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| Open AccessStructural and molecular insights into the mechanism of action of human angiogenin-ALS variants in neurons
Mutations in human angiogenin are implicated in the progression of amyotrophic lateral sclerosis. Thiyagarajan and colleagues show that structural differences between angiogenin variants affect neuronal survival, and the ability to induce stress granules in neuronal cell lines.
- Nethaji Thiyagarajan
- , Ross Ferguson
- & K. Ravi Acharya
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Atmospheric phosphorus deposition may cause lakes to revert from phosphorus limitation back to nitrogen limitation
Increased atmospheric input of nitrogen has shifted planktonic lake nutrient systems from natural nitrogen to human-induced phosphorus limitation. This study proposes that decades of increased atmospheric phosphorus in the Pyrenean lake district may have reverted the system from phosphorus back to nitrogen-limited.
- L. Camarero
- & J. Catalan
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Orphan receptor IL-17RD tunes IL-17A signalling and is required for neutrophilia
One of the five IL-17 receptors, IL-17RD lacks a motif thought to be required for downstream signalling. Melletet al. show that IL-17RD tunes IL-17A-dependent signalling; in its absence, MAPK signalling and neutrophil recruitment are impaired, but NF-κB activation is enhanced.
- Mark Mellett
- , Paola Atzei
- & Paul N. Moynagh
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Insight into the early evolution of the avian sternum from juvenile enantiornithines
The keeled sternum is a distinct skeletal element in extant birds. In this study, specimens of juvenile extinct birds—Enantiornithes—from the Early Cretaceous show a unique sequence of development in the sternum, suggesting differences between living birds and this extinct clade.
- Xiaoting Zheng
- , Xiaoli Wang
- & Zhonghe Zhou
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Mst1 regulates integrin-dependent thymocyte trafficking and antigen recognition in the thymus
Autoreactive T cells are eliminated as they encounter self-antigens during transit through the thymus. Uedaet al. reveal that mice lacking the Hippo homologue Mst1 develop autoimmunity as a result of impaired integrin-dependent T cell migration through this negatively selective niche.
- Yoshihiro Ueda
- , Koko Katagiri
- & Tatsuo Kinashi
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Article
| Open AccessStructure of a bacterial voltage-gated sodium channel pore reveals mechanisms of opening and closing
Sodium-gated ion channels open and close in response to the flow of ions. Here, McCusker et al.report the open structure of a sodium-gated ion channel pore from a bacterial homologue, and show, by comparison with the closed structure, that the movement of a C-terminal helix is sufficient to open the channel.
- Emily C. McCusker
- , Claire Bagnéris
- & B.A. Wallace
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Cobweb-weaving spiders produce different attachment discs for locomotion and prey capture
Spider webs consist of scaffolding silk, which supports the cobweb, and gumfoot silk, which can detach easily from the web upon contact with prey. Here, these different mechanical demands are shown to be met by silk attachments of two distinct architectures using the same pyriform silk secretions.
- Vasav Sahni
- , Jared Harris
- & Ali Dhinojwala
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Monosynaptic inputs to new neurons in the dentate gyrus
Adult neurogenesis in the mammalian brain is implicated in the storage and processing of memories. Vivaret al.label afferents to new dentate gyrus granule cells and find that they receive direct input from the perirhinal and lateral entorhinal cortex and that these inputs enable spatial pattern separation.
- Carmen Vivar
- , Michelle C. Potter
- & Henriette van Praag
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Cadherin selectivity filter regulates endothelial sieving properties
Endothelial cells provide a vital barrier system to the passage of water and ions but not large plasma proteins. Using fluorescently labelled dextrans, the authors show that regions of high or low adherens junction density differentially restrict the passage of molecules up to 70 kDa in size.
- Sadiqa K. Quadri
- , Li Sun
- & Jahar Bhattacharya
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Sound-induced length changes in outer hair cell stereocilia
In the inner ear, sound waves produce movements in hair cell sterocilia, triggering the opening of ion channels. Hakizimana and colleagues show that the resultant currents change the length of sterocilia, and that these length changes alter the efficiency by which sound is converted into electrical signals.
