Aims/hypothesis
Obesity and insulin resistance are associated with low-grade chronic inflammation. Glucagon-like peptide-1 (GLP-1) is known to reduce insulin resistance. We investigated whether GLP-1 ...has anti-inflammatory effects on adipose tissue, including adipocytes and adipose tissue macrophages (ATM).
Methods
We administered a recombinant adenovirus (rAd) producing GLP-1 (rAd-GLP-1) to an
ob/ob
mouse model of diabetes. We examined insulin sensitivity, body fat mass, the infiltration of ATM and metabolic profiles. We analysed the mRNA expression of inflammatory cytokines, lipogenic genes, and M1 and M2 macrophage-specific genes in adipose tissue by real-time quantitative PCR. We also examined the activation of nuclear factor κB (NF-κB), extracellular signal-regulated kinase 1/2 and Jun N-terminal kinase (JNK) in vivo and in vitro.
Results
Fat mass, adipocyte size and mRNA expression of lipogenic genes were significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Macrophage populations (F4/80
+
and F4/80
+
CD11b
+
CD11c
+
cells), as well as the expression and production of IL-6, TNF-α and monocyte chemoattractant protein-1, were significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Expression of M1-specific mRNAs was significantly reduced, but that of M2-specific mRNAs was unchanged in rAd-GLP-1-treated
ob/ob
mice. NF-κB and JNK activation was significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Lipopolysaccharide-induced inflammation was reduced by the GLP-1 receptor agonist, exendin-4, in 3T3-L1 adipocytes and ATM.
Conclusions/interpretation
We suggest that GLP-1 reduces macrophage infiltration and directly inhibits inflammatory pathways in adipocytes and ATM, possibly contributing to the improvement of insulin sensitivity.
Inner magnetospheric electrons are precipitated in the ionosphere via pitch‐angle (PA) scattering by lower band chorus (LBC), upper band chorus (UBC), and electrostatic electron cyclotron harmonic ...(ECH) waves. However, the PA scattering efficiency of low‐energy electrons (0.1–10 keV) has not been investigated via in situ observations because of difficulties in flux measurements within loss cones at the magnetosphere. In this study, we demonstrate that LBC, UBC, and ECH waves contribute to PA scattering of electrons at different energy ranges using the Arase (ERG) satellite observation data and successively detected the moderate loss cone filling, that is, approaching strong diffusion. Approaching strong diffusion by LBC, UBC, and ECH waves occurred at ∼2–20 keV, ∼1–10 keV, and ∼0.1–2 keV, respectively. The occurrence rate of the approaching strong diffusion by high‐amplitude LBC (>50 pT), UBC (>20 pT), and ECH (>10 mV/m) waves, respectively, reached ∼70%, ∼40%, and ∼30% higher than that without simultaneous wave activity. The energy range in which the occurrence rate was high agreed with the range where the PA diffusion rate of each wave exceeded the strong diffusion level based on the quasilinear theory.
Key Points
The pitch‐angle scattering efficiencies by plasma waves are statistically investigated using in situ observations
Lower band chorus waves caused approaching strong diffusion with the highest occurrence rate in the energy range of ∼2–20 keV
Electrostatic electron cyclotron harmonic waves could contribute approaching strong diffusion in the ∼0.1–1 keV energy range
Plasmaspheric hiss can cause energetic electron precipitation from the magnetosphere to the Earth's upper atmosphere and affect the ionospheric electron density profiles. In this study, we use Arase ...satellite measurements in the dayside plasmasphere to model the electron precipitation and the resultant ionospheric response, and compare the results to the electron density measured by the Poker Flat Incoherent Scatter Radar (PFISR). We analyzed two close conjunction events between Arase and PFISR at L ∼ 6 in the afternoon sector, when Arase was in the outer plasmasphere and traveled into the plasmaspheric plumes. Modest or strong hiss waves were observed with amplitudes higher than 50 pT during both events. Quasilinear modeling suggests that the hiss waves could cause intense electron precipitation ranging from several keV to several hundred keV energies. The electron density profiles at 60–90 km modeled by the Boulder Electron Radiation to Ionization (BERI) model suggest significant electron density enhancements due to the precipitating electrons. PFISR simultaneously observed electron density enhancements during both events, and provided evidence for the electron precipitation at altitudes down to <70 km. The temporal modulation of hiss caused the modulated density profiles in BERI modeling, but was not evident in PFISR observations. The modeled altitude profiles of the perturbed electron density overall agree with PFISR observation. At altitudes below 75 km, the modeled electron densities are lower than the observation, suggesting additional high energy electron precipitation possibly due to low frequency (<50 Hz) waves or hiss wave powers ducted to high latitudes.
