubble's Tuning Fork Diagram. They work in concert to set the speed of growth on the star-forming Main Sequence, transform a galaxy across the Green Valley, and maintain a galaxy's quenched appearance on the Red Sequence. Most baryons in halos more massive than 10^12 Msolar along with their high-energy physics and dynamics remain invisible because that gas is heated above the UV ionization states. We argue that information on many of the essential drivers of galaxy evolution is primarily contained in this "missing" hot gas phase. Completing the picture of galaxy formation requires uncovering the physical mechanisms behind stellar and SMBH feedback driving mass, metals, and energy into the CGM. By opening galactic hot halos to new wavebands, we not only obtain fossil imprints of >13 Gyrs of evolution, but observe on-going hot-mode accretion, the deposition of superwind outflows into the CGM, and the re-arrangement of baryons by SMBH feedback. A description of the flows of mass, metals, and energy will only be complete by observing the thermodynamic states, chemical compositions, structure, and dynamics of T>=10^6 K halos. These measurements are uniquely possible with a next-generation X-ray observatory if it provides the sensitivity to detect faint CGM emission, spectroscopic power to measure absorption lines and gas motions, and high spatial resolution to resolve structures

Unveiling Novel RecO Distant Orthologues Involved in Homologous Recombination

The generation of a RecA filament on single-stranded DNA is a critical step in homologous recombination. Two main pathways leading to the formation of the nucleofilament have been identified in bacteria, based on the protein complexes mediating RecA loading: RecBCD (AddAB) and RecFOR. Many bacterial species seem to lack some of the components involved in these complexes. The current annotation of the Helicobacter pylori genome suggests that this highly diverse bacterial pathogen has a reduced set of recombination mediator proteins. While it is now clear that homologous recombination plays a critical role in generating H. pylori diversity by allowing genomic DNA rearrangements and integration through transformation of exogenous DNA into the chromosome, no complete mediator complex is deduced from the sequence of its genome. Here we show by bioinformatics analysis the presence of a RecO remote orthologue that allowed the identification of a new set of RecO proteins present in all bacterial species where a RecR but not RecO was previously identified. HpRecO shares less than 15% identity with previously characterized homologues. Genetic dissection of recombination pathways shows that this novel RecO and the remote RecB homologue present in H. pylori are functional in repair and in RecA-dependent intrachromosomal recombination, defining two initiation pathways with little overlap. We found, however, that neither RecOR nor RecB contributes to transformation, suggesting the presence of a third, specialized, RecA-dependent pathway responsible for the integration of transforming DNA into the chromosome of this naturally competent bacteria. These results provide insight into the mechanisms that this successful pathogen uses to generate genetic diversity and adapt to changing environments and new hosts

Accretion Disks Around Black Holes: Twenty Five Years Later

We study the progress of the theory of accretion disks around black holes in last twenty five years and explain why advective disks are the best bet in explaining varied stationary and non-stationary observations from black hole candidates. We show also that the recently proposed advection dominated flows are incorrect.Comment: 30 Latex pages including figures. Kluwer Style files included. Appearing in `Observational Evidence for Black Holes in the Universe', ed. Sandip K. Chakrabarti, Kluwer Academic Publishers (DORDRECHT: Holland

Product market competition with differentiated goods and social welfare in the presence of an industry-wide union

Mainstream locus communis indicates that a more competitive product market leads to higher social welfare levels. Using a Conjectural Variation (CV) model, this research note analyzes the effects on welfare of different degrees of product market competition in a duopoly with differentiated goods. Bargaining between the firms and the industry-wide union occurs under the Efficient Bargaining (EB) model. The work indicates that, with close substitute goods, social welfare is maximized for the inter- mediate levels of market competition, whereas more independent goods lead to the standard result of a high welfare level under competitive markets.info:eu-repo/semantics/publishedVersio

d(Tree)-by-dx : automatic and exact differentiation of genetic programming trees

Genetic programming (GP) has developed to the point where it is a credible candidate for the `black box' modeling of real systems. Wider application, however, could greatly benefit from its seamless embedding in conventional optimization schemes, which are most efficiently carried out using gradient-based methods. This paper describes the development of a method to automatically differentiate GP trees using a series of tree transformation rules; the resulting method can be applied an unlimited number of times to obtain higher derivatives of the function approximated by the original, trained GP tree. We demonstrate the utility of our method using a number of illustrative gradient-based optimizations that embed GP models

Variation in LPA Is Associated with Lp(a) Levels in Three Populations from the Third National Health and Nutrition Examination Survey

The distribution of lipoprotein(a) [Lp(a)] levels can differ dramatically across diverse racial/ethnic populations. The extent to which genetic variation in LPA can explain these differences is not fully understood. To explore this, 19 LPA tagSNPs were genotyped in 7,159 participants from the Third National Health and Nutrition Examination Survey (NHANES III). NHANES III is a diverse population-based survey with DNA samples linked to hundreds of quantitative traits, including serum Lp(a). Tests of association between LPA variants and transformed Lp(a) levels were performed across the three different NHANES subpopulations (non-Hispanic whites, non-Hispanic blacks, and Mexican Americans). At a significance threshold of p<0.0001, 15 of the 19 SNPs tested were strongly associated with Lp(a) levels in at least one subpopulation, six in at least two subpopulations, and none in all three subpopulations. In non-Hispanic whites, three variants were associated with Lp(a) levels, including previously known rs6919246 (p = 1.18×10−30). Additionally, 12 and 6 variants had significant associations in non-Hispanic blacks and Mexican Americans, respectively. The additive effects of these associated alleles explained up to 11% of the variance observed for Lp(a) levels in the different racial/ethnic populations. The findings reported here replicate previous candidate gene and genome-wide association studies for Lp(a) levels in European-descent populations and extend these findings to other populations. While we demonstrate that LPA is an important contributor to Lp(a) levels regardless of race/ethnicity, the lack of generalization of associations across all subpopulations suggests that specific LPA variants may be contributing to the observed Lp(a) between-population variance