- Pierre Hakizimana
- , William E. Brownell
- & Anders Fridberger
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Robust photoregulation of GABAA receptors by allosteric modulation with a propofol analogue
The design of chemical photoswitches could potentially lead to the development of novel therapeutics that regulates neurotransmission. In this study, a light-sensitive modified derivative of propofol is shown to activate GABAA receptors in Xenopusoocytes, rat ganglion cells and mouse cerebellar slices.
- Lan Yue
- , Michal Pawlowski
- & David R. Pepperberg
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Food web expansion and contraction in response to changing environmental conditions
The analysis of food web properties under different environmental conditions informs us how the ecosystem functions. Here, Tunneyet al. use post-glacial lakes as model ecosystems to show how macroscopic patterns of food webs vary with changes in habitat and resource accessibility.
- Tyler D. Tunney
- , Kevin S. McCann
- & Brian J. Shuter
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Protein encapsulation within synthetic molecular hosts
Protein encapsulation in molecular cages has the potential to alter protein function and aid crystallization. Here, ubiquitin is encapsulated within a giant coordination cage; the protein is attached to a bidentate ligand, and the cage self-assembles upon addition of capping ligands and Pd(II) ions.
- Daishi Fujita
- , Kosuke Suzuki
- & Makoto Fujita
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Article
| Open AccessA kinase inhibitor screen identifies small-molecule enhancers of reprogramming and iPS cell generation
The efficiency of reprogramming somatic cells to induced pluripotent stem cells is low. To enhance reprogramming efficiency, Li and Rana used a chemical screen and identified several kinase inhibitors that enhance reprogramming, and show that blocking Aurora A, p38 and inositiol triphosphate 3-kinase signalling is important for this process.
- Zhonghan Li
- & Tariq M. Rana
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Article
| Open AccessEscherichia coli noncoding RNAs can affect gene expression and physiology of Caenorhabditis elegans
It is known that differences in the bacterial food ofCaenorhabditis elegans can alter their behaviour. In this study, bacteria expressing two different noncoding RNAs alter the chemosensory and longevity of C. elegans, suggesting a role in modulating C. elegansphysiology.
- Huijie Liu
- , Xueren Wang
- & Ge Shan
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Article
| Open AccessThe miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy
Heart failure is often a consequence of pathological growth of cardiomyocytes or cardiac hypertrophy. Here Ucar and colleagues report that the microRNAs miR-132 and miR-212 promote cardiac hypertrophy and inhibit autophagy in cardiomyocytes by downregulating the transcription factor FoxO3.
- Ahmet Ucar
- , Shashi K. Gupta
- & Thomas Thum
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Article
| Open AccessThyroid hormone determines the start of the sensitive period of imprinting and primes later learning
Filial imprinting allows precocial birds to form social attachment to other animals or objects soon after hatching. Yamaguchi and colleagues investigate the mechanisms responsible for this, and find that thyroid hormones circulating in the plasma regulate the sensitive period during which imprinting occurs.
- Shinji Yamaguchi
- , Naoya Aoki
- & Koichi J. Homma
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Genetic architecture supports mosaic brain evolution and independent brain–body size regulation
It has been controversial whether the sizes of different regions of the brain can evolve independently of each other. This study identifies genetic loci responsible for independent size regulation in different brain regions, and finds brain size to be regulated independently of body size.
- Reinmar Hager
- , Lu Lu
- & Robert W. Williams
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Article
| Open AccessDirect visualization of cell division using high-resolution imaging of M-phase of the cell cycle
Current methods for detecting proliferation in live cells cannot distinguish between dividing cells and cells that are progressing through the cell cycle. Here, a method is described that detects anillin in the contractile ring and in the midbody of cells during M-phase, providing a more accurate detection of dividing cells.
- Michael Hesse
- , Alexandra Raulf
- & Bernd K. Fleischmann
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Article
| Open AccessUncoupling of the endocannabinoid signalling complex in a mouse model of fragile X syndrome
Fragile X syndrome is a major genetic cause of autism and is caused by loss of the fragile X mental retardation protein. In a mouse model of fragile X syndrome, Junget al. show that an absence of neuronal endocannabinoid signalling is responsible for the neurophysiological and behavioural defects.
