Featured
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Article
| Open AccessConvergent evolution of fern nectaries facilitated independent recruitment of ant-bodyguards from flowering plants
Some plants use nectar to attract ant bodyguards. Here, the authors use a cross-kingdom phylogenetic approach to find that ferns and angiosperms evolved nectaries in the Cretaceous, coinciding with ant evolution, and that ferns recruited ant-bodyguards from existing ant-angiosperm partnerships.
- Jacob S. Suissa
- , Fay-Wei Li
- & Corrie S. Moreau
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Article
| Open AccessEnvironment modulates protein heterogeneity through transcriptional and translational stop codon readthrough
This study unveils that stop codon readthrough is prevalent in E. coli, particularly under stress conditions. It highlights the influence of stop codon type and genetic context, with both transcriptional and translational origins.
- Maria Luisa Romero Romero
- , Jonas Poehls
- & Agnes Toth-Petroczy
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Article
| Open AccessHDAC activity is dispensable for repression of cell-cycle genes by DREAM and E2F:RB complexes
Here, the authors investigate the interplay among DREAM, RB, SIN3 proteins, and HDACs in the context of cell-cycle gene repression, suggesting that E2F:RB and DREAM complexes can repress cell-cycle genes without relying on HDAC activity.
- Alison K. Barrett
- , Manisha R. Shingare
- & Gerd A. Müller
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Article
| Open AccessDeleting the mitochondrial respiration negative regulator MCJ enhances the efficacy of CD8+ T cell adoptive therapies in pre-clinical studies
Treatment failure following chimaeric antigen receptor (CAR) T cell therapy is common yet incompletely understood. In this study, the authors demonstrate that deletion of the mitochondrial negative regulator, MCJ, in CAR T cells promotes target cell killing ex vivo and augments their efficacy in an in vivo B cell leukaemia model.
- Meng-Han Wu
- , Felipe Valenca-Pereira
- & Mercedes Rincon
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Article
| Open AccessRelative dispersion ratios following fecal microbiota transplant elucidate principles governing microbial migration dynamics
Microbial migration profoundly impacts ecosystems. Here, the authors introduce a statistical approach to explore microbial dispersion following fecal microbiota transplant, uncovering dependencies between colonizing taxa, with insights into community dynamics.
- Yadid M. Algavi
- & Elhanan Borenstein
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Article
| Open AccessHeterogeneity in strategy use during arbitration between experiential and observational learning
People learn by observing others and from personal experience, but which strategy they favor varies. Here, the authors show that while some people dynamically arbitrate and switch to the strategy that is most reliable, others preferentially use one or a fixed mixture of strategies.
- Caroline J. Charpentier
- , Qianying Wu
- & John P. O’Doherty
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Article
| Open AccessUltrafast energy quenching mechanism of LHCSR3-dependent photoprotection in Chlamydomonas
The Light Harvesting Complex Stress-Related Protein (LHCSR) can protect algae from severe photodamage via energy-dependent quenching (qE). Here, the authors find that a photoproduct of carotenoid S1 state is populated in qE and depopulated in 7.5 ps.
- Mengyuan Zheng
- , Xiaojie Pang
- & Lijin Tian
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Article
| Open AccessImmune features are associated with response to neoadjuvant chemo-immunotherapy for muscle-invasive bladder cancer
In the phase 2 study LCCC1520 (NCT02690558), clinical activity of pembrolizumab in combination with gemcitabine and cisplatin as neoadjuvant therapy in patients with muscle-invasive bladder cancer has been reported. Here the authors present molecular and immune cellular features associated with response to neoadjuvant chemo-immunotherapy.
- Wolfgang Beckabir
- , Mi Zhou
- & Benjamin G. Vincent
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Article
| Open AccessH2AX promotes replication fork degradation and chemosensitivity in BRCA-deficient tumours
Histone H2AX has a known role in DNA damage repair but interestingly, its loss is associated with resistance to poly(ADP-ribose) polymerase (PARP) inhibition in BRCA-deficient tumours. Here, the authors identify a role of γH2AX in the degradation of replication forks and demonstrate that H2AX loss drives PARP inhibitor resistance via increased stressed fork stability in BRCA-deficient tumours.
