Biological sciences

  • Article
    | Open Access

    The molecular mechanism by which clock neurons transmit timing information to non-clock neurons is poorly understood. Here, the authors show that circadian clocks drive rhythmic expression of hundreds of genes in mushroom body neurons and drive calcium rhythms via NF1-cAMP/PKAC1 signalling in Drosophila.

    • Pedro Machado Almeida
    • , Blanca Lago Solis
    •  & Emi Nagoshi
  • Article
    | Open Access

    Neuroendocrine carcinomas (NECs) arise from different anatomic sites, but have similar histological and clinical features. Here, the authors show that the epigenetic landscape of a range of NECs converges towards a common epigenetic state, while distinct subtypes occur within neuroendocrine prostate cancer contributing to intratumor heterogeneity in clinical samples.

    • Paloma Cejas
    • , Yingtian Xie
    •  & Henry W. Long
  • Article
    | Open Access

    The increasing scale and scope of biomedical data is generating tremendous opportunities for improving health outcomes, but also raises new challenges ranging from data acquisition and storage to data analysis and utilization. To meet these challenges, the authors develop the Personal Health Dashboard, which provides an end-to-end solution for deep biomedical data analytics.

    • Amir Bahmani
    • , Arash Alavi
    •  & Michael P. Snyder
  • Article
    | Open Access

    Gene-regulatory networks are thought to be complex, and yet perturbation of just a few transcription factors (TFs) can have major consequences. Here the authors apply DNA polymer modelling and simulations to predict how 3D genome structure and TF-DNA interactions can give rise to transcriptional regulation operating over broad genomic regions, where small perturbations can have long-reaching effects.

    • C. A. Brackley
    • , N. Gilbert
    •  & D. Marenduzzo
  • Article
    | Open Access

    Lassa Fever is a rodent-borne viral haemorrhagic fever that is a public health problem in West Africa. Here, the authors develop a spatiotemporal model of the socioecological drivers of disease using surveillance data from Nigeria, and find evidence of climate sensitivity.

    • David W. Redding
    • , Rory Gibb
    •  & Chikwe Ihekweazu
  • Article
    | Open Access

    Here, the authors study the impact of Vibrio cholerae’s T6SS on human gut microbiota isolates and show that certain bacteria are protected from T6SS attacks in an immunity protein-independent manner. Specifically, protection occurred through superior T6SS weaponry in members of the Enterobacter cloacae complex and by molecular armors made of membrane-tethered capsular polysaccharides of diverse Klebsiella isolates.

    • Nicolas Flaugnatti
    • , Sandrine Isaac
    •  & Melanie Blokesch
  • Article
    | Open Access

    Small-molecule responsive protein switches are crucial components to control synthetic cellular activities. Here, we present a computational protein design strategy to repurpose drug-inhibited protein-protein interactions into OFF- and ON-switches active in cells.

    • Sailan Shui
    • , Pablo Gainza
    •  & Bruno E. Correia
  • Article
    | Open Access

    Moral judgments depend on relational context, with different normative cooperative expectations – relational norms – embedded in different social relationships, such as parent-child, romantic partners, siblings, or acquaintances. Here, the authors show how relational norms for care, hierarchy, reciprocity, and mating are embedded in a set of everyday social relationships in the United States, and use this information to predict out-of-sample moral judgments in relational context.

    • Brian D. Earp
    • , Killian L. McLoughlin
    •  & Molly J. Crockett
  • Article
    | Open Access

    The versatility of DNA has inspired many single-molecule investigations utilizing nanotechnology. Harashima et al. have a somewhat different take on the subject and study a zipper configuration bridging electrodes that resembles an active electro-mechanical component instead.

    • Takanori Harashima
    • , Shintaro Fujii
    •  & Tomoaki Nishino
  • Article
    | Open Access

    The mechanism-of-action of many electrohilic drugs remains poorly understood. Here, the authors use a redox-targeting approach to elucidate the basis for the innate immune cell toxicity of dimethyl fumarate, showing that it modifies Keap1 to trigger mitochondrial-targeted neutrophil/macrophage apoptosis.

    • Jesse R. Poganik
    • , Kuan-Ting Huang
    •  & Yimon Aye
  • Article
    | Open Access

    As corals struggle to survive under climate change, it is crucial to know whether they can withstand increasing seawater temperatures. Using a controlled thermal stress experiment across three divergent coral holobionts, this study examines metatranscriptomic responses to heat stress corresponding to the coral host, photosymbionts and associated microbiota.

