Biological sciences

  • Article
    | Open Access

    Met1-linked linear ubiquitination (M1-Ubi) is catalyzed by linear ubiquitin chain assembly complex (LUBAC). Here the authors show that Ago2 protein is M1-Ubi modified by LUBAC complex under hypoxia condition leading to less association of miRNA target mRNAs to Ago2 protein and de-repression of miRNA targets.

    • Hailong Zhang
    • , Xian Zhao
    •  & Jianxiu Yu
  • Article
    | Open Access

    Photoacoustic imaging is limited by a lack of contrast agents which can enable combined molecular and physiological imaging at depth. Here the authors address these limitations by developing and validating a contrast agent based on targeted liposomes loaded with J-aggregated indocyanine green dye.

    • Cayla A. Wood
    • , Sangheon Han
    •  & Richard R. Bouchard
  • Article
    | Open Access

    Epigenetic changes are implicated in Acute myeloid leukemia (AML) tumorigenesis. Here, the authors show that the ubiquitin ligase RNF5 and its substrate RBBP4 contribute to AML development by regulating epigenetic-controlled transcription which determines AML sensitivity to HDAC inhibitors.

    • Ali Khateb
    • , Anagha Deshpande
    •  & Ze’ev A. Ronai
  • Article
    | Open Access

    The identification of transcription factors (TFs) whose binding sites are affected by risk genetic variants remains crucial. Here, the authors develop a statistical framework to analyse ChIP-seq and GWAS data, identify 22 breast cancer risk-associated TFs and a core TF-transcriptional network for FOXA1 and co-factors.

    • Wanqing Wen
    • , Zhishan Chen
    •  & Xingyi Guo
  • Article
    | Open Access

    Understanding the molecular mechanisms underlying DNA methylation in cancer and its clinical relevance remains crucial. Here, the authors study RRBS-based profiles of 1538 breast tumours and 244 normal breast tissues from the METABRIC cohort and report epigenomic instability and cis-regulatory effects.

    • Rajbir Nath Batra
    • , Aviezer Lifshitz
    •  & Carlos Caldas
  • Article
    | Open Access

    Root-mycorrhizal interactions could help explain the heterogeneity of plant responses to CO2 fertilisation and nutrient availability. Here the authors combine tree-ring and metagenomic data to reveal that tree growth responses to increasing CO2 along a soil nutrient gradient depend on the nitrogen foraging traits of ectomycorrhizal fungi.

    • Peter T. Pellitier
    • , Inés Ibáñez
    •  & Kirk Acharya
  • Article
    | Open Access

    Activated sludge (AS) systems in wastewater treatment plants (WWTPs) contain high concentration of viruses. Here, the authors apply a systematic metagenomic pipeline and retrieve a catalogue of around 50,000 prokaryotic viruses from samples of six WWTPs, revealing a large and uncharacterized viral diversity in AS communities.

    • Yiqiang Chen
    • , Yulin Wang
    •  & Tong Zhang
  • Article
    | Open Access

    The SARS-CoV-2 Spike protein is essential for viral infectivity and binds to the host receptor ACE2. Here, the authors present MD simulations of the Spike protein and its variants of concern and observe that the Spike protein is destabilised by moderate static electric fields, and undergoes field-induced conformational changes that hinder binding to ACE2.

    • Claudia R. Arbeitman
    • , Pablo Rojas
    •  & Martin E. Garcia
  • Article
    | Open Access

    Metabolic alterations control the fate and function of immune cells in response to infections, but the function of NK cell metabolism in the context of acute viral infections is unclear. Here the authors show that acute NK cell responses to Friend retrovirus involve increased glycolysis and mitochondrial metabolism and require amino acid transport as well as iron sufficiency.

    • Elisabeth Littwitz-Salomon
    • , Diana Moreira
    •  & David K. Finlay
  • Article
    | Open Access

    RAD51 is a well known player of DNA repair and homologous recombination. Here the authors reveal a function for RAD51 in protecting under-replicated DNA in mitotic human cells, promoting mitotic DNA synthesis (MiDAS) and successful chromosome segregation.

    • Isabel E. Wassing
    • , Emily Graham
    •  & Fumiko Esashi
  • Article
    | Open Access

    Human metaplastic breast cancers (MpBC) are a rare, aggressive subclass of triple-negative breast cancers. Here, the authors show over-expression of histone reader TRIM24 is sufficient to generate tumors with a molecular signature of metabolic dysfunction and EMT in a mouse model of human MpBC.

    • Vrutant V. Shah
    • , Aundrietta D. Duncan
    •  & Michelle Craig Barton
  • Article
    | Open Access

    Trends in antimicrobial resistance (AMR) in aquatic food animals are seldom documented, particularly in Asia. Here, Schar et al. review 749 point prevalence surveys, describing AMR trends in Asian aquaculture and fisheries over two decades, and identifying resistance hotspots as well as regions that would benefit most from future surveillance efforts.

