Featured
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Article
| Open AccessEmergent digital bio-computation through spatial diffusion and engineered bacteria
Biological computing is a promising field with potential applications in biosafety, environmental monitoring, and personalized medicine. Here the authors create bio-computers using engineered E. coli colonies that respond to chemical gradients, producing different logic functions depending on how they are spatially arranged.
- Alex J. H. Fedorec
- , Neythen J. Treloar
- & Chris P. Barnes
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Article
| Open AccessThe Legionella collagen-like protein employs a distinct binding mechanism for the recognition of host glycosaminoglycans
The Legionella collagen-like protein (Lcl) is important for host adhesion in Legionella pneumophila. Here, the authors provide structural and biochemical data, which provides insights into a distinct “fuzzy” glycosaminoglycan binding mechanism.
- Saima Rehman
- , Anna Katarina Antonovic
- & James A. Garnett
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Perspective
| Open AccessLDL receptor in alphavirus entry: structural analysis and implications for antiviral therapy
Recently, studies have identified different low-density lipoprotein receptors as functional entry receptors for alphaviruses. In this Perspective, the authors compare the known alphavirus-receptor structures and discuss why it might be challenging to generate a broad-spectrum entry inhibitor.
- Ningning Wang
- , Andres Merits
- & Shuo Su
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Article
| Open AccessDOS-3 mediates cell-non-autonomous DAF-16/FOXO activity in antagonizing age-related loss of C. elegans germline stem/progenitor cells
By performing a tissue-specific transcriptome analysis, Zhang et al. show how age-related loss of germline stem/progenitor cells in C. elegans is regulated by a signal produced by non-niche cells within the same organ system.
- Zhifei Zhang
- , Haiyan Yang
- & Zhao Qin
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Article
| Open AccessDevelopment of deaminase-free T-to-S base editor and C-to-G base editor by engineered human uracil DNA glycosylase
Efficient base editors for direct thymine (T) editing are highly desirable. Here, authors develop two deaminase-free glycosylase-based base editors for direct T editing (gTBE) and C editing (gCBE) by rounds of structure-informed mutagenesis on human DNA glycosylase UNG and further engineering.
- Huawei Tong
- , Haoqiang Wang
- & Hui Yang
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Article
| Open AccessExploring plant-derived phytochrome chaperone proteins for light-switchable transcriptional regulation in mammals
Synthetic biology applications require finely tuned gene expression, often mediated by synthetic transcription factors. Here the authors validate two plant-derived proteins, FHY1 and FHL, acting as transactivators in mammalian cells for orthogonal, modular, and tunable control of gene transcription by forming a photosensing transcriptional regulation complex with PhyA.
- Deqiang Kong
- , Yang Zhou
- & Haifeng Ye
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Article
| Open AccessRule-based omics mining reveals antimicrobial macrocyclic peptides against drug-resistant clinical isolates
This study reports the genomics- and metabolomics-guided discovery of aminovinyl-(methyl-)cysteine-containing peptides (ACyP). One of these peptides, massatide A, demonstrates excellent activity against drug-resistant gram-positive pathogens.
- Zhuo Cheng
- , Bei-Bei He
- & Yong-Xin Li
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Article
| Open AccessArtificial cellulosic leaf with adjustable enzymatic CO2 sequestration capability
Developing artificial leaves is crucial for advancing Net Zero Future, but most artificial leaves rely on the use of metal or semiconductors catalysts that usually have a lower catalytic activity and selectivity compared to biocatalysts. Here the AUs report Ecoleaf, a biodegradable artificial leaf that mimics the controlled expansion and contraction of stomata and enables enzymic CO2 conversion.
- Xing Zhu
- , Chenxi Du
- & Bin He
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Article
| Open AccessTobacco-induced hyperglycemia promotes lung cancer progression via cancer cell-macrophage interaction through paracrine IGF2/IR/NPM1-driven PD-L1 expression
Tobacco smoking is an important risk factor for lung cancer. Here the authors report that tobacco carcinogens promote metabolic syndrome and metabolic reprogramming of macrophages, associated with lung cancer progression in preclinical models.
