Featured
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Parkin controls dopamine utilization in human midbrain dopaminergic neurons derived from induced pluripotent stem cells
Mutations in parkin, an ubiquitin ligase, cause an inherited form of Parkinson's disease. Here, Jianget al. generate induced pluripotent stem cells from two patients with parkin mutations and find that neurons derived from the stem cells have defects in dopamine release, dopamine uptake and oxidative metabolism.
- Houbo Jiang
- , Yong Ren
- & Jian Feng
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Article
| Open AccessImperfect interface of Beclin1 coiled-coil domain regulates homodimer and heterodimer formation with Atg14L and UVRAG
Beclin1 is a key regulator of VPS34-related processes, including autophagy. Liet al. solve the crystal structure of Beclin 1 CC domain, an antiparallel dimer that is rendered metastable by a series of a-d' pairings, which determines its ability to form distinct heterodimers either with Atg14L or UVRAG.
- Xiaohua Li
- , Liqiang He
- & Yanxiang Zhao
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EphB3 suppresses non-small-cell lung cancer metastasis via a PP2A/RACK1/Akt signalling complex
The role of ephrin receptors in tumour development and progression has remained controversial. Liet al. show that kinase activation of ephrin-B3 inhibits non-small-cell lung cancer migration both in vitro and in vivo, which depends on a novel interacting partner, RACK 1, in a ternary complex with PP2A and Akt.
- Guo Li
- , Xiao-Dan Ji
- & Dong Xie
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Rapid microbial response to the presence of an ancient relic in the Antarctic Dry Valleys
It is thought that turnover in soil microbiota occurs very slowly in the Antarctic Dry Valleys due to the extreme cold and aridity. Now, Tiaoet al. show that a transformation of microbial communities can happen in a matter of years in soils altered by the presence of a mummified seal.
- Grace Tiao
- , Charles K. Lee
- & S. Craig Cary
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Article
| Open AccessLoss of flight promotes beetle diversification
The loss of flight in some insect lineages may promote allopatric differentiation and result in a high speciation rate. Here, using the carrion beetle, loss of flight is shown to accelerate allopatric speciation with higher genetic differentiation than for flight-capable species.
- Hiroshi Ikeda
- , Masaaki Nishikawa
- & Teiji Sota
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Article
| Open AccessActivation of TRPC6 channels is essential for lung ischaemia–reperfusion induced oedema in mice
The signalling cascade involved in lung ischaemia–reperfusion-induced oedema is poorly understood. Using knockout mice, Weissmannet al. propose a model in which reactive oxygen species production by endothelial NOX2 leads to phospholipase C-γ activation, DAG kinase inhibition and subsequent TRPC6 activation.
- Norbert Weissmann
- , Akylbek Sydykov
- & Alexander Dietrich
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Article
| Open AccessThree-dimensional analysis of ribonucleoprotein complexes in influenza A virus
The influenza A virus genome consists of eight RNA segments, which permits genetic reassortment and contributes to the emergence of novel strains with pandemic potential. Here, electron tomography is used to study the three-dimensional structure of ribonucleoprotein complexes within progeny virions.
- Takeshi Noda
- , Yukihiko Sugita
- & Yoshihiro Kawaoka
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New evidence on the colour and nature of the isolated Archaeopteryx feather
Archaeopteryxcombined features of reptiles and birds, but the colour of its feathers has remained unclear. In this study, based on data from fossilized colour-imparting melanosomes, an isolated feather specimen fromArchaeopteryxis predicted to be black, providing clues to its plumage colour and function.
- Ryan M. Carney
- , Jakob Vinther
- & Jörg Ackermann
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The genetic origin and history of speed in the Thoroughbred racehorse
A genetic variation in the horsemyostatingene is found at a very high frequency in the best Thoroughbred sprinters. This study shows, using molecular and pedigree data from modern and historic horses, that a single introduction of the variant occurred at the foundation stages of the Thoroughbred from a British native mare.
- Mim A. Bower
- , Beatrice A. McGivney
- & Emmeline W. Hill
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Article
| Open AccessELL facilitates RNA polymerase II pause site entry and release
The super elongation complex, which is involved in transcriptional elongation, contains the Eleven-nineteen Lysine-rich Leukemia protein (ELL). In this study, ELL is shown to stabilize RNA polymerase II prior to recruitment into the super elongation complex, suggesting ELL has a role in early transcription elongation.
- Jung S. Byun
- , Temesgen D. Fufa
- & Kevin Gardner
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Article
| Open AccessABL1 regulates spindle orientation in adherent cells and mammalian skin
A systematic approach for identifying the genes responsible for the regulation of spindle orientation in mammals has been lacking. Now, Matsumuraet al. perform a kinase-targeting RNAi screen and identify ABL1, which through the direct phosphorylation of NuMa, is a novel regulator of spindle orientation.
