Featured
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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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Article
| Open AccessResponses of marine trophic levels to the combined effects of ocean acidification and warming
Marine organisms are increasingly exposed to both ocean acidification and warming. Here, the authors report a meta-analysis of fully factorial experiments with both acidification and warming treatments, finding that synergistic interactions are less common than expected.
- Nan Hu
- , Paul E. Bourdeau
- & Johan Hollander
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Comment
| Open AccessInflammation and mitophagy are mitochondrial checkpoints to aging
Cellular and organismal aging have been consistently associated with mitochondrial dysfunction and inflammation. Accumulating evidence indicates that aging-related inflammatory responses are mechanistically linked to compromised mitochondrial integrity coupled with mtDNA-driven CGAS activation, a process that is tonically inhibited by mitophagy.
- Emma Guilbaud
- , Kristopher A. Sarosiek
- & Lorenzo Galluzzi
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Article
| Open AccessIntegrating taxonomic signals from MAGs and contigs improves read annotation and taxonomic profiling of metagenomes
Metagenomic taxonomic profiling usually relies either on reads or assembled contigs/MAGs. Here, authors present RAT, a tool that integrates taxonomic signals from reads, contigs, and MAGs into one profile with high precision and sensitivity. RAT provides a comprehensive view of the microbiome.
- Ernestina Hauptfeld
- , Nikolaos Pappas
- & F. A. Bastiaan von Meijenfeldt
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Article
| Open AccessAn ancestral SARS-CoV-2 vaccine induces anti-Omicron variants antibodies by hypermutation
Repeat vaccination with COVID-19 mRNA vaccines has been shown to increase breadth of the antibody response. Here the authors demonstrate that B cell clones induced by the ancestral COVID-19 vaccine develop into daughter clones with different reactivity to individual SARS-CoV-2 variants through the accumulation of somatic hypermutations.
- Seoryeong Park
- , Jaewon Choi
- & Junho Chung
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Article
| Open AccessDeviations in RSV epidemiological patterns and population structures in the United States following the COVID-19 pandemic
Non-pharmaceutical interventions for COVID-19 also impacted the transmission of other viruses including respiratory syncytial virus (RSV). Here the authors describe the changing epidemiology, clinical severity, and genetic diversity of RSV in Chicago, Illinois, from July 2010 to April 2023.
- Estefany Rios-Guzman
- , Lacy M. Simons
- & Judd F. Hultquist
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Article
| Open AccessGENESIS CGDYN: large-scale coarse-grained MD simulation with dynamic load balancing for heterogeneous biomolecular systems
Here, the authors report the development of heterogeneous domain decomposition with load balancing for large biological molecular dynamics simulations using residue-level coarse-grained models.
- Jaewoon Jung
- , Cheng Tan
- & Yuji Sugita
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Article
| Open AccessA patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments
Realistic tumour models are critical for the development of clinically relevant treatments. Here, the authors develop a lung cancer assembloid model which recapitulates key components of the primary tumour, and can be used to predict clinical outcome.
- Yanmei Zhang
- , Qifan Hu
- & Zhuo Xiong
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Article
| Open AccessTAD boundary deletion causes PITX2-related cardiac electrical and structural defects
This study identifies an altered chromatin conformation associated to a cardiac disorder observed in 7 independent families. A deletion of 2 diverging CTCF binding sites on 4q25 induces TAD fusion and leads to PITX2 expression dysregulation.
- Manon Baudic
- , Hiroshige Murata
- & Julien Barc
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Comment
| Open AccessShining light on dinoflagellate photosystem I
Dinoflagellates are ecologically important and essential to corals and other cnidarians as phytosymbionts, but their photosystems had been underexplored. Recently, photosystem I (PSI) of dinoflagellate Symbiodinium sp. was structurally characterized using cryo-Electron Microscopy (cryo-EM). These analyses revealed a distinct organization of the PSI supercomplex, including two previously unidentified subunits, PsaT and PsaU, and shed light on interactions between light harvesting antenna proteins and the PSI core. These results have implications with respect to the evolution of dinoflagellates and their association with cnidarians.