- Hyun-Ji Jang
- , Hye-Young Min
- & Ho-Young Lee
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Article
| Open AccessOptimizing cell therapy by sorting cells with high extracellular vesicle secretion
Extracellular vesicles have been exploited as potential therapeutic agents. Here, the authors apply a nanovial technology to select sub-populations of cells that secrete high levels of extracellular vesicles, leading to improved therapeutic efficacy when delivered in vivo.
- Doyeon Koo
- , Xiao Cheng
- & Dino Di Carlo
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Article
| Open AccessEvolution of connectivity architecture in the Drosophila mushroom body
Brain evolution at the cellular level is understudied. Here, the authors compare olfactory circuits from three Drosophila species, finding species-specific connectivity patterns associated with food odours and suggesting that more connectivity may be related to learning performance.
- Kaitlyn Elizabeth Ellis
- , Sven Bervoets
- & Sophie Jeanne Cécile Caron
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Article
| Open AccessDepth-enhanced high-throughput microscopy by compact PSF engineering
Implementing point spread function (PSF) engineering in high-throughput microscopy has proved challenging. Here, the authors propose a compact PSF engineering approach, which allows for enhanced depth of field and for the recovery of 3D information using single snapshots.
- Nadav Opatovski
- , Elias Nehme
- & Yoav Shechtman
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Article
| Open AccessA YAP-centered mechanotransduction loop drives collective breast cancer cell invasion
Aligned collagen I is associated with the emergence of leader cells that are responsible for collective invasion. Here, the authors show that Collagen I and Yap signalling are in a feed-forward loop to drive the collective invasion of basal-like tumour cells.
- Antoine A. Khalil
- , Daan Smits
- & Johan de Rooij
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Article
| Open AccessMicrobial community organization designates distinct pulmonary exacerbation types and predicts treatment outcome in cystic fibrosis
In this work, authors show that exacerbations of respiratory symptoms in persons with cystic fibrosis (CF) were associated with either CF pathogen-driven or anaerobe-based changes in airway bacterial community structure.
- Stefanie Widder
- , Lisa A. Carmody
- & John J. LiPuma
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Article
| Open AccessGermline variation contributes to false negatives in CRISPR-based experiments with varying burden across ancestries
The role of ancestry in target discovery remains to be systematically explored. Here, the authors analyse data from 611 genome scale CRISPR/Cas9 viability experiments in human cell line models as part of The Cancer Dependency Map and identify ancestry-associated genetic dependencies.
- Sean A. Misek
- , Aaron Fultineer
- & Jesse S. Boehm
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Article
| Open AccessASXLs binding to the PHD2/3 fingers of MLL4 provides a mechanism for the recruitment of BAP1 to active enhancers
Human methyltransferase MLL4 mediates embryonic development and is dysregulated in diseases. Zhang et al. found that binding of PHD fingers of MLL4 to ASXL1/2 is required for recruitment of the deubiquitinase BAP1 to MLL4-bound active enhancers in vitro.
- Yi Zhang
- , Guojia Xie
- & Tatiana G. Kutateladze
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Article
| Open AccessAn effective and rapidly degradable disinfectant from disinfection byproducts
Here, authors highlight ecological risks of a widely used disinfectant, chloroxylenol, and identify a more efficient and safer alternative from halo-phenolic disinfection byproducts, 2,6-dichlorobenzoquinone. They leverage seawater’s slightly alkaline nature to enhance its degradability via hydrolysis.
- Jiarui Han
- , Wanxin Li
- & Xiangru Zhang
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Article
| Open AccessMultiomic ALS signatures highlight subclusters and sex differences suggesting the MAPK pathway as therapeutic target
Multiomic brain tissue analysis identified sex-specific molecular changes in Amyotrophic lateral sclerosis (ALS), revealing subgroups within the disease and pointing to the MAPK pathway as an early disease mechanism and potential therapeutic target.
- Lucas Caldi Gomes
- , Sonja Hänzelmann
- & Paul Lingor
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Article
| Open AccessMapping and annotating genomic loci to prioritize genes and implicate distinct polygenic adaptations for skin color
Here, the authors perform a large GWAS for objectively quantified skin color in an East Asian population (N = 48,433), identifying potential causal genes, polygenic adaptations, and interaction between genetic variants and sun-exposure at polygenic level.
