Featured
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Article
| Open AccessStructural and dynamic insights into the activation of the μ-opioid receptor by an allosteric modulator
Here, the authors utilise NMR and cryo-EM to characterise the binding of an allosteric modulator to μ-opioid receptor (MOR), revealing modulator binding can potentiate receptor activation by altering the conformational dynamics in the core region of MOR.
- Shun Kaneko
- , Shunsuke Imai
- & Ichio Shimada
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Article
| Open AccessMultiscale modelling of chromatin 4D organization in SARS-CoV-2 infected cells
In this work, the authors apply polymer models to reconstruct the 3D structure of the genome during SARS-CoV-2 infection and examine how the virus impacts key mechanisms of chromatin organization.
- Andrea M. Chiariello
- , Alex Abraham
- & Mario Nicodemi
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Article
| Open AccessNonuniform and pathway-specific laminar processing of spatial frequencies in the primary visual cortex of primates
The uniformity of laminar processing in a cortex remains not fully understood. Here authors show that high spatial frequency stimuli elicit distinct active patterns across V1 layers, arising from multiple mechanisms involving M and P pathways.
- Tian Wang
- , Weifeng Dai
- & Dajun Xing
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Article
| Open AccessThe structural basis for 2′−5′/3′−5′-cGAMP synthesis by cGAS
Here, the authors provide structural and biochemical data describing the mechanism through which cGAS synthesizes 2′−5′/3′−5′-cGAMP.
- Shuai Wu
- , Sandra B. Gabelli
- & Jungsan Sohn
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Article
| Open AccessThe basal forebrain to lateral habenula circuitry mediates social behavioral maladaptation
Maladaptive fear is linked to many neuropsychiatric disorders, while its neural basis is not fully understood. Here, the authors show that the hyperactivity of the basal forebrain to lateral habenula glutamatergic circuit is crucial for social fear behavior.
- Jun Wang
- , Qian Yang
- & Han Xu
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Article
| Open AccessDynamic microvilli sculpt bristles at nanometric scale
Bristleworms possess dedicated cells that can synthesize highly stereotypical bristles with sub-micrometric precision. Here, Ikeda and colleagues shed light on the underlying dynamics of cellular protrusions, revealing an extension-disassembly cycle that resembles a 3D printer.
- Kyojiro N. Ikeda
- , Ilya Belevich
- & Florian Raible
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Article
| Open AccessPlatelets favor the outgrowth of established metastases
It is unclear if platelets regulate the growth of established metastases. Using syngeneic mouse models of metastasis, the authors show that platelets support the outgrowth of established metastases via immune suppression, and that targeting the platelet-specific receptor GPVI, efficiently reduces established metastases, providing a promising therapeutic avenue for inhibiting cancer metastasis.
- Maria J. Garcia-Leon
- , Cristina Liboni
- & Jacky G. Goetz
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Article
| Open AccessA cell-free nutrient-supplemented perfusate allows four-day ex vivo metabolic preservation of human kidneys
As demand for organ transplants exceeds availability there has been an unmet need to extend preservation of deceased donor kidneys. Here, the authors show that a cell-free nutrient-supplemented perfusate allows 4-day preservation of human kidneys using spatially resolved lipidomics and metabolomics.
- Marlon J. A. de Haan
- , Marleen E. Jacobs
- & Ton J. Rabelink
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Article
| Open AccessStructural basis of human NOX5 activation
NADPH oxidase 5 (NOX5) is activated by Ca2+ signaling, catalyzing superoxide production by transferring electrons from intracellular NADPH to extracellular oxygen. Here the authors uncover the molecular basis of NOX5 activation and electron transfer.
- Chenxi Cui
- , Meiqin Jiang
- & Ji Sun
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Article
| Open AccessEnhancing genome editing in hPSCs through dual inhibition of DNA damage response and repair pathways
Precise genome editing is crucial. Here the authors demonstrate that dual inhibition of p53-mediated cell death and distinct activation of the DNA damage repair system upon DNA damage by cytosine base editor (CBE) or prime editor (PE) additively enhanced editing efficiency in hPSCs.
- Ju-Chan Park
- , Yun-Jeong Kim
- & Hyuk-Jin Cha
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Article
| Open AccessStructural insights into drug transport by an aquaglyceroporin
Pentamidine and melarsoprol are drugs used to treat sleeping sickness caused by Trypanosoma brucei. Here, authors present cryo-EM structures of TbAQP2 with molecular dynamic simulations, revealing mechanisms shaping substrate specificity and drug permeation.
