1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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2. |
- Forrest, ARR, et al.
(författare)
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A promoter-level mammalian expression atlas
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 507:7493, s. 462-
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Tidskriftsartikel (refereegranskat)
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3. |
- Hudson, Lawrence N., et al.
(författare)
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The PREDICTS database : a global database of how local terrestrial biodiversity responds to human impacts
- 2014
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:24, s. 4701-4735
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Tidskriftsartikel (refereegranskat)abstract
- Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
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4. |
- Abramowski, A., et al.
(författare)
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DISCOVERY OF THE HARD SPECTRUM VHE gamma-RAY SOURCE HESS J1641-463
- 2014
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 794:1, s. L1-
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Tidskriftsartikel (refereegranskat)abstract
- This Letter reports the discovery of a remarkably hard spectrum source, HESS J1641-463, by the High Energy Stereoscopic System (H.E.S.S.) in the very high energy (VHE) domain. HESS J1641-463 remained unnoticed by the usual analysis techniques due to confusion with the bright nearby source HESS J1640-465. It emerged at a significance level of 8.5 standard deviations after restricting the analysis to events with energies above 4 TeV. It shows a moderate flux level of phi(E > 1TeV) = (3.64 +/- 0.44(stat)+/- 0.73(sys)) x 10(-13) cm(-2) s(-1), corresponding to 1.8% of the Crab Nebula flux above the same energy, and a hard spectrum with a photon index of Gamma = 2.07 +/- 0.11(stat)+/- 0.20(sys). It is a point-like source, although an extension up to a Gaussian width of sigma = 3 arcmin cannot be discounted due to uncertainties in the H.E.S.S. point-spread function. The VHE gamma-ray flux of HESS J1641-463 is found to be constant over the observed period when checking time binnings from the year-by-year to the 28 minute exposure timescales. HESS J1641-463 is positionally coincident with the radio supernova remnant SNR G338.5+0.1. No X-ray candidate stands out as a clear association; however, Chandra and XMM-Newton data reveal some potential weak counterparts. Various VHE gamma-ray production scenarios are discussed. If the emission from HESS J1641-463 is produced by cosmic ray protons colliding with the ambient gas, then their spectrum must extend close to 1 PeV. This object may represent a source population contributing significantly to the galactic cosmic ray flux around the knee.
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5. |
- Abramowski, A., et al.
(författare)
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Discovery of the Hard Spectrum VHE γ-Ray Source HESS J1641–463
- 2014
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 794:1, s. Article ID: L1-
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Tidskriftsartikel (refereegranskat)abstract
- This Letter reports the discovery of a remarkably hard spectrum source, HESS J1641-463, by the High Energy Stereoscopic System (H.E.S.S.) in the very high energy (VHE) domain. HESS J1641-463 remained unnoticed by the usual analysis techniques due to confusion with the bright nearby source HESS J1640-465. It emerged at a significance level of 8.5 standard deviations after restricting the analysis to events with energies above 4 TeV. It shows a moderate flux level of phi(E > 1TeV) = (3.64 +/- 0.44(stat)+/- 0.73(sys)) x 10(-13) cm(-2) s(-1), corresponding to 1.8% of the Crab Nebula flux above the same energy, and a hard spectrum with a photon index of Gamma = 2.07 +/- 0.11(stat)+/- 0.20(sys). It is a point-like source, although an extension up to a Gaussian width of sigma = 3 arcmin cannot be discounted due to uncertainties in the H.E.S.S. point-spread function. The VHE gamma-ray flux of HESS J1641-463 is found to be constant over the observed period when checking time binnings from the year-by-year to the 28 minute exposure timescales. HESS J1641-463 is positionally coincident with the radio supernova remnant SNR G338.5+0.1. No X-ray candidate stands out as a clear association; however, Chandra and XMM-Newton data reveal some potential weak counterparts. Various VHE gamma-ray production scenarios are discussed. If the emission from HESS J1641-463 is produced by cosmic ray protons colliding with the ambient gas, then their spectrum must extend close to 1 PeV. This object may represent a source population contributing significantly to the galactic cosmic ray flux around the knee.
