Biological sciences

  • Article
    | Open Access

    Biomonitoring of sweat from fingertips overcomes current limitations in time-resolved metabolomic profiling of humans and may prove to become a powerful, noninvasive tool for precision medicine. Here, in a feasibility study of short interval sampling of sweat from fingertips, the authors assay individual dynamic metabolic patterns of endogenous and exogenous molecules.

    • Julia Brunmair
    • , Mathias Gotsmy
    •  & Christopher Gerner
  • Article
    | Open Access

    Both ubiquitin and NEDD8 can be phosphorylated, but the biological role of NEDD8 phosphorylation remains unclear. Here, the authors identify similarities and differences of ubiquitin and NEDD8 phosphorylation, showing that phosphorylated NEDD8 has a distinct interactome and regulates HSP70 proteins.

    • Katrin Stuber
    • , Tobias Schneider
    •  & Martin Scheffner
  • Article
    | Open Access

    Genetic susceptibility loci for oropharyngeal cancer have been reported but these studies have not always examined human papillomavirus (HPV) status. Here, the authors perform genome-wide analysis taking into account HPV16 serology status and report two independent loci in the HLA region, suggesting the protective role of HLA variants against HPV infection.

    • Aida Ferreiro-Iglesias
    • , James D. McKay
    •  & Paul Brennan
  • Article
    | Open Access

    Arab populations are relatively understudied, especially their genetic architecture and historical relationship with early founders of the ancient Near East. Here, the authors examine 6,218 Qatari whole genomes, revealing insights on migration, population history and genetic structure of populations across the Middle Eastern region.

    • Rozaimi Mohamad Razali
    • , Juan Rodriguez-Flores
    •  & Younes Mokrab
  • Article
    | Open Access

    Systemic sclerosis (SSc) disease involves multisystem fibrosis and autoimmunity with limited treatment options. Here the authors demonstrate that IL-31 and IL-31RA are overexpressed in dermal fibroblasts from SSc patients and show that fibrosis and cytokine release can be reduced upon blocking of IL-31/IL-31RA.

    • Ai Kuzumi
    • , Ayumi Yoshizaki
    •  & Shinichi Sato
  • Article
    | Open Access

    A localized Wnt3a signal has been shown to induce asymmetric division of mouse embryonic stem cells. Here the authors develop SET-seq, an approach to jointly profile epigenome and transcriptome in the same single cell and use it to provide mechanistic insights into the gene regulatory programs for maintaining and resetting stem cell fate during differentiation.

    • Zhongxing Sun
    • , Yin Tang
    •  & Dong Fang
  • Article
    | Open Access

    Rapid and spontaneous estimation of number is observed in many animals. Here the authors show that perceived number of items modulates the pupillary light response in humans, confirming its spontaneous nature, and introducing pupillometry as a tool to study numerical cognition.

    • Elisa Castaldi
    • , Antonella Pomè
    •  & Paola Binda
  • Article
    | Open Access

    Land use is a key control of insect communities. Here the authors investigate relationships of insect biomass and richness with land use along a climate gradient, finding evidence of urbanisation and agriculture as drivers of decline, and of biomass and species richness not being suitable as mutual surrogates.

    • Johannes Uhler
    • , Sarah Redlich
    •  & Jörg Müller
  • Article
    | Open Access

    Exercise induces structural and functional adaptations in skeletal muscle that involve transcriptomic remodeling, including of miRNA expression. Here the authors examine the expression of miRNAs in human muscle following exercise training and investigate the functions of miR-19b-3p on glucose metabolism in cells and mouse muscle.

    • Julie Massart
    • , Rasmus J. O. Sjögren
    •  & Anna Krook
  • Article
    | Open Access

    Leptomeningeal metastases from solid tumors are a rare complication with a very poor prognosis. Here the authors report the efficacy and safety of combined ipilimumab and nivolumab in patients with leptomeningeal carcinomatosis.

    • Priscilla K. Brastianos
    • , Matthew R. Strickland
    •  & Ryan J. Sullivan
  • Article
    | Open Access

    Microswimmers can navigate porous environments, however the impact of their directed motility on their movement in fluid flow remains an open issue. The authors show that the motility of magnetotactic bacteria in flow through a porous constriction gives rise to nonlinear flow conductivity similar to electrical diodes.

    • Nicolas Waisbord
    • , Amin Dehkharghani
    •  & Jeffrey S. Guasto
  • Article
    | Open Access

    Leptomeningeal disease (LMD) is a serious complication of metastatic solid tumors with a poor prognosis. Here, by using single-cell RNA sequencing of cerebrospinal fluid, the authors report genomic and immune correlates of response to immunotherapy in two cohorts of patients with LMD treated with immune checkpoint inhibitors.

    • Sanjay M. Prakadan
    • , Christopher A. Alvarez-Breckenridge
    •  & Alex K. Shalek
  • Article
    | Open Access

    Changes in cell mechanics contribute to cancer cell dissemination. Here the authors show that high plasma membrane (PM) tension inhibits cancer dissemination by counteracting mechanosensitive BAR family protein assembly, while restoration of PM tension phenotypically convert malignant cells into a non-motile epithelial cell state.

