Search

Protein serial crystallography at X-ray free-electron lasers (XFELs) is a powerful technique for structure determination. Here, authors present a device for sample delivery designed to abate challenges to non-specialists allowing for compound screening.

High-speed atomic force imaging allows for the visualisation of molecular‐level activity in real-time. Here, the authors use HS-AFM to image the activity of an antimicrobial peptide on a membrane and are able to detect previously unknown molecular mechanisms behind its action.

The authors use surface acoustic waves, focused in a Gaussian geometry, to manipulate the spin state of divacancy defects in silicon carbide via mechanical driving. They demonstrate that shear strain is important in controlling the spin transitions.

An mRNA-based therapeutic can drive expression of a functional antibody in humans at levels capable of neutralizing Chikungunya virus ex vivo.

Step-economical and efficient syntheses of Spongistatin 1 analogs are desirable for the development of potent anti-proliferative agents. Here, the authors report a 22-step synthesis of a D-ring modified Spongistatin 1 analog with retained picomolar potency among a group of C(15) ester derivatives.

Improving the stability of proteins for biotechnological applications is challenging. Now, Gillam and co-workers show that the thermal stability and longevity of enzymes can be remarkably enhanced in a single step from sequences of recent ancestors of primitive vertebrates that existed in mild conditions.

Computational methods for the de novo design of conformationally restricted peptides produce exceptionally stable short peptides stabilized by backbone cyclization and/or internal disulfide bonds that are promising starting points for a new generation of peptide-based drugs.

Bacteria and archaea use tripartite ATP-independent periplasmic (TRAP) transporters to import essential nutrients. Davies et al. report a high resolution structure of a TRAP and show that it uses an ‘elevator-with-an operator’ mechanism.

Abrupt changes in atmospheric methane through the last deglaciation were largely the result of tropical sources responding to shifting rainfall patterns, according to a comparison of precisely dated ice cores in Greenland and Antarctica.

Super-resolution imaging of the dynamics of organelle structures in live cells is facilitated by blinking, far-red dyes.

The ability of T cells to migrate is a central component of their functionality and is known to require WNK1 kinase that is linked to the influx of ions into the cell. Here the authors show that T cell migration requires WNK1 mediated ion and water influx to swell the membrane of the leading edge and support actin polymerisation and forward motility.

An orally bioavailable small-molecule active-site inhibitor of the phosphatases PTPN2 and PTPN1, ABBV-CLS-484, demonstrates immunotherapeutic efficacy in mouse models of cancer resistant to PD-1 blockade.

Although immune checkpoint blockade is a standard treatment for patients with malignant mesothelioma, only a minority of patients exhibit radiological response. In a phase II clinical trial (MIST4) investigating the efficacy, safety and molecular correlates of response following treatment with atezolizumab and bevacizumab, the authors demonstrate that the gut microbiota may modulate responsiveness to treatment.

The strange metal phase in unconventional superconductors is probed by Hall measurements. This reveals that quantum criticality drives the Hall effect, which also correlates with the superconductivity. This indicates that all three may be linked.

The allocation of remaining fossil fuel production has stimulated a discussion around issues of equitable allocation but the implications of different options are unclear. Here the authors show that shifting production to low-medium human development regions has limited economic benefits under strong climate policy.

McConnell et al. develop TANGERINE, a computationally frugal, open-source foundation model for analyzing 3D low-dose chest computed tomography (CT) scans. The model achieves strong generalisation and label efficiency across multiple lung diseases while requiring minimal computational resources.

Spin waves can provide efficient alternatives to microelectronics in applications such as image processing, but are difficult to realize on the nanoscale. Here, the authors develop a magnonic grating coupler, which allows for the conversion of microwaves to short-wavelength spin waves with large amplitudes.

The viral Protein Kinase-1 (PK-1) phosphorylates the regulatory protein p6.9, which facilitates baculoviral genome release. Here, the authors combine X-ray crystallography with biophysical and biochemical analyses as well as molecular dynamics simulations to characterize Cydia pomenella granulovirus PK-1, which forms a dimer with a parallel side-to-side arrangement of the kinase domains and furthermore, they provide insights into its catalytic mechanism and evolutionary relationships with other kinases.

Superconductivity is often destroyed under magnetic field larger than a critical value called Pauli limit. Here, the authors report superconductivity beyond the Pauli limit in bulk single crystals of NbS₂, suggesting the development of a Fulde-Ferrell-Larkin-Ovchinnikov state.

Characterization of the interaction between PTH and its G-protein-coupled receptor, PTHR, shows conformational changes coupled to residues interacting with His9, which helps position the PTH N terminus at the PTHR transmembrane domain to facilitate β-arrestin coupling.

Here the authors describe a functional screening platform in human stem cells to identify and optimize protein-based gene editing additives that increase homologous directed recombination and have potential to improve gene therapy workflows.

The insertion of metal atoms and heteroaromatic units provides a way to tune the optical, electronic and magnetic properties of graphene nanoribbons. Now the synthesis of a porphyrin-fused graphene nanoribbon with a narrow bandgap and high charge mobility has been achieved, and this material used to fabricate field-effect and single-electron transistors.

Here, the relationship between unfolding and amyloid aggregation of glaucoma-associated myocilin is probed, showing that myocilin is not at equilibrium and pathogenic aggregation competes directly with unfolding.

A prespecified analysis of the DELIVER clinical trial shows that the sodium/glucose cotransporter 2 inhibitor dapagliflozin benefits patients categorized as having heart failure with improved ejection fraction, a class of patients at high risk of cardiac events but for which limited treatment data are available.