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6. |
- Kuboki, T.a, et al.
(författare)
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Measurement of interaction cross-sections for neutron-rich Na isotopes
- 2011
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Ingår i: Acta Physica Polonica B. - : Jagellonian University. - 0587-4254 .- 1509-5770. ; 42:3-4, s. 765-768
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Tidskriftsartikel (refereegranskat)abstract
- The interaction cross-sections (σI) of neutron-rich Na isotopes, 23-35Na, on C target have been measured at 250A MeV using the RI beam factory (RIBF) at RIKEN. Mass dependence of σI for 27-35Na suggests monotonic growth of the skin thickness. The root-mean-square nuclear matter radii (rm) of 23-35Na were deduced from observed σI via a Glauber-type calculation. These rm are in a good agreement with the theoretical prediction by relativistic mean field model (RMF). rm of 33-35Na were determined for the first time.
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7. |
- Takechi, M., et al.
(författare)
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Interaction cross sections for Ne isotopes towards the island of inversion and halo structures of 29Ne and 31Ne
- 2012
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Ingår i: Physics Letters B. - Elsevier : Elsevier BV. - 0370-2693 .- 1873-2445. ; 707:3-4, s. 357-361
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Tidskriftsartikel (refereegranskat)abstract
- Interaction cross sections (σI) for Ne isotopes from the stability line to the vicinity of the neutron dripline have been measured at around 240 MeV/nucleon using BigRIPS at RIBF, RIKEN. The σI for 27–32Ne in every case exceed the systematic mass-number dependence of σI for stable nuclei, which can be explained by considering the nuclear deformation. In particular the σI for 29Ne and 31Ne are significantly greater than those of their neighboring nuclides. These enhancements of σI for 29Ne and 31Ne cannot be explained by a single-particle model calculation under the assumption that the valence neutron of 29Ne (31Ne) occupies the 0d3/2 (0f7/2 ) orbital, as expected from the standard spherical shell ordering. The present data suggest an s dominant halo structure of 29Ne and s- or p-orbital halo in 31Ne.
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8. |
- Ozawa, A., et al.
(författare)
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Charge-changing cross sections of 30Ne, 32,33Na with a proton target
- 2014
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 89, s. 044602-1-044602-5
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Tidskriftsartikel (refereegranskat)abstract
- The total charge-changing, charge pick-up, and partial charge-changing cross sections of very neutron-rich nuclei (30Ne, 32,33Na) with a proton target have been measured at ~240A MeV for the first time. We introduced the phenomenological correction factor in Glauber-model calculations for the total charge-changing cross sections with the proton target, and applied it to deduce the proton radii of these nuclei. For 30Ne and 32Na, the neutron skin thicknesses of the nuclei were deduced by comparing the proton radii with the matter radii deduced from the interaction cross-section measurements. A significant thick neutron-skin has been observed for the nuclei. We also found that the charge pick-up cross sections are much larger than those in the systematics of stable nuclei.
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9. |
- Fukuda, M., et al.
(författare)
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Reaction cross section studies at NIRS and RIBF
- 2010
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Ingår i: American Institute of Physics Conference Series. - American Institute of Physics : AIP. ; , s. 270-273
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Konferensbidrag (refereegranskat)abstract
- Reaction cross sections for stable nuclei at intermediate energies have been measured precisely and systematically. The data have been found to be reproduced nicely by the optical‐limit approximation of Glauber theory modified to include the nucleon multiple scattering effect and the Fermi‐motion effect. Applying this prescription, the nucleon density distribution of 17Ne has been studied. The surface structure of 8B and 11Be has been also studied using this prescription and hydrogen targets. Using the RIBF that has just started application to studies of exotic nuclei, neutron‐rich Ne isotopes around the Island of Inversion have been investigated through measurements of their interaction cross sections.
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10. |
- Takechi, M., et al.
