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Article
| Open Access
Self-renewing human naïve pluripotent stem cells dedifferentiate in 3D culture and form blastoids spontaneously
Blastoids are emerging models for early embryo development exploration in vitro. Here, authors found self-renewing human naïve PSCs spontaneously and efficiently give rise to blastoids upon three-dimensional suspension culture.
- Mingyue Guo
- , Jinyi Wu
- & José C. R. Silva
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Article
| Open Access
Nanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models
Here the authors screen different lipid nanoparticle (LNP) formulations for intramuscular delivery of plasmid DNA and uptake by antigen-presenting cells. The lead LNP exhibits immunogenicity and protection in small animal models that is comparable to approved SARS-CoV-2 mRNA vaccine formulations.
- Lays Cordeiro Guimaraes
- , Pedro Augusto Carvalho Costa
- & Pedro Pires Goulart Guimaraes
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Article
| Open Access
Antibody-dependent enhancement of toxicity of myotoxin II from Bothrops asper
The recent emergence of monoclonal antibodies able to neutralize snake toxins have revolutionized the approach of developing novel therapies to treat snakebite envenoming, at least in animal models. Here, the authors show antibody-dependent enhancement of toxicity (ADET) for a toxin derived from snake venom and highlight the importance of this phenomenon when testing therapeutic antibodies against snake venoms in animal models.
- Christoffer V. Sørensen
- , Julián Fernández
- & Andreas H. Laustsen
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Article
| Open Access
Reprogramming mechanism dissection and trophoblast replacement application in monkey somatic cell nuclear transfer
Somatic cloning of rhesus monkey has not been successful until now. Here, authors report epigenetic abnormalities in SCNT embryos and placentas and develop a trophoblast replacement method that enables them to successful clone of a healthy male rhesus monkey.
- Zhaodi Liao
- , Jixiang Zhang
- & Qiang Sun
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Article
| Open Access
DiffDomain enables identification of structurally reorganized topologically associating domains
Topologically associating domains (TADs) are critical structural units in 3D genome organization, and their reorganization between health and disease states is associated with essential genome functions. However, computational methods for identifying reorganized TADs are still in the early stages of development. Here, the authors present an algorithm leveraging random matrix theory to identify reorganized TADs.
- Dunming Hua
- , Ming Gu
- & Dechao Tian
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Article
| Open Access
Massively parallel profiling of RNA-targeting CRISPR-Cas13d
Systematic understanding of CRISPR enzyme RNA binding specificity and cleavage is lacking. Here the authors report RNA chip-hybridised association-mapping platform (RNA-CHAMP), a workflow that repurposes next generation DNA sequencing chips to measure the binding affinity for RNA targets.
- Hung-Che Kuo
- , Joshua Prupes
- & Ilya J. Finkelstein
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| Open Access
Direct RNA sequencing coupled with adaptive sampling enriches RNAs of interest in the transcriptome
It can be difficult to find rare transcripts when sequencing a transcriptome. Here the authors show adaptive sampling on direct RNA runs to increase the likelihood of finding less frequent ones while selectively ejecting the higher-abundance transcripts.
- Jiaxu Wang
- , Lin Yang
- & Yue Wan
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Article
| Open Access
Single-sided magnetic resonance-based sensor for point-of-care evaluation of muscle
Magnetic resonance imaging is a useful clinical tool, but its widespread use is constrained by size, cost, and time. Here, the authors report the development of a magnetic resonance sensor for the clinical detection of muscle tissue, allowing for new point-of-care quantitative diagnostic measurements
- Sydney E. Sherman
- , Alexa S. Zammit
- & Michael J. Cima
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Article
| Open Access
Non-Faradaic optoelectrodes for safe electrical neuromodulation
Nanoscale optoelectrodes hold the potential to optically stimulate individual neuron. Here, the authors form nanoscale capacitive optoelectrodes by incorporating zinc porphyrin into nanorods, coated by TiO2, a design that allows for far-field optical modulation of neurons with efficiency and negligible side effects.
- Jian Chen
- , Yanyan Liu
- & Wenbo Bu
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Article
| Open Access
A full-body transcription factor expression atlas with completely resolved cell identities in C. elegans
Invariant cell lineage in C. elegans enables the analysis of transcriptional regulatory mechanisms controlling the fate of each cell at spatiotemporal resolution. Here, the authors develop a tool automating C. elegans cell identification and create an expression atlas of 620 transcription factors.
