Biological sciences

  • Article
    | Open Access

    Actin-based structures in cells and tissues are built and maintained through a poorly understood balance between assembly and disassembly. Here, our findings provide insights into how factors known to promote these opposing effects dynamically integrate to shape cells and tissue systems.

    • Elena E. Grintsevich
    • , Giasuddin Ahmed
    •  & Jonathan R. Terman
  • Article
    | Open Access

    Replicative hexameric helicases are fundamental components of replisomes. Here the authors resolve a cryo-EM structure of the E1 helicase from papillomavirus bound to a DNA replication fork, providing insights into the mechanism of DNA unwinding by these hexameric enzymes.

    • Abid Javed
    • , Balazs Major
    •  & Elena V. Orlova
  • Article
    | Open Access

    Here, Shaban et al. show that coronaviruses modulate ER stress and the unfolded protein response. The ER stress inducer thapsigargin exerts potent antiviral effects, partially reverses the virus-induced translational shut-down, reprograms the host proteome and suppresses autophagic flux, thereby inhibiting coronavirus replication at multiple levels.

    • Mohammed Samer Shaban
    • , Christin Müller
    •  & Michael Kracht
  • Article
    | Open Access

    A strategy to control HIV-1 infection is to stably repress HIV-1 and induce “deep latency”. Here the authors show that a recombinant anti-HIV-1-1 protein can be packaged as mRNA into exosomes and delivered systemically to repress HIV-1-1 within the context of virus infected mice and achieve long term silencing of HIV-1-1 expression.

    • Surya Shrivastava
    • , Roslyn M. Ray
    •  & Kevin V. Morris
  • Article
    | Open Access

    While hepatoblastoma is the most common pediatric liver cancer, its molecular background has not been fully characterised. Here, the authors perform genomic and epigenomic profiling of 163 untreated pediatric liver tumours and suggest the upregulation of ASCL2 and methylation patterns of IGF2 promoters in driving hepatoblast carcinogenesis.

    • Genta Nagae
    • , Shogo Yamamoto
    •  & Eiso Hiyama
  • Article
    | Open Access

    The high dimensional and complex nature of mass spectrometry imaging (MSI) data poses challenges to downstream analyses. Here the authors show an application of artificial intelligence in mining MSI data revealing biologically relevant metabolomic and proteomic information from data acquired on different mass spectrometry platforms.

    • Walid M. Abdelmoula
    • , Begona Gimenez-Cassina Lopez
    •  & Nathalie Y. R. Agar
  • Article
    | Open Access

    Nail-patella syndrome (NPS) is characterized by nail dysplasia, absent/hypoplastic patellae, chronic kidney disease, and glaucoma and can be caused by haploinsufficiency of LMX1B; however, not all patients harbor pathogenic LMX1B mutations. Here the authors show that loss-of-function variations in upstream enhancer sequences are responsible for a limb specific form of human NPS.

    • Endika Haro
    • , Florence Petit
    •  & Kerby C. Oberg
  • Article
    | Open Access

    Distinct brain regions are claimed to respond selectively to faces, places and bodies, but what counts as a face, place or body is less well defined. Here we build computational models that accurately predict the response of these regions to novel images, enabling stronger tests and confirmation of their selectivity.

    • N. Apurva Ratan Murty
    • , Pouya Bashivan
    •  & Nancy Kanwisher
  • Article
    | Open Access

    Here, Kodama et al. describe the discovery, isolation and characterization of a novel tick-borne orthonairovirus, designated Yezo virus (YEZV), from patients with an acute febrile illness in Japan. Serological testing of wildlife and molecular screening of ticks suggest an endemic circulation of YEZV in Japan.