- Kwang-Mook Jung
- , Marja Sepers
- & Olivier J. Manzoni
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The nuclear hormone receptor PPARγ counteracts vascular calcification by inhibiting Wnt5a signalling in vascular smooth muscle cells
Vascular calcification is commonly associated with advanced stages of atherosclerosis. Woldtet al. show that the nuclear hormone receptor PPARγ in vascular smooth muscle cells protects mice from vascular calcification by inhibiting Wnt5a signalling triggered by activation of the cell-surface receptor LRP1.
- Estelle Woldt
- , Jérome Terrand
- & Philippe Boucher
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Insights into the biomedical effects of carboxylated single-wall carbon nanotubes on telomerase and telomeres
Single-walled carbon nanotubes can selectively stabilize telomeric i-motif DNA and have been suggested as a treatment for cancer. Here, carbon nanotubes are found to inhibit telomerase activity by stabilizing i-motif DNA, leading to telomere uncapping and altered telomere function in cancer cells.
- Yong Chen
- , Konggang Qu
- & Xiaogang Qu
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Delivery of endosomes to lysosomes via microautophagy in the visceral endoderm of mouse embryos
Nutrients and growth factors initiate endocytotic processes in the embryonic endoderm that control embryonic patterning. Here, Kawamuraet al.show that the small GTP-binding protein rab7 controls a unique microautophagy-like process that is involved in endocytosis in the endoderm of mouse embryos.
- Nobuyuki Kawamura
- , Ge-Hong Sun-Wada
- & Yoh Wada
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Article
| Open AccessEndogenous Wnt signalling in human embryonic stem cells generates an equilibrium of distinct lineage-specified progenitors
Human embryonic stem cell cultures are morphologically heterogeneous. Here, differences in Wnt signalling are shown to contribute to this heterogeneity, cells containing high levels of Wnt form endodermal and cardiac cells, whereas cells with low Wnt form neuroectodermal cells, when differentiation is induced.
- Timothy A. Blauwkamp
- , Shelly Nigam
- & Roel Nusse
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Production of α-L-iduronidase in maize for the potential treatment of a human lysosomal storage disease
The lysosomal storage disease mucopolysaccharidosis I is treated with recombinant α-L-iduronidase but production of the enzyme is expensive. In this study, α-L-iduronidase is compartmentalized within the endosperm of maize via a unique mRNA strategy yielding the active, correctly glycosylated protein.
- Xu He
- , Thomas Haselhorst
- & Allison R. Kermode
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Article
| Open AccessEnhanced HSP70 lysine methylation promotes proliferation of cancer cells through activation of Aurora kinase B
HSP70 is a molecular chaperone that aids protein folding. In this study, HSP70 is shown to be methylated and this post-translationally modified protein is elevated in expression in human cancers and promotes the activity of Aurora kinase B.
- Hyun-Soo Cho
- , Tadahiro Shimazu
- & Ryuji Hamamoto
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Dynamic evolution of venom proteins in squamate reptiles
The evolution of venom toxins is an area of intense study but has been hampered by the lack of non-toxin protein homologues. Here, phylogenetic analyses of non-toxin genes sourced from transcriptomic studies are found placed within groups of venom toxins, revealing dynamic changes in the sites of toxin expression.
- Nicholas R. Casewell
- , Gavin A. Huttley
- & Wolfgang Wüster
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p47 negatively regulates IKK activation by inducing the lysosomal degradation of polyubiquitinated NEMO
The IKK complex activates the NF-κB pathway and can culminate in inflammation, which needs to be tightly controlled. NEMO is part of the IKK complex and, in this study, is shown to associate with the golgi-reassembly protein p47, resulting in the lysosomal degradation of NEMO and inhibition of NF-κB activation.
- Yuri Shibata
- , Masaaki Oyama
- & Jun-ichiro Inoue
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Article
| Open AccessEvidence of an inhibitory restraint of seizure activity in humans
Seizure activity in the brain is characterized by the recruitment of cortical neuronal activity. Schevon and colleagues study seizure activity in human subjects and find that the recruitment of neurons is hypersynchronous and that there is an intrinsic restraint on the propagation of this activity.
