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Current antimalarials often fail to target mature stage V gametocytes. To aid antimalarial drug discovery, the authors present a preclinical malaria transmission-blocking drug research platform, using engineered parasites, that facilitates the screening for gametocytocidal compounds in vitro and the evaluation of transmission-blocking drug activity in vivo.

Flores et al. show that brain-penetrant eIF2B agonists suppress ISR activation in cellular and mouse models of ALS and reduce ISR biomarkers in humans, enabling further clinical studies of ISR inhibition in individuals with neurological diseases

The oncogenic potential of pks⁺ Escherichia coli depends critically on bacterial adhesion to host epithelial cells mediated by the type 1 pilus adhesin FimH and the F9 pilus adhesin FmlH.

Electrical magnetochiral anisotropy phenomenon describes the change in resistance of chiral materials caused by the interplay between chirality, conductivity and magnetic fields. Pop et al.show here for the first time the occurrence of this phenomenon in a bulk chiral molecular conductor.

Magneto-chiral dichroism is an effect in which unpolarized light is absorbed differently for parallel and antiparallel propagation with respect to an applied magnetic field. Previous observations have only seen a rather weak demonstration of this effect. Following a challenging synthesis, strong magneto-dichroism has now been observed in enantiopure chiral ferromagnets.

Aetiology of colitis is highly complex and incompletely understood. Here the authors show in mouse models that A20 deubiquitinase limits pro-inflammatory cytokine production in myeloid cells while inhibiting proapoptotic response to these cytokines in enterocytes, and that only upon losing both functions intestinal pathologies develop.

Kucharska, Ivanochko and Hailemariam and colleagues solved cryo-EM structures of Pfs48/45, needed for Plasmodium falciparum development, with potent antibodies. The work revealed conformational epitopes, with implications for design of therapies against malaria.

Mass spectrometric profiling of a glycan library reveals that sialylated glycans, especially sialic acid-containing gangliosides, interact with the RBD of the SARS-CoV-2 spike protein and are involved in ACE2-dependent viral infection.

OTULIN is a deubiquitinase for linear ubiquitin chains. Here the authors show, using genetic mouse models and single-cell RNA-sequencing, that deficiency of OTULIN in keratinocytes causes skin inflammation and verrucous carcinoma via the induction of keratinocyte death, thereby implicating a function of OTULIN in keratinocyte homeostasis.

Maintaining the intestinal barrier function requires a balance of multiple signalling pathways. Here the authors show that A20, an anti-inflammatory and anti-apoptotic protein, and Atg1611, an autophagy regulator, cross-regulate their respective protein levels and function to serve compensatory and redundant roles in fine-tuning gut barrier homeostasis.

Binding of a sialoglycan-based primary receptor by the spike protein of the common cold human coronavirus HKU1 triggers conformational changes to a state that would allow binding to a second receptor required for cell entry.

Understanding the physical mechanisms of photon–atom interactions on ultrafast timescales is challenging, but a new theoretical framework enables the interpretation of attoclock experiments measuring tunnelling times in hydrogen.

Gringhuis and colleagues show that the extent of type I IFN responses induced by fungal stimulation in human DCs modulate the activation of TGF-β and the production of pathogenic or non-pathogenic T_H17 cells.

Spatial positioning of the division plane in plant cells is determined premitotically by the preprophase band of microtubules. Spinner et al. show that its formation in Arabidopsisrequires a PP2A complex containing FASS and TON1 which is recruited to cortical microtubules by the TRM protein family.

Population differences in immune responses to SARS-CoV-2 can be explained by environmental exposures, but also by local adaptation acting through genetic variants acquired after admixture with archaic hominin forms.

Accurate estimates of tropical forest carbon stocks are needed for policies to reduce emissions from loss of forests. By looking at a central area in the Congo Basin, Kearsleyet al.find that inconsistencies in height–diameter relationships across Central Africa cause overestimations between regions.

Transcriptomic, genetic and pharmacological analysis identifies SLC7A11 as an inhibitor of efferocytosis in dendritic cells, and increased expression of this protein may cause slower wound healing in diabetes.

Interactions between synaptotagmin-1 and the SNARE syntaxin-1 are known to mediate synaptic-vesicle exocytosis. Fusion experiments with artificial lipid membranes combined with the crystal structure of synaptotagmin's C2B domain bound to phosphoserine indicate that PIP2 clusters, organized by syntaxin, act as molecular beacons for vesicle docking and direct Ca²⁺-dependent membrane fusion.

A first-in-patient trial of UB-312, an active immunotherapeutic for Parkinson’s disease, was well tolerated and elicited antibodies that engage misfolded α-synuclein.

During each replication cycle of P. falciparum in the human bloodstream, a small proportion of parasites commits to sexual development and differentiates into transmission-relevant gametocytes. Applying CRISPR-based genome editing, Boltryk et al. engineer P. falciparum lines with sexual commitment rates of 75% to promote future studies on gametocyte biology.

The recently identified Wuhan spiny eel influenza virus (WSEIV) sequence is more closely related to influenza B than A viruses. Here, the authors functionally characterize the putative surface glycoproteins of WSEIV and show that its NA-like protein has sialidase activity and its HA-like protein binds monosialic ganglioside 2.