    • Fumihiro Kodama
    • , Hiroki Yamaguchi
    •  & Keita Matsuno
  • Article
    | Open Access

    m6Am is a modification of the 5′ end of mRNAs catalyzed by PCIF1. Here, Zhang et al. show that HIV infection induces a decrease in m6Am of cellular mRNAs through Vpr-mediated PCIF1 ubiquitination and degradation, resulting in increased HIV replication through regulation of host transcription factors.

    • Qiong Zhang
    • , Yuqi Kang
    •  & Tariq M. Rana
  • Article
    | Open Access

    Scalable trajectory inference for multi-omic single cell datasets is challenging in terms of capturing non-tree complex topologies. Here the authors present a method, VIA, that scales to millions of cells across multiple omic modalities using lazy-teleporting random walks.

    • Shobana V. Stassen
    • , Gwinky G. K. Yip
    •  & Kevin K. Tsia
  • Article
    | Open Access

    Isopropenyl ethers (IPPEs) are essential intermediates for obtaining ketal-based prodrugs and biomaterials, but traditional approaches for their synthesis are limited by poor functional group compatibility and harsh reaction conditions. Here, the authors report an organocatalytic transisopropenylation approach for IPPE synthesis in mild reaction conditions and with wide range of substrates, and use it to prepare acid-sensitive ketal-linked prodrugs and biomaterials.

    • Na Yu
    • , Yang Xu
    •  & Shutao Guo
  • Article
    | Open Access

    Radiation-induced high-grade gliomas (RIGs) are an incurable late complication of cranial radiation therapy. In the largest study to date, we report the results of DNA methylation profiling, RNA-Seq and genomic sequencing of 32 RIG tumors, and an in vitro drug screen in two RIG cell lines.

    • John DeSisto
    • , John T. Lucas Jr.
    •  & Adam L. Green
  • Article
    | Open Access

    Rapid identification of host genes essential for virus replication may expedite the generation of therapeutic interventions. Here the authors generate mutant clonal intestinal organoids for 19 host genes previously implicated in coronavirus biology and identify the cell surface protease TMPRSS2 as a potential therapeutic target.

    • Joep Beumer
    • , Maarten H. Geurts
    •  & Hans Clevers
  • Article
    | Open Access

    Understanding the structural basis for the inhibition of archaeal eukaryotic-like RNA polymerases (RNAPs) during virus infection is of interest for drug design. Here, the authors present the cryo-EM structures of apo Sulfolobus acidocaldarius RNAP and the RNAP complex structures with two regulatory factors, RIP and TFS4 that inhibit transcription and discuss their inhibitory mechanisms.

    • Simona Pilotto
    • , Thomas Fouqueau
    •  & Finn Werner
  • Article
    | Open Access

    Drug and target discovery for advanced liver disease are hampered by a lack of suitable models for clinical translation. Here the authors present a human liver cell-based system modeling a clinical prognostic signature allowing to propose nizatidine for treatment of advanced liver fibrosis and hepatocellular carcinoma prevention.

    • Emilie Crouchet
    • , Simonetta Bandiera
    •  & Thomas F. Baumert
  • Article
    | Open Access

    Transcription in archaea is known to be regulated through the recruitment of RNA polymerase to promoters. Here, the authors show that the archaeon Saccharolobus solfataricus regulates transcription globally through a rate-limiting promoter-proximal elongation step.

    • Fabian Blombach
    • , Thomas Fouqueau
    •  & Finn Werner
  • Article
    | Open Access

    Perilla is a young allotetraploid species within the mint family Lamiaceae. Here, the authors assemble the genomes of a tetraploid species and its diploid progenitor, characterize the incipient diploidization of the tetraploid, conduct population genetics analyses, and identify loci associate with pigmentation and oil content.

    • Yujun Zhang
    • , Qi Shen
    •  & Shilin Chen
  • Article
    | Open Access

    Fibrotic scar tissue limits central nervous system regeneration. Here, Dias et al. show that fibrotic scarring is common in mice and humans, following distinct lesions to the adult brain and spinal cord, and derives from a discrete population of GLAST-expressing perivascular cells.