- Beomsu Kim
- , Dan Say Kim
- & Hong-Hee Won
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Article
| Open AccessThe role of promiscuous molecular recognition in the evolution of RNase-based self-incompatibility in plants
Self-incompatibility evolved to avoid self-fertilization among hermaphroditic plants, yet it remains murky how this compatibility recognition evolved. This study constructs a theoretical framework incorporating promiscuous molecular recognition into the evolutionary model of incompatibility.
- Keren Erez
- , Amit Jangid
- & Tamar Friedlander
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Article
| Open AccessParvalbumin-expressing basal forebrain neurons mediate learning from negative experience
Whether and how parvalbumin-expressing neural population from Basal forebrain (BFPVNs) nuclei play a role in associative learning are not fully understood. Here authors show that BFPVNs mediate aversive associative learning via playing crucial roles in encoding outcome-related information.
- Panna Hegedüs
- , Bálint Király
- & Balázs Hangya
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Article
| Open AccessHarbinger transposon insertion in ethylene signaling gene leads to emergence of new sexual forms in cucurbits
In flowering plants, hermaphroditism is widespread. Here the authors identified a transposon insertion that triggers plant sexual transition. This study highlights the role of transposons in plant adaptation and evolution.
- Hsin-Ya Huang
- , Siqi Zhang
- & Abdelhafid Bendahmane
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Article
| Open AccessQuantitative profiling of m6A at single base resolution across the life cycle of rice and Arabidopsis
The authors profile single-base resolution maps at each modified mRNA m6A site in rice and Arabidopsis, and uncover a suppression-activation dual regulation model in shaping m6A distribution patterns in different species.
- Guanqun Wang
- , Haoxuan Li
- & Chuan He
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Article
| Open AccessSeasonal switching of integrated leaf senescence controls in an evergreen perennial Arabidopsis
A study of perennial Arabidopsis in its natural habitat revealed a seasonal switch in leaf senescence control that optimizes resource production, storage, and translocation, making the evergreen strategy adaptively relevant in seasonal environments.
- Genki Yumoto
- , Haruki Nishio
- & Hiroshi Kudoh
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Article
| Open AccessRevealing brain cell-stratified causality through dissecting causal variants according to their cell-type-specific effects on gene expression
Here, the authors develop an approach to find cell-stratified causal associations by integrating summary-level GWAS and single-cell eQTL data. They apply the approach to BMI, prioritizing cell types as a link between BMI and diseases.
- Ruo-Han Hao
- , Tian-Pei Zhang
- & Tie-Lin Yang
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Article
| Open AccessOmecamtiv mecarbil and Mavacamten target the same myosin pocket despite opposite effects in heart contraction
Omecamtiv mecarbil and Mavacamten are small molecules directly modulating the force produced by β-cardiac myosin. In this work, the authors describe how the modulators Omecamtiv mecarbil and Mavacamten can have opposite effects on cardiac myosin force production despite occupying the same pocket.
- Daniel Auguin
- , Julien Robert-Paganin
- & Anne Houdusse
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Article
| Open AccessProtein translation rate determines neocortical neuron fate
Here the authors demonstrate how protein translation, controlled by Ire1α, regulates neuronal diversification in the developing neocortex.
- Ekaterina Borisova
- , Andrew G. Newman
- & Mateusz C. Ambrozkiewicz
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Article
| Open AccessDevelopment of an improved blood-stage malaria vaccine targeting the essential RH5-CyRPA-RIPR invasion complex
RH5, which is part of the trimeric RCR-complex essential for invasion, is a vaccine candidate for malaria. Here, Williams et al. show that monoclonal antibodies targeting each of the three proteins in the RCR-complex can work together to more effectively block the invasion of red blood cells by Plasmodium falciparum and design a combination vaccine candidate.
- Barnabas G. Williams
- , Lloyd D. W. King
- & Simon J. Draper
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Article
| Open AccessStabilization of V1 interneuron-motor neuron connectivity ameliorates motor phenotype in a mouse model of ALS
The overexpression of Esyt1 presynaptic organiser in V1 spinal interneurons restores connectivity, increases motor neuron survival, and ameliorates motor phenotypes in ALS mice. So, inhibitory interneurons are a target to attenuate ALS symptoms.
