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| Open AccessGenome-wide functional screening of miR-23b as a pleiotropic modulator suppressing cancer metastasis
microRNAs are known to be deregulated in cancer. Using a screen for microRNAs that alter cell migration, Zhanget al. show that mir-23b blocks cell migration in vitro and in vivoand is reduced in expression in human colon cancer, suggesting a therapeutic potential for this microRNA.
- Hanshuo Zhang
- , Yang Hao
- & Jianzhong Jeff Xi
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TRPA1 mediates spinal antinociception induced by acetaminophen and the cannabinoid Δ9-tetrahydrocannabiorcol
TRPA1 is a key ion channel in pain signalling. This study shows that activation of TRPA1 in the spinal cord by acetaminophen metabolites and a non-electrophilic cannabinoid produces antinociception that is lost in mice lacking TRPA1, providing an explanation for the analgesic activity of acetaminophen.
- David A Andersson
- , Clive Gentry
- & Peter M Zygmunt
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Article
| Open AccessDendritic spine formation and synaptic function require neurobeachin
Most excitatory synapses in the brain are found on dendritic spines, but the mechanisms underlying synapse formation are poorly understood. Niesmannet al. investigate the role of neurobeachin in synaptogenesis, and find that its deletion leads to fewer spinous synapses and altered postsynaptic currents.
- Katharina Niesmann
- , Dorothee Breuer
- & Markus Missler
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Article
| Open AccessThe Gibberellin perception system evolved to regulate a pre-existing GAMYB-mediated system during land plant evolution
Plant male reproduction is controlled by gibberellin signalling via the transcription factor GAMYB. Here, deletion of GAMYB in a moss species lacking a gibberellin signalling pathway gives rise to abnormal spores, suggesting that primitive plants used GAMYB for the control of sexual organ development.
- Koichiro Aya
- , Yuji Hiwatashi
- & Makoto Matsuoka
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gp96 expression in neutrophils is critical for the onset of Escherichia coli K1 (RS218) meningitis
E. coliK1 can elude the innate immune system and cause neonatal meningitis. This study shows thatE. coli K1 enters polymorphonuclear leukocytes (PMNs) using gp96 to reduce the oxidative burst, and that PMN-depleted mice are resistant to E. coliK1 infection, suggesting that PMNs permit bacterial survival in the host.
- Rahul Mittal
- & Nemani V. Prasadarao
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Metabolomic high-content nuclear magnetic resonance-based drug screening of a kinase inhibitor library
Metabolism is altered in many diseases, and monitoring metabolic changes during treatment could facilitate investigations into treatment efficacy and cellular responses. This study reports an NMR-based method to screen the metabolic responses of mammalian cells to drugs.
- Stefano Tiziani
- , Yunyi Kang
- & Giovanni Paternostro
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Genetic dissection of axon regeneration via in vivo electroporation of adult mouse sensory neurons
Dorsal root ganglion neurons can regenerate after injury, but the mechanisms underlying axon regrowth are unclear. To address this, an electroporation transfection method is developed that can alter the gene expression of dorsal root ganglion cells in a living adult mouse, providing a tool to study axon regeneration.
- Saijilafu
- , Eun-Mi Hur
- & Feng-Quan Zhou
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Identification of a link between Wnt/β-catenin signalling and the cell fusion pathway
Cell fusion is involved in many different cellular processes including the fusion of trophoblast cells in the placenta. Matsuuraet al. identify a role for the β-catenin signalling pathway in the regulation of the transcription factor GCM1 and therefore the fusion of syncytiotrophoblast cells.
- Ken Matsuura
- , Takafumi Jigami
- & Tetsu Akiyama
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P-Rex1 is required for efficient melanoblast migration and melanoma metastasis
The processes that regulate melanoblast migration during development are also thought to be involved in melanoma metastasis. Here, Prex1 null mice are shown to have a melanoblast migration defect and, when crossed to a mouse model of melanoma, are resistant to metastasis, suggesting a role for Prex1 in metastatic melanoma.
- Colin R. Lindsay
- , Samuel Lawn
- & Owen J. Sansom
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Tactile stimulation lowers stress in fish
The health benefits of massage therapy, like the reduction of stress, have so far only been shown in humans. This study uses modelling to demonstrate that, while visiting cleaner fish to have ectoparasites removed, the physical stimulation also acts to reduce stress in the coral reef fish,Ctenochaetus striatus.