- Shigeru Matsumura
- , Mayumi Hamasaki
- & Fumiko Toyoshima
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c-Src and IL-6 inhibit osteoblast differentiation and integrate IGFBP5 signalling
Osteoblast maturation is regulated by c-Src and IL-6, but how these signalling pathways are integrated is not known. Here c-Src is shown to induce 1GFBP5 in immature osteoblasts in a STAT3 and IL-6-dependent manner, in mature osteoblasts, which express lower levels of c-Src, this signalling is lost.
- Barbara Peruzzi
- , Alfredo Cappariello
- & Anna Teti
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Article
| Open AccessRapid and adaptive evolution of MHC genes under parasite selection in experimental vertebrate populations
In vertebrates parasite-mediated selection is thought to maintain polymorphism in MHC genes where specific resistance MHC alleles increase under emerging selection. Here, experimental evidence is shown from six stickleback fish populations that varying parasite selection helps maintain MHC polymorphism.
- Christophe Eizaguirre
- , Tobias L. Lenz
- & Manfred Milinski
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Two rotating cilia in the node cavity are sufficient to break left–right symmetry in the mouse embryo
The left–right asymmetry of an organism is patterned during development and is determined by fluid flow created by the movement of cilia. In this study, the asymmetry is shown to be determined early after the movement of cilia is established and that only two rotating cilia are required for breaking symmetry.
- Kyosuke Shinohara
- , Aiko Kawasumi
- & Hiroshi Hamada
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Structural rearrangements underlying ligand-gating in Kir channels
Inward rectifier potassium channels are regulated by a range of ligands that act on a common gate, but the structural details of gating are unclear. Here, the molecular motions associated with gating of KirBac1.1 channels are assessed using small molecule fluorescent probes attached to introduced cysteines.
- Shizhen Wang
- , Sun-Joo Lee
- & Colin G. Nichols
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Programmable multivalent display of receptor ligands using peptide nucleic acid nanoscaffolds
Multivalent display of integrin antagonists enhances their efficacy, but current synthetic scaffolds used to display ligands are limited in range and precision. Englundet al. develop a new scaffold to study the multivalent effects of integrin antagonists across wide ranges of ligand number, density, and 3D arrangement.
- Ethan A. Englund
- , Deyun Wang
- & Daniel H. Appella
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Mouse and human strategies identify PTPN14 as a modifier of angiogenesis and hereditary haemorrhagic telangiectasia
Hereditary haemorrhagic telangiectasia (HTT) is caused by mutations in TGFβ/bone morphogenetic protein signalling genes. Here, Benzinouet al. show that variants of PTPN14, a gene within a mouse Tgfb1 modifier locus, associate with pulmonary arteriovenous malformation in HTT patients, shedding light on the molecular aetiology of this disease.
- Michael Benzinou
- , Frederic F. Clermont
- & Rosemary J. Akhurst
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Biomedical photoacoustics beyond thermal expansion using triggered nanodroplet vaporization for contrast-enhanced imaging
A dual-contrast agent has been developed for combined ultrasound and photoacoustic imaging. This agent uses vaporization for ultrasound contrast enhancement and photoacoustic signal generation, providing significantly higher signals than thermal expansion, the most commonly used photoacoustic mechanism.
- Katheryne Wilson
- , Kimberly Homan
- & Stanislav Emelianov
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| Open AccessAdvantage of rare infanticide strategies in an invasion experiment of behavioural polymorphism
The origin and maintenance of non-parental infanticide is a puzzling phenomenon in wild animal populations. This study of infanticide in a population of bank voles confirms negative frequency-dependent selection in nature and shows potential benefits of this apparently harmful behaviour.
- Tapio Mappes
- , Jouni Aspi
- & Juha Tuomi
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Article
| Open AccessStructure-based mutagenesis reveals the albumin-binding site of the neonatal Fc receptor
Albumin transport proteins circulate in the blood and are protected from degradation by interaction with the neonatal Fc receptor. Andersenet al. investigate the albumin binding site of the neonatal Fc receptor and find pH sensitive ionic networks at the binding interface.
- Jan Terje Andersen
- , Bjørn Dalhus
- & Inger Sandlie
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Article
| Open AccessExistence of long-lasting experience-dependent plasticity in endocrine cell networks
Experience-dependent plasticity and functional adaptation are thought to be restricted to the central nervous and immune systems. This study shows that long-lasting experience-dependent plasticity is a key feature of endocrine cell networks, allowing improved tissue function and hormone output following repeat demand.
