Fungal pathogen uses sex pheromone receptor for chemotropic sensing of host plant signals
Nature 527, 7579 (2015). doi:10.1038/nature15516
Authors: David Turrà, Mennat El Ghalid, Federico Rossi & Antonio Di Pietro
For more than a century, fungal pathogens and symbionts have been known to orient hyphal growth towards chemical stimuli from the host plant. However, the nature of the plant signals as well as the mechanisms underlying the chemotropic response have remained elusive. Here we show that directed growth of the soil-inhabiting plant pathogen Fusarium oxysporum towards the roots of the host tomato (Solanum lycopersicum) is triggered by the catalytic activity of secreted class III peroxidases, a family of haem-containing enzymes present in all land plants. The chemotropic response requires conserved elements of the fungal cell integrity mitogen-activated protein kinase (MAPK) cascade and the seven-pass transmembrane protein Ste2, a functional homologue of the Saccharomyces cerevisiae sex pheromone α receptor. We further show that directed hyphal growth of F. oxysporum towards nutrient sources such as sugars and amino acids is governed by a functionally distinct MAPK cascade. These results reveal a potentially conserved chemotropic mechanism in root-colonizing fungi, and suggest a new function for the fungal pheromone-sensing machinery in locating plant hosts in a complex environment such as the soil.
In situ structures of the segmented genome and RNA polymerase complex inside a dsRNA virus
Nature 527, 7579 (2015). doi:10.1038/nature15767
Authors: Xing Zhang, Ke Ding, Xuekui Yu, Winston Chang, Jingchen Sun & Z. Hong Zhou
Viruses in the Reoviridae, like the triple-shelled human rotavirus and the single-shelled insect cytoplasmic polyhedrosis virus (CPV), all package a genome of segmented double-stranded RNAs (dsRNAs) inside the viral capsid and carry out endogenous messenger RNA synthesis through a transcriptional enzyme complex (TEC). By direct electron-counting cryoelectron microscopy and asymmetric reconstruction, we have determined the organization of the dsRNA genome inside quiescent CPV (q-CPV) and the in situ atomic structures of TEC within CPV in both quiescent and transcribing (t-CPV) states. We show that the ten segmented dsRNAs in CPV are organized with ten TECs in a specific, non-symmetric manner, with each dsRNA segment attached directly to a TEC. The TEC consists of two extensively interacting subunits: an RNA-dependent RNA polymerase (RdRP) and an NTPase VP4. We find that the bracelet domain of RdRP undergoes marked conformational change when q-CPV is converted to t-CPV, leading to formation of the RNA template entry channel and access to the polymerase active site. An amino-terminal helix from each of two subunits of the capsid shell protein (CSP) interacts with VP4 and RdRP. These findings establish the link between sensing of environmental cues by the external proteins and activation of endogenous RNA transcription by the TEC inside the virus.
Backlash after Frontiers journals added to list of questionable publishers
Nature 526, 7575 (2015). doi:10.1038/526613f
Author: Mollie Bloudoff-Indelicato
Open-access publisher is the latest addition to controversial ‘Beall’s List’.
Malaria vaccine cautiously recommended for use in Africa
Nature 526, 7575 (2015). http://www.nature.com/doifinder/10.1038/nature.2015.18638
Authors: Ewen Callaway & Amy Maxmen
World Health Organization advisory committee endorses use of the RTS,S vaccine in small-scale demonstrations.
US astronomers stuck in grant-rejection cycle
Nature 526, 7575 (2015). http://www.nature.com/doifinder/10.1038/nature.2015.18631
Author: Chris Cesare
The plummeting success rates in grant applications in the last decade are linked to flat budgets and more resubmitted proposals.
Incoming space junk a scientific opportunity
Nature 526, 7575 (2015). http://www.nature.com/doifinder/10.1038/nature.2015.18642
Author: Traci Watson
Astronomers prepare to observe an impact off the coast of Sri Lanka.
