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Cryptochrome 4 from the night-migratory European robin displays magnetically sensitive photochemistry in vitro, in which four successive flavin–tryptophan radical pairs generate magnetic-field effects and stabilize potential signalling states.

Comparison between structures of human, mouse and rat P2X7 receptors define ortholog-specific pharmacology and facilitated structure-based drug design of UB-MBX-46, an antagonist that selectively inhibits the human P2X7 receptor with sub-nanomolar potency.

The kinesin-1 motor protein accesses open active and closed autoinhibited states. These states are regulated by a flexible elbow within a complex coiled-coil architecture. Now, a conformational switch has been developed by engineering the elbow to create a closed state that can be controllably opened with a de novo designed peptide to increase kinesin transport inside cells.

IκBζ is a rather unknown transcriptional co-factor of NF-κB. Here, the authors show that constitutive IκBζ expression in a subgroup of patients with melanoma drives immunotherapy resistance and enhanced tumor growth.

LC–HRMS is used for metabolomics studies in the biomedical and environmental sciences. MetaboAnalyst (metaboanalyst.ca) can be used to address challenges in data processing, statistical analysis, functional interpretation and multi-omics integration.

Here the authors discover that SET1 complexes function as transcription anti-termination factors that bind to CpG islands and protect low to moderately transcribed genes from the pervasive termination activity of the ZC3H4 complex.

Neutrophils actively induce tumour necrosis, driving vascular occlusion, pleomorphic necrosis and metastasis.

Seropositive samples of SARS-CoV-2 were detected as early as mid-February in patients at Mount Sinai Hospital in New York City, and antibody positivity increased during the first wave of the pandemic and remained stable afterwards.

The cell adhesion molecule E-selectin regulates haematopoietic stem cell self-renewal in the bone marrow vascular niche. Here, the authors show E-selectin adhesion directly induces survival signaling in acute myeloid leukaemia and therapeutic inhibition improves chemotherapy outcomes in mice.

Loss of PP2A activity is often associated with cancer but the underlying mechanism remains unclear. Here, the authors show that decreased methylation of PP2A catalytic C subunit caused by loss of LCMT-1 in prostate cancer abrogates the tumor suppressor activity of PP2A on AR/MED1-dependent gene expression, proposing decreased methyl-PP2A-C as a prognostic marker for prostate cancer progression.

Cancer cell motility is necessary for cell invasion and metastasis. Here, the authors identify CNK2 as a key mediator of cancer cell motility, linking extracellular stimuli via AXL signalling and downstream activation of ARF6 GTPase, resulting in increased metastasis in preclinical models.

Cells use clathrin-mediated endocytosis to internalize biomolecular cargo. The authors demonstrate that the Epsin1 protein ensures uptake of ubiquitylated cargo through ubiquitin-dependent regulation of the stability of endocytic protein networks.

Knockout studies using CRISPR–Cas9 identify PCDH10 as a selective host cellular receptor for western equine encephalitis virus.

A method called MEDUSA was developed for identifying death regulatory genes in chemo-genetic profiling data, which enables characterization of a previously unappreciated mechanism of death induced by DNA damage in p53-deficient cells.

IFNλ4 has posed a conundrum in human immunology, leading to structural and functional questions about the protein. Here, the authors use protein engineering and cryoEM to determine the cytokine-receptor complex structure and lend explanations to its different activity from other type III interferons.

PUB30/31 ensure the optimal signalling output of ERECTA for proper plant growth and stomatal development. A heterodimeric partner BAK1 is a kinase and a scaffold that activates PUB30/31, which in turn ubiquitinate ligand-activated ERECTA for degradation.

Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

How neural crest development is specifically regulated by splicing factors and its vulnerability to splicing dysregulation remains unclear. Here, the authors identify neural crest-specific and somite-specific splicing complexes that confer distinct susceptibility to splicing perturbation.

SPTBN1 mutations cause a neurodevelopmental syndrome characterized by intellectual disability, language and motor delays, autism, seizures and other features. The variants disrupt βII-spectrin function and disturb cytoskeletal organization and dynamics.

How a lasso cyclase ties a lasso peptide into its characteristic knot has remained poorly understood. Here the authors identify key molecular interactions that guide lasso peptide folding and cyclase substrate tolerance to inform cyclase engineering for expanded lasso peptide diversity.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Caloric restriction improves Alzheimer’s Disease outcomes in mice, but this diet not only reduces calories, but imposes a prolonged fast between meals. Here, the authors show this fast is essential to improve Alzheimer’s pathology and cognition.

Olfactomedin-2 is a pleiotropic glycoprotein emerging as a regulator of energy homeostasis via the hypothalamus. The present findings functionally connect adipose-specific OLFM2 to obesity, and highlight its significance in maintaining adipocyte commitment to avoid metabolic disease.

Vaccination efficiency in HIV infection is hampered by the low immunogenicity of HIV-1 Env glycoprotein (Env). Here authors optimise the neutralising antibody response to Env by stabilizing the Env trimers in the context of expressing them in a Newcastle Disease Virus-like particle and providing conditions that mimics replicating virus infection.

