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| 14. |
- 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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| 15. |
- Blach, S., et al.
(författare)
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Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study
- 2022
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Ingår i: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 7:5, s. 396-415
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Tidskriftsartikel (refereegranskat)abstract
- Background Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends. Methods This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age =0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published sources and grey literature (including government reports and personal communications) and were validated among country and territory experts. A Markov model was used to forecast disease burden and cascade of care from 1950 to 2050 for countries and territories with data. Model outcomes were extracted from 2015 to 2030 to calculate population-weighted regional averages, which were used for countries or territories without data. Regional and global estimates of HCV prevalence, cascade of care, and disease burden were calculated based on 235 countries and territories. Findings Models were built for 110 countries or territories: 83 were approved by local experts and 27 were based on published data alone. Using data from these models, plus population-weighted regional averages for countries and territories without models (n=125), we estimated a global prevalence of viraemic HCV infection of 0.7% (95% UI 0.7-0.9), corresponding to 56.8 million (95% UI 55.2-67.8) infections, on Jan 1, 2020. This number represents a decrease of 6.8 million viraemic infections from a 2015 (beginning of year) prevalence estimate of 63.6 million (61.8-75.8) infections (0.9% [0.8-1.0] prevalence). By the end of 2020, an estimated 12.9 million (12.5-15.4) people were living with a diagnosed viraemic infection. In 2020, an estimated 641 000 (623 000-765 000) patients initiated treatment. Interpretation At the beginning of 2020, there were an estimated 56.8 million viraemic HCV infections globally. Although this number represents a decrease from 2015, our forecasts suggest we are not currently on track to achieve global elimination targets by 2030. As countries recover from COVID-19, these findings can help refocus efforts aimed at HCV elimination. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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| 18. |
- Revel, A., et al.
(författare)
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Extending the Southern Shore of the Island of Inversion to F-28
- 2020
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Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 124:15
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Tidskriftsartikel (refereegranskat)abstract
- Detailed spectroscopy of the neutron-unbound nucleus F-28 has been performed for the first time following proton/neutron removal from Ne-29/F-29 beams at energies around 230 MeV=nucleon. The invariant-mass spectra were reconstructed for both the F-27((*)) + n and F-26((*)) + 2n coincidences and revealed a series of well-defined resonances. A near-threshold state was observed in both reactions and is identified as the F-28 ground state, with S-n(F-28) = -199(6) keV, while analysis of the 2n decay channel allowed a considerably improved S-n(F-27) = 1620(60) keV to be deduced. Comparison with shell-model predictions and eikonal-model reaction calculations have allowed spin-parity assignments to be proposed for some of the lower-lying levels of F-28. Importantly, in the case of the ground state, the reconstructed F-27 + n momentum distribution following neutron removal from F-29 indicates that it arises mainly from the 1p(3/2) neutron intruder configuration. This demonstrates that the island of inversion around N = 20 includes F-28, and most probably F-29, and suggests that O-28 is not doubly magic.
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| 19. |
- Wang, H., et al.
(författare)
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Intruder configurations in 29 Ne at the transition into the island of inversion: Detailed structure study of 28 Ne
- 2023
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 843
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Tidskriftsartikel (refereegranskat)abstract
- Detailed γ-ray spectroscopy of the exotic neon isotope 28Ne has been performed for the first time using the one-neutron removal reaction from 29Ne on a liquid hydrogen target at 240 MeV/nucleon. Based on an analysis of parallel momentum distributions, a level scheme with spin-parity assignments has been constructed for 28Ne and the negative-parity states are identified for the first time. The measured partial cross sections and momentum distributions reveal a significant intruder p-wave strength providing evidence of the breakdown of the N=20 and N=28 shell gaps. Only a weak, possible f-wave strength was observed to bound final states. Large-scale shell-model calculations with different effective interactions do not reproduce the large p-wave and small f-wave strength observed experimentally, indicating an ongoing challenge for a complete theoretical description of the transition into the island of inversion along the Ne isotopic chain.
