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| Open AccessSm-like protein Rof inhibits transcription termination factor ρ by binding site obstruction and conformational insulation
Said et al. used cryoEM, biochemistry and bioinformatics to uncover how the Sm-like protein Rof regulates transcription termination. Rof binds termination factor ρ, inhibiting ρ ring closure and its association with RNA or transcription complexes.
- Nelly Said
- , Mark Finazzo
- & Markus C. Wahl
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Article
| Open AccessOptogenetic control of mRNA condensation reveals an intimate link between condensate material properties and functions
Biomolecular condensates play important roles in diverse cellular activities. Here the authors employ optogenetic tool and single-molecule mRNA imaging, showing that sequestering target mRNAs into condensates lead to translation inhibition.
- Min Lee
- , Hyungseok C. Moon
- & Yongdae Shin
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Article
| Open AccessDynamic inter-domain transformations mediate the allosteric regulation of human 5, 10-methylenetetrahydrofolate reductase
Here the authors present the cryo-EM structure of active and inhibited human MTHFR, revealing a dynamic inhibitory mechanism dependent on dual SAM binding. The resulting closed conformation features an autoinhibitory element effectively blocking enzymatic activity.
- Linnea K. M. Blomgren
- , Melanie Huber
- & Thomas J. McCorvie
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Article
| Open AccessConjunctive encoding of exploratory intentions and spatial information in the hippocampus
The hippocampus maps space, but its role in encoding investigatory intentions is unclear. Here the authors show that certain CA1 neurons encode both spatial information and animals’ intention to explore, depending on input from lateral entorhinal cortex.
- Yi-Fan Zeng
- , Ke-Xin Yang
- & Ning Zhou
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Article
| Open AccessDonor regulatory T cells rapidly adapt to recipient tissues to control murine acute graft-versus-host disease
Graft-versus-Host disease is a major complication after allogeneic bone marrow transplantation and is ameliorated by adoptively transferred donor regulatory T cells. Here, the authors apply transcriptomic and TCR profiling to assess regulatory T cell organ-specific adaptation in murine bone marrow transplantation models.
- David J. Dittmar
- , Franziska Pielmeier
- & Michael Rehli
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Article
| Open AccessReciprocal antagonism of PIN1-APC/CCDH1 governs mitotic protein stability and cell cycle entry
Unveiling the regulation of mitotic protein degradation is crucial for cancer therapy. Here, the authors reveal that a reciprocal inhibition of PIN1-APC/CCDH1 controls the cell cycle and mitotic protein degradation, offering a synergistic anti-tumor strategy.
- Shizhong Ke
- , Fabin Dang
- & Kun Ping Lu
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Article
| Open AccessAn experimental framework to assess biomolecular condensates in bacteria
The small cell size of bacteria is a key hurdle in studying condensates. To address this challenge, the authors develop an experimental framework to assess bacterial condensates based on how they form, dissolve, tune shape and size, and transition between material states.
- Y Hoang
- , Christopher A. Azaldegui
- & Anthony G. Vecchiarelli
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Article
| Open AccessKdpD is a tandem serine histidine kinase that controls K+ pump KdpFABC transcriptionally and post-translationally
KdpD is known as the sensory histidine kinase of two-component system KdpDE that controls the transcription of the kdpFABC genes. Here, the authors show that KdpD acts as atypical serine kinase, which post-translationally regulates KdpFABC.
- Jakob M. Silberberg
- , Sophie Ketter
- & Inga Hänelt
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Article
| Open AccessMicroenvironmental reorganization in brain tumors following radiotherapy and recurrence revealed by hyperplexed immunofluorescence imaging
Improved imaging techniques are required to help advance our understanding of the complex role of the tumour microenvironment (TME). Here, the authors develop a high-throughput, highly multiplexed tissue visualisation workflow and demonstrate its utility by characterising the response of the TME to radiotherapy in preclinical models of glioblastoma.
- Spencer S. Watson
- , Benoit Duc
- & Johanna A. Joyce
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Article
| Open AccessGlobal meta-analysis reveals overall higher nocturnal than diurnal activity in insect communities
Entomologists expect that more insects are active at night than during daytime. Here, the authors use a global meta-analysis of insect community diel patterns to show highly variable and context-dependent but overall higher nocturnal activity of insects.
