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Plasma proteomics plays a key role in advancing clinical research and biomarker discovery. Here, the authors show in a large MSCoreSys multicenter benchmark study that DIA outperforms DDA, delivering robust, precise, and reproducible label-free protein quantification across sites.

A mode of bidirectional microglia–neuron crosstalk through Hex–GM2–MGL2 and centred around GM2 ganglioside turnover is essential for homeostatic regulation of central nervous system membrane components.

The transcription factor ATF6 causes an enrichment in long-chain fatty acids in the colonic epithelium, which leads to changes in the gut microbiota and contributes to the development of colorectal cancer in humans and mice, thereby linking endoplasmic reticulum stress responses to lipid metabolism and tumorigenesis.

Gut microbiota contribute to the pathogenesis of ulcerative colitis (UC), but the molecular mechanisms are still unclear. Here the authors show that colonic fluid from patients with UC is enriched for bacteria extracellular vesicles (BEV) coated with host IgA, and that these IgA-coated BEV may activate CD89⁺ immune cells to aggravate inflammation and colitis in mouse models.

Human transplantation with allogeneic donor organs results in non-matching of MHC and differential presentation of T cell antigens. Here the authors show that in a lung transplanted SARS-CoV-2 infected patient T cell responses generated from the host may not be able to recognise infected cells within the graft and this may contribute to virus persistence.

The function of DNMT1 (DNA methyltransferase 1) in these subsets of immature, migrating cortical inhibitory interneurons is not fully understood. This study shows that DNMT1 regulates cortical development by orchestrating the migration of postmitotic SST+ interneurons and their signaling to cortical progenitors, with implications for proper cortical architecture and function.

Eco-friendly processing of plastics could leverage the advantages of plastics while maximizing their environmental sustainability. Here the authors show a cellulose cinnamate polymer that could be repeatedly programmed into various 2D or 3D stable shapes through a sustainable hydrosetting process.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

The authors present a novel channel rhodopsin variant with enhanced Ca²⁺ conductance in megakaryocytes and platelets.

Epithelial cells express two isoforms of cytoplasmic actin, γ- and β-actin, and whether isoform-specific functions exist is debated. Here, the authors report a feedback circuitry whereby γ-actin regulates the expression of β-actin and nonmuscle myosin-2A, and modulate apical membrane cortex mechanics and cytoplasmic tight junction protein dynamics.

In situ cryoEM and modelling of the Campylobacter jejuni flagellar motor characterize the periplasmic scaffold and the structural basis for increased torque generation.

The pupil is known to assist retinal adaptation to light level changes. Here, the authors find a mechanism for how the pupillary light reflex drives monocular and binocular retinal activity in mice and shapes conscious visual perception in humans.

The liver has the remarkable ability to regenerate. Applying single-cell transcriptomics and iterative immunofluorescence imaging on patient-derived samples, this study revealed cellular gene expression changes linked to altered tissue architecture.

Pulmonary hypertension due to left heart disease is characterized by pulmonary arterial stiffening that results from extracellular matrix remodeling. Here, the authors show that elastin stabilization improves arterial biomechanics and attenuates pulmonary hypertension.

Tim17 contains conserved negative charges close to the intermembrane space side of the bilayer, which are essential to initiate presequence protein translocation along a distinct transmembrane cavity of Tim17 for both classes of preproteins.

Hallmarks of post-acute consequences of SARS-CoV-2 infection are still insufficiently understood. Here, the authors identify alveolar bronchiolization, interstitial fibrosis, and exercise-induced lung function impairment as features of respiratory long COVID in aged hamsters.

The Omicron variant is partially attenuated, likely because it fails to efficiently infect lung cells. Here, Hoffmann et. al. show that this defect can be lost during Omicron evolution as demonstrated for the subvariant BA.5 that robustly infects lung cells in vitro and in vivo.

Magnetic resonance imaging of swollen tendons suggests that the elasticity and stress relaxation of extracellular matrix depend on electrostatic repulsions between proteoglycans rather than on hydration-associated changes.

Soil-dwelling ectomycorrhizal fungi trigger remodelling of root architecture as part of a mutualistic symbiotic relationship with host plants. Here, Ditengou et al. identify fungal-derived sesquiterpenes as volatile signals capable of stimulating lateral root production in Arabidopsis and Populus.

Flagellated oomycetes frequently infect unicellular algae, thus limiting their proliferation. Here, the authors show that an oomycete rewires the metabolome of a marine bloom-forming diatom, thereby promoting infection success.

Here the authors investigate the regulatory mechanisms of acetyl-CoA (Ac-CoA) biosynthesis in Bacillus subtilis, probing the interaction between acetyl-CoA synthetase (AcsA) and acetyltransferase (AcuA). They capture a stable AcsA-AcuA complex that inhibits AcsA activity in the absence of Ac-CoA.

The filamentous fungus expression system Thermothelomyces heterothallica (C1) is a protein expression system that may be useful for large scale antibody production. Here the authors characterise the production of a human monoclonal antibody that neutralises SARS-CoV-2 and compare functional properties in vitro and in animal models to antibodies produced using other methods.

Here, the authors identify interleukin-3 as a predictive marker for severity and outcome of SARS-CoV-2 infection in a multi-center, prospective study and find that patients with severe COVID-19 have reduced circulating plasmacytoid dendritic cell levels compared to non-severe COVID-19 patients.

