The protein-phosphatome of the human malaria parasite Plasmodium falciparum

<p>Abstract</p> <p>Background</p> <p>Malaria, caused by the parasitic protist <it>Plasmodium falciparum</it>, represents a major public health problem in the developing world. The <it>P. falciparum </it>genome has been sequenced, which provides new opportunities for the identification of novel drug targets. We report an exhaustive analysis of the <it>P. falciparum </it>genomic database (PlasmoDB) aimed at identifying and classifying all protein phosphatases (PP) in this organism.</p> <p>Results</p> <p>Using a variety of bioinformatics tools, we identified 27 malarial putative PP sequences within the four major established PP families, plus 7 sequences that we predict to dephosphorylate "non-protein" substrates. We constructed phylogenetic trees to position these sequences relative to PPs from other organisms representing all major eukaryotic phyla except Cercozoans (for which no full genome sequence is available). Predominant observations were: (i) <it>P. falciparum </it>possessed the smallest phosphatome of any of the organisms investigated in this study; (ii) no malarial PP clustered with the tyrosine-specific subfamily of the PTP group (iii) a cluster of 7 closely related members of the PPM/PP2C family is present, and (iv) some <it>P. falciparum </it>protein phosphatases are present in clades lacking any human homologue.</p> <p>Conclusion</p> <p>The considerable phylogenetic distance between Apicomplexa and other Eukaryotes is reflected by profound divergences between the phosphatome of malaria parasites and those of representative organisms from all major eukaryotic phyla, which might be exploited in the context of efforts for the discovery of novel targets for antimalarial chemotherapy.</p

Spectral Variability of Quasars in the Sloan Digital Sky Survey. II: The C IV Line

We examine the variability of the high-ionizaton C IV line in a sample of 105 quasars observed at multiple epochs by the Sloan Digital Sky Survey. We find a strong correlation between the change in the C IV line flux and the change in the line width, but no correlations between the change in flux and changes in line center and skewness. The relation between line flux change and line width change is consistent with a model in which a broad line base varies with greater amplitude than the line core. The objects studied here are more luminous and at higher redshift than those normally studied for variability, ranging in redshift from 1.65 to 4.00 and in absolute r-band magnitude from roughly -24 to -28. Using moment analysis line-fitting techniques, we measure line fluxes, centers, widths and skewnesses for the C IV line at two epochs for each object. The well-known Baldwin Effect is seen for these objects, with a slope beta = -0.22. The sample has a median intrinsic Baldwin Effect slope of beta = -0.85; the C IV lines in these high-luminosity quasars appear to be less responsive to continuum variations than those in lower luminosity AGN. Additionally, we find no evidence for variability of the well known blueshift of the C IV line with respect to the low-ionization Mg II line in the highest flux objects, indicating that this blueshift might be useful as a measure of orientation.Comment: 52 pages, 14 figures, accepted for publication in Ap

Formin-2 drives polymerisation of actin filaments enabling segregation of apicoplasts and cytokinesis in Plasmodium falciparum

Plasmodium falciparum actin, apart from its role in erythrocyte invasion, is implicated in endocytosis, cytokinesis and inheritance of the chloroplast-like organelle - the apicoplast. However, the inability to visualise filamentous actin (F-actin) dynamics, a limitation we recently overcame for Toxoplasma (Periz et al, 2017), restricted characterisation of both F-actin and actin regulatory proteins. Here, we expressed and validated actin-binding chromobodies as F-actin-sensors in Plasmodium falciparum and characterised in-vivo actin dynamics. F-actin could be chemically modulated, and genetically disrupted upon conditionally deleting actin-1. In a comparative approach, we demonstrate that Formin-2, a predicted nucleator of F-actin, is responsible for apicoplast inheritance in both Plasmodium and Toxoplasma, and additionally mediates efficient cytokinesis in Plasmodium. Finally, time-averaged local intensity measurements of F-actin in Toxoplasma conditional mutants revealed molecular determinants of spatiotemporally regulated F-actin flow. Together, our data indicate that Formin-2 is the primary F-actin nucleator during apicomplexan intracellular growth, mediating multiple essential functions

The Spectral Energy Distributions of Red 2MASS AGN

We present infrared (IR) to X-ray spectral energy distributions (SEDs) for 44 red AGN selected from the 2MASS survey on the basis of their red J-K$_S$ color (>2 mag) and later observed by Chandra. In comparison with optically-, radio-, and X-ray selected AGN, their median SEDs are red in the optical and near-IR with little/no blue bump. It thus seems that near-IR color selection isolates the reddest subset of AGN that can be classified optically. The shape of the SEDs is generally consistent with modest absorption by gas (in the X-ray) and dust (in the optical-IR). The levels of obscuration, estimated from X-rays, far-IR and our detailed optical/near-IR color modeling are all consistent implying N_H < few*10^{22} cm^{-2}. We present SED models that show how the AGN optical/near-IR colors change due to differing amounts of reddening, AGN to host galaxy ratio, redshift and scattered light emission and apply them to the sources in the sample. We find that the 2MASS AGN optical color, B-R, and to a lesser extent the near-IR color, J-K$_S$, are strongly affected by reddening, host galaxy emission, redshift, and in few, highly polarized objects, also by scattered AGN light. The obscuration/inclination of the AGN allows us to see weaker emission components which are generally swamped by the AGN.Comment: 52 pages, 17 figures, accepted for publication in Ap