(författare)
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Measurements of nuclear radii for neutron-rich Ne isotopes 28-32Ne
- 2010
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Ingår i: Nuclear Physics A. - Elsevier : Elsevier BV. - 0375-9474 .- 1873-1554. ; 834:1-4, s. 412c-415c
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Tidskriftsartikel (refereegranskat)abstract
- Interaction cross sections (σI) for neutron-rich Ne isotopes, 28-32Ne on C target have been measured at 240A MeV using the RIBF at RIKEN. A large enhancement of σI beyond the systematics of stable nuclei have been observed for neutron-rich Ne isotopes, particularly for 31Ne. The possible halo structure for 29,31Ne which would be caused by the lowering of the pf-shell and nuclear deformation of Ne isotopes are discussed by the preliminary analysis.
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11. |
- Ehara, M., et al.
(författare)
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Symmetry and vibrationally resolved absorption spectra near the N K edges of N2O : experiment and theory
- 2011
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Ingår i: Physical Review A. Atomic, Molecular, and Optical Physics. - 1050-2947 .- 1094-1622. ; 83:6, s. 062506-
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Tidskriftsartikel (refereegranskat)abstract
- In this study, angle-resolved energetic-ion yield spectra were measured in the N 1s excitation region of N2O. A Franck-Condon analysis based on ab initio two-dimensional potential energy surfaces of the core-excited Rydberg states, which were calculated by the symmetry-adapted cluster-configuration interaction method, reproduced observed vibrational excitations specific to the individual Rydberg states well and enabled quantitative assignments. Geometric changes in the terminal nitrogen N-t 1s and the central nitrogen N-c 1s excited states with respect to the 3p pi, 3p sigma, and 4s sigma transitions were analyzed. The coupling of these valence and Rydbergs states was examined based on the second moment analysis. Irregular Rydberg-state behavior in the N-c 1s(-1) 4s sigma state was observed.
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12. |
- Takahashi, H., et al.
(författare)
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A thermal-neutron detector with a phoswich system of LiCaAlF6 and BGO crystal scintillators onboard PoGOLite
- 2010
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Ingår i: 2010 IEEE Nuclear Science Symposium, Medical Imaging Conference, NSS/MIC 2010 and 17th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors, RTSD 2010. ; , s. 32-37
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Konferensbidrag (refereegranskat)abstract
- To measure the flux of atmospheric neutrons and study the neutron contribution to the background of the main detector of the PoGOLite (Polarized Gamma-ray Observer) balloon-borne experiment, a thermal-neutron detector with a phoswich system of LiCaAlF6 (Eu) and BGO crystal scintillators is developed. The performance to separate thermal-neutron events from those of gamma-rays and charged particles is validated with 252Cf on ground. The detector is attached to the PoGOLite instrument and is launched in 2011 from the Esrange facility in the North of Sweden. Although the emission wavelength of the LiCaAlF6 (Ce) is 300 nm and overlaps with the absorption wavelength of the BGO, the phoswich capability of the LiCaAlF6 (Ce) with the BGO is also confirmed with installing a waveform shifter.
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13. |
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14. |
- Moriguchi, T., et al.
(författare)
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Density distribution of 14Be from reaction cross-section measurements
- 2014
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Ingår i: Nuclear Physics A. - : Elsevier BV. - 0375-9474 .- 1873-1554. ; 929:0, s. 83-93
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Tidskriftsartikel (refereegranskat)abstract
- Abstract We measured the reaction cross sections of the two-neutron halo nucleus 14Be with proton and carbon targets at about 41 and 76 MeV/nucleon. Based on a Glauber model calculation, we deduced the matter density distribution of 14Be in which previously measured interaction cross sections at relativistic energies were also included. An s-wave dominance in 14Be has been confirmed, although the halo tail of 14Be is not distributed as much as that of 11Li. Significant mixing of the p-wave in addition to the s- and d-wave is also suggested.
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15. |
- Moriguchi, T., et al.