Expression of TMPRSS2—a protease that activates SARS-CoV-2 for entry into cells—renders SARS-CoV-2 insensitive to chloroquine.

Heydemann et al. investigate alveolar regeneration mechanisms after SARS-CoV-2 infection in the hamster model, offering insight into the pathomechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC).

An approach based on the average trajectory of moving particles allows for the quantification of the mechanics of living systems, namely, the non-equilibrium energy and viscoelastic properties of cells, in a non-invasive manner.

Here the authors demonstrate how protein translation, controlled by Ire1α, regulates neuronal diversification in the developing neocortex.

Plants have evolved pattern-recognition receptors to perceive pathogens. Here, the authors demonstrate that microbial small cysteine-rich proteins are eminent immune targets that led to convergent evolution of distinct immune receptors in plants.

The ribosomal protein uL23 contacts the signal recognition particle to monitor the translational status of emerging polypeptides.

Many enzymes form homo-oligomers, but it is often not clear why. This study follows the evolution self-assembly in citrate synthases across their phylogeny and finds it to be variable and not obviously related to enzyme function.

The Hedgehog morphogen creates gradients during development, but diffusion alone cannot explain its spatiotemporal dynamics. Hedgehog transport requires binding heparan sulfate sugar chains, and the authors now show that Hedgehogs can spread by interacting with sequential heparan molecules.

Glucocorticoids reprogram the mitochondrial metabolism of macrophages, resulting in increased and sustained production of the anti-inflammatory metabolite itaconate and, as a consequence, inhibition of the inflammatory response.

Alternative σ factors regulate the activity of RNA polymerases under specific conditions and are regulated through various mechanisms, most of which depend on anti-σ factors to regulate their on/off status. This study reports a new mode of σ factor regulation that does not require an anti-σ factor, but instead σ factor phosphorylation in response to the presence of an antibiotic.

Citrate synthase from the cyanobacterium Synechococcus elongatus is shown to self-assemble into Sierpiński triangles, a finding that opens up the possibility that other naturally occurring molecular-scale fractals exist.

Medulloblastoma in children is a difficult cancer to treat and the immune response to this tumour is not fully understood. Here the authors characterise and validate T cell epitopes from these cancers using an immunopeptidomics approach, comparing different molecular subtypes.

The Tibetan Kobresia pastures store 2.5% of the world’s soil organic carbon. Here the authors show that soil degradation and microbial shifts may irreversibly diminish the carbon sink function and accelerate nutrient losses.

Licheva, Pflaum, Babic, Mancilla et al. show that low-affinity cargo–receptor interactions promote autophagy receptor mobility and condensation of the scaffold protein Atg11 to trigger initiation hub and phagophore formation.

This study describes the second, shortened chloroplast variant of the ribosome-associated molecular chaperone termed trigger factor. While lacking chaperone activity, it rather contributes to maturation of the 50S ribosome subunit, particularly during plant cold acclimation.

Neutrophils rapidly respond to bacterial and fungal infections but can cause substantial collateral tissue damage if not restrained. Rosenbauer and colleagues show that the transcription factor PU.1 serves a cell-intrinsic role to prevent over-exuberant neutrophil responses to fungal infection.

Exhaustion is the functional deterioration of T cells following chronic stimulation. Here, Wu et al. show that mitochondrial dysfunction drives T cell exhaustion by inhibiting HIF-1α degradation and transcriptional metabolic reprogramming.

Using cryo-electron microscopy, the authors determine the structure of cGAS bound to nucleosomes and present evidence for the mechanism by which nucleosome binding to cGAS prevents cGAS dimerization and its binding to free double-stranded DNA.

ILCs are considered preformed effector cells. Gasteiger and colleagues report that ILC1s undergo effector differentiation after lineage commitment. Hobit⁺ ILC1s emerge as cKit⁺TCF-1^hi cells that generate tissue-specific helper- and cytotoxic-like cells along a Hobit-dependent trajectory.

Rift Valley fever virus (RVFV) can cause severe diseases in humans, including encephalitis. Here the authors show that NSs, the major virulence factor of RVFV, is an amyloidogenic protein forming fibrils in infected mouse brains and causing increased mortality in mice.

DMSP is a ubiquitous organosulfur compound in the ocean that, once degraded by bacteria, plays key roles in global biogeochemical cycles and climate regulation. Here, the authors use single-cell measurements of transcription to investigate the intricate dynamics of bacterial DMSP degradation.

Urinary albumin-to-creatinine ratio (UCAR) is associated with various clinical outcomes such as kidney disease and cardiovascular disease. Here, the authors report genome-wide meta-analysis in over 500,000 individuals and find 68 UACR loci, followed by statistical fine-mapping, gene prioritization and experimental validation in flies.

The t(8;21) translocation is often found in acute myeloid leukaemia but is not sufficient for development of the disease. In this study, the authors identify frequent mutations in the transcriptional repressor, ZBTB7A, in these patients and show that the mutations reduce DNA binding activity.

A structurally unusual zwitterionic metabolite, dimethylsulfoxonium propionate (DMSOP), is synthesized by several dimethylsulfoniopropionate-producing microalgae and marine bacteria and is readily metabolized into dimethylsulfoxide by marine bacteria, expanding our knowledge of the marine organosulfur cycle.