Optical and X-ray Variability in The Least Luminous AGN, NGC4395

We report the detection of optical and X-ray variability in the least luminous known Seyfert galaxy, NGC4395. The featureless continuum changed by a factor of 2 in 6 months, which is typical of more luminous AGN. The largest variation was seen at shorter wavelengths, so that the spectrum becomes `harder' during higher activity states. In a one week optical broad band monitoring program, a 20% change was seen between successive nights. In a 1 month period the spectral shape changed from a power law with spectral index alpha ~0 (characteristic of quasars) to a spectral index alpha ~2 (as observed in other dwarf AGN). ROSAT HRI and PSPC archive data show a variable X-ray source coincident with the galactic nucleus. A change in X-ray flux by a factor \~2 in 15 days has been observed. When compared with more luminous AGN, NGC4395 appears to be very X-ray quiet. The hardness ratio obtained from the PSPC data suggests that the spectrum could be absorbed. We also report the discovery of weak CaIIK absorption, suggesting the presence of a young stellar cluster providing of the order of 10% of the blue light. Using HST UV archive data, together with the optical and X-ray observations, we examine the spectral energy distribution for NGC4395 and discuss the physical conditions implied by the nuclear activity under the standard AGN model. The observations can be explained by either an accreting massive black hole emitting at about 10^(-3) L_(Edd) or by a single old compact SNR with an age of 50 to 500 yr generated by a small nuclear starburst.Comment: 19 pages, 9 figures, to appear in MNRA

FRET imaging of hemoglobin concentration in Plasmodium falciparum-infected red cells.

BACKGROUND: During its intraerythrocytic asexual reproduction cycle Plasmodium falciparum consumes up to 80% of the host cell hemoglobin, in large excess over its metabolic needs. A model of the homeostasis of falciparum-infected red blood cells suggested an explanation based on the need to reduce the colloid-osmotic pressure within the host cell to prevent its premature lysis. Critical for this hypothesis was that the hemoglobin concentration within the host cell be progressively reduced from the trophozoite stage onwards. METHODOLOGY/PRINCIPAL FINDINGS: The experiments reported here were designed to test this hypothesis by direct measurements of the hemoglobin concentration in live, infected red cells. We developed a novel, non-invasive method to quantify the hemoglobin concentration in single cells, based on Förster resonance energy transfer between hemoglobin molecules and the fluorophore calcein. Fluorescence lifetime imaging allowed the quantitative mapping of the hemoglobin concentration within the cells. The average fluorescence lifetimes of uninfected cohorts was 270+/-30 ps (mean+/-SD; N = 45). In the cytoplasm of infected cells the fluorescence lifetime of calcein ranged from 290+/-20 ps for cells with ring stage parasites to 590+/-13 ps and 1050+/-60 ps for cells with young trophozoites and late stage trophozoite/early schizonts, respectively. This was equivalent to reductions in hemoglobin concentration spanning the range from 7.3 to 2.3 mM, in line with the model predictions. An unexpected ancillary finding was the existence of a microdomain under the host cell membrane with reduced calcein quenching by hemoglobin in cells with mature trophozoite stage parasites. CONCLUSIONS/SIGNIFICANCE: The results support the predictions of the colloid-osmotic hypothesis and provide a better understanding of the homeostasis of malaria-infected red cells. In addition, they revealed the existence of a distinct peripheral microdomain in the host cell with limited access to hemoglobin molecules indicating the concentration of substantial amounts of parasite-exported material

Proper motions of field L and T dwarfs -II

By using images taken with WFCAM on UKIRT and SofI on the NTT and combining them with 2MASS we have measured proper motions for 126 L and T dwarfs in the dwarf archive. Two of these L dwarfs appear to have M dwarf common proper motion companions, and 2 also appear to be high velocity dwarfs, indicating possible membership of the thick disc. We have also compared the motion of these 126 objects to that of numerous moving groups, and have identified new members of the Hyades, Ursa Major and Pleiades moving groups. These new objects, as well as those identified in Jameson et al. (2008) have allowed us to refine the L dwarf sequence for Ursa Major that was defined by Jameson et al. (2008).Comment: Accepted for publication in MNRAS. 10 pages, 3 figure