    • David O. Dias
    • , Jannis Kalkitsas
    •  & Christian Göritz
  • Article
    | Open Access

    Here, the authors present a hierarchical disorder model for the analysis of disorder in both crystal and cryo-EM structures. They apply their approach to several structures of three proteins, including SARS-CoV-2 proteins, and discuss mechanistic and dynamical implications.

    • Nicholas M. Pearce
    •  & Piet Gros
  • Article
    | Open Access

    Here, cryo-EM reconstructions of human cytomegalovirus (HCMV) virions reveal host tRNAs associated with the virion’s capsid-bound tegument protein, pp150. tRNA recruitment is mediated by the interactions specific for HCMV only, suggesting the explanation for the absence of such tRNA densities in related herpesviruses.

    • Yun-Tao Liu
    • , David Strugatsky
    •  & Z. Hong Zhou
  • Article
    | Open Access

    Faster, higher throughput antibody engineering methods are needed. Here the authors present CeVICA, a cell-free nanobody engineering platform using ribosome display and computational clustering analysis for in vitro selection; they use this to develop nanobodies against the RBD of SARS-CoV-2 spike protein.

    • Xun Chen
    • , Matteo Gentili
    •  & Aviv Regev
  • Article
    | Open Access

    Post transcriptional modifications to RNA may be important in the function of NK cells but this is not fully known. Here the authors show that m6A-methyltransferase METTL3 deletion in NK cells leads to reduced function and protection against tumour challenge through suppressing response to IL-15.

    • Hao Song
    • , Jiaxi Song
    •  & Zhigang Tian
  • Article
    | Open Access

    Harmful algal and bacterial blooms are increasingly frequent in lakes and rivers. From the Sydney Basin, Australia, this study uses fossil, sedimentary and geochemical data to reveal bloom events following forest ecosystem collapse during the end-Permian event and that blooms have consistently followed warming-related extinction events, inhibiting the recovery of freshwater ecosystems for millennia.

    • Chris Mays
    • , Stephen McLoughlin
    •  & Vivi Vajda
  • Article
    | Open Access

    Peptide signals generated during plant microbe interactions can trigger immune responses in plants. Here the authors show that SCOOP12, a member of a family of peptides present in Brassicaceae plants, and SCOOP12-like motifs in Fusarium fungi, can trigger immune responses following perception by the MIK2 receptor kinase.

    • Shuguo Hou
    • , Derui Liu
    •  & Ping He
  • Article
    | Open Access

    Soluble guanylate cyclase (sGC) is a validated drug target for cardiovascular diseases. Here, the authors report structures of human sGC in complex with NO and sGC stimulators or activator, providing insight into the mechanism of sGC activation by pharmacological compounds.

    • Rui Liu
    • , Yunlu Kang
    •  & Lei Chen
  • Article
    | Open Access

    Comparing changes in behaviour across various species is not always trivial, especial across significantly divergent species. Here, the authors develop a deep learning framework that allows them to map changes in locomotion demonstrated on dopamine-deficient humans, mice and worms.

    • Takuya Maekawa
    • , Daiki Higashide
    •  & Susumu Takahashi
  • Article
    | Open Access

    Kinase inhibitors are widely used to treat cancer, however patients frequently develop resistance. Here, the authors investigate adaption mechanisms during drug persistence and show that stimulation of the innate immunity sensor RIG-I enhances cancer cell death when combined with kinase inhibition.

    • Johannes Brägelmann
    • , Carina Lorenz
    •  & Martin L. Sos
  • Article
    | Open Access

    The ever-growing need for highly functional, compact, and integrated microfluidic devices often incurs lengthy and expensive manufacturing processes. Here, authors introduce a generalized 3D printing process that enables fast parallel fabrication of miniaturized, high resolution 3D components.