Galaxy Clusters in the IRAC Dark Field. II. Mid-Infrared Sources

We present infrared (IR) luminosities, star formation rates (SFR), colors, morphologies, locations, and active galactic nuclei (AGNs) properties of 24 μm detected sources in photometrically detected high-redshift clusters in order to understand the impact of environment on star formation (SF) and AGN evolution in cluster galaxies. We use three newly identified z = 1 clusters selected from the IRAC dark field; the deepest ever mid-IR survey with accompanying, 14 band multiwavelength data including deep Hubble Space Telescope imaging and deep wide-area Spitzer MIPS 24 μm imaging. We find 90 cluster members with MIPS detections within two virial radii of the cluster centers, of which 17 appear to have spectral energy distributions dominated by AGNs and the rest dominated by SF. We find that 43% of the star-forming sample have IR luminosities L_(IR) > 10^(11) L_☉(luminous IR galaxies). The majority of sources (81%) are spirals or irregulars. A large fraction (at least 25%) show obvious signs of interactions. The MIPS-detected member galaxies have varied spatial distributions as compared to the MIPS-undetected members with one of the three clusters showing SF galaxies being preferentially located on the cluster outskirts, while the other two clusters show no such trend. Both the AGN fraction and the summed SFR of cluster galaxies increase from redshift zero to one, at a rate that is a few times faster in clusters than over the same redshift range in the field. Cluster environment does have an effect on the evolution of both AGN fraction and SFR from redshift one to the present, but does not affect the IR luminosities or morphologies of the MIPS sample. SF happens in the same way regardless of environment making MIPS sources look the same in the cluster and field, however the cluster environment does encourage a more rapid evolution with time as compared to the field

The Soft X-Ray Properties of a Complete Sample of Optically Selected Quasars II. Final Results

We present the final results of a ROSAT PSPC program to study the soft X-ray emission properties of a complete sample of low $z$ quasars. The main results are: 1. There is no evidence for significant soft excess emission or excess foreground absorption by cold gas in 22 of the 23 quasars. 2. The mean 0.2-2 keV continuum of quasars agrees remarkably well with an extrapolation of the mean 1050-350A continuum recently determined by Zheng et al. (1996), indicating that there is no steep soft component below 0.2 keV. 3. The occurrence of warm absorbers in quasars is rather rare, in sharp contrast to lower luminosity AGN. 4. The strongest correlation found is between the spectral slope, alpha_x, and the Hb FWHM. This remarkably strong correlation may result from a dependence of alpha_x on L/L_Edd, as seen in Galactic black hole candidates. 5. There appears to exist a distinct class of ``X-ray weak'' quasars. These may be quasars where the direct X-ray source is obscured, and only scattered X-rays are observed. 6. Thin accretion disk models cannot reproduce the observed optical to soft X-ray spectral shape. An as yet unknown physical mechanism maintains a strong correlation between the optical and soft X-ray emission. 7. The well known difference in alpha_x between radio-loud and radio-quiet quasars may be due only to their different Hb FWHM. 8. The agreement of the 21 cm and X-ray columns implies that He in the diffuse H II component of the Galactic ISM is ionized to He II or He III (shortened abstract).Comment: 19 pages of text only, uses aas2pp4.sty file, to appear in ApJ vol. 447, 3/1/97, complete postscript version of 34 pages including 5 tables and 8 figures available at http://physics.technion.ac.il/~laor/rosat/paper.p

The Far-Infrared Spectral Energy Distributions of X-ray-selected Active Galaxies

[Abridged] We present ISO far-infrared (IR) observations of 21 hard X-ray selected AGN from the HEAO-1 A2 sample. We compare the far-IR to X-ray spectral energy distributions (SEDs) of this sample with various radio and optically selected AGN samples. The hard-X-ray selected sample shows a wider range of optical/UV shapes extending to redder near-IR colors. The bluer objects are Seyfert 1s, while the redder AGN are mostly intermediate or type 2 Seyferts. This is consistent with a modified unification model in which the amount of obscuring material increases with viewing angle and may be clumpy. Such a scenario, already suggested by differing optical/near-IR spectroscopic and X-ray AGN classifications, allows for different amounts of obscuration of the continuum emission in different wavebands and of the broad emission line region which results in a mixture of behaviors for AGN with similar optical emission line classifications. The resulting limits on the column density of obscuring material through which we are viewing the redder AGN are 100 times lower than for the standard optically thick torus models. The resulting decrease in optical depth of the obscuring material allows the AGN to heat more dust at larger radial distances. We show that an AGN-heated, flared, dusty disk with mass 10^9 solar and size of few hundred pc is able to generate optical-far-IR SEDs which reproduce the wide range of SEDs present in our sample with no need for an additional starburst component to generate the long-wavelength, cooler part of the IR continuum.Comment: 40 pages, 14 figures, accepted for publication in Astrophysical Journal, V. 590, June 10, 200

