Stress response silencing by an E3 ligase mutated in neurodegeneration.

Stress response pathways detect and alleviate adverse conditions to safeguard cell and tissue homeostasis, yet their prolonged activation induces apoptosis and disrupts organismal health1-3. How stress responses are turned off at the right time and place remains poorly understood. Here we report a ubiquitin-dependent mechanism that silences the cellular response to mitochondrial protein import stress. Crucial to this process is the silencing factor of the integrated stress response (SIFI), a large E3 ligase complex mutated in ataxia and in early-onset dementia that degrades both unimported mitochondrial precursors and stress response components. By recognizing bifunctional substrate motifs that equally encode protein localization and stability, the SIFI complex turns off a general stress response after a specific stress event has been resolved. Pharmacological stress response silencing sustains cell survival even if stress resolution failed, which underscores the importance of signal termination and provides a roadmap for treating neurodegenerative diseases caused by mitochondrial import defects.

Polar vortex crystals: Emergence and structure.

Vortex crystals are quasiregular arrays of like-signed vortices in solid-body rotation embedded within a uniform background of weaker vorticity. Vortex crystals are observed at the poles of Jupiter and in laboratory experiments with magnetized electron plasmas in axisymmetric geometries. We show that vortex crystals form from the free evolution of randomly excited two-dimensional turbulence on an idealized polar cap. Once formed, the crystals are long lived and survive until the end of the simulations (300 crystal-rotation periods). We identify a fundamental length scale, Lγ=(U/γ)1/3, characterizing the size of the crystal in terms of the mean-square velocity U of the fluid and the polar parameter γ=fp/a2p, with fp the Coriolis parameter at the pole and ap the polar radius of the planet.

Ubiquitin-dependent remodeling of the actin cytoskeleton drives cell fusion.

Cell-cell fusion is a frequent and essential event during development, and its dysregulation causes diseases ranging from infertility to muscle weakness. Fusing cells need to repeatedly remodel their plasma membrane through orchestrated formation and disassembly of actin filaments, but how the dynamic reorganization of the cortical actin cytoskeleton is controlled is still poorly understood. Here, we identified a ubiquitin-dependent toggle switch that establishes reversible actin bundling during mammalian cell fusion. We found that EPS8-IRSp53 complexes stabilize cortical actin bundles at sites of cell contact to promote close membrane alignment. EPS8 monoubiquitylation by CUL3KCTD10 displaces EPS8-IRSp53 from membranes and counteracts actin bundling, a dual activity that restricts actin bundling to allow paired cells to progress with fusion. We conclude that cytoskeletal rearrangements during development are precisely controlled by ubiquitylation, raising the possibility of modulating the efficiency of cell-cell fusion for therapeutic benefit.

Jupiter's Overturning Circulation: Breaking Waves Take the Place of Solid Boundaries.

Cloud-tracked wind observations document the role of eddies in putting momentum into the zonal jets. Chemical tracers, lightning, clouds, and temperature anomalies document the rising and sinking in the belts and zones, but questions remain about what drives the flow between the belts and zones. We suggest an additional role for the eddies, which is to generate waves that propagate both up and down from the cloud layer. When the waves break they deposit momentum and thereby replace the friction forces at solid boundaries that enable overturning circulations on terrestrial planets. By depositing momentum of one sign within the cloud layer and momentum of the opposite sign above and below the clouds, the eddies maintain all components of the circulation, including the stacked, oppositely rotating cells between each belt-zone pair, and the zonal jets themselves.

Modeling the stability of polygonal patterns of vortices at the poles of Jupiter as revealed by the Juno spacecraft.

