Biological techniques articles within Nature Communications

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  • Article
    | Open Access

    Amyloid-β (Aβ) deposition occurs in Alzheimer's disease but its relation to disease features such as local brain hypometabolism or cognitive decline is unclear. Here, the authors show that Aβ aggregation in the brain’s default mode network leads to hypometabolism in distant but functionally connected areas.

    • Tharick A. Pascoal
    • , Sulantha Mathotaarachchi
    •  & Pedro Rosa-Neto

  • Article
    | Open Access

    Different sensory experiences can affect longevity in Drosophila. Here the authors find that exposure of Drosophila directly to dead conspecifics affects longevity via a serotonergic mechanism, and that Drosophila exposed to dead conspecifics also become an aversive stimulus to naïve choosers.

    • Tuhin S. Chakraborty
    • , Christi M. Gendron
    •  & Scott D. Pletcher

  • Article
    | Open Access

    Acyl carrier proteins (ACPs), a universal and highly conserved carrier of acyl intermediates during fatty acid and polyketide synthesis, are difficult to visualise. Here, the authors developed a facile, Raman spectroscopy-based method to detect ACP-substrate interactions.

    • Samuel C. Epstein
    • , Adam R. Huff
    •  & Louise K. Charkoudian

  • Article
    | Open Access

    Single-cell CRISPR screening combines pooled CRISPR screening with scRNA-seq analysis to expand the resolution power of genetic screening. Here, the authors develop MUSIC, a computational pipeline for analyzing single-cell CRISPR screening data.

    • Bin Duan
    • , Chi Zhou
    •  & Qi Liu

  • Article
    | Open Access

    Here the authors fuse hRad51 and variants thereof to Cas9 nickase to facilitate homology-directed repair without generating double strand breaks, minimizing indel formation and off-target editing. This tool represents progress towards the goal of performing HDR without an excess of undesired side products.

    • Holly A. Rees
    • , Wei-Hsi Yeh
    •  & David R. Liu

  • Article
    | Open Access

    Complete gene expression deconvolution remains a challenging problem. Here, the authors provide a solution based on the recognition that expression levels of cell type specific genes are mutually linear across mixtures and mutually linear gene clusters correspond to cell type-specific signatures.

    • Konstantin Zaitsev
    • , Monika Bambouskova
    •  & Maxim N. Artyomov

  • Article
    | Open Access

    Schizogony is essential for blood stage infection of Plasmodium parasites and produces several daughter cells. Here, Rudlaff et al. identify PfCINCH and interacting proteins as essential components of the basal complex required to establish daughter cell boundaries.

    • Rachel M. Rudlaff
    • , Stephan Kraemer
    •  & Jeffrey D. Dvorin

  • Article
    | Open Access

    Reversible cysteine modifications play important roles in cellular redox signaling. Here, the authors develop a chemical proteomics strategy that enables the quantitative analysis of endogenous cysteine nitrosylation sites and their dynamic regulation under nitrosative stress conditions.

    • Ruzanna Mnatsakanyan
    • , Stavroula Markoutsa
    •  & René P. Zahedi

  • Article
    | Open Access

    Wnt signaling is necessary for colorectal cancer tumorigenesis and stem cell maintenance. Here, the authors identify MEK1/2 inhibitors as potent activators of Wnt/β-catenin signalling and show that clinically approved MEK inhibitors inadvertently induce stem cell plasticity in colorectal cancer

    • Tianzuo Zhan
    • , Giulia Ambrosi
    •  & Michael Boutros

  • Article
    | Open Access

    Cultured adult cardiac tissue undergoes rapid dedifferentiation, which hinders chronic in vitro studies. Here the authors investigate biomimetic electromechanical stimulation of adult myocardial slices applying different preload conditions, identifying the optimum sarcomere length for prolonged culturing, and investigating transcriptional profiles associated with functional preservation.

    • Samuel A. Watson
    • , James Duff
    •  & Cesare M. Terracciano

  • Article
    | Open Access

    In-depth characterization of complex glycomes is complicated by the immense structural diversity of glycans. Here, the authors present a mass spectrometry-based strategy for untargeted, sensitive glycan profiling and identify 167 N-glycan compositions in total human plasma.

    • Guinevere S. M. Lageveen-Kammeijer
    • , Noortje de Haan
    •  & Manfred Wuhrer

  • Article
    | Open Access

    Master transcription factors dominantly direct cell fate and barriers ensuring their tissue specific silencing are not clearly defined. Here, the authors demonstrate that inefficient targeted transactivation of Sox1 in neural progenitor cells is surmountable through targeted promoter demethylation using dCas9-Tet1.

