Periodic Emission from the Gamma-ray Binary 1FGL J1018.6-5856

Gamma-ray binaries are stellar systems containing a neutron star or black hole with gamma-ray emission produced by an interaction between the components. These systems are rare, even though binary evolution models predict dozens in our Galaxy. A search for gamma-ray binaries with the Fermi Large Area Telescope (LAT) shows that IFGL JI018.6-5856 exhibits intensity and spectral modulation with a 16.6 day period. We identified a variable X-ray counterpart, which shows a sharp maximum coinciding with maximum gamma-ray emission, as well as an 06V f) star optical counterpart and a radio counterpart that is also apparently modulated on the orbital period. IFGL J1018.6-5856 is thus a gamma-ray binary, and its detection suggests the presence of other fainter binaries in the Galaxy

Histone H3 Serine 57 and Lysine 56 Interplay in Transcription Elongation and Recovery from S-Phase Stress

Contains fulltext : 84400.pdf (publisher's version ) (Open Access

Very-high-energy γ -Ray Emission from Young Massive Star Clusters in the Large Magellanic Cloud

The Tarantula Nebula in the Large Magellanic Cloud is known for its high star formation activity. At its center lies the young massive star cluster R136, providing a significant amount of the energy that makes the nebula shine so brightly at many wavelengths. Recently, young massive star clusters have been suggested to also efficiently produce very high-energy cosmic rays, potentially beyond PeV energies. Here, we report the detection of very-high-energy γ-ray emission from the direction of R136 with the High Energy Stereoscopic System, achieved through a multicomponent, likelihood-based modeling of the data. This supports the hypothesis that R136 is indeed a very powerful cosmic-ray accelerator. Moreover, from the same analysis, we provide an updated measurement of the γ-ray emission from 30 Dor C, the only superbubble detected at TeV energies presently. The γ-ray luminosity above 0.5 TeV of both sources is (2–3) × 1035 erg s−1. This exceeds by more than a factor of 2 the luminosity of HESS J1646−458, which is associated with the most massive young star cluster in the Milky Way, Westerlund 1. Furthermore, the γ-ray emission from each source is extended with a significance of >3σ and a Gaussian width of about 30 pc. For 30 Dor C, a connection between the γ-ray emission and the nonthermal X-ray emission appears likely. Different interpretations of the γ-ray signal from R136 are discussed

Detection of the Characteristic Pion-Decay Signature in Supernova Remnants

Cosmic rays are particles (mostly protons) accelerated to relativistic speeds. Despite wide agreement that supernova remnants (SNRs) are the sources of galactic cosmic rays, unequivocal evidence for the acceleration of protons in these objects is still lacking. When accelerated protons encounter interstellar material, they produce neutral pions, which in turn decay into gamma rays. This offers a compelling way to detect the acceleration sites of protons. The identification of pion-decay gamma rays has been difficult because high-energy electrons also produce gamma rays via bremsstrahlung and inverse Compton scattering. We detected the characteristic pion-decay feature in the gamma-ray spectra of two SNRs, IC 443 and W44, with the Fermi Large Area Telescope. This detection provides direct evidence that cosmic-ray protons are accelerated in SNRs.Fil: Ackerman, M.. Deutsches Elektronen Synchrotron DESY; AlemaniaFil: Ajello, M.. University of California; Estados UnidosFil: Allafort, A.. University Of Stanford; Estados UnidosFil: Baldini, L.. Universita Degli Studi Di Pisa; ItaliaFil: Ballet, J.. Universit´e Paris Diderot; FranciaFil: Garbiellini, G.. Universit`a di Trieste; ItaliaFil: Baring, M. G.. Rice University; Estados UnidosFil: Bastieri, D.. Universita Di Padova; ItaliaFil: Bechtol, K.. University Of Stanford; Estados UnidosFil: Bellazzini, R.. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Blandford, R. D.. University Of Stanford; Estados UnidosFil: Bloom, E. D.. University Of Stanford; Estados UnidosFil: Bonamente, E.. Universita degli Studi di Perugia; ItaliaFil: Borgland, A. W.. University of Stanford; Estados UnidosFil: Bottaccini, E.. University Of Stanford; Estados UnidosFil: Brandt, T. J.. National Aeronautics And Space Administration. Goddart Institute For Space Studies; Estados UnidosFil: Bregeon, J.. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Brigida, M.. Universit`a e del Politecnico di Bari; ItaliaFil: Bruel, P.. Ecole polytechnique, CNRS; FranciaFil: Buehler, R.. University Of Stanford; Estados UnidosFil: Busetto, G.. Universita di Padova; ItaliaFil: Buson, S..Fil: Caliandro, G. A.. Institut de Ciencies de l’Espai (IEEE-CSIC); EspañaFil: Cameron, R. A.. University Of Stanford; Estados UnidosFil: Caraveo, P. A.. INAF-Istituto di Astrofisica Spaziale e Fisica Cosmica; ItaliaFil: Casandjian, J. M.. Universite Paris Diderot; FranciaFil: Cecchi, C.. Universita degli Studi di Perugia; ItaliaFil: Celic, O.. National Aeronautics And Space Administration. Goddart Institute For Space Studies; Estados UnidosFil: Charles, E.. University Of Stanford; Estados UnidosFil: Cillis, Analia Nilda. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; Argentin

