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Photon upconversion methods demonstrated thus far involve challenging requirements. Here Weingartenet al. demonstrate a mechanism called cooperative energy pooling, in which multiple photoexcited sensitizers resonantly and simultaneously transfer their energies to a higher-energy state on a single acceptor.

Studying membrane contact sites at high spatiotemporal resolution is still challenging. Here, authors introduce a series of dynamic chemogenetic reporters to visualize these subcellular regions and study the associated calcium signals.

The E. colimechanosensitive channel MscS responds to hypoosmotic swelling by opening a weakly anion-selective pore. Here, the authors report that the structural determinants of this selectivity are located not in the pore, but in the large water-filled cytoplasmic domain.

The development of highly luminescent materials such as large Stokes shift fast emitters is desirable for their potential application in photonics. Here the authors engineer hetero-ligand metal-organic frameworks nanoparticles to achieve high emission yield, large Stokes shift and realize a prototypal fast scintillator.

Human acetyltransferases MOZ and MORF mediate development programs and are dysregulated in diseases. Here the authors identified two winged helix (WH) domains in MORF/MOZ and characterized their DNA binding functions, including targeting of CpG by WH1.

Ataxia telangiectasia and Rad3-related kinase (ATR) is a rational radiosensitization target. This trial evaluates the combination of the ATR inhibitor, ceralasertib, with palliative radiotherapy in 27 patients with advanced solid tumors.

Bioreactors need to separate the internal environment from the bulk, while also allowing entry and exit of substrate and product. Here, the authors make highly uniform, semipermeable droplets using an aqueous two-phase system, and show potential as microreactors based on a ribozyme cleavage reaction.

Papa et al. show that phosphorylation by PKA of four residues in Rad, a calcium channel inhibitor, is required to mediate the β-adrenergic-induced increase in calcium current and contractile force. Additionally, Rad-phosphosite-mutant mice showed reduced basal heart rate and contractility. Conversely, expression of mutant calcium channel unable to bind wild-type or phosphosite-mutant Rad was sufficient to enhance basal calcium influx and contractility, independently of β-adrenergic stimulation.

Studies on protein–protein interactions using proteins containing d- or l-amino acids show that stereoselectivity of binding varies with the degree of disorder within the complex.

Amyloid self-assembly is linked to type 2 diabetes and Alzheimer’s disease. Here the authors designed constrained peptides which are nanomolar amyloid inhibitors of the key polypeptides IAPP and Aβ42 and act via supramolecular nanofiber co-assembly.

This study identifies a cytolytic peptide toxin in the opportunistic human fungal pathogen Candida albicans—the peptide is both a crucial virulence factor that permeabilizes the host cell plasma membrane and a key signal that triggers a host danger response pathway.

This study proposes an unreported molecular mechanism of substrate inhibition in enzymes. It shows that a competitive inhibitor reduces substrate inhibition and identifies unique enzyme-substrate complexes, suggesting an unreported paradigm for enzyme regulation.

Using integrated silicon high-contrast sub-wavelength gratings and organic cavity exciton-polaritons at room temperature, we realize all-optical transistor action with picosecond switching and amplification, as well as ultracompact footprint.

Catch bonds are unique protein-protein interactions where the bond lifetime increases under external pulling forces. Here, the authors engineer an artificial catch bond based on a non-catch bonding human gut bacterial adhesion protein complex.

The presence of conformational substates of a catalytically competent 'closed' state in the ligand-free form of adenylate kinase is detected. Molecular dynamics simulations indicated that the partially closed conformations were sampled in nanoseconds, and NMR and single-molecule FRET experiments revealed the sampling of a fully closed conformation occurring on the microsecond-to-millisecond timescale.

Sea-level rise in African large marine ecosystem has accelerated markedly since 2010, mostly due to ice sheet loss and land subsidence, with the Red Sea and Guinea Current rising fastest, according to an analysis of 30 years of satellite altimetry data

How histone modifications crosstalk with DNA methylation to regulate epigenomic patterning and genome stability in mammals remains elusive. Here, the authors show that DNA methyltransferase DNMT1 is a reader for histone H4K20 trimethylation via its BAH1 domain, which leads to optimal maintenance of DNA methylation at repetitive LINE-1 elements.

A head-to-head double-ring complex of the human multifunctional DNA repair protein RAD52 mediates protection of stalled replication forks during replication stress, protecting them from reversal by SMARCAL1 motor.

Nucleosomes tightly wrap ~147 DNA base pairs around an octamer of histone proteins, but how nucleosome structural dynamics affect genome functioning is not completely clear. Here authors employ all-atom molecular dynamics simulations of nucleosome core particles and observe that octamer dynamics and plasticity enable DNA unwrapping and sliding.