Functional diversity and community assembly of river invertebrates show globally consistent responses to decreasing glacier cover

Global change threatens invertebrate biodiversity and its central role in numerous ecosystem functions and services. Functional trait analyses have been advocated to uncover global mechanisms behind biodiversity responses to environmental change, but the application of this approach for invertebrates is underdeveloped relative to other organism groups. From an evaluation of 363 records comprising >1.23 million invertebrates collected from rivers across nine biogeographic regions on three continents, consistent responses of community trait composition and diversity to replicated gradients of reduced glacier cover are demonstrated. After accounting for a systematic regional effect of latitude, the processes shaping river invertebrate functional diversity are globally consistent. Analyses nested within individual regions identified an increase in functional diversity as glacier cover decreases. Community assembly models demonstrated that dispersal limitation was the dominant process underlying these patterns, although environmental filtering was also evident in highly glacierized basins. These findings indicate that predictable mechanisms govern river invertebrate community responses to decreasing glacier cover globally.This work was funded by the following organisations: The UK Natural Environment Research Council grants and studentships GR9/2913, NE/E003729/1, NE/E004539/1, NE/E004148/1, 20 NE/G523963/1, NER/S/A/2003/11192, and NE/L002574/1; the European Union Environment and Climate Programme Arctic and Alpine Stream Ecosystem Research (AASER) project (ENV-CT95-0164); EU-FP7 Assessing Climate impacts on the Quality and quantity of WAter (ACQWA) project (212250); Icelandic Research Council (954890095, 954890096); University of Iceland Research Fund (GMG96, GMG97, GMG98), Wyoming Center for Environmental Hydrology and Geophysics-National Science Foundation (1208909); USA-Wyoming NASA Space Grant Faculty Research Initiation (#NNX10A095H); USA-NSF Wyoming Epscor; Nationalpark Hohe Tauern, Austria; the Royal Society (International Outgoing Grant 2006/R4); the Leverhulme Trust; the Universities of Leeds, Birmingham, Iceland and Innsbruck; European Centre for Arctic Environmental Research (ARCFAC): a Research Infrastructures Action of the European Community FP6 (026129-2008- 72); the Stelvio National Park (2000-2001); the Autonomous Province of Trento (HIGHEST project, 2001-2004, del. PAT n. 1060/2001; VETTA project, 2003-2006, del. PAT n. 3402/2002); MUSE-Museo delle Scienze. We are grateful to Russell Taylor and Mike Winterbourn at the University of Canterbury, NZ, who helped to collect NZ invertebrate data and assisted with identification, and to Hakon Adalsteinsson who contributed to data collection in Iceland. Many other people, too numerous to mention, assisted with fieldwork at all of the study locations. The European Science Foundation sponsored an exploratory ┘ﾗヴﾆゲｴﾗヮ WﾐデｷデﾉWS さGﾉ;IｷWヴ-fed rivers, hydroecology and climate change: current knowledge and future network of monitoring sites (GLAC-HYDROECO-NETぶざ デｴ;デ ┘;ゲ ｴWﾉS ｷﾐ Birmingham, UK in September of 2013 where some of the ideas in this paper were first discussedPeer Reviewe

Beyond Simple AGN Unification with Chandra-observed 3CRR Sources at 0.5 &lt; z &lt; 1

Low-frequency radio selection finds radio-bright galaxies regardless of the amount of obscuration by gas and dust. We report \chandra\ observations of a complete 178~MHz-selected, and so orientation unbiased, sample of 44 $0.5<z<1$ 3CRR sources. The sample is comprised of quasars and narrow-line radio galaxies (NLRGs) with similar radio luminosities, and the radio structure serves as both an age and an orientation indicator. Consistent with Unification, intrinsic obscuration (measured by \nh, X-ray hardness ratio, and X-ray luminosity) generally increases with inclination. However, the sample includes a population not seen in high-$z$ 3CRR sources: NLRGs viewed at intermediate inclination angles with \nh~$<10^{22}$~cm$^{-2}$. Multiwavelength analysis suggests these objects have lower $L/L_{\rm Edd}$ than typical NLRGs at similar orientation. Thus both orientation and $L/L_{\rm Edd}$ are important, and a "radiation-regulated Unification" provides a better explanation of the sample's observed properties. In comparison with the 3CRR sample at $1<z<2$, our lower-redshift sample shows a higher fraction of Compton-thin NLRGs (45\% vs.\ 29\%) but similar Compton-thick fraction (20\%), implying a larger covering factor of Compton-thin material at intermediate viewing angles and so a more "puffed-up" torus atmosphere. We posit that this is due to a range of $L/L_{\rm Edd}$ extending to lower values in this sample. In contrast, at high redshifts the narrower range and high $L/L_{\rm Edd}$ values allowed orientation (and so simple Unification) to dominate the sample's observed properties