Mutations in genes critical for proper intra-Golgi transport can cause human syndromes due to defects in glycosylation of proteins. Here, the authors identify a human variant of Syntaxin-5 that causes fatal multisystem disease and mislocalization of glycosyltransferases due to altered Golgi transport.

There is no universal reference material to develop extracellular vesicle (EV) separation methods and carry out calibration and normalization. Here the authors use HIV-derived gag proteins to assemble recombinant fluorescent EV as a trackable reference material resembling the physical and biochemical properties of sample EV.

Defects and defect migration are detrimental for perovskite solar cell efficiency and long-term stability. Li et al. show that fluoride is able to suppress the formation of halide anion and organic cation vacancy defects by restraining the relative ions via ionic and hydrogen bonds.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

IgG glycosylation is an important factor in immune function, yet the molecular details of protein glycosylation remain poorly understood. The data-driven approach presented here uses large-scale plasma IgG mass spectrometry measurements to infer new biochemical reactions in the glycosylation pathway.

Synaptotagmin promotes SNARE-mediated membrane fusion in a Ca²⁺-dependent manner, but the mechanism by which it acts is still unclear. In vitro studies have shown that synaptotagmin can make interactions with its own vesicle membrane, inhibiting its ability to stimulate fusion with target membranes. New data now suggest that ATP and other polybasic anions may have a role in directing synaptotagmin to its target membrane in vivo.

Synaptotagmin-1 is known to accelerate membrane fusion during neuronal exocytosis in response to Ca²⁺, but how it does this is unclear. By probing the activity of synaptotagmin-1 under conditions of low ionic strength, it is now shown that SNARE-mediated fusion is dependent on synaptotagmin-1, which tethers liposomes together but at distances too far for fusion. Ca²⁺ then induces synaptotagmin-1 to bring the liposomes closer together, allowing fusion to proceed.

Mixed halide perovskite undergoes halide segregation under illumination, which impairs its functionality as solar cells. Bobbert et al. present a unified thermodynamic theory to explain the phase separation behaviour that takes into account both ground state compositional and electronic part of free energy in the presence of photocarriers.

The spindle assembly checkpoint protects against premature chromosome segregation during mitosis but it is not known whether microtubule attachment to the kinetochore, or force generated from this interaction, is being monitored. Here the authors uncouple these processes and show that microtubule attachment is sufficient to satisfy the checkpoint.

Driver mutations in early T-cell precursor leukaemia (ETP-ALL) are poorly characterized. Here the authors show that Zeb2overexpression is often found in ETP-ALL, can recapitulate the disease in transgenic mice and confers survival advantage by upregulating IL-7 signalling.

Narcolepsy has genetic and environmental risk factors, but the specific genetic risk loci and interaction with environmental triggers are not well understood. Here, the authors identify genetic loci for narcolepsy, suggesting infection as a trigger and dendritic and helper T cell involvement.

Perovskite light emitting diodes suffer from operational stability, showing rapid decay of performance within minutes to hours after turn-on. Here, the authors investigate how the steric and Coulomb interaction of ammonium passivation molecules with varying alkyl chain length can improve device stability by suppressing iodide ion migration.

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.

Naturally acquired antibodies may inhibit Plasmodium survival in mosquitoes, alter malaria transmission dynamics, and form the basis for transmission-blocking vaccines. Here, using sera from malaria-exposed individuals, Stone et al. reveal novel antibody correlates of transmission-reducing activity.

Carreras-Sureda et al. uncover a non-canonical role for IRE1α as a scaffold that stabilizes InsP₃Rs at MAMs to control calcium uptake, fine-tunes ER–mitochondrial communication and regulates energy metabolism via AMPK.

The band gap of metal halide perovskites can be tuned by changing composition, but the underlying mechanism is not well understood. Here the authors determine, by experiments and theoretical analysis, the energy levels of all primary tin- and lead-based perovskites, relating them to the levels of the composing ions.

Plants can regenerate tissues after injury. The heterodimeric transcription factor complex ERF115–PAT1 is activated by the cell death of neighbouring cells, and is crucial for stem cell replenishment and the high regenerative potential of plants.

Using the CRISPR/Cas9 system, up to four frequently occurring colorectal cancer mutations were introduced alone or in combination into stem cell organoids derived from human small intestinal or colon tissue, allowing an in-depth investigation of the contribution of these mutations to cancer progression.

Podosomes are adhesive cytoskeletal structures found in several cell types, but whether or how they are interconnected is not known. Here the authors demonstrate mesoscale connectivity of podosome clusters by imaging directional flow patterns of podosome components vinculin, talin and F-actin.

Metagenomic studies of microbial communities often report DNA sequences from unidentified viruses. Here, Dutilh et al. analyse metagenomic data to reveal the complete genome of an abundant, ubiquitous virus from human faeces, and predict that the virus infects bacteria of the Bacteroides group.

Imputation uses genotype information from SNP arrays to infer the genotypes of missing markers. Here, the authors show that an imputation reference panel derived from whole-genome sequencing of 3,781 samples from the UK10K project improves the imputation accuracy and coverage of low frequency variants compared to existing methods.