Search

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

Crystalline materials for optical applications are synthesized in living dinoflagellates.

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.

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.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Smart microscopy is an emerging technology which integrates real-time analysis with adaptive acquisition to enhance imaging efficiency. Here the authors introduce “outcome-driven microscopy,” an approach that uses optogenetics and real-time feedback to control cell behaviour and protein dynamics.

The catalytic mechanism of [Fe]-hydrogenases is not well understood. Now a signal-enhanced nuclear magnetic resonance method based on parahydrogen is introduced to study [Fe]-hydrogenase under turnover conditions in situ, revealing intermediates of the catalytic cycle.

Lymphostatin is a large protein required for Escherichia coli virulence. Here, Griessmann et al. use electron cryo-microscopy to describe the structure of lymphostatin determined at different pH values, showing three conformations, six distinct domains, and long inter-domain linkers that occlude the catalytic sites of the N-terminal glycosyltransferase and protease domains.

Platelets are known to have functions beyond those in thrombosis and haemostasis. Here the authors use multi-colour flow cytometry and proteomics to analyse platelet phenotypes in psoriatic disease and proteins that are potentially involved in the interaction of platelets with immune cells.

Sarcomas are a group of mesenchymal malignancies which are molecularly heterogeneous. Here, the authors develop an in vivo muscle electroporation system for gene delivery to generate distinct subtypes of orthotopic genetically engineered mouse models of sarcoma, as well as syngeneic allograft models with scalability for preclinical assessment of therapeutics.

Bat influenza viruses use MHCII, not sialic acids, for entry. Using high-resolution microscopy. on live cells, the authors show at the nanoscale that viral particles attach to clusters of MHCII. and attract additional molecules to the attachment site.

By unifying data from engineered β-barrel nanopores and supported by modelling, it is demonstrated that the lumen charge in a β-barrel nanopore governs rectification and voltage-driven gating, with applications in computing using nanofluidic synapses.

Pathology-oriented multiplexing (PathoPlex) represents a framework for widespread access to multiplexed imaging and computational image analysis of clinical specimens at a relatively high throughput and subcellular resolution.

In theory, driven biological oscillators can display complex dynamic behaviors, but these are experimentally difficult to observe. Here the authors, using microfluidics, show that a synthetic cell-free gene oscillator displays period doubling and even quadrupling.

Staphylococcal pathogens adhere to their human targets using adhesins, which can withstand extremely high forces. Here, authors use single-molecule force spectroscopy to determine the similarly high unfolding forces of B domains that link the adhesin to the bacterium.

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.

Hofer et al. show that fasting promotes the synthesis of spermidine, which stimulates eIF5A hypusination to induce autophagy and increase lifespan in various species in a conserved manner.

Antimicrobial peptide LL37 can bind nucleic acids and potentiate their sensing by endosomal TLRs. Here the authors show that LL37 binds to RNA from neutrophil extracellular traps (NETs), which amplifies inflammation and production of more LL37 and NETs via TLR8/13, suggesting that LL37 contribution to psoriasis may be fueled by NET-associated RNA.

Retroviral integration of DNA into the host genome is a point of no return in the replication cycle but how efficient integration can take place remains unclear. Here the authors demonstrate that consecutive nucleoprotein intermediates are increasingly stable, resulting in a net forward rate.

CRISPR activation enables multiplexed, cell-type-specific and stable gene expression in plants. Houbaert et al. successfully reprogrammed gene expression in the root endodermis and restored flavonoid production in mutants, displaying the power of this synthetic biology tool.

Melanoma cells can switch between proliferative and invasive phenotypes. Here the authors show that the embryonic stem cell factor Sall4 is a negative regulator of melanoma phenotype switching where its loss leads to the acquisition of an invasive phenotype, due to derepression of invasiveness genes.

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.

Single-particle cryo-EM, cryo-electron tomography and AlphaFold modeling reveal the structural architecture of the poxvirus core and identify trimers of protein A10 as the key component of the palisade layer.

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.

This study reveals the structural basis of auxin import by the AUX/LAX family. LAX3 binds auxin as well as herbicides via a proton-coupled mechanism, which offers insights into hormone recognition that is essential for lateral root growth.

The disassembly of a parent zeolite and its reassembly into two zeolites with targeted topologies is described. This process demonstrates that it is possible to target specific ring sizes in a zeolite by replacing one size of unit in the structure with alternative units of a different size.

This study describes sensing of circulating cell-free DNA after stroke as the mechanism leading to recurrent ischemic events.

