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Article
| Open AccessEmergence of enhancers at late DNA replicating regions
Here the authors report that enhancers appear more often in late-replicating DNA regions and are enriched for mutations affecting TF binding. This relationship with DNA replication time is seen in species evolution and cancer, suggesting a fundamental principle of genome evolution.
- Paola Cornejo-Páramo
- , Veronika Petrova
- & Emily S. Wong
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Perspective
| Open AccessAutomated in vivo enzyme engineering accelerates biocatalyst optimization
Achieving cost-competitive bio-based processes requires development of stable and selective biocatalysts. In this Perspective, the authors propose an integrated solution combining growth-coupled selection with machine learning and automated workflows to accelerate development pipelines.
- Enrico Orsi
- , Lennart Schada von Borzyskowski
- & Steffen N. Lindner
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Article
| Open AccessPatrilineal segmentary systems provide a peaceful explanation for the post-Neolithic Y-chromosome bottleneck
Prior work has identified a male-only effective population size bottleneck 3-5000 years ago. While violent competition has been proposed as a cause, the authors here show that a segmentary patrilineal system with lineal fission provides a peaceful alternative explanation.
- Léa Guyon
- , Jérémy Guez
- & Raphaëlle Chaix
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Article
| Open AccessChromosome organization shapes replisome dynamics in Caulobacter crescentus
Whether bacterial replisome progression follows a “factory” or “track” model remains a long-standing controversy. Here, the authors find that cells can switch between the two models, in a process governed by dynamic chromosome organization processes.
- Chen Zhang
- , Asha Mary Joseph
- & Suliana Manley
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Article
| Open AccessFunctional synergy of a human-specific and an ape-specific metabolic regulator in human neocortex development
Cell metabolism has emerged as a major factor implicated in human brain evolution. Here, the authors show that an ape-specific enzyme enhances the ability of a human-specific enzyme to increase glutaminolysis and therefore expand the size of the human neocortex.
- Lei Xing
- , Vasiliki Gkini
- & Takashi Namba
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Article
| Open AccessGoal-directed and flexible modulation of syllable sequence within birdsong
Birdsong contains strings of syllables and is essential for their communication. Using a new song decoder to annotates song in a quasi-real-time manner, and rewarding specific syllable sequences, this study shows Bengalese finches can flexibly modify the content of their song in a goal-directed way.
- Takuto Kawaji
- , Mizuki Fujibayashi
- & Kentaro Abe
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Article
| Open AccessFlexible TAM requirement of TnpB enables efficient single-nucleotide editing with expanded targeting scope
Here the authors report that a thermophilic archaeal TnpB enables efficient gene editing in the natural host: they see that the TnpB has different TAM requirements for eliciting cell death and for facilitating gene editing. They show that TnpB can be harnessed for flexible single-nucleotide editing with templated repair.
- Xu Feng
- , Ruyi Xu
- & Qunxin She
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Article
| Open AccessThe phosphorylation of carboxyl-terminal eIF2α by SPA kinases contributes to enhanced translation efficiency during photomorphogenesis
The non-canonical C-term-phosphorylation of eIF2α mediated by SPA protein kinases plays a significant positive role in eIF2 ternary complex formation and light-induced translation during photomorphogenesis.
- Hui-Hsien Chang
- , Lin-Chen Huang
- & Mei-Chun Cheng
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Article
| Open AccessMYADM binds human parechovirus 1 and is essential for viral entry
Host factors required for parechovirus entry are not well understood. Here, the authors identify MYADM as an essential host entry factor that directly binds human parechovirus 1 and that is required for PeV-A infection in cell lines and human gastrointestinal epithelial organoids.
- Wenjie Qiao
- , Christopher M. Richards
- & Jan E. Carette
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Article
| Open AccessSingle cell tracing of Pomc neurons reveals recruitment of ‘Ghost’ subtypes with atypical identity in a mouse model of obesity
Whether and how hypothalamic neurons can lose or change their identity in adulthood has remained elusive. Here, the authors show that mature pro-opiomelanocortin (Pomc) neurons contain invisible ‘Ghost’ subsets with atypical identities that are recruited in response to obesogenic stimuli.
