Chromatin Profiles of Chromosomally Integrated Human Herpesvirus-6A

Human herpesvirus-6A (HHV-6A) and 6B (HHV-6B) are two closely related betaherpesviruses that are associated with various diseases including seizures and encephalitis. The HHV-6A/B genomes have been shown to be present in an integrated state in the telomeres of latently infected cells. In addition, integration of HHV-6A/B in germ cells has resulted in individuals harboring this inherited chromosomally integrated HHV-6A/B (iciHHV-6) in every cell of their body. Until now, the viral transcriptome and the epigenetic modifications that contribute to the silencing of the integrated virus genome remain elusive. In the current study, we used a patient-derived iciHHV-6A cell line to assess the global viral gene expression profile by RNA-seq, and the chromatin profiles by MNase-seq and ChIP-seq analyses. In addition, we investigated an in vitro generated cell line (293-HHV-6A) that expresses GFP upon the addition of agents commonly used to induce herpesvirus reactivation such as TPA. No viral gene expression including miRNAs was detected from the HHV-6A genomes, indicating that the integrated virus is transcriptionally silent. Intriguingly, upon stimulation of the 293-HHV-6A cell line with TPA, only foreign promoters in the virus genome were activated, while all HHV-6A promoters remained completely silenced. The transcriptional silencing of latent HHV-6A was further supported by MNase-seq results, which demonstrate that the latent viral genome resides in a highly condensed nucleosome-associated state. We further explored the enrichment profiles of histone modifications via ChIP-seq analysis. Our results indicated that the HHV-6 genome is modestly enriched with the repressive histone marks H3K9me3/H3K27me3 and does not possess the active histone modifications H3K27ac/H3K4me3. Overall, these results indicate that HHV-6 genomes reside in a condensed chromatin state, providing insight into the epigenetic mechanisms associated with the silencing of the integrated HHV-6A genome

Characterization of human herpesvirus 6A/B U94 as ATPase, helicase, exonuclease and DNA-binding proteins

Human herpesvirus-6A (HHV-6A) and HHV-6B integrate their genomes into the telomeres of human chromosomes, however, the mechanisms leading to integration remain unknown. HHV-6A/B encode a protein that has been proposed to be involved in integration termed U94, an ortholog of adeno-associated virus type 2 (AAV-2) Rep68 integrase. In this report, we addressed whether purified recombinant maltose-binding protein (MBP)-U94 fusion proteins of HHV-6A/B possess biological functions compatible with viral integration. We could demonstrate that MBP-U94 efficiently binds both dsDNA and ssDNA containing telomeric repeats using gel shift assay and surface plasmon resonance. MBP-U94 is also able to hydrolyze adenosine triphosphate (ATP) to ADP, providing the energy for further catalytic activities. In addition, U94 displays a 3′ to 5′ exonuclease activity on dsDNA with a preference for 3′-recessed ends. Once the DNA strand reaches 8–10 nt in length, the enzyme dissociates it from the complementary strand. Lastly, MBP-U94 compromises the integrity of a synthetic telomeric D-loop through exonuclease attack at the 3′ end of the invading strand. The preferential DNA binding of MBP-U94 to telomeric sequences, its ability to hydrolyze ATP and its exonuclease/helicase activities suggest that U94 possesses all functions required for HHV-6A/B chromosomal integratio

Whales as marine ecosystem engineers

Baleen and sperm whales, known collectively as the great whales, include the largest animals in the history of life on Earth. With high metabolic demands and large populations, whales probably had a strong influence on marine ecosystems before the advent of industrial whaling: as consumers of fish and invertebrates; as prey to other large-bodied predators; as reservoirs of and vertical and horizontal vectors for nutrients; and as detrital sources of energy and habitat in the deep sea. The decline in great whale numbers, estimated to be at least 66% and perhaps as high as 90%, has likely altered the structure and function of the oceans, but recovery is possible and in many cases is already underway. Future changes in the structure and function of the world\u27s oceans can be expected with the restoration of great whale populations

Mental Health Treatment Involvement and Religious Coping among African American, Hispanic, and White Veterans of the Wars of Iraq and Afghanistan

Although racial/ethnic differences have been found in the use of mental health services for depression in the general population, research among Veterans has produced mixed results. This study examined racial/ethnic differences in the use of mental health services among 148 Operation Enduring/Iraqi Freedom (OEF/OIF) Veterans with high levels of depression and posttraumatic stress disorder (PTSD) symptoms and evaluated whether religious coping affected service use. No differences between African American, Hispanic, and Non-Hispanic white Veterans were found in use of secular mental health services or religious counseling. Women Veterans were more likely than men to seek secular treatment. After controlling for PTSD symptoms, depression symptom level was a significant predictor of psychotherapy attendance but not medication treatment. African American Veterans reported higher levels of religious coping than whites. Religious coping was associated with participation in religious counseling, but not secular mental health services