Key Points
Two Poker Flat Incoherent Scatter Radar (PFISR)‐Arase conjunction events are identified at the dayside plasmasphere when hiss wave amplitudes reach 50–100 pT at L ∼ 6
Hiss‐driven electron precipitation obtained from quasilinear simulation is used to model ionospheric density profiles at 60–90 km altitude
Modeled electron densities overall agree with PFISR observations with differences in the temporal modulation and at altitudes below 75 km
We present observations of an equatorward detachment of the auroral arc from the main oval and magnetically conjugate measurements made by the Arase satellite in the inner magnetosphere. The all‐sky ...imager at Gakona (magnetic latitude = 63.6°N), Alaska, shows the detachment of the auroral arc in both red and green lines at local midnight (∼0130–0230 MLT) on 30 March 2017. The electron density derived from the Arase in‐situ observations shows that this arc occurred outside the plasmapause. At the arc crossing, the electron flux of energies ∼0.1–2 keV is found to be locally enhanced at L∼4.3–4.5. We estimated auroral intensities for both red and green lines by using the Arase low‐energy (0.1–19 keV) electron flux data. The peak latitude of the estimated intensity shows reasonably good correspondence with the observed intensity mapped at the ionospheric footprints of the Arase satellite. These findings indicate that the observed arc detachment at Gakona was associated with the localized enhancement of low‐energy electrons (∼0.1–2 keV) at the inner edge of the electron plasma sheet. Further, we employ the simulation results of the Community Coordinated Modeling Center (CCMC), the BATS‐R‐US–CIMI 3‐D MHD code to understand the conditions in the inner magnetosphere around the time of detachment. Although the simulation could not reproduce the lower‐energy component responsible for the arc detachment, it successfully reproduced two earthward convection events at the lower radial distance (R) (R ≤ ∼4) around the time of arc detachment and the features of enhanced convection in similarity with the observations.
Key Points
Conjugate measurements of an equatorward detachment of the auroral arc from the main oval and the Arase satellite in the inner magnetosphere
Equatorward detachment of the auroral arc coincided with a localized enhancement of electrons of energies ∼0.1–2 keV deeper down to L∼4.3–4.5
BATS‐R‐US–CIMI model successfully reproduced the enhancement of lower‐energy electrons (∼8–40 keV) at a lower radial distance (R < 4)
Using first-principles calculations, we predict a family group of two-dimensional semimetals MX (M = Pd, Pt; X = S, Se, Te), which has a zig-zag type mono-layer structure in the
Pmma
(no. 41) layer ...group. Band structure analysis reveals that node-line features are caused by band inversion and the inversion exists even in the absence of spin-orbital-coupling. First-principles calculations show the robust lattice stability of these predicted materials. This work provides the possibility of making a group of novel two-dimensional materials with semimetal features.
Using first-principles calculations, we predict a family group of two-dimensional semimetals MX (M = Pd, Pt; X = S, Se, Te), which has a zig-zag type mono-layer structure in the
Pmma
(no. 41) layer group.
