Showing papers in "Scientific Reports in 2017"

Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness

Abstract: Signaling through the Ror2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion. Here, we identify intraflagellar transport 20 (IFT20) as a new target of this signaling in tumors that lack primary cilia, and find that IFT20 mediates the ability of Ror2 signaling to induce the invasiveness of these tumors. We also find that IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex, which promotes Golgi ribbon formation in achieving polarized secretion for cell migration and invasion. Furthermore, IFT20 promotes the efficiency of transport through the Golgi complex. These findings shed new insights into how Ror2 signaling promotes tumor invasiveness, and also advance the understanding of how Golgi structure and transport can be regulated.

SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules

Abstract: To be effective as a drug, a potent molecule must reach its target in the body in sufficient concentration, and stay there in a bioactive form long enough for the expected biologic events to occur. Drug development involves assessment of absorption, distribution, metabolism and excretion (ADME) increasingly earlier in the discovery process, at a stage when considered compounds are numerous but access to the physical samples is limited. In that context, computer models constitute valid alternatives to experiments. Here, we present the new SwissADME web tool that gives free access to a pool of fast yet robust predictive models for physicochemical properties, pharmacokinetics, drug-likeness and medicinal chemistry friendliness, among which in-house proficient methods such as the BOILED-Egg, iLOGP and Bioavailability Radar. Easy efficient input and interpretation are ensured thanks to a user-friendly interface through the login-free website http://www.swissadme.ch. Specialists, but also nonexpert in cheminformatics or computational chemistry can predict rapidly key parameters for a collection of molecules to support their drug discovery endeavours.

QuPath: Open source software for digital pathology image analysis

Abstract: QuPath is new bioimage analysis software designed to meet the growing need for a user-friendly, extensible, open-source solution for digital pathology and whole slide image analysis. In addition to offering a comprehensive panel of tumor identification and high-throughput biomarker evaluation tools, QuPath provides researchers with powerful batch-processing and scripting functionality, and an extensible platform with which to develop and share new algorithms to analyze complex tissue images. Furthermore, QuPath’s flexible design makes it suitable for a wide range of additional image analysis applications across biomedical research.

Limb proportions show developmental plasticity in response to embryo movement.

Abstract: Animals have evolved limb proportions adapted to different environments, but it is not yet clear to what extent these proportions are directly influenced by the environment during prenatal development. The developing skeleton experiences mechanical loading resulting from embryo movement. We tested the hypothesis that environmentally-induced changes in prenatal movement influence embryonic limb growth to alter proportions. We show that incubation temperature influences motility and limb bone growth in West African Dwarf crocodiles, producing altered limb proportions which may, influence post-hatching performance. Pharmacological immobilisation of embryonic chickens revealed that altered motility, independent of temperature, may underpin this growth regulation. Use of the chick also allowed us to merge histological, immunochemical and cell proliferation labelling studies to evaluate changes in growth plate organisation, and unbiased array profiling to identify specific cellular and transcriptional targets of embryo movement. This disclosed that movement alters limb proportions and regulates chondrocyte proliferation in only specific growth plates. This selective targeting is related to intrinsic mTOR (mechanistic target of rapamycin) pathway activity in individual growth plates. Our findings provide new insights into how environmental factors can be integrated to influence cellular activity in growing bones and ultimately gross limb morphology, to generate phenotypic variation during prenatal development.

Gut microbiome alterations in Alzheimer's disease.

Abstract: Alzheimer’s disease (AD) is the most common form of dementia. However, the etiopathogenesis of this devastating disease is not fully understood. Recent studies in rodents suggest that alterations in the gut microbiome may contribute to amyloid deposition, yet the microbial communities associated with AD have not been characterized in humans. Towards this end, we characterized the bacterial taxonomic composition of fecal samples from participants with and without a diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals. We identified phylum- through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD participants. Furthermore, we observed correlations between levels of differentially abundant genera and cerebrospinal fluid (CSF) biomarkers of AD. These findings add AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.

Topological-insulator-based terahertz modulator

Abstract: Three dimensional topological insulators, as a new phase of quantum matters, are characterized by an insulating gap in the bulk and a metallic state on the surface. Particularly, most of the topological insulators have narrow band gaps, and hence have promising applications in the area of terahertz optoelectronics. In this work, we experimentally demonstrate an electronically-tunable terahertz intensity modulator based on Bi1:5Sb0:5Te1:8Se1:2 single crystal, one of the most insulating topological insulators. A relative frequency-independent modulation depth of ~62% over a wide frequency range from 0.3 to 1.4 THz has been achieved at room temperature, by applying a bias current of 100 mA. The modulation in the low current regime can be further enhanced at low temperature. We propose that the extraordinarily large modulation is a consequence of thermally-activated carrier absorption in the semiconducting bulk states. Our work provides a new application of topological insulators for terahertz technology.

