Mdm2 has been well characterized as a negative regulator of the tumor suppressor p53. Recent studies have shown that Mdm2 is activated in response to a variety of oncogenic pathways independent of ...p53. Although its role as an oncogene via suppression of p53 function remains clear, growing evidence argues for p53-independent effects, as well as the remarkable possibility that Mdm2 has tumor suppressor functions in the appropriate context. Hence, Mdm2 is proving to be a key player in human cancer in its own right, and thus an important target for therapeutic intervention.
The p53 tumor suppressor protein is a major sensor of cellular stresses, and upon stabilization, activates or represses many genes that control cell fate decisions. While the mechanism of ...p53-mediated transactivation is well established, several mechanisms have been proposed for p53-mediated repression. Here, we demonstrate that the cyclin-dependent kinase inhibitor p21 is both necessary and sufficient for the downregulation of known p53-repression targets, including survivin, CDC25C, and CDC25B in response to p53 induction. These same targets are similarly repressed in response to p16 overexpression, implicating the involvement of the shared downstream retinoblastoma (RB)-E2F pathway. We further show that in response to either p53 or p21 induction, E2F4 complexes are specifically recruited onto the promoters of these p53-repression targets. Moreover, abrogation of E2F4 recruitment via the inactivation of RB pocket proteins, but not by RB loss of function alone, prevents the repression of these genes. Finally, our results indicate that E2F4 promoter occupancy is globally associated with p53-repression targets, but not with p53 activation targets, implicating E2F4 complexes as effectors of p21-dependent p53-mediated repression.
The proton light yield of liquid scintillators is an important property in the context of their use in large-scale neutrino experiments, with direct implications for neutrino-proton scattering ...measurements and the discrimination of fast neutrons from inverse
β
-decay coincidence signals. This work presents the first measurement of the proton light yield of a water-based liquid scintillator (WbLS) formulated from 5% linear alkyl benzene (LAB), at energies below 20 MeV, as well as a measurement of the proton light yield of a pure LAB + 2 g/L 2,5-diphenyloxazole (PPO) mixture (LABPPO). The measurements were performed using a double time-of-flight method and a pulsed neutron beam from the 88-Inch Cyclotron at Lawrence Berkeley National Laboratory. The proton light yields were measured relative to that of a 477 keV electron. The relative proton light yield of WbLS was approximately 3.8% lower than that of LABPPO, itself exhibiting a relative proton light yield 15–20% higher than previous measurements of an analogous anoxic sample. The observed quenching is not compatible with the Birks model for either material, but is well described with the addition of Chou’s bimolecular quenching term.
Rovers and landers on Mars have experienced local, regional, and planetary‐scale dust storms. However, in situ documentation of active lifting within storms has remained elusive. Over 5–11 January ...2022 (LS 153°–156°), a dust storm passed over the Perseverance rover site. Peak visible optical depth was ∼2, and visibility across the crater was briefly reduced. Pressure amplitudes and temperatures responded to the storm. Winds up to 20 m s−1 rotated around the site before the wind sensor was damaged. The rover imaged 21 dust‐lifting events—gusts and dust devils—in one 25‐min period, and at least three events mobilized sediment near the rover. Rover tracks and drill cuttings were extensively modified, and debris was moved onto the rover deck. Migration of small ripples was seen, but there was no large‐scale change in undisturbed areas. This work presents an overview of observations and initial results from the study of the storm.
Plain Language Summary
Mars commonly has local and regional dust storms, some of which grow into global dust storms. Until now, no lander or rover on Mars has observed the meteorology and processes within an active lifting storm center. The Perseverance rover experienced a large regional storm in Jezero crater over six sols (Martian days) in January 2022. It documented active dust lifting and winds reshaping the Martian sediment. Winds increased as the storm approached but were only directly monitored until the afternoon of the first sol, when the wind sensor failed during high winds. Winds, even after the loss of the wind sensor, were powerful enough to blow sand and lift dust around the rover. Rover imaging showed 21 dust devils and other dust lifting events near noon of the first sol. Images of the rover and terrain showed that there were several incidents of sediment mobilization immediately around the rover. Rover tracks were erased or heavily modified, cuttings from a recent drilling were removed, and sediment was deposited across the rover's deck. The changes wrought by the storm were concentrated on areas where the rover had previously modified the terrain, except for sand motion including the migration of small sand ripples.
