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Ubhi et al. describe the contribution of APOBEC family members A3C and A3D in the gemcitabine resistance mechanism in the context of pancreatic cancer, which is mediated by facilitating the restart of treatment-induced stalled replication forks.

The relationship between fMRI-BOLD and neural activity in the brain is not well understood. Here, the authors combine calcium imaging and fMRI in the mouse brain to compare network organization derived from these imaging modalities.

OICR-41103 is a potent, selective probe targeting the DCAF1 WDR domain and displacing viral Vpr protein. It enables new opportunities in cancer research, antiviral therapy, and targeted protein degradation via PROTACs.

As pregnant women are considered vulnerable to SARSCoV-2 infection, it is important to investigate the actual risks involved. The authors show here that, while a T cell-dominant inflammatory response is observed at the maternal-foetal interface, the virus remains undetectable in the placenta but triggers specific immune responses in the neonatal (umbilical cord blood) circulation.

A hydrogel serving as a high-capacity drug depot and combining a dissipative tough matrix on one side and a tendon-adhesive surface on the other side boosts tissue healing in rat models of tendon rupture.

A potent and selective inhibitor of KRAS^G12D, the most common mutant form of the KRAS oncoprotein, has anti-tumor efficacy in multiple pre-clinical cancer models, opening the possibility to therapeutically target this highly prevalent oncogenic driver.

There is currently no disease-modifying treatment for Parkinson’s disease, a common neurodegenerative disorder. Here, the authors use genetic variation associated with gene and protein expression to find putative drug targets for Parkinson’s disease using Mendelian randomization of the druggable genome.

Kang et al. reveal that GAB, classically known as a neurotransmitter, can control pro-inflammatory T_H17 cell and anti-inflammatory iT_reg cell differentiation in a cell-autonomous manner, thus modulating T cell-mediated inflammation.

‘Cooperative redox enhancement (CORE) effects, which arise through the coupling of oxidative dehydrogenation and oxygen reduction reactions, can lead to increased rates of reaction over spatially separated bimetallic heterogeneous catalysts.

Small molecule drugs promise to remain a valuable tool in controlling the ongoing COVID-19 pandemic. Here the authors describe optimized drug-like small molecule inhibitors of the SARS-CoV-2 3CL protease for potential treatment of COVID-19.

The mechanisms underlying epilepsy development are not well understood. Here the authors show that loss of a key component of the so called blood-brain barrier drives seizures in mice and is also lost in humans with treatment resistant epilepsy

M. pneumoniae, a model organism for a minimal cell, has a dedicated protein, namely P116, to specifically extract essential lipids. The structure of P116 has a previously unseen fold, resembling a left-handed baseball glove forming a huge hydrophobic cavity.

ER stress is associated with various neurodegenerative diseases. This study found that FDA approved drug, maprotiline, inhibits histamine receptor H1-mediated ER stress and provides significant neuroprotection in mouse glaucoma model.

A vision–language foundation model, trained on a dataset of more than 1 million echocardiogram video–text pairs, is able to assess various cardiac structural and functional parameters despite not having been directly trained on any specific image interpretation task.

Cardiovascular calcification is a serious pathology for which effective pharmacological treatments are lacking. Here the authors show that an optimized oligo(ethylene glycol) derivative of inositol phosphate interferes with calcium phosphate crystallization and inhibits soft tissue calcification in vivo following subcutaneous injection.

A vascularized human bone-marrow-on-a-chip improves the maintenance of patient-derived CD34⁺ cells, and recapitulates clinically relevant aspects of bone marrow injury as well as key haematopoietic defects of patients with a rare genetic disorder.

Case report of an individual heterozygous for a rare RELN-COLBOS variant that confers resilience, via a gain-of-function mechanism, to Alzheimer’s disease.

Adoptive T cell therapy has shown remarkable promise for the treatment of haematological malignancies. Here, the authors show that a cryogel platform for the simultaneous delivery of autologous T cells and recruitment of local antigen-presenting cells promotes long-lasting responses against solid tumours in mice.

Somatically determined preferential allelic expression of select genes that when mutated cause inborn errors of immunity corresponds with disease phenotypes, suggesting that the penetrance and expressivity of monogenic disorders is also dependent on the ‘transcriptotype’.

Early alcohol drinking confers greater risk for alcohol use disorder in women than men. Here authors show that ovarian-derived estrogen rapidly drives binge alcohol drinking via signaling with membrane-associated estrogen receptors in the extended amygdala.

