Genome-Wide Association and Linkage Analysis of Quantitative Traits: Comparison pf Likelihood-Ratio Test and Conditional Score Statistic

Over the past decade, genetic analysis has shifted from linkage studies, which identify broad regions containing putative trait loci, to genome-wide association studies, which detect the association of a marker with a specific phenotype. Because linkage and association analysis provide complementary information, developing a method to combine these analyses may increase the power to detect a true association. In this paper we compare a linkage score and association score test as well as a newly proposed combination of these two scores with traditional linkage and association methods.National Institutes of Health (National Institute of General Medical Sciences R01 GM031575, National Center for Research Resources Shared Instrumentation grant 1S10RR163736-01A1

Genome-wide association and linkage analysis of quantitative traits: comparison of likelihood-ratio test and conditional score statistic

Over the past decade, genetic analysis has shifted from linkage studies, which identify broad regions containing putative trait loci, to genome-wide association studies, which detect the association of a marker with a specific phenotype. Because linkage and association analysis provide complementary information, developing a method to combine these analyses may increase the power to detect a true association. In this paper we compare a linkage score and association score test as well as a newly proposed combination of these two scores with traditional linkage and association methods

The Large-scale Distribution of Cool Gas around Luminous Red Galaxies

We present a measurement of the correlation function between luminous red galaxies and cool gas traced by Mg II \lambda \lambda 2796, 2803 absorption, on scales ranging from about 30 kpc to 20 Mpc. The measurement is based on cross-correlating the positions of about one million red galaxies at z~0.5 and the flux decrements induced in the spectra of about 10^5 background quasars from the Sloan Digital Sky Survey. We find that: (i) This galaxy-gas correlation reveals a change of slope on scales of about 1 Mpc, consistent with the expected transition from a dark matter halo dominated environment to a regime where clustering is dominated by halo-halo correlations. Assuming that, on average, the distribution of Mg II gas follows that of dark matter up to a gas-to-mass ratio, we find the standard halo model to provide an accurate description of the gas distribution over three orders of magnitude in scale. Within this framework we estimate the average host halo mass of luminous red galaxies to be about 10^{13.5} M_solar, in agreement with other methods. We also find the Mg II gas-to-mass ratio around LRGs to be consistent with the cosmic value estimated on Mpc scales. Combining our galaxy-gas correlation and the galaxy-mass correlation function from galaxy-galaxy lensing analyses we can directly measure the Mg II gas-to-mass ratio as a function of scale and reach the same conclusion. (ii) From line-width estimates, we show that the velocity dispersion of the gas clouds also shows the expected 1- and 2-halo behaviors. On large scales the gas distribution follows the Hubble flow, whereas on small scales we observe the velocity dispersion of the Mg II gas clouds to be lower than that of collisionless dark matter particles within their host halo. This is in line with the fact that cool clouds are subject to the pressure of the virialized hot gas.Comment: 18 pages, 11 figures, 1 table, submitted to MNRA

Herpesviruses and Autophagy: Catch Me If You Can!

Autophagy is an evolutionarily conserved cellular degradation pathway involving the digestion of intracellular components via the lysosomal pathway. The autophagic pathway constitutively maintains cellular homeostasis by recycling cytoplasmic organelles and proteins, but it is also stimulated by environmental stress conditions, such as starvation, oxidative stress, and the accumulation of misfolded proteins. It also acts as a cellular defense mechanism against microorganisms by contributing to both the innate and adaptive immunity, and by eliminating intracellular pathogens (xenophagy). There is growing evidence that host cells try to control Herpesvirus infections by activating the autophagic machinery. However, it is well-known that Herpesviruses are smart pathogens and several, such as HSV-1, HCMV and HHV-8, are known to have developed numerous defense strategies for evading the host’s immune response. Inhibition of the antiviral autophagic mechanism has also been reported. Autophagy has also been shown to enhance the major histocompatibility complex presentation of at least two viral proteins, the EBV-encoded EBNA-1 and the HSV-1 encoded gB. In this review, we present an overview of recent advances in our understanding of the complex interplay between autophagy and Herpesviruses

Small-scale fisheries catch and fishing effort in the Socotra Archipelago (Yemen) between 1950 and 2019

