Unraveling the landscapes and regulation of scanning, leaky scanning, and 48S initiation complex conformations.

Scanning and initiation are critical steps in translation. Here, we utilized translation complex profiling (TCP-seq) to investigate 48S organization and eIF4G1-eIF1 inhibition impact. We provide global views of scanning and leaky scanning, uncovering a central role of eIF4G1-eIF1 in their regulation. We confirm AUG context importance, with non-leaky genes featuring a Kozak context and cytosine at positions -1 and +5. Capturing 48S complexes associated with eIF1, eIF4G1, eIF3, and eIF2 through selective TCP-seq revealed that the eIF3-scanning ribosome is highly vulnerable to eIF4G1-eIF1 inhibition, and eIF1 tends to dissociate upon AUG recognition. Initiation-site footprint analysis revealed a class spanning -12 to +18/19 from the AUG, representing the entire 48S and enriched with eIF2, eIF1, and eIF4G1, indicative of early initiation. Another eIF3-dependent class extends up to +26 and exhibits reduced eIF2 and eIF4G1 association, suggesting a late/alternative initiation complex. Our analysis provides an overview of scanning, initiation, and evidence for conformational rearrangements in vivo.

Extracellular symbiont colonizes insect during embryo development.

Insects typically acquire their beneficial microbes early in development. Endosymbionts housed intracellularly are commonly integrated during oogenesis or embryogenesis, whereas extracellular microbes are only known to be acquired after hatching by immature instars such as larvae or nymphs. Here, however, we report on an extracellular symbiont that colonizes its host during embryo development. Tortoise beetles (Chrysomelidae: Cassidinae) host their digestive bacterial symbiont Stammera extracellularly within foregut symbiotic organs and in ovary-associated glands to ensure its vertical transmission. We outline the initial stages of symbiont colonization and observe that although the foregut symbiotic organs develop 3 days prior to larval emergence, they remain empty until the final 24 h of embryo development. Infection by Stammera occurs during that timeframe and prior to hatching. By experimentally manipulating symbiont availability to embryos in the egg, we describe a 12-h developmental window governing colonization by Stammera. Symbiotic organs form normally in aposymbiotic larvae, demonstrating that these Stammera-bearing structures develop autonomously. In adults, the foregut symbiotic organs are already colonized following metamorphosis and host a stable Stammera population to facilitate folivory. The ovary-associated glands, however, initially lack Stammera. Symbiont abundance subsequently increases within these transmission organs, thereby ensuring sufficient titers at the onset of oviposition ~29 days following metamorphosis. Collectively, our findings reveal that Stammera colonization precedes larval emergence, where its proliferation is eventually decoupled in adult beetles to match the nutritional and reproductive requirements of its host.

Soundscape enrichment increases larval settlement rates for the brooding coral Porites astreoides.

Coral reefs, hubs of global biodiversity, are among the world's most imperilled habitats. Healthy coral reefs are characterized by distinctive soundscapes; these environments are rich with sounds produced by fishes and marine invertebrates. Emerging evidence suggests these sounds can be used as orientation and settlement cues for larvae of reef animals. On degraded reefs, these cues may be reduced or absent, impeding the success of larval settlement, which is an essential process for the maintenance and replenishment of reef populations. Here, in a field-based study, we evaluated the effects of enriching the soundscape of a degraded coral reef to increase coral settlement rates. Porites astreoides larvae were exposed to reef sounds using a custom solar-powered acoustic playback system. Porites astreoides settled at significantly higher rates at the acoustically enriched sites, averaging 1.7 times (up to maximum of seven times) more settlement compared with control reef sites without acoustic enrichment. Settlement rates decreased with distance from the speaker but remained higher than control levels at least 30 m from the sound source. These results reveal that acoustic enrichment can facilitate coral larval settlement at reasonable distances, offering a promising new method for scientists, managers and restoration practitioners to rebuild coral reefs.

Present-day thermal and water activity environment of the Mars Sample Return collection.