From its pole-to-pole orbit, the Juno spacecraft discovered arrays of cyclonic vortices in polygonal patterns around the poles of Jupiter. In the north, there are eight vortices around a central vortex, and in the south there are five. The patterns and the individual vortices that define them have been stable since August 2016. The azimuthal velocity profile vs. radius has been measured, but vertical structure is unknown. Here, we ask, what repulsive mechanism prevents the vortices from merging, given that cyclones drift poleward in atmospheres of rotating planets like Earth? What atmospheric properties distinguish Jupiter from Saturn, which has only one cyclone at each pole? We model the vortices using the shallow water equations, which describe a single layer of fluid that moves horizontally and has a free surface that moves up and down in response to fluid convergence and divergence. We find that the stability of the pattern depends mostly on shielding-an anticyclonic ring around each cyclone, but also on the depth. Too little shielding and small depth lead to merging and loss of the polygonal pattern. Too much shielding causes the cyclonic and anticyclonic parts of the vortices to fly apart. The stable polygons exist in between. Why Jupiter's vortices occupy this middle range is unknown. The budget-how the vortices appear and disappear-is also unknown, since no changes, except for an intruder that visited the south pole briefly, have occurred at either pole since Juno arrived at Jupiter in 2016.

The General Practice and Residential Aged Care Facility Concordance of Medication (GRACEMED) study.

BACKGROUND: The lack of interoperable IT systems between residential aged care facilities (RACF) and general practitioners (GP) in primary care settings in Australia introduces the potential for medication discrepancies and other medication errors. The aim of the GRACEMED study is to determine the extent and potential severity of medication discrepancies between general practice and RACFs, and identify factors associated with medication discrepancies. METHODS: A cross sectional study of medication discrepancies between RACF medication orders and GP medication lists was conducted in the Sydney North Health Network, Australia. A random sample of RACF residents was included from practice lists provided by the general practices. RACF medication orders and GP medication lists for the included residents were compared, and medication discrepancies between the two sources were identified and characterised in terms of discrepancy type, potential for harm and associated factors. RESULTS: 31 GPs and 203 residents were included in the study. A total of 1777 discrepancies were identified giving an overall discrepancy rate of 72.6 discrepancies for every 100 medications. Omissions were the most common discrepancy type (35.2%,) followed by dose discrepancies (34.4%) and additions (30.4%). 48.5% of residents had a discrepancy with the potential to result in moderate harm and 9.8% had a discrepancy with the potential for severe harm. Number of medications prescribed was the only factor associated with medication discrepancies. CONCLUSION: Increased use of systems that allow information sharing and improved interoperability of clinical information is urgently needed to address medication safety issues experienced by RACF residents.

Small lightning flashes from shallow electrical storms on Jupiter.

Lightning flashes have been observed by a number of missions that visited or flew by Jupiter over the past several decades. Imagery led to a flash rate estimate of about 4 × 10-3 flashes per square kilometre per year (refs. 1,2). The spatial extent of Voyager flashes was estimated to be about 30 kilometres (half-width at half-maximum intensity, HWHM), but the camera was unlikely to have detected the dim outer edges of the flashes, given its weak response to the brightest spectral line of Jovian lightning emission, the 656.3-nanometre Hα line of atomic hydrogen1,3-6. The spatial resolution of some cameras allowed investigators to confirm 22 flashes with HWHM greater than 42 kilometres, and to estimate one with an HWHM of 37 to 45 kilometres (refs. 1,7-9). These flashes, with optical energies comparable to terrestrial 'superbolts'-of (0.02-1.6) × 1010 joules-have been interpreted as tracers of moist convection originating near the 5-bar level of Jupiter's atmosphere (assuming photon scattering from points beneath the clouds)1-3,7,8,10-12. Previous observations of lightning have been limited by camera sensitivity, distance from Jupiter and long exposures (about 680 milliseconds to 85 seconds), meaning that some measurements were probably superimposed flashes reported as one1,2,7,9,10,13. Here we report optical observations of lightning flashes by the Juno spacecraft with energies of approximately 105-108 joules, flash durations as short as 5.4 milliseconds and inter-flash separations of tens of milliseconds, with typical terrestrial energies. The flash rate is about 6.1 × 10-2 flashes per square kilometre per year, more than an order of magnitude greater than hitherto seen. Several flashes are of such small spatial extent that they must originate above the 2-bar level, where there is no liquid water14,15. This implies that multiple mechanisms for generating lightning on Jupiter need to be considered for a full understanding of the planet's atmospheric convection and composition.