- Yongbin Li
- , Siyu Chen
- & Xiao Liu
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Article
| Open Access
VESPA: an optimized protocol for accurate metabarcoding-based characterization of vertebrate eukaryotic endosymbiont and parasite assemblages
DNA sequencing methods for characterizing microbial communities are well developed for bacteria, archaea and fungi, but less so for eukaryotic parasites and commensals. Here, the authors present an optimized and validated metabarcoding protocol for host-associated eukaryotic communities.
- Leah A. Owens
- , Sagan Friant
- & Tony L. Goldberg
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Editorial
| Open AccessEfficient genetic improvement of orphan crops cannot follow the old path
Orphan crops hold the potential to diversify our food systems. Considering their unique characteristics, our deep understanding of major crops, and the availability of modern genomic tools, taking a different research path from what major crops have gone through could accelerate the genetic improvement of orphan crops.
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Article
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Single-cell mapping of lipid metabolites using an infrared probe in human-derived model systems
Current metabolic imaging studies are limited by low resolution and low specificity. Here, the authors present a single-cell metabolic imaging platform to monitor lipid metabolism with high specificity in various human-derived 2D and 3D culture systems.
- Yeran Bai
- , Carolina M. Camargo
- & Kenneth S. Kosik
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Article
| Open Access
Conformational coupling of the sialic acid TRAP transporter HiSiaQM with its substrate binding protein HiSiaP
Tripartite ATP-independent periplasmic (TRAP) transporters use an extra substrate binding protein to transport a variety of substrates in bacteria and archaea. Here the authors use a disulfide engineering approach to lock the TRAP transporter HiSiaPQM from H. influenzae in different conformational states for characterisation.
- Martin F. Peter
- , Jan A. Ruland
- & Gregor Hagelueken
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Article
| Open Access
Gene drive and genetic sex conversion in the global agricultural pest Ceratitis capitata
Homing-based gene drives are novel interventions promising the area-wide, species-specific genetic control of harmful insect populations. Here the authors demonstrate the feasibility of a gene drive approach for the genetic control of the agricultural pest, the medfly, based on complete female-to-male sex conversion.
- Angela Meccariello
- , Shibo Hou
- & Nikolai Windbichler
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Article
| Open Access
PIEZO1 loss-of-function compound heterozygous mutations in the rare congenital human disorder Prune Belly Syndrome
PIEZO1 is a mechanosensitive ion channel. Here, authors identify PIEZO1 human mutations in Prune Belly Syndrome. At a single molecule level these mutations exhibit loss-of-function characteristics.
- Nathalia G. Amado
- , Elena D. Nosyreva
- & Ruhma Syeda
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Article
| Open Access
Enhancing geometric representations for molecules with equivariant vector-scalar interactive message passing
Utilising geometric information and reducing computational costs are key challenges in the molecular modelling field. Here, authors propose ViSNet, which efficiently extracts geometric features, accurately predicts molecular properties, and drives simulations with interpretability.
- Yusong Wang
- , Tong Wang
- & Tie-Yan Liu
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Article
| Open Access
Muscle abnormalities worsen after post-exertional malaise in long COVID
In this longitudinal, case-controlled, cohort design study, authors show that post-exertional malaise is associated with severe exercise-induced myopathy, local and systemic metabolic disturbances and infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID.
- Brent Appelman
- , Braeden T. Charlton
- & Rob C. I. Wüst
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Article
| Open Access
Drosophila activins adapt gut size to food intake and promote regenerative growth
While activins are critical regulators of early development, their role in maintaining adult tissue homeostasis remains obscure. Here the authors explore the role of activins in promoting intestinal regeneration and nutrient-dependent gut resizing in Drosophila.
- Christian F. Christensen
- , Quentin Laurichesse
- & Ditte S. Andersen
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Article
| Open Access
Angiogenesis-on-a-chip coupled with single-cell RNA sequencing reveals spatially differential activations of autophagy along angiogenic sprouts
The functional heterogeneity of autophagy in endothelial cells during angiogenesis remains incompletely understood. Here, the authors apply a 3D angiogenesis-on-a-chip coupled with single-cell RNA sequencing to find distinct autophagy functions in two different endothelial cell populations during angiogenic sprouting.