- Diego Dibitetto
- , Martin Liptay
- & Sven Rottenberg
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Article
| Open AccessHyperactivity of indirect pathway-projecting spiny projection neurons promotes compulsive behavior
Striatal hyperactivity has been linked to compulsive behavior, but cell-type and pathway specific mechanisms are unclear. Here, the authors show excessive grooming in Sapap3-KO mice is associated with indirect pathway hyperactivity and suppression of hyperactivity normalizes grooming.
- Sean C. Piantadosi
- , Elizabeth E. Manning
- & Susanne E. Ahmari
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Article
| Open AccessStructure and inhibition of the human lysosomal transporter Sialin
Sialin transports multiple substrates including sialic acid out of lysosomes, and neurotransmitters into synaptic vesicles. This study reports the cryo-EM structures of Sialin in multiple states revealing its transport and pH-sensing mechanisms.
- Philip Schmiege
- , Linda Donnelly
- & Xiaochun Li
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Article
| Open AccessImpact of secretin receptor homo-dimerization on natural ligand binding
GPCRs can form functionally important dimers. Here, authors study impact of dimerization of the secretin receptor on peptide ligand binding and show high receptor conformational dynamics that facilitate G protein recruitment and activation.
- Kaleeckal G. Harikumar
- , Sarah J. Piper
- & Laurence J. Miller
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Article
| Open AccessAutophagy-deficient macrophages exacerbate cisplatin-induced mitochondrial dysfunction and kidney injury via miR-195a-5p-SIRT3 axis
Tubulointerstitial inflammation occurs frequently in acute kidney injury (AKI), and Mφ autophagy is a known contributor to inflammation-related diseases. Here, Yuan et al. show that Mφ autophagy deficiency induces systemic inflammation, impairs mitochondria, and worsens kidney injury in AKI mice.
- Yujia Yuan
- , Longhui Yuan
- & Yanrong Lu
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Article
| Open AccessAngle between DNA linker and nucleosome core particle regulates array compaction revealed by individual-particle cryo-electron tomography
Here, using cryo-ET, the 3D structures of individual nucleosome particles were characterized to observe changes under varying ionic strengths and in the presence of protein H1, revealing key regulatory roles in chromatin organization dynamics.
- Meng Zhang
- , César Díaz-Celis
- & Gang Ren
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Article
| Open AccessZO-1 interacts with YB-1 in endothelial cells to regulate stress granule formation during angiogenesis
ZO-1, a cell junction protein, is essential for angiogenesis. Here the authors identify in endothelial cells unexpected associations of ZO-1 with stress granule proteins, such as YB-1, that are crucial for cytoprotection, implicating the ZO-1-YB-1 interaction in angiogenesis.
- Yassine El Bakkouri
- , Rony Chidiac
- & Jean-Philippe Gratton
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Article
| Open AccessA comprehensive benchmarking with interpretation and operational guidance for the hierarchy of topologically associating domains
TAD hierarchy demonstrates cell-to-cell variability, leading to the development of numerous callers. Here, authors present a comprehensive benchmark of TAD hierarchy callers and introduce the ‘air conditioner’ model to illustrate TAD hierarchy’s role in transcription.
- Jingxuan Xu
- , Xiang Xu
- & Hebing Chen
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Article
| Open AccessIlluminating the function of the orphan transporter, SLC22A10, in humans and other primates
Orphan transporters can be found in over 20 families in the SLC superfamily. Here, the authors show that human SLC22A10 is a unitary pseudogene due to a fixed missense mutation, P220; while in great apes, its orthologs transport sex steroid conjugates.
- Sook Wah Yee
- , Luis Ferrández-Peral
- & Kathleen M. Giacomini
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Article
| Open AccessDevelopment of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus
Highly pathogenic avian influenza viruses from H5 clade 2.3.4.4b are circulating widely in birds and have recently caused large outbreaks in mammals. Here, Furey et al. develop a clade 2.3.4.4b HA-expressing mRNA-LNP vaccine and show that it elicits strong protective immune responses in mice and ferrets.
- Colleen Furey
- , Gabrielle Scher
- & Scott E. Hensley
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Article
| Open AccessEnteric nervous system regeneration and functional cure of experimental digestive Chagas disease with trypanocidal chemotherapy
The digestive form of Chagas disease (American trypanosomiasis) involves damage to the nervous system of the gastrointestinal tract and problems with peristalsis. Here, Khan et al show that infection causes damage to the colon that can be reversed if it is successfully treated early in the process.