Molecular Identification of a Malaria Merozoite Surface Sheddase

Proteolytic shedding of surface proteins during invasion by apicomplexan parasites is a widespread phenomenon, thought to represent a mechanism by which the parasites disengage adhesin-receptor complexes in order to gain entry into their host cell. Erythrocyte invasion by merozoites of the malaria parasite Plasmodium falciparum requires the shedding of ectodomain components of two essential surface proteins, called MSP1 and AMA1. Both are released by the same merozoite surface “sheddase,” but the molecular identity and mode of action of this protease is unknown. Here we identify it as PfSUB2, an integral membrane subtilisin-like protease (subtilase). We show that PfSUB2 is stored in apical secretory organelles called micronemes. Upon merozoite release it is secreted onto the parasite surface and translocates to its posterior pole in an actin-dependent manner, a trafficking pattern predicted of the sheddase. Subtilase propeptides are usually selective inhibitors of their cognate protease, and the PfSUB2 propeptide is no exception; we show that recombinant PfSUB2 propeptide binds specifically to mature parasite-derived PfSUB2 and is a potent, selective inhibitor of MSP1 and AMA1 shedding, directly establishing PfSUB2 as the sheddase. PfSUB2 is a new potential target for drugs designed to prevent erythrocyte invasion by the malaria parasite

Rescue of DNA damage after constricted migration reveals a mechano-regulated threshold for cell cycle.

Migration through 3D constrictions can cause nuclear rupture and mislocalization of nuclear proteins, but damage to DNA remains uncertain, as does any effect on cell cycle. Here, myosin II inhibition rescues rupture and partially rescues the DNA damage marker γH2AX, but an apparent block in cell cycle appears unaffected. Co-overexpression of multiple DNA repair factors or antioxidant inhibition of break formation also exert partial effects, independently of rupture. Combined treatments completely rescue cell cycle suppression by DNA damage, revealing a sigmoidal dependence of cell cycle on excess DNA damage. Migration through custom-etched pores yields the same damage threshold, with ∼4-µm pores causing intermediate levels of both damage and cell cycle suppression. High curvature imposed rapidly by pores or probes or else by small micronuclei consistently associates nuclear rupture with dilution of stiff lamin-B filaments, loss of repair factors, and entry from cytoplasm of chromatin-binding cGAS (cyclic GMP-AMP synthase). The cell cycle block caused by constricted migration is nonetheless reversible, with a potential for DNA misrepair and genome variation

An ecological perspective on children’s play with digital technologies in South Africa and the United Kingdom

This paper reports a mixed-methods study of the play of children (3–11) with digital technologies in South Africa (SA) and the United Kingdom (UK), discussing the interrelatedness of access to devices and the Internet, contextual realities, and adult-child relations. An adapted ecological model [Bronfenbrenner (1979) The ecology of human development: Experiments by nature and design. Harvard University Press] guided analysis. Parents and carers in the UK were more likely than their SA counterparts to report children's engagement in object, construction and transgressive digital play, correlating with access differences, especially to tablet devices. However, play incorporating technologies was extensive, even in contexts in SA with limited access to a wide range of devices or readily available internet. Despite relying primarily on smartphones, children in SA were more likely to create digital content unassisted than those in the UK. The qualitative data complicate understandings of particular play types, including transgressive digital play

Subcellular discharge of a serine protease mediates release of invasive malaria parasites from host erythrocytes.

The most virulent form of malaria is caused by waves of replication of blood stages of the protozoan pathogen Plasmodium falciparum. The parasite divides within an intraerythrocytic parasitophorous vacuole until rupture of the vacuole and host-cell membranes releases merozoites that invade fresh erythrocytes to repeat the cycle. Despite the importance of merozoite egress for disease progression, none of the molecular factors involved are known. We report that, just prior to egress, an essential serine protease called PfSUB1 is discharged from previously unrecognized parasite organelles (termed exonemes) into the parasitophorous vacuole space. There, PfSUB1 mediates the proteolytic maturation of at least two essential members of another enzyme family called SERA. Pharmacological blockade of PfSUB1 inhibits egress and ablates the invasive capacity of released merozoites. Our findings reveal the presence in the malarial parasitophorous vacuole of a regulated, PfSUB1-mediated proteolytic processing event required for release of viable parasites from the host erythrocyte

The crust and upper mantle structure of central and West Antarctica from Bayesian inversion of Rayleigh Wave and receiver functions