- Marta C. Soares
- , Rui F. Oliveira
- & Redouan Bshary
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Article
| Open AccessA gustatory receptor involved in host plant recognition for oviposition of a swallowtail butterfly
Female Swallowtail butterflies will only lay their eggs on a small number of plants, which they choose by detecting specific chemicals on the leaf surface. Here, a gustatory receptor,PxutGr1, is identified in Papilio xuthus, which is used by the butterfly to detect synephrine when selecting a host plant.
- Katsuhisa Ozaki
- , Masasuke Ryuda
- & Hiroshi Yoshikawa
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MPP8 mediates the interactions between DNA methyltransferase Dnmt3a and H3K9 methyltransferase GLP/G9a
The methylation of DNA and histone H3 lysine 9 in chromatin are positively correlated. This study shows that the DNA methyl transferase Dnmt3a is methylated, and a crystal structure of Dnmt3a bound to the chromodomain protein MPP8 suggests a molecular mechanism.
- Yanqi Chang
- , Lidong Sun
- & Xiaodong Cheng
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Functionalized arrays of Raman-enhancing nanoparticles for capture and culture-free analysis of bacteria in human blood
Detecting bacteria in clinical samples usually requires culture processes that are time consuming and impede rapid diagnoses. Now, a surface-enhanced Raman spectroscopic method is reported that allows the label- and culture-free detection and analysis of bacteria.
- Ting-Yu Liu
- , Kun-Tong Tsai
- & Yuh-Lin Wang
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Self-assembly of DNA nanotubes with controllable diameters
DNA nanotubes could be used to transport nano-cargo and incorporated into nano-devices. In this study, rolling circle amplification is used to generate DNA subunits, and their thermodynamic growth results in the formation of nanotubes with a controlled diameter.
- Ofer I. Wilner
- , Ron Orbach
- & Itamar Willner
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Malaria parasite tyrosyl-tRNA synthetase secretion triggers pro-inflammatory responses
Parasites such as malaria elicit an immune response in their host, causing cytokine levels to increase. In this study, a parasite housekeeping gene, tyrosyl-tRNA synthetase, is shown to bind to host macrophages and, once inside the cells, enhance the levels of proinflammatory cytokines.
- Tarun Kumar Bhatt
- , Sameena Khan
- & Amit Sharma
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miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells
The microRNA miR-137 is enriched in the brain of mice and induces the differentiation of adult neural stem cells. Now, Sun and colleagues report that miR-137 negatively regulates proliferation of neurons in embryonic mice and that TLX and LSD1 cooperate to negatively regulate miR-137 expression, blocking premature differentiation.
- GuoQiang Sun
- , Peng Ye
- & Yanhong Shi
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Article
| Open AccessExtrasynaptic vesicle recycling in mature hippocampal neurons
In the classical model, fast neuronal signalling occurs at specialized presynaptic terminals. Now, Ratnayakaet al. show that stimulus-driven fusion and recycling of synaptic vesicles can occur at axonal sites remote from conventional synapses. These findings have implications for dynamic forms of neuron–neuron communication.
- Arjuna Ratnayaka
- , Vincenzo Marra
- & Kevin Staras
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Modulation of rod photoreceptor output by HCN1 channels is essential for regular mesopic cone vision
At light levels where both rods and cones are active, their signals converge into shared downstream retinal circuitry. Using HCN1 deficient mice, this study shows that the signals from cone photoreceptors are overwhelmed when rod output is not regulated, suggesting a mechanism for how these systems interact.
- Mathias W. Seeliger
- , Arne Brombas
- & Frank Müller
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Epithelial organisation revealed by a network of cellular contacts
Differences in the arrangement of cells is a fundamental precursor to the establishment of different organs. In this study, network theory is applied at the level of individual cells to map patterns in cell-to-cell contacts, creating a new approach to objectively characterise epithelia.