Foreign DNA capture during CRISPR–Cas adaptive immunity
Nature 527, 7579 (2015). doi:10.1038/nature15760
Authors: James K. Nuñez, Lucas B. Harrington, Philip J. Kranzusch, Alan N. Engelman & Jennifer A. Doudna
Bacteria and archaea generate adaptive immunity against phages and plasmids by integrating foreign DNA of specific 30–40-base-pair lengths into clustered regularly interspaced short palindromic repeat (CRISPR) loci as spacer segments. The universally conserved Cas1–Cas2 integrase complex catalyses spacer acquisition using a direct nucleophilic integration mechanism similar to retroviral integrases and transposases. How the Cas1–Cas2 complex selects foreign DNA substrates for integration remains unknown. Here we present X-ray crystal structures of the Escherichia coli Cas1–Cas2 complex bound to cognate 33-nucleotide protospacer DNA substrates. The protein complex creates a curved binding surface spanning the length of the DNA and splays the ends of the protospacer to allow each terminal nucleophilic 3′-OH to enter a channel leading into the Cas1 active sites. Phosphodiester backbone interactions between the protospacer and the proteins explain the sequence-nonspecific substrate selection observed in vivo. Our results uncover the structural basis for foreign DNA capture and the mechanism by which Cas1–Cas2 functions as a molecular ruler to dictate the sequence architecture of CRISPR loci.
Quantum physics: Death by experiment for local realism
Nature 526, 7575 (2015). doi:10.1038/nature15631
Authors: Howard Wiseman
A fundamental scientific assumption called local realism conflicts with certain predictions of quantum mechanics. Those predictions have now been verified, with none of the loopholes that have compromised earlier tests. See Letter p.682
Loophole-free Bell inequality violation using electron spins separated by 1.3 kilometres
Nature 526, 7575 (2015). doi:10.1038/nature15759
Authors: B. Hensen, H. Bernien, A. E. Dréau, A. Reiserer, N. Kalb, M. S. Blok, J. Ruitenberg, R. F. L. Vermeulen, R. N. Schouten, C. Abellán, W. Amaya, V. Pruneri, M. W. Mitchell, M. Markham, D. J. Twitchen, D. Elkouss, S. Wehner, T. H. Taminiau & R. Hanson
More than 50 years ago, John Bell proved that no theory of nature that obeys locality and realism can reproduce all the predictions of quantum theory: in any local-realist theory, the correlations between outcomes of measurements on distant particles satisfy an inequality that can be violated if the particles are entangled. Numerous Bell inequality tests have been reported; however, all experiments reported so far required additional assumptions to obtain a contradiction with local realism, resulting in ‘loopholes’. Here we report a Bell experiment that is free of any such additional assumption and thus directly tests the principles underlying Bell’s inequality. We use an event-ready scheme that enables the generation of robust entanglement between distant electron spins (estimated state fidelity of 0.92 ± 0.03). Efficient spin read-out avoids the fair-sampling assumption (detection loophole), while the use of fast random-basis selection and spin read-out combined with a spatial separation of 1.3 kilometres ensure the required locality conditions. We performed 245 trials that tested the CHSH–Bell inequalityS ≤ 2 and found S = 2.42 ± 0.20 (where S quantifies the correlation between measurement outcomes). A null-hypothesis test yields a probability of at most P = 0.039 that a local-realist model for space-like separated sites could produce data with a violation at least as large as we observe, even when allowing for memory in the devices. Our data hence imply statistically significant rejection of the local-realist null hypothesis. This conclusion may be further consolidated in future experiments; for instance, reaching a value of P = 0.001 would require approximately 700 trials for an observed S = 2.4. With improvements, our experiment could be used for testing less-conventional theories, and for implementing device-independent quantum-secure communication and randomness certification.