Auroral brightening is one of the most common phenomena that occur during substorm onset and is usually recognized as a projection of the substorm‐associated magnetospheric plasma dynamics to the ...ionosphere. However, electromagnetic fields and plasma features associated with the substorm brightening arc have not been well understood. In this study, we present a comprehensive observation of the source plasma and field variations of a substorm brightening aurora in the inner magnetosphere. We performed a unique conjugate observation of a substorm brightening auroral arc observed by a ground‐based camera and by the Arase satellite in the magnetospheric source region at L ∼ 6. The event was observed at Tromsø (69.6°N, 19.2°E), Norway, on 12 October 2017. The brightening arc indicates east‐west structures with longitudinal scales of ∼0.5°–2.0°. Field‐aligned bi‐directional electrons with an energy range between 66 and 1,800 eV were detected by the satellite, simultaneously with the appearance of the brightening arc in the camera. These electrons were probably supplied from the auroral brightening region in the ionosphere, indicating that the satellite was on the same field line of the brightening aurora. The magnetic and electric field data show characteristic fluctuations and earthward Poynting flux around the time that the satellite crossed the aurora. Anti‐phase oscillations between the thermal pressure and the magnetic pressure are also reported. Based on these observations, we suggest the possibility that a ballooning instability occurred in the source region of the substorm brightening arc in the inner magnetosphere at L ∼ 6.
Plain Language Summary
A frequently occurring source of variations in the magnetosphere is the substorm, a process that causes energy dissipation into the atmosphere. Substorm is presented as the development of aurorae at high latitudes in the ionosphere. The study of substorm processes helps in understanding the near‐Earth space environment and the space weather. Along Earth's magnetic field lines, the aurora at a latitude of ∼65°N can be traced to ∼4–7 Earth radii away from the Earth at the equatorial plane in space. Using a ground‐based auroral camera, we can construct the correspondence between auroral motion and field and plasma variation at the satellite. This study reports such a unique event of substorm brightening arc observed at Tromsø, Norway, on 12 October 2017. Satellite observed bi‐directional electrons prove the connection between aurora break‐up at ∼100 km altitude and its source region in the magnetosphere at ∼30,000 km away from Earth. Based on the magnetic wave spectrograms, auroral bead‐like structures and other observational results, we suggest the possibility that a ballooning plasma instability occurred in the source region of the substorm brightening arc in the inner magnetosphere.
Key Points
Observation of plasma and field features in the source region of a sudden brightening auroral arc during a minor substorm onset at L ∼ 6
Energization of particles, field‐aligned electrons, and electromagnetic field fluctuations were observed during the arc crossing by Arase
Several observational facts indicate the possibility of ballooning instability occurring at this substorm onset
Prolonged expression of the CRISPR-Cas9 nuclease and gRNA from viral vectors may cause off-target mutagenesis and immunogenicity. Thus, a transient delivery system is needed for therapeutic genome ...editing applications. Here, we develop an extracellular nanovesicle-based ribonucleoprotein delivery system named NanoMEDIC by utilizing two distinct homing mechanisms. Chemical induced dimerization recruits Cas9 protein into extracellular nanovesicles, and then a viral RNA packaging signal and two self-cleaving riboswitches tether and release sgRNA into nanovesicles. We demonstrate efficient genome editing in various hard-to-transfect cell types, including human induced pluripotent stem (iPS) cells, neurons, and myoblasts. NanoMEDIC also achieves over 90% exon skipping efficiencies in skeletal muscle cells derived from Duchenne muscular dystrophy (DMD) patient iPS cells. Finally, single intramuscular injection of NanoMEDIC induces permanent genomic exon skipping in a luciferase reporter mouse and in mdx mice, indicating its utility for in vivo genome editing therapy of DMD and beyond.
Medium‐scale traveling ionospheric disturbances (MSTIDs) are a phenomenon widely and frequently observed over the ionosphere from high to low latitudes. Night time MSTIDs are caused generally by the ...polarization electric field in the ionosphere. However, propagation of this polarization electric field to the magnetosphere has not yet been identified. Here, we report the first observation of the polarization electric field and associated density variations of a night time MSTID in the magnetosphere. The MSTID event was observed by an all‐sky airglow imager at Gakona (geographical latitude: 62.39°N, geographical longitude: 214.78°E, magnetic latitude: 63.20°N), Alaska. The Arase satellite passed over the MSTID in the inner magnetosphere at 0530–0800 UT (2030–2300 LT) on November 3, 2018. This MSTID, observed in 630 nm airglow images, was propagating westward with a horizontal wavelength of ∼165 km, a north–south phase front, and a phase velocity of ∼80 m/s. The Arase satellite footprint on the ionosphere crossed the MSTID in the direction nearly perpendicular to the MSTID phase fronts. The electric field and electron density observed by the Arase satellite showed periodic variation associated with the MSTID structure with amplitudes of ∼2 mV/m and ∼150 cm−3, respectively. The electric field variations projected to the ionosphere are mainly in the east‐west direction and are consistent with the direction of the polarization electric field expected from MSTID growth by E × B drift. This observation indicates that the polarization electric field associated with the MSTID in the ionosphere is projected onto the magnetosphere, causing plasma density fluctuations in the magnetosphere.