- Luis M. Escudero
- , Luciano da F. Costa
- & M. Madan Babu
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Review Article |
Integrating the biophysical and molecular mechanisms of auditory hair cell mechanotransduction
Hair cells of the inner ear transduce vibrations of the basilar membrane into electrical signals by a process known as mechanotransduction. Recent advances in genetic and molecular tools have led to an improved understanding of mechanotransduction as Peng and colleagues summarize in this Review.
- Anthony W. Peng
- , Felipe T. Salles
- & Anthony J. Ricci
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Super-resolution surface mapping using the trajectories of molecular probes
Surface characterization of soft materialsin situis challenging due to the importance of non-covalent interactions. Now, a new chemical imaging method is reported that generates images of surface interactions by combining many molecular probe trajectories.
- Robert Walder
- , Nathaniel Nelson
- & Daniel K. Schwartz
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CD91-dependent programming of T-helper cell responses following heat shock protein immunization
Heat shock proteins bind to CD91 on antigen presenting cells, resulting in the presentation of chaperoned peptides to T cells. Here, heat shock protein binding is shown to induce phosphorylation of CD91 and stimulate the production of cytokines, thus priming various T-helper cell responses.
- Sudesh Pawaria
- & Robert J. Binder
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Experimental drying intensifies burning and carbon losses in a northern peatland
Peatlands are a sink for atmospheric carbon dioxide and make up a large soil carbon reservoir. Here, studies of the interaction between drainage and fire show that long-term carbon emissions will likely exceed rates of carbon uptake, reducing the northern peatland carbon sink.
- M.R. Turetsky
- , W.F. Donahue
- & B.W. Benscoter
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Disrupted erythropoietin signalling promotes obesity and alters hypothalamus proopiomelanocortin production
Erythropoietin circulates in the blood and is essential for erythropoiesis but its role in metabolic homeostasis has not been examined. Tenget al. show that when the erythropoietin receptor is only expressed in erthyroid cells, mice develop obesity and insulin resistance, suggesting that the receptor has a key role in fat mass accumulation.
- Ruifeng Teng
- , Oksana Gavrilova
- & Constance Tom Noguchi
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Large-scale DNA editing of retrotransposons accelerates mammalian genome evolution
APOBEC3 is a DNA editing enzyme that is important for antiviral responses. In this study, Carmi and colleagues show that APOBEC3 editing of retrotransposon sequences in mammalian genomes is widespread, with implications for the evolution of retrotransposons.
- Shai Carmi
- , George M. Church
- & Erez Y. Levanon
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Article
| Open AccessThe NMR structure of stomagen reveals the basis of stomatal density regulation by plant peptide hormones
Stomagen is a positive regulator of stomatal development in plants, whereas epidermal patterning factors 1 and 2 are negative regulators. Ohkiet al. present the NMR structure of stomagen and show that the stomagen loop domain is sufficient to positively regulate stomatal development.
- Shinya Ohki
- , Makoto Takeuchi
- & Masashi Mori
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Synapse microarray identification of small molecules that enhance synaptogenesis
Large scale synapse assays can facilitate identification of drug leads. Shiet al. develop a 'synapse microarray' technology that enables sensitive, high-throughput, quantitative screening of synaptogenic events, and use it to identify novel histone deacetylase inhibitors that enhance synaptogenesis.
- Peng Shi
- , Mark A. Scott
- & Mehmet Fatih Yanik
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Article
| Open AccessSelective inhibition of microRNA accessibility by RBM38 is required for p53 activity
MicroRNAs bind to the 3′-untranslated region of genes to regulate expression. In this study, an RNA-binding protein, RMB38, is shown to selectively regulate the access of some microRNAs to their targets, and control the expression of some p53 target genes.
- Nicolas Léveillé
- , Ran Elkon
- & Reuven Agami
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Article
| Open AccessProliferating versus differentiating stem and cancer cells exhibit distinct midbody-release behaviour
During cell division, a cytoplasmic bridge—the midbody—forms between the nascent daughter cells, but it has been unclear under which conditions this is retained by a daughter cell or released. Now, Ettinger and colleagues show that midbody-release occurs more frequently in stem cells compared with cancer cells.
- Andreas W. Ettinger
- , Michaela Wilsch-Bräuninger
- & Wieland B. Huttner
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Behavioural memory reconsolidation of food and fear memories
Memory retrieval followed by extinction training has been shown to erase fear memories. Flavellet al. show that this approach also erases appetitive memories in rats and results from a modification of memory reconsolidation, which could be useful for the treatment of drug addiction.