In a mouse model, maternal obesity during pregnancy can lead to fatty liver disease in the offspring, driven by aberrant developmental programming of Kuppfer cells.

Three-dimensional analysis of the intact bone marrow within whole long bones remains very challenging. Here, the authors present a method that stabilizes the marrow and provides subcellular resolution of fluorescent signals throughout the murine femur.

Endothelial cells play a critical role in the adaptation of tissues to injury and show a remarkable plasticity. Here the authors show, using single cell sequencing, that endothelial cells acquire a transient mesenchymal state associated with metabolic adaptation after myocardial infarction.

Reproduction in numerous marine organisms is timed to specific moon phases, but the mechanisms for sensing moon phases are incompletely understood. Here the authors report that an ancient, light-sensitive protein L-Cryptochrome in a marine bristle worm can discriminate between sun- and moonlight, enabling the animals to properly decode moon phases.

Mechanistic origins of force stability and bond kinetics of interaction of the receptor-binding domain from the SARS-CoV-2 spike protein with angiotensin-converting enzyme 2, a key selection factor for mutations, are revealed at the single-molecule resolution using magnetic tweezers and molecular dynamics simulations.

The mechanisms of intratumoral subtype heterogeneity in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Here, the authors analyse PDAC tumours and preclinical models using multi-omics and imaging; they demonstrate that AP1 dichotomy influences tumor plasticity, heterogeneity, and immune response, with potential therapeutic implications.

Cas12a is a useful alternative to Cas9 for genome editing and regulation. Here the authors design strand displacement gRNAs that can add functionality to Cas12a by acting as multi-input logic gates.

Cell-type-resolved spatial proteomics of the skin from patients with toxic epidermal necrolysis reveals that it is driven by JAK/STAT signaling, leading to successful treatment of this potentially fatal condition in patients using JAK inhibitors.

Antimicrobial resistance is a global health threat and the development of alternative strategies to overcome it is of high interest. Here, the authors report proteolysis targeting chimeras active in bacteria (BacPROTACs) that bind to ClpC1, a component of the mycobacterial protein degradation machinery, and apply them for targeting a range of mycobacterial strains, including antibiotic-resistant ones.

Fusion proteins between roGFP2 and glutaredoxins are used for intracellular redox measurements. Here, the authors determined all rate constants of the reaction cycle for roGFP2 measurements and identified an alternative glutaredoxin mechanism.

Most aerial organs of vascular plants are covered by a waxy cuticle that limits water loss. Here the authors show that the asymmetric architecture of the cuticle creates a polarity gradient to ensure directional movement of water through olive and ivy leaf cuticles and construct bioinspired artificial membranes that mimic cuticle behaviour.

Anaplastic lymphoma kinase (ALK) inhibitors are currently being considered in neuroblastoma (NB), but its acquired resistance is reported in non-small cell lung cancers. Here, the authors have found PIM1 overexpression decreases sensitivity to ALK inhibitors in NB and combined ALK and PIM1 inhibition enhances anti-tumour efficacy in vitro and in PDX models.

Targeting of diseased cells is key to the development of next-generation pharmaceuticals, but is often hindered by a lack of specific cell surface markers. Here the authors develop an RNA-based approach, which allows precise control of gene expression, with translation only occurring within preselected cell types of interest.

The human genome still contains numerous uncharacterized genes. Here, the authors identify a fast evolving Factor associated with Metabolism and Energy (FAME) that is associated with altered body weight, energy expenditure, and metabolism and study its function in knockout mouse models.

BCL2-inhibitor venetoclax is used to treat relapsed/refractory chronic lymphocytic leukemia (CLL). Here, the authors show the clonal dynamics towards venetoclax resistance by performing whole-exome sequencing of 8 CLL patients undergoing venetoclax treatment.

MINSTED quantifies tiny movements of individual biomolecules with high spatiotemporal precision to successfully resolve the steps of the molecular motor protein kinesin-1 labeled with a single fluorophore as it switches protofilaments.

The structure of a human exosome–ribosome supercomplex reveals the mechanisms behind the formation of active cytoplasmic exosomes and their role in co-translational RNA decay.

Polymerase Bcs3, which allows the fermentation-free synthesis of Haemophilus influenzae type b capsule for vaccine development, adopts a basket-like shape with all six active sites facing the interior, creating a protected environment for catalysis.

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.

Gs heterotrimers are considered to be poor providers of free Gβγ subunits. Here, the authors show that—despite this—Gs-derived Gβγ dimers are active transducers of GPCR-initiated Ca2+ signals involving phosphoinositide-based signaling routes.