Changes in intracellular GTP levels are not considered as a regulatory event in RAC1 activation in live cells since total GTP levels are substantially higher than the RAC1 GTP dissociation constant determined in vitro. Here, the authors demonstrate that the availability of free GTP in live cells controls the activity of RAC1 and cell invasion.

UM171 promotes corepressor degradation by acting as a molecular glue to induce KBTBD4–HDAC1/2 interactions with the help of inositol hexakisphosphate.

Conventional Dendritic cells (cDCs) continually migrate from peripheral tissues in homeostasis. Here, the authors analyse the homeostatic turnover of cDC subsets in the intestine from tissue entry to migration to the draining lymph nodes, noting a dynamic life cycle with changes in transcriptome and proliferation rates.

We show that gain-of-function cancer mutations in the KBTBD4 E3 ligase promote neodegradation of substrates via a shape-complementarity-based mechanism, which converges with the mechanism of action of the UM171 molecular glue degrader and can be blocked by HDAC1/2 inhibitors.

The bird hand is thought to derive from the second, third and fourth digits of an ancestral five-digit hand. However, the three-fingered hand of theropod dinosaurs, which are the closest extinct relatives of birds, are thought to derive from the first, second and third digits. The discovery of a small, primitive herbivorous theropod from the Jurassic period of China with a stub of the first digit alongside more developed second, third and fourth digits, sheds light on this problem.

NMDA receptors convert chemical signals into electrical signals in the brain, and function is fine-tuned by the subunit composition. Here the authors use smFRET to uncover a bi-directional communication pathway between different parts of the receptor.

To overcome the limitation of FRET data being too sparse to cover all structural details, FRET experiments need to be carefully designed and complemented with simulations. Here the authors present a toolkit for automated design of FRET experiments, which determines how many and which FRET pairs should be used to maximize the accuracy, and for FRET-assisted structural modeling and refinement at the atomistic level.

Morphogenesis of tissue sheets is well studied, but mechanisms that shape bulk tissues are unclear. Here, the authors show that mesenchymal cells intercalate in 3D to shape the mouse branchial arch, with cortical forces driving intercalations in a Wnt5a-, Yap/Taz- and Piezo1-dependent manner.

The shock breakout (SBO) is the first electromagnetic signature of a supernova (SN) explosion. Förster et al. find that in nearly all type II SNe they survey that the SBO occurs on a timescale of days, indicating that the progenitors were surrounded by thick circumstellar matter when they exploded.

Sulfonylureas are widely used anti-diabetic drugs, which promote insulin release by blocking a pancreatic ion channel. Here the authors create a photoswitchable sulfonylurea derivative and use it to control insulin release from cultured cells and isolated pancreatic islets by illumination with blue light.

spFRET microscopy analysis reveals how FACT reversibly uncoils DNA from nucleosomes during remodeling, thus modulating DNA accessibility in vitro and in vivo.

Parkin and PINK1 are involved in damaged mitochondria clearance; however the sequence of events of Parkin activation is not clear. Here, the authors show that binding to phospho-ubiquitin on mitochondria enables Parkin phosphorylation, which allows Repressor Element of Parkin removal, E3 ligase activation and mitophagy.

Here the authors present a pH-sensitive DNA origami nanoswitch that hides ligands for death receptors and displays them as a cytotoxic hexagonal pattern in acidic tumour microenvironments. This reduces tumour growth in a murine model of breast cancer with minimal on-target, off-tumour toxicity.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

The human Shu complex promotes homologous recombination by regulating RAD51. Here the authors reveal that the Shu complex proteins, SWSAP1-SWS1, decorate the RAD51 filament on ssDNA and facilitate its strand exchange reaction by stimulating RPA diffusion on ssDNA. Lastly, that SWSAP1-SWS1 knockouts are Olaparib sensitive.

Nanoparticle-based ‘microgauges’ are developed for in vivo force sensing and deployed in C. elegans to investigate how mechanical force correlates with electrical signalling in neuromuscular organs.

Transcription factor binding to DNA is vital for gene regulation. Here, the authors determine the kinetics of DNA binding for RBPJ in living cells. They find that the binding is kinetically rather than thermodynamically stable evident from the effective binding energy landscape.

Matrix stiffness induced nuclear deformation regulates gene expression. This study finds that cell spreading on a stiff matrix induces tension in the nuclear lamina which promotes nuclear localization of yes associated protein (YAP), a transcriptional co-activator.

The observations of Virgil and of a Quaker chemist converge on canvas.

The chaperones Hsp70 and Hsp90 are physically linked via the cochaperone Sti1/Hop, that has two binding sites for Hsp70. Here, Röhl et al.show that binding of Hsp90 changes the conformation of Sti1/Hop and determines to which site Hsp70 binds, perhaps facilitating transfer of client proteins from Hsp70 to Hsp90.

Coherence observed in chemical and biological systems suggests that even in the presence of disorder and noise the phenomenon may yield transformative ways for improving function.