Understanding and controlling the spread of antimalarial resistance, particularly to artemisinin and its partner drugs, is a top priority.
Plasmodium falciparum
parasites resistant to chloroquine, ...amodiaquine, or piperaquine harbor mutations in the
P. falciparum
chloroquine resistance transporter (PfCRT), a transporter resident on the digestive vacuole membrane that in its variant forms can transport these weak-base 4-aminoquinoline drugs out of this acidic organelle, thus preventing these drugs from binding heme and inhibiting its detoxification. The structure of PfCRT, solved by cryogenic electron microscopy, shows mutations surrounding an electronegative central drug-binding cavity where they presumably interact with drugs and natural substrates to control transport.
P. falciparum
susceptibility to heme-binding antimalarials is also modulated by overexpression or mutations in the digestive vacuole membrane-bound ABC transporter PfMDR1 (
P. falciparum
multidrug resistance 1 transporter). Artemisinin resistance is primarily mediated by mutations in
P. falciparum
Kelch13 protein (K13), a protein involved in multiple intracellular processes including endocytosis of hemoglobin, which is required for parasite growth and artemisinin activation. Combating drug-resistant malaria urgently requires the development of new antimalarial drugs with novel modes of action.
► We model compressible convection to explore the properties of zonal winds in rapidly rotating spherical shells. ► We perform a systematic parametric study for various density scaleheights. ► Zonal ...jets properties remain fairly independent of the density stratification.
The banded structures observed on the surfaces of the gas giants are associated with strong zonal winds alternating in direction with latitude. We use three-dimensional numerical simulations of compressible convection in the anelastic approximation to explore the properties of zonal winds in rapidly rotating spherical shells. Since the model is restricted to the electrically insulating outer envelope, we therefore neglect magnetic effects.
A systematic parametric study for various density scaleheights and Rayleigh numbers allows to explore the dependence of convection and zonal jets on these parameters and to derive scaling laws.
While the density stratification affects the local flow amplitude and the convective scales, global quantities and zonal jets properties remain fairly independent of the density stratification. The zonal jets are maintained by Reynolds stresses, which rely on the correlation between zonal and cylindrically radial flow components. The gradual loss of this correlation with increasing supercriticality hampers all our simulations and explains why the additional compressional source of vorticity hardly affects zonal flows.
All these common features may explain why previous Boussinesq models were already successful in reproducing the morphology of zonal jets in gas giants.
The widely used antimalarial combination therapy dihydroartemisinin + piperaquine (DHA + PPQ) has failed in Cambodia. Here, we perform a genomic analysis that reveals a rapid increase in the ...prevalence of novel mutations in the Plasmodium falciparum chloroquine resistance transporter PfCRT following DHA + PPQ implementation. These mutations occur in parasites harboring the K13 C580Y artemisinin resistance marker. By introducing PfCRT mutations into sensitive Dd2 parasites or removing them from resistant Cambodian isolates, we show that the H97Y, F145I, M343L, or G353V mutations each confer resistance to PPQ, albeit with fitness costs for all but M343L. These mutations sensitize Dd2 parasites to chloroquine, amodiaquine, and quinine. In Dd2 parasites, multicopy plasmepsin 2, a candidate molecular marker, is not necessary for PPQ resistance. Distended digestive vacuoles were observed in pfcrt-edited Dd2 parasites but not in Cambodian isolates. Our findings provide compelling evidence that emerging mutations in PfCRT can serve as a molecular marker and mediator of PPQ resistance.
Stellar differential rotation can be separated into two main regimes: solar-like when the equator rotates faster than the poles and antisolar when the polar regions rotate faster than the equator. We ...investigate the transition between these two regimes with 3D numerical simulations of rotating spherical shells. We conduct a systematic parameter study which also includes models from different research groups. We find that the direction of the differential rotation is governed by the contribution of the Coriolis force in the force balance, independently of the model setup (presence of a magnetic field, thickness of the convective layer, density stratification). Rapidly rotating cases with a small Rossby number yield solar-like differential rotation, while weakly rotating models sustain antisolar differential rotation. Close to the transition, the two kinds of differential rotation are two possible bistable states. This study provides theoretical support for the existence of antisolar differential rotation in cool stars with large Rossby numbers.
