Physiologic Responses to Dietary Sulfur Amino Acid Restriction in Mice Are Influenced by Atf4 Status and Biological Sex

Background: Dietary sulfur amino acid restriction (SAAR) improves body composition and metabolic health across several model organisms in part through induction of the integrated stress response (ISR). Objective: We investigate the hypothesis that activating transcription factor 4 (ATF4) acts as a converging point in the ISR during SAAR. Methods: Using liver-specific or global gene ablation strategies, in both female and male mice, we address the role of ATF4 during dietary SAAR. Results: We show that ATF4 is dispensable in the chronic induction of the hepatokine fibroblast growth factor 21 while being essential for the sustained production of endogenous hydrogen sulfide. We also affirm that biological sex, independent of ATF4 status, is a determinant of the response to dietary SAAR. Conclusions: Our results suggest that auxiliary components of the ISR, which are independent of ATF4, are critical for SAAR-mediated improvements in metabolic health in mice

Precise interpolar phasing of abrupt climate change during the last ice age

The last glacial period exhibited abrupt Dansgaard–Oeschger climatic oscillations, evidence of which is preserved in a variety of Northern Hemisphere palaeoclimate archives¹. Ice cores show that Antarctica cooled during the warm phases of the Greenland Dansgaard–Oeschger cycle and vice versa[superscript 2,3], suggesting an interhemispheric redistribution of heat through a mechanism called the bipolar seesaw[superscript 4–6]. Variations in the Atlantic meridional overturning circulation (AMOC) strength are thought to have been important, but much uncertainty remains regarding the dynamics and trigger of these abrupt events[superscript 7–9]. Key information is contained in the relative phasing of hemispheric climate variations, yet the large, poorly constrained difference between gas age and ice age and the relatively low resolution of methane records from Antarctic ice cores have so far precluded methane-based synchronization at the required sub-centennial precision[superscript 2,3,10]. Here we use a recently drilled high-accumulation Antarctic ice core to show that, on average, abrupt Greenland warming leads the corresponding Antarctic cooling onset by 218 ± 92 years (2σ) for Dansgaard–Oeschger events, including the Bølling event; Greenland cooling leads the corresponding onset of Antarctic warming by 208 ± 96 years. Our results demonstrate a north-to-south directionality of the abrupt climatic signal, which is propagated to the Southern Hemisphere high latitudes by oceanic rather than atmospheric processes. The similar interpolar phasing of warming and cooling transitions suggests that the transfer time of the climatic signal is independent of the AMOC background state. Our findings confirm a central role for ocean circulation in the bipolar seesaw and provide clear criteria for assessing hypotheses and model simulations of Dansgaard–Oeschger dynamics

Imaging flow cytometry reveals that granulocyte colony-stimulating factor treatment causes loss of erythroblastic islands in the mouse bone marrow

The erythroblastic island (EBI) is a multicellular structure forming an erythropoietic niche consisting of a central macrophage surrounded by a rosette of maturing erythroblasts. Since their discovery more than 60 years ago, simultaneous quantification and visualization of EBIs remain difficult. Although flow cytometry enables high-throughput quantification of cell aggregates co-expressing macrophage and erythroblast markers, it cannot visually confirm whether the aggregates are genuine EBIs. While immunofluorescence microscopy allows visualization of EBIs, its low throughput limits its use for quantification. In the current study we employed nine-channel imaging flow cytometry (IFC) to develop a method to directly visualize and quantify EBIs in the mouse bone marrow. We found that EBI central macrophages do express F4/80, VCAM-1, and CD169, but not CD11b or Ly6G, and that CD11bLy6GF4/80 granulocytes are found associated at the periphery of 40%–60% EBIs. Furthermore, we show for the first time using IFC that in vivo treatment with the hematopoietic stem cell-mobilizing cytokine granulocyte colony-stimulating factor (G-CSF) reduced EBI frequency in the bone marrow by more than 100-fold. These results indicate that mobilizing doses of G-CSF cause a collapse of EBIs in the bone marrow

Video2_Using MEPED observations to infer plasma density and chorus intensity in the radiation belts.MP4

Efforts to model and predict energetic electron fluxes in the radiation belts are highly sensitive to local wave-particle interactions. In this study, we use multi-point measurements of precipitating and trapped electron fluxes to investigate the dynamic variation of chorus wave-particle interactions during the 17 March 2013 storm. Quasilinear theory characterizes the chorus wave-particle interaction as a diffusive process, with the diffusion coefficients depending on the particle energy and pitch angle, as well as the background plasma parameters such as the wave intensity and plasma density. These plasma parameters in the radiation belts are spatially localized and time-varying, so we construct event-specific diffusion coefficients using MEPED (onboard POES/MetOp) measurements of electron fluxes at low Earth orbit. This new method provides realistic diffusion coefficients for chorus waves that account for changes in the wave intensity, the plasma density, and the magnetic field strength in the outer radiation belt. We show that the inferred chorus intensity is significantly lower than previous estimates that use MEPED observations since the same amount of increased precipitation by 30–300 keV electrons can be explained by a change in the plasma density. This technique therefore allows for us to create time varying, global maps of the plasma-gyrofrequency ratio (fpe/fce), and therefore plasma density, in the outer radiation belts using the MEPED measurements. The global density estimates compare reasonably well to in situ density measurements from RBSP-B.</p