The Socotra Archipelago (Yemen), a group of four islands off the north-eastern tip of Africa in the western Indian Ocean, has a population that relies heavily on small-scale fishing for livelihoods and food security. However, the reporting of fisheries catches by Yemen has consistently been incomplete, with artisanal (small-scale, commercial) catches underreported and small-scale non-commercial subsistence and recreational catches not reported at all. Here, we reconstruct the total small-scale catches and fishing effort from the waters of the Socotra Archipelago for 1950 to 2019, and derive catch-per-unit-effort (CPUE) estimates for these fisheries. The catch officially reported by the Food and Agriculture Organization on behalf of Yemen that was assumed taken from the archipelago is thought to be around 20% of the total reconstructed catch for the archipelago. The reconstructed small-scale catch increased from ~1,500 t in 1950 to an all-time peak of 12,000 t in 2000 before declining to 3,300 t by 2014. Thereafter, catches increased again slightly to just over 3,700 t·year-1 by 2019. Artisanal catches accounted for around 70% of total small-scale catches prior to 2010, but made up only around 46% by 2019. Conversely, subsistence catches increased from ~1,000 t in 2010 to ~2,000 t in 2019, and accounted for 54% of total catches by 2019. Small-scale fishing effort increased by over 1000% since 1950 and reached over 11 million kWdays by 2019. The CPUE derived for small-scale fisheries declined by 78% since 1950, from 1.4 kg·kWday-1 to 0.3 kg·kWday-1 in 2019, with most of the decline occurring after 2000. Our findings suggest resource overexploitation, and may assist efforts to more sustainably manage the Socotra Archipelago’s fish stocks. Small-scale fisheries support food and nutrient security of the local population, not least during political and humanitarian crises such as in Yemen

Enzymatic and structural characterization of HAD5, an essential phosphomannomutase of malaria-causing parasites

The malaria-causing parasite Plasmodium falciparum is responsible for over 200 million infections and 400,000 deaths per year. At multiple stages during its complex life cycle, P. falciparum expresses several essential proteins tethered to its surface by glycosylphosphatidylinositol (GPI) anchors, which are critical for biological processes such as parasite egress and reinvasion of host red blood cells. Targeting this pathway therapeutically has the potential to broadly impact parasite development across several life stages. Here, we characterize an upstream component of parasite GPI anchor biosynthesis, the putative phosphomannomutase (PMM) (EC 5.4.2.8), HAD5 (PF3D7_1017400). We confirmed the PMM and phosphoglucomutase activities of purified recombinant HAD5 by developing novel linked enzyme biochemical assays. By regulating the expression of HAD5 in transgenic parasites with a TetR-DOZI-inducible knockdown system, we demonstrated that HAD5 is required for malaria parasite egress and erythrocyte reinvasion, and we assessed the role of HAD5 in GPI anchor synthesis by autoradiography of radiolabeled glucosamine and thin layer chromatography. Finally, we determined the three-dimensional X-ray crystal structure of HAD5 and identified a substrate analog that specifically inhibits HAD5 compared to orthologous human PMMs in a time-dependent manner. These findings demonstrate that the GPI anchor biosynthesis pathway is exceptionally sensitive to inhibition in parasites and that HAD5 has potential as a specific, multistage antimalarial target

Antenatal depression, treatment with selective serotonin reuptake inhibitors, and neonatal brain structure: A propensity-matched cohort study

The aim of this propensity-matched cohort study was to evaluate the impact of prenatal SSRI exposure and a history of maternal depression on neonatal brain volumes and white matter microstructure. SSRI-exposed neonates (n = 27) were matched to children of mothers with no history of depression or SSRI use (n=54). Additionally, neonates of mothers with a history of depression, but no prenatal SSRI exposure (n=41), were matched to children of mothers with no history of depression or SSRI use (n=82). Structural magnetic resonance imaging and diffusion weighted imaging scans were acquired with a 3T Siemens Allegra scanner. Global tissue volumes were characterized using an automatic, atlas-moderated expectation maximization segmentation tool. Local differences in gray matter volumes were examined using deformation-based morphometry. Quantitative tractography was performed using an adaptation of the UNC-Utah NA-MIC DTI framework. SSRI-exposed neonates exhibited widespread changes in white matter microstructure compared to matched controls. Children exposed to a history of maternal depression but no SSRIs showed no significant differences in brain development compared to matched controls. No significant differences were found in global or regional tissue volumes. Additional research is needed to clarify whether SSRIs directly alter white matter development or whether this relationship is mediated by depressive symptoms during pregnancy

