Csaba Kiss

Human herpesvirus-8-encoded LNA-1 accumulates in heterochromatin-associated nuclear bodies

Subnuclear distribution of the human herpesvirus-8 (HHV-8)- encoded nuclear protein LNA-1 was analysed at high resolution in body cavity (BC) lymphoma-derived cell lines, in cell hybrids between BC cells and various human and mouse cells and in freshly infected K562 and ECV cell lines. Three-dimensional reconstruction of nuclei from optical sections and quantitative analysis of the distribution of LNA-1 fluorescence in relation to chromatin showed that LNA-1 associates preferentially with the border of heterochromatin in the interphase nuclei. This was further confirmed in the following systems: in endo- and exonuclease-digested nuclei, in human-mouse (BC-1-Sp2- 0) hybrids and on chromatin spreads. LNA-1 was found to bind to mitotic chromosomes at random. Epstein-Barr virus (EBV), but not HHV-8, was rapidly lost from mouse-human hybrid cells in parallel with the loss of human chromosomes. HHV-8 could persist on the residual mouse background for more than 8 months. In early human-mouse hybrids that contain a single fused nucleus, LNA-1 preferentially associates with human chromatin. After the gradual loss of the human chromosomes, LNA-1 becomes associated with the murine pericentromeric heterochromatin. In human-human hybrids derived from the fusion of the HHV-8-carrying BCBL-1 cells and the EBV-immortalized lymphoblastoid cell line IB4, LNA-1 did not co-localize with EBNA-1, EBNA-2, EBNA-5 or EBNA-6. LNA-1 was not associated with PML containing ND10 bodies either. DNase but not RNase or detergent treatment of isolated nuclei destroys LNA-1 bodies. In advanced apoptotic cells LNA- 1 bodies remain intact but are not included in the apoptotic bodies themselves.

TNOs are Cool: A survey of the trans-Neptunian region

Aims. Trans-Neptunian objects (TNOs) are bodies populating the Kuiper belt and they are believed to retain the most pristine and least altered material of the solar system. The Herschel open time key programme entitled “TNOs are Cool: A survey of the trans-Neptunian region” has been awarded 373 h to investigate the albedo, size distribution and thermal properties of TNOs and Centaurs. Here we focus on the brightest targets observed by both the PACS and SPIRE multiband photometers: the dwarf planet Haumea, six TNOs (Huya, Orcus, Quaoar, Salacia, 2002 UX25, and 2002 TC302), and two Centaurs (Chiron and Chariklo).Methods. Flux densities are derived from PACS and SPIRE instruments using optimised data reduction methods. The spectral energy distribution obtained with the Herschel PACS and SPIRE instruments over 6 bands (centred at 70, 100, 160, 250, 350, and 500 μm), with Spitzer-MIPS at 23.7 and 71.4 μm, and with WISE at 11.6 and 22.1 μm in the case of 10199 Chariklo, has been modelled with the NEATM thermal model in order to derive the albedo, diameter, and beaming factor. For the Centaurs Chiron and Chariklo and for the 1000 km sized Orcus and Quaoar, a thermophysical model was also run to better constrain their thermal properties.Results. We derive the size, albedo, and thermal properties, including thermal inertia and surface emissivity, for the 9 TNOs and Centaurs. Several targets show a significant decrease in their spectral emissivity longwards of ~300 μm and especially at 500 μm. Using our size estimations and the mass values available in the literature, we also derive the bulk densities for the binaries Quaoar/Weywot (2.18-0.36+0.43 g/cm3), Orcus/Vanth (1.53-0.13+0.15 g/cm3), and Salacia/Actea (1.29-0.23+0.29 g/cm3). Quaoar’s density is similar to that of the other dwarf planets Pluto and Haumea, and its value implies high contents of refractory materials mixed with ices.

“TNOs are Cool”: a survey of the trans-Neptunian region - VI. Herschel/PACS observations and thermal modeling of 19 classical Kuiper belt objects

Trans-Neptunian objects (TNO) represent the leftovers of the formation of the Solar System. Their physical properties provide constraints to the models of formation and evolution of the various dynamical classes of objects in the outer Solar System. Based on a sample of 19 classical TNOs we determine radiometric sizes, geometric albedos and beaming parameters. Our sample is composed of both dynamically hot and cold classicals. We study the correlations of diameter and albedo of these two subsamples with each other and with orbital parameters, spectral slopes and colors. We have done three-band photometric observations with Herschel/PACS and we use a consistent method for data reduction and aperture photometry of this sample to obtain monochromatic flux densities at 70.0, 100.0 and 160.0 \mu m. Additionally, we use Spitzer/MIPS flux densities at 23.68 and 71.42 \mu m when available, and we present new Spitzer flux densities of eight targets. We derive diameters and albedos with the near-Earth asteroid thermal model (NEATM). As auxiliary data we use reexamined absolute visual magnitudes from the literature and data bases, part of which have been obtained by ground based programs in support of our Herschel key program. We have determined for the first time radiometric sizes and albedos of eight classical TNOs, and refined previous size and albedo estimates or limits of 11 other classicals. The new size estimates of 2002 MS4 and 120347 Salacia indicate that they are among the 10 largest TNOs known. Our new results confirm the recent findings that there are very diverse albedos among the classical TNOs and that cold classicals possess a high average albedo (0.17 +/- 0.04). Diameters of classical TNOs strongly correlate with orbital inclination in our sample. We also determine the bulk densities of six binary TNOs.

