Search

Using a combination of X-ray crystallography and biochemical approaches, the authors have characterized a plasmid-encoded Type II-A CRISPR-Cas system inhibitor, namely AcrIIA19, that exhibits broad-spectrum inhibition across divergent Cas9 orthologs. This work also identifies the WED domain as a strategic target for developing species-agnostic CRISPR regulatory tools for biotechnology and therapeutic applications.

Using a genome-wide association studies approach and patient brain tissue, Kim, Hwang et al. link Ebp1 to Alzheimer’s disease (AD). They show that a conditional Ebp1 knockout mouse model mimics phenotypes of sporadic AD and find that EBP1 reduces amyloid β production by inhibiting γ-secretase.

In Alzheimer's disease, increased MAOB activity in reactive astrocytes leads to enhanced GABA release, and blockage of this pathway ameliorates memory dysfunction in mouse models.

Cryptococcus neoformans is a fungal pathogen that causes meningoencephalitis. Here the authors describe the production of a gene-deletion mutant collection representing most C. neoformansnon-essential transcription factors, providing insight into the signalling networks that govern the biology and pathogenicity of this fungus.

Adenine nucleotide translocase (ANT) 2 promotes ADP/ATP exchange across the mitochondrial inner membrane. Choet al. show that liver specific Ant2 deletion increases uncoupled respiration and protects mice against fatty liver and obesity-induced insulin resistance.

An irreversible small-molecule inhibitor of histone methyltransferase NSD1 is developed, which binds covalently to the C2062 residue in the catalytic SET domain and represses H3K36 dimethylation and target gene expression in leukemia cells.

Idiopathic pulmonary fibrosis (IPF) is a fatal adult lung disease. Here the authors investigate the functional significance of PDCD5 in club cells as a mediator of lung fibrosis and potential therapeutic target for IPF.

Ductular reaction is associated with liver disease progression, but there are currently no pharmacologic drugs targeting ductular reaction. Here, authors identify a mechanism by which vitamin D attenuates ductular reaction, liver inflammation and fibrosis in mice via TXNIP upregulation.

Reconstruction of damaged meninges is important for reducing neuronal damage after a brain injury. Here the authors identify AKAP12 as an effector that modulates meningeal reconstruction, and show that its expression is regulated by the upstream signals TGF-ß1, retinoic acid and oxygen tension.

Comparison of paired primary and recurrent glioblastomas at the single-cell transcriptomic level describes molecular and cellular trajectories associated with tumor recurrence, highlighting extensive heterogeneity and microenvironmental co-evolution.

Integrated single-cell transcriptomic and genetic characterization of 121 adult glioblastomas identifies heterogeneity at cell type, cell state and baseline expression program levels associated with specific mutations that form three stereotypical ecosystems.

Gold nanoparticles carrying Cas9 ribonucleoprotein and donor DNA, and complexed with endosomal disruptive polymers, correct the DNA mutation that causes Duchenne muscular dystrophy in mice, with minimal off-target effects.

Excessive NLRP3 inflammasome activation underlies inflammatory diseases such as gout. Here the authors show that orphan nuclear receptor small heterodimer partner protein (SHP) negatively regulates NLRP3, and its loss leads to accumulation of damaged mitochondria and gout-like immunopathology.

Phytochrome is a photoreceptor forming a membraneless organelle called a photobody. The authors isolated the photobody and found that the photobody is made of not only phytochrome but also its primary and secondary interacting proteins.

Organometal halide perovskite materials have been the subject of intensive research efforts in the context of photovoltaic applications. Here the authors exploit dynamic equilibrium to photocatalytically generate hydrogen from aqueous HI solutions using methylammonium lead iodide.

Insulin resistance is associated with development of type 2 diabetes. Here the authors show that TAZ interacts with c-Jun and Tead4, inducing expression of the insulin receptor substrate 1 (IRS1) leading to increased glucose uptake in muscle, and that its activity is counteracted by statin administration.

The physical properties of gel materials makes them attractive options in various applications, but supramolecular gels typically lack mechanical strength. Here, the authors present a calix[4]arene-based supramoleculer gel tuned to possess high tensile strength.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Cost, scalability, and durability are critical factors determining the application of artificial photosynthesis systems. Here, the authors address these problems by inserting a carbon nanofiber into the chloroplast of green algae to transfer of electrons for photosynthesis and demonstrate H2 production up to 50 days.

Though wearable electronics remain an attractive technology for bioelectronics, fabrication methods that precisely print biocompatible materials for electronics are needed. Here, the authors report an additive manufacturing process that yields all-printed nanomaterial-based wireless electronics.

PEDOT:PSS is a conductive polymer with potential as electrodes in flexible electronics, but conductivity is not always satisfactory. Here, the authors report the use of dodecyl sulfate in place of polystyrene sulfonate to prepare a durable and conductive film with large crystal domains.

Ataxia telangiectasia mutated (ATM) directly interacts with and phosphorylates the V-ATPase V₁ subunit ATP6V1G1, thereby decreasing V₁-V₀ assembly in the V-ATPase. Attenuation of ATM activity results in lysosomal pH acidification, recovery of autophagy and alleviation of senescence.

Despite significant efforts to improve the thermoelectric properties of polycrystalline SnSe, precise control of texturing and doping is a challenge. Here, the authors report hole doped and highly textured SnSe thin films prepared by low cost, scalable solution processing.

EGFR mutant lung tumours do not respond favourably to immunotherapy. Here, using single cell sequencing, the authors find that tissue resident memory CD8⁺ T like cells are reduced in the immune landscape of EGFR mutant tumours in comparison to wild type tumours and the presence of these cells may predict response to immunotherapy.

The identity of hair cells’ mechanoelectrical transduction (MET) channel-complex components is unknown. Here, the authors used multiple biochemical, genetic, and functional approaches to show that mouse hair cells utilize Piezo1 and Piezo2 isoforms as part of the MET-complex component.

The emergence of cisplatin resistance and side-effects are important factors in cancer treatment failure. Here, the authors identify autophagy-mediated EGFR hyperactivation by TRPV1 promotion as a mechanism of cisplatin resistance and demonstrate the efficacy of a TRPV1 inhibitor to sensitize lung cancer to cisplatin.

A modular de novo designed biosensor platform consisting of a cage and key molecule is developed, and used to create sensors for seven distinct proteins including the spike protein from SARS-CoV-2 and anti-SARS antibodies.

PlGF is an important vascular endothelial growth factor which has not been widely implicated in immune function. Kim and colleagues demonstrate that PlGF is selectively secreted by T_H17 cells to promote angiogenesis but in turn also strongly supports T_H17 cell differentiation yet inhibits regulatory T cell function.

Gene editing of a single gene in the brain of an adult mouse model of fragile X syndrome, achieved via the intracranial injection of a nonviral Cas9 delivery vehicle, rescues mice from the exaggerated repetitive behaviours caused by the disease.

Hyo-Jun Lee et al. show that submergence in Arabidopsis deactivates wound-induced defence against herbivore attack by suppressing the expression of jasmonic acid biosynthesis genes and increasing expression of ethylene-responsive genes. These results shed light on how flooding may impact plant defence systems.

Ha and colleagues show that loss of PD-1 expression on regulatory T cells in the tumor environment reduces their metabolic fitness and proliferative capacity.