The Vanishing of the Primary Emission Region in PKS 1510-089

In 2021 July, PKS 1510-089 exhibited a significant flux drop in the high-energy γ-ray (by a factor 10) and optical (by a factor 5) bands and remained in this low state throughout 2022. Similarly, the optical polarization in the source vanished, resulting in the optical spectrum being fully explained through the steady flux of the accretion disk and the broad-line region. Unlike the aforementioned bands, the very-high-energy γ-ray and X-ray fluxes did not exhibit a significant flux drop from year to year. This suggests that the steady-state very-high-energy γ-ray and X-ray fluxes originate from a different emission region than the vanished parts of the high-energy γ-ray and optical jet fluxes. The latter component has disappeared through either a swing of the jet away from the line of sight or a significant drop in the photon production efficiency of the jet close to the black hole. Either change could become visible in high-resolution radio images

The Elg1 Clamp Loader Plays a Role in Sister Chromatid Cohesion

Mutations in the ELG1 gene of yeast lead to genomic instability, manifested in high levels of genetic recombination, chromosome loss, and gross chromosomal rearrangements. Elg1 shows similarity to the large subunit of the Replication Factor C clamp loader, and forms a RFC-like (RLC) complex in conjunction with the 4 small RFC subunits. Two additional RLCs exist in yeast: in one of them the large subunit is Ctf18, and in the other, Rad24. Ctf18 has been characterized as the RLC that functions in sister chromatid cohesion. Here we present evidence that the Elg1 RLC (but not Rad24) also plays an important role in this process. A genetic screen identified the cohesin subunit Mcd1/Scc1 and its loader Scc2 as suppressors of the synthetic lethality between elg1 and ctf4. We describe genetic interactions between ELG1 and genes encoding cohesin subunits and their accessory proteins. We also show that defects in Elg1 lead to higher precocious sister chromatid separation, and that Ctf18 and Elg1 affect cohesion via a joint pathway. Finally, we localize both Ctf18 and Elg1 to chromatin and show that Elg1 plays a role in the recruitment of Ctf18. Our results suggest that Elg1, Ctf4, and Ctf18 may coordinate the relative movement of the replication fork with respect to the cohesin ring

The Elongator Complex Interacts with PCNA and Modulates Transcriptional Silencing and Sensitivity to DNA Damage Agents

