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Sökning: WFRF:(Zeitlin C.)

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  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • 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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3.
  • Reifarth, R., et al. (författare)
  • Nuclear astrophysics with radioactive ions at FAIR
  • 2016
  • Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 665:1
  • Konferensbidrag (refereegranskat)abstract
    • The nucleosynthesis of elements beyond iron is dominated by neutron captures in the s and r processes. However, 32 stable, proton-rich isotopes cannot be formed during those processes, because they are shielded from the s-process flow and r-process beta-decay chains. These nuclei are attributed to the p and rp process. For all those processes, current research in nuclear astrophysics addresses the need for more precise reaction data involving radioactive isotopes. Depending on the particular reaction, direct or inverse kinematics, forward or time-reversed direction are investigated to determine or at least to constrain the desired reaction cross sections. The Facility for Antiproton and Ion Research (FAIR) will offer unique, unprecedented opportunities to investigate many of the important reactions. The high yield of radioactive isotopes, even far away from the valley of stability, allows the investigation of isotopes involved in processes as exotic as the r or rp processes.
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4.
  • Guzewich, Scott D., et al. (författare)
  • Mars Science Laboratory Observations of the 2018/Mars Year 34 Global Dust Storm
  • 2019
  • Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 46:1, s. 71-79
  • Tidskriftsartikel (refereegranskat)abstract
    • Mars Science Laboratory Curiosity rover observations of the 2018/Mars year 34 global/planet‐encircling dust storm represent the first in situ measurements of a global dust storm with dedicated meteorological sensors since the Viking Landers. The Mars Science Laboratory team planned and executed a science campaign lasting approximately 100 Martian sols to study the storm involving an enhanced cadence of environmental monitoring using the rover's meteorological sensors, cameras, and spectrometers. Mast Camera 880‐nm optical depth reached 8.5, and Rover Environmental Monitoring Station measurements indicated a 97% reduction in incident total ultraviolet solar radiation at the surface, 30K reduction in diurnal range of air temperature, and an increase in the semidiurnal pressure tide amplitude to 40 Pa. No active dust‐lifting sites were detected within Gale Crater, and global and local atmospheric dynamics were drastically altered during the storm. This work presents an overview of the mission's storm observations and initial results.
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5.
  • Pinsky, L., et al. (författare)
  • Measurement of Fragmentation Products including Angular Distributions for 3, 5, and 10 GeV/A C and Si on several nuclear targets at the AGS
  • 2010
  • Ingår i: 2009 12th International Conference on Nuclear Reaction Mechanisms, NRM 2009; Varenna; Italy; 15 June 2009 through 19 June 2009. - 2078-8835. - 9789290833413 ; 2, s. 431-437
  • Konferensbidrag (refereegranskat)abstract
    • Motivated by differences in the predicted fragmentation of heavy ions at energies around 5 GeV/A as employed in the event generators used by the FLUKA Monte Carlo Code [1], a set of measurements were carried out at the AGS facility at the Brookhaven National Laboratory to determine as much information as possible about the cross sections to allow harmonization of those event generators for these incident lab energies. The FLUKA Code employs the RQMD event generator of Sorge [2] for heavy ion interactions starting at 100 MeV/A and extending into the region around 5 GeV/A. Above those energies the DPMJET code of Ranft and Roesler [3] is typically employed to simulate such interactions. The detailed predictions of these event generators had some disagreement in the vicinity of this crossover energy and in order to tune these codes to be in closer harmony at the transition, and of course to be simulating nature as closely as possible, data were taken at 3, 5 and 10 GeV/A with beams of Fe, Si and C on a variety of targets including C, A1. Fe and Cu. The Fe data have not been fully analyzed, but results from the C and Si beams are available and the forward fragment spectrum along with a measurement of the charged particle angular distribution in a set of Si strip detectors out to about 45 degrees in the lab are available. These include sufficient statistics to provide the charged particle distributions as a function of the major projectile fragment. The detectors used in this measurement were based on what were reasonably available to us, and as such were limited in capability, and required separate data acquisition systems. Nevertheless, spectra were obtained that should be sufficient to enable the harmonization of the event generator codes at the crossover energy. This paper discusses only the experimental results and not the impact of those results on the FLUKA code.
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  • Mittler, Eva, et al. (författare)
  • Structural and mechanistic basis of neutralization by a pan-hantavirus protective antibody
  • 2023
  • Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 15:700
  • Tidskriftsartikel (refereegranskat)abstract
    • Emerging rodent-borne hantaviruses cause severe diseases in humans with no approved vaccines or therapeutics. We recently isolated a monoclonal broadly neutralizing antibody (nAb) from a Puumala virus-experienced human donor. Here, we report its structure bound to its target, the Gn/Gc glycoprotein heterodimer comprising the viral fusion complex. The structure explains the broad activity of the nAb: It recognizes conserved Gc fusion loop sequences and the main chain of variable Gn sequences, thereby straddling the Gn/Gc heterodimer and locking it in its prefusion conformation. We show that the nAb's accelerated dissociation from the divergent Andes virus Gn/Gc at endosomal acidic pH limits its potency against this highly lethal virus and correct this liability by engineering an optimized variant that sets a benchmark as a candidate pan-hantavirus therapeutic.
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  • Bonamy, AKE, et al. (författare)
  • Wide variation in severe neonatal morbidity among very preterm infants in European regions
  • 2019
  • Ingår i: Archives of disease in childhood. Fetal and neonatal edition. - : BMJ. - 1468-2052 .- 1359-2998. ; 104:1, s. F36-F45
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate the variation in severe neonatal morbidity among very preterm (VPT) infants across European regions and whether morbidity rates are higher in regions with low compared with high mortality rates.DesignArea-based cohort study of all births before 32 weeks of gestational age.Setting16 regions in 11 European countries in 2011/2012.PatientsSurvivors to discharge from neonatal care (n=6422).Main outcome measuresSevere neonatal morbidity was defined as intraventricular haemorrhage grades III and IV, cystic periventricular leukomalacia, surgical necrotizing enterocolitis and retinopathy of prematurity grades ≥3. A secondary outcome included severe bronchopulmonary dysplasia (BPD), data available in 14 regions. Common definitions for neonatal morbidities were established before data abstraction from medical records. Regional severe neonatal morbidity rates were correlated with regional in-hospital mortality rates for live births after adjustment on maternal and neonatal characteristics.Results10.6% of survivors had a severe neonatal morbidity without severe BPD (regional range 6.4%–23.5%) and 13.8% including severe BPD (regional range 10.0%–23.5%). Adjusted inhospital mortality was 13.7% (regional range 8.4%–18.8%). Differences between regions remained significant after consideration of maternal and neonatal characteristics (P<0.001) and severe neonatal morbidity rates were not correlated with mortality rates (P=0.50).ConclusionSevere neonatal morbidity rates for VPT survivors varied widely across European regions and were independent of mortality rates.
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