Biological sciences articles within Nature Communications

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  • Article
    | Open Access

    Paediatric therapy-related myeloid neoplasms (tMN) have a dismal prognosis and have not been comprehensively profiled. Here the authors characterise the molecular landscape of 84 paediatric tMN patients, and find that, unlike adult tMNs, these do not emerge from pre-existing clones and that MECOM dysregulation is frequent.

    • Jason R. Schwartz
    • , Jing Ma
    •  & Jeffery M. Klco

  • Article
    | Open Access

    The arginine methyltransferase PRMT5 is over-expressed in cancer and has a role in the maintenance of stem cells. Here, the authors show that PRMT5 inhibitors can block the growth of patient derived glioblastoma stem cell cultures in vitro and in vivo, suggesting that PRMT5 inhibition may be a useful therapeutic strategy

    • Patty Sachamitr
    • , Jolene C. Ho
    •  & Peter B. Dirks

  • Article
    | Open Access

    Nematode P granules are cytoplasmic RNA–protein biomolecule condensates central to germ cell development. Here the authors show that dimerization of the PGL-1 scaffolding protein is crucial to granule formation and mRNA repression, and that the WAGO-1 Argonaute protein is a cofactor in repressing PGL-1 bound mRNAs.

    • Scott Takeo Aoki
    • , Tina R. Lynch
    •  & Judith Kimble

  • Article
    | Open Access

    The transcriptional adaptation processes of harmful self-reactive CD8+ T cells in the central nervous system are not well understood. Here the authors use a system in which self-reactive and virally generated CD8+ T cells are directly compared in vivo and demonstrate that TOX expression contributes to maintenance of auto-reactive CD8+ T cells through alteration of chromatin accessibility.

    • Nicolas Page
    • , Sylvain Lemeille
    •  & Doron Merkler

  • Article
    | Open Access

    While genetic loci shared between cancer types have been identified, cross-cancer relationships for polygenic risk scores have not been well studied. Here, the authors have developed polygenic risk scores for 16 cancers in two large cohorts and identified positive and inverse cross-cancer associations.

    • Rebecca E. Graff
    • , Taylor B. Cavazos
    •  & Lori C. Sakoda

  • Article
    | Open Access

    While size exaggeration is common in the animal kingdom, Pisanski & Reby show that human listeners can detect deceptive vocal signals of people trying to sound bigger or smaller, and recalibrate their estimates accordingly, especially men judging the heights of other men, with implications for the evolution of vocal communication.

    • Katarzyna Pisanski
    •  & David Reby

  • Article
    | Open Access

    Epigallocatechin gallate (EGCG) is a catechin flavonoid which induces apoptosis in cancerous cells, but the underlying molecular mechanisms remain poorly understood. Here authors use an interdisciplinary approach to show a direct interaction between EGCG and the tumor suppressor p53 and demonstrate that EGCG inhibits ubiquitination of p53 by MDM2.

    • Jing Zhao
    • , Alan Blayney
    •  & Chunyu Wang

  • Article
    | Open Access

    Here Arndt et al. establish rotating-crystal magneto-optical detection (RMOD) as a near-point-of-care diagnostic tool for malaria detection and report a sensitivity and specificity of 82% and 84%, respectively, as validated by analyzing a clinical population in a high transmission setting in Papua New Guinea.

    • L. Arndt
    • , T. Koleala
    •  & S. Karl

  • Article
    | Open Access

    Colibactin-producing pks+ Escherichia coli are frequent constituents of the human intestinal microbiota. Here, the authors show that short exposure of cells to pks+ E. coli induces chromosomal aberrations, genomic instability, and multiple features of transformation reminiscent of colorectal cancer.

    • Amina Iftekhar
    • , Hilmar Berger
    •  & Thomas F. Meyer

  • Article
    | Open Access

    The viral Protein Kinase-1 (PK-1) phosphorylates the regulatory protein p6.9, which facilitates baculoviral genome release. Here, the authors combine X-ray crystallography with biophysical and biochemical analyses as well as molecular dynamics simulations to characterize Cydia pomenella granulovirus PK-1, which forms a dimer with a parallel side-to-side arrangement of the kinase domains and furthermore, they provide insights into its catalytic mechanism and evolutionary relationships with other kinases.

    • Michael R. Oliver
    • , Christopher R. Horne
    •  & James M. Murphy

  • Article
    | Open Access

    Structures of mu-opioid receptor (mOR) in complex with morphine derivatives have been determined; but the structural basis of mOR activation by fentanyl-like synthetic opioids remains unclear. Here, authors use state-of-the-art simulation techniques and discover a secondary binding mode which is only accessible when the conserved His297 adopts a neutral HID tautomer state.