- Senjie Lin
- , Shuaishuai Wu
- & Arthur R. Grossman
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Article
| Open AccessCdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila
Mitochondrial fission, performed by Drp1, is carefully regulated, particularly in neurons. Here, the authors examine Drosophila Cdk8/CDK19 function in mitochondrial fission and uncover a role phosphorylating Drp1 in the cytoplasm and show overexpression suppresses a Parkinson’s disease model.
- Jenny Zhe Liao
- , Hyung-lok Chung
- & Esther M. Verheyen
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Article
| Open AccessTracing genetic diversity captures the molecular basis of misfolding disease
Pei et al. applied Gaussian process-based machine learning to capture dynamic spatial covariance relationships managed by proteostasis to mediate cooperative folding on a residue basis as a standard model for precision disease management.
- Pei Zhao
- , Chao Wang
- & William E. Balch
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Article
| Open AccessModulation of peroxisomal import by the PEX13 SH3 domain and a proximal FxxxF binding motif
Import of proteins into peroxisomes depends on PEX5, PEX13 and PEX14. Here the authors obtain crystal structures and NMR data to show the recognition of diaromatic peptide motifs on a noncanonical surface of the PEX13 SH3 domain, revealing a dynamic network which modulates peroxisomal matrix import.
- Stefan Gaussmann
- , Rebecca Peschel
- & Michael Sattler
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Article
| Open AccessRNA targeting and cleavage by the type III-Dv CRISPR effector complex
Here, Schwartz, Bravo, and Ahsan et al. show how multi-subunit fusion proteins are arranged around a crRNA in a type III CRISPR-Cas effector to cleave target RNA. Structures and molecular dynamics of this complex show three distinct active sites that can be used for programmable RNA cleavage.
- Evan A. Schwartz
- , Jack P. K. Bravo
- & David W. Taylor
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Article
| Open AccessThe genetic landscape of a metabolic interaction
Reynolds and colleagues examine a biochemically-mediated epistatic interaction between metabolic enzymes involved in folate metabolism and show that biochemical coupling shapes the range of enzyme activities sufficient to rescue cell growth.
- Thuy N. Nguyen
- , Christine Ingle
- & Kimberly A. Reynolds
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Article
| Open AccessPosition- and scale-invariant object-centered spatial localization in monkey frontoparietal cortex dynamically adapts to cognitive demand
The neural basis of spatial localization is poorly understood. Here the authors showed that when planning a reach towards an object, neural coding in the frontoparietal network dynamically changes between allocentric and egocentric spatial reference frames where the transition is controlled by task demands.
- Bahareh Taghizadeh
- , Ole Fortmann
- & Alexander Gail
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Article
| Open AccessLKRSDH-dependent histone modifications of insulin-like peptide sites contribute to age-related circadian rhythm changes
Age has an impact on circadian rhythm. Here, the authors report that LKRSDH-dependent H3R17me2 and H3K27me3 at insulin-like peptide sites contribute to age-related circadian rhythm change in Drosophila.
- Pengfei Lv
- , Xingzhuo Yang
- & Juan Du
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Article
| Open AccessCell cycle dependent coordination of surface layer biogenesis in Caulobacter crescentus
Surface layers (S-layers) are proteinaceous, two-dimensional paracrystalline arrays that constitute a major component of the cell envelope in many prokaryotic species. Here, Herdman et al. investigate S-layer biogenesis in the bacterium Caulobacter crescentus, providing insights into its coordination with the synthesis of other cell envelope components.