- Somin Lee
- , Hyunkyung Kim
- & Noo Li Jeon
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Comment
| Open Access
From lab to life: how wearable devices can improve health equity
Wearable devices can provide personalised medicine at the point of need, potentially increasing access to health services and therefore improving health equity. Here the authors discuss their experiences developing wearable devices for vulnerable patient populations, including neonates and pregnant individuals.
- Jessica R. Walter
- , Shuai Xu
- & John A. Rogers
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Article
| Open Access
ECOLE: Learning to call copy number variants on whole exome sequencing data
Copy number variants (CNV) are shown to contribute to the etiology of various genetic disorders. Here, authors present ECOLE, a deep learning-based somatic and germline CNV caller for WES data. Utilising a variant of the transformer architecture, the model is trained to call CNVs per exon.
- Berk Mandiracioglu
- , Furkan Ozden
- & A. Ercument Cicek
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Article
| Open Access
Dynamic stability of Sgt2 enables selective and privileged client handover in a chaperone triad
Newly synthesized tail-anchored membrane proteins (TAs) are relayed in a chaperone triad, Hsp70, Sgt2, and Get3, for delivery to the endoplasmic reticulum. Here, the authors show how the conformational dynamics of the cochaperone Sgt2 generates a decision point to enable efficient and selective TA targeting.
- Hyunju Cho
- , Yumeng Liu
- & Shu-ou Shan
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Article
| Open Access
Hijacking of internal calcium dynamics by intracellularly residing viral rhodopsins
Rhodopsins are ubiquitous light-driven membrane proteins that have diverse functions in nature, and value as optogenetics tools. Here the authors characterise type 1 viral channelrhodopsins, showing that they regulate intracellular calcium and can be used for the photocontrol of muscle contraction in vivo.
- Ana-Sofia Eria-Oliveira
- , Mathilde Folacci
- & Michel Vivaudou
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Article
| Open Access
Decoding the gene regulatory network of endosperm differentiation in maize
The cereal endosperm constitutes most of the grain by volume. Here the authors use single-cell analysis of maize developing endosperm to decode gene regulatory networks that likely control endosperm growth and offer a framework for crop improvement.
- Yue Yuan
- , Qiang Huo
- & Zeyang Ma
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Article
| Open Access
Optogenetic spatial patterning of cooperation in yeast populations
Microbial communities are the siege of complex metabolic interactions including cooperation and competition. Here, the authors report the utilization of optogenetics and spatial light-patterning to activate the expression of the invertase SUC2 at selected locations and selectively switch cooperation and competition roles of the yeast cells.
- Matthias Le Bec
- , Sylvain Pouzet
- & Pascal Hersen
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Article
| Open Access
Design automation of microfluidic single and double emulsion droplets with machine learning
Generating microfluidic droplets with application-specific desired characteristics is hard. Here the authors report fluid-agnostic machine learning models capable of accurately predicting device geometries and flow conditions required to generate stable single and double emulsions.
- Ali Lashkaripour
- , David P. McIntyre
- & Polly M. Fordyce
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Article
| Open Access
Terminal modifications independent cell-free RNA sequencing enables sensitive early cancer detection and classification
Cell free RNA is a potentially valuable resource to detect cancer, however, its low concentration in plasma can limit usefulness. Here, the authors devise a library preparation method from 100ul of plasma, and apply to multiple cancer types to detect and classify cancer patients
- Jun Wang
- , Jinyong Huang
- & Deming Gou
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Article
| Open Access
Human apical-out nasal organoids reveal an essential role of matrix metalloproteinases in airway epithelial differentiation
Airway organoids made in Matrigel are in basal-out orientation. Here, authors present apical-out nasal organoids using a biochemically defined hydrogel system, revealing that matrix metalloproteinases are required for normal epithelial development.
- Liyue Li
- , Linyi Jiao
- & Chunwei Li
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Article
| Open Access
Selective blockade of Cav1.2 (α1C) versus Cav1.3 (α1D) L-type calcium channels by the black mamba toxin calciseptine
L-type voltage-gated calcium channels are involved in multiple physiological functions. Here the authors identify calciseptine, a toxin purified from black mamba venom, as a selective inhibitor of Cav1.2 L-type Ca2+ channels.