The molecular characterisation of Escherichia coli K1 isolated from neonatal nasogastric feeding tubes

Background: The most common cause of Gram-negative bacterial neonatal meningitis is E. coli K1. It has a mortality rate of 10–15%, and neurological sequelae in 30– 50% of cases. Infections can be attributable to nosocomial sources, however the pre-colonisation of enteral feeding tubes has not been considered as a specific risk factor. Methods: Thirty E. coli strains, which had been isolated in an earlier study, from the residual lumen liquid and biofilms of neonatal nasogastric feeding tubes were genotyped using pulsed-field gel electrophoresis, and 7-loci multilocus sequence typing. Potential pathogenicity and biofilm associated traits were determined using specific PCR probes, genome analysis, and in vitro tissue culture assays. Results: The E. coli strains clustered into five pulsotypes, which were genotyped as sequence types (ST) 95, 73, 127, 394 and 2076 (Achman scheme). The extra-intestinal pathogenic E. coli (ExPEC) phylogenetic group B2 ST95 serotype O1:K1:NM strains had been isolated over a 2 week period from 11 neonates who were on different feeding regimes. The E. coli K1 ST95 strains encoded for various virulence traits associated with neonatal meningitis and extracellular matrix formation. These strains attached and invaded intestinal, and both human and rat brain cell lines, and persisted for 48 h in U937 macrophages. E. coli STs 73, 394 and 2076 also persisted in macrophages and invaded Caco-2 and human brain cells, but only ST394 invaded rat brain cells. E. coli ST127 was notable as it did not invade any cell lines. Conclusions: Routes by which E. coli K1 can be disseminated within a neonatal intensive care unit are uncertain, however the colonisation of neonatal enteral feeding tubes may be one reservoir source which could constitute a serious health risk to neonates following ingestion

Do galaxy global relationships emerge from local ones? The SDSS IV MaNGA surface mass density-metallicity relation

We present the stellar surface mass density versus gas metallicity (Σ*-Z) relation for more than 500 000 spatially resolved star-forming resolution elements (spaxels) from a sample of 653 disc galaxies included in the SDSS IV MaNGA survey. We find a tight relation between these local properties, with higher metallicities as the surface density increases. This relation extends over three orders of magnitude in the surface mass density and a factor of 4 in metallicity. We show that this local relationship can simultaneously reproduce two well-known properties of disc galaxies: their global mass–metallicity relationship and their radial metallicity gradients. We also find that the Σ*-Z relation is largely independent of the galaxy's total stellar mass and specific star formation rate (sSFR), except at low stellar mass and high sSFR. These results suggest that in the present-day universe local properties play a key role in determining the gas-phase metallicity in typical disc galaxies

The Ninth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-III Baryon Oscillation Spectroscopic Survey

The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median z=0.52), 102,100 new quasar spectra (median z=2.32), and 90,897 new stellar spectra, along with the data presented in previous data releases. These spectra were obtained with the new BOSS spectrograph and were taken between 2009 December and 2011 July. In addition, the stellar parameters pipeline, which determines radial velocities, surface temperatures, surface gravities, and metallicities of stars, has been updated and refined with improvements in temperature estimates for stars with T_eff<5000 K and in metallicity estimates for stars with [Fe/H]>-0.5. DR9 includes new stellar parameters for all stars presented in DR8, including stars from SDSS-I and II, as well as those observed as part of the SDSS-III Sloan Extension for Galactic Understanding and Exploration-2 (SEGUE-2). The astrometry error introduced in the DR8 imaging catalogs has been corrected in the DR9 data products. The next data release for SDSS-III will be in Summer 2013, which will present the first data from the Apache Point Observatory Galactic Evolution Experiment (APOGEE) along with another year of data from BOSS, followed by the final SDSS-III data release in December 2014.Comment: 9 figures; 2 tables. Submitted to ApJS. DR9 is available at http://www.sdss3.org/dr