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Unilateral occipitotemporal resection in children with drug-resistant epilepsy reveals both typical and reorganized category maps, with word/face selectivity competing in the preserved ventral visual pathway over time, reflecting plasticity.

Regiospecific cyclizations of reactive poly-β-keto intermediates are known to lead to the structural variability of aromatic products of fungal nonreducing, multidomain iterative polyketide synthases (NR-PKS group of IPKSs), but questions about the process remain. The crystal structure and mutational studies of a dissected product template monodomain from PksA, the NR-PKS that initiates the biosynethesis of the hepatocarcinogen aflatoxin B₁, are now presented.

Gut microbiota play a critical role in drug metabolism. Now, by exploring the human gut microbial metabolism of G-protein-coupled receptor (GPCR)-targeting drugs, uncommon pathways and biotransformations are elucidated, revealing how the activity of the metabolized drugs against target GPCRs is modulated.

Robert de Moya et al. use comparative genomics of avian lice to reconstruct the phylogeny of these parasites. They show that feather lice diversified on the common ancestor of waterfowl and landfowl, and then radiated onto other avian lineages through host-switching.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Differential carbohydrate metabolism elicits distinct pyrazine and pyrazinone autoinducer signalling pathways in Klebsiella oxytoca, which impact bacterial virulence programs.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Hagenbeek et al. identify a small-molecule pan-TEAD inhibitor that blocks the interaction between YAP/TAZ and TEAD proteins. They demonstrate that treatment with the inhibitor leads to antitumor activity and can synergize with KRAS G12C inhibition.

Findings suggest that l-ornithine could serve as a novel nutraceutical to ameliorate LACC1-associated immunological dysfunctions.

GIANT, a genetically informed brain atlas, integrates genetic heritability with neuroanatomy. It shows strong neuroanatomical validity and surpasses traditional atlases in discovery power for brain imaging genomics.

Cell-type-specific chromatin accessibility QTL during neurogenesis allow fine mapping of causal variants and more complete underlying of regulatory mechanisms underlying noncoding loci associated with gene expression and neuropsychiatric disorders.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Enterococcus faecalis-derived adenine increases enterohaemorrhagic Escherichia coli virulence by relieving Hha-dependent repression of Type 3 Secretion System activity.

Genotoxic small molecules from the bacterial colibactin pathway — a gut-associated non-ribosomal peptide synthetase–polyketide synthase hybrid gene cluster linked to colorectal cancer — have remained elusive due to their instability. Now, one of these, the colibactin warhead, an unprecedented substituted spirobicyclic structure, has been characterized and shown to crosslink duplex DNA in vitro.

Precolibactin 886 is a complex microbiome-derived metabolite implicated in colorectal cancer and produced by the clb gene cluster. A chemical synthesis and analysis of precolibactin 886 is reported which shows that its biosynthetic precursor degrades to other known clb metabolites. The data also provide insights into the structures and reactivity of advanced clb products.

Clinical trials of BAFF blockade with belimumab have shown partial efficacy for the treatment of systemic lupus erythematosus (SLE), so other therapeutic options are required. Here, the authors present a new small molecule inhibitor that targets NIK with a similar efficacy to BAFF inhibition in two mouse models of SLE.

The Vertebrate Genome Project has used an optimized pipeline to generate high-quality genome assemblies for sixteen species (representing all major vertebrate classes), which have led to new biological insights.

An extensive map of human DNase I hypersensitive sites, markers of regulatory DNA, in 125 diverse cell and tissue types is described; integration of this information with other ENCODE-generated data sets identifies new relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns.

IL-10 exerts its anti-inflammatory activity in macrophages by increasing the expression of enzymes that promote fatty acid desaturation and downstream regulation of the transcription factor REL.

Molecular analyses of modern and fossil skeletal samples reveal that elevated metabolic rates consistent with endothermy evolved independently in mammals and plesiosaurs, and ornithodirans: Exceptional metabolic rates are ancestral to dinosaurs and pterosaurs and were acquired before energetically costly adaptations, such as flight.