Context. Dynamo action in giant planets and rapidly rotating stars leads to a broad variety of magnetic field geometries including small-scale multipolar and large-scale dipole-dominated topologies. ...Previous dynamo models suggest that solutions become multipolar once inertia is influential. Being tailored for terrestrial planets, most of these models neglected the background density stratification. Aims. We investigate the influence of the density stratification on convection-driven dynamo models. Methods. Three-dimensional nonlinear simulations of rapidly rotating spherical shells were employed using the anelastic approximation to incorporate density stratification. A systematic parametric study for various density stratifications and Rayleigh numbers at two different aspect ratios allowed us to explore the dependence of the magnetic field topology on these parameters. Results. Anelastic dynamo models tend to produce a broad range of magnetic field geometries that fall on two distinct branches with either strong dipole-dominated or weak multipolar fields. As long as inertia is weak, both branches can coexist, but the dipolar branch vanishes once inertia becomes influential. The dipolar branch also vanishes for stronger density stratifications. The reason is that the convective columns are concentrated in a narrow region close to the outer boundary equator, a configuration that favors nonaxisymmetric solutions. In multipolar solutions, zonal flows can become significant and participate in the toroidal field generation. Parker-dynamo waves may then play an important role close to onset of dynamo action, leading to a cyclic magnetic field behavior. Conclusions. These results are compatible with the magnetic fields of gas planets that are likely generated in their deeper conducting envelopes where the density stratification is only mild. Our simulations also suggest that the dipolar or multipolar magnetic fields of late M dwarfs can be explained in two ways. They may differ either because of the relative influence of inertia or fall into the regime where both types of solutions coexist.
In December 2019, the International Association of Geomagnetism and Aeronomy (IAGA) Division V Working Group (V-MOD) adopted the thirteenth generation of the International Geomagnetic Reference Field ...(IGRF). This IGRF updates the previous generation with a definitive main field model for epoch 2015.0, a main field model for epoch 2020.0, and a predictive linear secular variation for 2020.0 to 2025.0. This letter provides the equations defining the IGRF, the spherical harmonic coefficients for this thirteenth generation model, maps of magnetic declination, inclination and total field intensity for the epoch 2020.0, and maps of their predicted rate of change for the 2020.0 to 2025.0 time period.
ABSTRACT
The analysis of the recent gravity measurements of Jupiter and Saturn reveal that the zonal winds observed on their surfaces reach several thousand kilometres deep into their atmospheres. ...However, it remains unclear which mechanism prevents them from penetrating deeper. Recent models suggest that a stably stratified region would yield the desired effect. In this numerical study we systematically explore the dynamics of flow in a rotating spherical shell where the lower third is stably stratified while convection in the outer region drives multiple zonal winds, similar to those observed on Jupiter or Saturn. When using a rigid lower boundary condition, only an equatorial jet pair is formed without an underlying stable layer. When including a stable layer, fierce multiple jets also develop at mid to high latitudes, once the stable stratification is strong enough to effectively decouple the jet dynamics from the lower boundary. We find that the decay of the jet amplitude near the stable layer boundary is controlled by Ω/N, where Ω is the rotation rate and N the Brunt-Väisälä frequency that quantifies the degree of stable stratification. Furthermore, the penetration distance of the jets is proportional to the jet width. In the convective region, the winds are invariant along the axis of rotation, whereas their extension in the stable layer tends to become radially aligned.
The spherical Couette system, consisting of a viscous fluid between two differentially rotating concentric spheres, is studied using numerical simulations and compared with experiments performed at ...BTU Cottbus-Senftenberg, Germany. We concentrate on the case where the outer boundary rotates fast enough for the Coriolis force to play an important role in the force balance, and the inner boundary rotates slower or in the opposite direction as compared to the outer boundary. As the magnitude of differential rotation is increased, the system is found to transition through three distinct hydrodynamic regimes. The first regime consists of the emergence of the first non-axisymmetric instability. Thereafter one finds the onset of ‘fast’ equatorially antisymmetric inertial modes, with pairs of inertial modes forming triadic resonances with the first instability. A further increase in the magnitude of differential rotation leads to the flow transitioning to turbulence. Using an artificial excitation, we study how the background flow modifies the inertial mode frequency and structure, thereby causing departures from the eigenmodes of a full sphere and a spherical shell. We investigate triadic resonances of pairs of inertial modes with the fundamental instability. We explore possible onset mechanisms through numerical experiments.
The magnetometer instrument MPO-MAG on-board the Mercury Planetary Orbiter (MPO) of the BepiColombo mission en-route to Mercury is introduced, with its instrument design, its calibration and ...scientific targets. The instrument is comprised of two tri-axial fluxgate magnetometers mounted on a 2.9 m boom and are 0.8 m apart. They monitor the magnetic field with up to 128 Hz in a
±
2048
nT range. The MPO will be injected into an initial
480
×
1500
km polar orbit (2.3 h orbital period). At Mercury, we will map the planetary magnetic field and determine the dynamo generated field and constrain the secular variation. In this paper, we also discuss the effect of the instrument calibration on the ability to improve the knowledge on the internal field. Furthermore, the study of induced magnetic fields and field-aligned currents will help to constrain the interior structure in concert with other geophysical instruments. The orbit is also well-suited to study dynamical phenomena at the Hermean magnetopause and magnetospheric cusps. Together with its sister instrument Mio-MGF on-board the second satellite of the BepiColombo mission, the magnetometers at Mercury will study the reaction of the highly dynamic magnetosphere to changes in the solar wind. In the extreme case, the solar wind might even collapse the entire dayside magnetosphere. During cruise, MPO-MAG will contribute to studies of solar wind turbulence and transient phenomena.