- David J. Hodson
- , Marie Schaeffer
- & Patrice Mollard
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Article
| Open AccessMuscle-derived stem/progenitor cell dysfunction limits healthspan and lifespan in a murine progeria model
The function of adult stem cells is diminished with age but the role this dysfunction plays in the aging process is unknown. Here, the injection of muscle-derived stem/progenitor cells from young mice rescues symptoms in progeroid mice and is shown to regenerate tissues independent of engraftment.
- Mitra Lavasani
- , Andria R. Robinson
- & Johnny Huard
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Article
| Open AccessSynthetic quorum-sensing circuit to control consortial biofilm formation and dispersal in a microfluidic device
Engineered biofilms have applications in biorefineries. Here, Honget al. engineer bacteria to produce a combination of dispersal proteins and quorum sensing factors, and show that one dispersing bacterium can eliminate a biofilm formed by a colonizing bacterium.
- Seok Hoon Hong
- , Manjunath Hegde
- & Thomas K. Wood
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Inhibition of specific gene expressions by protein-mediated mRNA interference
RNA can be silenced in a sequence-specific manner but whether proteins can silence RNA in this way is unknown. Now, Yamaguchi and colleagues show that an enzyme isolated fromHaloquadra walsbyi cleaves 7-base-pair sequences in Escherichia coli, and this high sequence specificity permits the silencing of targeted genes.
- Yoshihiro Yamaguchi
- , Hirofumi Nariya
- & Masayori Inouye
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Article
| Open AccessBRCA1 is an essential regulator of heart function and survival following myocardial infarction
The tumour suppressor BRCA1 is mutated in familial breast and ovarian cancer. Now, Shuklaet al.demonstrate that mice lacking BRCA1 in cardiomyocytes are more sensitive to ischaemia than control mice, and that BRCA1 is elevated in human tissues exposed to ischaemia, suggesting a cardioprotective role for BRCA1.
- Praphulla C. Shukla
- , Krishna K. Singh
- & Subodh Verma
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Rapid adaptation to food availability by a dopamine-mediated morphogenetic response
Food availability elicits behavioural and developmental responses. Adamset al. show that, in sea urchin larvae, food availability mediates developmental plasticity by regulating changes in arm length through dopamine signalling, a pathway widely used to mediate food-induced behavioural responses.
- Diane K. Adams
- , Mary A. Sewell
- & Lynne M. Angerer
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Article
| Open AccessPKA regulatory subunits mediate synergy among conserved G-protein-coupled receptor cascades
G-protein-coupled receptors sense extracellular cues and transmit the signal to distinct trimeric G-proteins. Stefanet al.show that in response to cAMP, a central and conserved component of the Gαs-coupled receptor cascade, the RII subunit of PKA, specifically binds to and participates in Gαi signaling.
- Eduard Stefan
- , Mohan K. Malleshaiah
- & Stephen W. Michnick
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Article
| Open AccessCompetition for FcRn-mediated transport gives rise to short half-life of human IgG3 and offers therapeutic potential
The half-life of IgG is regulated by binding to the neonatal Fc receptor and, in the case of IgG3, is reduced compared to other IgG proteins. In this study, a mutation in IgG3 is shown to reduce binding to the neonatal Fc receptor, which can be competitively blocked by IgG1.
- Nigel M. Stapleton
- , Jan Terje Andersen
- & Gestur Vidarsson
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River-margin habitat of Ardipithecus ramidus at Aramis, Ethiopia 4.4 million years ago
The habitat where early humans, hominins, lived provides information about the early part of human evolution. In this study, sedimentological and stable carbon and oxygen isotope data suggest homininArdipithecus ramiduslived in a river-margin forest in a wooded grassland landscape at Aramis, Ethiopia.
- M. Royhan Gani
- & Nahid D. Gani
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A role for T-bet-mediated tumour immune surveillance in anti-IL-17A treatment of lung cancer
The tumour microenvironment is often found to be immunosuppressive. Reppert and colleagues show that human and murine lung tumours harbour IL-17A-producing T cells, and that blocking IL-17A increases survival in mice, suggesting that anti-IL-17A therapy may be useful in treating lung cancer.
- S. Reppert
- , I. Boross
- & S. Finotto
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Article
| Open AccessPromotion of plasma membrane repair by vitamin E
Membrane repair of myocytes is important to prevent such disease as muscular dystrophy but the properties of this repair are not well characterised. In this study, vitamin E is shown to be important in the repair of myocyte cell membranes in cultured cells and in intact muscle.
- Amber C. Howard
- , Anna K. McNeil
- & Paul L. McNeil
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O-Linked-N-acetylglucosamine on extracellular protein domains mediates epithelial cell–matrix interactions
The modification of proteins with O-linked-N-acetylglucosamine causes regulation of multiple cellular processes. In this study, Sakaidani and colleagues identify an endoplasmic reticulum O-linked-N-acetylglucosamine transferase in Drosophilathat regulates the adhesion of epithelial cells to the extracellular matrix.