The Mars Sample Return mission intends to retrieve a sealed collection of rocks, regolith, and atmosphere sampled from Jezero Crater, Mars, by the NASA Perseverance rover mission. For all life-related research, it is necessary to evaluate water availability in the samples and on Mars. Within the first Martian year, Perseverance has acquired an estimated total mass of 355 g of rocks and regolith, and 38 µmoles of Martian atmospheric gas. Using in-situ observations acquired by the Perseverance rover, we show that the present-day environmental conditions at Jezero allow for the hydration of sulfates, chlorides, and perchlorates and the occasional formation of frost as well as a diurnal atmospheric-surface water exchange of 0.5-10 g water per m2 (assuming a well-mixed atmosphere). At night, when the temperature drops below 190 K, the surface water activity can exceed 0.5, the lowest limit for cell reproduction. During the day, when the temperature is above the cell replication limit of 245 K, water activity is less than 0.02. The environmental conditions at the surface of Jezero Crater, where these samples were acquired, are incompatible with the cell replication limits currently known on Earth.

Lowering mutant huntingtin by small molecules relieves Huntington's disease symptoms and progression.

Huntington's disease (HD) is an incurable inherited disorder caused by a repeated expansion of glutamines in the huntingtin gene (Htt). The mutant protein causes neuronal degeneration leading to severe motor and psychological symptoms. Selective downregulation of the mutant Htt gene expression is considered the most promising therapeutic approach for HD. We report the identification of small molecule inhibitors of Spt5-Pol II, SPI-24 and SPI-77, which selectively lower mutant Htt mRNA and protein levels in HD cells. In the BACHD mouse model, their direct delivery to the striatum diminished mutant Htt levels, ameliorated mitochondrial dysfunction, restored BDNF expression, and improved motor and anxiety-like phenotypes. Pharmacokinetic studies revealed that these SPIs pass the blood-brain-barrier. Prolonged subcutaneous injection or oral administration to early-stage mice significantly delayed disease deterioration. SPI-24 long-term treatment had no side effects or global changes in gene expression. Thus, lowering mutant Htt levels by small molecules can be an effective therapeutic strategy for HD.

Magnetic Field Modeling and Visualization of the Europa Clipper Spacecraft.

The goal of NASA's Europa Clipper Mission is to investigate the habitability of the subsurface ocean within the Jovian moon Europa using a suite of ten investigations. The Europa Clipper Magnetometer (ECM) and Plasma Instrument for Magnetic Sounding (PIMS) investigations will be used in unison to characterize the thickness and electrical conductivity of Europa's subsurface ocean and the thickness of the ice shell by sensing the induced magnetic field, driven by the strong time-varying magnetic field of the Jovian environment. However, these measurements will be obscured by the magnetic field originating from the Europa Clipper spacecraft. In this work, a magnetic field model of the Europa Clipper spacecraft is presented, characterized with over 260 individual magnetic sources comprising various ferromagnetic and soft-magnetic materials, compensation magnets, solenoids, and dynamic electrical currents flowing within the spacecraft. This model is used to evaluate the magnetic field at arbitrary points around the spacecraft, notably at the locations of the three fluxgate magnetometer sensors and four Faraday cups which make up ECM and PIMS, respectively. The model is also used to evaluate the magnetic field uncertainty at these locations via a Monte Carlo approach. Furthermore, both linear and non-linear gradiometry fitting methods are presented to demonstrate the ability to reliably disentangle the spacecraft field from the ambient using an array of three fluxgate magnetometer sensors mounted along an 8.5-meter (m) long boom. The method is also shown to be useful for optimizing the locations of the magnetometer sensors along the boom. Finally, we illustrate how the model can be used to visualize the magnetic field lines of the spacecraft, thus providing very insightful information for each investigation. Supplementary Information: The online version contains supplementary material available at 10.1007/s11214-023-00974-y.

Mission to Psyche: Including Undergraduates and the Public on the Journey to a Metal World.

