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Efficient removal of apoptotic cells by phagocytosis underlies tissue development, wound repair, host defense and organ homeostasis. Here, authors identify TRPM7 as a regulator of cargo acidification and Ca2+ signaling during apoptotic cell clearance.

Cells use fluid flow to deliver proteins to their leading edge. An actin barrier creates a compartment where contraction drives flow, steering proteins toward growing regions. This mechanism coordinates protein distribution with cell shape changes.

Stable and cell-specific transgene expression can be achieved through in vivo site-specific integration of large DNA payloads using a two-vector system of enveloped delivery vehicles and adeno-associated viruses.

Davies et al. identify a putative mechanism underlying the childhood neurological disorder AP-4 deficiency syndrome. In the absence of AP-4, an enzyme that makes 2-AG is not transported to the axon, leading to axonal growth defects, which can be rescued by inhibition of 2-AG breakdown.

The extreme oxygen sensitive character of hydrogenases is a longstanding issue for hydrogen production in bacteria. Here, the authors build carboxysome shells in E. coli and incorporate catalytically active hydrogenases and functional partners within the empty shell for the production of hydrogen.

Responsive exocytosis in neutrophil leukocytes involves actin depolymerisation-dependent sequential release of gelatinase granules, then strongly pro-inflammatory azurophilic granules. Here authors show that the actin nucleator protein WASH facilitates the initial step of innate immune activation by gelatinase granules while inhibiting release of pro-inflammatory granules.

Endoplasmic reticulum (ER) and lysosomes mutually influence each other’s function. This study shows that ER-located ryanodine receptors physically connect with lysosomes, favoring lysosomal availability for autophagy over lysosomal secretion.

The variability in clinical outcomes of SARS-CoV-2 infection is partly due to deficiencies in production or response to type I interferons (IFN). Here, the authors describe a FIP200-dependent lysosomal degradation pathway, independent of canonical autophagy and type I IFN, that restricts SARS-CoV-2 replication, offering insights into critical COVID-19 pneumonia mechanisms.

This Review explores how reciprocal brain–heart interactions can cause dysfunction in one of these organs to adversely affect the other. The authors discuss clinical conditions, such as Takotsubo syndrome and stroke–heart syndrome, in which these interactions are particularly prominent and address sex and gender differences in brain–heart interactions.

One of two papers that has developed four-dimensional imaging of the yeast Saccharomyces cerevisiae and have now shown that Golgi cisternae mature in a dynamic manner.

Polymers are promising for mRNA delivery, but can have limited efficacy in hard to transfect cells. Here, the authors report charge-altering releasable transporters for improved mRNA transfection in primary T-lymphocytes and enhanced and selective protein expression in vivo.

Zhou and colleagues identify SNX4–SNX5–SNX17 as a multiunit complex that mediates the recycling of autophagosomal components from autolysosomes.

How injured mitochondria are targeted for autophagic degradation is not well understood. Chu and colleagues find that pro-mitophagy stimuli induce externalization of cardiolipin to the outer mitochondrial membrane of neuronal cells, and find that this is required for binding of the autophagy protein LC3 to mitochondria and mitophagy.

The Nuclear Pore Complex has been linked to DNA damage processing. Here the authors reveal that the Nup1 C-terminus is critical for the relocalization of eroded telomeres to nuclear pores and that modification of Nup1 promotes sister chromatid recombination and unleashes a new telomere maintenance mechanism.

Implant-associated infections with Staphylococcus aureus pose serious clinical challenges. Here, the authors develop a biosensor based on toxin-responsive liposomes encapsulating gold nanoclusters, providing a non-invasive, colourimetric diagnostic tool for bacterial infection detection with urinary readout.

Recycling from endosomes to the plasma membrane is an important step in cell homeostasis. The retromer/SNX27/WASH complex recycles numerous receptors, but key ones are still unaccounted for. Now a related conserved heterotrimer, called retriever, has been identified that, together with SNX17, the CCC complex and WASH, mediates the recycling of α₅β₁ integrins.

The small GTPase Arf6 regulates intracellular transport, phosphoinositide signalling and cholesterol homeostasis. Here, Marquer et al. show that loss of Arf6 causes cholesterol accumulation in endosomes due to defects in phosphoinositide-dependent retromer-mediated trafficking of CI-M6PR and NPC2.

Automated fabrication of microneedle patch mRNA vaccines for COVID-19 may improve vaccine access.

The two-partner secretion system transports proteins across the bacterial outer membrane but the molecular mechanisms involved are poorly understood. Here, Baud et al. use site-specific crosslinking to track the path of a protein substrate through the β-barrel of its Omp85 transporter.

The detection of conserved motifs by pattern recognition receptors is a crucial component of the innate detection of pathogens and danger signals via conserved pattern recognition receptors. Here the authors define a pathway that transfers partially digested material from the phagolysosomal pathway of macrophages to release at the plasma membrane which is associated with enhanced inflammatory potential, by a process they introduce as eructophagy.

The ADP-ribosylation factor (ARF) and ARF-like (ARL) family of G proteins, which are known to regulate membrane traffic and organelle structure, are emerging as regulators of diverse processes, including lipid and cytoskeletal transport. Although traditionally viewed as part of a linear signalling pathway, ARFs and their regulators must now be considered to exist within functional networks, in which both the 'inactive' ARF and the regulators themselves can mediate distinct effects.

Although most eukaryotic proteins are secreted through the conventional endoplasmic reticulum–Golgi secretory pathway, both cytoplasmic and nuclear proteins have been shown to reach the cell surface by non-conventional transport pathways. The mechanisms and molecular components of unconventional protein secretion are beginning to emerge.