Non-receptor tyrosine kinases such as Src play fundamental roles in host–pathogen interactions and phagocytosis. Here, Young et al. show that an enteropathogenic Escherichia coli(EPEC) protein, EspJ, inhibits Src activity by simultaneous amidation and ADP ribosylation of a conserved residue on the kinase.

Orofacial movements for feeding can be triggered, coordinated and rhythmically organised at the level of the brainstem. Here, the authors show two nuclei can organise the stereotyped movements for ingesting fluids in mammals, these neuronal groups are marked by expression of Phox2b and are located in the intermediate reticular formation of the medulla and around the motor nucleus of the trigeminal nerve.

SNP rs17713054 in the 3p21.31 COVID-19 risk locus is identified as a probable causative variant for disease association. Chromatin conformation and gene expression data indicate that LZTFL1 is impacted by rs17713054 in pulmonary epithelial cells.

Solution processed colloidal quantum dots are emerging photovoltaic materials with tuneable infrared bandgaps. Here, Yang et al. create a class of quantum dot bulk heterojunction solar cell via ligand design, enabling longer photocarrier diffusion lengths for greater photocurrent and performance.

A study shows that rhombohedral graphene is an ideal platform for well-controlled tests of many-body theory and reveals that magnetism in moiré materials is fundamentally itinerant in nature.

Red–green colour blindness is the most common single locus genetic disorder. Gene therapy is now used in adult monkeys, colour blind since birth, to provide the receptoral basis for trichromatic colour vision. Despite the expectation from classic visual deprivation experiments that neural connections established during development are incapable of processing an input not present from birth, treated monkeys displayed trichromatic colour vision behaviour.

Progesterone receptor membrane component 2 is required to transport haem from the mitochondria to the nucleus, where, in adipose tissue, it has roles in regulation of thermogenesis and glucose metabolism.

Black phosphorus/molybdenum disulfide mid-wave infrared photodiodes with external quantum efficiencies of 35% across 2.5–3.5 μm at room temperature and a peak detectivity of 1.1 × 10¹⁰ cm Hz^1/2 W^–1 at 3.8 μm are demonstrated.

Bacteria represent an unexploited reservoir of biosensing proteins. Here the authors use genomic screens and functional assays to isolate a progesterone sensing allosteric transcription factor and use a FRET-based method to develop an optical progesterone sensor.

T cell tolerance is established in the thymus via interactions with medullary thymic epithelial cells (mTEC) expressing tissue-restricted self antigens. Here, the authors suggest, using new transgenic mouse lines and single cell transcriptome analyses, that specific mTEC subsets are associated with distinct T cell fates.

A crystal structure of human ESCRT-I headpiece reveals a helical assembly that is required for autophagosome closure and HIV-1 release in cells. The work suggests that ESCRT-I assembly templates ESCRT-III assembly for membrane scission.

The interaction between TASL and SLC15A4 links endolysosomal Toll-like receptors to the transcription factor IRF5, providing a mechanistic explanation for the involvement of the complex in systemic lupus erythematosus.

The intermembrane complexes mediating calcium signals are crucial but poorly understood. Here the authors identify a Phe-His pair in the calcium-sensing STIM1 protein that controls both activation and pairing of STIM1 with Orai channels to generate calcium signals

Physicochemical heterogeneity poses a significant constraint in photocatalyst advancement. Here the authors introduce a multimodal optical microscopy platform to assess activity and defects concurrently in photoelectrocatalysts, revealing that disorder can unexpectedly enhance local photoelectrocatalytic performance in certain instances.

The crystal structure of the heterohexameric origin recognition complex (ORC), essential for coordinating DNA replication onset in eukaryotes, is resolved at 3.5 Å resolution.

Direct sequencing of RNA molecules in real time using nanopores allows for the detection of splice variants and hold promises for profiling RNA modifications.

Coastal upwelling sustains some of the most productive ocean regions. Here, the authors find that spatial patterns and temporal changes in nutrient supply explain marine microbial community structure and diversity in the Southern California Current region.

For future ultrafast opto-electronic circuits, optical signals must be interfaced with coherent electronic signals. The authors develop asymmetric plasmonic nanojunctions that convert fs light pulses to THz electronic transients that can propagate on-chip for up to a mm, enabling such an interface.

A method that minimizes strain and doping can be used to fabricate metal contacts to encapsulated ultraclean tungsten diselenide monolayers with contact resistances of 5 kΩ μm and transfer lengths of 1 μm.

The E2 enzyme Cdc34 plays a critical role in cell cycle progression but the structural bases for its activities are unknown. Here, the authors present crystal structures of Cdc34 alone, in complex with E1, and in complex with Ub that provide insights into the mechanism of Cdc34 activity in the cell.

Approximately 30% of known drugs target G protein-coupled receptors (GPCRs), but all the published structures of GPCRs to date are from the class A family of GPCRs; here the first X-ray crystal structure of a member of the class B family of GPCRs, the human corticotropin-releasing factor receptor 1, is determined.

Bulk RNA sequencing of organs and plasma proteomics at different ages across the mouse lifespan is integrated with data from the Tabula Muris Senis, a transcriptomic atlas of ageing mouse tissues, to describe organ-specific changes in gene expression during ageing.

In contrast to direct-targeting monoclonal antibodies, low affinity confers agonistic monoclonal antibodies with more potency.

It is unclear whether stream detritivore diversity enhances decomposition across climates. Here the authors manipulate litter diversity and examine detritivore assemblages in a globally distributed stream litterbag experiment, finding a positive diversity-decomposition relationship stronger in tropical streams, where detritivore diversity is lower.