Ropeless fishing to prevent large whale entanglements: Ropeless Consortium report

The 2017 North Atlantic right whale (NARW) unusual mortality event and an increase in humpback whale entanglements off the U.S. West Coast have driven significant interest in ropeless trap/pot fishing. Removing the vertical buoy lines used to mark traps on the sea floor and haul them up would dramatically reduce or eliminate entanglements, the leading cause of NARW mortality, while potentially allowing fishermen to harvest in areas that would otherwise need to be closed to protect whales. At the first annual Ropeless Consortium meeting, researchers, fishing industry representatives, manufacturers, conservationists, and regulators discussed existing and developing technological replacements for the marking and retrieval functions of buoy lines. Fishermen and NGO partners shared their experience demonstrating ropeless systems and provided feedback to improve the designs. U.S. and Canadian federal regulators discussed prospects to use ropeless fishing gear in areas closed to fishing with vertical lines, as well as other options to reduce entanglements, and a Massachusetts official shared additional regulatory considerations involved in ropeless fishing in state waters. Sustainable seafood experts discussed consumer market advantages and endangered, threatened, and protected species impacts in sustainability standards and certifications. Moving forward, there is an immediate need to (1) work with industry partners to iteratively test and improve ropeless retrieval and marking systems to adapt them to the specific conditions of the relevant trap/pot fisheries, (2) create data sharing and communications protocols for ropeless gear location marking, and (3) develop regulatory procedures and enforcement capacity to allow legal ropeless gear use.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.2020-06-2

Direct-write fabrication of zinc oxide varistors

Zinc oxide (ZnO)-based pastes with tailored rheological properties have been developed for direct-write fabrication of thick-film varistor elements in highly integrated, multifunctional electroceramic devices. Such pastes exhibited pseudoplastic behavior with a low shear apparent viscosity of roughly 1 ؋ 10 4 Pa⅐s. Upon aging, the pastes attained printable, steady-state viscosities of approximately 3 ؋ 10 2 Pa⅐s at 10 s ؊1 . Square and rectangular elements were patterned on dense alumina substrates and sintered at varying temperatures between 800°and 1250°C. Varistor elements fired at 900°C exhibited nonlinearity coefficients (␣ ‫؍‬ 30) that were equivalent to high-density (>95%) varistors formed by cold isostatic pressing at 100 MPa (15 ksi) of a similar chemically derived powder heat-treated under analogous conditions

Searches For High-Frequency Variations In The B-8 Solar Neutrino Flux At The Sudbury Neutrino Observatory

We have performed three searches for high-frequency signals in the solar neutrino flux measured by the Sudbury Neutrino Observatory, motivated by the possibility that solar g-mode oscillations could affect the production or propagation of solar B-8 neutrinos. The first search looked for any significant peak in the frequency range 1-144 day(-1), with a sensitivity to sinusoidal signals with amplitudes of 12% or greater. The second search focused on regions in which g-mode signals have been claimed by experiments aboard the Solar and Heliospheric Observatory satellite, and was sensitive to signals with amplitudes of 10% or greater. The third search looked for extra power across the entire frequency band. No statistically significant signal was detected in any of the three searches.Natural Sciences and Engineering Research Council, CanadaIndustry Canada, CanadaNational Research Council, CanadaNorthern Ontario Heritage Fund, CanadaAtomic Energy of Canada, Ltd., CanadaOntario Power Generation, CanadaHigh Performance Computing Virtual Laboratory, CanadaCanada Foundation for InnovationDept. of Energy, USNational Energy Research Scientific Computing Center, USScience and Technologies Facilities Council, UKAstronom

Independent measurement of the total active B8 solar neutrino flux using an array of He3 proportional counters at the Sudbury Neutrino Observatory

The Sudbury Neutrino Observatory (SNO) used an array of 3He proportional counters to measure the rate of neutral-current interactions in heavy water and precisely determined the total active (νx) 8B solar neutrino flux. This technique is independent of previous methods employed by SNO. The total flux is found to be 5.54-0.31+0.33(stat)-0.34+0.36(syst)×106  cm-2 s-1, in agreement with previous measurements and standard solar models. A global analysis of solar and reactor neutrino results yields Δm2=7.59-0.21+0.19×10-5  eV2 and θ=34.4-1.2+1.3 degrees. The uncertainty on the mixing angle has been reduced from SNO’s previous results