(författare)
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Density distributions of 11Li deduced from reaction cross-section measurements
- 2013
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 88:2, s. 024610-1-024610-7
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Tidskriftsartikel (refereegranskat)abstract
- We measured the reaction cross sections of the two-neutron halo nucleus 11Li with solid hydrogen and carbon targets at around 31 and 41 MeV/nucleon. The neutron density distribution of 11Li was deduced for the first time by the Glauber model calculation based on the optical limit approximation. The uncertainty of the matter density of 11Li was improved, compared with earlier measurements. The present root-mean-square radius of the proton distribution agrees with the previous one derived from an optical isotope shift measurement. The present root-mean-square radii reproduce theoretical calculations by the tensor optimized shell model by assuming core excitation. This consistency suggests the possibility that 9Li in 11Li is excited and the disappearance of the N=8 shell gap of 11Li is caused by correlations originating from the nucleon force, such as the tensor and the pairing.
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16. |
- Nagata, Toshi, et al.
(författare)
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Emerging concepts on microbial processes in the bathypelagic ocean – ecology, biogeochemistry and genomics
- 2010
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Ingår i: Deep-sea research. Part II, Topical studies in oceanography. - : Elsevier BV. - 0967-0645 .- 1879-0100. ; 57:16, s. 1519-1536
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Tidskriftsartikel (refereegranskat)abstract
- This paper synthesizes recent findings regarding microbial distributions and processes in the bathypelagic ocean (depth > 1000 m). Abundance, production and respiration of prokaryotes reflect supplies of particulate and dissolved organic matter to the bathypelagic zone. Better resolution of carbon fluxes mediated by deep microbes requires further testing on the validity of conversion factors. Archaea, especially marine Crenarchaeota Group I, are abundant in deep waters where they can fix dissolved inorganic carbon. Viruses appear to be important in the microbial loop in deep waters, displaying remarkably high virus to prokaryote abundance ratios in some oceanic regions. Sequencing of 18S rRNA genes revealed a tremendous diversity of small-sized protists in bathypelagic waters. Abundances of heterotrophic nanoflagellates (HNF) and ciliates decrease with depth more steeply than prokaryotes; nonetheless, data indicated that HNF consumed half of prokaryote production in the bathypelagic zone. Aggregates are important habitats for deep-water microbes, which produce more extracellular enzymes (on a per-cell basis) than surface communities. The theory of marine gel formation provides a framework to unravel complex interactions between microbes and organic polymers. Recent data on the effects of hydrostatic pressure on microbial activities indicate that bathypelagic microbial activity is generally higher under in situ pressure conditions than at atmospheric pressures. High-throughput sequencing of 16S rRNA genes revealed a remarkable diversity of Bacteria in the bathypelagic ocean. Metagenomics and comparative genomics of piezophiles reveal not only the high diversity of deep sea microbes but also specific functional attributes of these piezophilic microbes, interpreted as an adaptation to the deep water environment. Taken together, the data compiled on bathypelagic microbes indicate that, despite high-pressure and low-temperature conditions, microbes in the bathypelagic ocean dynamically interact with complex mixtures of organic matter, responding to changes in the ocean's biogeochemical state.
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17. |
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18. |
- Royo, H, et al.
(författare)
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ATR acts stage specifically to regulate multiple aspects of mammalian meiotic silencing
- 2013
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Ingår i: Genes & development. - : Cold Spring Harbor Laboratory. - 1549-5477 .- 0890-9369. ; 27:13, s. 1484-1494
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Tidskriftsartikel (refereegranskat)abstract
- In mammals, homologs that fail to synapse during meiosis are transcriptionally inactivated. This process, meiotic silencing, drives inactivation of the heterologous XY bivalent in male germ cells (meiotic sex chromosome inactivation [MSCI]) and is thought to act as a meiotic surveillance mechanism. The checkpoint protein ATM and Rad3-related (ATR) localizes to unsynapsed chromosomes, but its role in the initiation and maintenance of meiotic silencing is unknown. Here we show that ATR has multiple roles in silencing. ATR first regulates HORMA (Hop1, Rev7, and Mad2) domain protein HORMAD1/2 phosphorylation and localization of breast cancer I (BRCA1) and ATR cofactors ATR-interacting peptide (ATRIP)/topoisomerase 2-binding protein 1 (TOPBP1) at unsynapsed axes. Later, it acts as an adaptor, transducing signaling at unsynapsed axes into surrounding chromatin in a manner that requires interdependence with mediator of DNA damage checkpoint 1 (MDC1) and H2AFX. Finally, ATR catalyzes histone H2AFX phosphorylation, the epigenetic event leading to gene inactivation. Using a novel genetic strategy in which MSCI is used to silence a chosen gene in pachytene, we show that ATR depletion does not disrupt the maintenance of silencing and that silencing comprises two phases: The first is dynamic and reversible, and the second is stable and irreversible. Our work identifies a role for ATR in the epigenetic regulation of gene expression and presents a new technique for ablating gene function in the germline.