- Archie A. Khan
- , Harry C. Langston
- & Michael D. Lewis
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Article
| Open AccessThe patatin-like protein PlpD forms structurally dynamic homodimers in the Pseudomonas aeruginosa outer membrane
The Omp85 superfamily is a widely distributed class of outer membrane proteins found in Gram-negative bacteria, mitochondria and chloroplasts. Here the authors show that PlpD has a different structure and topology than other Omp85 proteins that have been studied.
- Sarah E. Hanson
- , Tyrone Dowdy
- & Harris D. Bernstein
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Article
| Open AccessA rationally designed miniature of soluble methane monooxygenase enables rapid and high-yield methanol production in Escherichia coli
Soluble methane monooxygenase (sMMO) is a potentially value biocatalyst, but production of active recombinant sMMO is very challenging. Here the authors report the rational design and construction of a catalytically active miniature sMMO which enables high-yield production of methanol in E. coli.
- Yeonhwa Yu
- , Yongfan Shi
- & Jeewon Lee
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Article
| Open AccessSolutes unmask differences in clustering versus phase separation of FET proteins
Biomolecular condensates form via phase separation of multivalent macromolecules. Phase separation is governed by solubility whereas multivalence drives percolation, also known as gelation. The authors in this work identify the distinct energy and length scales that influence phase separation versus percolation.
- Mrityunjoy Kar
- , Laura T. Vogel
- & Rohit V. Pappu
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Article
| Open AccessSingle molecule delivery into living cells
Controlled manipulation of cultured cells by delivery of exogenous macromolecules is a cornerstone of experimental biology. Here, the authors describe a platform to deliver defined numbers of macromolecules into cultured cell lines at single molecule resolution.
- Chalmers C. Chau
- , Christopher M. Maffeo
- & Paolo Actis
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Article
| Open AccessThe brain structure, inflammatory, and genetic mechanisms mediate the association between physical frailty and depression
Identifying modifiable risk factors that could prevent depression is important. Here, the authors show increased risks of incident depression in pre-frail and frail individuals and highlight the mediating role of brain structure and inflammation.
- Rongtao Jiang
- , Stephanie Noble
- & Dustin Scheinost
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Article
| Open AccessIn-depth organic mass cytometry reveals differential contents of 3-hydroxybutanoic acid at the single-cell level
Comprehensive single-cell metabolic profiling is critical for revealing phenotypic heterogeneity and elucidating the molecular mechanisms underlying biological processes. Here, the authors establish a novel single-cell metabolomics platform for in-depth organic mass cytometry.
- Shaojie Qin
- , Yi Zhang
- & Yu Bai
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Article
| Open AccessReduction of specific enterocytes from loss of intestinal LGR4 improves lipid metabolism in mice
How LGR4 impacts nutrition absorption and energy homeostasis is unknown. Here, the authors show that LGR4 loss in the intestinal epithelium decreases the proportion of enterocytes selective for long-chain fatty acid absorption, reducing lipid absorption and improving lipid and glucose metabolism.
- Yuan Liang
- , Chao Luo
- & Yue Yin
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Article
| Open AccessSingle-cell and spatial transcriptomics analysis of non-small cell lung cancer
Myeloid cell populations play a critical role in lung cancer progression. Here, the authors use scRNA-seq and spatial transcriptomics to identify changes in the phenotype of macrophages within the tumour microenvironment.
- Marco De Zuani
- , Haoliang Xue
- & Ana Cvejic
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Article
| Open AccessTranslation initiation factor eIF1.2 promotes Toxoplasma stage conversion by regulating levels of key differentiation factors
Wang et al. show that Toxoplasma gondii translation initiation factor eIF1.2 is critical for acute to chronic stage transition during infection, underscoring the importance of protein translation in controlling stage differentiation.
- Fengrong Wang
- , Michael J. Holmes
- & Vern B. Carruthers
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Article
| Open AccessAn integrated spatio-temporal view of riverine biodiversity using environmental DNA metabarcoding
Using intensive eDNA sampling in space and time across five rivers in Europe and North America, this study shows that eDNA gives relevant information on freshwater diversity and ecology across broad taxonomic groups, and with limited downstream transport. The findings demonstrate that eDNA is vital for freshwater biodiversity monitoring in a time of anthropogenic change.
- William Bernard Perry
- , Mathew Seymour
- & Simon Creer
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Article
| Open AccessA nutrient responsive lipase mediates gut-brain communication to regulate insulin secretion in Drosophila
Amplification of glucose stimulated insulin secretion by lipids is not fully understood due to complex inter organ communication in glycemic regulation. Here the authors show Vaha, a Drosophila lipase synthesized in the gut, concentrates in insulin producing cells in the brain to regulate insulin like peptide release.