The NASA Psyche mission's program to engage university undergraduates and the public in the mission is inspired by and built upon the extensive foundation of public engagement, educational outreach activities, and expertise of NASA and mission partner institutions. The program leverages the enthusiasm and contributions of undergraduates nationwide to the benefit of the mission, the students and their institutions and communities, and the broader public. Psyche Student Collaborations consists of four main programs, two (Psyche Capstone and Psyche Inspired) are available solely to undergraduates enrolled at universities or community colleges in the United States and its territories and two (Innovation Toolkit free online courses and Science Outreach Interns and Docents) invite broader participation by engaging the talents and creativity of undergraduate interns to help create content and events to reach the public and lifelong learners. Together, these offerings provide multiple entry points and a spectrum of intensity of experiences, numbers of participants, disciplinary diversity, and mode of delivery. Involving undergraduates in all phases of the program supports the development of the next generation of explorers, contributes to the nation's workforce preparation, and complements NASA's existing undergraduate offerings by providing long-term opportunities for students to participate with the mission through established postsecondary education structures like capstone courses.

The Psyche Magnetometry Investigation.

The objective of the Psyche Magnetometry Investigation is to test the hypothesis that asteroid (16) Psyche formed from the core of a differentiated planetesimal. To address this, the Psyche Magnetometer will measure the magnetic field around the asteroid to search for evidence of remanent magnetization. Paleomagnetic measurements of meteorites and dynamo theory indicate that a diversity of planetesimals once generated dynamo magnetic fields in their metallic cores. Likewise, the detection of a strong magnetic moment ( > 2 × 10 14 Am 2 ) at Psyche would likely indicate that the body once generated a core dynamo, implying that it formed by igneous differentiation. The Psyche Magnetometer consists of two three-axis fluxgate Sensor Units (SUs) mounted 0.7 m apart along a 2.15-m long boom and connected to two Electronics Units (EUs) located within the spacecraft bus. The Magnetometer samples at up to 50 Hz, has a range of ± 80 , 000 nT , and an instrument noise of 39 pT axis - 1 3 σ integrated over 0.1 to 1 Hz. The two pairs of SUs and EUs provide redundancy and enable gradiometry measurements to suppress noise from flight system magnetic fields. The Magnetometer will be powered on soon after launch and acquire data for the full duration of the mission. The ground data system processes the Magnetometer measurements to obtain an estimate of Psyche's dipole moment.

Compositions and Interior Structures of the Large Moons of Uranus and Implications for Future Spacecraft Observations.

The five large moons of Uranus are important targets for future spacecraft missions. To motivate and inform the exploration of these moons, we model their internal evolution, present-day physical structures, and geochemical and geophysical signatures that may be measured by spacecraft. We predict that if the moons preserved liquid until present, it is likely in the form of residual oceans less than 30 km thick in Ariel, Umbriel, and less than 50 km in Titania, and Oberon. The preservation of liquid strongly depends on material properties and, potentially, on dynamical circumstances that are presently unknown. Miranda is unlikely to host liquid at present unless it experienced tidal heating a few tens of million years ago. We find that since the thin residual layers may be hypersaline, their induced magnetic fields could be detectable by future spacecraft-based magnetometers. However, if the ocean is maintained primarily by ammonia, and thus well below the water freezing point, then its electrical conductivity may be too small to be detectable by spacecraft. Lastly, our calculated tidal Love number (k 2) and dissipation factor (Q) are consistent with the Q/k 2 values previously inferred from dynamical evolution models. In particular, we find that the low Q/k 2 estimated for Titania supports the hypothesis that Titania currently holds an ocean.

Not1 and Not4 inversely determine mRNA solubility that sets the dynamics of co-translational events.

BACKGROUND: The Ccr4-Not complex is mostly known as the major eukaryotic deadenylase. However, several studies have uncovered roles of the complex, in particular of the Not subunits, unrelated to deadenylation and relevant for translation. In particular, the existence of Not condensates that regulate translation elongation dynamics has been reported. Typical studies that evaluate translation efficiency rely on soluble extracts obtained after the disruption of cells and ribosome profiling. Yet cellular mRNAs in condensates can be actively translated and may not be present in such extracts. RESULTS: In this work, by analyzing soluble and insoluble mRNA decay intermediates in yeast, we determine that insoluble mRNAs are enriched for ribosomes dwelling at non-optimal codons compared to soluble mRNAs. mRNA decay is higher for soluble RNAs, but the proportion of co-translational degradation relative to the overall mRNA decay is higher for insoluble mRNAs. We show that depletion of Not1 and Not4 inversely impacts mRNA solubilities and, for soluble mRNAs, ribosome dwelling according to codon optimality. Depletion of Not4 solubilizes mRNAs with lower non-optimal codon content and higher expression that are rendered insoluble by Not1 depletion. By contrast, depletion of Not1 solubilizes mitochondrial mRNAs, which are rendered insoluble upon Not4 depletion. CONCLUSIONS: Our results reveal that mRNA solubility defines the dynamics of co-translation events and is oppositely regulated by Not1 and Not4, a mechanism that we additionally determine may already be set by Not1 promoter association in the nucleus.