- Pietro Mesirca
- , Jean Chemin
- & Joël Nargeot
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Article
| Open Access
Deep learning-driven fragment ion series classification enables highly precise and sensitive de novo peptide sequencing
Accurate and high-throughput sequencing methods for proteins are lacking. Here the authors report Spectralis which improves de novo peptide sequencing using a convolutional layer that connects peaks in spectra spaced by amino acid masses, fragment ion series classification and a peptide-spectrum match confidence score.
- Daniela Klaproth-Andrade
- , Johannes Hingerl
- & Julien Gagneur
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Article
| Open Access
Open access repository-scale propagated nearest neighbor suspect spectral library for untargeted metabolomics
Interpreting untargeted mass spectrometry (MS) data is challenging due to incomplete reference libraries. Here, the authors created the nearest neighbor suspect spectral library from largescale public MS data, significantly enhancing the ability to hypothesize structures for unknown mass spectra.
- Wout Bittremieux
- , Nicole E. Avalon
- & Pieter C. Dorrestein
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Article
| Open Access
Building synthetic chromosomes from natural DNA
Building synthetic chromosomes from natural components is an unexplored alternative to de novo chromosome synthesis that may have many potential applications. In this paper, the authors report CReATiNG, a method for constructing synthetic chromosomes from natural components in yeast.
- Alessandro L. V. Coradini
- , Christopher Ne Ville
- & Ian M. Ehrenreich
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Article
| Open Access
Blue-shift photoconversion of near-infrared fluorescent proteins for labeling and tracking in living cells and organisms
Photolabeling of intracellular molecules is an invaluable approach to study multiple cellular processes. Here, the authors report on the near-infrared to far-red photoconversion in the miRFP family of fluorescent proteins, which enables photolabeling entirely performed in the near-infrared range.
- Francesca Pennacchietti
- , Jonatan Alvelid
- & Ilaria Testa
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Article
| Open Access
Voltage sensors of a Na+ channel dissociate from the pore domain and form inter-channel dimers in the resting state
It is believed that voltage sensor domains (VSD) of voltage-gated Na+ channels are always attached to the channel. Here, authors find that VSDs detach from the channel to form inter-channel dimers.
- Ayumi Sumino
- , Takashi Sumikama
- & Katsumasa Irie
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Article
| Open Access
High resolution mapping of the tumor microenvironment using integrated single-cell, spatial and in situ analysis
The integration of single-cell and spatial data can provide a more comprehensive picture of the network of cells within the tumour microenvironment. Here the authors use a combination of single-cell and spatial technologies including 10x Xenium to characterise serial formalin-fixed, paraffin-embedded human breast cancer sections.
- Amanda Janesick
- , Robert Shelansky
- & Sarah E. B. Taylor
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Article
| Open Access
Functional-metabolic coupling in distinct renal cell types coordinates organ-wide physiology and delays premature ageing
Spatially resolved metabolism in complex tissues is vital but poorly understood. Here, the authors establish the Drosophila renal system as a paradigm for linking mechanistic analysis of metabolism at single-cell resolution to organ-wide physiology.
- Jack Holcombe
- & Helen Weavers
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Article
| Open Access
Extending the toolbox for RNA biology with SegModTeX: a polymerase-driven method for site-specific and segmental labeling of RNA
It has been challenging to make long RNAs with site-specific modifications for NMR study. Here the authors present SegModTeX: a method for site-specific and segmental labeling of RNAs independent of their sequence or segment length, with applications for biological- and artificial NTP analogues at purity and scale sufficient for NMR.
- Raphael Haslecker
- , Vincent V. Pham
- & Victoria M. D’Souza
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Article
| Open Access
Mapping protein states and interactions across the tree of life with co-fractionation mass spectrometry
Co-fractionation mass spectrometry (CF-MS) is a powerful technique for mapping protein interactions under physiological conditions. Here, the authors uniformly re-process 411 CF-MS experiments and carry out meta-analyses of protein abundance, protein-protein interactions, and phosphorylation sites in the resulting resource.