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| 20. |
- Holl, Matthias, 1986, et al.
(författare)
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Border of the island of inversion: Unbound states in Ne-29
- 2022
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Ingår i: Physical Review C. - 2469-9985 .- 2469-9993. ; 105:3
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Tidskriftsartikel (refereegranskat)abstract
- The nucleus Ne-29 is situated at the border of the island of inversion. Despite significant efforts, no bound low-lying intruder f(7/2) state, which would place Ne-29 firmly inside the island of inversion, has yet been observed. Here, the first investigation of unbound states of Ne-29 is reported. The states were populated in Ne-30(p, pn) and Na-30(p, 2p) reactions at a beam energy of around 230 MeV/nucleon, and analyzed in terms of their resonance properties, partial cross sections, and momentum distributions. The momentum distributions are compared to calculations using the eikonal, direct reaction model, allowing assignments for the observed states. The lowest lying resonance at an excitation energy of 1.48(4) MeV shows clear signs of a significant l = 3 component, giving first evidence for f(7/2) single particle strength in Ne-29. The excitation energies and strengths of the observed states are compared to shell-model calculations using the SDPF-U-MIX interaction.
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| 21. |
- Kondo, Y., et al.
(författare)
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First observation of 28 O
- 2023
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 620:7976, s. 965-970
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Tidskriftsartikel (refereegranskat)abstract
- Subjecting a physical system to extreme conditions is one of the means often used to obtain a better understanding and deeper insight into its organization and structure. In the case of the atomic nucleus, one such approach is to investigate isotopes that have very different neutron-to-proton (N/Z) ratios than in stable nuclei. Light, neutron-rich isotopes exhibit the most asymmetric N/Z ratios and those lying beyond the limits of binding, which undergo spontaneous neutron emission and exist only as very short-lived resonances (about 10−21s), provide the most stringent tests of modern nuclear-structure theories. Here we report on the first observation of 28O and 27O through their decay into 24O and four and three neutrons, respectively. The 28O nucleus is of particular interest as, with the Z = 8 and N = 20 magic numbers1,2, it is expected in the standard shell-model picture of nuclear structure to be one of a relatively small number of so-called ‘doubly magic’ nuclei. Both 27O and 28O were found to exist as narrow, low-lying resonances and their decay energies are compared here to the results of sophisticated theoretical modelling, including a large-scale shell-model calculation and a newly developed statistical approach. In both cases, the underlying nuclear interactions were derived from effective field theories of quantum chromodynamics. Finally, it is shown that the cross-section for the production of 28O from a 29F beam is consistent with it not exhibiting a closed N = 20 shell structure.
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| 22. |
- Frischknecht, R., et al.
(författare)
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Comparison of the greenhouse gas emissions of a high-rise residential building assessed with different national LCA approaches - IEA EBC Annex 72
- 2020
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Ingår i: IOP Conference Series. - : IOP Publishing. ; , s. 022029-
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Konferensbidrag (refereegranskat)abstract
- Introduction: The international research project IEA EBC Annex 72 investigates the life cycle related environmental impacts caused by buildings. The project aims inter alia to harmonise LCA approaches on buildings. Methods: To identify major commonalities and discrepancies among national LCA approaches, reference buildings were defined to present and compare the national approaches. A residential high-rise building located in Tianjin, China, was selected as one of the reference buildings. The main construction elements are reinforced concrete shear walls, beams and floor slabs. The building has an energy reference area of 4566 m2 and an operational heating energy demand of 250 MJ/m2a. An expert team provided information on the quantities of building materials and elements required for the construction, established a BIM model and quantified the operational energy demand. Results: The greenhouse gas emissions and environmental impacts of the building were quantified using 17 country-specific national assessment methods and LCA databases. Comparisons of the results are shown on the level of building elements as well as the complete life cycle of the building. Conclusions: The results of these assessments show that the main differences lie in the LCA background data used, the scope of the assessment and the reference study period applied. Despite the variability in the greenhouse gas emissions determined with the 17 national methods, the individual results are relevant in the respective national context of the method, data, tool and benchmark used. It is important that environmental benchmarks correspond to the particular LCA approach and database of a country in which the benchmark is applied. Furthermore, the results imply to include building technologies as their contribution to the overall environmental impacts is not negligible. Grant support: The authors thank the IEA for its organizational support and the funding organizations in the participating countries for their financial support.