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19. |
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20. |
- Ito, Yuki, et al.
(författare)
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Helicobacter pylori Cholesteryl α-Glucosides Contribute to Its Pathogenicity and Immune Response by Natural Killer T Cells
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 10-15% of individuals infected with Helicobacter pylori will develop ulcer disease (gastric or duodenal ulcer), while most people infected with H. pylori will be asymptomatic. The majority of infected individuals remain asymptomatic partly due to the inhibition of synthesis of cholesteryl α-glucosides in H. pylori cell wall by α1,4-GlcNAc-capped mucin O-glycans, which are expressed in the deeper portion of gastric mucosa. However, it has not been determined how cholesteryl α-glucosyltransferase (αCgT), which forms cholesteryl α-glucosides, functions in the pathogenesis of H. pylori infection. Here, we show that the activity of αCgT from H. pylori clinical isolates is highly correlated with the degree of gastric atrophy. We investigated the role of cholesteryl α-glucosides in various aspects of the immune response. Phagocytosis and activation of dendritic cells were observed at similar degrees in the presence of wild-type H. pylori or variants harboring mutant forms of αCgT showing a range of enzymatic activity. However, cholesteryl α-glucosides were recognized by invariant natural killer T (iNKT) cells, eliciting an immune response in vitro and in vivo. Following inoculation of H. pylori harboring highly active αCgT into iNKT cell-deficient (Jα18(-/-)) or wild-type mice, bacterial recovery significantly increased in Jα18(-/-) compared to wild-type mice. Moreover, cytokine production characteristic of Th1 and Th2 cells dramatically decreased in Jα18(-/-) compared to wild-type mice. These findings demonstrate that cholesteryl α-glucosides play critical roles in H. pylori-mediated gastric inflammation and precancerous atrophic gastritis.
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21. |
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22. |
- Kole, Merlin, et al.
(författare)
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Neutron background detection for a hard X-ray balloon-borne polarimeter
- 2014
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Ingår i: Proceedings of Science. - : Proceedings of Science (PoS).
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Konferensbidrag (refereegranskat)abstract
- PoGOLite is a balloon-borne hard X-ray polarimeter. It determines polarisation by measuring the azimuthal angular distribution of Compton scattered photons in a plastic scintillator array. The use of an all-plastic target yields a relatively large, low-mass detection area. The dominant source of background for these measurements has been shown, through Geant4 simulations, to originate from high energy (MeV range) atmospheric neutrons. Neutrons can pass the instrument's Bismuth Germanium Oxide (BGO) anti-coincidence shield undetected and subsequently scatter between plastic scintillator elements to produce a polarisation signature. A passive 15 cm thick polyethylene shield surrounding the polarimeter reduces the neutron induced background by an order of magnitude. The background level remains however significant, prompting the need for active monitoring of the continuously changing neutron flux. For this purpose PoGOLite makes use of a phoswich scintillator cell. The phoswich cell consists of a 5 mm thick Lithium Calcium Aluminium Fluoride (LiCAF) scintillator, used for neutron detection. The LiCAF is surrounded by a BGO anti-coincidence system. This small light weight detector can therefore be used to measure the neutron flux even in high radiation environments. This type of neutron detector was tested on a separate dedicated stratospheric balloon mission in March 2013, called PoGOLino, prior to the PoGOLite flight which took place in July 2013. Results from the test flight and implications for the measurements performed on the PoGOLite flight will be discussed.
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