Biological sciences articles within Nature Communications

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  • Article
    | Open Access

    Spy is an ATP independent chaperone that can act as both a holdase and a foldase towards topologically simple substrates. Assessing the interaction of Spy and apoflavodoxin, a complex client, the authors show that Spy’s activity is substrate specific. Spy binds partially unfolded states of apoflavodoxin tightly, which limits the possibility of folding and converts Spy to a pure holdase.

    • Rishav Mitra
    • , Varun V. Gadkari
    •  & James C. A. Bardwell

  • Article
    | Open Access

    Genomic prediction of phenotype may be improved by using DNA mutations with functional, evolutionary, and pleiotropic consequences. Here the authors describe a method for genome-wide fine-mapping of QTLs and develop a genotyping array for improved prediction of genetic values for cattle traits.

    • Ruidong Xiang
    • , Iona M. MacLeod
    •  & Michael E. Goddard

  • Article
    | Open Access

    Spread of SARS-CoV-2 in the early phase of the pandemic has been driven by high population susceptibility, but virus sensitivity to climate may play a role in future outbreaks. Here, the authors simulate SARS-CoV-2 dynamics in winter assuming climate dependence is similar to an endemic coronavirus strain.

    • Rachel E. Baker
    • , Wenchang Yang
    •  & Bryan T. Grenfell

  • Article
    | Open Access

    Phase response curves reveal how biological clocks respond to stimuli applied during different circadian phases but can be costly to produce. Here Masuda et al. show that phase response curves for plants can be reconstructed by monitoring how a desynchronized population responds to a single stimulus.

    • Kosaku Masuda
    • , Isao T. Tokuda
    •  & Hirokazu Fukuda

  • Article
    | Open Access

    Cancer cell clusters metastasize to distant organ by polyclonal manner. Here, the authors show that malignant subclone induces fibrotic niche generation in the liver by hepatic stellate cell activation, supporting survival and colonization of non-metastatic cells to develop polyclonal metastasis.

    • Sau Yee Kok
    • , Hiroko Oshima
    •  & Masanobu Oshima

  • Article
    | Open Access

    Biosynthesis of the statin precursor lovastatin depends on the LovB–LovC megasynthase complex. Here, the authors present cryoEM structures of LovB–LovC and core LovB, providing structural insights into the catalytic cycle underlying lovastatin production.

    • Jialiang Wang
    • , Jingdan Liang
    •  & Zhijun Wang

  • Article
    | Open Access

    Autocatalytic networks may have started evolution during the origin of life. Here, the authors establish a landscape of thousands of RNA networks by barcoded sequencing and microfluidics, and derive relationships between topology and Darwinian properties such as variation and differential reproduction.

    • Sandeep Ameta
    • , Simon Arsène
    •  & Philippe Nghe

  • Article
    | Open Access

    The conversion of auditory and vestibular stimuli into electrical signals is initiated by force transmitted to a mechanotransduction channel through the tip link. Here authors show that a single tip-link bond is more mechanically stable relative to classic cadherins, and that the double stranded tip-link connection is stabilized by single strand rebinding facilitated by strong cis-dimerization domains.

    • Eric M. Mulhall
    • , Andrew Ward
    •  & Wesley P. Wong

  • Article
    | Open Access

    Systemic AL amyloidosis is a protein misfolding disease caused by the aggregation and fibrillation of immunoglobulin light chains (LCs). Here, the authors present the cryo-EM structures of λ3 LC-derived amyloid fibrils that were isolated from patient tissue and they observe structural breaks, where the two different fibril structures co-exist at different z-axial positions within the same fibril.

    • Lynn Radamaker
    • , Julian Baur
    •  & Marcus Fändrich

  • Article
    | Open Access

    The spatial arrangement of bacterial strains and species within microbial communities is considered crucial for their ecology. Here, Krishna Kumar et al. use a droplet-based printing method to arrange different bacterial genotypes across a sub-millimetre array, and show that micron-scale changes in spatial distributions can drive major shifts in ecology.