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| 23. |
- Mandt, K. E., et al.
(författare)
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RPC observation of the development and evolution of plasma interaction boundaries at 67P/Churyumov-Gerasimenko
- 2016
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 462, s. S9-S22
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Tidskriftsartikel (refereegranskat)abstract
- One of the primary objectives of the Rosetta Plasma Consortium, a suite of five plasma instruments on-board the Rosetta spacecraft, is to observe the formation and evolution of plasma interaction regions at the comet 67P/Churyumov-Gerasimenko (67P/CG). Observations made between 2015 April and 2016 February show that solar wind-cometary plasma interaction boundaries and regions formed around 2015 mid-April and lasted through early 2016 January. At least two regions were observed, separated by an ion-neutral collisionopause boundary. The inner region was located on the nucleus side of the boundary and was characterized by low-energy water-group ions, reduced magnetic field pileup and enhanced electron densities. The outer region was located outside of the boundary and was characterized by reduced electron densities, water-group ions that are accelerated to energies above 100 eV and enhanced magnetic field pileup compared to the inner region. The boundary discussed here is outside of the diamagnetic cavity and shows characteristics similar to observations made on-board the Giotto spacecraft in the ion pileup region at 1P/Halley. We find that the boundary is likely to be related to ion-neutral collisions and that its location is influenced by variability in the neutral density and the solar wind dynamic pressure.
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| 24. |
- Storck, Sonja, et al.
(författare)
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Lifetime measurement of the 26 0 g.s. At SAMURAI
- 2020
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 1643:1
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Konferensbidrag (refereegranskat)abstract
- The ground state of the neutron unbound nucleus O is speculated to have a lifetime in the pico-second regime. In order to determine the decay lifetime of the O ground state with high sensitivity and precision, a new method has been applied. The experiment was performed in December 2016 at the Superconducting Analyzer for MUlti-particle from Radio Isotope Beams (SAMURAI) at the Radioactive Isotope Beam Factory (RIBF) at RIKEN. A F beam was produced in the fragment separator BigRIPS and impinged on a W/Pt target stack where O was produced. According to the lifetime, the decay of O happens either in or outside the target. Thus, the velocity difference between the decay neutrons and the fragment O delivers a characteristic spectrum from which the lifetime can be extracted.
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| 25. |
- Akula, Murali K, et al.
(författare)
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Control of the innate immune response by the mevalonate pathway
- 2016
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Ingår i: Nature Immunology. - : Springer Science and Business Media LLC. - 1529-2908 .- 1529-2916. ; 17:8, s. 922-9
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Tidskriftsartikel (refereegranskat)abstract
- Deficiency in mevalonate kinase (MVK) causes systemic inflammation. However, the molecular mechanisms linking the mevalonate pathway to inflammation remain obscure. Geranylgeranyl pyrophosphate, a non-sterol intermediate of the mevalonate pathway, is the substrate for protein geranylgeranylation, a protein post-translational modification that is catalyzed by protein geranylgeranyl transferase I (GGTase I). Pyrin is an innate immune sensor that forms an active inflammasome in response to bacterial toxins. Mutations in MEFV (encoding human PYRIN) result in autoinflammatory familial Mediterranean fever syndrome. We found that protein geranylgeranylation enabled Toll-like receptor (TLR)-induced activation of phosphatidylinositol-3-OH kinase (PI(3)K) by promoting the interaction between the small GTPase Kras and the PI(3)K catalytic subunit p110 delta. Macrophages that were deficient in GGTase I or p110 delta exhibited constitutive release of interleukin 1 beta that was dependent on MEFV but independent of the NLRP3, AIM2 and NLRC4 inflammasomes. In the absence of protein geranylgeranylation, compromised PI(3)K activity allows an unchecked TLR-induced inflammatory responses and constitutive activation of the Pyrin inflammasome.
