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This study discovers human SERF2 as a key partner in stress granule formation by binding specific RNA G-quadruplexes. SERF2 and these RNAs provide a detailed structural model of protein-RNA interactions driving liquid-liquid phase separation in condensates.

Li, Burgos-Bravo and colleagues report that NDF phase separation regulates FACT condensation, which enhances transcription by generating a localized biochemical environment that promotes nucleosome disassembly while preserving chromatin integrity by retaining histones.

Extracellular vesicles (EVs) can provide critical information for diagnostics, but analysis can be difficult. Here, the authors develop a super-resolution imaging method that combines rolling circle amplification with expansion microscopy to reveal surface/internal markers in single EVs for cancer diagnosis and immunotherapy prediction.

Human papillomavirus (HPV) DNA testing is the preferred method for cervical cancer screening, but existing tests are inaccessible for resource-limited settings. Here, authors develop a low-cost, simple HPV DNA assay suitable for bedside testing and demonstrate strong performance in Mozambique.

Resolution of G4s has been suggested to be required for efficient DNA replication. Here, the authors show that the nuclease DNA2 and the DNA repair complex MutSα (MSH2-MSH6) are required to remove G4 stabilized by environmental compounds to allow efficient telomere replication.

A general method for enzymatic synthesis of base-modified RNA was developed using engineered thermostable DNA polymerases enabling introduction of site-specific modifications or synthesis of hypermodified RNA not accessible by in vitro transcription.

The iRGD tumor-penetrating peptide can achieve tumor specific drug delivery but whether and how it can penetrate into desmoplastic tumors is unknown. Here, the authors show that β5 integrin expression on tumor cells, mediated by CAFs-derived TGF-β, is required for iRGD penetration into the desmoplastic PDAC microenvironment and that iRGD-based combination therapy is effective in PDAC mouse models.

Immune check point therapies have not been successful for prostate cancers, but the underlying mechanisms are unclear. Here the authors show that a transcription factor, YY1, may promote the SUMOylation and stability of HIF-1α to suppress anti-tumor immunity, while targeting YY1 helps improve tumor control, in mouse prostate cancer models.

Using data from the CoVPN 3008 study, the authors show that the neutralizing antibody correlate of risk holds in people living with HIV. However, the nAb correlate was weaker and shorter-lived in a vaccine-immunity versus hybrid-immunity population.

Standard approaches for identifying pleiotropic genetic variants may lead to spurious results. Here the authors present a new statistical method and show that it uncovers five genes linked to metabolites in METSIM participants, which were previously undetected by existing methods.

Rates of Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) continue to rise in Hispanics and Latinos. Authors developed a digital PCR assay to quantify activation-induced cytidine deaminase activity at risk loci involved in cancer etiology that may contribute to this health disparity.

The authors report a Yin-Yang balance between α-Synuclein and β-Synuclein via regulating phase separation in physiological states and Parkinson’s disease. AI-designed peptides mitigate the symptoms and prolong the lifespan of C. elegans PD models.

Paclitaxel, a first line chemotherapeutic drug, suffers from poor water solubility and low tissue selectivity. Here, the authors report a water-soluble nucleolin aptamer-paclitaxel conjugate that selectively accumulates in ovarian tumor issues displaying reduced toxicity and improved activity profiles.

Biomolecular condensates (BCs) are ubiquitous compartments that regulate key functions in cells. Authors demonstrate that phase separation is suppressed with glycine by using model heterotypic condensates composed of nucleophosmin 1 and ribosomal ribonucleic acid.

This study found E. coli phylogenetic background shapes TEM-1 beta-lactamase expression and co-amoxiclav resistance. Phylogeny alone shifted isolates from susceptible to resistant, stressing a need for lineage-sensitive genotype-phenotype prediction.

Genetic testing is crucial for precision cancer medicine. Here, the authors develop a one-pot ERA-CRISPR assay to detect variable same-site indels, using an engineered AsCas12a variant with improved mismatch tolerance and broadened PAM scope.

RNA delivery for disease treatment often has low uptake efficiencies and cytotoxicity. Here the authors produce extracellular vesicles from red blood cells for in vivo cargo delivery.

This study presents DNA-origami biocatalytic modular nanocompartments for programmed regulation of protein unfolding and degradation. These artificial nanofactories augment reaction kinetics, improve enzyme performance and reduce off-target effects.

Cerebrovascular changes and astrogliosis occur in Alzheimer’s disease (AD). Using an in vivo phage display technique, the authors identified a peptide that upon systematic administration, can home to brain endothelial cells and astrocytes in mouse models of AD at the early stages of the disease.

Biallelic expansion of an intronic AAGGG repeat in RFC1 is identified here as a common cause of late-onset ataxia. This expansion occurs in the poly(A) tail of an AluSx3 element and is observed at a carrier frequency of 0.7% in populations of European ancestry.