- Charlotte R. Flavell
- , David J. Barber
- & Jonathan L.C. Lee
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Article
| Open AccessEngineering modular and orthogonal genetic logic gates for robust digital-like synthetic biology
Biological digital sensors require the fabrication of modular genetic logic gates. Using thePseudomonas syringae hrpsystem, Wang and colleagues generate AND, NOT and NAND gates, demonstrating the ability to engineer a modular system from biological elements.
- Baojun Wang
- , Richard I Kitney
- & Martin Buck
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NMDA receptor activation requires remodelling of intersubunit contacts within ligand-binding heterodimers
In non-NMDA glutamate receptors, intersubunit contacts within agonist binding domains affect functional desensitization. Now, NMDA receptor activation, but not desensitization, is shown to involve rearrangements at the heterodimer interface, suggesting that the intersubunit contacts of NMDA and non-NMDA receptors may have distinct functional roles.
- William F. Borschel
- , Swetha E. Murthy
- & Gabriela K. Popescu
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The ubiquitin ligase HACE1 regulates Golgi membrane dynamics during the cell cycle
The Golgi membrane is fragmented during mitosis and is subsequently fused following cell division and this process is known to be controlled by ubiquitination. In this study, the ubiquitin ligase HACE1 is shown to be targeted to the Golgi membrane and is required for fusion after the completion of mitosis.
- Danming Tang
- , Yi Xiang
- & Yanzhuang Wang
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Electrosensory ampullary organs are derived from lateral line placodes in bony fishes
Ampullary organs are involved in electroreception, but whether these are derived from placodes, thickened ectoderm, is unclear. In this study, the ampullary organs of the primitive ray-finned fish,Polyodon spathula, are shown to develop from lateral line placodes, suggesting that this is the ancestral state in bony fishes.
- Melinda S. Modrell
- , William E. Bemis
- & Clare V.H. Baker
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Article
| Open AccessTravelling and splitting of a wave of hedgehog expression involved in spider-head segmentation
During development, waves of gene expression are required for segmentation of the body axis. In this study, repeated splitting of a wave of hedgehog gene expression is shown during segmentation of the spiderAchaearanea tepidariorum.
- Masaki Kanayama
- , Yasuko Akiyama-Oda
- & Hiroki Oda
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A mitochondria-targeted inhibitor of cytochrome c peroxidase mitigates radiation-induced death
Radiomitigating compounds could be used to protect against ionizing radiation. In this study, mitochondria-targeted oleic and stearic acid derivatives are shown to inhibit pro-apoptotic oxidative events, prevent cell death, and protect mice against lethal doses of radiation.
- Jeffrey Atkinson
- , Alexandr A. Kapralov
- & Valerian E. Kagan
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Single-molecule fluorescence spectroscopy maps the folding landscape of a large protein
The folding of multidomain proteins can involve metastable intermediate states. Here, a single-molecule FRET based method is developed and used to identify six metastable states in the folding landscape of the three-domain protein adenylate kinase.
- Menahem Pirchi
- , Guy Ziv
- & Gilad Haran
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Pericytes resident in postnatal skeletal muscle differentiate into muscle fibres and generate satellite cells
The fusion of satellite cells to muscle fibres during adult life is required for both muscle growth and regeneration but it is unknown whether non-muscle cells contribute to this process. Now, Dellavalle and colleagues show that pericytes, cells associated with the vasculature can contribute to both growth and regeneration of muscle fibres.
- A. Dellavalle
- , G. Maroli
- & G. Cossu
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Phosphatidylinositol(4,5)bisphosphate coordinates actin-mediated mobilization and translocation of secretory vesicles to the plasma membrane of chromaffin cells
The role of phosphatidylinositol(4,5)bisphosphate in exocytosis is unclear. This study shows that inhibition of the p110δ isoform of PI3-kinase promotes a transient increase in phosphatidylinositol(4,5)bisphosphate, leading to a potentiation of exocytosis in chromaffin cells.
