Featured
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Article
| Open AccessAlternative splicing controls teneurin-3 compact dimer formation for neuronal recognition
This study reveals how two splice inserts alter the conformation and dimeric arrangement of the teneurin-3 extracellular region. These insights elucidate the role of teneurin isoforms in neuronal recognition and circuit wiring.
- Christos Gogou
- , J. Wouter Beugelink
- & Dimphna H. Meijer
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Article
| Open AccessHIV transmission dynamics and population-wide drug resistance in rural South Africa
There is limited data on drug resistance in South African communities strongly affected by HIV. In this study, the authors observed low levels of resistance to newer drugs but widespread resistance to older HIV medications in a South African community. Resistance to rilpivirine was detected even in untreated individuals.
- Steven A. Kemp
- , Kimia Kamelian
- & Ravindra K. Gupta
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Article
| Open AccessStress-shape misalignment in confluent cell layers
When studying nematic ordering of cells in a monolayer, it is commonly assumed that the principal stress and cell shape axes are tightly coupled. Here, the authors measure cell shape and cell-generated contractile stresses and show that cells in monolayers form correlated, dynamic domains in which the stresses are systematically misaligned with the cell bodies.
- Mehrana R. Nejad
- , Liam J. Ruske
- & Julia M. Yeomans
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Article
| Open AccessA secondary mechanism of action for triazole antifungals in Aspergillus fumigatus mediated by hmg1
Triazole antifungals are widely used and exert their action by inhibiting ergosterol biosynthesis. Here, Rybak et al show that these drugs both inhibit ergosterol biosynthesis and induce accumulation of pathway intermediates that directly induce inhibition of sterol synthesis.
- Jeffrey M. Rybak
- , Jinhong Xie
- & Jarrod R. Fortwendel
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Article
| Open AccessDynamic diversity of SARS-CoV-2 genetic mutations in a lung transplantation patient with persistent COVID-19
In this study, the authors report the case of a patient who underwent lung transplantation and subsequently developed COVID-19 that resulted in persistent infection. Following antiviral treatment, SARS-CoV-2 (BA.5) showed dynamic genetic diversity with remdesivir resistant mutations leading to enhanced fusogenicity.
- Hidetoshi Igari
- , Seiichiro Sakao
- & Eiji Ido
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Article
| Open AccessDistinguishing individual photobodies using Oligopaints reveals thermo-sensitive and -insensitive phytochrome B condensation at distinct subnuclear locations
Photobodies form via the condensation of the light and temperature sensor phytochrome B. Here, the authors label photobodies using nuclear landmarks to demonstrate the nonrandom thermos-sensitive and -insensitive seeding of distinct photobodies.
- Juan Du
- , Keunhwa Kim
- & Meng Chen
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Article
| Open AccessMitochondrial complex I deficiency stratifies idiopathic Parkinson’s disease
Idiopathic Parkinson’s disease can be stratified according to the severity of neuronal respiratory complex I deficiency. The emerging disease subtypes show distinct molecular and clinical profiles.
- Irene H. Flønes
- , Lilah Toker
- & Charalampos Tzoulis
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Article
| Open AccessNew Late Pleistocene age for the Homo sapiens skeleton from Liujiang southern China
Here the authors provide new radiocarbon, U-series, and OSL dates for Homo sapiens fossils from Tongtianyan cave, southern China, placing them at 33-23 thousand years ago and indicating widespread presence of Homo sapiens across eastern Asia in the Late Pleistocene.
- Junyi Ge
- , Song Xing
- & Qingfeng Shao
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Article
| Open AccessSubstrate binding plasticity revealed by Cryo-EM structures of SLC26A2
SLC26A2 transports crucial ions and mutations in it cause diverse diseases. Here, authors present cryo-EM structures of SLC26A2 with substrates, revealing details of its homodimer assembly, dynamic substrate binding, and effects of mutations.
- Wenxin Hu
- , Alex Song
- & Hongjin Zheng
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Article
| Open AccessSulfur oxidation and reduction are coupled to nitrogen fixation in the roots of the salt marsh foundation plant Spartina alterniflora
The mechanisms underlying plant-microbe interactions in coastal ecosystems are little explored. Here, the authors use multi-omics and biogeochemical measurements to investigate the saltmarsh cordgrass root microbiome and its role in coupling nitrogen fixation and sulfur cycling.