    • Valentin Baumann
    • , Maximilian Wiesbeck
    •  & Stefan H. Stricker

  • Article
    | Open Access

    Size and shape of bones are important for height and body shape. Here, Styrkarsdottir et al identify 12 loci in a GWAS for bone area derived from DXA scans and show that these loci associate with other bone-related phenotypes including osteoarthritis, height, bone mineral density and risk of hip fracture.

    • Unnur Styrkarsdottir
    • , Olafur A. Stefansson
    •  & Kari Stefansson

  • Article
    | Open Access

    The bacterial protein Cnu together with the transcription repressor H-NS regulate expression of virulence factors in an osmo-sensitive manner. Here authors show that the structure of Cnu swells with decreasing ionic strength driving the oligomerization of H-NS and regulating osmo-sensory response.

    • Abhishek Narayan
    • , Soundhararajan Gopi
    •  & Athi N. Naganathan

  • Article
    | Open Access

    3D single molecule localization microscopy suffers from several experimental biases that degrade the resolution or localization precision. Here the authors present a dual-view detection scheme combining supercritical angle fluorescence and astigmatic imaging to obtain precise and unbiased 3D super resolution images.

    • Clément Cabriel
    • , Nicolas Bourg
    •  & Sandrine Lévêque-Fort

  • Article
    | Open Access

    Understanding gene regulation will require mapping specific chromain features in a small number of cells at high resolution. Here the authors describe CUT&Tag, which uses antibody-mediated tethering of Tn5 transposase to a chromatin protein to generate high resolution libraries.

    • Hatice S. Kaya-Okur
    • , Steven J. Wu
    •  & Steven Henikoff

  • Article
    | Open Access

    The default mode network (DMN) is a core brain network in humans. Here, the authors show that marmoset primates also possess a DMN-like network but, unlike in the human DMN, dlPFC is a more prominent node than mPFC, suggesting mPFC is more developed in humans than in other primates.

    • Cirong Liu
    • , Cecil Chern-Chyi Yen
    •  & Afonso C. Silva

  • Article
    | Open Access

    Analysis of Hi-C datasets is limited by the current existing methods for data normalization, with detection of features such as TADs and chromatin loops being inconsistent amongst different approaches. Here the authors develop Binless, a method that allows for reproducible normalization of Hi-C data independent of its resolution and compare how Binless performs in comparison with other methods.

    • Yannick G. Spill
    • , David Castillo
    •  & Marc A. Marti-Renom

  • Review Article
    | Open Access

    Generation of transgenic mice has become routine in studying gene function and disease mechanisms, but often this is not enough to fully understand human biology. Here, the authors review the current state of the art of targeted genomic humanisation strategies and their advantages over classic approaches.

    • Fei Zhu
    • , Remya R. Nair
    •  & Thomas J. Cunningham

  • Article
    | Open Access

    The transcriptional regulator YAP is regarded as the universal mechanotransducer, largely from 2D culture studies. Here the authors show that in breast cancer patient tissues and cells in 3D culture, mechanical signals are transduced independently of YAP, questioning YAP as a therapeutic target.

    • Joanna Y. Lee
    • , Jessica K. Chang
    •  & Ovijit Chaudhuri

  • Article
    | Open Access

    Dishevelled (DVL) is the key component of Wnt signaling pathway that acts as a signaling hub. Here, authors study the conformational dynamics of DVL3 in vivo using their engineered FlAsH-based FRET biosensors and describe how Wnt activation opens DVL and facilitates Frizzled recruitment.

    • Jakub Harnoš
    • , Maria Consuelo Alonso Cañizal
    •  & Vítězslav Bryja

  • Article
    | Open Access

    Human antibodies cross-reactive for several viruses within the Ebolavirus genus have been identified. Here the authors present the crystal structure of such a neutralizing monoclonal antibody (mAb) targeting the stalk of Bundibugyo virus glycoprotein and show that mAb binding may interfere with trimeric bundle assembly and/or the viral membrane.

    • Liam B. King
    • , Brandyn R. West
    •  & Erica Ollmann Saphire

  • Article
    | Open Access

    The understanding of liquid-liquid phase separation is crucial to cell biology and benefits from cell-mimicking in vitro assays. Here, the authors develop a microfluidic platform to study coacervate formation inside liposomes and show the potential of these hybrid systems to create synthetic cells.

    • Siddharth Deshpande
    • , Frank Brandenburg
    •  & Cees Dekker

  • Article
    | Open Access

    Personalized approaches to diagnosis and treatment monitoring could improve the management of cystic fibrosis patients. Here the authors show that multiscale differential dynamic microscopy can assess changes in cilia beating dynamics and coordination in patient-derived airway epithelial cells, in response to different CFTR-modulating drugs, in a patient-specific manner.