- Alka Singh
- , Kandahalli Venkataranganayaka Abhilasha
- & Usha R. Acharya
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Article
| Open AccessCompound mortality impacts from extreme temperatures and the COVID-19 pandemic
Extreme weather and pandemics are classified as two of the most serious risks facing the UK in its National Risk Register. Here, the authors investigate the compound mortality impacts of extreme high and low temperatures and COVID-19 in England and Wales.
- Y. T. Eunice Lo
- , Dann M. Mitchell
- & Antonio Gasparrini
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Article
| Open AccessFar-East Asian Toxoplasma isolates share ancestry with North and South/Central American recombinant lineages
The population genome structure of Asian Toxoplasma remains incompletely understood. This study analyzes intercontinental genomic admixture in 17 isolates from Japan and China, providing insights into the evolution of parasites and their impact on public health.
- Fumiaki Ihara
- , Hisako Kyan
- & Masahiro Yamamoto
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Article
| Open AccessPrediction of Klebsiella phage-host specificity at the strain level
Bacterial viruses (phages) are promising alternatives to treat antibiotic-resistant bacterial infections, but finding matching phages against bacteria of interest is challenging. Here, Boeckaerts et al. present a machine learning approach that predicts phage-bacteria pairs at the strain level for Klebsiella pathogens.
- Dimitri Boeckaerts
- , Michiel Stock
- & Yves Briers
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Article
| Open AccessEnvironmental conditions associated with initial northern expansion of anatomically modern humans
Past global human migration was the result of environmental and cultural factors. Here, the authors develop a statistical approach that combines archaeological, genetic, and palaeoclimate data to identify regional environmental conditions facilitating population expansion routes in northern Eurasia and the Americas.
- Frédérik Saltré
- , Joël Chadœuf
- & Corey J. A. Bradshaw
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Article
| Open AccessHippocampal sharp-wave ripples correlate with periods of naturally occurring self-generated thoughts in humans
Whether and how sharp-wave ripples (SWRs) accompany mental states that are less closely linked to events in the immediate environment are not fully understood. Here authors recorded SWRs from hippocampus of 10 epilepsy patients for up to 15 days with experience sampling. SWR rates showed circadian fluctuation and were associated with self-generated thoughts such as mind wandering.
- Takamitsu Iwata
- , Takufumi Yanagisawa
- & Haruhiko Kishima
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Review Article
| Open AccessControlled oxygen delivery to power tissue regeneration
This review explores the role of oxygen and its delivery via engineered biomaterials in a plethora of physiological processes. This piece emphasises on the application of advanced oxygen delivery strategies, as well as discussing advances in oxygen-generating materials and oxygen-perfusing devices.
- Elizabeth Zoneff
- , Yi Wang
- & Lilith M. Caballero-Aguilar
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Article
| Open AccessCystine-knot peptide inhibitors of HTRA1 bind to a cryptic pocket within the active site region
Here the authors use phage display to develop cystine-knot peptides that inhibit the trimeric serine protease HTRA1. Structural and biochemical characterisation uncovered binding of the peptides to a cryptic pocket that locked the active site in a noncompetent state.
- Yanjie Li
- , Yuehua Wei
- & Daniel Kirchhofer
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Article
| Open AccessA modular framework for multi-scale tissue imaging and neuronal segmentation
Tools to segment cellular and sub-cellular neuronal structures can be hindered by high neuronal density and low signal-to-noise in thick samples. Here, the authors present SENPAI, a framework for imaging and segmenting neurons from conventional and super-resolution microscopy of clarified brain tissues.
- Simone Cauzzo
- , Ester Bruno
- & Nicola Vanello
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Article
| Open AccessRevealing the mechanism and function underlying pairwise temporal coupling in collective motion
It is known that spatially localized interactions can give rise to self-organized collective motion. Here, by studying pairwise interactions in juvenile zebrafish, authors reveal the role of reciprocal temporal coupling and find that temporal coordination considerably improves spatial responsiveness, such as reacting to changes in the direction of motion of a partner.