- Wanbiao Chen
- , Rongfeng Zou
- & Chongyuan Wang
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Article
| Open AccessThe greenbeard gene tgrB1 regulates altruism and cheating in Dictyostelium discoideum
Greenbeards encode perceptible signals, signal recognition ability, and altruism towards others displaying the signal. This study shows that activation of the greenbeard receptor gene tgrB1 increases altruism and inactivation causes kin-specific cheating in the social amoeba Dictyostelium discoideum.
- Mariko Katoh-Kurasawa
- , Peter Lehmann
- & Gad Shaulsky
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Article
| Open AccessDetection of Anaplasma and Ehrlichia bacteria in humans, wildlife, and ticks in the Amazon rainforest
In this study, the authors detect diverse Ehrlichia and Anaplasma bacteria in samples from Amazonian wildlife, humans and ticks that are mostly distinct from pathogens detected in the Northern Hemisphere and that might indicate emerging health hazards from tick-borne diseases in the Amazon rainforests.
- Marie Buysse
- , Rachid Koual
- & Olivier Duron
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Article
| Open AccessRegulation of cerebral blood flow boosts precise brain targeting of vinpocetine-derived ionizable-lipidoid nanoparticles
Despite advances in active drug-targeting for blood-brain barrier penetration, challenges related to brain biodistribution, and drug accumulation persist. Here the authors show a molecular library design centered on cyclic tertiary amine compounds and develop a self-enhanced brain-targeted nucleic acid delivery system inspired by the neuroprotective properties of vinpocetine.
- Xufei Bian
- , Ling Yang
- & Chong Li
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Article
| Open AccessAn integrated multi-omics approach reveals polymethoxylated flavonoid biosynthesis in Citrus reticulata cv. Chachiensis
Citrus reticulata cv. Chachiensis (CRC) is used in traditional Chinese medicine to treat various ailments. Here Wen et al. provide genomic, transcriptomic and metabolomic resources for CRC and propose a possible biosynthetic pathway for bioactive components.
- Jiawen Wen
- , Yayu Wang
- & Huan Liu
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Article
| Open AccessEffects of SPI1-mediated transcriptome remodeling on Alzheimer’s disease-related phenotypes in mouse models of Aβ amyloidosis
Although SPI1 gene was identified as a risk factor for Alzheimer’s disease, its role in the disease remains unclear. Here, the authors show that decreasing SPI1 level exacerbates disease symptoms, whereas increasing its level ameliorates phenotypes.
- Byungwook Kim
- , Luke Child Dabin
- & Jungsu Kim
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Article
| Open AccessCerebellar Purkinje cells in male macaques combine sensory and motor information to predict the sensory consequences of active self-motion
Neural basis of the sensory suppression signal required to cancel peripheral vestibular input is not fully understood. Here authors show that cerebellar Purkinje cells combine sensory and motor information to predict the sensory consequences of active self-motion, thereby establishing how vestibular reafference is distinguished to cancel self-generated sensory input.
- Omid A. Zobeiri
- & Kathleen E. Cullen
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Article
| Open AccessHigh-confidence 3D template matching for cryo-electron tomography
Enabling visual proteomics with high-confidence 3D template matching (TM) in CryoET. 3D TM precisely localizes macromolecular complexes, individual subunits, and different functional states in situ, revealing molecular interactions within cells.
- Sergio Cruz-León
- , Tomáš Majtner
- & Gerhard Hummer
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Article
| Open AccessMolecular basis of bacterial DSR2 anti-phage defense and viral immune evasion
The defense-associated sirtuin 2 (DSR2) system protects bacteria from phages by depleting NAD+. Here, authors elucidate the molecular mechanisms underlying DSR2 assembly, activation, and inhibition, providing important insights into bacterial anti-phage defense.
- Jiafeng Huang
- , Keli Zhu
- & Ang Gao
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Article
| Open AccessMutational dissection of a hole hopping route in a lytic polysaccharide monooxygenase (LPMO)
Lytic polysaccharide monooxygenases (LPMOs) are mono copper enzymes with outstanding industrial applicability. Here, the authors investigate the “hole hopping” mechanism in a bacterial LPMO and show that a strictly conserved tryptophan is critical for radical formation and hole transference, as well as reveal a correlation between the efficiency of hole transference and enzyme performance under oxidative stress.