    • Jose L. Sanchez Noriega
    • , Nicholas A. Chartrand
    •  & Gregory P. Nordin
  • Article
    | Open Access

    Ribonucleoprotein (RNP) granules are responsible for mRNA transport and local translation required for neuronal and oocyte maturation. Here the authors show that loss of the Drosophila Ub ligase Hecw enlarges RNP granules, leads to a liquid to gel-like transition, and results in defective oogenesis and neuronal loss.

    • Valentina Fajner
    • , Fabio Giavazzi
    •  & Simona Polo
  • Article
    | Open Access

    Evolutionary arms races can drive adaptations in hosts and parasites as well as among competing parasites. A combination of multi-omics and functional tests identifies a set of genes that allow a parasitic wasp to minimize intraspecific competition by inducing hosts to escape before more wasps can parasitize them.

    • Jiani Chen
    • , Gangqi Fang
    •  & Jianhua Huang
  • Article
    | Open Access

    The authors show that post-transcriptional regulation of the cilia-driven leftward flow target dand5 is central to symmetry breakage in frog, fish and mouse and is mediated by a 139 nt Bicc1 responsive element in the dand5 3′UTR, and they present evidence that Pkd2 regulates this Bicc1/dand5 module.

    • Markus Maerker
    • , Maike Getwan
    •  & Axel Schweickert
  • Article
    | Open Access

    Modular, rather than integrated systems are classically thought to allow functional diversity to evolve rapidly. A study of cichlid fish shows integration between divergent jaw systems at the phylogenetic, population, and genetic scales, suggesting integration can and does facilitate rapid, coordinated trait evolution.

    • Andrew J. Conith
    •  & R. Craig Albertson
  • Article
    | Open Access

    Implant infection is the most common mode of joint replacement failure with serious complications. Here, the authors report on the in vivo application of a prophylactic coating technology that can incorporate a range of antibiotics and be applied in the operating room prior to implantation.

    • Weixian Xi
    • , Vishal Hegde
    •  & Tatiana Segura
  • Article
    | Open Access

    XopC2 effectors are present in many plant bacterial pathogens. Here the authors show that XopC2 has kinase activity and enhances disease susceptibility by phosphorylating the OSK1 protein, which increases its interaction with the jasmonate receptor COI1b to promote JA signaling and stomatal opening.

    • Shanzhi Wang
    • , Shuai Li
    •  & Wenxian Sun
  • Article
    | Open Access

    Humans adapt decision strategies in response to environmental demands. Here the authors show that decisions in a virtual foraging task can be modelled based on perceived patch value, which includes reward, competition and threat, and is associated with activity in ventromedial prefrontal and medial cingulate cortices.

    • Brian Silston
    • , Toby Wise
    •  & Dean Mobbs
  • Article
    | Open Access

    Studying the role of predator–prey interactions in food-web stability and species coexistence in the environment is arduous. Here, Cohen et al. use a combination of community and single-cell analyses to show that bacterial predators can regulate prey populations in the species-rich environments of wastewater treatment plants.

    • Yossi Cohen
    • , Zohar Pasternak
    •  & Edouard Jurkevitch
  • Article
    | Open Access

    Latitudinal ecosystem boundaries in the global upper ocean may be driven by many factors. Here the authors investigate pole-to-pole eukaryotic phytoplankton metatranscriptomes, gene co-expression networks, and beta diversity, finding that geographic patterns are best explained by temperature gradients.

    • Kara Martin
    • , Katrin Schmidt
    •  & Thomas Mock
  • Article
    | Open Access

    Dual-energy X-ray absorptiometry and the Fracture Risk Assessment Tool are recommended tools for osteoporotic fracture risk evaluation, but are underutilized. Here, the authors present an opportunistic tool to identify fractures, predict bone mineral density and evaluate fracture risk using plain pelvis and lumbar spine radiographs.

    • Chen-I Hsieh
    • , Kang Zheng
    •  & Chang-Fu Kuo