Search

Device inspired by nature clings to surfaces using 'liquid bridges'.

The high-resolution crystal structure of the SHOC2–MRAS–PP1C complex provides insights into the complex assembly, RAF dephosphorylation, MRAS selectivity versus canonical RAS isoforms, and the impact of Noonan syndrome mutations on complex formation.

Nuclear translocation of the p50/p65 heterodimer is essential for NF-κB signaling. Here, the authors identify a bipartite Nuclear Localization Signal in the NF-κB p50/p65 heterodimer that is recognized with high affinity by importin α3.

Dense calcium imaging combined with co-registered high-resolution electron microscopy reconstruction of the brain of the same mouse provide a functional connectomics map of tens of thousands of neurons of a region of the primary cortex and higher visual areas.

Anti-disialoganglioside (GD2) antibody therapy has proven beneficial to neuroblastoma patients and intra-tumoral copper levels have been associated with immune evasion. Here the authors show that copper chelation potentiates anti-GD2 immunotherapy through improved infiltration and function of Fc receptor bearing neutrophils.

Proper cellular proteostasis requires a network of the chaperonin TRiC/CCT with cochaperones prefoldin (PFD) and phosducin-like proteins (PhLPs) to facilitate the folding of essential eukaryotic proteins. Here, the authors characterized the ATP-driven cycle of TRiC-PFD-PhLP2A interaction using cryoEM and biochemical analyses.

Using a specialized tip as a detector, the fingerprints of a single atom of iron and terbium are observed in synchrotron X-ray absorption spectra, allowing elemental and chemical characterization one atom at a time.

Hepatitis B virus (HBV) infection and DNA integration is a frequent cause of hepatocellular carcinoma (HCC), but the consequences of this process are not fully understood. Here the authors use whole-genome and long-read sequencing data from HCC patient samples to study the timing and alterations induced by HBV insertions.

Following spinal injury in zebrafish, non-neural cells establish an extracellular matrix to promote axon re-growth but how this is regulated is unclear. Here, the authors show that Wnt/β-catenin signaling in fibroblast-like cells at a lesion activates axon re-growth via deposition of Collagen XII.

Studies of cell heterogeneity in white matter in primates have been limited to date. Here the authors describe a marmoset brain cell atlas that bridges rodent and human data, revealing strong gray-white matter glial segregation.

De novo designed interleukin-4 mimetics were engineered that induce biased signaling activation and exhibit high thermal stability. These mimetics offer insight into cytokine signaling and can be directly incorporated into 3D-printed biomaterials

An in situ only fabrication process for networks of topological insulator–superconductor Josephson junctions with high interface transparency is introduced, which holds some potential for the production of future topological quantum computing networks.

Amaryllidaceae alkaloids, such as the Alzheimer’s medication galantamine, are currently extracted from low-yielding daffodils. Here, authors pair biosensor-assisted screening with machine learning-guided protein design to rapidly engineer an improved Amaryllidaceae enzyme in a microbial host.

Two highly charged disordered human proteins phase-separate into viscous complex coacervates while retaining their rapid conformational dynamics through pico- to nanosecond exchange of short-lived side-chain interactions.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

HPS is a rare autosomal recessive disorder that cause dysfunctions of the lungs, intestine, kidneys, and heart. Here, the authors report the structure of the BLOC complex, BLOC-3 and provides a framework to understand how BLOC-3 cooperates with Rab GTPases (RAB32/38 and RAB9A) to regulate the biogenesis of lysosome-related organelles.

IL-33, released by epithelial cells in response to stress, is a potent activator of inflammation. Here Cohenet al. show that secreted IL-33 is rapidly inactivated by disulfide bond formation that prevents binding to its receptor, and that IL-33-related cytokines are susceptible to similar oxidation.

AMBRA1-mediated degradation of cyclin D through CRL4–DDB1 regulates cell proliferation and prevents replication stress in neurodevelopment and cancer.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

Colobomatous microphthalmia often lacks a genetic diagnosis despite its developmental complexity. Here, the authors show that rare variants in NR6A1 cause a syndromic form with eye, kidney, and vertebral defects, supported by zebrafish functional validation.

The NMR-derived structural model of the dynamic interaction between synaptotagmin-1 and the SNARE complex contributes to addressing the longstanding problem of how synaptotagmin-1 triggers neurotransmitter release.

High-resolution structure of the E. coli ribosome highlights rRNA and protein modifications and provides details on solvation characteristics and the structural impacts of ribosome modifications.