In this Review, Crawford and Turocy examine diverse small molecule metabolites produced by the human microbiota, their role as potential risk factors for cancer development as well as novel mechanistic insights demonstrating their association with gastrointestinal cancer.

cBAF is a negative determinant of memory T cell fate and the manipulation of cBAF early in T cell differentiation can improve cancer immunotherapy.

Progressive diseases tend to be heterogeneous in their underlying aetiology mechanism, disease manifestation, and disease time course. Here, Young and colleagues devise a computational method to account for both phenotypic heterogeneity and temporal heterogeneity, and demonstrate it using two neurodegenerative disease cohorts.

Astroviruses are the leading cause of pediatric diarrhea, but which cells are the main targets in the gut remains unclear. Here, using an in vivo model of murine astrovirus, the authors show that the virus infects goblet cells and that this alters mucus production and increases mucus-associated bacterial communities in the gut.

CRISPR–Cas9 knockout screens in chemotherapy-treated acute myeloid leukemia cells help map the drug-dependent genetic basis of fitness trade-offs (antagonistic pleiotropy) for the design of evolutionary traps that target drug resistance in cancer.

In Alzheimer’s disease (AD) tau and neurodegeneration have complex regional relationships. Here, the authors show neuronal hypometabolism discordant with tau burden defines functional resilience or susceptibility to Alzheimer’s pathology via limbic/cortical axes. Susceptible groups have faster cognitive decline and evidence of non-Alzheimer’s pathologies.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

The transduction of mechanical forces into signals that alter cardiac contractility is important for heart function. Here the authors show that integrin-linked kinase acts as a mechanosensor in cardiomyocytes, and affects cardiac contractility by regulating SERCA-2a and phospholamban.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

Metagenomic sequencing, bioinformatic analysis and heterologous expression of an orphan biosynthetic gene cluster widely found in the environment led to the discovery and structural characterization of a novel group of calcium-dependent antibiotics hidden in plain sight.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Identifying the genes responsible for each step of a natural product biosynthesis has allowed the synthesis to be 'hijacked' to make bioactive compounds, and reveals that some suspected transporter enzymes could have other important roles in fungal defence systems.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Neuroendocrine differentiation of epithelial tumor cells can contribute to cancer cell resistance and survival. Here, the authors show that dysregulated c-Myc promotes neuroendocrine differentiation in pancreatic ductal adenocarcinoma, leading to poor survival and chemoresistance.

The next step after sequencing a genome is to figure out how the cell actually uses it as an instruction manual. A large international consortium has examined 1% of the genome for what part is transcribed, where proteins are bound, what the chromatin structure looks like, and how the sequence compares to that of other organisms.

Thomas and colleagues describe how multiple SARS-CoV-2 antigen exposures, including mRNA vaccine boosters, primary infection and breakthrough infection, shape T cell immunity.

Subinhibitory levels of sulfamethoxazole, an antibiotic used to treat Escherichia coli infections, trigger a previously undescribed metabolic pathway in E. coli that comprises a family of hybrid pterin–phenylpyruvate conjugates called colipterins. These metabolites are antioxidants, have immunomodulatory properties and improve colitis in a murine model.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

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.

Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

Tau accumulation is associated with disease progression in Alzheimer’s disease. Here the authors use resting state fMRI and tau-PET to demonstrate that baseline connectivity in Alzheimer's disease is associated with tau spreading.

The great structural diversity of polyketide natural products stems from their mode of synthesis by polyketide synthases. Crawford and Townsend review the latest progress in our understanding of the mode of action of fungal polyketide synthases, including starter unit selection, chain length control and cyclization specificity.

The interplay between amyloid and tau pathology in Alzheimer’s disease is still not well understood. Here, the authors show that amyloid-related increased in soluble p-tau is related to subsequent accumulation of tau aggregates and cognitive decline in early stage of the disease.