- J. L. Rolando
- , M. Kolton
- & J. E. Kostka
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Article
| Open AccessSnail-inspired robotic swarms: a hybrid connector drives collective adaptation in unstructured outdoor environments
The authors introduce a 3D terrestrial robotic swarm equipped with a snail-inspired two-mode connection system for self-reconfigurability and mobility in unstructured environments.
- Da Zhao
- , Haobo Luo
- & Tin Lun Lam
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Article
| Open AccessGut microbiome composition and metabolic activity in women with diverticulitis
Here, the authors present a multi-omics examination of stool samples obtained from individuals with diverticulitis and controls, uncovering disruptions in the balance of microbial composition and metabolites, as well as co-occurring microbe-metabolite associations relevant to the disease.
- Wenjie Ma
- , Yiqing Wang
- & Andrew T. Chan
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Article
| Open AccessscLENS: data-driven signal detection for unbiased scRNA-seq data analysis
Single-cell RNA sequencing data analysis is limited by noise and high dimensionality. Here, authors present scLENS, a tool that automates accurate signal detection without manual input, particularly in complex datasets.
- Hyun Kim
- , Won Chang
- & Jae Kyoung Kim
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Article
| Open AccessEfficient gene knockout and genetic interaction screening using the in4mer CRISPR/Cas12a multiplex knockout platform
Paralog synthetic lethals have been assessed with multiple CRISPR-based methods, but systematic comparison among these platforms is unavailable. Here, the authors systematically compare combinatorial perturbation platforms and establish the in4mer CRISPR/Cas12a multiplex knockout platform.
- Nazanin Esmaeili Anvar
- , Chenchu Lin
- & Traver Hart
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Article
| Open AccessLinear interaction between replication and transcription shapes DNA break dynamics at recurrent DNA break Clusters
In neural progenitor cells, recurrent DNA break clusters (RDCs) occur to genes crucial for brain function. Here the authors find that most RDCs emerge at long-traveling unidirectional replication forks, and often unrelated to R-loops.
- Lorenzo Corazzi
- , Vivien S. Ionasz
- & Pei-Chi Wei
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Article
| Open AccessA vascularized breast cancer spheroid platform for the ranked evaluation of tumor microenvironment-targeted drugs by light sheet fluorescence microscopy
Assessing tumour microenvironment-targeted drug candidates remains challenging. Here, the authors develop a comprehensive screening platform that allows for monitoring, quantifying, and ranking drug-induced effects in self-organizing, vascularized tumour spheroids.
- David Ascheid
- , Magdalena Baumann
- & Erik Henke
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Article
| Open AccessThe pRb/RBL2-E2F1/4-GCN5 axis regulates cancer stem cell formation and G0 phase entry/exit by paracrine mechanisms
Cancer stem cells (CSCs) are associated with chemoresistance and poor prognosis in multiple cancer types. Here, the authors investigate the role of secreted Wnt ligands in pancreatic and breast CSCs and identify E2F1/4-GCN5-pRb/RBL2 as a regulatory axis underlying Wnt secretion.
- Chao-Hui Chang
- , Feng Liu
- & Siim Pauklin
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Article
| Open AccessThe hinge-engineered IgG1-IgG3 hybrid subclass IgGh47 potently enhances Fc-mediated function of anti-streptococcal and SARS-CoV-2 antibodies
Here, the authors elongated the hinge structure of IgG1 monoclonal antibodies. The modified IgG1-IgG3 hybrid subclass showed enhanced Fc-mediated function compared to IgG1 in two distinct biological systems, Streptococcus pyogenes and SARS-CoV-2.
- Arman Izadi
- , Yasaman Karami
- & Pontus Nordenfelt
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Article
| Open AccessCyclodipeptide oxidase is an enzyme filament
Many cyclic dipeptide natural products can be modified by cyclodipeptide oxidase enzymes. Here, the authors report the structural characterization of the cyclodipeptide oxidase AlbAB and show that it assembles into heterooligomeric enzyme filaments.
- Michael P. Andreas
- & Tobias W. Giessen
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Article
| Open AccessStimulus-responsive assembly of nonviral nucleocapsids
A stimulus-responsive approach for recapitulating nonviral nucleocapsid assembly on demand under controlled conditions provides a robust platform for applications in synthetic biology and mRNA nanomedicine.