- Mark K. L. Wong
- & Raphael K. Didham
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Article
| Open AccessFunctional protein dynamics in a crystal
Work by Klyshko and Kim et al. lays the foundation for simulating pump-probe experiments and demonstrates how the dynamic behaviour of proteins extends to the crystal environment, emphasizing the need for an ensemble view in understanding functional motions.
- Eugene Klyshko
- , Justin Sung-Ho Kim
- & Sarah Rauscher
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Article
| Open AccessTrace gas oxidation sustains energy needs of a thermophilic archaeon at suboptimal temperatures
Diverse bacteria can use the low levels of hydrogen and carbon monoxide present in the air as energy sources for growth and survival. Here, Leung et al. show that ability is also found in thermophilic archaea of the order Sulfolobales.
- Pok Man Leung
- , Rhys Grinter
- & Chris Greening
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Article
| Open AccessAn ensemble penalized regression method for multi-ancestry polygenic risk prediction
Great efforts are being made to develop advanced polygenic risk scores (PRS) to improve the prediction of complex traits and diseases. However most existing PRS are primarily trained on European ancestry populations, limiting their transferability to non-European populations. Here the authors propose a new multi-ancestry PRS method, PROSPER, to reduce disparity of PRS performance across ancestry groups.
- Jingning Zhang
- , Jianan Zhan
- & Nilanjan Chatterjee
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Article
| Open AccessRemote loop evolution reveals a complex biological function for chitinase enzymes beyond the active site
Loop regions play a key role in protein evolution. Herein the authors demonstrate how GH19 chitinase acquired additional antifungal activity by introducing remote loops, without compromising its original function. This work offers an innovative approach to expand enzyme function.
- Dan Kozome
- , Adnan Sljoka
- & Paola Laurino
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Article
| Open AccessDiversity and potential host-interactions of viruses inhabiting deep-sea seamount sediments
Little is known about viral communities in deep-sea seamounts. In this study, the authors performed metagenomic and virome analysis from sediments in the western Pacific Ocean and characterize the diversity, distribution and potential ecological roles of viruses in deep-sea seamount sediments.
- Meishun Yu
- , Menghui Zhang
- & Min Jin
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Article
| Open AccessNerve growth factor receptor limits inflammation to promote remodeling and repair of osteoarthritic joints
Osteoarthritis is a painful and debilitating condition. Here, the authors show that NGFR, a receptor for NGF, restricts NF-κB activation and its deficiency in skeletal cells impairs the remodeling and repair of osteoarthritic joints.
- Lan Zhao
- , Yumei Lai
- & Jian Huang
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Article
| Open AccessAlkyne-tagged SERS nanoprobe for understanding Cu+ and Cu2+ conversion in cuproptosis processes
Simultaneously quantifying mitochondrial Cu+ and Cu2+ levels is vital for understanding the molecular mechanism of mitochondria-related biological events. Here the authors report an alkynyl-labeled SERS probe to simultaneously monitor free Cu+ and Cu2+ in mitochondria, and unveil their roles during ischemia and cuproptosis processes.
- Sihan Zhang
- , Yuxiao Mei
- & Yang Tian
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Article
| Open AccessA widely conserved protein Rof inhibits transcription termination factor Rho and promotes Salmonella virulence program
Bacterial protein Rof (Rho-off) directly interacts with bacterial factor Rho and inhibits Rho-dependent transcription termination. Here, authors report cryo-EM structure of Rho-Rof antitermination complex and reveal their role in bacterial pathogenesis.
- Jing Zhang
- , Shuo Zhang
- & Chengyuan Wang
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Article
| Open AccessX-ray-activated polymerization expanding the frontiers of deep-tissue hydrogel formation
Photo-crosslinking polymerization facilitates precise control of hydrogel formation for various applications including tissue engineering, but most existing photo-crosslinking methods fail to achieve deep-tissue penetration, especially within bone structures. Here the authors report a strategy of low-dose X-ray-activated polymerization that enables deep-tissue hydrogel formation.
- Hailei Zhang
- , Boyan Tang
- & Gang Han
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Article
| Open AccessPerinatal outcomes after admission with COVID-19 in pregnancy: a UK national cohort study
The impacts of maternal SARS-CoV-2 infection on newborns are not well understood. Here, the authors perform a national cohort study using data on births in the UK from March 2020—March 2022 and find that moderate to severe maternal COVID-19 was associated with adverse perinatal outcomes.