- Catherine A. Schevon
- , Shennan A. Weiss
- & Andrew J. Trevelyan
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TGFβ induces the formation of tumour-initiating cells in claudinlow breast cancer
TGF-β signalling suppresses tumorigenesis in breast cancer cells but its effects on breast cancer initiating cells have not been reported. Using cells in culture, Brunaet al. show that TGF-β increases breast cancer initiating cell numbers in cells that have low levels of the tight junction protein claudin.
- Alejandra Bruna
- , Wendy Greenwood
- & Carlos Caldas
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Attention gates visual coding in the human pulvinar
The pulvinar nucleus is involved in modulating visual information. Fischer and Whitney use brain imaging to study the pulvinar during visual attention, and find that the positions and orientations of attended objects are precisely encoded in the pulvinar, while information about ignored objects is gated out.
- Jason Fischer
- & David Whitney
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Real-time in vivo imaging of the beating mouse heart at microscopic resolution
Microscopic imaging techniques have a high spatio-temporal resolution but, in living animals, are hampered by cardiac and respiratory motion. This paper describes a microscopic setup that allows fluorescent confocal imaging of the beating mouse heart over a period of several hours.
- Sungon Lee
- , Claudio Vinegoni
- & Ralph Weissleder
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Article
| Open AccessHigh-fat or ethinyl-oestradiol intake during pregnancy increases mammary cancer risk in several generations of offspring
Environmental factors can influence one's susceptibility to cancer, but it is not clear whether such an influence extends beyond the directly exposed generations. Here, feeding pregnant rats with a high-fat diet or a hormone derivative, the authors observe increased breast cancer risk in up to three subsequent generations.
- Sonia de Assis
- , Anni Warri
- & Leena Hilakivi-Clarke
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Article
| Open AccessGreatwall kinase and cyclin B-Cdk1 are both critical constituents of M-phase-promoting factor
Cyclin B–Cdk1 is thought to be synonymous with the promoting factor that drives entry into M-phase of the cell cycle. Here, Greatwall kinase is shown to be required for the breakdown of the nuclear envelope and the assembly of the spindle on entry into M-phase, suggesting that it too is a part of the M-phase-promoting factor.
- Masatoshi Hara
- , Yusuke Abe
- & Takeo Kishimoto
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Discovery of acetylene hydratase activity of the iron–sulphur protein IspH
The iron–sulphur enzyme IspH catalyses the final step of the methylerythritol phosphate isoprenoid biosynthesis pathway. Spanet al. report that IspH can hydrate acetylenes to aldehydes and ketones, in addition to its role as a 2H+/2e−reductase.
- Ingrid Span
- , Ke Wang
- & Michael Groll
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The amniote paratympanic organ develops from a previously undiscovered sensory placode
The paratympanic organ in the avian middle ear is similar to the fish spiracular organ, but its developmental origin is unresolved. O'Neillet al. use fate mapping techniques to show that the avian paratympanic organ and its afferent neurons arise from a previously undiscovered neurogenic placode.
- Paul O'Neill
- , Siu-Shan Mak
- & Clare V.H. Baker
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The use of the sex pheromone as an evolutionary solution to food source selection in caterpillars
Sex pheromones are used by adult members of a species to attract a mate. This study proposes that the larvae of the cotton leafwormSpodoptera littoralisare attracted to sex pheromones and prefer a food source containing it, suggesting an alternative use of the sex pheromone to trigger food search in caterpillars.
- Erwan Poivet
- , Kacem Rharrabe
- & Emmanuelle Jacquin-Joly
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Lysine methylation of VCP by a member of a novel human protein methyltransferase family
Methyltransferases modify cellular proteins in addition to DNA and histones. These authors identify a new family of lysine-specific methyltransferases and show that a member of this family, which is associated with tumour metastasis, methylates the ATP-dependent protein chaperone VCP/p97.
- Stefan Kernstock
- , Erna Davydova
- & Pål Ø. Falnes
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Article
| Open AccessThe allosteric vestibule of a seven transmembrane helical receptor controls G-protein coupling
Class A seven transmembrane helical receptors harbour vestibules at the entrance to the ligand-binding domain. Here, Bocket al. use probes to monitor the conformation of the M2 muscarinic receptor and show that the vestibule alters the extent of receptor movement.