Direct age constraints on the magnetism of Jack Hills zircon.

A potential record of Earth's magnetic field going back 4.2 billion years (Ga) ago is carried by magnetite inclusions in zircon grains from the Jack Hills. This magnetite may be secondary in nature, however, meaning that the magnetic record is much younger than the zircon crystallization age. Here, we use atom probe tomography to show that Pb-bearing nanoclusters in magnetite-bearing Jack Hills zircons formed during two discrete events at 3.4 and <2 Ga. The older population of clusters contains no detectable Fe, whereas roughly half of the younger population of clusters is Fe bearing. This result shows that the Fe required to form secondary magnetite entered the zircon sometime after 3.4 Ga and that remobilization of Pb and Fe during an annealing event occurred more than 1 Ga after deposition of the Jack Hills sediment at 3 Ga. The ability to date Fe mobility linked to secondary magnetite formation provides new possibilities to improve our knowledge of the Archean geodynamo.

Geological, multispectral, and meteorological imaging results from the Mars 2020 Perseverance rover in Jezero crater.

Perseverance's Mastcam-Z instrument provides high-resolution stereo and multispectral images with a unique combination of spatial resolution, spatial coverage, and wavelength coverage along the rover's traverse in Jezero crater, Mars. Images reveal rocks consistent with an igneous (including volcanic and/or volcaniclastic) and/or impactite origin and limited aqueous alteration, including polygonally fractured rocks with weathered coatings; massive boulder-forming bedrock consisting of mafic silicates, ferric oxides, and/or iron-bearing alteration minerals; and coarsely layered outcrops dominated by olivine. Pyroxene dominates the iron-bearing mineralogy in the fine-grained regolith, while olivine dominates the coarse-grained regolith. Solar and atmospheric imaging observations show significant intra- and intersol variations in dust optical depth and water ice clouds, as well as unique examples of boundary layer vortex action from both natural (dust devil) and Ingenuity helicopter-induced dust lifting. High-resolution stereo imaging also provides geologic context for rover operations, other instrument observations, and sample selection, characterization, and confirmation.

Preinitiation Complex Loading onto mRNAs with Long versus Short 5' TLs.

The first step in translation initiation consists in the recruitment of the small ribosome onto the mRNA. This preinitiation complex (PIC) loads via interactions with eIF4F that has assembled on the 5' cap. It then scans the 5' TL (transcript leader) to locate a start site. The molecular architecture of the PIC-mRNA complex over the cap is beginning to be resolved. As part of this, we have been examining the role of the 5' TL length. We observed in vivo initiation events on AUG codons positioned within 3 nts of the 5' cap and robust initiation in vitro at start sites immediately downstream of the 5' end. Ribosomal toe-printing confirmed the positioning of these codons within the P site, indicating that the ribosome reads from the +1 position. To explore differences in the eIF4E-5' cap interaction in the context of long versus short TL, we followed the fate of the eIF4E-cap interaction using a novel solid phase in vitro expression assay. We observed that ribosome recruitment onto a short TL disrupts the eIF4E-cap contact releasing all the mRNA from the solid phase, whereas with a long the mRNA distributes between both phases. These results are discussed in the context of current recruitment models.

Morphological adaptation for ectosymbiont maintenance and transmission during metamorphosis in Lagria beetles.

