Macrophage polarization is a process whereby macrophages acquire distinct effector states (M1 or M2) to carry out multiple and sometimes opposite functions. We show here that translational ...reprogramming occurs during macrophage polarization and that this relies on the Elongator complex subunit Elp3, an enzyme that modifies the wobble uridine base U34 in cytosolic tRNAs. Elp3 expression is downregulated by classical M1‐activating signals in myeloid cells, where it limits the production of pro‐inflammatory cytokines via FoxO1 phosphorylation, and attenuates experimental colitis in mice. In contrast, alternative M2‐activating signals upregulate Elp3 expression through a PI3K‐ and STAT6‐dependent signaling pathway. The metabolic reprogramming linked to M2 macrophage polarization relies on Elp3 and the translation of multiple candidates, including the mitochondrial ribosome large subunit proteins Mrpl3, Mrpl13, and Mrpl47. By promoting translation of its activator Ric8b in a codon‐dependent manner, Elp3 also regulates mTORC2 activation. Elp3 expression in myeloid cells further promotes Wnt‐driven tumor initiation in the intestine by maintaining a pool of tumor‐associated macrophages exhibiting M2 features. Collectively, our data establish a functional link between tRNA modifications, mTORC2 activation, and macrophage polarization.
Synopsis
Translational reprogramming occurs during macrophage polarization and involves tRNA modifications. The tRNA‐modifying enzyme Elp3 limits M1 but favors M2 macrophage polarization by promoting the translation of the mTORC2 regulator Ric8b in a codon‐dependent manner.
Elp3 expression is downregulated by LPS/IFNγ but induced by IL‐4/IL13
Elp3 deficiency exacerbates colitis and blocks M2 macrophage polarization in mice
Elp3 regulates mTORC2 activation by promoting Ric8b mRNA translation in a codon‐dependent manner.
Metabolic reprogramming linked to M2 macrophage polarization requires Elp3‐mediated production of mitochondrial ribosome large subunit proteins Mrpl3, Mrpl13, and Mrpl47.
The catalytic subunit of the Elongator complex, Elp3, differentially regulates macrophage polarization by promoting the translation of the mTORC2 regulator Ric8b.
Understanding the physical processes in the solar wind and corona that actively contribute to heating, acceleration, and dissipation is a primary objective of NASA's Parker Solar Probe (PSP) mission. ...Observations of circularly polarized electromagnetic waves at ion scales suggest that cyclotron resonance and wave-particle interactions are dynamically relevant in the inner heliosphere. A wavelet-based statistical study of circularly polarized events in the first perihelion encounter of PSP demonstrates that transverse electromagnetic waves at ion resonant scales are observed in 30-50% of radial field intervals. Average wave amplitudes of approximately 4 nT are measured, while the mean duration of wave events is on the order of 20 s; however, long-duration wave events can exist without interruption on hour-long timescales. Determination of wave vectors suggests propagation parallel/antiparallel to the mean magnetic field. Though ion-scale waves are preferentially observed during intervals with a radial mean magnetic field, we show that measurement constraints, associated with single spacecraft sampling of quasi-parallel waves superposed with anisotropic turbulence, render the measured coherent ion-wave spectrum unobservable when the mean magnetic field is oblique to the solar wind flow; these results imply that the occurrence of coherent ion-scale waves is not limited to a radial field configuration. The lack of radial scaling of characteristic wave amplitudes and duration suggests that the waves are generated in situ through plasma instabilities. Additionally, observations of proton distribution functions indicate that temperature anisotropy may drive the observed ion-scale waves.
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► GPU accelerated coarse-grained molecular dynamics used to investigate premicelles. ► These models predict small surfactant clusters above and below the CMC. ► Monomer exchange ...kinetics depend strongly on aggregate size.
Many unusual phenomena in surfactant solutions below the critical micelle concentration have been attributed to the existence of premicelles. Here we investigate the properties of premicelles in aqueous solutions of non-ionic surfactants surrounding the critical micelle concentration (CMC) using advanced computer simulations. The concentration of premicelles increases with total concentration up to the CMC, above which the concentrations of free monomers and premicelles remain nearly constant. Analysis shows premicellar structures ranging from spherical to chain-like. Monomer exchange kinetics are observed to depend strongly on the aggregate size, with premicelles exhibiting extremely short (1.3ns) relaxation times relative to full sized micelles (72ns).