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| 26. |
- Alonso-Blanco, Carlos, et al.
(författare)
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1,135 Genomes Reveal the Global Pattern of Polymorphism in Arabidopsis thaliana
- 2016
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Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 166:2, s. 481-491
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Tidskriftsartikel (refereegranskat)abstract
- Arabidopsis thaliana serves as a model organism for the study of fundamental physiological, cellular, and molecular processes. It has also greatly advanced our understanding of intraspecific genome variation. We present a detailed map of variation in 1,135 high-quality re-sequenced natural inbred lines representing the native Eurasian and North African range and recently colonized North America. We identify relict populations that continue to inhabit ancestral habitats, primarily in the Iberian Peninsula. They have mixed with a lineage that has spread to northern latitudes from an unknown glacial refugium and is now found in a much broader spectrum of habitats. Insights into the history of the species and the fine-scale distribution of genetic diversity provide the basis for full exploitation of A. thaliana natural variation through integration of genomes and epigenomes with molecular and non-molecular phenotypes.
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| 27. |
- Frischknecht, R., et al.
(författare)
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Comparison of the environmental assessment of an identical office building with national methods
- 2019
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Ingår i: IOP Conference Series: Earth and Environmental Science. - : IOP Publishing. - 1755-1307 .- 1755-1315. ; , s. 012037-
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Konferensbidrag (refereegranskat)abstract
- The IEA EBC Annex 72 focuses on the assessment of the primary energy demand, greenhouse gas emissions and environmental impacts of buildings during production, construction, use (including repair and replacement) and end of life (dismantling), i.e. during the entire life cycle of buildings. In one of its activities, reference buildings (size, materialisation, operational energy demand, etc.) were defined on which the existing national assessment methods are applied using national (if available) databases and (national/regional) approaches. The "be2226" office building in Lustenau, Austria was selected as one of the reference buildings. TU Graz established a BIM model and quantified the amount of building elements as well as construction materials required and the operational energy demand. The building assessment was carried out using the same material and energy demand but applying the LCA approach used in the different countries represented by the participating Annex experts. The results of these assessments are compared in view of identifying major discrepancies. Preliminary findings show that the greenhouse gas emissions per kg of building material differ up to a factor of two and more. Major differences in the building assessments are observed in the transports to the construction site (imports) and the construction activities as well as in the greenhouse gas emissions of the operational energy demand (electricity). The experts document their practical difficulties and how they overcame them. The results of this activity are used to better target harmonisation efforts.
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| 28. |
- Zhang, Y. S., et al.
(författare)
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Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 114:12, s. E2293-E2302
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Tidskriftsartikel (refereegranskat)abstract
- Organ-on-a-chip systems areminiaturizedmicrofluidic 3D human tissue and organ models designed to recapitulate the important biological and physiological parameters of their in vivo counterparts. They have recently emerged as a viable platform for personalized medicine and drug screening. These in vitro models, featuring biomimetic compositions, architectures, and functions, are expected to replace the conventional planar, static cell cultures and bridge the gap between the currently used preclinical animal models and the human body. Multiple organoid models may be further connected together through the microfluidics in a similar manner in which they are arranged in vivo, providing the capability to analyze multiorgan interactions. Although a wide variety of human organ-on-a-chip models have been created, there are limited efforts on the integration of multisensor systems. However, in situ continual measuring is critical in precise assessment of the microenvironment parameters and the dynamic responses of the organs to pharmaceutical compounds over extended periods of time. In addition, automated and noninvasive capability is strongly desired for long-term monitoring. Here, we report a fully integrated modular physical, biochemical, and optical sensing platform through a fluidics-routing breadboard, which operates organ-on-a-chip units in a continual, dynamic, and automated manner.We believe that this platform technology has paved a potential avenue to promote the performance of current organ-on-a-chip models in drug screening by integrating a multitude of real-time sensors to achieve automated in situ monitoring of biophysical and biochemical parameters.