A Survey of Small-Scale Waves and Wave-Like Phenomena in Jupiter's Atmosphere Detected by JunoCam.

In the first 20 orbits of the Juno spacecraft around Jupiter, we have identified a variety of wave-like features in images made by its public-outreach camera, JunoCam. Because of Juno's unprecedented and repeated proximity to Jupiter's cloud tops during its close approaches, JunoCam has detected more wave structures than any previous surveys. Most of the waves appear in long wave packets, oriented east-west and populated by narrow wave crests. Spacing between crests were measured as small as ~30 km, shorter than any previously measured. Some waves are associated with atmospheric features, but others are not ostensibly associated with any visible cloud phenomena and thus may be generated by dynamical forcing below the visible cloud tops. Some waves also appear to be converging, and others appear to be overlapping, possibly at different atmospheric levels. Another type of wave has a series of fronts that appear to be radiating outward from the center of a cyclone. Most of these waves appear within 5° of latitude from the equator, but we have detected waves covering planetocentric latitudes between 20°S and 45°N. The great majority of the waves appear in regions associated with prograde motions of the mean zonal flow. Juno was unable to measure the velocity of wave features to diagnose the wave types due to its close and rapid flybys. However, both by our own upper limits on wave motions and by analogy with previous measurements, we expect that the waves JunoCam detected near the equator are inertia-gravity waves.

Cassini Exploration of the Planet Saturn: A Comprehensive Review.

Before Cassini, scientists viewed Saturn's unique features only from Earth and from three spacecraft flying by. During more than a decade orbiting the gas giant, Cassini studied the planet from its interior to the top of the atmosphere. It observed the changing seasons, provided up-close observations of Saturn's exotic storms and jet streams, and heard Saturn's lightning, which cannot be detected from Earth. During the Grand Finale orbits, it dove through the gap between the planet and its rings and gathered valuable data on Saturn's interior structure and rotation. Key discoveries and events include: watching the eruption of a planet-encircling storm, which is a 20- or 30-year event, detection of gravity perturbations from winds 9000 km below the tops of the clouds, demonstration that eddies are supplying energy to the zonal jets, which are remarkably steady over the 25-year interval since the Voyager encounters, re-discovery of the north polar hexagon after 25 years, determination of elemental abundance ratios He/H, C/H, N/H, P/H, and As/H, which are clues to planet formation and evolution, characterization of the semiannual oscillation of the equatorial stratosphere, documentation of the mysteriously high temperatures of the thermosphere outside the auroral zone, and seeing the strange intermittency of lightning, which typically ceases to exist on the planet between outbursts every 1-2 years. These results and results from the Jupiter flyby are all discussed in this review.

Prevalent lightning sferics at 600 megahertz near Jupiter's poles.

Lightning has been detected on Jupiter by all visiting spacecraft through night-side optical imaging and whistler (lightning-generated radio waves) signatures1-6. Jovian lightning is thought to be generated in the mixed-phase (liquid-ice) region of convective water clouds through a charge-separation process between condensed liquid water and water-ice particles, similar to that of terrestrial (cloud-to-cloud) lightning7-9. Unlike terrestrial lightning, which emits broadly over the radio spectrum up to gigahertz frequencies10,11, lightning on Jupiter has been detected only at kilohertz frequencies, despite a search for signals in the megahertz range 12 . Strong ionospheric attenuation or a lightning discharge much slower than that on Earth have been suggested as possible explanations for this discrepancy13,14. Here we report observations of Jovian lightning sferics (broadband electromagnetic impulses) at 600 megahertz from the Microwave Radiometer 15 onboard the Juno spacecraft. These detections imply that Jovian lightning discharges are not distinct from terrestrial lightning, as previously thought. In the first eight orbits of Juno, we detected 377 lightning sferics from pole to pole. We found lightning to be prevalent in the polar regions, absent near the equator, and most frequent in the northern hemisphere, at latitudes higher than 40 degrees north. Because the distribution of lightning is a proxy for moist convective activity, which is thought to be an important source of outward energy transport from the interior of the planet16,17, increased convection towards the poles could indicate an outward internal heat flux that is preferentially weighted towards the poles9,16,18. The distribution of moist convection is important for understanding the composition, general circulation and energy transport on Jupiter.