- Stéphane Leon
- , Vincent Simon
- & Carmelo Quarta
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Article
| Open AccessWild-type IDH2 is a therapeutic target for triple-negative breast cancer
Isocitrate dehydrogenase (IDH) mutations are associated with cancer development and IDH-mutant inhibitors are approved to treat IDH-mutant cancer. Here, the authors show in preclinical murine models that wild-type IDH2 is a potential therapeutic target for triple-negative breast cancer.
- Jiang-jiang Li
- , Tiantian Yu
- & Peng Huang
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Article
| Open AccessEZH2 mutations in follicular lymphoma distort H3K27me3 profiles and alter transcriptional responses to PRC2 inhibition
Cells carrying EZH2 mutations found in lymphoma show a specific transcriptional response to PRC2 inhibition. A longitudinal study reveals unexpected genetic heterogeneity in follicular lymphomas, with implications for therapeutic strategies.
- Pierre Romero
- , Laia Richart
- & Raphaël Margueron
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Article
| Open AccessTANGO1 inhibitors reduce collagen secretion and limit tissue scarring
Uncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring. Here the authors describe membrane permeable peptides that target the interface of TANGO1 and cTAGE5, inhibit secretion of ECM components and could be of therapeutic benefit during wound healing and fibrotic processes.
- Ishier Raote
- , Ann-Helen Rosendahl
- & Vivek Malhotra
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Article
| Open AccessF-actin architecture determines the conversion of chemical energy into mechanical work
F-actin architecture modulates transmission and generation of stresses in cells, yet its impact on myosin ATP hydrolysis remains unknown. The authors perform experiments measuring myosin ATP hydrolysis rates, showing that F-actin architecture can control myosin energy consumption.
- Ryota Sakamoto
- & Michael P. Murrell
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Article
| Open AccessSynergism between two BLA-to-BNST pathways for appropriate expression of anxiety-like behaviors in male mice
How distinct circuits get coordinated to allow individuals to express appropriate level of anxiety is unclear. Here, authors show there are two functionally opposing BLA-BNST pathways interacting via the local inhibitory networks to enable anxiety expression with environmental needs.
- Ren-Wen Han
- , Zi-Yi Zhang
- & Bing-Xing Pan
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Article
| Open AccessA giant virus infecting the amoeboflagellate Naegleria
This is the first report on a virus infecting the amoeboflagellate Naegleria, including the lethal human pathogen N. fowleri. The new virus isolate, Catovirus naegleriensis (Naegleriavirus, NiV), shows hallmarks of giant viruses (Nucleocytoviricota) and unique adaptations to its protist host.
- Patrick Arthofer
- , Florian Panhölzl
- & Matthias Horn
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Article
| Open AccessLarge-scale cross-ancestry genome-wide meta-analysis of serum urate
This large-scale cross-ancestry genome-wide association study reveals the genetic architecture of serum urate across ancestries and identifies urate-associated diseases and potential targets of urate-lowering drugs.
- Chamlee Cho
- , Beomsu Kim
- & Hong-Hee Won
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Article
| Open AccessLong-term monitoring of SARS-CoV-2 seroprevalence and variants in Ethiopia provides prediction for immunity and cross-immunity
Detailed data on SARS-CoV-2 dynamics in Africa remain limited. Here, the authors use longitudinal serology and SARS-CoV-2 sequencing data from Ethiopia between August 2020 and July 2022 to characterise circulating variants, identify infection pathways, and explore cross-immunity properties.
- Simon Merkt
- , Solomon Ali
- & Andreas Wieser
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Article
| Open AccessA comprehensive synthetic library of poly-N-acetyl glucosamines enabled vaccine against lethal challenges of Staphylococcus aureus
Poly-β-(1–6)-N-acetylglucosamine (PNAG) is an important vaccine target, but the impact of the number and position of free amine vs N-acetylation on its antigenicity is not well understood. Here, the authors report a divergent strategy to synthesize a comprehensive library of PNAG pentasaccharides, enabling the identification of enhanced epitopes for vaccines against Staphylococcus aureus including drug resistant strains.
- Zibin Tan
- , Weizhun Yang
- & Xuefei Huang
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Article
| Open AccessStructural and biochemical analysis of family 92 carbohydrate-binding modules uncovers multivalent binding to β-glucans
Carbohydrate binding modules (CBMs) are non-catalytic domains found within multi-modular carbohydrate-active enzymes like glycoside hydrolases. Here, the authors show the crystal structures of two CBM family 92 members, which use three different surface binding sites to bind to β-glucans.