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| 29. |
- Lumpkin, A. H., et al.
(författare)
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Evidence for microbunching "sidebands" in a saturated free-electron laser using coherent optical transition radiation
- 2002
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Ingår i: Physical Review Letters. - 1079-7114. ; 88:23, s. 4-4
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Tidskriftsartikel (refereegranskat)abstract
- We report the first measurements of z -dependent coherent optical transition radiation (COTR) due to electron-beam microbunching at high gains (>10(4) ) including saturation of a self-amplified spontaneous emission free-electron laser (FEL). In these experiments the fundamental wavelength was near 530 nm, and the COTR spectra exhibit the transition from simple spectra to complex spectra (5% spectral width) after saturation. The COTR intensity growth and angular distribution data are reported as well as the evidence for transverse spectral dependencies and an "effective" core of the beam being involved in microbunching.
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| 30. |
- Ryu, J., et al.
(författare)
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Evaluation of Three-Dimensional Bioprinted Human Cartilage Powder Combined with Micronized Subcutaneous Adipose Tissues for the Repair of Osteochondral Defects in Beagle Dogs
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 23:5
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Tidskriftsartikel (refereegranskat)abstract
- Cartilage lesions are difficult to repair due to low vascular distribution and may progress into osteoarthritis. Despite numerous attempts in the past, there is no proven method to regenerate hyaline cartilage. The purpose of this study was to investigate the ability to use a 3D printed biomatrix to repair a critical size femoral chondral defect using a canine weight-bearing model. The biomatrix was comprised of human costal-derived cartilage powder, micronized adipose tissue, and fibrin glue. Bilateral femoral condyle defects were treated on 12 mature beagles staged 12 weeks apart. Four groups, one control and three experimental, were used. Animals were euthanized at 32 weeks to collect samples. Significant differences between control and experimental groups were found in both regeneration pattern and tissue composition. In results, we observed that the experimental group with the treatment with cartilage powder and adipose tissue alleviated the inflammatory response. Moreover, it was found that the MOCART score was higher, and cartilage repair was more organized than in the other groups, suggesting that a combination of cartilage powder and adipose tissue has the potential to repair cartilage with a similarity to normal cartilage. Microscopically, there was a welldefined cartilage-like structure in which the mid junction below the surface layer was surrounded by a matrix composed of collagen type I, II, and proteoglycans. MRI examination revealed significant reduction of the inflammation level and progression of a cartilage-like growth in the experimental group. This canine study suggests a promising new surgical treatment for cartilage lesions. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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| 31. |
- Shigeto, Makoto, et al.
(författare)
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GLP-1 stimulates insulin secretion by PKC-dependent TRPM4 and TRPM5 activation
- 2015
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Ingår i: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738 .- 1558-8238. ; 125:12, s. 4714-4728
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Tidskriftsartikel (refereegranskat)abstract
- Strategies aimed at mimicking or enhancing the action of the incretin hormone glucagon-like peptide 1 (GLP-1) therapeutically improve glucose-stimulated insulin secretion (GSIS); however, it is not clear whether GLP-1 directly drives insulin secretion in pancreatic islets. Here, we examined the mechanisms by which GLP-1 stimulates insulin secretion in mouse and human islets. We found that GLP-1 enhances GSIS at a half-maximal effective concentration of 0.4 pM. Moreover, we determined that GLP-1 activates PLC, which increases submembrane diacylglycerol and thereby activates PKC, resulting in membrane depolarization and increased action potential firing and subsequent stimulation of insulin secretion. The depolarizing effect of GLP-1 on electrical activity was mimicked by the PKC activator PMA, occurred without activation of PKA, and persisted in the presence of PKA inhibitors, the K-ATP channel blacker tolbutamide, and the L-type Ca2+ channel blacker isradipine; however, depolarization was abolished by lowering extracellular Na+. The PKC-dependent effect of GLP-1 on membrane potential and electrical activity was mediated by activation of NW-permeable TRPM4 and TRPM5 channels by mobilization of intracellular Ca2+ from thapsigargin-sensitive Ca2+ stores. Concordantly, GLP-1 effects were negligible in Trpm4 or Trpm5 KO islets. These data provide important insight into the therapeutic action of GLP-1 and suggest that circulating levels of this hormone directly stimulate insulin secretion by beta cells.