Earth's changing global atmospheric energy cycle in response to climate change.

The Lorenz energy cycle is widely used to investigate atmospheres and climates on planets. However, the long-term temporal variations of such an energy cycle have not yet been explored. Here we use three independent meteorological data sets from the modern satellite era, to examine the temporal characteristics of the Lorenz energy cycle of Earth's global atmosphere in response to climate change. The total mechanical energy of the global atmosphere basically remains constant with time, but the global-average eddy energies show significant positive trends. The spatial investigations suggest that these positive trends are concentrated in the Southern Hemisphere. Significant positive trends are also found in the conversion, generation and dissipation rates of energies. The positive trends in the dissipation rates of kinetic energies suggest that the efficiency of the global atmosphere as a heat engine increased during the modern satellite era.

Implications of the ammonia distribution on Jupiter from 1 to 100 bars as measured by the Juno microwave radiometer.

The latitude-altitude map of ammonia mixing ratio shows an ammonia-rich zone at 0-5°N, with mixing ratios of 320-340 ppm, extending from 40-60 bars up to the ammonia cloud base at 0.7 bars. Ammonia-poor air occupies a belt from 5-20°N. We argue that downdrafts as well as updrafts are needed in the 0-5°N zone to balance the upward ammonia flux. Outside the 0-20°N region, the belt-zone signature is weaker. At latitudes out to ±40°, there is an ammonia-rich layer from cloud base down to 2 bars which we argue is caused by falling precipitation. Below, there is an ammonia-poor layer with a minimum at 6 bars. Unanswered questions include how the ammonia-poor layer is maintained, why the belt-zone structure is barely evident in the ammonia distribution outside 0-20°N, and how the internal heat is transported through the ammonia-poor layer to the ammonia cloud base.

Complex cis-regulatory landscape of the insulin receptor gene underlies the broad expression of a central signaling regulator.

Insulin signaling plays key roles in development, growth and metabolism through dynamic control of glucose uptake, global protein translation and transcriptional regulation. Altered levels of insulin signaling are known to play key roles in development and disease, yet the molecular basis of such differential signaling remains obscure. Expression of the insulin receptor (InR) gene itself appears to play an important role, but the nature of the molecular wiring controlling InR transcription has not been elucidated. We characterized the regulatory elements driving Drosophila InR expression and found that the generally broad expression of this gene is belied by complex individual switch elements, the dynamic regulation of which reflects direct and indirect contributions of FOXO, EcR, Rbf and additional transcription factors through redundant elements dispersed throughout ∼40 kb of non-coding regions. The control of InR transcription in response to nutritional and tissue-specific inputs represents an integration of multiple cis-regulatory elements, the structure and function of which may have been sculpted by evolutionary selection to provide a highly tailored set of signaling responses on developmental and tissue-specific levels.

Vortices in Saturn's Northern Hemisphere (2008-2015) Observed by Cassini ISS.

We use observations from the Imaging Science Subsystem on Cassini to create maps of Saturn's Northern Hemisphere (NH) from 2008 to 2015, a time period including a seasonal transition (i.e., Spring Equinox in 2009) and the 2010 giant storm. The processed maps are used to investigate vortices in the NH during the period of 2008-2015. All recorded vortices have diameters (east-west) smaller than 6000 km except for the largest vortex that developed from the 2010 giant storm. The largest vortex decreased its diameter from ~11000 km in 2011 to ~5000 km in 2015, and its average diameter is ~6500 km during the period of 2011-2015. The largest vortex lasts at least 4 years, which is much longer than the lifetimes of most vortices (less than 1 year). The largest vortex drifts to north, which can be explained by the beta drift effect. The number of vortices displays varying behaviors in the meridional direction, in which the 2010 giant storm significantly affects the generation and development of vortices in the middle latitudes (25-45°N). In the higher latitudes (45-90°N), the number of vortices also displays strong temporal variations. The solar flux and the internal heat do not directly contribute to the vortex activities, leaving the temporal variations of vortices in the higher latitudes (45-90°N) unexplained.