Stochastic heating refers to an increase in the average magnetic moment of charged particles interacting with electromagnetic fluctuations whose frequencies are smaller than the particles’ cyclotron ...frequencies. This type of heating arises when the amplitude of the gyroscale fluctuations exceeds a certain threshold, causing particle orbits in the plane perpendicular to the magnetic field to become stochastic rather than nearly periodic. We consider the stochastic heating of protons by Alfvén-wave (AW) and kinetic-Alfvén-wave (KAW) turbulence, which may make an important contribution to the heating of the solar wind. Using phenomenological arguments, we derive the stochastic-proton-heating rate in plasmas in which
$\unicodeSTIX{x1D6FD}_{\text{p}}\sim 1$
–30, where
$\unicodeSTIX{x1D6FD}_{\text{p}}$
is the ratio of the proton pressure to the magnetic pressure. (We do not consider the
$\unicodeSTIX{x1D6FD}_{\text{p}}\gtrsim 30$
regime, in which KAWs at the proton gyroscale become non-propagating.) We test our formula for the stochastic-heating rate by numerically tracking test-particle protons interacting with a spectrum of randomly phased AWs and KAWs. Previous studies have demonstrated that at
$\unicodeSTIX{x1D6FD}_{\text{p}}\lesssim 1$
, particles are energized primarily by time variations in the electrostatic potential and thermal-proton gyro-orbits are stochasticized primarily by gyroscale fluctuations in the electrostatic potential. In contrast, at
$\unicodeSTIX{x1D6FD}_{\text{p}}\gtrsim 1$
, particles are energized primarily by the solenoidal component of the electric field and thermal-proton gyro-orbits are stochasticized primarily by gyroscale fluctuations in the magnetic field.
Eine Schlüsseleigenschaft lichtaktivierbarer Markierungen für die ultrahochauflösende Bildgebung ist die Zahl der pro Molekül emittierten Photonen. In der Zuschrift auf S. 1755 ff. beschreiben L. D. ...Lavis et al. eine neue Markierung für die Lokalisierungsmikroskopie, photoaktivierbares Si‐Q‐Rhodamin, die bessere Photonenzahlen liefert und ausreichend rotverschoben für eine Mehrfarben‐Bildgebung emittiert. Der Farbstoff eignet sich für hochentwickelte Bildgebungsexperimente und stellt ein neues Gerüst für rot‐fluorogene Moleküle dar.
Parker Solar Probe (PSP) routinely observes magnetic field deflections in the solar wind at distances less than 0.3 au from the Sun. These deflections are related to structures commonly called ...'switchbacks' (SBs), whose origins and characteristic properties are currently debated. Here, we use a database of visually selected SB intervals - and regions of solar wind plasma measured just before and after each SB - to examine plasma parameters, turbulent spectra from inertial to dissipation scales, and intermittency effects in these intervals. We find that many features, such as perpendicular stochastic heating rates and turbulence spectral slopes are fairly similar inside and outside of SBs. However, important kinetic properties, such as the characteristic break scale between the inertial to dissipation ranges differ inside and outside these intervals, as does the level of intermittency, which is notably enhanced inside SBs and in their close proximity, most likely due to magnetic field and velocity shears observed at the edges. We conclude that the plasma inside and outside of a SB, in most of the observed cases, belongs to the same stream, and that the evolution of these structures is most likely regulated by kinetic processes, which dominate small scale structures at the SB edges.
We study the damping of collisionless Alfvénic turbulence by two mechanisms: stochastic heating (whose efficiency depends on the local turbulence amplitude \(\delta z_\lambda\)) and linear Landau ...damping (whose efficiency is independent of \(\delta z_\lambda\)), describing in detail how they affect and are affected by intermittency. The overall efficiency of linear Landau damping is not affected by intermittency in critically balanced turbulence, while stochastic heating is much more efficient in the presence of intermittent turbulence. Moreover, stochastic heating leads to a drop in the scale-dependent kurtosis over a narrow range of scales around the ion gyroscale.
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