Key Points
The Perseverance rover documented the meteorology and effects of a dust storm as it passed over Jezero crater, Mars
The storm brought damaging winds and wide‐spread dust lifting, while modifying the pressure amplitudes and thermal cycle at the site
Winds extensively modified previously disturbed areas, while sand motion and small‐scale ripple migration occurred all around the rover
Before the Perseverance rover landing, the acoustic environment of Mars was unknown. Models predicted that: (1) atmospheric turbulence changes at centimetre scales or smaller at the point where ...molecular viscosity converts kinetic energy into heat
, (2) the speed of sound varies at the surface with frequency
and (3) high-frequency waves are strongly attenuated with distance in CO
(refs.
). However, theoretical models were uncertain because of a lack of experimental data at low pressure and the difficulty to characterize turbulence or attenuation in a closed environment. Here, using Perseverance microphone recordings, we present the first characterization of the acoustic environment on Mars and pressure fluctuations in the audible range and beyond, from 20 Hz to 50 kHz. We find that atmospheric sounds extend measurements of pressure variations down to 1,000 times smaller scales than ever observed before, showing a dissipative regime extending over five orders of magnitude in energy. Using point sources of sound (Ingenuity rotorcraft, laser-induced sparks), we highlight two distinct values for the speed of sound that are about 10 m s
apart below and above 240 Hz, a unique characteristic of low-pressure CO
-dominated atmosphere. We also provide the acoustic attenuation with distance above 2 kHz, allowing us to explain the large contribution of the CO
vibrational relaxation in the audible range. These results establish a ground truth for the modelling of acoustic processes, which is critical for studies in atmospheres such as those of Mars and Venus.
Many neutron star properties, such as the proton fraction, reflect the symmetry energy contributions to the equation of state that dominate when neutron and proton densities differ strongly. To ...constrain these contributions at suprasaturation densities, we measure the spectra of charged pions produced by colliding rare isotope tin (Sn) beams with isotopically enriched Sn targets. Using ratios of the charged pion spectra measured at high transverse momenta, we deduce the slope of the symmetry energy to be 42<L<117 MeV. This value is slightly lower but consistent with the L values deduced from a recent measurement of the neutron skin thickness of ^{208}Pb.
NASA’s InSight mission to Mars will measure seismic signals to determine the planet’s interior structure. These highly sensitive seismometers are susceptible to corruption of their measurements by ...environmental changes. Magnetic fields, atmosphere pressure changes, and local winds can all induce apparent changes in the seismic records that are not due to propagating ground motions. Thus, InSight carries a set of sensors called the Auxiliary Payload Sensor Suite (APSS) which includes a magnetometer, an atmospheric pressure sensor, and a pair of wind and air temperature sensors. In the case of the magnetometer, knowledge of the amplitude of the fluctuating magnetic field at the InSight lander will allow the separation of seismic signals from potentially interfering magnetic signals of either natural or spacecraft origin. To acquire such data, a triaxial fluxgate magnetometer was installed on the deck of the lander to obtain magnetic records at the same cadence as the seismometer. Similarly, a highly sensitive pressure sensor is carried by InSight to enable the removal of local ground-surface tilts due to advecting pressure perturbations. Finally, the local winds (speed and direction) and air temperature are estimated using a hot-film wind sensor with heritage from REMS on the Curiosity rover. When winds are too high, seismic signals can be ignored or discounted. Herein we describe the APSS sensor suite, the test programs for its components, and the possible additional science investigations it enables.
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