The diversity and success of holometabolous insects is partly driven by metamorphosis, which allows for the exploitation of different niches and decouples growth and tissue differentiation from reproduction. Despite its benefits, metamorphosis comes with the cost of temporal vulnerability during pupation and challenges associated with tissue reorganizations. These rearrangements can also affect the presence, abundance, and localization of beneficial microbes in the host. However, how symbionts are maintained or translocated during metamorphosis and which adaptations are necessary from each partner during this process remains unknown for the vast majority of symbiotic systems. Here, we show that Lagria beetles circumvent the constraints of metamorphosis by maintaining defensive symbionts on the surface in specialized cuticular structures. The symbionts are present in both sexes throughout larval development and during the pupal phase, in line with a protective role during the beetle's immature stages. By comparing symbiont titer and morphology of the cuticular structures between sexes using qPCR, fluorescence in situ hybridization, and micro-computed tomography, we found that the organs likely play an important role as a symbiont reservoir for transmission to female adults, since symbiont titers and structures are reduced in male pupae. Using symbiont-sized fluorescent beads, we demonstrate transfer from the region of the dorsal symbiont-housing organs to the opening of the reproductive tract of adult females, suggesting that symbiont relocation on the outer surface is possible, even without specialized symbiont adaptations or motility. Our results illustrate a strategy for holometabolous insects to cope with the challenge of symbiont maintenance during metamorphosis via an external route, circumventing problems associated with internal tissue reorganization. Thereby, Lagria beetles keep a tight relationship with their beneficial partners during growth and metamorphosis.

Inhibitors of eIF4G1-eIF1 uncover its regulatory role of ER/UPR stress-response genes independent of eIF2α-phosphorylation.

During translation initiation, eIF4G1 dynamically interacts with eIF4E and eIF1. While the role of eIF4E-eIF4G1 is well established, the regulatory functions of eIF4G1-eIF1 are poorly understood. Here, we report the identification of the eIF4G1-eIF1 inhibitors i14G1-10 and i14G1-12. i14G1s directly bind eIF4G1 and inhibit translation in vitro and in the cell, and their effects on translation are dependent on eIF4G1 levels. Translatome analyses revealed that i14G1s mimic eIF1 and eIF4G1 perturbations on the stringency of start codon selection and the opposing roles of eIF1-eIF4G1 in scanning-dependent and scanning-independent short 5' untranslated region (UTR) translation. Remarkably, i14G1s activate ER/unfolded protein response (UPR) stress-response genes via enhanced ribosome loading, elevated 5'UTR translation at near-cognate AUGs, and unexpected concomitant up-regulation of coding-region translation. These effects are, at least in part, independent of eIF2α-phosphorylation. Interestingly, eIF4G1-eIF1 interaction itself is negatively regulated by ER stress and mTOR inhibition. Thus, i14G1s uncover an unknown mechanism of ER/UPR translational stress response and are valuable research tools and potential drugs against diseases exhibiting dysregulated translation.

Distinguishing the Origin of Asteroid (16) Psyche.

The asteroid (16) Psyche may be the metal-rich remnant of a differentiated planetesimal, or it may be a highly reduced, metal-rich asteroidal material that never differentiated. The NASA Psyche mission aims to determine Psyche's provenance. Here we describe the possible solar system regions of origin for Psyche, prior to its likely implantation into the asteroid belt, the physical and chemical processes that can enrich metal in an asteroid, and possible meteoritic analogs. The spacecraft payload is designed to be able to discriminate among possible formation theories. The project will determine Psyche's origin and formation by measuring any strong remanent magnetic fields, which would imply it was the core of a differentiated body; the scale of metal to silicate mixing will be determined by both the neutron spectrometers and the filtered images; the degree of disruption between metal and rock may be determined by the correlation of gravity with composition; some mineralogy (e.g., modeled silicate/metal ratio, and inferred existence of low-calcium pyroxene or olivine, for example) will be detected using filtered images; and the nickel content of Psyche's metal phase will be measured using the GRNS.

Deciphering Redox State for a Metal-Rich World.