- Meng-Shu Hao
- , Scott Mazurkewich
- & Lauren S. McKee
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Article
| Open AccessTemporal coordination of the transcription factor response to H2O2 stress
H2O2 stress is known to activate a slew of transcription factors that restore redox balance. Here, the authors use live-cell imaging and single-cell analysis to reveal that the transcription factors that are activated and their timing of activation is dose dependent.
- Elizabeth Jose
- , Woody March-Steinman
- & Andrew L. Paek
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Article
| Open AccessFreshwater genome-reduced bacteria exhibit pervasive episodes of adaptive stasis
Here, by applying evolutionary genomics approaches to metagenomics data of lake microbiomes, the authors reveal that freshwater species with small genomes face extended periods with their niche adaptation capabilities frozen.
- Lucas Serra Moncadas
- , Cyrill Hofer
- & Adrian-Stefan Andrei
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Article
| Open AccessTargeting NRAS via miR-1304-5p or farnesyltransferase inhibition confers sensitivity to ALK inhibitors in ALK-mutant neuroblastoma
Targeting oncogenic ALK activity in neuroblastoma is an attractive therapeutic strategy but success has been limited by resistance to ALK inhibitors. Here, the authors identify loss of miR-1304-5p as a driver of ALK inhibitor resistance via regulation of NRAS, and therapeutically target this axis with the addition of a farnesyltransferase inhibitor in preclinical models of neuroblastoma.
- Perla Pucci
- , Liam C. Lee
- & Suzanne D. Turner
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Article
| Open AccessA genomic basis of vocal rhythm in birds
Little is known about the genetic basis of the rhythmic component of bird song, an important trait in sexual selection and species recognition. By studying a system with innate vocalizations, the Pogoniulus tinkerbirds, this study finds candidate genes that underlie differences in speed in vocal rhythm in this system.
- Matteo Sebastianelli
- , Sifiso M. Lukhele
- & Alexander N. G. Kirschel
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Article
| Open AccessNitrogen and Nod factor signaling determine Lotus japonicus root exudate composition and bacterial assembly
Nod factor signaling, and nitrate distinctly affect Lotus japonicus root exudate, microbiome composition and connectivity, emphasizing the role of signaling between plant and distinct members of soil microbiota in shaping the overall assemblies.
- Ke Tao
- , Ib T. Jensen
- & Simona Radutoiu
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Article
| Open AccessBrightness illusions drive a neuronal response in the primary visual cortex under top-down modulation
The neural mechanisms underpinning visual illusions remains poorly understood. Here, the authors recorded the neural responses of mouse primary visual cortex to illusory grating and found delayed responses to illusory brightness, showing that optogenetic inhibition of higher visual areas reduced V1 response to illusions but not to real gratings.
- Alireza Saeedi
- , Kun Wang
- & Masataka Watanabe
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Article
| Open AccessPhytoalexin sakuranetin attenuates endocytosis and enhances resistance to rice blast
Sakuranetin is an important phytoalexin. The authors find that sakuranetin in rice attenuates endocytosis of effectors from the fungus Magnaporthe oryzae and enhances resistance against rice blast.
- Lihui Jiang
- , Xiaoyan Zhang
- & Yunlong Du
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Article
| Open AccessIn situ captured antibacterial action of membrane-incising peptide lamellae
Inspired by the alternating chirality backbone pattern of some effective peptide antimicrobials, here authors design lysine-rich heterochiral peptides that show antimicrobial activity.
- Kamal el Battioui
- , Sohini Chakraborty
- & Tamás Beke-Somfai
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Article
| Open AccessLineage specific transcription factor waves reprogram neuroblastoma from self-renewal to differentiation
This study identifies temporal and coordinately regulated cell-state-specific super-enhancers driving the expression of transcription factors that control circuits needed to switch neuroblastoma tumor cells from self-renewal to differentiation.