- Hilde Marie Engjom
- , Rema Ramakrishnan
- & Marian Knight
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Article
| Open AccessDeep learning predictions of TCR-epitope interactions reveal epitope-specific chains in dual alpha T cells
Prediction of the specificity of a T cell receptor from amino acid sequence has been performed using different methods and approaches. Here the authors use TCRab sequences with known specificity to develop a deep learning TCR-epitope interaction predictor and use this method to predict specificity of dual alpha chain TCRs and TCRs specific for different antigens.
- Giancarlo Croce
- , Sara Bobisse
- & David Gfeller
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Article
| Open AccessDynamics of DNA damage-induced nuclear inclusions are regulated by SUMOylation of Btn2
Maintaining a healthy nuclear proteome during DNA damage is important but its regulation is poorly understood. The authors here show that a SUMO modification of the small heat shock protein Btn2 regulates yeast nuclear protein sequestration during stress.
- Arun Kumar
- , Veena Mathew
- & Peter C. Stirling
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Article
| Open AccessInfluenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children
In this study, the authors assessed influenza-specific antibody responses in a cohort of seasonally vaccinated children and report that seasonal vaccination is beneficial by enhancing pandemic influenza virus-specific antibodies and cross-reactive effector functions.
- Janice Z. Jia
- , Carolyn A. Cohen
- & Sophie A. Valkenburg
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Article
| Open AccessA plant NLR receptor employs ABA central regulator PP2C-SnRK2 to activate antiviral immunity
Huang et al. show how plant Sw-5b NLR mimics the ABA receptor to activate ABA-dependent antiviral immunity via the PP2C-SnRK2 complex. They reveal that Sw-5b NLR induces ABA accumulation, upregulates ABA response genes, and triggers defense against viral infections by releasing SnRK2 from PP2C inhibition.
- Shen Huang
- , Chunli Wang
- & Xiaorong Tao
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Article
| Open AccessOne substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse
With structural models now available on a proteome scale, Malatesta et al. show that structure-based screening can help identify proteins catalyzing orphan reactions in metabolic pathways, offering functional insights beyond sequence-based approaches.
- Marco Malatesta
- , Emanuele Fornasier
- & Riccardo Percudani
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Article
| Open AccessPositive selection underlies repeated knockout of ORF8 in SARS-CoV-2 evolution
SARS-CoV-2 constantly evolves but the roles of resulting mutations are not always clear. In this study, the authors report that ORF8 knockout confers a fitness advantage to SARS-CoV-2 using genomic surveillance data, highlighting how different types of adaptations across the SARS-CoV-2 genome can drive variant fitness.
- Cassia Wagner
- , Kathryn E. Kistler
- & Trevor Bedford
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Article
| Open AccessLipopolysaccharide binding protein resists hepatic oxidative stress by regulating lipid droplet homeostasis
Oxidative stress triggers lipid accumulation in cells by sequestering triglycerides in lipid droplets. Here, the authors show that lipopolysaccharide-binding protein interacts with redox sensor PRDX4 to control lipid-redox balance and promotes triglyceride accumulation in droplets by capturing unsaturated lipids.
- Qilun Zhang
- , Xuting Shen
- & Haoshu Fang
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Comment
| Open AccessAll-inclusive nitrifiers in Antarctic soils
Multidisciplinary culture-dependent and -independent techniques elucidate the unique microbial nitrogen cycle in nutrient-poor coastal Antarctica soils and reveal the contribution of novel key microbes to their nitrogen budget.
- Maximiliano Ortiz
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Article
| Open AccessA modular and synthetic biosynthesis platform for de novo production of diverse halogenated tryptophan-derived molecules
De novo fermentation and synthetic pathway construction for halogen-containing molecules remain relatively underexplored. Here, the authors report a mix-and-match co-culture platform to de novo generate a large array of halogenated tryptophan derivatives in E. coli from glucose.
- Kevin B. Reed
- , Sierra M. Brooks
- & Hal S. Alper
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Article
| Open AccessA hemoprotein with a zinc-mirror heme site ties heme availability to carbon metabolism in cyanobacteria
Heme is an abundant cofactor required by nearly all known organisms. Here, authors discover a cyanobacterial protein with a distinct Zn-mirror heme site, which may function to sense heme and regulate energy metabolism.