Greening disease threatens the productivity of citrus crops worldwide yet the pathosystem is poorly understood. Here, Clark et al. show that an effector cloned from the associated bacteria can suppress host plant papain-like cysteine proteases' activity, suggesting its probable role in pathogenesis.

Liver dysfunctions are understudied in myotonic dystrophy (DM1) but impact metabolic health, drug sensitivity and treatment paradigms for the affected population. Here, Dewald et al. generated liver-specific DM1 mice to demonstrate that CUG-repeat RNA toxicity predisposes the liver to MAFLD and drug metabolism defects.

The development of specific anti-cytokine/chemokine therapeutic strategies for atherosclerotic disease is challenging. Here, the authors have designed a peptide-based ectodomain mimic of the chemokine receptor CXCR4 that selectively targets MIF but not CXCL12 and blocks experimental atherosclerosis in vivo.

Supraphysiological T cell activation by chimeric antigen receptor (CAR) contributes to T cell exhaustion and adverse events in CAR T cell therapies. Here the authors engineer a synthetic antigen receptor that integrates into the endogenous TCR complex, preserving natural regulatory circuits and achieving improved performance in mouse tumor models.

The ability to produce homogeneous glycoproteins is expected to advance fundamental understanding in glycoscience, but current in vivo-based production systems have several limitations. Here, the authors develop an E. coli extract-based one-pot system for customized production of N-linked glycoproteins.

Photocaged inositol-pyrophosphates offer a tool to study cellular signalling, but their challenging synthesis has precluded any biological studies so far. Here, the authors report the synthesis and cellular delivery of a photocaged analogue, and show that it mediates protein translocation in cellulo.

A bright and photostable far-red fluorescent protein, smURFP, was developed from a cyanobacterial phycobiliprotein. smURFP uniquely binds a highly cell-permeable biliverdin derivative to obtain fluorescence brightness comparable to that of eGFP in cells.

Delivering therapeutics to the brain is challenging because of the hard-to-cross blood–brain barrier. Here, the authors show that HER3, which is expressed on the surface of many metastatic tumours, is associated with the brain endothelium and can drive accumulation of HER3-targeted nanoparticles within the brain, for therapy against HER3-positive tumours.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

Most polygenic risk score (PRS) methods focus only on individuals with distinct primary continental ancestry, without accommodating recently-admixed individuals. Here, the authors develop a novel penalized regression-based PRS method specifically designed for admixed individuals.

Circular RNAs are exported from the nucleus by Ran-GTP, exportin-2 and IGF2BP1 in a mechanism analogous to protein export rather than mRNA export.

The FET family proteins FUS, EWSR1 and TAF15 are RNA-binding proteins with diverse nuclear functions. PAR-CLIP analyses now reveal the genome-wide RNA targets of all three human FET proteins and of two FUS mutants that cause amyotrophic lateral sclerosis. Although the RNA-binding properties of the mutants remain unchanged, the spectrum of RNA targets is altered because of the changed subcellular localization of the mutants.

The ability of synthetic amyloid β-protein to bind to prion proteins and alter synaptic plasticity has been previously reported. Here the relevance of this binding is investigated in brains of Alzheimer's disease patients and the interaction is shown to be blocked by antibodies to two distinct regions of prion proteins.

Proteostasis is maintained through a number of molecular mechanisms, some of which function to protect the folded state of proteins. Here the authors demonstrate the use of TPE-MI in a fluorigenic dye assay for the quantitation of unfolded proteins that can be used to assess proteostasis on a cellular or proteome scale.

Dondelinger et al. and Menon et al. show that MAPKAP kinase-2 (MK2) phosphorylates RIPK1 to regulate TNF-mediated cell death as well as RIPK1 signalling in inflammation and bacterial infection.

Here the authors show that DNA damage induced RNA m5C in R-loops competes with PARP1- mediated PARylation in transcribed genomes to promote cell survival which could be targeted be in cancer therapy.

Genome-scale CRISPR–Cas9-based synthetic lethality screens identify PKMYT1 as a potential therapeutic target in tumours with CCNE1 amplification.

The interpretation of somatic variants in cancer is challenging due to the scale and complexity of sequencing data. Here, the authors present PORI, an open-source framework for interpreting somatic variants in cancer using graph knowledge base tools, automated reporting, and manual curation.

FAM72A differentially controls mutation rates by regulating uracil processing at different stages of the cell cycle, thereby regulating somatic hypermutation and class-switch recombination in B cells.

Community-associated Staphylococcus aureus strains show heightened wall teichoic acid production, which correlates with virulence and abscess formation.

Cells survive starvation by activating protective pathways. Here, the authors describe that kinase EFK-1/eEF2K defends against oxidative damage in long term starvation in C. elegans independently from its kinase activity and translation regulation.

G-quadruplex are higher-order nucleotide structures within G-rich sequences with regulatory roles. Here, the authors provide the structure of a viral genomic RNA G-quadruplex using X-ray crystallography. They report unusual features of the West Nile virus NS5B quadruplex which expands our knowledge of quadruplex complexity and will aid in designing molecules to target them.