- Mao Hori
- , Angela Steinauer
- & Donald Hilvert
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Article
| Open AccessLoss of NEDD8 in cancer cells causes vulnerability to immune checkpoint blockade in triple-negative breast cancer
NEDD8 is a ubiquitin-like protein that governs protein neddylation, previously demonstrated to be essential for cell survival. Here the authors show that NEDD8 loss in breast cancer cells is associated with enhanced immunogenicity and increased sensitivity to PD-1 blockade in preclinical cancer models.
- Irineos Papakyriacou
- , Ginte Kutkaite
- & Yumeng Mao
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Article
| Open AccessLifecycle of a predatory bacterium vampirizing its prey through the cell envelope and S-layer
The predatory bacterium Bdellovibrio exovorus attaches on the surface on other bacteria and feeds on them. Here, the authors study the lifecycle of B. exovorus, showing that it proliferates by non-binary division, firm junctions are established between prey and predator outer membranes, and a proteinaceous S-layer does not protect prey cells against predation.
- Yoann G. Santin
- , Adrià Sogues
- & Géraldine Laloux
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Article
| Open AccessAstroglial Kir4.1 potassium channel deficit drives neuronal hyperexcitability and behavioral defects in Fragile X syndrome mouse model
Fragile X syndrome is a neurodevelopmental disorder with altered neuronal excitability and behavior. Here, the authors show that dysfunction of astroglial Kir4.1 potassium channels drives neuronal and behavioral impairments in a fragile X mouse model.
- Danijela Bataveljic
- , Helena Pivonkova
- & Nathalie Rouach
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Article
| Open AccessA MTA2-SATB2 chromatin complex restrains colonic plasticity toward small intestine by retaining HNF4A at colonic chromatin
The large intestine mucosa possesses a surprising plasticity to switch on small intestine genes. Here, Wei G. et al. show that a chromatin complex composed of SATB2, MTA2 and HNF4A regulates this tissue plasticity in the adult gut.
- Wei Gu
- , Xiaofeng Huang
- & Qiao Zhou
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Article
| Open AccessMechanism of DNA unwinding by MCM8-9 in complex with HROB
MCM8-9 and HROB function together in DNA damage response. Here, the authors describe the mechanism of DNA unwinding by MCM8-9 and its activation by HROB. HROB makes direct contacts with both MCM8 and MCM9 and promotes DNA unwinding downstream of MCM8-9 loading and hexameric ring formation on DNA.
- Ananya Acharya
- , Hélène Bret
- & Petr Cejka
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Article
| Open AccessReservoir displacement by an invasive rodent reduces Lassa virus zoonotic spillover risk
Mastomys natalensis is a rodent species native to West Africa that is the primary reservoir host for Lassa virus. Here, the authors investigate whether the invasive rodent Rattus rattus decreases M. natalensis density and could therefore indirectly decrease zoonotic transmission of Lassa virus to humans.
- Evan A. Eskew
- , Brian H. Bird
- & Scott L. Nuismer
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Article
| Open AccessMacrophage-fibroblast JAK/STAT dependent crosstalk promotes liver metastatic outgrowth in pancreatic cancer
An inflammatory-fibrotic tumor microenvironment supports metastatic disease progression in pancreatic ductal adenocarcinoma (PDAC). Here the authors show that metastasis-infiltrating macrophages influence metastasis-associated fibroblast (MAF) heterogeneity in liver metastatic PDAC, by promoting JAK/STAT signalling pathway activation in MAFs.
- Meirion Raymant
- , Yuliana Astuti
- & Michael C. Schmid
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Article
| Open AccessClimate-forced Hg-remobilization associated with fern mutagenesis in the aftermath of the end-Triassic extinction
This study provides evidence for long-term effects of volcanic emissions of large quantities of gaseous mercury (Hg) and plant mutagenesis by recording high abundances of malformed fern spores across the Triassic-Jurassic boundary and Early Jurassic.
- Remco Bos
- , Wang Zheng
- & Bas van de Schootbrugge
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Article
| Open AccessComposition and metabolism of microbial communities in soil pores
The work proposes the concept of distinct micro-habitats within an intact soil matrix and describes composition and metabolic pathways of their bacterial inhabitants, as a first step towards a generalizable C processing-focused classification of soil micro-environmental conditions.
- Zheng Li
- , Alexandra N. Kravchenko
- & Evgenia Blagodatskaya
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Article
| Open AccessHuman connectome topology directs cortical traveling waves and shapes frequency gradients
The factors that determine the direction of traveling waves in the brain are not well understood. Here, the authors show that the sum of incoming structural connection strengths shape both traveling wave direction and frequency gradients.