Histone chaperones CAF-1 and Asf1 function to deposit newly synthesized histones onto replicating DNA to promote nucleosome formation in a proliferating cell nuclear antigen (PCNA) dependent process. The DNA replication- or DNA repair-coupled nucleosome assembly pathways are important for maintenance of transcriptional gene silencing and genome stability. However, how these pathways are regulated is not well understood. Here we report an interaction between the Elongator histone acetyltransferase and the proliferating cell nuclear antigen. Cells lacking Elp3 (K-acetyltransferase Kat9), the catalytic subunit of the six-subunit Elongator complex, partially lose silencing of reporter genes at the chromosome VIIL telomere and at the HMR locus, and are sensitive to the DNA replication inhibitor hydroxyurea (HU) and the damaging agent methyl methanesulfonate (MMS). Like deletion of the ELP3, mutation of each of the four other subunits of the Elongator complex as well as mutations in Elp3 that compromise the formation of the Elongator complex also result in loss of silencing and increased HU sensitivity. Moreover, Elp3 is required for S-phase progression in the presence of HU. Epistasis analysis indicates that the elp3Δ mutant, which itself is sensitive to MMS, exacerbates the MMS sensitivity of cells lacking histone chaperones Asf1, CAF-1 and the H3 lysine 56 acetyltransferase Rtt109. The elp3Δ mutant has allele specific genetic interactions with mutations in POL30 that encodes PCNA and PCNA binds to the Elongator complex both in vivo and in vitro. Together, these results uncover a novel role for the intact Elongator complex in transcriptional silencing and maintenance of genome stability, and it does so in a pathway linked to the DNA replication and DNA repair protein PCNA

Histone Deacetylase Inhibitors Globally Enhance H3/H4 Tail Acetylation Without Affecting H3 Lysine 56 Acetylation

Histone deacetylase inhibitors (HDACi) represent a promising avenue for cancer therapy. We applied mass spectrometry (MS) to determine the impact of clinically relevant HDACi on global levels of histone acetylation. Intact histone profiling revealed that the HDACi SAHA and MS-275 globally increased histone H3 and H4 acetylation in both normal diploid fibroblasts and transformed human cells. Histone H3 lysine 56 acetylation (H3K56ac) recently elicited much interest and controversy due to its potential as a diagnostic and prognostic marker for a broad diversity of cancers. Using quantitative MS, we demonstrate that H3K56ac is much less abundant than previously reported in human cells. Unexpectedly, in contrast to H3/H4 N-terminal tail acetylation, H3K56ac did not increase in response to inhibitors of each class of HDACs. In addition, we demonstrate that antibodies raised against H3K56ac peptides cross-react against H3 N-terminal tail acetylation sites that carry sequence similarity to residues flanking H3K56

Emerging evidence of a link between the polycystins and the mTOR pathways

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease characterized by the formation of renal cysts. This disease can be caused by mutations in two genes, PKD1 and PKD2, which encode polycystin-1 (PC-1) and -2 (PC-2), respectively

The DNA Damage Response Pathway Contributes to the Stability of Chromosome III Derivatives Lacking Efficient Replicators

In eukaryotic chromosomes, DNA replication initiates at multiple origins. Large inter-origin gaps arise when several adjacent origins fail to fire. Little is known about how cells cope with this situation. We created a derivative of Saccharomyces cerevisiae chromosome III lacking all efficient origins, the 5ORIΔ-ΔR fragment, as a model for chromosomes with large inter-origin gaps. We used this construct in a modified synthetic genetic array screen to identify genes whose products facilitate replication of long inter-origin gaps. Genes identified are enriched in components of the DNA damage and replication stress signaling pathways. Mrc1p is activated by replication stress and mediates transduction of the replication stress signal to downstream proteins; however, the response-defective mrc1AQ allele did not affect 5ORIΔ-ΔR fragment maintenance, indicating that this pathway does not contribute to its stability. Deletions of genes encoding the DNA-damage-specific mediator, Rad9p, and several components shared between the two signaling pathways preferentially destabilized the 5ORIΔ-ΔR fragment, implicating the DNA damage response pathway in its maintenance. We found unexpected differences between contributions of components of the DNA damage response pathway to maintenance of ORIΔ chromosome derivatives and their contributions to DNA repair. Of the effector kinases encoded by RAD53 and CHK1, Chk1p appears to be more important in wild-type cells for reducing chromosomal instability caused by origin depletion, while Rad53p becomes important in the absence of Chk1p. In contrast, RAD53 plays a more important role than CHK1 in cell survival and replication fork stability following treatment with DNA damaging agents and hydroxyurea. Maintenance of ORIΔ chromosomes does not depend on homologous recombination. These observations suggest that a DNA-damage-independent mechanism enhances ORIΔ chromosome stability. Thus, components of the DNA damage response pathway contribute to genome stability, not simply by detecting and responding to DNA template damage, but also by facilitating replication of large inter-origin gaps