    • Ravinash Krishna Kumar
    • , Thomas A. Meiller-Legrand
    •  & Kevin R. Foster

  • Article
    | Open Access

    Fluorescent protein reporters based on GFP exist, but have intrinsic disadvantages. Here the authors incorporate pH, Ca2+ and protein–protein interaction sensing modalities into de novo designed mini-fluorescence-activating proteins (mFAPs), with increased photostability and smaller size, which bind a range of DFHBI chromophore variants.

    • Jason C. Klima
    • , Lindsey A. Doyle
    •  & David Baker

  • Article
    | Open Access

    Enzalutamide, an approved drug for prostate cancer, acts on TMPRSS2 expression, a key mediator for SARS-CoV-2 infection. Here, the authors characterize the anti-SARS-CoV-2 effects of Enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and in hACE2-transduced Tmprss2 knockout mice and show lack antiviral action in human lung cells and human lung organoids, likely due to the AR-independent TMPRSS2 expression in mouse and human lung epithelial cells.

    • Fei Li
    • , Ming Han
    •  & Dong Gao

  • Article
    | Open Access

    C9orf72 expansion mutations are the most common genetic cause of ALS and FTD, which have limited therapies. The authors generate stereopure oligonucleotides that selectively deplete expansion-containing transcripts and protect against expansion-associated pathologies in preclinical models.

    • Yuanjing Liu
    • , Jean-Cosme Dodart
    •  & Robert H. Brown Jr.

  • Article
    | Open Access

    CD19-negative relapses are observed in patients with B-cell acute lymphoblastic leukemia (B-ALL) treated with anti-CD19 CAR-T cells. Here, by single-cell RNA sequencing of leukemic cells in a patient with B-ALL, the authors show that pre-existing CD19 negative leukemic subclones are present before CAR-T cell therapy and can account for the relapse.

    • Tracy Rabilloud
    • , Delphine Potier
    •  & Dominique Payet-Bornet

  • Article
    | Open Access

    Synthetic gene circuits may not function as expected due to the resource competition between modules. Here the authors build cascading bistable switches to achieve two successive cell fate transitions but found a ‘winner-takes-all’ behaviour, which is overcome by a division of labour strategy.

    • Rong Zhang
    • , Hanah Goetz
    •  & Xiao-Jun Tian

  • Article
    | Open Access

    The humoral immune response to SARS-CoV-2 infection is not yet fully understood. Here, Marot et al. monitor the longitudinal profile and neutralizing activity of IgG, IgA, and IgM among 26 healthcare workers and provide evidence for a short-lasting humoral immune protection due to a decrease of neutralizing antibody titers within 3 months.

    • Stéphane Marot
    • , Isabelle Malet
    •  & Anne-Geneviève Marcelin

  • Article
    | Open Access

    Synaptic vesicles store neurotransmitters and fuse with the pre-synaptic membrane when an action potential arrives at the nerve terminal. Here authors apply cross-linking mass spectrometry to study interactions of synaptic vesicle proteins and describe a protein network of vesicle sub-populations and functional assemblies.

    • Sabine Wittig
    • , Marcelo Ganzella
    •  & Carla Schmidt

  • Article
    | Open Access

    The beating heart adapts cardiac output to changes in mechanical load via incompletely understood mechanotransduction mechanisms. Here the authors show that the mechanosensitive Piezo1 channel serves as a mechanotransducer for directly converting mechanical stretch of cardiomyocytes into Ca2+ and ROS signaling and consequently maintaining normal heart function.

    • Fan Jiang
    • , Kunlun Yin
    •  & Bailong Xiao

  • Article
    | Open Access

    Liquid ribonucleoprotein condensates typically involve a dense network of multiple proteins and RNAs. Here, the authors employ a minimal system composed of Prion-like polypeptides (PLP), Arg-rich polypeptides (RRP), and RNA to form biphasic condensates with diverse morphologies tunable via mixture stoichiometry and hierarchy of intermolecular interactions.