Author Posting. © American Geophysical Union, 2018. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Solid Earth 123 (2018): 7824-7849, doi:10.1029/2017JB015346.We construct a new seismic model for central and West Antarctica by jointly inverting Rayleigh wave phase and group velocities along with P wave receiver functions. Ambient noise tomography exploiting data from more than 200 seismic stations deployed over the past 18 years is used to construct Rayleigh wave phase and group velocity dispersion maps. Comparison between the ambient noise phase velocity maps with those constructed using teleseismic earthquakes confirms the accuracy of both results. These maps, together with P receiver function waveforms, are used to construct a new 3‐D shear velocity (Vs) model for the crust and uppermost mantle using a Bayesian Monte Carlo algorithm. The new 3‐D seismic model shows the dichotomy of the tectonically active West Antarctica (WANT) and the stable and ancient East Antarctica (EANT). In WANT, the model exhibits a slow uppermost mantle along the Transantarctic Mountains (TAMs) front, interpreted as the thermal effect from Cenozoic rifting. Beneath the southern TAMs, the slow uppermost mantle extends horizontally beneath the traditionally recognized EANT, hypothesized to be associated with lithospheric delamination. Thin crust and lithosphere observed along the Amundsen Sea coast and extending into the interior suggest involvement of these areas in Cenozoic rifting. EANT, with its relatively thick and cold crust and lithosphere marked by high Vs, displays a slower Vs anomaly beneath the Gamburtsev Subglacial Mountains in the uppermost mantle, which we hypothesize may be the signature of a compositionally anomalous body, perhaps remnant from a continental collision.National Science Foundation Grant Numbers: PLR‐1142518, PLR‐1246712, PLR 1246151, PLR‐1246416, PLR‐1744883, PLR‐ 17448832019-03-2

Formation of the Food Vacuole in Plasmodium falciparum: A Potential Role for the 19 kDa Fragment of Merozoite Surface Protein 1 (MSP119)

Plasmodium falciparum Merozoite Surface Protein 1 (MSP1) is synthesized during schizogony as a 195-kDa precursor that is processed into four fragments on the parasite surface. Following a second proteolytic cleavage during merozoite invasion of the red blood cell, most of the protein is shed from the surface except for the C-terminal 19-kDa fragment (MSP119), which is still attached to the merozoite via its GPI-anchor. We have examined the fate of MSP119 during the parasite's subsequent intracellular development using immunochemical analysis of metabolically labeled MSP119, fluorescence imaging, and immuno-electronmicroscopy. Our data show that MSP119 remains intact and persists to the end of the intracellular cycle. This protein is the first marker for the biogenesis of the food vacuole; it is rapidly endocytosed into small vacuoles in the ring stage, which coalesce to form the single food vacuole containing hemozoin, and persists into the discarded residual body. The food vacuole is marked by the presence of both MSP119 and the chloroquine resistance transporter (CRT) as components of the vacuolar membrane. Newly synthesized MSP1 is excluded from the vacuole. This behavior indicates that MSP119 does not simply follow a classical lysosome-like clearance pathway, instead, it may play a significant role in the biogenesis and function of the food vacuole throughout the intra-erythrocytic phase

Transdimensional inversion of receiver functions and surface wave dispersion

International audienceWe present a novel method for joint inversion of receiver functions and surface wave dispersion data, using a transdimensional Bayesian formulation. This class of algorithm treats the number of model parameters (e.g. number of layers) as an unknown in the problem. The dimension of the model space is variable and a Markov chain Monte Carlo (McMC) scheme is used to provide a parsimonious solution that fully quantifies the degree of knowledge one has about seismic structure (i.e constraints on the model, resolution, and trade-offs). The level of data noise (i.e. the covariance matrix of data errors) effectively controls the information recoverable from the data and here it naturally determines the complexity of the model (i.e. the number of model parameters). However, it is often difficult to quantify the data noise appropriately, particularly in the case of seismic waveform inversion where data errors are correlated. Here we address the issue of noise estimation using an extended Hierarchical Bayesian formulation, which allows both the variance and covariance of data noise to be treated as unknowns in the inversion. In this way it is possible to let the data infer the appropriate level of data fit. In the context of joint inversions, assessment of uncertainty for different data types becomes crucial in the evaluation of the misfit function. We show that the Hierarchical Bayes procedure is a powerful tool in this situation, because it is able to evaluate the level of information brought by different data types in the misfit, thus removing the arbitrary choice of weighting factors. After illustrating the method with synthetic tests, a real data application is shown where teleseismic receiver functions and ambient noise surface wave dispersion measurements from the WOMBAT array (South-East Australia) are jointly inverted to provide a probabilistic 1D model of shear-wave velocity beneath a given station