    • Kazuya Tsujita
    • , Reiko Satow
    •  & Toshiki Itoh
  • Article
    | Open Access

    Aberrant EGFR activation is commonly found in non-small cell lung cancer (NSCLC). Here the authors show that E3 ubiquitin ligase FBXL2 targets EGFR and EGFR tyrosine kinase inhibitor (TKI)-resistant mutants for proteasome-mediated degradation to inhibit EGFR-driven NSCLC growth and TKI resistance.

    • Mengmeng Niu
    • , Jing Xu
    •  & Zhi-Xiong Jim Xiao
  • Article
    | Open Access

    The effectiveness of digital contact tracing for COVID-19 control remains uncertain. Here, the authors use data from the Smittestopp app, used in Norway in spring 2020, and estimate that 80% of nearby devices were detected by the app, and at least 11% of close contacts were not visible to manual contact tracing.

    • Ahmed Elmokashfi
    • , Joakim Sundnes
    •  & Olav Lysne
  • Article
    | Open Access

    Existing approaches to sharing of distributed medical data either provide only limited protection of patients’ privacy or sacrifice the accuracy of results. Here, the authors propose a federated analytics system, based on multiparty homomorphic encryption (MHE), to overcome these issues.

    • David Froelicher
    • , Juan R. Troncoso-Pastoriza
    •  & Jean-Pierre Hubaux
  • Article
    | Open Access

    Movement of the ribosome along an mRNA requires the universally-conserved translocase (EF-G in bacteria) that couples GTP hydrolysis to directed movement. Here the authors use time-resolved Cryo-EM to visualize the GTPase-powered step on native translocating ribosomes and capture key translocation intermediates.

    • Valentyn Petrychenko
    • , Bee-Zen Peng
    •  & Niels Fischer
  • Article
    | Open Access

    Molecular orientation is often ignored during single-molecule localisation microscopy. Here, the authors use a Vortex point spread function in order to simultaneously estimate the 3D position, dipole orientation and degree of rotational constraint, within 30% of the Cramér-Rao bound limit.

    • Christiaan N. Hulleman
    • , Rasmus Ø. Thorsen
    •  & Bernd Rieger
  • Article
    | Open Access

    Iron-sulfur (FeS) proteins are involved in electron transfer and CO2 fixation. Here, the authors show that FeS clusters can form spontaneously in the presence of the amino acid cysteine, in conditions similar those expected in Hadean alkaline hydrothermal vents, suggesting a plausible mechanism of their emergence at the origin of life.

    • Sean F. Jordan
    • , Ioannis Ioannou
    •  & Nick Lane
  • Article
    | Open Access

    OTULIN is a deubiquitinase for linear ubiquitin chains. Here the authors show, using genetic mouse models and single-cell RNA-sequencing, that deficiency of OTULIN in keratinocytes causes skin inflammation and verrucous carcinoma via the induction of keratinocyte death, thereby implicating a function of OTULIN in keratinocyte homeostasis.

    • Esther Hoste
    • , Kim Lecomte
    •  & Geert van Loo
  • Article
    | Open Access

    OTULIN is a negative regulator of linear ubiquitination, and its deficiency in human causes multi-organ inflammations including the skin. Here the authors show, by combining various genetic tools with epidermis-specific Otulin knockout mice, that Otulin suppresses skin inflammation predominantly by inhibiting RIPK1-mediated keratinocytes necroptosis.

    • Hannah Schünke
    • , Ulrike Göbel
    •  & Manolis Pasparakis
  • Article
    | Open Access

    ADP-ribosylation is regulated by HPF1 and ARH3, but the cellular target spectrum of these enzymes is not fully understood. Here, the authors use quantitative proteomics to define the HPF1- and ARH3-dependent ADP-ribosylome, providing evidence that mono-ADP-ribosylation of serine predominates in cells.

    • Ivo A. Hendriks
    • , Sara C. Buch-Larsen
    •  & Michael L. Nielsen
  • Article
    | Open Access

    ABCA4 is an ATP-binding cassette (ABC) transporter that flips N-retinylidenephosphatidylethanolamine (N-Ret-PE) to the cytoplasmic leaflet of photoreceptor membranes. ABCA4 mutations are associated with loss of vision. Here, structures of ABCA4 with and without substrate bound provide insight into N-Ret-PE binding and suggest a lateral access mechanism.

    • Jessica Fernandes Scortecci
    • , Laurie L. Molday
    •  & Robert S. Molday
  • Article
    | Open Access

    Application of adenine base editors (ABE) has been precluded by low activity. Here the authors show the generation of a human cell based ABE directional screening system and identification of ABE variant (NG-ABEmax-KR) exhibiting a significant increase in activity for human and mouse genome manipulation.

    • Junhao Fu
    • , Qing Li
    •  & Feng Gu
  • Article
    | Open Access

    In situ transcriptomics maps RNA expression patterns across intact tissues taking our understanding of gene expression to a new level. Here, the authors present a computational method that uncovers gene expression, cell niche, and tissue region patterns from 2D and 3D spatial transcriptomics.

