Biological techniques articles within Nature Communications

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  • Article
    | Open Access

    Here, the authors show that reticulocytes derived from immortalized erythroblasts support invasion and development of Plasmodium falciparum and use CRISPR-mediated gene knockout and complementation of an invasion receptor to demonstrate utility of this model system for research in malaria invasion.

    • Timothy J. Satchwell
    • , Katherine E. Wright
    •  & Jake Baum

  • Article
    | Open Access

    The COP9 signalosome (CSN) regulates Cullin-RING Ligase 2 (CRL2) but the molecular basis for their interaction is unknown. Here the authors use structural mass spectrometry and cryo-EM approaches to assess the structures and dynamics of CSN-CRL2 complexes.

    • Sarah V. Faull
    • , Andy M. C. Lau
    •  & Argyris Politis

  • Article
    | Open Access

    Whether marmosets can exhibit complex motor tasks in controlled experimental designs has not yet been demonstrated. Here, the authors show that marmoset monkeys can be trained to call on command in controlled operant conditioning tasks.

    • Thomas Pomberger
    • , Cristina Risueno-Segovia
    •  & Steffen R. Hage

  • Article
    | Open Access

    Microelectromechanical neural probes can cause tissue damage and often cannot record from distant brain areas. Here the authors combine electrical recording, optical stimulation and microfluidic drug delivery in one multi-shank probe with thinner shanks to reduce damage and a flexible design to target long-range neural circuits.

    • Hyogeun Shin
    • , Yoojin Son
    •  & Il-Joo Cho

  • Article
    | Open Access

    Tuberculosis meningitis (TBM) is a severe form of TB with limited treatment options. Here, the authors perform RNA sequencing on whole blood and on ventricular and lumbar cerebrospinal fluid (CSF) samples from pediatric patients treated for TBM to characterize the immune response and tissue damage.

    • Ursula K. Rohlwink
    • , Anthony Figaji
    •  & Rachel P. J. Lai

  • Article
    | Open Access

    High frequency semen exposure has been associated with activation of anti-HIV mechanisms in HIV negative sex workers. Here, Abdulhaqq et al. show that repeated vaginal exposure to semen reduces vaginal infection by SIV in non-human primates, and is associated with lower CCR5 expression in CD4 T-cells and a local type-I interferon response.

    • Shaheed A. Abdulhaqq
    • , Melween Martinez
    •  & Luis J. Montaner

  • Article
    | Open Access

    The transient receptor potential channel member 2 (TRPM2) ion channel has a function in redox-dependent signaling. Here the authors present the cryo-EM structures of zebrafish TRPM2 in the ligand-free form, with Ca2+ and both ADP-ribose/Ca2+ and observe two-fold symmetric quaternary structure rearrangements in the ligand-bound structures that likely represent intermediate gating states.

    • Ying Yin
    • , Mengyu Wu
    •  & Seok-Yong Lee

  • Article
    | Open Access

    Pilocytic astrocytoma is a low-grade pediatric glioma, characterized by a single BRAF rearrangement. Here, Reitman and colleagues use single-cell RNA sequencing to reveal molecular hallmarks of the disease that might be targeted therapeutically.

    • Zachary J. Reitman
    • , Brenton R. Paolella
    •  & Rameen Beroukhim

  • Article
    | Open Access

    Detection of viral biomarkers is important for disease treatment and prevention. Here, the authors report on a system that uses an electrical pulse-induced electrochemical sensor for the detection of hepatitis E virus, and demonstrate potential application of the device.

    • Ankan Dutta Chowdhury
    • , Kenshin Takemura
    •  & Enoch Y. Park

  • Article
    | Open Access

    Proper mitochondrial structure is critical for normal function. Here, the authors show with SIM that the mitochondrial Ca2+ uniporter complex and localization of component MICU1 is critical to maintaining cristae junction stability and overall mitochondrial membrane structure.

    • Benjamin Gottschalk
    • , Christiane Klec
    •  & Wolfgang F. Graier

  • Article
    | Open Access

    Super-resolution microscopy is a valuable tool in bioimaging, but often requires complex systems or post-processing. Here, the authors present super-linear excitation-emission (SEE) microscopy, which overcomes these limitations by taking advantage of markers with super-linear dependence between emission and excitation power.

    • Denitza Denkova
    • , Martin Ploschner
    •  & James A. Piper

  • Article
    | Open Access

    Multi-omic profiling is a powerful approach to dissecting molecular mechanisms in disease. Here the authors generate whole proteome, phosphoproteome and transcriptome profiles from two mouse models of high-grade glioma driven by different oncogenes, and validate identified master regulators with a CRISPR screen.

    • Hong Wang
    • , Alexander K. Diaz
    •  & Junmin Peng

  • Article
    | Open Access

    Fluorescence correlation spectroscopy is widely used for in vivo and in vitro applications, yet extracting information from experiments still requires long acquisition times. Here, the authors exploit Bayesian non-parametrics to directly analyze the output of confocal fluorescence experiments thereby probing physical processes on much faster timescales.