- Matthew Herdman
- , Buse Isbilir
- & Tanmay A. M. Bharat
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Article
| Open AccessAn esophagus cell atlas reveals dynamic rewiring during active eosinophilic esophagitis and remission
Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus with unclear immune cell involvement. Here the authors generate a single cell transcriptomic dataset with 400k cells from the esophageal mucosa of active EoE patients, remission EoE patients, and healthy individuals to characterise esophageal cellular composition, phenotype and interaction in this disease.
- Jiarui Ding
- , John J. Garber
- & Ramnik J. Xavier
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Article
| Open AccessLocal environment in biomolecular condensates modulates enzymatic activity across length scales
Here, the authors show that biomolecular condensates can enhance enzymatic rates by creating distinct solvent environments compared to the surrounding solution, and this emergent property can manifest within assemblies as small as nanometers.
- Marcos Gil-Garcia
- , Ana I. Benítez-Mateos
- & Paolo Arosio
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Article
| Open AccessRapid evolutionary change in trait correlations of single proteins
Trait correlations impact evolvability as selection on one trait can influence others. Here, the authors examine trait correlation in two proteins, a fluorescent protein & an antibiotic resistance enzyme, observing rapid evolution of trait correlations through changes in the biophysical properties of these proteins.
- Pouria Dasmeh
- , Jia Zheng
- & Andreas Wagner
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Article
| Open AccessConsistent survival in consecutive cases of life-supporting porcine kidney xenotransplantation using 10GE source pigs
Xenotransplantation is an imminent clinical reality but concerns remain around the logistics of procurement and the experimental immunosuppression regimens required to achieve long-term xenograft survival. Here the authors show more than 6 month survival of genetically modified porcine kidneys in baboons after regulatory compliant organ procurements, clinically relevant organ preservation times and FDA-approved immunosuppressive reagents.
- Daniel Eisenson
- , Yu Hisadome
- & Kazuhiko Yamada
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Article
| Open AccessAntiviral cellular therapy for enhancing T-cell reconstitution before or after hematopoietic stem cell transplantation (ACES): a two-arm, open label phase II interventional trial of pediatric patients with risk factor assessment
Viral infection is a common risk for immune-compromised individuals, particularly pediatric patients receiving hematopoietic stem cell transplants. Here the authors report a phase II trial testing adoptive transfer of third party, virus-specific T cells on the feasibility, safety, clinical responses, as well as homeostasis of antiviral immunity in the recipients.
- Michael D. Keller
- , Patrick J. Hanley
- & Michael A. Pulsipher
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Article
| Open AccessCD20/MS4A1 is a mammalian olfactory receptor expressed in a subset of olfactory sensory neurons that mediates innate avoidance of predators
How animals sense and properly avoid predators remains incompletely understood. Here, Jiang et al. show that the B cell co-receptor, CD20 also functions as an olfactory receptor and mediates the innate avoidance of predator derived odors.
- Hao-Ching Jiang
- , Sung Jin Park
- & Paul L. Greer
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Article
| Open AccessPerceptography unveils the causal contribution of inferior temporal cortex to visual perception
The precise role that inferotemporal cortex plays in object recognition remains poorly understood. Here, the authors combine high-throughput behavioral optogenetics in non-human primates with machine learning to graphically capture perceptual events evoked by local stimulation in the high-level visual cortex.
- Elia Shahbazi
- , Timothy Ma
- & Arash Afraz
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Article
| Open AccessMembrane to cortex attachment determines different mechanical phenotypes in LGR5+ and LGR5- colorectal cancer cells
The mechanical properties of heterogeneous cell populations in colorectal tumors and the relevance to cancer metastasis remain not fully understood. Here, the authors suggest that the variations in malignant phenotypes between LGR5-positive cancer stem cells and LGR5-negative cells could be due to their distinct mechanical phenotypes observed in vitro, determined by the membrane to cortex attachment proteins Ezrin/Radixin/Moesin.