    • Daniel Schar
    • , Cheng Zhao
    •  & Thomas P. Van Boeckel
  • Article
    | Open Access

    Photosynthetic Complex I (PS-CI) is proposed to couple ferredoxin oxidation and plastoquinone reduction to proton pumping across thylakoid membranes. Here the authors determine the reduction potentials of the iron-sulphur clusters of PS-CI and thus the bioenergetics of the electron transfer relay.

    • Katherine H. Richardson
    • , John J. Wright
    •  & Maxie M. Roessler
  • Article
    | Open Access

    Inability to image large numbers of growth plate chondrocytes while retaining their spatial context during analysis has hindered the study of bone development. Here, the authors present a pipeline called 3D MAPs and use it to uncover morphogenic behaviors and growth strategies in normal bones as well as  aberrations in Gdf5 KO bones.

    • Sarah Rubin
    • , Ankit Agrawal
    •  & Elazar Zelzer
  • Article
    | Open Access

    Activation of brown adipose tissue thermogenesis increases energy expenditure and promotes weight loss in mice. Here the authors identify neurotrophic factor neurotrophin 3 (NT-3) as an adipokine that regulates sympathetic nervous system growth and innervation in adipose tissue and increases white adipose beiging.

    • Xin Cui
    • , Jia Jing
    •  & Hang Shi
  • Article
    | Open Access

    The large and small subunits of the ribosome are synthesized independently within the nucleolus — a membrane-less compartment within the nucleus — before being exported into the cytoplasm. Here, the authors use in situ cryo-ET to observe ribosome maturation and reveal the native organization of the nucleolus.

    • Philipp S. Erdmann
    • , Zhen Hou
    •  & Wolfgang Baumeister
  • Article
    | Open Access

    Here, using metagenomic profiling in 180 individuals from the Democratic Republic of the Congo, the authors find associations between the gut microbiome and konzo, a neurodegenerative disease that mostly affects children and is caused by the consumption improperly processed cassava.

    • Matthew S. Bramble
    • , Neerja Vashist
    •  & Eric Vilain
  • Article
    | Open Access

    The molecular basis of Alzheimer’s Disease has been obscured by heterogeneity and scarcity of brain gene expression data, which limit effectiveness in complex models. Here, the authors introduce a multi-task deep learning framework to learn generalizable and nuanced relationships between gene expression and neuropathology.

    • Nicasia Beebe-Wang
    • , Safiye Celik
    •  & Su-In Lee
  • Article
    | Open Access

    A. aegypti is the principal vector for arboviruses that impact on human health and wellbeing. Here the authors use precision guided sterile insect technique—pgSIT—to suppress or eliminate mosquito populations in multigeneration cage experiments.

    • Ming Li
    • , Ting Yang
    •  & Omar S. Akbari
  • Article
    | Open Access

    Phytoplankton form the base of the marine ecosystem but current ocean models used for climate change projections are too simple to assess potential changes in plankton community structure. This study analyses a complex ecosystem model with 35 phytoplankton types to evaluate the changes in phytoplankton community composition, turnover and size structure over the 21st century.

    • Stephanie A. Henson
    • , B. B. Cael
    •  & Stephanie Dutkiewicz
  • Article
    | Open Access

    Newly emerged pathogens are inherently difficult to forecast, due to many unknowns about their biology early in an epidemic. Here, the authors assess forecasts of a suite of models during the Zika epidemic in Colombia, finding that the models that performed best changed over the course of the epidemic.

    • Rachel J. Oidtman
    • , Elisa Omodei
    •  & T. Alex Perkins
  • Article
    | Open Access

    Polycomb repressive complexes (PRC1 and PRC2) repress genes that are crucial for development via epigenetic modifications; however, their role in differentiation is not well known. Here the authors reveal that a PCGF1-containing PRC1 variant facilitates exit from pluripotency by downregulating target genes and recruiting PRC2.

    • Hiroki Sugishita
    • , Takashi Kondo
    •  & Haruhiko Koseki
  • Article
    | Open Access

    The Spike protein of SARS-CoV-2 has a C-terminal cytoplasmic tail. Here the authors show that this tail binds trafficking machinery via sequences that appear optimised to ensure that Spike accumulates at the site of viral budding in the Golgi but that some can also traffic to the cell surface to induce syncytia formation.

    • Jérôme Cattin-Ortolá
    • , Lawrence G. Welch
    •  & Sean Munro
  • Article
    | Open Access

    Complex biomolecular networks are fundamental to the functioning of living systems, both at the cellular level and beyond. In this paper, the authors develop a systems framework to elucidate the interplay of networks and the spatial localisation of network components.

    • Govind Menon
    •  & J. Krishnan
  • Article
    | Open Access

    Biodiversity-ecosystem functioning relationships may vary with climate. Here, the authors study relationships of plant and soil microbial diversity with soil nutrient multifunctionality in 130 dryland sites in China, finding a shift towards greater importance of soil microbial diversity in arid conditions.

