Biological techniques articles within Nature Communications

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  • Article
    | Open Access

    The transcriptional signature of embryonic lethality has not been defined. Here, the authors, as part of the Deciphering the Mechanisms of Developmental Disorders programme, define genes causing murine embryonic lethality around E9.5 and identify developmental delay transcriptional signatures.

    • John E. Collins
    • , Richard J. White
    •  & Elisabeth M. Busch-Nentwich

  • Article
    | Open Access

    The left hemisphere of the brain is especially involved in processing social vocalizations and (in humans) language, but the mechanisms of this lateralization of function are unclear. Here, the authors compared left and right auditory cortex in mice and show lateralized, experience-dependent circuit-motifs.

    • Robert B. Levy
    • , Tiemo Marquarding
    •  & Hysell V. Oviedo

  • Article
    | Open Access

    Existing methods for protein polymer engineering suffer from low efficiency especially for synthesis large size polyproteins. Here, Deng et al. construct homo-polymer and co-polymer up to decamer by stepwise ligation and cleavage validated by atomic force microscopy-based single-molecule force spectroscopy.

    • Yibing Deng
    • , Tao Wu
    •  & Peng Zheng

  • Article
    | Open Access

    Obesity is associated with leptin resistance and rising blood leptin levels while central leptin exposure may be limited. Here, the authors show that brain leptin infusion reduces hepatic lipid content in rats by increasing hepatic VLDL secretion and lowering liver de novo lipogenesis via a vagal mechanism.

    • Martina Theresa Hackl
    • , Clemens Fürnsinn
    •  & Thomas Scherer

  • Article
    | Open Access

    The dopamine transporter is responsible for termination of neurotransmission through Na+-driven reuptake of neurotransmitter from the extracellular space. Here authors use hydrogen-deuterium exchange mass spectrometry to monitor Na+- and dopamine-induced conformational dynamics of the dopamine transporter.

    • Anne Kathrine Nielsen
    • , Ingvar R. Möller
    •  & Claus J. Loland

  • Article
    | Open Access

    The activity of the membrane-bound enzyme pMMO depends on copper but the location of the copper centers is still under debate. Here, the authors reconstitute pMMO in nanodiscs and use native top-down MS to localize its copper centers, providing insights into which sites are essential for activity.

    • Soo Y. Ro
    • , Luis F. Schachner
    •  & Amy C. Rosenzweig

  • Article
    | Open Access

    Transcranial Magnetic Stimulation (TMS) can modulate human brain activity, but the extent of the cortical area activated by TMS is unclear. Here, the authors show that TMS affects monkey single neuron activity in an area less than 2 mm diameter, while TMS-induced activity and task-related activity do not summate.

    • Maria C. Romero
    • , Marco Davare
    •  & Peter Janssen

  • Article
    | Open Access

    Metabolic engineering requires the balancing of gene expression to obtain optimal output. Here the authors present COMPASS – COMbinatorial Pathway ASSembly – which uses plant-derived artificial transcription factors and cloning of thousands of DNA constructs in parallel to rapidly optimise pathways.

    • Gita Naseri
    • , Jessica Behrend
    •  & Bernd Mueller-Roeber

  • Article
    | Open Access

    In vitro blood-brain barrier (BBB) models do not fully recapitulate the in vivo barrier function. Here the authors develop an organ-on-a-chip BBB model using iPS-derived human brain endothelial cells differentiated under hypoxia, primary human pericytes and astrocytes, which maintains in vivo-like BBB barrier and shuttling functions for a week.

    • Tae-Eun Park
    • , Nur Mustafaoglu
    •  & Donald E. Ingber

  • Article
    | Open Access

    Type VI secretion systems (T6SS) are important for bacterial interaction, competition and virulence, but the abundance and assembly of their components is still not well understood. Here, the authors apply targeted proteomics to measure the abundance of T6SS components across different species and conditions.

    • Lin Lin
    • , Emmanuelle Lezan
    •  & Marek Basler

  • Article
    | Open Access

    Transcranial alternating current stimulation (TACS) of the brain is widely used in neuroscience, but the electric fields produced when multiple stimulation electrodes are used are not well understood. Here, the authors directly record electric fields in primate brains during multi-electrode TACS.

    • Ivan Alekseichuk
    • , Arnaud Y. Falchier
    •  & Alexander Opitz

  • Article
    | Open Access

    Fiber optic implantation in deep areas of the rodent’s brain for MRI combined with optogenetics is challenging. Here the authors use an MRI-guided robotic arm as the navigation method for accurate fiber optic placement and precise microinjection during multi-modal fMRI, optogenetics and calcium recordings.

    • Yi Chen
    • , Patricia Pais-Roldan
    •  & Xin Yu

  • Article
    | Open Access

    Brown macroalgae is a good candidate feedstock for biorefinery, but the major carbohydrate alginate cannot be digested by current industrial microbes. Here, the authors isolate Vibrio sp. dhg and engineer it to produce value-added biochemicals from alginate using newly developed genetic tools.

    • Hyun Gyu Lim
    • , Dong Hun Kwak
    •  & Gyoo Yeol Jung

  • 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

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