Search

Ionic covalent organic frameworks (iCOFs) are new examples of porous materials and show great potential for various applications. Here, the authors demonstrate functionalization of an iCOFs with suitable emission sites and application as chemosensor for amine detection with high sensitivity which can be used to monitor meat spoilage.

Polyamines prevent the action of kinases on acidic phosphorylatable motifs in spliceosomal proteins, thus providing a mechanism for metabolite-mediated regulation of alternative splicing in cells.

CCR9 is chemokine receptor involved in gut inflammation and cancer. Here, the authors use AI-based modeling, protein engineering and pharmacological experiments to reveal the unusual anatomy of CCR9 activation by its endogenous chemokine agonist CCL25.

D7 proteins are highly abundant in the salivary glands of several blood feeding insects. Here, the authors study the ligand binding specificity and physiological roles of the mosquito D7 proteins CxD7L1 and CxD7L2, showing that CxD7L1 acquired ADP-binding properties to enhance blood feeding in mammals.

Abemaciclib is a third generation CDK-directed drug used in the treatment of HR + /HER2 negative advanced or metastatic breast cancer. Here the authors demonstrate that members of the Homeodomain-interacting protein kinases (HIPKs) HIPK3 and DYRK1A are also targeted by Abemaciclib.

Tutas et al. show an unconventional role for autophagy in the regulation of glycolytic flux in cerebellar Purkinje cells by maintaining the levels of the glucose transporter GLUT2.

The discovery of a specific CDK12 bivalent degrader, BSJ-4-116, reveals that chronic exposure of MOLT-4 and Jurkat cells to BSJ-4-116 leads to acquired resistance to the compound via point mutations in the CDK12 kinase domain.

Lymphatic malformation (LM) is a debilitating often incurable vascular disease. Using a mouse model of LM driven by a disease-causative PIK3CA mutation, the authors show that vascular growth is dependent on the upstream lymphangiogenic VEGF-C signalling, permitting effective therapeutic intervention.

The contamination of water by per- and polyfluorinated substances is a pressing global issue. Here, the authors explore a cationic covalent-organic framework for efficient detection and removal of perfluorooctanoic acid (PFOA) from water.

Implant-associated infections with Staphylococcus aureus pose serious clinical challenges. Here, the authors develop a biosensor based on toxin-responsive liposomes encapsulating gold nanoclusters, providing a non-invasive, colourimetric diagnostic tool for bacterial infection detection with urinary readout.

The function of many bacterial processes depends on the formation of functional membrane microdomains (FMMs), which resemble the lipid rafts of eukaryotic cells. Here, Ukleja et al. show that FMMs mediate ATP-independent stabilization of unfolded proteins, which is essential for bacterial viability under cellular stress and during infection.

The success of targeting KRAS for cancer therapy is limited by resistance due to compensatory mechanism, making combinatorial approaches attractive. Here, the authors use a KRAS signature drug repurposing screen and identify the multityrosine kinase PKC inhibitor Midostaurin as synergistic with MEK and KRAS inhibitors in KRAS-mutated lung adenocarcinoma.

Current cysteine bioconjugation strategies for protein-drug conjugates synthesis often yield heterogeneous and poorly stable products. Here, the authors use carbonylacrylic derivatives to selectively modify cysteine residues and synthesize biologically functional antibody conjugates highly stable in plasma.

PHDGH heterogeneity in primary tumours could be a sign of tumour aggressiveness.

Staphylococcus aureus is increasingly recognized as a facultative intracellular pathogen, but it is unclear whether the intracellular lifestyle is a general feature or is restricted to some isolates. Here, Rodrigues Lopes et al. profile the interaction of 191 clinical isolates with four host cell types over time, showing that almost all isolates are internalized and that a large fraction replicate and persist within host cells.

Characterization of the vaginal microbiome and metabolome reveals that vaginal metabolites, including several exogenous xenobiotics, are predictive of spontaneous preterm birth.

Fendt and colleagues find that pre-metastatic niche formation and a high-fat diet increase palmitate availability in future organs of metastases and show that breast cancer cells use palmitate to generate acetyl-CoA, acetylate the NF-κB subunit p65 and induce pro-metastatic signaling.

Chemical profiling in hyponeddylated cells coupled with multi-omics target deconvolution led to the identification of molecular glue degraders of cyclin K that function by inducing proximity between the CRL adaptor DDB1 and a CDK12–cyclin K complex.

Sequencing of the bonobo genome shows that more than three per cent of the human genome is more closely related to either the bonobo genome or the chimpanzee genome than those genomes are to each other.

Diphtheria toxin selectively kills cells engineered to express the diphtheria toxin receptor (DTR). Here the authors report a PEGylated version of diphtheria toxin that does not enter the brain, allowing for ablation of only peripheral cells when using Cre lines that drive DTR expression in both the periphery and in the brain.

Nematodes define a new role for sirtuins in lifespan extension, in which the sirtuin product nicotinamide is converted to a substrate for aldehyde oxidase; turnover of this enzyme generates hydrogen peroxide, causing upregulation of defense mechanisms that promote longevity.

The precise underpinnings of Parkinson's disease and other disorders associated with the accumulation of α-synuclein are unclear. This study shows that PrP^C mediates α-synuclein-associated synaptic dysfunction and memory deficits. Blocking specific events in receptor biology rescued cognitive deficits in mice, suggesting new possibilities for intervention in synucleinopathies.

Spagnolli, Massignan, Astolfi et al. design a new drug discovery approach, termed Pharmacological Protein Inactivation by Folding Intermediate Targeting, in which folding intermediates of disease-causing proteins are targeted. They test it on the cellular prion protein, identifying ligands stabilizing a folding intermediate and consequently promoting its degradation by the cellular quality control machinery.

This article reviews the fundamentals and applications of scanning probe lithography, focusing on the methods that offer genuinely lithographic capabilities such as those based on thermal effects, chemical reactions and voltage-induced processes.

Gregor Andelfinger and colleagues identify mutations in SGOL1 that cause a novel cohesinopathy characterized by chronic atrial and intestinal dysrhythmia, termed CAID syndrome. SGOL1 encodes a component of the cohesin complex, suggesting that cardiac and gut rhythm are regulated by this complex.

A gluten-free diet is currently the only effective treatment for coeliac disease but an increased understanding of disease pathogenesis has led to the identification of several potential therapeutic targets. This Review provides a broad overview of current and emerging therapies for coeliac disease.

The incorporation of mechanical bonds into porous materials offers opportunities for new functionality. Here a covalent organic framework is synthesized by polymerization of a cucurbituril-viologen complex, imparting improved thickness, stability, and luminescence compared to the unrotaxanated viologen-based COF.