- Sefora Conti
- , Valeria Venturini
- & Xavier Trepat
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Article
| Open AccessMassively parallel screen uncovers many rare 3′ UTR variants regulating mRNA abundance of cancer driver genes
The function of rare non-coding variants remains challenging to decipher. Here, the authors developed MapUTR to uncover 10,524 functional rare 3’ UTR variants regulating mRNA abundance, many of which reside in cancer driver genes.
- Ting Fu
- , Kofi Amoah
- & Xinshu Xiao
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Article
| Open AccessMonkeypox virus genomic accordion strategies
The 2023 monkeypox outbreak was caused by a subclade IIb monkeypox virus (MPXV). Here, using advanced sequencing techniques, the authors identify variations on low-complexity regions of the MPXV genome and describe their potential as evolutionary drivers.
- Sara Monzón
- , Sarai Varona
- & Gustavo Palacios
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Article
| Open AccessDetecting m6A at single-molecular resolution via direct RNA sequencing and realistic training data
Direct RNA-seq offers the possibility to identify RNA modifications on single molecules. Here, the authors report on the synthesis of biologically realistic training data and the development of mAFiA that accurately detects m6A on single read level.
- Adrian Chan
- , Isabel S. Naarmann-de Vries
- & Christoph Dieterich
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Article
| Open AccessStructural basis for antiepileptic drugs and botulinum neurotoxin recognition of SV2A
SV2A is a receptor for botulinum neurotoxin (BoNT) and new generation antiepileptic drugs (AEDs). Here the authors report cryo-EM structures of SV2A in complex with BoNT receptor binding domain and AEDs highlighting the difference in the binding affinity between AEDs.
- Atsushi Yamagata
- , Kaori Ito
- & Mikako Shirouzu
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Article
| Open AccessIlluminating the complete ß-cell mass of the human pancreas- signifying a new view on the islets of Langerhans
The pancreatic islets of Langerhans play a pivotal role in regulating blood glucose homeostasis through the regulated secretion of the hormones insulin and glucagon. Here, the authors use deep tissue 3D imaging to re-construct the entire human pancreas at microscopic resolution and display previously unrecognized heterogeneities in the islet’s cellularity with pre-clinical and clinical implications.
- Joakim Lehrstrand
- , Wayne I. L. Davies
- & Ulf Ahlgren
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Article
| Open AccessTowards establishing a fungal economics spectrum in soil saprobic fungi
Challenges in obtaining empirical trait data hinder the development of trait-based frameworks for soil microbes. Here, the authors analyse traits of saprobic fungal isolates from a grassland site to propose a fungal economics spectrum, suggesting a general trait framework for soil fungi.
- Tessa Camenzind
- , Carlos A. Aguilar-Trigueros
- & Matthias C. Rillig
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Article
| Open AccessMechanoelectronic stimulation of autologous extracellular vesicle biosynthesis implant for gut microbiota modulation
Pathogenic gut microbiota is responsible for a few debilitating gastrointestinal Diseases. Here, the authors develop a wireless mechanoelectronic device designed to manufacture of functional vesicles in vivo to regulate microbiome.
- Shuangshuang Wan
- , Kepeng Wang
- & Lianhui Wang
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Article
| Open AccessImpact of PEG sensitization on the efficacy of PEG hydrogel-mediated tissue engineering
Concerns over the immunogenicity of poly(ethylene glycol) (PEG) are growing, and the implications for tissue engineering are unknown. Here the authors evaluate the impact of anti-PEG antibodies and PEG immunogenicity on the efficacy of a PEG hydrogel-based tissue engineering therapy.
- Alisa H. Isaac
- , Sarea Y. Recalde Phillips
- & Daniel L. Alge
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Article
| Open AccessLate-stage meta-C–H alkylation of pharmaceuticals to modulate biological properties and expedite molecular optimisation in a single step
Installation of small aliphatic motifs within pharmaceuticals provides a medicinally relevant tool in drug discovery programmes. Here, the authors report a late-stage meta-C–H alkylation method facilitating the biological properties modulation of therapeutic agents.