Thalamic control of sensory selection in divided attention
Nature 526, 7575 (2015). doi:10.1038/nature15398
Authors: Ralf D. Wimmer, L. Ian Schmitt, Thomas J. Davidson, Miho Nakajima, Karl Deisseroth & Michael M. Halassa
How the brain selects appropriate sensory inputs and suppresses distractors is unknown. Given the well-established role of the prefrontal cortex (PFC) in executive function, its interactions with sensory cortical areas during attention have been hypothesized to control sensory selection. To test this idea and, more generally, dissect the circuits underlying sensory selection, we developed a cross-modal divided-attention task in mice that allowed genetic access to this cognitive process. By optogenetically perturbing PFC function in a temporally precise window, the ability of mice to select appropriately between conflicting visual and auditory stimuli was diminished. Equivalent sensory thalamocortical manipulations showed that behaviour was causally dependent on PFC interactions with the sensory thalamus, not sensory cortex. Consistent with this notion, we found neurons of the visual thalamic reticular nucleus (visTRN) to exhibit PFC-dependent changes in firing rate predictive of the modality selected. visTRN activity was causal to performance as confirmed by bidirectional optogenetic manipulations of this subnetwork. Using a combination of electrophysiology and intracellular chloride photometry, we demonstrated that visTRN dynamically controls visual thalamic gain through feedforward inhibition. Our experiments introduce a new subcortical model of sensory selection, in which the PFC biases thalamic reticular subnetworks to control thalamic sensory gain, selecting appropriate inputs for further processing.
CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase
Nature 526, 7575 (2015). doi:10.1038/nature15510
Authors: Weiwei He, Ge Bai, Huihao Zhou, Na Wei, Nicholas M. White, Janelle Lauer, Huaqing Liu, Yi Shi, Calin Dan Dumitru, Karen Lettieri, Veronica Shubayev, Albena Jordanova, Velina Guergueltcheva, Patrick R. Griffin, Robert W. Burgess, Samuel L. Pfaff & Xiang-Lei Yang
Selective neuronal loss is a hallmark of neurodegenerative diseases, which, counterintuitively, are often caused by mutations in widely expressed genes. Charcot–Marie–Tooth (CMT) diseases are the most common hereditary peripheral neuropathies, for which there are no effective therapies. A subtype of these diseases—CMT type 2D (CMT2D)—is caused by dominant mutations in GARS, encoding the ubiquitously expressed enzyme glycyl-transfer RNA (tRNA) synthetase (GlyRS). Despite the broad requirement of GlyRS for protein biosynthesis in all cells, mutations in this gene cause a selective degeneration of peripheral axons, leading to deficits in distal motor function. How mutations in GlyRS (GlyRSCMT2D) are linked to motor neuron vulnerability has remained elusive. Here we report that GlyRSCMT2D acquires a neomorphic binding activity that directly antagonizes an essential signalling pathway for motor neuron survival. We find that CMT2D mutations alter the conformation of GlyRS, enabling GlyRSCMT2D to bind the neuropilin 1 (Nrp1) receptor. This aberrant interaction competitively interferes with the binding of the cognate ligand vascular endothelial growth factor (VEGF) to Nrp1. Genetic reduction of Nrp1 in mice worsens CMT2D symptoms, whereas enhanced expression of VEGF improves motor function. These findings link the selective pathology of CMT2D to the neomorphic binding activity of GlyRSCMT2D that antagonizes the VEGF–Nrp1 interaction, and indicate that the VEGF–Nrp1 signalling axis is an actionable target for treating CMT2D.