- Michael A. Skinnider
- , Mopelola O. Akinlaja
- & Leonard J. Foster
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Article
| Open Access
Profiling ubiquitin signalling with UBIMAX reveals DNA damage- and SCFβ-Trcp1-dependent ubiquitylation of the actin-organizing protein Dbn1
Using Xenopus egg extracts, the authors developed a mass spectrometry method (UBIMAX) to identify proteins ubiquitylated in response to defined DNA lesions. Highlighting UBIMAX’s versatility, they describe the ubiquitylation of the actin regulator Dbn1 in response to DNA double-strand breaks.
- Camilla S. Colding-Christensen
- , Ellen S. Kakulidis
- & Michael L. Nielsen
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Article
| Open Access
Induced formation of primordial germ cells from zebrafish blastomeres by germplasm factors
Primordial germ cell (PGC) transplantation is an important technology for developmental biology and genetic breeding. Here, Wang et al. develop an approach for PGC induction that enhances the efficiency of PGC transplantation in zebrafish.
- Xiaosi Wang
- , Junwen Zhu
- & Yonghua Sun
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Article
| Open Access
A computational toolbox for the assembly yield of complex and heterogeneous structures
Predicting the effective assembly of a set of proteins into a desired structure has traditionally been a challenging task. Here, authors demonstrate that advancements in automatic differentiation make it possible to address this problem using classical statistical mechanics.
- Agnese I. Curatolo
- , Ofer Kimchi
- & Michael P. Brenner
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Article
| Open Access
Proximity extracellular protein-protein interaction analysis of EGFR using AirID-conjugated fragment of antigen binding
Extracellular protein-protein interactions (exPPIs) are essential for understanding the biological function of membrane receptor proteins. Here, the authors demonstrate the FabID technology as a new proximity biotinylation approach that can analyse exPPIs dynamically modulated by drugs and ligands.
- Kohdai Yamada
- , Ryouhei Shioya
- & Tatsuya Sawasaki
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Article
| Open Access
Atypical flagella assembly and haploid genome coiling during male gamete formation in Plasmodium
Gametogenesis is critical for sexual reproduction. Using volume electron microscopy, Hair et al report the structural organisation of the haploid nucleus coiled around the axoneme of the Plasmodium berghei male microgamete.
- Molly Hair
- , Flávia Moreira-Leite
- & Sue Vaughan
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Article
| Open Access
Selenium-based metabolic oligosaccharide engineering strategy for quantitative glycan detection
Metabolic oligosaccharide engineering (MOE) is a classical strategy for carbohydrate perception but suffers from glycan quantification. Here the authors develop a selenium-based metabolic oligosaccharide engineering strategy (SeMOE), based on elemental analysis, to quantitatively detect and visualize glycans both in vitro and in vivo.
- Xiao Tian
- , Lingna Zheng
- & Ran Xie
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Article
| Open Access
Single-cell spatial metabolomics with cell-type specific protein profiling for tissue systems biology
The authors developed a framework for joint protein-metabolite profiling at the single-cell level in human tissue combining targeted multiplexed protein imaging and untargeted spatial metabolomics in a single pipeline.
- Thomas Hu
- , Mayar Allam
- & Ahmet F. Coskun
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Article
| Open Access
GNTD: reconstructing spatial transcriptomes with graph-guided neural tensor decomposition informed by spatial and functional relations
Reconstructing transcriptome-wide spatially-resolved gene expressions requires modelling nonlinear patterns and spatial structures in RNA profiling data. Here, authors introduce a graph-guided neural hierarchical tensor decomposition model that incorporates spatial and functional relations for the task.
- Tianci Song
- , Charles Broadbent
- & Rui Kuang
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Article
| Open Access
Single-photon microscopy to study biomolecular condensates
The wide variety of cellular processes involving biomolecular condensation makes their quantification a challenging task. Here, the authors present an integrated platform based on single-photon microscopy to study complex biomolecular processes.
- Eleonora Perego
- , Sabrina Zappone
- & Giuseppe Vicidomini
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Comment
| Open Access
Is Protein BLAST a thing of the past?
Will protein structure search tools like AlphaFold replace protein sequence search with BLAST? We discuss the promises, using structure search for remote homology detection, and why protein BLAST, as the leading sequence search tool, should strive to incorporate structural information
- Ali Al-Fatlawi
- , Martin Menzel
- & Michael Schroeder
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