- Lucas Guillemard
- , Lutz Ackermann
- & Magnus J. Johansson
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Matters Arising
| Open AccessThe wheat stripe rust resistance gene YrNAM is Yr10
- Katherine Dibley
- , Matthias Jost
- & Peng Zhang
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Article
| Open AccessImprovement of immune dysregulation in individuals with long COVID at 24-months following SARS-CoV-2 infection
Post-acute sequelae of COVID (PASC) or long-COVID can affect a proportion of those infected but this is not well understood. Here the authors perform a single cell transcriptomics analysis of immune cells from long-COVID patients at 24 months and find that cell changes observed at 3 and 8 months do not persist to 24 months.
- Chansavath Phetsouphanh
- , Brendan Jacka
- & Gail V. Matthews
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Article
| Open AccessInflammation and cytomegalovirus viremia during pregnancy drive sex-differentiated differences in mortality and immune development in HIV-exposed infants
HIV exposed but uninfected infants may face an increased risk of serious infection and mortality. In this work, the authors utilise a cohort from rural Zimbabwe to explore the biological mechanisms underlying infant mortality.
- Ceri Evans
- , Kuda Mutasa
- & Andrew J. Prendergast
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Article
| Open AccessMmcA is an electron conduit that facilitates both intracellular and extracellular electron transport in Methanosarcina acetivorans
Methanogens conserve energy through methane generation, however the biochemical details of anaerobic respiration in methanogens remain unclear. Here, authors show a multiheme c-type cytochrome, MmcA, plays a critical role in methanogenesis and anaerobic respiration.
- Dinesh Gupta
- , Keying Chen
- & Dipti D. Nayak
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Article
| Open AccessCross-link assisted spatial proteomics to map sub-organelle proteomes and membrane protein topologies
The spatial mapping of proteins can give important functional insights. Here, Zhu et al. develop a cross-linking mass spectrometry-based spatial proteomics method that does not require protein engineering, affords sub-organelle resolution, and elucidates both protein locations and membrane topologies.
- Ying Zhu
- , Kerem Can Akkaya
- & Fan Liu
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Article
| Open AccessAn pair of an atypical NLR encoding genes confer Asian soybean rust resistance in soybean
Asian soybean rust (ASR) is a devastating disease of soybean. Here, the author report the identification of an atypical pair of nucleotide-binding leucine-rich repeat (NLR) encoding genes and how they function together to confer broad-spectrum resistance to ASR.
- Qingnan Hao
- , Hongli Yang
- & Xinan Zhou
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Article
| Open AccessPhylogenomic profiles of whole-genome duplications in Poaceae and landscape of differential duplicate retention and losses among major Poaceae lineages
Grasses share a whole-genome duplication called rho, but the adaptive implications are unclear. Here, the authors conduct phylogenomic and phylotranscriptomic analyses of 363 grasses, identifying additional whole-genome duplications and finding that duplicates are implicated in environmental adaptations or morphogenesis.
- Taikui Zhang
- , Weichen Huang
- & Hong Ma
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Article
| Open AccessData-driven recombination detection in viral genomes
Here, the authors present RecombinHunt, a computational method based on big data analysis, that enhances community-based detection of recombinant viral lineages.
- Tommaso Alfonsi
- , Anna Bernasconi
- & Stefano Ceri
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Article
| Open AccessThe DEAD-box ATPase Dbp10/DDX54 initiates peptidyl transferase center formation during 60S ribosome biogenesis
Cruz et al. describe the role of Dbp10/DDX54 in remodeling rRNA structure within the immature eukaryotic peptidyl transferase center of the ribosome, coupling energy-dependent catalysis to a post-catalytic role in factor exchange during 60S ribosomal subunit assembly.
- Victor E. Cruz
- , Christine S. Weirich
- & Jan P. Erzberger
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