The Psyche mission's Oxidation-Reduction Working Group is focused on understanding, determining, and applying the redox state of (16) Psyche to understand the origin of a metal-rich world. The oxidation-reduction state of an asteroid, along with its temperature, parent body size, and composition, is a key parameter in determining the history of an asteroid. Determining the redox state from spacecraft data is most easily done by examining potential metal-oxide buffer pairs. The occurrence of Ni, Fe, C, Cr, P and Si, in that order, in the metal or sulfide phase of an asteroidal body indicates increasingly reduced conditions. Key observations by the Imager and Gamma-Ray and Neutron Spectrometer (GRNS) of Psyche can bracket the redox state using metal-oxide buffers. The presence of Fe,Ni metal can be confirmed by the ratios of Fe/O or Fe/Si and the concentration of Ni variability in metal across the asteroid can be determined by GRNS. The FeO concentration of silicates is complementary to the Ni concentration of metal and can be constrained using filters on the Imager. The presence of FeO in silicates from ground-based observations is one of the few measurements we already have of redox state, although available data permit a wide range of silicate compositions and mineralogies. The presence of C, P or Si concentrated in the metallic, Fe-rich portion of the asteroid, as measured by GRNS, or Ca-sulfide, determined by imaging, would indicate increasingly reducing conditions. Linkage to known types of meteorites, whether metal-rich chondrites, stony-irons or irons, expands the mineralogical, chemical and isotopic data not available from remote observations alone. Redox also controls both silicate and metal mineralogy, influencing differentiation, solidification, and subsolidus cooling, including the relative abundance of sulfur in the core and possible magnetic signatures. The redox state of Psyche, if a fully-differentiated metallic core, might constrain the location and timing of both the formation of Psyche and any oxidation it might have experienced.

Abundance and Localization of Symbiotic Bacterial Communities in the Fly Parasitoid Spalangia cameroni.

Multicellular eukaryotes often host multiple microbial symbionts that may cooperate or compete for host resources, such as space and nutrients. Here, we studied the abundances and localization of four bacterial symbionts, Rickettsia, Wolbachia, Sodalis, and Arsenophonus, in the parasitic wasp Spalangia cameroni. Using quantitative PCR (qPCR), we measured the symbionts' titers in wasps that harbor different combinations of these symbionts. We found that the titer of each symbiont decreased as the number of symbiont species in the community increased. Symbionts' titers were higher in females than in males. Rickettsia was the most abundant symbiont in all the communities, followed by Sodalis and Wolbachia. The titers of these three symbionts were positively correlated in some of the colonies. Fluorescence in situ hybridization was in line with the qPCR results: Rickettsia, Wolbachia, and Sodalis were observed in high densities in multiple organs, including brain, muscles, gut, Malpighian tubules, fat body, ovaries, and testes, while Arsenophonus was localized to fewer organs and in lower densities. Sodalis and Arsenophonus were observed in ovarian follicle cells but not within oocytes or laid eggs. This study highlights the connection between symbionts' abundance and localization. We discuss the possible connections between our findings to symbiont transmission success. IMPORTANCE Many insects carry intracellular bacterial symbionts (bacteria that reside within the cells of the insect). When multiple symbiont species cohabit in a host, they may compete or cooperate for space, nutrients, and transmission, and the nature of such interactions would be reflected in the abundance of each symbiont species. Given the widespread occurrence of coinfections with maternally transmitted symbionts in insects, it is important to learn more about how they interact, where they are localized, and how these two aspects affect their co-occurrence within individual insects. Here, we studied the abundance and the localization of four symbionts, Rickettsia, Wolbachia, Sodalis, and Arsenophonus, that cohabit the parasitic wasp Spalangia cameroni. We found that symbionts' titers differed between symbiotic communities. These results were corroborated by microscopy, which shows differential localization patterns. We discuss the findings in the contexts of community ecology, possible symbiont-symbiont interactions, and host control mechanisms that may shape the symbiotic community structure.

Paleomagnetic evidence for a disk substructure in the early solar system.

Astronomical observations and isotopic measurements of meteorites suggest that substructures are common in protoplanetary disks and may even have existed in the solar nebula. Here, we conduct paleomagnetic measurements of chondrules in CO carbonaceous chondrites to investigate the existence and nature of these disk substructures. We show that the paleomagnetism of chondrules in CO carbonaceous chondrites indicates the presence of a 101 ± 48 µT field in the solar nebula in the outer solar system (~3 to 7 AU from the Sun). The high intensity of this field relative to that inferred from inner solar system (~<3 AU) meteorites indicates a factor of ~5 to 150 mismatch in nebular accretion between the two reservoirs. This suggests substantial mass loss from the disk associated with a major disk substructure, possibly due to a magnetized disk wind.