- Deblina Banerjee
- , Sukriti Bagchi
- & Carol J. Thiele
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Article
| Open AccessThe gut microbiome-prostate cancer crosstalk is modulated by dietary polyunsaturated long-chain fatty acids
Here, using murine models of prostate cancer, the authors show that reduced fecal microbiota alpha-diversity correlates with increased prostate tumor burden, and that Omega-3 prebiotic supplementation reduces prostate cancer up-grading associated with a reduction of gut Ruminococcaceae and fecal butyrate levels.
- Gabriel Lachance
- , Karine Robitaille
- & Vincent Fradet
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Article
| Open AccessPhysiography, foraging mobility, and the first peopling of Sahul
The speed and route by which Homo sapiens colonised Sahul is an ongoing topic of research. Here, the authors model the physical environment as it changes through time in combination with Lévy walk foraging patterns to suggest a wave of dispersal following coastlines and rivers.
- Tristan Salles
- , Renaud Joannes-Boyau
- & Manon Lorcery
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Article
| Open AccessProspective de novo drug design with deep interactome learning
The use of data-driven generative models for drug design is challenging due to the scarcity of data. Here, the authors introduce a “zero-shot" generative deep model to enable the generation of molecules by both structure- and ligand-based drug design and apply it to design PPARγ agonists with desired properties.
- Kenneth Atz
- , Leandro Cotos
- & Gisbert Schneider
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Article
| Open AccessTyrosine phosphorylation of CARM1 promotes its enzymatic activity and alters its target specificity
Coactivator-associated arginine methyltransferase 1 (CARM1) is an important target in hematologic malignancies. In this work, the authors show that the hyperactivation of Janus kinase 2 (JAK2) by the V617F mutation phosphorylates CARM1 which regulates its methyltransferase activity and alters its target specificity.
- Hidehiro Itonaga
- , Adnan K. Mookhtiar
- & Stephen D. Nimer
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Article
| Open AccessIntracellular magnesium optimizes transmission efficiency and plasticity of hippocampal synapses by reconfiguring their connectivity
How synapses at dendrites are organized to optimize information processing remains elusive. Here, the authors found that intracellular magnesium optimizes transmission, plasticity, and coding capacity of synapses by reconfiguring their connectivity at dendrites.
- Hang Zhou
- , Guo-Qiang Bi
- & Guosong Liu
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Article
| Open AccessBiomolecular condensates form spatially inhomogeneous network fluids
Here, the authors use small angle neutron scattering and coarse-grained molecular dynamics simulations to demonstrate that condensates based on the granular components of nucleoli are network fluids.
- Furqan Dar
- , Samuel R. Cohen
- & Rohit V. Pappu
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Article
| Open AccessLSD1 drives intestinal epithelial maturation and controls small intestinal immune cell composition independent of microbiota in a murine model
Post birth the gastrointestinal tract undergoes development including the establishment of the microbiome, establishment of tolerance and maturation of the epithelium. Here the authors show a histone demethylase LSD1 is required for postnatal intestinal epithelium maturation and how this impacts local immune cell composition and gut homeostasis.
- Alberto Díez-Sánchez
- , Håvard T. Lindholm
- & Menno J. Oudhoff
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Article
| Open AccessPrediction error processing and sharpening of expected information across the face-processing hierarchy
Perception and neural processing of sensory information are influenced by prior expectations. Here the authors show investigate how prior expectations contribute to face processing in the brain.
- Annika Garlichs
- & Helen Blank
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Article
| Open AccessPD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus
Basophils have been implicated in systemic lupus erythematosus (SLE), as evidenced by the fact that basophil-deficient mice do not develop the disease. Here, the authors demonstrate that PD-L1 and IL-4 expression in basophils promotes the pathogenic accumulation of follicular helper T cells in patients with SLE and murine models.
- John TCHEN
- , Quentin SIMON
- & Nicolas CHARLES
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Article
| Open AccessSelective lipid recruitment by an archaeal DPANN symbiont from its host
The symbiont Ca. Nanohaloarchaeum antarcticus is dependent on its host Halorubrum lacusprofundi for lipids due to a lack of certain biosynthetic genes. Here, the authors characterize the lipidome dynamics of this symbiotic relationship.
- Su Ding
- , Joshua N. Hamm
- & Anja Spang
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Article
| Open AccessStructural insights into the transporting and catalyzing mechanism of DltB in LTA D-alanylation
Here, the authors structurally and functionally characterise DltB, a member of the Membrane-Bound O-AcylTransferase (MBOAT) superfamily responsible for D-alanine incorporation in the cell wall of gram-positive bacteria.