- Nicolas Grosjean
- , Estella F. Yee
- & Crysten E. Blaby-Haas
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Article
| Open AccessA hippocampus-accumbens code guides goal-directed appetitive behavior
The dorsal hippocampus plays an important role for spatial memory, but how its outputs guide behavior is not fully understood. Here, the authors show that nucleus accumbens-specific hippocampal projection neurons carry a highly conjunctive code of spatial and action information that directs spatial reward memory-guided appetitive behaviors.
- Oliver Barnstedt
- , Petra Mocellin
- & Stefan Remy
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Article
| Open AccessNeurocomputational mechanisms involved in adaptation to fluctuating intentions of others
Humans often interact without knowing the cooperative or competitive intentions of others. Here, the authors determined the neurocomputational mechanisms engaged in adapting to fluctuating intentions of others over repeated social interactions.
- Rémi Philippe
- , Rémi Janet
- & Jean-Claude Dreher
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Article
| Open AccessIntegrated proteogenomic and metabolomic characterization of papillary thyroid cancer with different recurrence risks
Papillary thyroid cancers (PTC) generally have good prognosis, but their recurrence rate remains high. Here, the authors use proteogenomics and metabolomics to identify molecular features in PTC tumours and determine PTC subtypes that are associated with prognosis and potential targeted therapies.
- Ning Qu
- , Di Chen
- & Rongliang Shi
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Article
| Open AccessTumor phylogeography reveals block-shaped spatial heterogeneity and the mode of evolution in Hepatocellular Carcinoma
Hepatocellular carcinomas (HCC) present spatial intratumour heterogeneity (sITH). Here, the authors perform a genomic and phylogenetic analysis of spatially-sampled HCC tumour sections, observe block-shaped sITH, and find ongoing natural selection where ancestral and derived clones spatially compete in the same tumor.
- Xiaodong Liu
- , Ke Zhang
- & Weiwei Zhai
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Article
| Open AccessSemmaphorin 3 A causes immune suppression by inducing cytoskeletal paralysis in tumour-specific CD8+ T cells
Interactions between Semaphorin-3A (SEMA3A) and Neuropilin-1 (NRP1) and Plexin-A1 and Plexin-A4 have been shown to affect T cell development. Here the authors investigate how these interactions affect CD8+ T cells in tumour immunity, showing that NRP-1, Plexin-A1 and Plexin-A4 are upregulated on T cells allowing tumour derived SEMA3A to inhibit CD8+ T cell migration and function.
- Mike B. Barnkob
- , Yale S. Michaels
- & Vincenzo Cerundolo
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Article
| Open AccessAnnelid adult cell type diversity and their pluripotent cellular origins
The cellular atlas of Pristina leidyi reveals cell type diversity in adult annelids by single cell transcriptomics, discovering several novel cell types and suggesting a pluripotent stem cell signature associated with adult cell type differentiation
- Patricia Álvarez-Campos
- , Helena García-Castro
- & Jordi Solana
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Article
| Open AccessIntrogression and disruption of migration routes have shaped the genetic integrity of wildebeest populations
The evolutionary genetics of a keystone savannah species the blue wildebeest, and the related black wildebeest, remain largely unexplored. This study finds evidence for archaic introgression of black wildebeest to blue wildebeest and detrimental effects of human activities on migratory populations.
- Xiaodong Liu
- , Long Lin
- & Rasmus Heller
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Article
| Open AccessReciprocating RNA Polymerase batters through roadblocks
During transcription, RNA polymerases may encounter protein roadblocks along template DNA. Here, Qian et al. use magnetic tweezers to show that RNA polymerases can backtrack and ram into longer lived roadblocks to transit through them.
- Jin Qian
- , Allison Cartee
- & Laura Finzi
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Article
| Open AccessStimulus encoding by specific inactivation of cortical neurons
How neural ensembles encode information remains poorly understood. Here, the authors identify “offsembles”—neurons that are specifically inactivated by sensory stimuli—which, when combined with “onsemble” neurons that are turned on by the stimulus, provide enhanced encoding power to the cortex.
- Jesús Pérez-Ortega
- , Alejandro Akrouh
- & Rafael Yuste
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Article
| Open AccessSplice modulators target PMS1 to reduce somatic expansion of the Huntington’s disease-associated CAG repeat
Somatic expansion of a CAG repeat in HTT drives onset of Huntington’s disease. Using a human cell line model and splice modulators, here the authors show that PMS1 is an enhancer of CAG repeat expansion, making it a target for therapeutic intervention.