Video1_Using MEPED observations to infer plasma density and chorus intensity in the radiation belts.MP4

Efforts to model and predict energetic electron fluxes in the radiation belts are highly sensitive to local wave-particle interactions. In this study, we use multi-point measurements of precipitating and trapped electron fluxes to investigate the dynamic variation of chorus wave-particle interactions during the 17 March 2013 storm. Quasilinear theory characterizes the chorus wave-particle interaction as a diffusive process, with the diffusion coefficients depending on the particle energy and pitch angle, as well as the background plasma parameters such as the wave intensity and plasma density. These plasma parameters in the radiation belts are spatially localized and time-varying, so we construct event-specific diffusion coefficients using MEPED (onboard POES/MetOp) measurements of electron fluxes at low Earth orbit. This new method provides realistic diffusion coefficients for chorus waves that account for changes in the wave intensity, the plasma density, and the magnetic field strength in the outer radiation belt. We show that the inferred chorus intensity is significantly lower than previous estimates that use MEPED observations since the same amount of increased precipitation by 30–300 keV electrons can be explained by a change in the plasma density. This technique therefore allows for us to create time varying, global maps of the plasma-gyrofrequency ratio (fpe/fce), and therefore plasma density, in the outer radiation belts using the MEPED measurements. The global density estimates compare reasonably well to in situ density measurements from RBSP-B.</p

Video3_Using MEPED observations to infer plasma density and chorus intensity in the radiation belts.MP4

Efforts to model and predict energetic electron fluxes in the radiation belts are highly sensitive to local wave-particle interactions. In this study, we use multi-point measurements of precipitating and trapped electron fluxes to investigate the dynamic variation of chorus wave-particle interactions during the 17 March 2013 storm. Quasilinear theory characterizes the chorus wave-particle interaction as a diffusive process, with the diffusion coefficients depending on the particle energy and pitch angle, as well as the background plasma parameters such as the wave intensity and plasma density. These plasma parameters in the radiation belts are spatially localized and time-varying, so we construct event-specific diffusion coefficients using MEPED (onboard POES/MetOp) measurements of electron fluxes at low Earth orbit. This new method provides realistic diffusion coefficients for chorus waves that account for changes in the wave intensity, the plasma density, and the magnetic field strength in the outer radiation belt. We show that the inferred chorus intensity is significantly lower than previous estimates that use MEPED observations since the same amount of increased precipitation by 30–300 keV electrons can be explained by a change in the plasma density. This technique therefore allows for us to create time varying, global maps of the plasma-gyrofrequency ratio (fpe/fce), and therefore plasma density, in the outer radiation belts using the MEPED measurements. The global density estimates compare reasonably well to in situ density measurements from RBSP-B.</p

Heppa III Intercomparison Experiment on Electron Precipitation Impacts: 2. Model-Measurement Intercomparison of Nitric Oxide (NO) During a Geomagnetic Storm in April 2010

Precipitating auroral and radiation belt electrons are considered to play an important part in the natural forcing of the middle atmosphere with a possible impact on the climate system. Recent studies suggest that this forcing is underestimated in current chemistry-climate models. The HEPPA III intercomparison experiment is a collective effort to address this point. In this study, we apply electron ionization rates from three data-sets in four chemistry-climate models during a geomagnetically active period in April 2010. Results are evaluated by comparison with observations of nitric oxide (NO) in the mesosphere and lower thermosphere. Differences between the ionization rate data-sets have been assessed in a companion study. In the lower thermosphere, NO densities differ by up to one order of magnitude between models using the same ionization rate data-sets due to differences in the treatment of NO formation, model climatology, and model top height. However, a good agreement in the spatial and temporal variability of NO with observations lends confidence that the electron ionization is represented well above 80 km. In the mesosphere, the averages of model results from all chemistry-climate models differ consistently with the differences in the ionization-rate data-sets, but are within the spread of the observations, so no clear assessment on their comparative validity can be provided. However, observed enhanced amounts of NO in the mid-mesosphere below 70 km suggest a relevant contribution of the high-energy tail of the electron distribution to the hemispheric NO budget during and after the geomagnetic storm on April 6.ISSN:0148-0227ISSN:2169-938