    • Viridiana Avila-Magaña
    • , Bishoy Kamel
    •  & Mónica Medina
  • Article
    | Open Access

    Understanding the potential impacts of new variants of SARS-CoV-2 is important for pandemic planning. Here, the authors develop a model incorporating hypothetical new variants with varying transmissibility and immune evasion properties, and use it to project possible future epidemic waves in the UK.

    • Louise Dyson
    • , Edward M. Hill
    •  & Matt J. Keeling
  • Article
    | Open Access

    Nerve/glial antigen 2 (NG2) glia can sense synaptic inputs from neurons. Here, the authors show NG2 glia form functional GABAergic synapses by regulating inhibitory synaptic transmission onto adjacent hippocampal interneurons, and activation of NG2 glia induces anxiety-like behaviour in a mouse model of chronic social defeat stress.

    • Xiao Zhang
    • , Yao Liu
    •  & Xiaoping Tong
  • Article
    | Open Access

    Studies show the cancer transcriptome correlates poorly with the cancer proteome, questioning the role of chromatin regulation. Here the authors demonstrate proximal-gene-body chromatin elements and transcription predict abundances of differentially expressed proteins in thyroid and breast cancers.

    • Akshay Sanghi
    • , Joshua J. Gruber
    •  & Michael P. Snyder
  • Article
    | Open Access

    A phylogeny of Nymphalidae butterflies unveils the origin of the latitudinal diversity gradient. This study showed that the modern pattern of species richness emerged from dynamics of dispersal and diversification that varied through time and across regions, and that global climate change throughout the Cenozoic probably played a major role in generating the biodiversity pattern.

    • Nicolas Chazot
    • , Fabien L. Condamine
    •  & Niklas Wahlberg
  • Article
    | Open Access

    The causal relationship between DNA demethylation and gene expression regulation has not yet been fully resolved. Here the authors develop a nuclease-dead Cas9 (dCas9) and gRNA site-specific targeting approach to physically block DNA methylation at specific promoters to cause DNA demethylation in cells and tackle this question.

    • Daniel M. Sapozhnikov
    •  & Moshe Szyf
  • Article
    | Open Access

    The TOM and TIM23 complexes facilitate the transport of nuclear-encoded proteins into the mitochondrial matrix. Here, the authors use a stalled client protein to purify the translocation supercomplex and gain insight into the TOM-TIM23 interface and the mechanism of protein handover from the TOM to the TIM23 complex.

    • Ridhima Gomkale
    • , Andreas Linden
    •  & Peter Rehling
  • Article
    | Open Access

    CHARGE syndrome that affects cerebellar development can be caused by haploinsufficiency of the chromatin remodeling enzyme CHD7; however the precise role of CHD7 remains unknown. Here the authors show CHD7 promotes chromatin accessibility and enhancer activity in granule cell precursors and regulates morphogenesis of the cerebellar cortex, where loss of CHD7 triggers cerebellar polymicrogyria.

    • Naveen C. Reddy
    • , Shahriyar P. Majidi
    •  & Harrison W. Gabel
  • Article
    | Open Access

    Single-cell profiling has led to the identification of diverse cell types. Here, the authors generate a harmonized cell atlas of the mouse post-natal spinal cord. They also provide spatial analysis of the distribution of the identified cell types and an open-source cell type classifier.

    • Daniel E. Russ
    • , Ryan B. Patterson Cross
    •  & Ariel J. Levine
  • Article
    | Open Access

    Bacterial biofilms are aggregates of surface-associated cells embedded in an extracellular polysaccharide (EPS) matrix. Here, the authors describe a unique mode of collective movement by self-propelled, surface-associated spherical microcolonies with EPS cores in the gliding bacterium Flavobacterium johnsoniae.

    • Chao Li
    • , Amanda Hurley
    •  & David J. Beebe
  • Article
    | Open Access

    Biofilm formation in Bacillus subtilis requires expression of matrix production genes, which are upregulated by transcriptional activator RemA. Here, the authors show that RemA forms octameric rings with the potential to form a 16-meric superstructure, suggesting that the protein can wrap DNA through a LytTR-related domain.

    • Tamara Hoffmann
    • , Devid Mrusek
    •  & Gert Bange
  • Article
    | Open Access

    Simultaneous detection of multiple analytes from a sample is currently difficult. Here the authors present protocell arrays in a customisable platform integrating cell-free expression with a polymer-based aqueous two-phase system; they use this for detection of chemically diverse targets from biofluids.