Yap-dependent reprogramming of Lgr5+ stem cells drives intestinal regeneration and cancer
Nature 526, 7575 (2015). doi:10.1038/nature15382
Authors: Alex Gregorieff, Yu Liu, Mohammad R. Inanlou, Yuliya Khomchuk & Jeffrey L. Wrana
The gut epithelium has remarkable self-renewal capacity that under homeostatic conditions is driven by Wnt signalling in Lgr5+ intestinal stem cells (ISCs). However, the mechanisms underlying ISC regeneration after injury remain poorly understood. The Hippo signalling pathway mediates tissue growth and is important for regeneration. Here we demonstrate in mice that Yap, a downstream transcriptional effector of Hippo, is critical for recovery of intestinal epithelium after exposure to ionizing radiation. Yap transiently reprograms Lgr5+ ISCs by suppressing Wnt signalling and excessive Paneth cell differentiation, while promoting cell survival and inducing a regenerative program that includes Egf pathway activation. Accordingly, growth of Yap-deficient organoids is rescued by the Egfr ligand epiregulin, and we find that non-cell-autonomous production of stromal epiregulin may compensate for Yap loss in vivo. Consistent with key roles for regenerative signalling in tumorigenesis, we further demonstrate that Yap inactivation abolishes adenomas in the ApcMin mouse model of colon cancer, and that Yap-driven expansion of Apc−/− organoids requires the Egfr module of the Yap regenerative program. Finally, we show that in vivo Yap is required for progression of early Apc mutant tumour-initiating cells, suppresses their differentiation into Paneth cells, and induces a regenerative program and Egfr signalling. Our studies reveal that upon tissue injury, Yap reprograms Lgr5+ ISCs by inhibiting the Wnt homeostatic program, while inducing a regenerative program that includes activation of Egfr signalling. Moreover, our findings reveal a key role for the Yap regenerative pathway in driving cancer initiation.
Nature 526, 7574 (2015). doi:10.1038/526475b
Scientists, meeting organizers and the media must take care with preliminary findings.
Pick and mix
Nature 526, 7574 (2015). doi:10.1038/526756a
Food regulators are right to place new forms of data on the safety menu.
Planetary science: Pluto hosts wildly varying terrain
Nature 526, 7574 (2015). doi:10.1038/526478a
The first published findings from NASA's New Horizons mission to Pluto confirm that the dwarf planet has geological features that resemble those found on Mars and various moons in the Solar System.NASA's spacecraft flew past Pluto in July, sending back reams of data that
Nanomaterials: Droplets surf graphene waves
Nature 526, 7574 (2015). doi:10.1038/526478b
Tiny particles of liquid move quickly across thin layers of carbon by 'surfing' waves that ripple through the sheets.Angelos Michaelides at University College London and his colleagues used computer simulations to investigate how liquids move across graphene — a layer of carbon one atom
Prosthetics: Bionic touch lights up neurons
Nature 526, 7574 (2015). doi:10.1038/526478c
A thin, flexible device can sense a wide range of pressures and produces signals that stimulate nerve cells in a dish.Zhenan Bao of Stanford University in California and her collaborators embedded carbon nanotubes in a rubbery polymer and attached that material to a flexible
Ecology: Caffeine keeps bees coming back
Nature 526, 7574 (2015). doi:10.1038/526478d
Caffeine-infused nectar tricks honeybees into changing their foraging behaviour in ways that may benefit the plant.Many plants produce the bitter-tasting caffeine to deter herbivores, but also rely on bees to spread their pollen for reproduction. To look at caffeine's effect on pollinators, Margaret Couvillon
Animal behaviour: Electric eels use shocks to sense
Nature 526, 7574 (2015). doi:10.1038/526479a
Electric eels send out strong zaps to track moving prey by their electrical conductivity, enabling the eels to strike with remarkable precision.Electric eels (Electrophorus electricus; pictured) are known to use electricity to stun their prey, and have electrical sensors (pictured in
Agroecology: Wild flowers are a pesticide source
Nature 526, 7574 (2015). doi:10.1038/526479b
Commonly used insecticides have been found on wild flowers as well as on crops.Neonicotinoid pesticides applied to the seeds of some crops end up in the nectar and pollen of adult plants, so the chemicals are a suspected cause of the global decline in