Time-resolved drone imaging of potato crop development and seed tuber microbiome data can be used to predict potato vigour, or growth potential, in next-season crops in trial fields.

The Longobards invaded and conquered much of Italy after the fall of the Western Roman Empire. Here, the authors sequence and analyze ancient genomic DNA from 63 samples from two cemeteries associated with the Longobards and identify kinship networks and two distinct genetic and cultural groups in each.

Chemical and structural imaging of Komodo dragon teeth reveals that they maintain their sharp cutting edges through iron-enriched coatings, a unique adaptation compared with theropod dinosaurs (for which they have previously been used as an extant model).

Small molecule antagonists of CCR6 are potential drugs for autoimmune disorders. Here the authors present inactive structures of CCR6 bound by different allosteric antagonists from two series simultaneously, offering multiple approaches to inhibit CCR6.

Arbuscular mycorrhizal fungi help plants to overcome soil nutrient limitations. To promote symbiosis these fungi use effector proteins. The authors show that the SP7 effector family modulates host alternative splicing, impacting host development.

Mercury deposition pathways from the atmosphere to the ocean remain uncertain, but mercury stable isotope measurements from the Atlantic and Mediterranean show that ocean uptake of gaseous elemental mercury is more important than previously thought.

A low singlet-triplet energy gap, necessary for delayed fluorescence organic semiconductors, results in a small radiative rate that limits performance in OLEDs. Here, the authors show that it is possible to reconcile these conflicting requirements in materials that can access both high oscillator strength intramolecular excitations and intermolecular charge transfer states.

Enterococcus strains harbour a plasmid-encoded defence against reuterin, a toxin produced by Limosilactobacillus reuteri, mediating a mutualistic metabolic interaction between these two gut microbiota members.

The Gulf Stream was positioned further south during the Little Ice Age than today as a result of strengthened Labrador and Deep Western Boundary Currents and negative North Atlantic Oscillation, according to a high-resolution magnesium record from a Bermudan stalagmite

In Saccharomyces cerevisiae, unchecked proliferation of Ty1 retrotransposons is controlled by the process of copy number control (CNC), which requires the p22/p18 protein, translated from an internal transcript within the Ty1 GAG gene. Here, the authors present the 2.8 Å crystal structure of a minimal p18 from Ty1-Gag that is able to restrict Ty1 transposition and identify two dimer interfaces in p18, whose roles were probed by mutagenesis both in vitro and in vivo. As p22/p18 contains only one of two conserved domains required for retroelement Gag assembly, they propose that p22/p18-Gag interactions block the Ty1 virus-like particle assembly pathway, resulting in defective particles incapable of supporting retrotransposition.

A modular de novo designed biosensor platform consisting of a cage and key molecule is developed, and used to create sensors for seven distinct proteins including the spike protein from SARS-CoV-2 and anti-SARS antibodies.

Cyanobacteria are shown to produce alkanes that sustain communities of pentadecane-degrading bacteria, and possibly archaea, as part of an alkane cycle in the ocean.

Serological detection of antibodies against SARS-CoV-2 can help establish rates of seroconversion. Here the authors develop a red cell agglutination test to detect antibodies against the receptor binding domain for distribution free of charge to qualified research groups.

Humans are exposed to millions of chemicals but mass spectrometry (MS)-based targeted biomonitoring assays are usually limited to a few hundred known hazards. Here, the authors develop a workflow for MS-based untargeted exposome profiling of known and unidentified environmental chemicals.

Choice-relevant computations across the medial prefrontal cortex differ only quantitatively between areas. Here the authors suggest these computations may be organized along a functional gradient.

Mirchandani and colleagues show that tissue hypoxia alters the number and phenotype of circulating monocytes and their differentiation into lung macrophages, with important implications for the resolution of inflammation in the lung.

The relationship between the structural configurations of M-N-C electrocatalysts and their performances in neutral environments has been insufficiently investigated. Here the authors demonstrate that an ultralow metal-loaded Co-N-C electrocatalyst, featuring the asymmetric Co-C/N/O configuration, exhibit exceptional efficiency in electrochemically producing hydrogen peroxide under neutral conditions.

Fatty acid amide hydrolase (FAAH) is a key regulator of endocannabinoid signalling. Here, the authors develop a knock-in mouse that recapitulates a common human mutation in the FAAH gene and demonstrate parallel neural and behavioural alterations across species, suggesting a gain-of-function in fear regulation.