- Iván Ayuso-Fernández
- , Tom Z. Emrich-Mills
- & Vincent G. H. Eijsink
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Article
| Open AccessGenetic and functional diversity of β-N-acetylgalactosamine-targeting glycosidases expanded by deep-sea metagenome analysis
Four β-N-acetylgalactosaminidase gene families were identified via deep-sea metagenome analysis. The biochemical and structural characterization of the aforementioned enzymes revealed their functional diversity and monophyletic evolutionary history.
- Tomomi Sumida
- , Satoshi Hiraoka
- & Takuro Nunoura
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Article
| Open AccessTemperature alters the predator-prey size relationships and size-selectivity of Southern Ocean fish
Using prey size measurements from ten Southern Ocean lanternfish species sampled across >10° of latitude, this study shows that higher temperatures were associated with smaller fish and an overall decrease in the size of fish relative to their prey. Ocean warming may therefore alter the diversity and size structuring of trophic interactions, reducing the stability of marine ecosystems.
- Patrick Eskuche-Keith
- , Simeon L. Hill
- & Eoin J. O’Gorman
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Article
| Open AccessMultimodal binding and inhibition of bacterial ribosomes by the antimicrobial peptides Api137 and Api88
Proline-rich antimicrobial peptides (PrAMPs) inhibit bacterial protein biosynthesis. Here, the authors show that the honey-bee derived PrAMPs Api137 and Api88 inhibit bacterial ribosomes through multiple mechanisms, promising for drug development.
- Simon M. Lauer
- , Maren Reepmeyer
- & Ralf Hoffmann
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Article
| Open AccessFragment ion intensity prediction improves the identification rate of non-tryptic peptides in timsTOF
Immunopeptidomics is crucial for the discovery of potential immunotherapy and vaccine candidates. Here, the authors generate a ground truth timsTOF dataset to fine-tune the deep learning model Prosit, improving peptide-spectrum match rescoring by up to 3-fold during immunopeptide identification.
- Charlotte Adams
- , Wassim Gabriel
- & Kurt Boonen
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Article
| Open AccessUnveiling the A-to-I mRNA editing machinery and its regulation and evolution in fungi
A-to-I editing in animals is catalyzed by enzymes of the Adenosine Deaminase Acting on RNA family, orthologues of which do not exist in fungi. Here, Feng et al. characterise the enzymes involved in A-to-I mRNA editing in Fusarium graminearum.
- Chanjing Feng
- , Kaiyun Xin
- & Huiquan Liu
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Article
| Open AccessAn integrated technology for quantitative wide mutational scanning of human antibody Fab libraries
Limited experimental platforms exist for assessing quantitative sequence-function relationships for multiple antibodies. Here, authors develop a deep-sequencing based technology called MAGMA-seq, that determines the quantitative properties of antibody libraries.
- Brian M. Petersen
- , Monica B. Kirby
- & Timothy A. Whitehead
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Article
| Open AccessMultiplexed bulk and single-cell RNA-seq hybrid enables cost-efficient disease modeling with chimeric organoids
IPSC-derived organoids model diseases. Multiplexed coculture and demultiplexing natural genetic barcodes aid in studying genetic effects. Here, authors introduce Vireo-bulk to deconvolve bulk RNA-seq data, quantify donor abundance and identify differentially expressed genes.
- Chen Cheng
- , Gang Wang
- & Jin Zhang
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Article
| Open AccessThree concurrent mechanisms generate gene copy number variation and transient antibiotic heteroresistance
Bacterial heteroresistance is a medically relevant phenotype where small antibiotic-resistant subpopulations coexist within predominantly susceptible bacterial populations. Here, Nicoloff et al. describe how three different mechanisms that increase the copy number of resistance genes can lead to unstable and transient heteroresistance.
- Hervé Nicoloff
- , Karin Hjort
- & Helen Wang
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Article
| Open AccessDiscovering allatostatin type-C receptor specific agonists
Pesticides safeguard crops against pest infestations and mitigate associated risks. In this work, the authors develop a pesticide targeting AlstR-C of T.pityocampa pests, showing promising results without harming other insects, and advancing the development of GPCR-targeted pesticides for insect control.