- Peter J. Wen
- , Shona L. Osborne
- & Frédéric A. Meunier
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Reprogramming within hours following nuclear transfer into mouse but not human zygotes
The generation of human cell lines using somatic cell nuclear transfer has been difficult to achieve. In this study, Egliet al. show that while mouse eggs reprogram somatic cells within hours, human eggs arrest after nuclear transfer which may be due to a lack of genome transcription.
- Dieter Egli
- , Alice E. Chen
- & Kevin Eggan
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Article
| Open AccessDesigning attractive models via automated identification of chaotic and oscillatory dynamical regimes
Modelling of chaos and oscillations is usually done indirectly and quantitatively by fitting models to a finite number of data-points. Here, a qualitative framework is developed where the characteristics of the underlying dynamical system are directly specified, revealing new properties of such systems.
- Daniel Silk
- , Paul D.W. Kirk
- & Michael P.H. Stumpf
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Review Article |
Capturing the essence of folding and functions of biomolecules using coarse-grained models
Coarse-grained models can be used to study the folding of biological macromolecules such as DNA, RNA and proteins. In this Review, Hyeon and Thirumalai describe recent advances in the use of these theoretical models to describe dynamic processes in biology.
- Changbong Hyeon
- & D. Thirumalai
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Article
| Open AccessA shift of the TOR adaptor from Rictor towards Raptor by semaphorin in C. elegans
What controls the binding partner selection of the target of rapamycin protein, TOR, is unknown. Using theCaenorhabditis elegans tail as a model, Nukazuka et al. determine that signals of semaphorin through plexin control the binding partner selection of TOR and are required for the correct organization of rays in the tail.
- Akira Nukazuka
- , Shusaku Tamaki
- & Shin Takagi
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Article
| Open AccessIdentification and microbial production of a terpene-based advanced biofuel
Advanced biofuels with comparable properties to petroleum-based fuels could be microbially produced from lignocellulosic biomass. In this study,Escherichia coliis engineered to produce bisabolene, the immediate precursor of bisabolane, a biosynthetic alternative to D2 diesel.
- Pamela P. Peralta-Yahya
- , Mario Ouellet
- & Taek Soon Lee
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Article
| Open AccessThe collagen-binding protein of Streptococcus mutans is involved in haemorrhagic stroke
The risk factors associated with both ischemic and haemorrhagic stroke are not fully understood. Here a certain strain of the bacteria,Streptococcus mutans, which expresses a collagen-binding protein, is shown to be associated with haemorrhagic stroke in both animal models and human patients.
- Kazuhiko Nakano
- , Kazuya Hokamura
- & Takashi Ooshima
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A chloroplast envelope-bound PHD transcription factor mediates chloroplast signals to the nucleus
Retrograde chloroplast signals are essential in coordinating nuclear gene expression, but the mechanism that relays chloroplast signals to the nucleus remains elusive. In this study, a chloroplast envelope-bound transcription factor PTM is shown to transmit chloroplast signals to the nucleus.
- Xuwu Sun
- , Peiqiang Feng
- & Lixin Zhang
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Article
| Open AccessAn energy transduction mechanism used in bacterial flagellar type III protein export
A bacterial export gate complex transports flagellar proteins across the cytoplasmic membrane, but the mechanism of this process is unclear. Here, the export gate complex is revealed as a proton–protein antiporter that uses separate components of the proton motive force for different steps of the export process.
- Tohru Minamino
- , Yusuke V. Morimoto
- & Keiichi Namba
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Late Cretaceous origin of the rice tribe provides evidence for early diversification in Poaceae
In this study, fossils from the Late Cretaceous period in India are described and are assigned to the rice tribe based on phylogenetic comparison of morphological traits with modern grasses; these findings suggest that the evolutionary origins of the grass family, Poaceae, occurred earlier than previously thought.
- V. Prasad
- , C.A.E. Strömberg
- & A. Sahni
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Article
| Open AccessGenome-wide association mapping reveals a rich genetic architecture of complex traits in Oryza sativa
Understanding the genetics and physiology of domesticated species is important for crop improvement. By studying natural variation and the phenotypic traits of 413 diverse accessions of rice, Zhao et al. identify many common genetic variants that influence quantitative traits such as seed size and flowering time.
- Keyan Zhao
- , Chih-Wei Tung
- & Susan R. McCouch
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