Latent nuclear antigen of Kaposi’s sarcoma herpesvirus/human herpesvirus-8 induces and relocates RING3 to nuclear heterochromatin regions

LANA, the major latency-associated nuclear antigen of Kaposis sarcoma herpesvirus/human herpesvirus-8 (KSHV/HHV-8), binds RING3 protein, one of five human homologues of the fsh (female sterile homeotic) gene product of Drosophila. In KSHV/HHV-8-infected cells LANA and the viral episomes accumulate in heterochromatin-associated nuclear bodies. Here we show that in several KSHV/HHV-8-negative cell lines derived from carcinomas, sarcomas and lymphomas, RING3 was expressed at low levels, primarily localized to the euchromatin, and dissociated from the chromosomes during mitosis. In contrast, in KSHV/HHV-8-infected body cavity lymphoma cells the bulk of RING3 localizes to the LANA nuclear bodies and remains associated with the chromosomes during cell division. KSHV/HHV-8-infected body cavity lymphoma cells expressed RING3 at much higher levels than cells without the virus. Transfection of full-length LANA, but not the C terminus alone, greatly induced RING3 gene expression, and LANA and RING3 co-localized even in the transfected cells, in the absence of KSHV/HHV-8 viral DNA. High levels of LANA expression led to the disappearance of heterochromatin in both human and mouse cells. We suggest that LANA and RING3 may create a local euchromatic microenvironment around the viral episomes that are anchored to the heterochromatin.

TNOs are Cool: A survey of the trans-Neptunian region III. Thermophysical properties of 90482 Orcus and 136472 Makemake

Context. The goal of the Herschel open time programme “TNOs are Cooll” is to derive the physical and thermal properties for a large sample of Centaurs, and trans-Neptunian objects (TNOs), including resonant, classical, detached and scattered disk objects. Aims. Based on observations of two targets we tried (i) to optimise the SPIRE observing technique for faint (close to the background confusion noise), slowly moving targets; (ii) to test different thermal model techniques; (iii) to determine radiometric diameter and albedo values; (iv) to compare with Spitzer results whenever possible. Methods. We obtained SPIRE photometry on two targets and PACS photometry on one of the targets. Results. We present results for the two targets, (90482) Orcus and (136472) Makemake, observed with SPIRE and for one of those targets, Makemake, observed with PACS. We adopt pv = 0.27 and D = 850 km as our best estimate of the albedo and diameter of Orcus using single terrain models. With two-terrain models for Makemake, the bright terrain is fitted by, 0.78 \textless pv \textless 0.90, and the dark terrain 0.02 \textless pv \textless 0.12, giving 1360 \textless D \textless 1480 km. Conclusions. A single terrain model was derived for Orcus through the SPIRE photometry combined with MIPS data. The Makemake data from MIPS, PACS and SPIRE combined are not compatible with a single terrain model, but can be modelled with a two-terrain fit. These science demonstration observations have shown that the scanning technique, which allows us to judge the influence of background structures, has proved to be a good basis for this key programme.

TNOs are cool: A survey of the trans-Neptunian region - V. Physical characterization of 18 Plutinos using Herschel-PACS observations

Context. The Herschel open time key programme TNOs are Cool: A survey of the trans-Neptunian region aims to derive physical and thermal properties for a set of similar to 140 Centaurs and trans-Neptunian objects (TNOs), including resonant, classical, detached and scattered disk objects. One goal of the project is to determine albedo and size distributions for specific classes and the overall population of TNOs. Aims. We present Herschel-PACS photometry of 18 Plutinos and determine sizes and albedos for these objects using thermal modeling. We analyze our results for correlations, draw conclusions on the Plutino size distribution, and compare to earlier results. Methods. Flux densities are derived from PACS mini scan-maps using specialized data reduction and photometry methods. In order to improve the quality of our results, we combine our PACS data with existing Spitzer MIPS data where possible, and refine existing absolute magnitudes for the targets. The physical characterization of our sample is done using a thermal model. Uncertainties of the physical parameters are derived using customized Monte Carlo methods. The correlation analysis is performed using a bootstrap Spearman rank analysis. Results. We find the sizes of our Plutinos to range from 150 to 730 km and geometric albedos to vary between 0.04 and 0.28. The average albedo of the sample is 0.08 +/- 0.03, which is comparable to the mean albedo of Centaurs, Jupiter family comets and other TNOs. We were able to calibrate the Plutino size scale for the first time and find the cumulative Plutino size distribution to be best fit using a cumulative power law with q = 2 at sizes ranging from 120-400 km and q = 3 at larger sizes. We revise the bulk density of 1999 TC36 and find (sic) = 0.64(-0.11)(+0.15) g cm(-3). On the basis of a modified Spearman rank analysis technique our Plutino sample appears to be biased with respect to object size but unbiased with respect to albedo. Furthermore, we find biases based on geometrical aspects and color in our sample. There is qualitative evidence that icy Plutinos have higher albedos than the average of the sample.