    • Sina Jazani
    • , Ioannis Sgouralis
    •  & Steve Pressé

  • Article
    | Open Access

    The glomerular filtration barrier is a complex structure in charge of renal ultrafiltration. Here the authors present a glomerulus-on-a-chip for disease modelling and high-throughput drug screening where human podocytes and human glomerular endothelial cells are separated by an extracellular matrix resembling the in vivo basement membrane.

    • Astgik Petrosyan
    • , Paolo Cravedi
    •  & Stefano Da Sacco

  • Article
    | Open Access

    Electrophoretic mobility shift assays are widely used in gel electrophoresis to study binding interactions between different molecular species, but these assays access only a subset of reaction possibilities. Here, the authors develop a band-collision gel electrophoresis (BCGE) approach that demonstrates a much wider variety of reaction types.

    • Dimitri A. Bikos
    •  & Thomas G. Mason

  • Article
    | Open Access

    Present understanding of Plasmodium vivax biology is hampered by its inability to grow in vitro. Here, the authors developed an in vitro culture of its simian counterpart, P. cynomolgi, which shares morphological and phenotypic similarities with P. vivax, initiating a new phase in vivax research.

    • Adeline C. Y. Chua
    • , Jessica Jie Ying Ong
    •  & Pablo Bifani

  • Article
    | Open Access

    Picornaviruses use modular RNA domains in their internal ribosome entry sites (IRESs) for translation through non-canonical, cap-independent mechanisms. Here the authors report the crystal structure of domain V from the IRES of hepatitis A virus (HAV) ssRNA genome, suggesting that the functional homology among different types of picornaviral IRESs is structure-based.

    • Deepak Koirala
    • , Yaming Shao
    •  & Joseph A. Piccirilli

  • Article
    | Open Access

    Cytosine base editors are limited by editing scope and potential off-target effects. Here the authors screen diversified lamprey cytidine deaminases along with different protein fusion architectures and present base editors with improved fidelity.

    • Tian-Lin Cheng
    • , Shuo Li
    •  & Zilong Qiu

  • Article
    | Open Access

    Squamous cell lung cancer has dismal prognosis due to the dearth of effective treatments. Here, the authors perform an integrated proteogenomic analysis of the disease, revealing three proteomics-based subtypes and suggesting potential therapeutic opportunities.

    • Paul A. Stewart
    • , Eric A. Welsh
    •  & Eric B. Haura

  • Article
    | Open Access

    Digital proximity ligation assay (dPLA) can measure proteins and mRNAs in single cells, but is not compatible with cell imaging and cannot quantify rare proteins due to a high dilution factor. Here the authors present an automated microfluidic device that combines live-cell imaging, chemical stimulation, and dPLA in a smaller reaction volume.

    • Jing Lin
    • , Christian Jordi
    •  & Savaş Tay

  • Article
    | Open Access

    Understanding of the genetic factors and molecular mechanisms underlying neurodevelopmental disorders remains incomplete. In this study, authors show that microdeletions in the gene ANKS1B lead to loss of the neuronal synapse-enriched protein AIDA-1 and to a novel neurodevelopmental syndrome

    • Abigail U. Carbonell
    • , Chang Hoon Cho
    •  & Bryen A. Jordan

  • Article
    | Open Access

    There are few studies of structural changes in ascending and descending sensorimotor pathways after stroke, beyond the corticospinal tract, in the brain. Here the authors identify changes in white matter structure in brainstem and spinal cord following stroke, and show its relationship to motor impairment.

    • Haleh Karbasforoushan
    • , Julien Cohen-Adad
    •  & Julius P. A. Dewald

  • Article
    | Open Access

    The expression of oncogenic MYC paralogs in small cell lung cancer is mutually exclusive. In this study, the authors show that MYC, but not MYCN or MYCL, represses BCL2, resulting in cells that are uniquely sensitive to apoptosis, and find that CHK1 and AURKA inhibitors may be useful for treating these cancers.

    • Marcel A. Dammert
    • , Johannes Brägelmann
    •  & Martin L. Sos

  • Article
    | Open Access

    In humans, copy-number variants of the CYFIP1 gene have been associated with autism spectrum disorders and schizophrenia. Here, the authors characterize Cyfip1-heterozygous mice, revealing that they display deficits in brain white matter structure and functional connectivity along with abnormal behaviours.

    • Nuria Domínguez-Iturza
    • , Adrian C. Lo
    •  & Claudia Bagni

  • Article
    | Open Access

    People with a genetic deletion of the 15q11.2 locus are at increased risk for psychiatric disorders and white matter disturbances, but the gene(s) responsible are unclear. Here, the authors show that low dosage of CYFIP1, present in the human 15q11.2 region, alters white matter structure and cognition in rats.