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| 32. |
- Broiles, Thomas W., et al.
(författare)
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Statistical analysis of suprathermal electron drivers at 67P/Churyumov-Gerasimenko
- 2016
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Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 462, s. S312-S322
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Tidskriftsartikel (refereegranskat)abstract
- We use observations from the Ion and Electron Sensor (IES) on board the Rosetta spacecraft to study the relationship between the cometary suprathermal electrons and the drivers that affect their density and temperature. We fit the IES electron observations with the summation of two kappa distributions, which we characterize as a dense and warm population (similar to 10 cm(-3) and similar to 16 eV) and a rarefied and hot population (similar to 0.01 cm(-3) and similar to 43 eV). The parameters of our fitting technique determine the populations' density, temperature, and invariant kappa index. We focus our analysis on the warm population to determine its origin by comparing the density and temperature with the neutral density and magnetic field strength. We find that the warm electron population is actually two separate sub-populations: electron distributions with temperatures above 8.6 eV and electron distributions with temperatures below 8.6 eV. The two sub-populations have different relationships between their density and temperature. Moreover, the two sub-populations are affected by different drivers. The hotter sub-population temperature is strongly correlated with neutral density, while the cooler sub-population is unaffected by neutral density and is only weakly correlated with magnetic field strength. We suggest that the population with temperatures above 8.6 eV is being heated by lower hybrid waves driven by counterstreaming solar wind protons and newly formed, cometary ions created in localized, dense neutral streams. To the best of our knowledge, this represents the first observations of cometary electrons heated through wave-particle interactions.
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| 33. |
- Kawakatsu, Taiji, et al.
(författare)
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Epigenomic Diversity in a Global Collection of Arabidopsis thaliana Accessions
- 2016
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Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 166:2, s. 492-505
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Tidskriftsartikel (refereegranskat)abstract
- The epigenome orchestrates genome accessibility, functionality, and three-dimensional structure. Because epigenetic variation can impact transcription and thus phenotypes, it may contribute to adaptation. Here, we report 1,107 high-quality single-base resolution methylomes and 1,203 transcriptomes from the 1001 Genomes collection of Arabidopsis thaliana. Although the genetic basis of methylation variation is highly complex, geographic origin is a major predictor of genome-wide DNA methylation levels and of altered gene expression caused by epialleles. Comparison to cistrome and epicistrome datasets identifies associations between transcription factor binding sites, methylation, nucleotide variation, and co-expression modules. Physical maps for nine of the most diverse genomes reveal how transposons and other structural variants shape the epigenome, with dramatic effects on immunity genes. The 1001 Epigenomes Project provides a comprehensive resource for understanding how variation in DNA methylation contributes to molecular and non-molecular phenotypes in natural populations of the most studied model plant.
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| 34. |
- Virkkala, Anna Maria, et al.