Physical properties of OSIRIS-REx target asteroid (101955) 1999 RQ36 - Derived from Herschel, VLT/ VISIR, and Spitzer observations

In September 2011, the Herschel Space Observatory performe d an observation campaign with the PACS photometer observin g the asteroid (101955) 1999 RQ 36 in the far infrared. The Herschel observations were analyse d, together with ESO VLT-VISIR and Spitzer-IRS data, by means of a thermophysical model in orde r to derive the physical properties of 1999 RQ 36. We find the asteroid has an e ffective diameter in the range 480 to 511 m, a slightly elongate d shape with a semi-major axis ratio of a /b=1.04, a geometric albedo of 0.045 +0.015 −0.012, and a retrograde rotation with a spin vector between -70 and -90 ◦ ecliptic latitude. The thermal emission at wavelengths below 12 μm -originating in the hot sub-solar regionshows that there may be large variations in roughness on the surface along the equatorial zone of 1999 RQ 36, but further measurements are required for final proof. We de t rmine that the asteroid has a disk-averaged thermal inertia of Γ=650 Jm−2s−0.5K−1 with a 3-σ confidence range of 350 to 950 Jm −2s−0.5K−1, equivalent to what is observed for 25143 Itokawa and suggestive that 1999 RQ 36 has a similar surface texture and may also be a rubble-pile in nature. The low albedo indicates that 1999 RQ 36 very likely contains primitive volatile-rich material, co nsistent with its spectral type, and that it is an ideal target for the OSIRIS-REx sample return mi ssion.

THE ALBEDO-COLOR DIVERSITY OF TRANSNEPTUNIAN OBJECTS

We analyze albedo data obtained using the Herschel Space Observatory that reveal the existence of two distinct types of surface among midsized trans-Neptunian objects. A color-albedo diagram shows two large clusters of objects, one redder and higher albedo and another darker and more neutrally colored. Crucially, all objects in our sample located in dynamically stable orbits within the classical Kuiper Belt region and beyond are confined to the bright red group, implying a compositional link. Those objects are believed to have formed further from the Sun than the dark neutral bodies. This color-albedo separation is evidence for a compositional discontinuity in the young solar system.

T cell leukemia I oncogene expression depends on the presence of Epstein–Barr virus in the virus- carrying Burkitt lymphoma lines

We used a modified subtractive suppression hybridization to identify cellular genes that show altered expression in Burkitt lymphomas (BLs) in the presence of Epstein–Barr virus (EBV). Comparison of the gene expression patterns of an EBV-negative clone of the originally EBV-positive BL line Akata, with its NeoR-EBV derivative, revealed a significant difference in the expression of the T cell leukemia 1 oncogene (TCL-1). Subsequent expression studies showed that the original EBV-positive Akata line and the EBV-reconstituted derivative expressed high levels of TCL-1, whereas the EBV-negative variant showed only a low level of expression. Two other independently established EBV-positive BLs (Mutu and OMA) that have also thrown off EBV showed a similar decrease in TCL-1 expression after virus loss. Reinfection with NeoR-EBV restored the TCL-1 expression levels in the EBV loss variants to as high a level as the originally EBV-positive lines. High-resolution immunostaining showed that TCL-1 was localized in both the cytoplasm and the nucleus. Our findings suggest that high expression of TCL-1 is necessary for the development of the BL phenotype. In view of the fact that germinal center B cells, regarded as the progenitors of BL, do not express TCL-1, we suggest that constitutive expression of this oncogene occurs by genetic or epigenetic changes in the EBV-negative BLs. In the originally EBV-positive BLs, the ability of the virus to switch on TCL-1 expression would obviate this need.

EBV-encoded EBNA-5 associates with P14ARF in extranucleolar inclusions and prolongs the survival of P14ARF-expressing cells.

Epstein‐Barr virus (EBV) carrying lymphoblastoid cells of normal origin express the full program of all 9 virus‐encoded, growth transformation associated proteins. They have an intact p53 pathway as a rule. This raises the question of whether any of the viral proteins impair the pathway functionally. Using a yeast 2‐hybrid system, we have shown that EBNA‐5 but not the other EBNAs interacts with the p14ARF protein, a regulator of the p53 pathway. The interaction was confirmed in vitro using a GST pull‐down assay. Moreover, expression of EBNA‐5 increased the survival of p14ARF‐transfected cells. EBV infection of resting B cells induced the expression of p14ARF mRNA without increased level of the protein. A fraction of the p14ARF localized to the nucleoli but the bulk of the protein accumulated in nuclear but extranucleolar inclusions. Formation of the extranucleolar inclusions led to complete relocalization of EBNA‐5 from nucleoplasm to these structures. The inclusions also contained p53 and HDM2, and were surrounded by PML bodies and proteasomes, which suggests that these inclusions could be targets for proteasome dependent protein degradation.