- Dominik P. Koller
- , Michael Schirner
- & Petra Ritter
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Article
| Open AccessHBO1 catalyzes lysine lactylation and mediates histone H3K9la to regulate gene transcription
The regulatory mechanism and functional consequence of lysine lactylation remain to be explored. Here, the authors identify HBO1 as a lysine lactyltransferase and suggest a potential role of HBO1 in tumorigenesis through H3K9la-mediated transcription regulation.
- Ziping Niu
- , Chen Chen
- & Kai Zhang
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Article
| Open AccessIdentification of triacylglycerol remodeling mechanism to synthesize unusual fatty acid containing oils
Triacylglycerol remodeling in Physaria fendleri changes the seed oil fatty acid composition after initial synthesis to overcome metabolic bottlenecks in the accumulation of valuable unusual fatty acids. This process enhances designer oil engineering.
- Prasad Parchuri
- , Sajina Bhandari
- & Philip D. Bates
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Article
| Open AccessOxygen enhances antiviral innate immunity through maintenance of EGLN1-catalyzed proline hydroxylation of IRF3
Oxygen is an essential requirement for aerobic organisms. Here the authors explore the role of oxygen in the antiviral innate response in multiple models of infection and suggest oxygen enhances the antiviral innate response via EGLN1 hydroxylation of IRF3.
- Xing Liu
- , Jinhua Tang
- & Wuhan Xiao
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Article
| Open AccessTargeted small molecule inhibitors blocking the cytolytic effects of pneumolysin and homologous toxins
The pore-forming toxin pneumolysin is responsible for the high mortality seen in pneumococcal infections unresponsive to antibiotics. In this work, authors report a small molecule inhibitor targeting pneumolysin and related ones as an anti-virulence strategy protecting human cells during infection.
- Umer Bin Abdul Aziz
- , Ali Saoud
- & Jörg Rademann
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Article
| Open AccessA mechanical-assisted post-bioprinting strategy for challenging bone defects repair
Bioprinting has revitalized tissue regeneration efforts, yet challenges persist due to cell damage during fabrication and mechanical instability of printed scaffolds. Here, the authors develop a mechanical-assisted post-bioprinting strategy for loading cells into hollow scaffolds that effectively repair challenging bone defects.
- Jirong Yang
- , Zhigang Chen
- & Changshun Ruan
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Article
| Open AccessUnravelling and reconstructing the biosynthetic pathway of bergenin
Bergenin is a rare C-glycoside of 4-O-methyl gallic acid with multiple pharmacological properties. Here, the authors report the elucidation of the biosynthetic pathway of bergenin in Ardisia japonica and its bioproduction by engineered E. coli.
- Ruiqi Yan
- , Binghan Xie
- & Lin Yang
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Article
| Open AccessStructural insights into the functional mechanism of the ubiquitin ligase E6AP
The human papillomavirus (HPV) E6 oncoprotein hijacks the ligase activity of the host E6AP to ubiquitinate the tumor suppressor p53. Here, the authors show how the presence of the HPV E6 oncoprotein transforms the inactive E6AP monomer into an active dimer, providing a structural understanding of the physiological and pathophysiological mechanisms of E6AP function.
- Zhen Wang
- , Fengying Fan
- & Xuekui Yu
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Article
| Open AccessThe airborne transmission of viruses causes tight transmission bottlenecks
Genomic analyses have indicated that a small number of virus particles usually found new infections. Here, the authors use a mathematical model to show that this small transmission bottleneck is a result of the physical processes of airborne virus emission, diffusion, and inhalation.
- Patrick Sinclair
- , Lei Zhao
- & Christopher J. R. Illingworth
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Article
| Open AccessRinRK1 enhances NF receptors accumulation in nanodomain-like structures at root-hair tip
RinRK1 interacts with NFR1 and NFR5 through their extracellular domains, facilitating a complex with Flot1. This interaction promotes their localization at root hair tip nanodomains, crucial for mediating the rhizobial infection.
- Ning Zhou
- , Xiaolin Li
- & Fang Xie
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Article
| Open AccessLSD1 inhibition circumvents glucocorticoid-induced muscle wasting of male mice
Even though glucocorticoids are potent anti-inflammatory agents, they can cause muscle wasting. Here, the authors show that targeting the glucocorticoid receptor coactivator LSD1 limits muscle loss without reducing the drugs’ efficiency on the immune system.