- Santiago Mora
- , Anna Stuckert
- & Ilary Allodi
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Article
| Open AccessMSGene: a multistate model using genetic risk and the electronic health record applied to lifetime risk of coronary artery disease
Coronary artery disease is the leading cause of death among adults worldwide, however current risk stratification methods lack the ability to incorporate new information throughout the life-course or to combine innate genetic risk factors with acquired lifetime risk. Here the authors introduce a multistate model to address these limitations.
- Sarah M. Urbut
- , Ming Wai Yeung
- & Pradeep Natarajan
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Article
| Open AccessMonths-long tracking of neuronal ensembles spanning multiple brain areas with Ultra-Flexible Tentacle Electrodes
Techniques to perform long-term recordings of brain activity from different areas are key to investigating many processes. Here, the authors introduce a tentacular implant with many independent fibers to track neuronal ensembles spanning multiple brain areas for months.
- Tansel Baran Yasar
- , Peter Gombkoto
- & Mehmet Fatih Yanik
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Article
| Open AccessNucleic acid mediated activation of a short prokaryotic Argonaute immune system
The SPARTA defense system, activated by invading DNA for NAD(P)+ hydrolysis, was recently identified in bacteria. Here, authors visualize SPARTA before and after nucleic acid binding and uncover the basis of its active assembly leading to abortive infection.
- Jithesh Kottur
- , Radhika Malik
- & Aneel K. Aggarwal
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Article
| Open AccessCis-regulatory evolution of the recently expanded Ly49 gene family
The Ly49 gene family mainly encodes inhibitory or activating surface receptors on natural killer cells. Here the authors show that in mice, inhibitory and activating Ly49 genes are regulated by two distinct sets of cis-regulatory elements, and that different Ly49 genes can be cross-regulated.
- Changxu Fan
- , Xiaoyun Xing
- & Ting Wang
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Article
| Open AccessInhibition and transport mechanisms of the ABC transporter hMRP5
Human multidrug resistance protein 5 (hMRP5) effluxes anticancer and antivirus drugs, driving multidrug resistance. Here, the authors present cryo-EM structures of hMRP5 in different states, showing that hMRP5 can be autoinhibited by a short peptide from its N-terminal tail, which prevents the entry of substrates into hMRP5’s transport pathway.
- Ying Huang
- , Chenyang Xue
- & Zhongmin Liu
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Article
| Open AccessKSHV infection of B cells primes protective T cell responses in humanized mice
Kaposi sarcoma associated herpesvirus (KSHV) and Epstein Barr virus often co-infect hosts and some malignancies, such as primary effusion lymphoma, are typically arising from dual-infected cells. Here authors recapitulate dual infection in a humanized mouse model, and find that under these conditions, an efficient and specific CD8+ T cell response is mounted against the lytic KSHV antigen K6.
- Nicole Caduff
- , Lisa Rieble
- & Christian Münz
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Article
| Open Accessm6a methylation orchestrates IMP1 regulation of microtubules during human neuronal differentiation
RNA-binding proteins play a pivotal role during neurodevelopment. Here, the authors show that m6A RNA methylation directs IGF2BP1/IMP1 protein to a set of mRNA targets, regulating a network of microtubule factors during neuronal differentiation.
- Pierre Klein
- , Marija Petrić Howe
- & Andres Ramos
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Article
| Open AccessPNPLA3 is a triglyceride lipase that mobilizes polyunsaturated fatty acids to facilitate hepatic secretion of large-sized very low-density lipoprotein
The PNPLA3 gene is associated with fatty liver disease. Here, the authors define a role for PNPLA3 as a polyunsaturated triglyceride lipase that maintains the balance between hepatic triglyceride storage and secretion.
- Scott M. Johnson
- , Hanmei Bao
- & Jun Liu
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Article
| Open AccessStructural basis of promoter recognition by Staphylococcus aureus RNA polymerase
Here, Yuan, Liu, and Xu et al. report cryo-EM structures of Staphylococcus aureus RNAP-promoter open complexes, highlighting distinct interactions of σA and σB with their cognate promoters.
- Linggang Yuan
- , Qingyang Liu
- & Yu Feng
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Article
| Open AccessPre-hypertrophic chondrogenic enhancer landscape of limb and axial skeleton development
Chondrocyte differentiation controls skeleton development and stature. Here, the authors map mouse fetal chondrocyte enhancers, highlighting their role in controlling bone genes and connecting stature to non-coding variants overlapping these enhancers.