- Zachariah L. McLean
- , Dadi Gao
- & James F. Gusella
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Article
| Open AccessSystematic investigation of chemo-immunotherapy synergism to shift anti-PD-1 resistance in cancer
The design of new combinatorial regimens represents an opportunity to improve response to immune checkpoint inhibitors in patients with cancer. Here the authors computationally model the interaction between chemotherapy and immunotherapy by studying treatment-induced expression changes associated with response to anti-PD-1, identifying chemotherapeutic drugs or small molecule inhibitors that can overcome resistance to anti-PD-1.
- Yue Wang
- , Dhamotharan Pattarayan
- & Da Yang
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Article
| Open AccessDynamic interplay of microtubule and actomyosin forces drive tissue extension
Actomyosin and microtubule-based forces are both important for tissue development, but how these systems interact in space and time remains unclear. Here, the authors study fly wing epithelium growth and determine aspects driving cell shape that are driven by microtubule or actomyosin-generated forces.
- Amrita Singh
- , Sameedha Thale
- & Maja Matis
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Article
| Open AccessEpidemiological, clinical, and genomic landscape of coccidioidomycosis in northeastern Brazil
Coccidioidomycosis, a WHO-listed mycosis, is neglected in South America. Analysis of 292 cases in Brazil, often tied to armadillo hunting, unveils unique disease patterns, environmental factors and pathogen genetics causing the disease.
- Kelsen Dantas Eulálio
- , Daniel R. Kollath
- & Marcus de Melo Teixeira
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Article
| Open AccessDiverse and abundant phages exploit conjugative plasmids
Some phages use plasmid-encoded conjugation proteins as receptors to infect their bacterial hosts, making their host range dependent on horizontal transfer of the plasmid. Here, the authors present a method for identification of new plasmid-dependent phages, and find that they are common and abundant in wastewater and their genetic diversity is largely unexplored.
- Natalia Quinones-Olvera
- , Siân V. Owen
- & Michael Baym
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Article
| Open AccessUtility of polygenic scores across diverse diseases in a hospital cohort for predictive modeling
Here, the authors analyze polygenic scores for 457 phenotypes, finding 49 with robust polygenic score predictive models ( > 0.6 AUC). They find that population diversity and environmental factor integration are key considerations to improving the model’s performance.
- Ting-Hsuan Sun
- , Chia-Chun Wang
- & Kai-Cheng Hsu
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Article
| Open AccessUnveiling unique microbial nitrogen cycling and nitrification driver in coastal Antarctica
This study reveals a unique microbial nitrogen cycling process in Antarctica’s coastal regions, with nitrification playing a significant role. The research notably identifies comammox Nitrospira clade B as a key driver of this process.
- Ping Han
- , Xiufeng Tang
- & Guitao Shi
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Article
| Open AccessSubthalamic stimulation modulates context-dependent effects of beta bursts during fine motor control
How movement speed is neurally modulated remains poorly understood. Here, the authors recorded invasive brain signals in Parkinson’s disease patients during drawing and deep brain stimulation, showing a context-dependent relationship between reductions of movement acceleration and dynamic activity of the basal ganglia.
- Manuel Bange
- , Gabriel Gonzalez-Escamilla
- & Sergiu Groppa
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Article
| Open AccessEvolution of T cells in the cancer-resistant naked mole-rat
Naked mole-rats are long-lived rodents with remarkable resistance to cancer. Here authors show that their T-cell compartment is different from that of mice in that they have a large population of circulating cytotoxic γδ T cells harboring a dominant clonotype, and the clonotypic diversity of their conventional cytotoxic αβ T cells is more modest than that of mice.
- Tzuhua D. Lin
- , Nimrod D. Rubinstein
- & Rochelle Buffenstein
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Article
| Open AccessRegulation by the RNA-binding protein Unkempt at its effector interface
How RNA-binding proteins (RBPs) regulate gene expression via effectors of RNA processing is unclear. Here, the authors dissect the effector interface of an essential RBP, Unkempt, and investigate its contribution to translational control in cells.
- Kriti Shah
- , Shiyang He
- & Jernej Murn
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