    • Taranpreet Kaur
    • , Muralikrishna Raju
    •  & Priya R. Banerjee

  • Article
    | Open Access

    Understanding patient-specific pathobiological pathways is a critical step for advancing precision medicine. Here the authors show that individualized protein-protein interaction networks provide key insight on patient-level pathobiology and clinically relevant pathophenotypic characteristics in a complex disease.

    • Bradley A. Maron
    • , Rui-Sheng Wang
    •  & Joseph Loscalzo

  • Article
    | Open Access

    Sarcomatoid and rhabdoid tumours are highly aggressive forms of renal cell carcinoma that are also responsive to immunotherapy. In this study, the authors perform a comprehensive molecular characterization of these tumours discovering an enrichment of specific alterations and an inflamed phenotype.

    • Ziad Bakouny
    • , David A. Braun
    •  & Toni K. Choueiri

  • Article
    | Open Access

    Pathogenesis of steroid-resistant gut acute graft-versus-host-disease (SR-Gut-aGVHD) remains unclear., Here the authors show in mouse models that dysbiosis caused by the expansion of Th/Tc22, as well as depletion of CX3CR1hi mononuclear phagocytes resulted from the reduction of Th/Tc1, contributes to SR-Gut-aGVHD onset.

    • Qingxiao Song
    • , Xiaoning Wang
    •  & Defu Zeng

  • Article
    | Open Access

    It has been suggested that pangolin coronaviruses may be the origin of SARS-CoV-2. Here the authors show that the Pangolin-CoV spike is structurally closely related to the closed form of SARS-CoV-2 spike and exhibits similar binding properties to human and pangolin ACE2; although neither spike binds bat ACE2.

    • Antoni G. Wrobel
    • , Donald J. Benton
    •  & Steven J. Gamblin

  • Article
    | Open Access

    Ryanodine Receptors (RyRs) release Ca2+ from the endoplasmic and sarcoplasmic reticulum. Mutations in RyR are linked to malignant hyperthermia (MH), myopathies, and arrhythmias. Here, a collection of cryoEM structures provides insights into the molecular consequences of MHrelated RyR mutation R615C, and how apoCaM opens RyR1.

    • Kellie A. Woll
    • , Omid Haji-Ghassemi
    •  & Filip Van Petegem

  • Article
    | Open Access

    Dynamic regulation of colonic secretory cell numbers is a critical component of the response to intestinal injury and inflammation. Here, the authors show that loss of the intracellular signalling regulator Sprouty2 in the intestinal epithelial cells is a protective response to injury that leads to increased secretory cell numbers, thus limiting colitis severity.

    • Michael A. Schumacher
    • , Jonathan J. Hsieh
    •  & Mark R. Frey

  • Article
    | Open Access

    Carbon dots have attracted much attention for biomedical applications but potential degradation and associated toxicity are still poorly understood. Here, the authors report on a study into the photo-degradation of carbon dots, the products produced and associated cytotoxicity.

    • Yue-Yue Liu
    • , Nan-Yang Yu
    •  & Ai-Jun Miao

  • Article
    | Open Access

    The core FADD:Caspase-8 complex and its regulatory partners, such as the cell death inhibitor c-FLIP, coordinate cell fate. Here authors present the structure of full-length procaspase-8 in a complex with FADD and reveal how recruitment of c-FLIPS into this complex inhibits Caspase-8 activity.

    • Joanna L. Fox
    • , Michelle A. Hughes
    •  & Marion MacFarlane

  • Article
    | Open Access

    Soil organic matter (SOM) is a huge sink of carbon, but the varied flux dynamics are challenging to predict. Here, the authors present a new model with the complexities of SOM cycling, including parameters for substrate accessibility, microbe diversity, and enzymatic substrate depolymerization.

    • Julien Sainte-Marie
    • , Matthieu Barrandon
    •  & Delphine Derrien

  • Article
    | Open Access

    eIF5A is critical for protein synthesis but has not yet been associated with congenital human disease. Here, the authors show that EIF5A variants cause a Mendelian disorder via reduced eIF5A-ribosome interactions and this phenotype is partially corrected by spermidine supplementation in yeast and zebrafish.