    • Yichun He
    • , Xin Tang
    •  & Xiao Wang
  • Article
    | Open Access

    Lipid droplet biogenesis is orchestrated by the conserved membrane protein Seipin via an unknown mechanism. Here, the authors use structural, biochemical and molecular dynamics simulation approaches to reveal the mechanism of lipid droplet formation by the yeast Seipin Sei1 and its partner Ldb16.

    • Yoel A. Klug
    • , Justin C. Deme
    •  & Pedro Carvalho
  • Article
    | Open Access

    The tumour microenvironment (TME) may change in response to cancer treatments such as KRAS G12C inhibition, with potential implications for combination therapies. Here, the authors provide an antibody panel and workflow for analysing the TME with imaging mass cytometry in pre-clinical mouse models.

    • Febe van Maldegem
    • , Karishma Valand
    •  & Julian Downward
  • Article
    | Open Access

    During meiosis, chromosomes undergo dramatic changes in morphology and intranuclear positioning. Here the authors mapped the 3D genome architecture throughout mouse spermatogenesis by Hi-C of sorted cells to reveal the contributions of transcriptional activity and mechanical force in modulating homolog alignment and recombination.

    • Wu Zuo
    • , Guangming Chen
    •  & Qian Bian
  • Article
    | Open Access

    Existing high-performance deep learning methods typically rely on large training datasets with high-quality manual annotations, which are difficult to obtain in many clinical applications. Here, the authors introduce an open-source framework to handle imperfect training datasets.

    • Shanshan Wang
    • , Cheng Li
    •  & Hairong Zheng
  • Article
    | Open Access

    RNA polymerase III (Pol III) employs termination-associated reinitiation-recycling to express high amounts of tRNAs, which involves the essential C11 subunit. Here the authors determine the functions of various C11 domains, finding that the N-terminal domain (NTD) stimulates termination, reinitiation-recycling requires an NTD-linker, and the C-terminal domain stimulates RNA 3′-cleavage.

    • Saurabh Mishra
    • , Shaina H. Hasan
    •  & Richard J. Maraia
  • Article
    | Open Access

    Antibiotic resistance is a major issue in medicine and new antimicrobials for treating resistant infection are needed. Here, the authors report on antibacterial peptoid polymers, prepared via NNCA ring-opening polymerization, demonstrating antibacterial function against MRSA in vitro and in in vivo infection models.

    • Jiayang Xie
    • , Min Zhou
    •  & Runhui Liu
  • Article
    | Open Access

    The Lake Malawi cichlid fishes are an example of extreme vertebrate radiation; however, there is very little sequence divergence among the species. Here the authors present a comparative genome-wide methylome study to suggest DNA methylation played a major role in the extensive phenotypic diversity amongst these fishes.

    • Grégoire Vernaz
    • , Milan Malinsky
    •  & Eric A. Miska
  • Article
    | Open Access

    Microbial evolution often involves transient phenotypes and sequential development of multiple mutations of unclear relevance. Here, the authors show that the evolution of non-growing E. coli cells can be driven by alterations in pyrimidine nucleoside levels associated with colony ageing and/or due to mutations in metabolic or regulatory genes.

    • Ida Lauritsen
    • , Pernille Ott Frendorf
    •  & Morten H. H. Nørholm
  • Article
    | Open Access

    While a correlation between epigenetic modifications and mutation rates has been observed, experimental evidence of causality is limited. Here the authors measure the mutation rate in fungal mutants lacking histone modifications and confirm experimentally a causal effect of epigenetic modifications on mutation rates.

    • Michael Habig
    • , Cecile Lorrain
    •  & Eva H. Stukenbrock
  • Article
    | Open Access

    Emerging SARS-CoV-2 variants raise concerns about vaccine effectiveness. Here, the authors show that the ChAdOx1 nCoV-19 (AZD1222) vaccine protects Syrian hamsters from pulmonary infection and disease after infection with SARS-CoV-2 B.1.351 or B.1.1.7 variants.

    • Robert J. Fischer
    • , Neeltje van Doremalen
    •  & Vincent J. Munster
  • Article
    | Open Access

    The glucose transporter GLUT1 is upregulated in multiple cancers and may contribute to tumour progression, but the underlying mechanisms are poorly understood. Here, the authors show that DHHC9-mediated GLUT1 palmitoylation at Cys207 is crucial for plasma membrane localisation of GLUT1 and for tumourigenesis in glioblastoma cells.

    • Zhenxing Zhang
    • , Xin Li
    •  & Xinjian Li
  • Article
    | Open Access

    The authors show that graded molecular heterogeneity in metabotropic pathways underlies a continuum of temporal responses in cerebellar unipolar brush cells (UBCs). This allows the UBC population to serve as a cell-autonomous basis for temporal integration and learning over multiple time scales.

    • Chong Guo
    • , Vincent Huson
    •  & Wade G. Regehr