- Kübra Kahveci
- , Mustafa Barbaros Düzgün
- & Necla Birgul Iyison
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Article
| Open AccessTFPI from erythroblasts drives heme production in central macrophages promoting erythropoiesis in polycythemia
The role of coagulation system in erythropoiesis is not clear. Here, the authors report that an anticoagulant protein TFPI from erythroblasts directs central macrophages to synthesize heme, which in turn promotes erythropoiesis in bone marrow.
- Jun-Kai Ma
- , Li-Da Su
- & Xin-Jiang Lu
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Article
| Open AccessPretreatment with IL-15 and IL-18 rescues natural killer cells from granzyme B-mediated apoptosis after cryopreservation
Natural killer (NK) cells are assessed for various therapies, but sub-optimal cryopreservation dampens their clinical feasibility. Here the authors show that pretreating human NK cells with IL-15/IL-18 prior to cryopreservation improves NK cell post-thaw viability and functions, potentially via anti-apoptosis gene induction and granzyme B degranulation.
- Abdulla Berjis
- , Deeksha Muthumani
- & Neil C. Sheppard
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Article
| Open AccessRegulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression
MYC regulates numerous genes involved in cell growth and proliferation. Here, Li-Bao et al. study the DNA regions that regulate Myc transcription in early mouse embryos and pluripotent stem cells. They report a specific region with independent modules dedicated to discrete temporal and spatial phases of Myc expression.
- Lin Li-Bao
- , Covadonga Díaz-Díaz
- & Miguel Torres
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Article
| Open AccessSpatial mapping of hepatic ER and mitochondria architecture reveals zonated remodeling in fasting and obesity
Hepatocytes are central for maintaining metabolic homeostasis during nutritional transitions. Here, we show that the structural remodelling of hepatic organelles is part of hepatocytes’ metabolic plasticity to adapt to cycles of fasting/feeding and this process is zonated in the liver.
- Güneş Parlakgül
- , Song Pang
- & Ana Paula Arruda
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Article
| Open AccessA nascent riboswitch helix orchestrates robust transcriptional regulation through signal integration
Here the authors unveil an intermediate state during the folding of the manganese riboswitch from L. lactis. This transient state allows the integration of multiple cellular signals including RNA polymerase pausing and transcription factor NusA.
- Adrien Chauvier
- , Shiba S. Dandpat
- & Nils G. Walter
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Article
| Open AccessFused in sarcoma (FUS) inhibits milk production efficiency in mammals
Efficient milk production in mammals confers advantages by facilitating the transmission of energy from mother to offspring. However, the factors for establishing the efficiency in mammals are unknown. Here, the authors identify FUS as a regulator of efficient milk production in mammals.
- Haili Shao
- , Jipeng Huang
- & Baowei Jiao
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Article
| Open AccessThe STING agonist IMSA101 enhances chimeric antigen receptor T cell function by inducing IL-18 secretion
It has been previously suggested that STING agonists can improve response to CAR-T therapy. Here the authors report the characterization of the STING agonist IMSA101, showing that STING-induced IL18 secretion enhances CAR-T activity in preclinical cancer models.
- Ugur Uslu
- , Lijun Sun
- & Carl H. June
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Article
| Open AccessAptameric hirudins as selective and reversible EXosite-ACTive site (EXACT) inhibitors
Inspired by the biologics of hematophagous organisms such as leeches, the authors in this work design and create inhibtors of thrombin and factor Xa by linking exosite-binding aptamers with small molecule active site inhibtors. They coin these inhibitors EXACT inhibitors.
- Haixiang Yu
- , Shekhar Kumar
- & Bruce A. Sullenger
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Article
| Open AccessA time-resolved multi-omics atlas of transcriptional regulation in response to high-altitude hypoxia across whole-body tissues
The mechanisms underlying high-altitude acclimatization remain unclear. Here authors use the sheep model to reveal multi-tissue temporal dynamics of gene transcription and regulation during acclimatization, and provide resources for hypoxia-related studies.
- Ze Yan
- , Ji Yang
- & Meng-Hua Li
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Article
| Open AccessConsensus-building conversation leads to neural alignment
Conversation is a primary means of social influence, but its effects on the brain aren’t well-understood. Here, the authors find evidence that people who are central in their social networks facilitate consensus-building conversations that align future brain activity.