- Andreas Bock
- , Nicole Merten
- & Klaus Mohr
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Article
| Open AccessEfficacy of the β2-adrenergic receptor is determined by conformational equilibrium in the transmembrane region
Many drugs exist that target the β-adrenergic receptor, but they have different efficacies. Kofukuet al. use NMR to show that methionine 82 in the transmembrane domain undergoes conformational changes depending on whether agonists or inverse agonists are bound, explaining the differential drug efficacy.
- Yutaka Kofuku
- , Takumi Ueda
- & Ichio Shimada
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Article
| Open AccessExtracellular ATP mediates mast cell-dependent intestinal inflammation through P2X7 purinoceptors
Mast cells are mediators of type I allergic disease and inflammation. Here, Kurashimaet al. show that mast cells are increased in the colons of mice with colitis, and that activation of the cells and subsequent inflammation can be blocked by inhibition of the purinoceptor, P2X7.
- Yosuke Kurashima
- , Takeaki Amiya
- & Hiroshi Kiyono
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Evidence for methane production by saprotrophic fungi
Methane is an important anthropogenic greenhouse gas and is thought to be produced by industrial processes and prokaryotic methanogenic Archaea. In this study, the saprotrophic fungi,Basidiomycetes, is shown to produce methane in the absence of methanogenic Archaea.
- Katharina Lenhart
- , Michael Bunge
- & Frank Keppler
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Imaging enzyme-triggered self-assembly of small molecules inside live cells
Supramolecular interactions allow some small molecules to self-assemble into nanofibres and hydrogels in aqueous environments. Gaoet al.report a hydrogelator that forms fluorescent nanofibres within cells, leading to the visualization of their self-assembly at the endoplasmic reticulum.
- Yuan Gao
- , Junfeng Shi
- & Bing Xu
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Identification of the functional binding pocket for compounds targeting small-conductance Ca2+-activated potassium channels
Small- and intermediate-conductance K+channels are activated by calcium-bound calmodulin and modulated by small molecules. In this study, a functional binding pocket for the 1-EBIO class of modulators is described and is located at the calmodulin-channel interface.
- Miao Zhang
- , John M. Pascal
- & Ji-Fang Zhang
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Biocompatibility of a genetically encoded calcium indicator in a transgenic mouse model
Calcium-sensing fluorescent proteins such as TN-XXL are valuable tools for studying cellular function but, when expressed in mice, may affect animal physiology and behaviour. The authors of this paper create transgenic mice expressing TN-XXL and show that long-term expression of TN-XXL is tolerated well.
- Stephan Direnberger
- , Marsilius Mues
- & Oliver Griesbeck
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Rotational dynamics of cargos at pauses during axonal transport
Vesicle trafficking in the cell is likely to involve a tug-of-war between motor proteins of opposing directionality. Guet al. use high-speed single-particle tracking in neurons to uncover rotation of paused cargo vesicles, providing insight into the changing forces as the vesicles change direction.
- Yan Gu
- , Wei Sun
- & Ning Fang
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Article
| Open AccessControlled rotation of the F1-ATPase reveals differential and continuous binding changes for ATP synthesis
Reverse rotation of the F1-ATPase results in the synthesis, rather than hydrolysis of ATP. Adachiet al. show that the molecular mechanism of ATP synthesis is the reverse of hydrolysis-driven rotation of the motor, and that ADP and ATP are discriminated by angle-dependent binding.
- Kengo Adachi
- , Kazuhiro Oiwa
- & Kazuhiko Kinosita Jr
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Article
| Open AccessActive learning framework with iterative clustering for bioimage classification
Semi-automated imaging systems help with the task of classifying large numbers of biological images. This study presents a novel framework—CARTA—with an active learning algorithm combined with a genetic algorithm, whose applications include the classification of magnetic resonance imaging of cancer cells.
- Natsumaro Kutsuna
- , Takumi Higaki
- & Seiichiro Hasezawa
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Structured neuronal encoding and decoding of human speech features
Speech is encoded by the firing patterns of speech-controlling neurons in different regions of the brain, which Tankus and colleagues analyse in this study. They find highly specific encoding of vowels in medial–frontal neurons and nonspecific tuning in superior temporal gyrus neurons.
- Ariel Tankus
- , Itzhak Fried
- & Shy Shoham
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