- Fabrice Darbellay
- , Anna Ramisch
- & Guillaume Andrey
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Article
| Open AccessUltrasound-mediated delivery of doxorubicin to the brain results in immune modulation and improved responses to PD-1 blockade in gliomas
Ultrasound-mediated blood-brain barrier opening has been exploited to improve drug delivery in the brain. Here the authors show that low-intensity pulsed ultrasound in combination with intravenous injection of microbubbles enhances the delivery of doxorubicin and anti-PD1 in gliomas, improving anti-tumor immune responses.
- Víctor A. Arrieta
- , Andrew Gould
- & Adam M. Sonabend
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Article
| Open AccessHigh-throughput screening unveils nitazoxanide as a potent PRRSV inhibitor by targeting NMRAL1
There are limited prevention or treatment options for PRRSV. Here, the authors identified nitazoxanide as a promising inhibitor of PRRSV and demonstrate its antiviral efficacy in reducing PRRSV replication and transmission in vivo.
- Zhanding Cui
- , Jinlong Liu
- & Zengjun Lu
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Article
| Open AccessCentral transcriptional regulator controls photosynthetic growth and carbon storage in response to high light
Researchers identify unique transcriptional regulation that controls photosynthetic response, growth and biochemical carbon storage in high light for two variants of the same algae species, offering a glimpse into diel control of plant and crop yields.
- Seth Steichen
- , Arnav Deshpande
- & Lieve M. L. Laurens
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Article
| Open AccessA single-cell and spatial RNA-seq database for Alzheimer’s disease (ssREAD)
A systematic collection for single-cell and spatial transcriptomics is critical for in-depth analysis and novel discovery in AD. Here, authors show ssREAD which covers over 7 million cells and 381 spatial samples from human and mouse, providing a comprehensive resource for AD research.
- Cankun Wang
- , Diana Acosta
- & Qin Ma
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Article
| Open AccessGlobal critical soil moisture thresholds of plant water stress
Using systematic satellite observations of land surface temperature and soil moisture during soil dry-downs, the spatially-explicit global distribution of the critical soil moisture threshold of plant water stress and its drivers is uncovered.
- Zheng Fu
- , Philippe Ciais
- & William K. Smith
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Article
| Open AccessThe hippocampus dissociates present from past and future goals
It is unclear how the brain prioritizes goals. Here, the authors show that the mental timestamps assigned to goals guide their dissociation along the anterior-posterior parts of the hippocampus, extending its long axis system to include temporal goal organization.
- Alison Montagrin
- , Denise E. Croote
- & Daniela Schiller
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Article
| Open AccessGenetic determinants of host- and virus-derived insertions for hepatitis E virus replication
In this study, the authors identify genetic insertions in the population of hepatitis E virus analyzed in serum samples of a patient with ribavirin treatment failure. They show that these genomic rearrangements promote viral replication without affecting ribavirin sensitivity.
- Michael Hermann Wißing
- , Toni Luise Meister
- & Daniel Todt
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Article
| Open AccessSpectro-temporal acoustical markers differentiate speech from song across cultures
What features distinguish speech from song? Here, the authors show that consistent acoustical spectro-temporal features are sufficient to distinguish speech and song across different societies throughout the world.
- Philippe Albouy
- , Samuel A. Mehr
- & Robert J. Zatorre
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Article
| Open AccessSingle-cell transcriptomic atlas reveals increased regeneration in diseased human inner ear balance organs
Loss of inner ear hair cells leads to permanent hearing loss and balance dysfunction. Whether human utricular cells regenerate is unknown. Here, the authors present a single-cell resource of utricular cells from organ donors and schwannoma patients and describe transcriptional changes during homeostasis and in response to damage.
- Tian Wang
- , Angela H. Ling
- & Alan G. Cheng
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Article
| Open AccessDevelopment and organization of the retinal orientation selectivity map
The functional organization rules of retinal orientation are not fully understood. Here the authors show that orientation detection, a crucial task for visual perception, is organized in the mouse retina along concentric axes, and that this organization develops even in the absence of visual experience or patterned spontaneous activity.
- Dominic J. Vita
- , Fernanda S. Orsi
- & Alexandre Tiriac
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