Plain Language Summary
Medium‐scale traveling ionospheric disturbances (MSTIDs) are propagation of electron density fluctuation in the ionospheric F‐layer. MSTIDs are a common phenomenon from high to low latitudes. From simultaneous observations of airglow imagers in both hemispheres, MSTIDs are known to have a mirror structure at magnetic conjugate hemispheres. If an MSTID is generated by ionospheric instabilities, the polarization electric field associated with the MSTID should propagate along the magnetic field lines. In this paper, we report the first simultaneous observation of an MSTID using a ground‐based airglow imager and the Arase satellite in the magnetosphere. The electric field variations and plasma density fluctuations observed by Arase showed periodic variations associated with the MSTID structure. This result indicates that the spatial inhomogeneity of the ionospheric Pedersen conductivity associated with the MSTID yields the polarization electric field in the ionosphere, and that this polarization electric field was projected onto the magnetosphere.
Key Points
First simultaneous observation of an medium‐scale traveling ionospheric disturbance (MSTID) using a ground‐based airglow imager and the Arase satellite in the magnetosphere
The polarization electric field associated with the MSTID in the ionosphere was projected to the magnetosphere and observed by Arase
The electric field and electron density observed by the Arase satellite showed a periodic variation associated with the MSTID structure
Topological insulators are insulating materials that display massless, Dirac-like surface states in which the electrons have only one spin degree of freedom on each surface. These states have been ...imaged by photoemission, but little information on their transport parameters, for example, mobility, is available. We report the observation of Shubnikov-de Haas oscillations arising from the surface states in nonmetallic crystals of Bi(2)Te(3). In addition, we uncovered a Hall anomaly in weak fields, which enables the surface current to be seen directly. Both experiments yield a surface mobility (9000 to 10,000 centimeter(2) per volt-second) that is substantially higher than in the bulk. The Fermi velocity of 4 x 10(5) meters per second obtained from these transport experiments agrees with angle-resolved photoemission experiments.
A physical mechanism to produce pulsating aurora (PsA) has been considered to be the interaction of the electron and the chorus wave generated near the equatorial plane of the magnetosphere. A recent ...observation of high temporal resolution of chorus waves by the Arase satellite revealed that the presence or absence of the internal modulation of PsA, which is a characteristic sub‐second scintillation at 3 ± 1 Hz within each optical pulsation, is closely related to the discreteness of the element structure of the chorus wave. However, it is still unclear what parameters (or conditions) control the discreteness of the element and the existence of the internal modulation of PsA. In this study, we discuss parameters that determine the presence or absence of the internal modulation of PsA and element structure of chorus by showing a conjugate observation of PsA/chorus by ground‐based cameras and the Arase satellite. During the event, the occurrence of internal modulation increased temporally. The wave data from the satellite show that the repetitive frequency of elements was ∼6 Hz when the internal modulation was indistinct, while the repetitive frequency was ∼3 Hz when the internal modulation was distinct. The particle measurements suggest that this difference was caused by changes in the density and the temperature anisotropy of the hot electron. The internal modulation was clearly observed when the density of hot electrons decreased and the temperature anisotropy relaxed after the injection. Observations of internal modulations from the ground might allow us to estimate the parameters such as energetic electron density and temperature anisotropy in the magnetosphere.
Key Points
We analyzed a pulsating aurora (PsA) event in which the occurrence frequency of internal modulation increased significantly with time
A conjugate observation with Arase suggests that a sudden enhancement of energetic electrons by the injection caused non‐modulated PsAs
The internal modulation may be more often observed after the injection as the density of energetic electrons decreases in the magnetosphere
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