- Guy Amichay
- , Liang Li
- & Iain D. Couzin
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Article
| Open AccessIntegrating cryo-OrbiSIMS with computational modelling and metadynamics simulations enhances RNA structure prediction at atomic resolution
Conventional structural biology techniques are limited in deciphering complex RNA structures and dynamic interactions. Here the authors show an integrated approach that combines cryogenic OrbiSIMS (cryo-OrbiSIMS) with computational methods for modelling RNA structures at atomic resolution.
- Shannon Ward
- , Alex Childs
- & Aditi N. Borkar
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Article
| Open AccessDNA methylation-based high-resolution mapping of long-distance chromosomal interactions in nucleosome-depleted regions
Here, the authors present MTAC, a method to map chromosomal interactions in budding yeast. By applying MTAC to various viewpoints, they find that most of the long-distance chromosomal interactions detected by MTAC reflect tethering by the nuclear pore complexes.
- Yi Li
- , James Lee
- & Lu Bai
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Article
| Open AccessIntegrating human endogenous retroviruses into transcriptome-wide association studies highlights novel risk factors for major psychiatric conditions
Duarte et al. report that common genetic variants linked to psychiatric disorders influence the regulation of ancient retroviruses integrated into the genome. This suggests ancient viruses acquired millions of years ago may have shaped modern human brain function.
- Rodrigo R. R. Duarte
- , Oliver Pain
- & Timothy R. Powell
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Article
| Open AccessArtificial intelligence enables precision diagnosis of cervical cytology grades and cervical cancer
Cervical screening is a key method for detecting cervical cancer, but is limited by pathologist detection. Here, the authors use artificial intelligence to predict cytology grades from whole slide images.
- Jue Wang
- , Yunfang Yu
- & Herui Yao
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Article
| Open AccessDual-mode harvest solar energy for photothermal Cu2-xSe biomineralization and seawater desalination by biotic-abiotic hybrid
Biotic-abiotic photosynthetic systems hold great promise to innovate solar-driven chemical transformation. Here, the authors construct a biotic-abiotic hybrid system composed of Shewanella oneidensis MR-1 and biogenic Se0 nanoparticles for photothermal Cu2-xSe biomineralization and then for seawater desalination.
- Sheng-Lan Gong
- , YangChao Tian
- & Li-Jiao Tian
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Article
| Open AccessLocalized and global representation of prior value, sensory evidence, and choice in male mouse cerebral cortex
The extent to which brains employ Bayesian principles remains unclear. Here, the authors provide evidence suggesting that neurons in the medial prefrontal cortex represent the modulation of reward expectation (i.e., prior values) with incoming sensory inputs to compute confidence values.
- Kotaro Ishizu
- , Shosuke Nishimoto
- & Akihiro Funamizu
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Article
| Open AccessAbrupt onset of intensive human occupation 44,000 years ago on the threshold of Sahul
Archaeological and genetic evidence suggest differing scenarios for human migration out of Africa. Here, the authors present archaeological evidence of intense occupation in Wallacea from 44 thousand years ago, suggesting that this occupation obscured genetic evidence of earlier dispersals.
- Ceri Shipton
- , Mike W. Morley
- & Sue O’Connor
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Perspective
| Open AccessRediscovery of mononuclear phagocyte system blockade for nanoparticle drug delivery
Temporal blockade of the mononuclear phagocyte system is an approach to enhance the therapeutic efficiency of nanocarrier drug-delivery systems but the broad applicability is hindered by the complexity of optimisation and management of potential side effects. Here, the authors review the development of this technique and show its efficiency using meta-analysis of the published data and discuss essential features for its successful translation to clinic.
- Ivan V. Zelepukin
- , Konstantin G. Shevchenko
- & Sergey M. Deyev
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Article
| Open AccessPost-COVID conditions following COVID-19 vaccination: a retrospective matched cohort study of patients with SARS-CoV-2 infection
The impact of COVID-19 vaccination on post-COVID conditions is not well understood. Here, the authors use electronic health record data from a network of eight integrated healthcare systems in the United States to compare rates of post-COVID conditions in those with and without vaccination.
- Debbie E. Malden
- , In-Lu Amy Liu
- & Sara Y. Tartof
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Article
| Open AccessCellular structure of dinosaur scales reveals retention of reptile-type skin during the evolutionary transition to feathers
The evolution of feathers is associated with the evolution of related skin microstructures. Here, the authors demonstrate that Psittacosaurus, a non-avian feathered dinosaur, retained scaled skin like its ancestors in body regions lacking feathers.
- Zixiao Yang
- , Baoyu Jiang
- & Maria E. McNamara
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