    • Quynh N. Vo
    • , Paween Mahinthichaichan
    •  & Christopher R. Ellis

  • Article
    | Open Access

    The genomic details of adaptation to extreme environments remain challenging to characterize. Using new methods to analyze flies experimentally evolved to survive extreme O2 conditions, the authors find a surprising level of synchronicity in selective sweeps, de novo mutations and adaptive recombination events.

    • Arya Iranmehr
    • , Tsering Stobdan
    •  & Gabriel G. Haddad

  • Article
    | Open Access

    Whether the perivascular niche (PVN) and the integration into multicellular networks by tumor microtubes (TMs) have a different role in glioblastoma progression and resistance to therapies is currently unclear. Here, the authors, by long-term tracking of individual glioma, demonstrate that both niches can partially compensate for each other and that glioma cells localized in both niches are resistant to radio- and chemotherapy.

    • Erik Jung
    • , Matthias Osswald
    •  & Frank Winkler

  • Article
    | Open Access

    Systemic AA amyloidosis is a protein misfolding disease caused by the formation of amyloid fibrils from serum amyloid A (SAA) protein. Here, the authors present the cryo-EM structures of AA amyloid fibrils isolated from mouse tissue and in vitro formed fibrils, which differ in their structures and they also show that the ex vivo fibrils are more resistant to proteolysis than the in vitro fibrils and propose that pathogenic amyloid fibrils might originate from proteolytic selection.

    • Akanksha Bansal
    • , Matthias Schmidt
    •  & Marcus Fändrich

  • Article
    | Open Access

    Diffuse intrinsic pontine glioma (DIPG) is an almost incurable malignant childhood brain tumor. Here, the authors show that the polyamine synthetic pathway is activated in DIPG and that the dual targeting of polyamine synthesis and uptake results in prolonged survival in animal models.

    • Aaminah Khan
    • , Laura D. Gamble
    •  & David S. Ziegler

  • Article
    | Open Access

    New Zealand has been relatively successful in controlling COVID-19 due to implementation of strict non-pharmaceutical interventions. Here, the authors demonstrate a striking decline in reports of influenza and other non-influenza respiratory pathogens over winter months in which the interventions have been in place.

    • Q. Sue Huang
    • , Tim Wood
    •  & Richard J. Webby

  • Review Article
    | Open Access

    Hypertension is one of the most important risk factors for cardiovascular disease. The kidneys, which have a very high metabolic rate, play a fundamental role in blood pressure regulation. In this review, the authors discuss recent studies on the role of renal metabolism in the development of hypertension.

    • Zhongmin Tian
    •  & Mingyu Liang

  • Article
    | Open Access

    Coiled-coil protein origami is a strategy for the de novo design of polypeptide nanostructures based on coiled-coil dimer forming peptides, where a single chain protein folds into a polyhedral cage. Here, the authors design a single-chain triangular bipyramid and also demonstrate that the bipyramid can be self-assembled as a heterodimeric complex, comprising pre-defined subunits.

    • Fabio Lapenta
    • , Jana Aupič
    •  & Roman Jerala

  • Article
    | Open Access

    Accurately predicting the secondary structure of non-coding RNAs can help unravel their function. Here the authors propose a method integrating thermodynamic information and deep learning to improve the robustness of RNA secondary structure prediction compared to several existing algorithms.

    • Kengo Sato
    • , Manato Akiyama
    •  & Yasubumi Sakakibara

  • Article
    | Open Access

    The Hsp70/Hsp40 system plays an important role in maintaining cellular proteostasis but so far it is not well understood how Hsp70 proteins are recruited to specific Hsp40 co-chaperones. Here, the authors combine biochemical and biophysical approaches to characterise the oligomeric mammalian Hsp40 DnaJB8. They identify an intra-oligomer DnaJB8 interaction between the N-terminal J-Domain and the C-terminal domain that occludes the J-Domain surface that binds Hsp70 and propose a model for DnaJB8-Hsp70 recruitment.

    • Bryan D. Ryder
    • , Irina Matlahov
    •  & Lukasz A. Joachimiak

  • Article
    | Open Access

    Coiled-coil protein origami (CCPO) is a strategy for the design of polyhedral cage-shaped protein folds based on coiled-coil (CC) dimer-forming peptides. Here, the authors show that CCPO proteins fold in a multistep process governed by the spatial distance between CC modules in the primary sequence and subsequent folding intermediates, which enables the use of identical CC modules for the CCPO tetrahedron design.

    • Jana Aupič
    • , Žiga Strmšek
    •  & Roman Jerala

  • Article
    | Open Access

    Germ-free mosquitoes generated with current methods exhibit developmental deficits. Here, the authors use genetically modified bacteria to allow complete decolonisation at any developmental stage of Aedes aegypti mosquitoes and show that bacteria support larval development by contributing to folate biosynthesis and enhancing energy storage.