- Yuta Sakaidani
- , Tomoko Nomura
- & Tetsuya Okajima
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Competitive and cooperative metabolic interactions in bacterial communities
Genome-scale metabolic models for bacterial species allow a systematic study of inter-species interactions. Here, competitive and cooperative potential is predicted between 6,903 pairs of species, to explore the role of these interactions in shaping coexistence patterns in natural communities.
- Shiri Freilich
- , Raphy Zarecki
- & Eytan Ruppin
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Evolution of the base of the brain in highly encephalized human species
Encephalization—increase of brain size relative to body size—has occurred in two distinct evolutionary lineages; Neanderthals and modern humans. However, the 3D endocranial surface shape analysis reported here reveals unique structures at the base of the brain inHomo sapiens, which may have contributed to learning and social capacities.
- Markus Bastir
- , Antonio Rosas
- & Jean-Jacques Hublin
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Binding of herpes simplex virus glycoprotein D to nectin-1 exploits host cell adhesion
Herpesvirus glycoprotein D binds to nectin 1 and the herpes virus entry mediator protein on the surface of host cells. In this study, Zhanget al. report the crystal structure of glycoprotein D in complex with the immunoglobulin-like domains of nectin 1, which suggests that binding of glycoprotein D to nectin 1 prevents nectin 1 dimerization.
- Na Zhang
- , Jinghua Yan
- & George F Gao
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Article
| Open AccessThe evolution of sensory divergence in the context of limited gene flow in the bumblebee bat
Populations of the same species living in different habitats can differ in sensory traits driving speciation, but it is not known if this variation limits gene flow. Here, a genetic and acoustic study of the bumblebee bat suggests that geographic distance, instead of echolocation divergence, limits gene flow.
- Sébastien J. Puechmaille
- , Meriadeg Ar Gouilh
- & Emma C. Teeling
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Low-concentration mechanical biosensor based on a photonic crystal nanowire array
Nanomechanical resonators are attractive as ultra-low concentration sensors of biomolecules, as their small scale allows for sensitive mass detection. Here, using a nanowire array as part of a photonic crystal, such a device is presented for light trapping, absorption and low-concentration sensing.
- Yuerui Lu
- , Songming Peng
- & Amit Lal
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Article
| Open AccessReinforcement learning in professional basketball players
Reinforcement learning quantifies the change in behaviour in response to past experience. Using field goal attempt data from basketball, Neiman and Loewenstein demonstrate that even one failed or made attempt has an impact on subsequent attempts, showing that players overgeneralize from their most recent actions.
- Tal Neiman
- & Yonatan Loewenstein
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Article
| Open AccessActivin enhances skin tumourigenesis and malignant progression by inducing a pro-tumourigenic immune cell response
Activin is known to have a role in wound healing, but its role in skin cancer is unknown. Antsiferovaet al. show that activin is elevated in human skin tumours, and by modulating epidermal immune cells, exacerbates tumour progression in a mouse model of skin cancer.
- Maria Antsiferova
- , Marcel Huber
- & Sabine Werner
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Article |
The use of referential gestures in ravens (Corvus corax) in the wild
Human children use referential gestures such as showing, offering and pointing, which are thought to form the foundation of language skills. Here, evidence is provided of ravens (Corvus corax) using showing and offering to direct other's attention, as an example of referential gesturing in a non-primate lineage.
- Simone Pika
- & Thomas Bugnyar
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Article
| Open AccessGlobal kinomic and phospho-proteomic analyses of the human malaria parasite Plasmodium falciparum
New approaches are required to combatPlasmodium falciparuminfection. In this proteome-wide study, 1305 phosphorylation sites are identified and 36 kinases are shown to have crucial roles in parasite survival, providing new insights into parasite biology and potential new drug targets for anti-malarial chemotherapy.
- Lev Solyakov
- , Jean Halbert
- & Christian Doerig
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Article
| Open AccessExperimental loss-tolerant quantum coin flipping
When two spatially separated parties flip a coin, it is impossible to choose between two alternatives in an unbiased manner. This study presents a quantum coin-flipping protocol that overcomes this problem and ensures a dishonest party cannot bias the outcome completely.
- Guido Berlín
- , Gilles Brassard
- & Wolfgang Tittel
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Specific inhibition of bacterial RNase T2 by helix 41 of 16S ribosomal RNA
The 30S ribosomal subunit ofEscherichia coliinhibits the RNA-degrading enzyme Ribonuclease T2. Using mutational studies and hybrid ribosomes, Kitahara and Miyazaki show that helix 41 of the 30S ribosomal subunit blocks the enzyme activity, suggesting that helix 41 is required for preventing RNase T2 toxicity.
- Kei Kitahara
- & Kentaro Miyazaki
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Article
| 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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Article |
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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