Ingo Braasch, John Postlethwait and colleagues report the genome of the spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before genome duplication. Their data provide insights into the evolution of genes involved in immunity, mineralization and development and facilitate the comparison of cis-regulatory elements between teleosts and humans.

ParA is an ATPase involved in the segregation of newly replicated DNA in bacteria. Here, structures of a ParA filament bound to DNA and of ParA in various nucleotide states offer insight into its conformational changes upon DNA binding and filament assembly, including the basis for ParA’s cooperative binding to DNA.

The X-ray crystal structure of the human glucagon receptor, a potential drug target for type 2 diabetes, offers a structural basis for molecular recognition by class B G-protein-coupled receptors.

In neonatal mice, scar-free healing after spinal cord injury is organized by microglia, and transplantation of neonatal microglia or peptidase-inhibitor-treated adult microglia into adult mice after injury improves healing and axon regrowth.

The Activin-A precursor protein undergoes proteolytic processing by furin and other proteases. Here the authors identify that kallikrein-8 mediates furin-independent cleavage of Activin-A precursor to promote tumor growth in a murine melanoma model.

Rashan, Bartlett and colleagues show that mammalian 4-hydroxy fatty acids are primarily catabolized by ACAD10 and ACAD11 (atypical mitochondrial and peroxisomal acyl-CoA dehydrogenases, respectively) that use phosphorylation in their reaction mechanisms.

Available enzymatic CO2 reduction strategies are not suitable for aerobic microorganisms and many industrial settings. Here, the authors design a new metabolic pathway that can operate under fully aerobic conditions, ambient CO2 levels, and seamlessly integrate with well-established C1-assimilation pathways.

Rif1 is involved in different processes such as telomere homeostasis, DNA replication timing, and DNA double strand break (DSB) repair pathway choice. Here, the authors reveal that Rif1 S-acylation facilitates the accumulation of Rif1 at DSBs, attenuation of DNA end-resection, and DSB repair by non-homologous end-joining.

Freely falling granular streams break up into characteristic droplet patterns similar to liquid flows, but the clustering mechanism remains unresolved. Here, imaging and microscopy data reveal that tiny cohesive forces are responsible, corresponding to a granular surface tension some 100,000 times weaker than in ordinary liquids.

While proinflammatory signalling is preventive to axon regrowth, activated macrophages can be beneficial, for example by limiting the inflammation. This study uses mutant zebrafish lines that lack macrophages and/or microglia to show that peripheral macrophages are necessary in axon regrowth following complete transection of spinal cord.

Hu et al. discovered that the truncated form of human epidermal growth factor receptor 2 (HER2), called p95HER2, drives tumor progression and resistance to the antibody–drug conjugate trastuzumab deruxtecan in HER2⁺ breast cancer. Blocking p95HER2 restores antitumor immunity.

The molecular mechanism by which rapid spider silk assembly occurs in the glands of spiders is challenging to investigate. Here, the authors perform site-directed mutagenesis of the N-terminal domain and propose a three-step mechanism that allows controlled aggregation of spidroins.

Rho kinases regulate the actin cytoskeleton by controlling stress fibre formation. Truebestein et al.show that the length of its coiled-coil determines ROCK2 function, and propose that the coiled coil acts as a spacer, targeting kinase activity to a discrete distance from the membrane.

Producing nacre-like ceramics with a tough, non-polymeric matrix remains a challenge. Here, the authors use the reactive wetting of a zirconium-based bulk metallic glass to successfully infiltrate a porous alumina and create a composite with improved flexural strength and fracture toughness.

The BioDIGS project is a nationwide initiative involving students, researchers and educators across more than 40 research and teaching institutions. Participants lead sample collection, computational analysis and results interpretation to understand the relationships between the soil microbiome, environment and health.

A hyper-stable de novo protein mimic of interleukin-2 computationally designed to not interact with a regulatory T-cell specific receptor subunit has improved therapeutic activity in mouse models of melanoma and colon cancer.

The crystal structure of the human κ-opioid receptor in complex with an antagonist, JDTic, is determined, with potential importance for the design of new therapeutic agents.

RH5, which is part of the trimeric RCR-complex essential for invasion, is a vaccine candidate for malaria. Here, Williams et al. show that monoclonal antibodies targeting each of the three proteins in the RCR-complex can work together to more effectively block the invasion of red blood cells by Plasmodium falciparum and design a combination vaccine candidate.

Carbohydrate esterases alter polysaccharides by removing ester groups. Here, the authors resolved crystal structures of two CE20 enzymes and discovered a novel, water-mediated catalytic triad essential for activity, offering insights into enzyme function and mechanism.