    • Ottavia Romoli
    • , Johan Claes Schönbeck
    •  & Mathilde Gendrin

  • Article
    | Open Access

    Winter wheat cultivar Forno harbors a race-specific leaf rust resistance locus Lr14a, but the causative gene is unknown. Here, the authors show that Lr14a encodes a membrane-localized protein containing ankyrin repeats and Lr14a-containing segments have been introgressed into the bread wheat gene pool multiple times.

    • Markus C. Kolodziej
    • , Jyoti Singla
    •  & Beat Keller

  • Article
    | Open Access

    Aspartate transcarbamoylase acts in de novo pyrimidine biosynthesis and in plants is regulated by feedback inhibition via uridine 5-monophosphate (UMP). Here Bellin et al. describe the structural basis for this feedback inhibition, showing that UMP blocks the active site by binding to a plant specific UMP recognition loop.

    • Leo Bellin
    • , Francisco Del Caño-Ochoa
    •  & Santiago Ramón-Maiques

  • Article
    | Open Access

    AtACINUS is an Arabidopsis homolog of a mammalian splicing regulator and previously found to be O-GlcNAcyated. Here Bi et al. characterize the interactors and targets of AtACINUS, show it is required for development and stress responses and provide evidence that its O-glycosylation affects alternative splicing.

    • Yang Bi
    • , Zhiping Deng
    •  & Zhi-Yong Wang

  • Article
    | Open Access

    Spindlin1 is an epigenetic reader that facilitates ribosomal RNA transcription. Here the authors reveal in vitro and structural evidence suggesting that Spindlin1 acts together with C11orf84 to recognize noncanonical bivalent mark of trimethylated lysine 4 and lysine 9 present on histone H3 tail (H3K4me3K9me3).

    • Yongming Du
    • , Yinxia Yan
    •  & Chengmin Qian

  • Article
    | Open Access

    Metabolites are indicators of health and disease; genetic studies can reveal variants influencing their levels. Here, the authors investigate the contribution of rare, exonic variants on the levels of urine metabolites and generate predictions on metabolic consequences underlying metabolic disease.

    • Yurong Cheng
    • , Pascal Schlosser
    •  & Anna Köttgen

  • Article
    | Open Access

    Here, using the K18-hACE2 transgenic mice model, the authors report the in vivo efficacy of a fully human neutralizing antibody against SARS-CoV-2 and show that when administered before or up to 3 days post infection, treated mice do not exhibit disease symptoms while 80% of control animals succumb to the infection.

    • Ronit Rosenfeld
    • , Tal Noy-Porat
    •  & Ohad Mazor

  • Article
    | Open Access

    The SARS-CoV-2 spike protein contains a multi-basic cleavage site. Here, the authors show how this multi-basic cleavage site affects entry of SARS-CoV-2 into cells and transmission in the hamster model and identify host factors affecting entry of SARS-CoV-2 in a genome-wide CRISPR screen.

    • Yunkai Zhu
    • , Fei Feng
    •  & Rong Zhang

  • Article
    | Open Access

    Mapping free energy landscapes of complex multi-funneled metamorphic proteins and weakly-funneled intrinsically disordered proteins (IDPs) remains challenging. Here authors present a parallel-tempering method that takes advantage of accelerated water dynamics for efficient and accurate conformational sampling across a wide variety of proteins.

    • Rajeswari Appadurai
    • , Jayashree Nagesh
    •  & Anand Srivastava

  • Article
    | Open Access

    Single-molecule fluorescence currently requires specialized imaging equipment due to the low signal of a single emitter. Here the authors introduce NanoAntennas with Cleared HOtSpots (NACHOS) to boost the signal sufficient for detection of a single emitter by a smartphone, opening the door to point-of-care applications.

    • Kateryna Trofymchuk
    • , Viktorija Glembockyte
    •  & Philip Tinnefeld

  • Article
    | Open Access

    The deglaciation of Marinoan snowball Earth (~635 Myr ago) has been associated with potentially extensive CH4 emissions in relation to transient marine euxinia. Here, the authors find that active methanogenesis occurred during the termination of Marinoan snowball Earth, fueled by methyl sulfide production in sulfidic seawater.

    • Zhouqiao Zhao
    • , Bing Shen
    •  & Haoran Ma

  • Article
    | Open Access

    Autoimmune Addison’s disease is a rare complex disease, which has not yet been characterized by non-biased genetic studies. Here, the authors perform the first GWAS for the disease, identifying nine loci including two coding variants in the gene Autoimmune Regulator (AIRE).