(författare)
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Statistical upscaling of ecosystem CO2 fluxes across the terrestrial tundra and boreal domain : Regional patterns and uncertainties
- 2021
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 27:17, s. 4040-4059
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Tidskriftsartikel (refereegranskat)abstract
- The regional variability in tundra and boreal carbon dioxide (CO2) fluxes can be high, complicating efforts to quantify sink-source patterns across the entire region. Statistical models are increasingly used to predict (i.e., upscale) CO2 fluxes across large spatial domains, but the reliability of different modeling techniques, each with different specifications and assumptions, has not been assessed in detail. Here, we compile eddy covariance and chamber measurements of annual and growing season CO2 fluxes of gross primary productivity (GPP), ecosystem respiration (ER), and net ecosystem exchange (NEE) during 1990–2015 from 148 terrestrial high-latitude (i.e., tundra and boreal) sites to analyze the spatial patterns and drivers of CO2 fluxes and test the accuracy and uncertainty of different statistical models. CO2 fluxes were upscaled at relatively high spatial resolution (1 km2) across the high-latitude region using five commonly used statistical models and their ensemble, that is, the median of all five models, using climatic, vegetation, and soil predictors. We found the performance of machine learning and ensemble predictions to outperform traditional regression methods. We also found the predictive performance of NEE-focused models to be low, relative to models predicting GPP and ER. Our data compilation and ensemble predictions showed that CO2 sink strength was larger in the boreal biome (observed and predicted average annual NEE −46 and −29 g C m−2 yr−1, respectively) compared to tundra (average annual NEE +10 and −2 g C m−2 yr−1). This pattern was associated with large spatial variability, reflecting local heterogeneity in soil organic carbon stocks, climate, and vegetation productivity. The terrestrial ecosystem CO2 budget, estimated using the annual NEE ensemble prediction, suggests the high-latitude region was on average an annual CO2 sink during 1990–2015, although uncertainty remains high.
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| 35. |
- Wilkes, MC, et al.
(författare)
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Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 3344-
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Tidskriftsartikel (refereegranskat)abstract
- Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome associated with ribosomal gene mutations that lead to ribosomal insufficiency. DBA is characterized by anemia, congenital anomalies, and cancer predisposition. Treatment for DBA is associated with significant morbidity. Here, we report the identification of Nemo-like kinase (NLK) as a potential target for DBA therapy. To identify new DBA targets, we screen for small molecules that increase erythroid expansion in mouse models of DBA. This screen identified a compound that inhibits NLK. Chemical and genetic inhibition of NLK increases erythroid expansion in mouse and human progenitors, including bone marrow cells from DBA patients. In DBA models and patient samples, aberrant NLK activation is initiated at the Megakaryocyte/Erythroid Progenitor (MEP) stage of differentiation and is not observed in non-erythroid hematopoietic lineages or healthy erythroblasts. We propose that NLK mediates aberrant erythropoiesis in DBA and is a potential target for therapy.
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- Fellström, Bengt, et al.
(författare)
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Rosuvastatin and cardiovascular events in patients undergoing hemodialysis.
- 2009
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Ingår i: The New England journal of medicine. - 1533-4406 .- 0028-4793. ; 360:14, s. 1395-407
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk. However, a benefit of statins in such patients who are undergoing hemodialysis has not been proved. METHODS: We conducted an international, multicenter, randomized, double-blind, prospective trial involving 2776 patients, 50 to 80 years of age, who were undergoing maintenance hemodialysis. We randomly assigned patients to receive rosuvastatin, 10 mg daily, or placebo. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary end points included death from all causes and individual cardiac and vascular events. RESULTS: After 3 months, the mean reduction in low-density lipoprotein (LDL) cholesterol levels was 43% in patients receiving rosuvastatin, from a mean baseline level of 100 mg per deciliter (2.6 mmol per liter). During a median follow-up period of 3.8 years, 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary end point (9.2 and 9.5 events per 100 patient-years, respectively; hazard ratio for the combined end point in the rosuvastatin group vs. the placebo group, 0.96; 95% confidence interval [CI], 0.84 to 1.11; P=0.59). Rosuvastatin had no effect on individual components of the primary end point. There was also no significant effect on all-cause mortality (13.5 vs. 14.0 events per 100 patient-years; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.51). CONCLUSIONS: In patients undergoing hemodialysis, the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. (ClinicalTrials.gov number, NCT00240331.)
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