- Beau Sievers
- , Christopher Welker
- & Thalia Wheatley
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Article
| Open AccessSex affects transcriptional associations with schizophrenia across the dorsolateral prefrontal cortex, hippocampus, and caudate nucleus
Schizophrenia research has traditionally overlooked sex differences. Here, the authors show the importance of sex-based analysis across multi-brain regions by identifying sex-specific genes and genetic interactions in schizophrenia and sex-specific risk.
- Kynon J. M. Benjamin
- , Ria Arora
- & Jennifer A. Erwin
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Article
| Open AccessThe translocation of a chloride channel from the Golgi to the plasma membrane helps plants adapt to salt stress
In Arabidopsis roots, NaCl induces the translocation of AtCLCf from the Golgi to the plasma membrane, mediated by the small GTPase AtRABA1b, where AtCLCf functions as a Cl− efflux channel and confers salinity tolerance to the plant.
- Sivamathini Rajappa
- , Pannaga Krishnamurthy
- & Prakash P. Kumar
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Article
| Open AccessComprehensive assessment of mRNA isoform detection methods for long-read sequencing data
Recently, various computational tools have emerged for detecting mRNA isoforms using long-read sequencing data. Here, the authors systemically evaluate and compare the performance of these tools.
- Yaqi Su
- , Zhejian Yu
- & Wanlu Liu
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Article
| Open AccessDistributed representations of prediction error signals across the cortical hierarchy are synergistic
Whether prediction errors are encoded by synergistic information across the cortex is unknown. Here, the authors demonstrate that distributed representations of prediction errors across the cortex can be highly synergistic.
- Frank Gelens
- , Juho Äijälä
- & Andres Canales-Johnson
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Article
| Open Access5′UTR G-quadruplex structure enhances translation in size dependent manner
In eukaryotes, G-quadruplex in mRNA (RG4) 5′ UTR inhibit translation initiation. Here the authors employ single molecule assay to show that RG4 in E. coli reporter increases translation efficiency by preventing ribosome dislodging.
- Chun-Ying Lee
- , Meera Joshi
- & Sua Myong
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Article
| Open AccessRapid expansion and international spread of M1UK in the post-pandemic UK upsurge of Streptococcus pyogenes
Exponential growth of toxigenic Streptococcus pyogenes M1UK lineage accounted for most of the 2022/2023 invasive infection upsurge in the UK. Authors provide evidence that M1UK first emerged in 2008, has genetic evidence of enhanced fitness, and has disseminated to 3 continents.
- Ana Vieira
- , Yu Wan
- & Shiranee Sriskandan
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Article
| Open AccessVOLTA: an enVironment-aware cOntrastive ceLl represenTation leArning for histopathology
While machine learning platforms can improve the assessment of Hematoxylin & Eosin (H&E) stained-tumour tissue images, current models typically require manual cell-type annotations in training. Here, the authors develop VOLTA, a self-supervised machine learning framework to improve cell representation learning in H&E images based on the cells environment
- Ramin Nakhli
- , Katherine Rich
- & Ali Bashashati
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Article
| Open AccessAssessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries
High levels of extended spectrum beta-lactamase (ESBL) and carbapenemase encoding genes were detected in bacterial isolates causing neonatal sepsis in LMICs. Authors assess the in vitro activity of three antibiotics (fosfomycin, flomoxef and amikacin) in combination against ESBL-producing Klebsiella pneumoniae and Escherichia coli isolates.
- Biljana Kakaraskoska Boceska
- , Tuba Vilken
- & Herman Goossens
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Article
| Open AccessHerpes simplex encephalitis due to a mutation in an E3 ubiquitin ligase
Encephalitis is a rare and severe complication of Herpes Simplex type 1 infection. Here, Bibert et al describe a genetic variant in a 2-year-old affected child that impairs interferon production in neuronal cells and enhances viral replication.
- Stéphanie Bibert
- , Mathieu Quinodoz
- & Pierre-Yves Bochud
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Matters Arising
| Open AccessReply to: Technical challenges of studying the impact of plasma components on the efficacy of lipid nanoparticles for vaccine and therapeutic applications
- Kai Liu
- , Elisa Lázaro-Ibáñez
- & Alan Sabirsh
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