Tau and the Retromer complex are both linked to Parkinson’s and Alzheimer’s disease. Using Drosophila neurodegeneration models, this study finds that low retromer activity induces a specific increase of a highly toxic truncated form of human Tau.

Toxic protein aggregation is a hallmark of various neurodegenerative diseases. Here, authors show that ATP-independent membrane protein chaperones can serve as a simple design platform for targeting proteotoxic aggregates linked to Huntington’s disease.

The CD1d pathway present lipid antigens resulting in the activation of iNKT cells but the complete pathway remains to be fully elucidated. Here, Chandra et al. use an siRNA screen and identify Mrp1 as crucial for CD1d lipid presentation and activation of iNKT in the context of Streptococcus pneumoniae infection.

Actin cables affect lifespan by supporting movement and inheritance of fitter mitochondria to daughter cells in yeast. Here the authors show that branched-chain amino acid (BCAA) levels affect actin cable stability and a role for YKL075C/AAN1 in control of BCAA metabolism and actin cable stability and function.

Inflammatory processes in atherosclerotic lesions promote disease progression and plaque rupture. Here the authors load the drug statin into nanoparticles made of recombinant high-density lipoprotein and show that these accumulate in atherosclerotic plaques and reduce plaque inflammation in mice.

We evaluated the use of chimeric antigen receptor-modified T cells targeting GD2 (GD2-CART) for H3K27M⁺ diffuse midline glioma (DMG), finding that intravenous administration of GD2-CART, followed by intracranial infusions, induced tumour regressions and neurological improvements in patients with H3K27M-mutant pontine or spinal DMG.

Alzheimer’s disease is often considered a disease of neurons. This study reveals that astrocytes are also impaired by the disease and that these cells contribute more to memory deterioration than previously thought.

The rate at which proteins are imported into the nucleus of a cell is shown to be regulated by their mechanical unfolding, a mechanism that identifies the nuclear pore machinery as a highly sensitive force detector.

Severe congenital development defects such as Jeune syndrome can result from the malfunction of primary cilia and dynein. Here Schmidts et al. report unique biallelic null mutations in a gene encoding a dynein light chain, helping to explain the nature of ciliopathies in human patients.

Amyotrophic lateral sclerosis (ALS) leads to selective loss of motor neurons. Using motor neurons derived from induced pluripotent stem cells from patients with ALS and FUS mutations, the authors demonstrate that axonal transport deficits that are observed in these cells can be rescued by HDAC6 inhibition.

Electric vehicles are increasingly adopted in the USA, with concurrent expansion of charging infrastructure and electricity demand. This Review details these trends and discusses their drivers and broader implications.

The extrusion of large extracellular vesicles is an important mechanism that facilitates cell-to-cell communication and maintains homoeostasis. Here, Atkin-Smith et al. use intravital microscopy to directly visualize the formation of large extracellular vesicles in bone marrow.

Excised signal circles are circular DNA by-products of V(D)J recombination that form a complex with the V(D)J recombinase, and when increased in abundance, result in increased mutagenesis, causing adverse outcomes in cancer.

Most chloroplast proteins are imported from the cytosol and thus transiently exposed to the cytosolic proteasome. Here the authors show that impairment of the cytosolic proteasome can elevate precursor protein abundance and photosynthetic activity suggesting that cytosolic protein turnover is a means to tune plastid function.

Innate immune cells such as dendritic cells and macrophages can activate the adaptive immune system against cancer by presenting cancer-specific antigens, although this activity is severely limited in macrophages due to their intrinsic lysosomal cysteine protease activity. Here the authors show that a DNA nanodevice specifically targeted to macrophage lysosomes can inhibit cysteine proteases in these cells, restoring their antigen-presenting capability.

Fibroblast heterogeneity is a recognized feature in chronic kidney disease, and although fibrosis is integrant to the pathology, it is lesser known which of the fibroblast populations contribute. Here authors describe a population of proinflammatory fibroblasts, which are found in close proximity to macrophages and may facilitate their recruitment and acquisition of a FOLR2+, pathogenic phenotype.

In the kidney, maintaining permeability of the filtration barrier is critical. Here, Sachs W. et al show that homeostasis of podocytes and glomerular endothelial cells relies on differing proteasome constitutions which orchestrate endocytic activity in addition to protein degradation.

Radiation from a previously unexploited region of the electromagnetic spectrum could hold the key to a new generation of security devices. Catherine Zandonella investigates.

Wall-free liquid channels surrounded by an immiscible magnetic liquid can be used to create liquid circuitry or to transport human blood without damaging the blood cells by moving permanent magnets.

Proteins of the Mycobacterium smegmatis Mce1 system assemble to form an elongated ABC transporter complex that is long enough to span the impermeable mycobacterial cell envelope.

Wnt/planar cell polarity (PCP) signalling regulates angiogenesis in vertebrates. Here the authors show that the E3 ubiquitin ligase PDZRN3 ubiquitinates the PCP-signalling protein Dishevelled 3 to promote Wnt/PCP signalling, directing embryonic and postnatal remodelling of the vasculature in mouse.

A method, RARE-seq, for sensitive detection of cell-free RNAs in blood is demonstrated to have diverse clinical applications including diagnosing and characterizing human cancers, and tracking response to RNA therapeutics.

Analysis of the hydrolysis kinetics of strigolactone receptors using enzyme-activated fluorescent probes revealed that the catalytic triad histidine of the receptor forms a covalent interaction with the strigolactone hydrolysis product, the D ring.

The transcriptional signature of embryonic lethality has not been defined. Here, the authors, as part of the Deciphering the Mechanisms of Developmental Disorders programme, define genes causing murine embryonic lethality around E9.5 and identify developmental delay transcriptional signatures.