    • Daniel Eriksson
    • , Ellen Christine Røyrvik
    •  & Eystein Sverre Husebye

  • Article
    | Open Access

    During the early phase of the COVID-19 pandemic there was a need for rapid dissemination of clinical findings. Here, Jung, Di Santo et al. perform a systematic review and cohort study providing evidence for lower methodological quality scores and faster time to publication of clinical studies related to COVID-19 than comparable studies.

    • Richard G. Jung
    • , Pietro Di Santo
    •  & Benjamin Hibbert

  • Article
    | Open Access

    Patch clamp recording of neurons is slow and labor-intensive. Here the authors present a method for automated deep learning driven label-free image guided patch clamp physiology to perform measurements on hundreds of human and rodent neurons.

    • Krisztian Koos
    • , Gáspár Oláh
    •  & Peter Horvath

  • Article
    | Open Access

    Hundreds of BRAF mutations have been identified in patients with cancer but currently approved drugs only target BRAF V600 mutants. Here, the authors develop a vemurafenib-based PROTAC that induces degradation of all classes of BRAF mutants without affecting wild-type RAF proteins.

    • Shanique Alabi
    • , Saul Jaime-Figueroa
    •  & Craig M. Crews

  • Article
    | Open Access

    Respiratory chains generate the proton motive force used for ATP synthesis. Cryo-EM structures of functional respiratory CIII2CIV supercomplex and native CIII2 from Rhodobacter capsulatus provide insight into CIII2CIV assembly and respiratory electron transport pathways in Gram-negative bacteria.

    • Stefan Steimle
    • , Trevor van Eeuwen
    •  & Fevzi Daldal

  • Review Article
    | Open Access

    The gastrointestinal tract participates in maintaining metabolic homeostasis in part through nutrient-sensing and subsequent gut-brain signalling. Here the authors review the role of small intestinal nutrient-sensing in regulation of energy intake and systemic glucose metabolism, and link high-fat diet, obesity and diabetes with perturbations in these pathways.

    • Frank A. Duca
    • , T. M. Zaved Waise
    •  & Tony K. T. Lam

  • Article
    | Open Access

    ORAI3 is part of pore forming calcium channels involved in T cell activation. Here the authors show that there is increased expression of ORAI3 in T cells from patients with rheumatoid arthritis and that the transcription factor IKAROS negatively regulates the ORAI3 promoter, indicating a regulatory loop that can control auto-reactivity of T cells in these patients.

    • Zhongde Ye
    • , Yi Shen
    •  & Jörg J. Goronzy

  • Article
    | Open Access

    A recent report suggested Black men with prostate cancer were more responsive to immunotherapy. Here, the authors analysed prostate cancer gene expression profiles and show tumours from Black men and men with African ancestry have an increased proportion of plasma cells compared to those of White men and this correlates with improved outcome following treatment.

    • Adam B. Weiner
    • , Thiago Vidotto
    •  & Edward M. Schaeffer

  • Article
    | Open Access

    B class AP3/PI and AGL6-like MADS proteins determine lips and sepals/petals identities in orchids. Here, the authors characterize the extended function of OAP3/OPI/OAGL6 in regulating the specific structure of the lateral sepals, pigmentation/senescence of the perianth and abscission of the pedicel.

    • Hsing-Fun Hsu
    • , Wei-Han Chen
    •  & Chang-Hsien Yang

  • Article
    | Open Access

    An important type of post-translational protein modification is the conversion of peptidyl amino acid into enzyme cofactor. Here, the authors report functional and structural characterization of a flavoprotein monooxygenase essential for biosynthesis of cysteine tryptophylquinone (CTQ) cofactor.

    • Toshinori Oozeki
    • , Tadashi Nakai
    •  & Toshihide Okajima

  • Article
    | Open Access

    Single-molecule localisation microscopy is limited by low labeling and detection efficiencies of the molecular probes. Here the authors report a framework to obtain absolute molecular quantities on a true molecular scale; the data reveal a ternary adhesion complex underlying cell-matrix adhesion.

    • Lisa S. Fischer
    • , Christoph Klingner
    •  & Carsten Grashoff

  • Article
    | Open Access

    Caveolae are spherical nanodomains of the plasma membrane generated by assembly of caveolin and cavin proteins. Here, the authors show that fuzzy electrostatic interactions between caveolin-1 and Cavin1 proteins, combined with membrane lipid interactions, are required to generate membrane curvature and a metastable caveola coat.

    • Vikas A. Tillu
    • , James Rae
    •  & Brett M. Collins

  • Article
    | Open Access

    The genetic basis of daytime napping and the directional effect of daytime napping on cardiometabolic health are unknown. Here, the authors perform a genome-wide association study on self-reported daytime napping in the UK Biobank and Mendelian randomization to explore causal associations.

    • Hassan S. Dashti
    • , Iyas Daghlas
    •  & Richa Saxena

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