Strong temporal variation over one Saturnian year: from Voyager to Cassini.

Here we report the combined spacecraft observations of Saturn acquired over one Saturnian year (~29.5 Earth years), from the Voyager encounters (1980-81) to the new Cassini reconnaissance (2009-10). The combined observations reveal a strong temporal increase of tropic temperature (~10 Kelvins) around the tropopause of Saturn (i.e., 50 mbar), which is stronger than the seasonal variability (~a few Kelvins). We also provide the first estimate of the zonal winds at 750 mbar, which is close to the zonal winds at 2000 mbar. The quasi-consistency of zonal winds between these two levels provides observational support to a numerical suggestion inferring that the zonal winds at pressures greater than 500 mbar do not vary significantly with depth. Furthermore, the temporal variation of zonal winds decreases its magnitude with depth, implying that the relatively deep zonal winds are stable with time.

Saturn: atmosphere, ionosphere, and magnetosphere.

The Cassini spacecraft has been in orbit around Saturn since 30 June 2004, yielding a wealth of data about the Saturn system. This review focuses on the atmosphere and magnetosphere and briefly outlines the state of our knowledge after the Cassini prime mission. The mission has addressed a host of fundamental questions: What processes control the physics, chemistry, and dynamics of the atmosphere? Where does the magnetospheric plasma come from? What are the physical processes coupling the ionosphere and magnetosphere? And, what are the rotation rates of Saturn's atmosphere and magnetosphere?

Dynamics of Saturn's south polar vortex.

The camera onboard the Cassini spacecraft has allowed us to observe many of Saturn's cloud features. We present observations of Saturn's south polar vortex (SPV) showing that it shares some properties with terrestrial hurricanes: cyclonic circulation, warm central region (the eye) surrounded by a ring of high clouds (the eye wall), and convective clouds outside the eye. The polar location and the absence of an ocean are major differences. It also shares properties with the polar vortices on Venus, such as polar location, cyclonic circulation, warm center, and long lifetime, but the Venus vortices have cold collars and are not associated with convective clouds. The SPV's combination of properties is unique among vortices in the solar system.

Imaging of Titan from the Cassini spacecraft.

Titan, the largest moon of Saturn, is the only satellite in the Solar System with a substantial atmosphere. The atmosphere is poorly understood and obscures the surface, leading to intense speculation about Titan's nature. Here we present observations of Titan from the imaging science experiment onboard the Cassini spacecraft that address some of these issues. The images reveal intricate surface albedo features that suggest aeolian, tectonic and fluvial processes; they also show a few circular features that could be impact structures. These observations imply that substantial surface modification has occurred over Titan's history. We have not directly detected liquids on the surface to date. Convective clouds are found to be common near the south pole, and the motion of mid-latitude clouds consistently indicates eastward winds, from which we infer that the troposphere is rotating faster than the surface. A detached haze at an altitude of 500 km is 150-200 km higher than that observed by Voyager, and more tenuous haze layers are also resolved.

Cassini imaging of Jupiter's atmosphere, satellites, and rings.

The Cassini Imaging Science Subsystem acquired about 26,000 images of the Jupiter system as the spacecraft encountered the giant planet en route to Saturn. We report findings on Jupiter's zonal winds, convective storms, low-latitude upper troposphere, polar stratosphere, and northern aurora. We also describe previously unseen emissions arising from Io and Europa in eclipse, a giant volcanic plume over Io's north pole, disk-resolved images of the satellite Himalia, circumstantial evidence for a causal relation between the satellites Metis and Adrastea and the main jovian ring, and information on the nature of the ring particles.