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PCR is an essential method for the amplification and manipulation of nucleic acids, but the requirement for a thermocycler limits access. Here, authors engineer a helicase to replace the heating step of PCR with enzymatic unwinding, allowing the isothermal amplification of fragments up to 6 kb.
Chemo-resistance and immune evasion are major challenges in osteosarcoma treatment. Here the authors show that doxorubicin promotes IL-18 secretion by tumor associated macrophages inducing LAT2-dependent CD47 upregulation in osteosarcoma cells, suggesting LAT2 inhibition as a therapeutic option in combination with doxorubicin.
Here the authors identify retinoblastoma (RB) protein as an intrinsic inhibitor of BRD4 and demonstrate that loss of RB induces BRD4 cistrome changes in the genome and enrichment of GPCR-cAMP signaling pathway, conferring resistance to small molecule BET inhibitor.
Immunoglobulin M (IgM) is the Ig isotype that serves as the first line of host defence during infection. Here, the authors image the full-length IgM pentamer by cryo-EM, revealing the structure and hinge motion of the antigen binding domains.
Systematic investigation of isomerism in covalent organic frameworks (COFs) can provide key insights into their properties. Here, the authors reveal that the constitutional isomerism of the linkage i.e., linkage orientations distinctly impact COFs’ structural and photophysical properties.
Monitoring of co-infections of SARS-CoV-2 variants is important to evaluate their clinical impact and the risk of emergence of recombinants. Here, the authors develop and validate a methodological pipeline to detect co-infections and apply it to samples from France in early 2022, when Delta and Omicron were co-circulating.
In this study, the authors analyse contact tracing records for ~650,000 suspected or confirmed COVID-19 cases in New York City during the second epidemic wave. They reconstruct transmission networks and find that vaccination and zone-based control policies likely contributed to control of the epidemic.
Presenilin isoforms (PS1 and PS2) containing γ-secretase show contrasting sensitivity to MRK-560. Here, the authors determined cryo-EM structures of PS1/PS2-complexes treated with MRK-560 and identified key residues responsible for the isoform-dependent selectivity.
The developed theory for coupled deformation, plastic strain-induced phase transformation, transformation-induced plasticity, and self-blown-up deformation-transformation-heating in shear band explains the main puzzles of deep-focus earthquakes.
The control of regioselectivity in Heck-type reactions of unactivated alkenes is challenging. Here, the authors realize regiodivergent Heck-type reactions of unactivated alkenes and N-fluoro-sulfonamides.
Rare-earth elements are vital to advanced technological applications ranging from spintronic devices to quantum information science. Here, the authors formed charged rare-earth complexes on a material surface and demonstrated atomically precise control on their rotational dynamics.
A desmoplastic stroma, enriched in cancer-associated fibroblasts (CAF), has been associated with resistance to therapy in patients with pancreatic ductal adenocarcinoma (PDAC). Here, after showing that chemotherapy promotes tumor fibrosis by increasing CAF frequency and activity, the authors develop a multi-paratopic VEGF decoy receptor for PD-L1 directed PlGF/VEGF blockade, promoting anti-fibrotic and anti-tumor effects in PDAC models.
The orbitofrontal cortex (OFC) encodes value, but how attention modulates its encoding is not clear. Here, the authors demonstrate that the representation of value in OFC is dominated by reward salience but only weakly modulated by spatial attention.
The biological and clinical implications of high genome instability in esophageal squamous cell carcinoma (ESCC) remain to be explored. Here, the authors analyse 528 whole genomes and investigate the landscape and molecular mechanisms underlying structural variations in ESCC patients.
Protein language models taking multiple sequence alignments as inputs capture protein structure and mutational effects. Here, the authors show that these models also encode phylogenetic relationships, and can disentangle correlations due to structural constraints from those due to phylogeny.
Many aspects of the tumourigenesis of endometrioid endometrial cancers (EEC) are still poorly understood. Here, the authors use single-cell transcriptomics to characterise EEC tumours and their microenvironment across different stages, and reveal potential cells of origin for EEC.
The stress response protein REDD1 is regulates inflammation and energy metabolism. Here the authors report that global or adipocyte-specific deletion of REDD1 inhibits diet induced obesity, insulin resistance, liver steatosis and inflammation in mice, at least in part via reduced atypical NF-κB activation.
Heskett et al. describe several members of a class of long non-coding RNAs, known as ASARs, which show distinct epigenetic regulation between subclonal lineages and are essential for normal DNA replication timing and stability of human autosomes.
Organic metal chalcogenides (OMCs) are organic-inorganic hybrid materials with continuous M-X (X = S, Se, Te) networks that are covalently connected by organic ligands. Here authors report a family of bimetallic OMCs synthesized via selective metal metathesis and oxidation transformation.
Face stimuli that are perceived as emotionally expressive rather than neutral are associated with specific neural responses in V1. Here the authors show that valence information perceived from facial expressions is computed in the amygdala and fed back to V1 via direct anatomical projections.