    • Weigang Hu
    • , Jinzhi Ran
    •  & Jianming Deng
  • Article
    | Open Access

    The assembly of branched actin networks depends on the heterodimeric capping protein CP/CapZ. Combining cryoEM, in vitro reconstitution and cell biological assays, the authors show that CP not only prevents actin filament elongation but also selectively masks actin filament ends to promote nucleation.

    • Johanna Funk
    • , Felipe Merino
    •  & Peter Bieling
  • Article
    | Open Access

    Protein binding by the Hsp70/J-domain protein (JDP) chaperones prevents aggregation of the client protein. Here, the authors show that DnaJC7 binds preferentially to natively folded wild-type tau, via a β-turn element in tau that contains the known amyloid motif, while aggregation-prone tau mutants are recognized with reduced affinity.

    • Zhiqiang Hou
    • , Pawel M. Wydorski
    •  & Lukasz A. Joachimiak
  • Article
    | Open Access

    Intratumour heterogeneity (ITH) and mutational signatures are typically analysed separately, even though they are not necessarily independent. Here, the authors present CloneSig, a tool for the joint estimation of ITH and mutational signatures, with which they analyse the TCGA and PCAWG datasets.

    • Judith Abécassis
    • , Fabien Reyal
    •  & Jean-Philippe Vert
  • Article
    | Open Access

    Borosins are ribosomally encoded and posttranslationally modified peptide (RiPP) natural products featuring amide-backbone α-N-methylation. Here, the authors report the discovery and characterization of type IV borosin ‘split’ pathways encoding distinct, separate α-N-methyltransferases and precursor peptide substrates.

    • Fredarla S. Miller
    • , Kathryn K. Crone
    •  & Michael F. Freeman
  • Article
    | Open Access

    The concentration of a biomarker in solution can be determined by counting single molecules. Here the authors report a digital immunoassay scheme with solid-state nanopore readout to quantify a target protein and use this to measure thyroid-stimulating hormone from human serum.

    • Liqun He
    • , Daniel R. Tessier
    •  & Vincent Tabard-Cossa
  • Article
    | Open Access

    Some autosomal genes are expressed in a random monoallelic manner, but its extent and mechanisms have remained unclear. Here the authors show robust monoallelic expression in cell lines and mice, where the silent allele can be reexpressed using epidrugs. Further, they find these genes display various modalities of allelic expression with different degrees of allelic imbalance.

    • Lucile Marion-Poll
    • , Benjamin Forêt
    •  & Edith Heard
  • Article
    | Open Access

    Bacteria adjust the expression of some of their metabolic enzymes through metabolite-sensing ribosome nascent chain complexes. Here the authors present a cryo-EM structure of an E. coli ribosome stalled during translation of the TnaC leader peptide and propose a model for L-Trp dependent ribosome stalling where L-Trp competes with release factor 2 for binding to the TnaC-ribosome complex.

    • Anne-Xander van der Stel
    • , Emily R. Gordon
    •  & C. Axel Innis
  • Article
    | Open Access

    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.

    • Julie Gonneaud
    • , Alex T. Baria
    •  & Etienne Vachon-Presseau
  • Article
    | Open Access

    The mechanisms underlying the activity of non-receptor tyrosine kinase, TNK1, in cancers are unclear. Here the authors show that MARK mediates 14-3-3 and TNK1 interaction which restrains TNK1 activity, while the release of TNK1 from 14-3-3 leads to TNK1 activation through its interaction with ubiquitin and thus results in TNK1-mediated tumor growth in vivo

    • Tsz-Yin Chan
    • , Christina M. Egbert
    •  & Joshua L. Andersen
  • Article
    | Open Access

    The lipid composition of the plasma membrane defines the localisation of KRAS and its oncogenic function. Here the authors show that EFR3A binds to active KRAS to recruit PI4KA and alters the lipid composition of the plasma membrane to promote KRAS oncogenic signalling and tumorigenesis.

    • Hema Adhikari
    • , Walaa E. Kattan
    •  & Christopher M. Counter
  • Article
    | Open Access

    Light-driven micromotors can convert energy to motion in sub-millimeter dimensions. Here, the authors extend this concept and introduce reconfigurable micromachines with multiple components, driven by optoelectronic tweezers, and demonstrate new functionalities.

    • Shuailong Zhang
    • , Mohamed Elsayed
    •  & Aaron R. Wheeler
  • Article
    | Open Access

    Intricate color patterns are a defining aspect of morphological diversity in the Felidae. Here the authors apply morphological and single-cell gene expression analysis to fetal skin of domestic cats to identify when, where, and how, during fetal development, felid color patterns are established.

    • Christopher B. Kaelin
    • , Kelly A. McGowan
    •  & Gregory S. Barsh
  • Article
    | Open Access

    Historical interbreeding between Neanderthals and humans should leave signatures of historical demographics in modern human genomes. Analysing the size distribution of Neanderthal fragments in non-African genomes suggests consistent differences in the generation interval across Eurasia, and that this could explain mutational spectrum variation.

    • Moisès Coll Macià
    • , Laurits Skov
    •  & Mikkel Heide Schierup