    • Yan Zhang
    • , Taisuke Kojima
    •  & Mark P. Styczynski
  • Article
    | Open Access

    The molecular mechanism underlying the DNA hypermethylation phenotype observed in the SPOP-mutant prostate cancers is unclear. Here, the authors show that mutant SPOP induces global aberrant DNA methylation patterns through GLP/G9a and renders prostate cancer cells susceptible to DNA demethylating agents.

    • Jianong Zhang
    • , Kun Gao
    •  & Haojie Huang
  • Article
    | Open Access

    A Bayesian framework based on partially observable Markov decision processes (POMDPs) not only predicts subjects’ confidence in a perceptual decision making task but also explains well-known discrepancies between confidence and choice accuracy as arising from incomplete knowledge of the environment.

    • Koosha Khalvati
    • , Roozbeh Kiani
    •  & Rajesh P. N. Rao
  • Article
    | Open Access

    Ufmylation is a well-established ubiquitin-like protein modification, but its mechanism is largely unclear. Here, the authors present a crystal structure of the ufmylation-specific E1-E2 complex, revealing differences to the ubiquitination machinery and mechanistic details of the ufmylation process.

    • Manoj Kumar
    • , Prasanth Padala
    •  & Reuven Wiener
  • Article
    | Open Access

    Genetic code expansion strategies are limited to specific codons that can be reassigned to new amino acids. Here the authors show that quadruplet-decoding tRNAs (qtRNAs) can be rapidly discovered and evolved to decode new quadruplet codons, enabling four independent decoding events in a single protein in living cells.

    • Erika A. DeBenedictis
    • , Gavriela D. Carver
    •  & Ahmed H. Badran
  • Article
    | Open Access

    The gastric H+,K+-ATPase is a proton pump that creates the acidic environment of the stomach lumen, maintaining high proton gradient across the gastric mucosa cell membrane. Here, structural analysis of rationally designed H+,K+-ATPase mutants provides insight into this and other P-type ATPases cation binding stoichiometry and mechanisms.

    • Kazuhiro Abe
    • , Kenta Yamamoto
    •  & Atsunori Oshima
  • Article
    | Open Access

    In vitro protein folding can often result in aggregation and low yields. Here the authors use nanoscale exoshells to improve soluble yield, functional yield and specific activity of folded proteins.

    • Samira Sadeghi
    • , Siddharth Deshpande
    •  & Chester L. Drum
  • Article
    | Open Access

    A comprehensive analysis of the ocular networks among various tissues is necessary to understand eye physiology in health and disease. Here the authors present a multi-species single-cell transcriptomic atlas consisting of cells of the cornea, iris, ciliary body, neural retina, retinal pigmented epithelium, and choroid.

    • Pradeep Gautam
    • , Kiyofumi Hamashima
    •  & Yuin-Han Loh
  • Article
    | Open Access

    Mutations within subunits of the tRNA splicing endonuclease complex (TSEN) are associated with pontocerebellar hypoplasia (PCH). Here the authors show that tRNA intron excision is catalyzed by tetrameric TSEN assembled from inactive heterodimers, and provide evidence that modulation of TSEN stability may contribute to PCH phenotypes.

    • Samoil Sekulovski
    • , Pascal Devant
    •  & Simon Trowitzsch
  • Article
    | Open Access

    The mechanisms involved in SLC4-mediated ion transport are still under debate. Here, the authors present a cryoEM structure of the Sodium-driven Chloride/Bicarbonate Exchanger NDCBE, which - together with computational modeling and mutagenesis - reveals molecular determinants of ion transport by SLC4.

    • Weiguang Wang
    • , Kirill Tsirulnikov
    •  & Ira Kurtz
  • Article
    | Open Access

    Differential expression analysis of single-cell transcriptomics allows scientists to dissect cell-type-specific responses to biological perturbations. Here, the authors show that many commonly used methods are biased and can produce false discoveries.

    • Jordan W. Squair
    • , Matthieu Gautier
    •  & Grégoire Courtine
  • Article
    | Open Access

    Cell migration is essential for many physiological processes. Its deregulation causes cancer metastasis and it is not well understood how it is tightly controlled. We identify NHSL1 as a negative regulator of actin nucleating Scar/WAVE-Arp2/3 complexes, cell protrusion stability, and cell migration.

    • Ah-Lai Law
    • , Shamsinar Jalal
    •  & Matthias Krause
  • Article
    | Open Access

    The vertebrate limb bud is a paradigm to uncover the fundamental mechanisms that govern embryogenesis and evolutionary diversification. Here the authors compare mouse and chicken limb bud development to study the impact of genome evolution on conserved and divergent gene regulatory interactions.

    • Shalu Jhanwar
    • , Jonas Malkmus
    •  & Rolf Zeller