- Pingfeng Zhang
- & Zheng Liu
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Article
| Open Accesshoxc12/c13 as key regulators for rebooting the developmental program in Xenopus limb regeneration
During organ regeneration, gene expression patterns similar to those in normal development are reestablished. Here, Kawasumi-Kita et al. explore core rebooting factors that operate during Xenopus limb regeneration. Their results indicate that hoxc12 and hoxc13 are critical for reactivating tissue growth.
- Aiko Kawasumi-Kita
- , Sang-Woo Lee
- & Yoshihiro Morishita
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Article
| Open AccessMulti-omics analysis reveals COVID-19 vaccine induced attenuation of inflammatory responses during breakthrough disease
Here, Drury et al study gene, microRNA and protein expression during COVID-19, in a randomised controlled trial of ChAdOx1 nCoV19 vaccine and find that ChAdOx1 nCoV-19 attenuates the inflammatory response, thought to be the basis for severe COVID-19.
- Ruth E. Drury
- , Susana Camara
- & Daniel O’Connor
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Article
| Open AccessA global meta-analysis on the effects of organic and inorganic fertilization on grasslands and croplands
Inorganic fertilization reduces plant biodiversity. Here, the authors conduct a global meta-analysis on the use of organic and inorganic fertilizer in croplands and grasslands, showing that while both fertilizers increase plant biomass, only organic fertilizer increases biodiversity.
- Ting-Shuai Shi
- , Scott L. Collins
- & Jian-Sheng Ye
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Article
| Open AccessPhosphorylation of the F-BAR protein Hof1 drives septin ring splitting in budding yeast
Cytokinesis in budding yeast is accompanied by a major rearrangement of septins into a double ring. Here, authors show that the F-BAR protein Hof1 contributes to septin remodeling upon its phosphorylation and relocalisation from septins to the division site.
- Maritzaida Varela Salgado
- , Ingrid E. Adriaans
- & Simonetta Piatti
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Article
| Open AccessEstimating the effects of temperature on transmission of the human malaria parasite, Plasmodium falciparum
Malaria transmission is affected by temperature but this relationship is not well characterised. Here, the authors experimentally determine the effect of temperature on parasite development in the mosquito and model how it impacts malaria transmission in Kenya under current and future climate scenarios.
- Eunho Suh
- , Isaac J. Stopard
- & Matthew B. Thomas
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Article
| Open AccessDiverse and asymmetric patterns of single-neuron projectome in regulating interhemispheric connectivity
How interhemispheric connections are organized and how interhemispheric communication are regulated are not fully understood. Here authors delineate the diverse single-neuron projection patterns of interhemispheric connections in mice and uncover their influence on functional dynamics, highlighting the importance of heterotopic projections in interhemispheric communication.
- Yao Fei
- , Qihang Wu
- & Cirong Liu
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Article
| Open AccessAn approach to identify gene-environment interactions and reveal new biological insight in complex traits
Here, the authors report 5 loci interacting with smoking/alcohol for serum lipids using a new method akin to Mendelian randomization. They unveil significant heritability through gene-environment interaction and mediation, enhancing understanding of complex trait genetics.
- Xiaofeng Zhu
- , Yihe Yang
- & Hugues Aschard
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Article
| Open AccessConsistent signatures in the human gut microbiome of old- and young-onset colorectal cancer
The rising incidence of young-onset sporadic colorectal cancer (yCRC) is global concern. Here, leveraging a substantial number of deep sequencing metagenomes, the authors show striking similarities in gut microbial patterns at both the taxonomic and selected gene marker levels between yCRC and old-onset CRC.
- Youwen Qin
- , Xin Tong
- & Pei-Rong Ding
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Article
| Open AccessClinical associations with a polygenic predisposition to benign lower white blood cell counts
Here, the authors find that a benign polygenic predisposition to lower white blood cell counts is associated with multiple clinical endpoints, suggesting that predisposed individuals are susceptible to escalations or alterations in clinical care that may be harmful or of little benefit.
- Jonathan D. Mosley
- , John P. Shelley
- & Vivian K. Kawai
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