    • Ana I. Silva
    • , Josephine E. Haddon
    •  & Lawrence S. Wilkinson

  • Article
    | Open Access

    Compared to bulk data, cell-type-specific DNA methylation data provide higher resolution of epigenetic variation. Here, the authors introduce Tensor Composition Analysis, a novel computational approach for learning cell-type-specific DNA methylation from tissue-level bulk data, and show its application in epigenome-wide association studies.

    • Elior Rahmani
    • , Regev Schweiger
    •  & Eran Halperin

  • Article
    | Open Access

    Atherosclerosis results from the accumulation of lipoproteins in the vascular wall. Here, Thierer et al. report the design of a chemiluminescent reporter for atherogenic lipoproteins using fusion of apolipoprotein-B to a luciferase enzyme, and find it bears potential for the identification of regulators of lipoprotein metabolism in vivo.

    • James H. Thierer
    • , Stephen C. Ekker
    •  & Steven A. Farber

  • Article
    | Open Access

    The identification of cross-linked peptides at a proteome scale for interactome analyses represents a complex challenge. Here the authors report an efficient and reliable search engine pLink 2 for proteome-scale cross-linking mass spectrometry analyses, and demonstrate how to systematically evaluate the credibility of search engines.

    • Zhen-Lin Chen
    • , Jia-Ming Meng
    •  & Si-Min He

  • Article
    | Open Access

    Single-molecule localization microscopy (SMLM) requires the use of fluorophores with specific sets of properties. Here the authors employ conventional BODIPY dyes as SMLM fluorophores by making use of rarely reported red-shifted ground state BODIPY dimers to image fatty acids, lipid droplets and lysosomes at single-molecule resolution.

    • Santosh Adhikari
    • , Joe Moscatelli
    •  & Elias M. Puchner

  • Article
    | Open Access

    The SWI2/SNF2-Related 1 chromatin remodeling complex (SWR1-C) is important for gene regulation, but its composition remains largely uncharacterized in plants. Here, the authors report that methyl-CpG-binding domain 9 (MBD9) is a SWR1-C interacting protein required for histone H2A.Z deposition in Arabidopsis.

    • Magdalena E. Potok
    • , Yafei Wang
    •  & Steven E. Jacobsen

  • Article
    | Open Access

    The liver parenchyma consists of several cell types, but the origin of this tissue in humans is unclear. Here, the authors perform single cell RNA sequencing of human fetal and adult liver to identify a hepatobiliary hybrid progenitor population of cells, which have a similar gene signature to mouse oval cells.

    • Joe M. Segal
    • , Deniz Kent
    •  & S. Tamir Rashid

  • Article
    | Open Access

    Construction of plasmids from multiple fragments often uses customised parts and leaves scars where fragments are joined. Here the authors develop a method for barcoding fragments and constructing plasmids in a scarless manner from a collection of standard parts.

    • Xiaoqiang Ma
    • , Hong Liang
    •  & Kang Zhou

  • Article
    | Open Access

    The depolarizing funny current contributing to cardiac pacemaking is upregulated in the myocardium of  failing and infarcted hearts, but whether the current is implied in disease mechanisms is unclear. Here the authors generate HCN4 transgenic mice and show that upregulation of funny current to the levels observed in human heart failure alters calcium homeostasis leading to cardiac remodelling and arrhythmia.

    • Pessah Yampolsky
    • , Michael Koenen
    •  & Patrick A. Schweizer

  • Review Article
    | Open Access

    Glycomics is gaining momentum in basic, translational and clinical research. Here, the authors review current reporting standards and analysis tools for mass-spectrometry-based glycomics, and propose an e-infrastructure for standardized reporting and online deposition of glycomics data.

    • Miguel A. Rojas-Macias
    • , Julien Mariethoz
    •  & Niclas G. Karlsson

  • Article
    | Open Access

    Secreted proteins present a rich resource of potential cancer biomarkers. Here, the authors use mass spectrometry to analyze secretome remodeling in pulmonary neuroendocrine lung cancer cell lines and validate potential biomarkers and therapeutic targets in vitro and in mouse models.

    • Xu-Dong Wang
    • , Rongkuan Hu
    •  & Yonghao Yu

  • Article
    | Open Access

    Although quantum biological electron transfer is important in many biological processes, imaging of the events in live cells has remained challenging. Here, the authors demonstrate real-time optical detection of quantum biological electron tunnelling between nanoparticles and cytochrome c inside living cells.

    • Hongbao Xin
    • , Wen Jing Sim
    •  & Luke P. Lee

  • Article
    | Open Access

    Asymmetric subcellular mRNA distribution is important for local translation of neuronal mRNAs. Here the authors employed MS2 live-cell imaging and showed that the reporter mRNA containing the 3’ UTR of Rgs4 shows an anterograde transport bias, dependent on neuronal activity and the protein Staufen2, and mediates sustained mRNA recruitment to synapses.

    • Karl E. Bauer
    • , Inmaculada Segura
    •  & Michael A. Kiebler

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