- Qingshuang Cai
- , Rajesh Sahu
- & Delphine Duteil
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Article
| Open AccessDiphthamide deficiency promotes association of eEF2 with p53 to induce p21 expression and neural crest defects
Rare disease DEDSSH1-associated DPH1 mutations impair eEF2 diphthamide modification that leads to eEF2 as a transcriptional coactivator for p53 to enhance expression of the cell proliferation inhibitor p21, resulting in birth defects.
- Yu Shi
- , Daochao Huang
- & Weihong Song
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Article
| Open AccessProbing the surface charge of condensates using microelectrophoresis
The surface charge and ζ-potential of biomolecular condensates is key to their interactions with membranes and proteins. Here, the authors developed a method to determine the ζ-potential of condensates using microelectrophoresis and single-droplet tracking.
- Merlijn H. I. van Haren
- , Brent S. Visser
- & Evan Spruijt
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Article
| Open AccessMucosal prime-boost immunization with live murine pneumonia virus-vectored SARS-CoV-2 vaccine is protective in macaques
Immunization via the respiratory route is predicted to increase the effectiveness of SARS-CoV-2 vaccines. Here, Kaiser et al. describe a murine pneumonia virus vectored vaccine expressing spike protein, and show that intranasal immunization of male rhesus macaques provides good mucosal and systemic immunogenicity and efficacy.
- Jaclyn A. Kaiser
- , Christine E. Nelson
- & Cyril Le Nouën
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Article
| Open AccessMechanism of Ψ-Pro/C-degron recognition by the CRL2FEM1B ubiquitin ligase
A key question in the ubiquitin-proteasome system is how E3 ligases select their substrates. Here, the authors reveal that CRL2FEM1B E3 ligase functions as a dimer and employs a bipartite mode of substrate recognition, requiring a C-terminal proline and an upstream aromatic residue in the target.
- Xinyan Chen
- , Anat Raiff
- & Chao Xu
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Article
| Open AccessAn individualized protein-based prognostic model to stratify pediatric patients with papillary thyroid carcinoma
Papillary thyroid carcinoma has a heterogenous outcome, particularly in paediatric patients. Here, the authors utilise machine learning to create a protein-based prognostic model to predict recurrence risk.
- Zhihong Wang
- , He Wang
- & Yaoting Sun
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Article
| Open AccessCAR affinity modulates the sensitivity of CAR-T cells to PD-1/PD-L1-mediated inhibition
It has been suggested that targeting the PD-1/PD-L1 axis can increase the anti-tumor properties of chimeric antigen receptor (CAR)-T cells. Here the authors report that CAR affinity modulates the sensitivity of CAR-T cells to PD-1/PD-L1-mediated inhibition.
- Irene Andreu-Saumell
- , Alba Rodriguez-Garcia
- & Sonia Guedan
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Article
| Open AccessA cluster-randomized trial of water, sanitation, handwashing and nutritional interventions on stress and epigenetic programming
A regulated stress response is essential for healthy child growth and development. Here, the authors show that a nutrition, water, sanitation, and hygiene intervention enhanced adaptive responses of the physiological stress system in early childhood.
- Audrie Lin
- , Andrew N. Mertens
- & Douglas A. Granger
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Article
| Open AccessMetabolomics facilitates differential diagnosis in common inherited retinal degenerations by exploring their profiles of serum metabolites
Diagnosing inherited retinal degeneration is challenging. This exploratory study showed that metabolomic profiles differ among different subtypes of IRD, and potential biomarkers could be identified to facilitate diagnosis workflow in the near future.
- Wei-Chieh Wang
- , Chu-Hsuan Huang
- & Ta-Ching Chen
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Article
| Open AccessBiocompatible aggregation-induced emission active polyphosphate-manganese nanosheets with glutamine synthetase-like activity in excitotoxic nerve cells
Glutamine synthetase (GS) relies on Adenosine triphosphate (ATP) to activate glutamate (Glu) and are vital for maintaining ammonia and Glu homeostasis, but GS function is impaired during ATP-deficient neurotoxic events. Here the authors report polyphosphate-manganese nanosheets having GS-like activity independent of ATP to promote the conversion of Glu to glutamine in excitatory neurotoxic cells.
- Jing Wang
- , Xinyang Zhao
- & Wei Wei
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