In this study, the authors determine the structure of a Type I-A retron from E. coli FORC82 and reveal the functional interplay between Reverse Transcriptases (RTs) and Structural Maintenance of Chromosomes (SMC) ATPases.’

Chemical modifications of aptamers can enhance binding properties, however, the design of suitable functional groups remains challenging. Here, the authors introduce cyclooctatetraene (COT)-modified nucleotides in SELEX experiments, identifying COT-aptamers with low nM dissociation constants, highlighting the potential of three-dimensional ligands in aptamer discovery.

The molecular determinants for primer synthesis are identified within the catalytic domain of primase-polymerase enzymes, elucidating the mechanisms underlying initiation of primer synthesis.

Zhang et al. identify GLP-1 receptor agonists mitigating Alzheimer’s disease-related cognitive decline and amyloid pathology in a transgenic mouse model via promoting phagocytosis and through activation of the CaMKK2–AMPK signaling pathway.

In this work, authors generate nanoconstructs that synergistically target cell wall synthesis in Candida pathogens, which induce potent antifungal effects and prolonged survival in candidiasis, providing an alternative treatment option to conventional drugs.

Nanoparticles carrying an antibiotic and conjugated with a peptide identified via phage display that binds specifically to Staphylococcus aureus effectively suppress staphylococcal infections in vivo.

Accurate treatment of traumatic brain injuries, a leading cause of neurological disability and death in young people, is hampered by poor accumulation of drugs in the brain. Here, the authors describe a tetrapeptide that can efficiently target brain injuries and deliver therapeutic or diagnostic payload.

Surgical nerve injuries can cause significant morbidity, yet no approved fluorescent agents exist for visualization. Here, the authors show in a Phase I multi-site trial that bevonescein was safe, established optimal dosing and timing, and provided a fluorescence signal for intraoperative nerve identification.

Here the authors report that DMDA-PatA, an anti-tumor compound, functions as a mRNA-selective translational inhibitor. This drug clamps the target eIF4A and DDX3 RNA-binding proteins on the GNG RNA motif, providing steric hindrance for scanning ribosomes.

Epigenetic causes of intra-tumoural heterogeneity are crucial in paediatric cancers with low mutation rates, such as hepatoblastoma. Here, the authors characterise transcriptional heterogeneity in hepatoblastoma using histology-guided RNA sequencing and functional studies in patient-derived tumoroids, and find how the embryonic biliary lineage program, Wnt, and paracrine signalling can promote tumour proliferation.

Köhler et al. present the crystal structure of fungal tRNA ligase Trl1-LIG bound to an activated RNA substrate, providing key insights into conserved substrate binding and activation, enzyme specificity and a tRNA substrate coordination model.

Fortilin promotes atherogenesis by enhancing macrophage survival, proliferation, and lipid uptake while suppressing their transdifferentiation into vascular smooth muscle cells, leading to increased foam cell accumulation and reduced plaque stability.

Natural buffer molecules ensure the controlled and precise delivery of specific molecules in biology. Here, the authors replicate the natural buffer systems using aptamers with controlled binding efficiency to control and maintain the levels of free drugs both in vitro and in vivo.

Delivering RNA therapies to the brain is challenging due to the blood-brain barrier. Here, the authors show in murine models that a berberine-inspired lipid nanoparticle system enhances brain targeting via dopamine D3 receptors, enabling effective treatment for neurological diseases.

APOBEC3A mutates its host DNA in human cancers to evolve drug resistance. Modified-DNA inhibitors suppress this mutagenic activity in cells, suggesting use as conjuvants in anti-cancer therapies. Here the authors reveal structural insights into how these inhibitors bind APOBEC3A.

R-loops formed by RNA hybridization to DNA template strand during transcription influence HIV-1 integration into the CD4⁺ T cell genome. The unwinding of R-loops by splicing helicase Aquarius facilitates integration into speckle-associated domains.

RNA targeting by the Sulfuricurvum type V single-effector nuclease SuCas12a2 drives abortive infection through non-specific cleavage of double-stranded DNA—after recognition of an RNA target through an activating protospacer-flanking sequence, SuCas12a2 efficiently degrades ssRNA, ssDNA and dsDNA.

Stapled α-helical peptides are promising for targeting challenging targets such as transcription factors, but achieving sufficient cell permeability while avoiding off-target cleavage is difficult. Here, the authors present workflows for identifying stapled peptides against Mdm2(X) with in vivo activity and no off-target effects based on comprehensive investigations of their properties.

Coating single cells with adhesive polymers through covalent click chemistry approaches increases cell adhesion to extra-cellular matrix proteins and endothelial cells. This strategy opens new avenues for improving therapeutic cell engraftment.

Peptide phage display reveals a non-catalytic binding site on the intervening domain of O-GlcNAc transferase. Its roles in substrate recognition, posttranslational modification (PTM) crosstalk and nutrient response provide insight into the function of this cryptic domain.