    • Víctor Faundes
    • , Martin D. Jennings
    •  & Siddharth Banka

  • Article
    | Open Access

    p23 is a co-chaperone of Hsp90 but its mode of action is mechanistically not well understood. Here, the authors combine in vitro and yeast in vivo assays, biochemical measurements and NMR experiments to characterize p23 and identify two conserved helical elements in the intrinsically disordered C-terminal tail of p23 that together with the folded domain of p23 regulate the Hsp90 ATPase activity and affect the binding and maturation of Hsp90 clients.

    • Maximilian M. Biebl
    • , Abraham Lopez
    •  & Johannes Buchner

  • Article
    | Open Access

    In a newly fertilized egg, maternal and paternal chromosomes are enclosed in two separate pronuclei but the mechanisms in mammals for pronuclear movement are unclear. Here, the authors report that both F-actin and microtubule polymerization act in concern to drive inward movement of pronuclei towards the cell centre.

    • Kathleen Scheffler
    • , Julia Uraji
    •  & Melina Schuh

  • Article
    | Open Access

    The analysis of AMPA-type glutamate receptor (AMPAR) trafficking is essential for understanding molecular mechanisms of learning and memory, but the analytical tools are currently limited. Here, the authors report a method that combines affinity-based receptor labeling and bioorthogonal click chemistry to quantify AMPAR distribution and trafficking under physiological conditions.

    • Kento Ojima
    • , Kazuki Shiraiwa
    •  & Shigeki Kiyonaka

  • Article
    | Open Access

    In this single-arm clinical trial, the authors show that treatment of COVID-19 patients with bevacizumab, an anti-vascular endothelial growth factor drug, can improve PaO2/FiO2 ratios and oxygen-support status. Relative to an external control group, bevacizumab shows clinical efficacy by improving oxygenation.

    • Jiaojiao Pang
    • , Feng Xu
    •  & Yihai Cao

  • Article
    | Open Access

    Sharing early evidence, as a trial is ongoing, is fundamental for both physicians and patients to make enrollment decisions. Here, the authors report the results of a simulation study evaluating the potential effects of early release of interim efficacy and safety data on the duration and validity of an ongoing clinical trial and demonstrate that positive interim results may shorten trial duration through increased enrollment.

    • Steffen Ventz
    • , Sergio Bacallado
    •  & Lorenzo Trippa

  • Article
    | Open Access

    Serum liver enzymes are used as markers of liver disease, their concentration influenced in part by genetic factors. Here the authors meta-analyse genome-wide association studies on the UK Biobank and BioBank Japan to evaluate the association of three liver enzymes with liver and other metabolic diseases.

    • Vincent L. Chen
    • , Xiaomeng Du
    •  & Elizabeth K. Speliotes

  • Article
    | Open Access

    Currently the most common method of COVID-19 diagnosis is by qRT-PCR which is slow and requires expensive instrumentation. Here the authors report an electrochemical biosensor based on isothermal rolling circle amplification for rapid detection of SARS-CoV-2 in clinical samples.

    • Thanyarat Chaibun
    • , Jiratchaya Puenpa
    •  & Benchaporn Lertanantawong

  • Article
    | Open Access

    The binding of cytoplasmic Ca2+ to the anion-selective channel TMEM16A triggers a conformational change around its binding site that is coupled to the release of a gate at the constricted neck. Here authors use cryo-EM and electrophysiology to identify three hydrophobic residues at the intracellular entrance of the neck as constituents of this gate.

    • Andy K. M. Lam
    • , Jan Rheinberger
    •  & Raimund Dutzler

  • Article
    | Open Access

    Secondary ion beam mass spectrometry (SIMS) is a method to obtain a chemical snapshot of biological tissue, but the spatial resolution is low. Here, the authors develop a computational and technology pipeline to localise a chemical signal in SIMS in 3D and sub-25 nm accuracy, called Ion Beam Tomography

    • Ahmet F. Coskun
    • , Guojun Han
    •  & Garry P. Nolan

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