    • M. Chioccioli
    • , L. Feriani
    •  & P. Cicuta

  • Article
    | Open Access

    Methods to track molecular motion in eukaryotic cells mostly rely on fluorescent labels, transfection or photobleaching. Here the authors use multimodal partial wave spectroscopy to perform label-free live cell measurements of nanoscale structure and macromolecular motion with millisecond temporal resolution.

    • Scott Gladstein
    • , Luay M. Almassalha
    •  & Vadim Backman

  • Article
    | Open Access

    Multicolour images are difficult to acquire with large-scale microscopy approaches. Here the authors present a microtome-assisted microscope capable of trichromatic two-photon excitation and label-free nonlinear modalities based on wavelength mixing, and use it to analyze astrocyte morphology and neuronal projections in thick brain samples.

    • Lamiae Abdeladim
    • , Katherine S. Matho
    •  & Emmanuel Beaurepaire

  • Article
    | Open Access

    Gene-drives use CRISPR-Cas9 to be transmitted in a super-Mendelian fashion. Here the authors develop an allelic-drive for selective inheritance of a desired allele.

    • Annabel Guichard
    • , Tisha Haque
    •  & Ethan Bier

  • Article
    | Open Access

    Gene correction in hematopoietic stem cells could be a powerful way to treat monogenic diseases of the blood and immune system. Here the authors develop a strategy using CRISPR-Cas9 and an aAdeno-Associated vVirus(AAV)-delivered IL2RG cDNA to correct X-linked sSevere Ccombined iImmunodeficiency (SCID-X1) with a high success rate.

    • Mara Pavel-Dinu
    • , Volker Wiebking
    •  & Matthew H. Porteus

  • Article
    | Open Access

    Designing effective genome engineering strategies requires an understanding of the impact that genomic locus has on CRISPR-Cas9 activity. Here the authors use TRIP integrations to profile editing outcomes genome-wide and observe that gRNA sequence influences the structure of the double strand break.

    • Santiago Gisler
    • , Joana P. Gonçalves
    •  & Maarten van Lohuizen

  • Article
    | Open Access

    Affinity purification-mass spectrometry (AP-MS) can identify endogenous protein interactions but the need for high amounts of input material still limits its applicability. Here, the authors present a microfluidic-based AP-MS workflow that can capture protein interactions from 50─100-fold less input material than conventional approaches.

    • Cristina Furlan
    • , René A. M. Dirks
    •  & Michiel Vermeulen

  • Article
    | Open Access

    Autophagic degradation of mitochondria (mitophagy) is a key quality control mechanism in cellular homeostasis, and its misregulation is involved in neurodegenerative diseases. Here the authors develop an optogenetic system for reversible induction of mitophagy and validate its use in cell culture and zebrafish embryos.

    • Pasquale D’Acunzo
    • , Flavie Strappazzon
    •  & Francesco Cecconi

  • Article
    | Open Access

    The spatial organization of the genome plays an important but unclearly defined role in gene regulation. Here, the authors integrate Hi-C, RNA-seq and ATAC-seq data to map cardiogenesis from pluripotent stem cells and describe an RBM20-dependent splicing factory assembling the TTN locus with other RBM20 targets.

    • Alessandro Bertero
    • , Paul A. Fields
    •  & Charles E. Murry

  • Article
    | Open Access

    Untargeted metabolomics detects large numbers of metabolites but their annotation remains challenging. Here, the authors develop a metabolic reaction network-based recursive algorithm that expands metabolite annotation by taking advantage of the mass spectral similarity of reaction-paired neighbor metabolites.

    • Xiaotao Shen
    • , Ruohong Wang
    •  & Zheng-Jiang Zhu

  • Article
    | Open Access

    The hippocampus is involved both in episodic memory recall and scene processing. Here, the authors show that hippocampal neurons first process scene cues before coordinating memory-guided pattern completion in adjacent entorhinal cortex.

    • Bernhard P. Staresina
    • , Thomas P. Reber
    •  & Florian Mormann

  • Article
    | Open Access

    Imaging the mouse brain using glass cranial windows has limitations in terms of flexibility and long-term imaging. Here the authors engineer transparent polymer skulls that can fit various skull morphologies and can be implanted for over 300 days, enabling simultaneous high resolution brain imaging and electrophysiology across large cortical areas.

    • Leila Ghanbari
    • , Russell E. Carter
    •  & Suhasa B. Kodandaramaiah

  • Article
    | Open Access

    D-lactic acidosis typically occurs in the context of short bowel syndrome; excess D-lactate is produced by intestinal bacteria. Here, the authors identify two point mutations in the human lactate dehydrogenase D (LDHD) gene that cause enzymatic loss of function and are associated with elevated plasma D-lactate.

    • Glen R. Monroe
    • , Albertien M. van Eerde
    •  & Judith J. Jans

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