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In targeted protein degradation, a degrader molecule brings a neosubstrate protein proximal to a hijacked E3 ligase for its ubiquitination. Here, pseudo-natural products derived from (−)-myrtanol—iDegs—are identified to inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDegs prime apo-IDO1 ubiquitination and subsequent degradation using its native proteolytic pathway.

Inflammatory monocytes are identified as important players in T cell restimulation in the tumour microenvironment.

Krisai et al. compare brain structure and cognitive function in elderly patients with and without atrial fibrillation using brain MRI and cognitive testing. They find that atrial fibrillation is associated with more brain lesions and lower cognitive function, but the cognitive impairment occurs primarily through direct effects of the arrhythmia rather than through brain damage.

Multivariable Mendelian randomization (MR) extends the standard MR framework to consider multiple risk factors in a single model. Here, Zuber et al. propose MR-BMA, a Bayesian variable selection approach to identify the likely causal determinants of a disease from many candidate risk factors as for example high-throughput data sets.

Observations from the Lunar Orbiter Laser Altimeter reveal the Moon’s Shackleton crater to be an ancient, unusually well-preserved simple crater whose interior walls are younger than its floor and rim; the relative brightness of the floor at 1,064 nanometres is most readily explained by minimal volatile accumulation since crater formation and decreased space weathering due to permanent shadow.

Gravity data show a rectangular pattern of narrow linear anomalies bordering the lunar Procellarum region that are interpreted to be the frozen remnants of lava-filled rifts and underlying feeder dykes.

Analysis of the spread of the 20E (EU1) variant of SARS-CoV-2 through Europe suggests that international travel and insufficient containment, rather than increased transmissibility, led to a resurgence of infections.

Analysis of single nuclei RNA-sequencing data across eight major brain cell types identifies putative causal associations between cell-type-specific expression and brain phenotypes.

RNA interference screens were used to identify chromatin-associated factors that impede reprogramming of somatic cells into iPS cells; suppression of the chromatin assembly factor CAF-1 enhances the generation of iPS cells by rendering chromatin more accessible to pluripotency transcription factors.

Genome-wide association meta-analysis of AAA identifies 121 independent risk loci and highlights potential therapeutic targets such as proprotein convertase, subtilisin/kexin-type 9 (PCSK9).

FOXP3 deficiency leads to dramatic loss of immune homeostasis. This multicenter collaborative group finds that loss of FOXP3 function only disrupts a few core genes, but this unmasks a degree of systemic inflammation, and it is this environment that then strongly perturbs T_reg cells.

Obenauf and colleagues report that acquired resistance to BRAF and MEK inhibitors in melanoma confers cross-resistance to immune checkpoint blockade by fostering a cancer cell–instructed, immune-evasive tumor microenvironment.

Linnerbauer and colleagues find that HB-EGF produced by reactive astrocytes is protective during autoimmune neuroinflammation, but epigenetically suppressed during late stages.

The geometry of putative ancient shorelines on Mars suggests that these features were deformed by the growth of a massive volcanic region — a finding that has implications for the climate, geology and hydrology of early Mars.

Sjögren’s syndrome, a disease that primarily affects women, is poorly understood. Here, the authors combine data from a large cohort of patients and healthy controls to identify biomarkers that distinguish patient subgroups to improve our understanding of the disease and facilitate drug development.

Guide RNA selection plays an essential role in CRISPR screens, the Vienna Bioactivity CRISPR (VBC) scoring system provides an improved selection for sgRNAs that generate loss-of-function alleles.

The Moon's cratered surface preserves the record of impacts that occurred during the late stages of its accretion. New simulations show that a collision with a companion moon may have formed the lunar farside highlands. See Letter p.69

There's a big problem with the idea of ancient oceans on Mars: if they were contained within the 'shoreline' visible today, sea level would not have been level. Could it be that Mars has since tipped over?

Ahuna Mons dome on Ceres formed by extrusion of a mixture of brine and solids sourced from a muddy mantle plume, according to numerical modelling of slurry rheology and a gravity anomaly found by the Dawn mission.

Analysis of the Moon's topography reveals that when its largest basins are removed, the lunar shape is consistent with processes controlled by early Earth tides, and implies a reorientation of the Moon's principal shape axes.

The hemispheric dichotomy between the southern highlands and northern lowlands on Mars is characterized by a change in crustal thickness along an apparently irregular boundary, which can be traced around the planet, except where it is presumably buried beneath the Tharsis volcanic rise. The gravity and topography of Mars is used to constrain the location of the dichotomy boundary beneath Tharsis, and finds that the dichotomy boundary along its entire path around the planet is accurately fit by an ellipse measuring about 10,600 by 8,500 km.

The NASA MESSENGER mission collected a rich dataset enabling determination of Mercury’s ephemeris. Here, the authors analyse MESSENGER data obtained over an extended period of time to quantify parameters related to General Relativity.

Combining each sgRNA with a unique molecular identifier in a genome-wide screen increases sensitivity and robustness in both positive and negative selection.

Spectacular images from the Mars Orbiter Camera — an instrument on the Mars Global Surveyor spacecraft — are providing new views of that planet. These images, and what can be inferred from them, add to knowledge of the processes that shaped the Martian surface; together with other data, they offer the hope that a self-consistent view of the planet's early climate can be pieced together.

Today, the Moon has no magnetic field, but analyses of lunar rocks suggest that it did in the past. Did changes in the lunar interior create a magnetic dynamo billions of years ago?

Organoids derived from human stem cells recapitulate the structure and functions of human blood vessels, and can be used to model and identify regulators of diabetic vasculopathy.

The origin of most chondrules (small, previously molten spherules inside meteorites) is shown to be impact jetting; chondrules form from the shock-melted material ejected from a protoplanet on impact, making meteorites a byproduct of planet formation.

This article outlines some of the issues surrounding the terminology used for cancer stem cells (CSCs) and how CSCs are defined, with an aim to develop a consensus. More precise reporting of parameters used to identify CSCs is also recommended to enhance our understanding of CSC biology and to ultimately eradicate these cells in patients.