Photonic crystal nanocavity assisted rejection ratio tunable notch microwave photonic filter

Abstract: Driven by the increasing demand on handing microwave signals with compact device, low power consumption, high efficiency and high reliability, it is highly desired to generate, distribute, and process microwave signals using photonic integrated circuits. Silicon photonics offers a promising platform facilitating ultracompact microwave photonic signal processing assisted by silicon nanophotonic devices. In this paper, we propose, theoretically analyze and experimentally demonstrate a simple scheme to realize ultracompact rejection ratio tunable notch microwave photonic filter (MPF) based on a silicon photonic crystal (PhC) nanocavity with fixed extinction ratio. Using a conventional modulation scheme with only a single phase modulator (PM), the rejection ratio of the presented MPF can be tuned from about 10 dB to beyond 60 dB. Moreover, the central frequency tunable operation in the high rejection ratio region is also demonstrated in the experiment.

Correction: Corrigendum: A dual specificity kinase, DYRK1A, as a potential therapeutic target for head and neck squamous cell carcinoma

Abstract: Scientific Reports 6: Article number: 36132; published online: 31 October 2016; updated: 26 June 2017. This Article contains errors. The Acknowledgements section is incomplete. “We thank the Department of Biotechnology (DBT), Government of India for research support to the Institute of Bioinformatics (IOB), Bangalore.

Structural and transport properties of ammonia along the principal Hugoniot.

Abstract: We investigate, via quantum molecular dynamics simulations, the structural and transport properties of ammonia along the principal Hugoniot for temperatures up to 10 eV and densities up to 2.6 g/cm3. With the analysis of the molecular dynamics trajectories by use of the bond auto-correlation function, we identify three distinct pressure-temperature regions for local chemical structures of ammonia. We derive the diffusivity and viscosity of strong correlated ammonia with high accuracy through fitting the velocity and stress-tensor autocorrelation functions with complex functional form which includes structures and multiple time scales. The statistical error of the transport properties is estimated. It is shown that the diffusivity and viscosity behave in a distinctly different manner at these three regimes and thus present complex features. In the molecular fluid regime, the hydrogen atoms have almost the similar diffusivity as nitrogen and the viscosity is dominated by the kinetic contribution. When entering into the mixture regime, the transport behavior of the system remarkably changes due to the stronger ionic coupling, and the viscosity is determined to decrease gradually and achieve minimum at about 2.0 g/cm3 on the Hugoniot. In the plasma regime, the hydrogen atoms diffuse at least twice as fast as the nitrogen atoms.

Tissue accumulation of microplastics in mice and biomarker responses suggest widespread health risks of exposure.

Abstract: Microplastics (MPs) are a significant environmental health issue and increasingly greater source of concern. MPs have been detected in oceans, rivers, sediments, sewages, soil and even table salts. MPs exposure on marine organisms and humans has been documented, but information about the toxicity of MPs in mammal is limited. Here we used fluorescent and pristine polystyrene microplastics (PS-MPs) particles with two diameters (5 μm and 20 μm) to investigate the tissue distribution, accumulation, and tissue-specific health risk of MPs in mice. Results indicated that MPs accumulated in liver, kidney and gut, with a tissue-accumulation kinetics and distribution pattern that was strongly depended on the MPs particle size. In addition, analyses of multiple biochemical biomarkers and metabolomic profiles suggested that MPs exposure induced disturbance of energy and lipid metabolism as well as oxidative stress. Interestingly, blood biomarkers of neurotoxicity were also altered. Our results uncovered the distribution and accumulation of MPs across mice tissues and revealed significant alteration in several biomarkers that indicate potential toxicity from MPs exposure. Collectively, our data provided new evidence for the adverse consequences of MPs.

Correction: Corrigendum: Comparative Transcriptome Analysis of Raccoon Dog Skin to Determine Melanin Content in Hair and Melanin Distribution in Skin

Abstract: Scientific Reports 7: Article number: 40903; published online: 18 January 2017; updated: 16 March 2017 This Article contains errors in Figure 1 where Figure 1C and Figure 1D were inadvertently duplicated, and Figure 1E and Figure 1F were omitted. The correct Figure 1 appears below as Figure 1.

Ion Concentration Polarization by Bifurcated Current Path.

Abstract: Ion concentration polarization (ICP) is a fundamental electrokinetic process that occurs near a perm-selective membrane under dc bias. Overall process highly depends on the current transportation mechanisms such as electro-convection, surface conduction and diffusioosmosis and the fundamental characteristics can be significantly altered by external parameters, once the permselectivity was fixed. In this work, a new ICP device with a bifurcated current path as for the enhancement of the surface conduction was fabricated using a polymeric nanoporous material. It was protruded to the middle of a microchannel, while the material was exactly aligned at the interface between two microchannels in a conventional ICP device. Rigorous experiments revealed out that the propagation of ICP layer was initiated from the different locations of the protruded membrane according to the dominant current path which was determined by a bulk electrolyte concentration. Since the enhancement of surface conduction maintained the stability of ICP process, a strong electrokinetic flow associated with the amplified electric field inside ICP layer was significantly suppressed over the protruded membrane even at condensed limit. As a practical example of utilizing the protruded device, we successfully demonstrated a non-destructive micro/nanofluidic preconcentrator of fragile cellular species (i.e. red blood cells).

Sensitivity to musical emotion is influenced by tonal structure in congenital amusia

Abstract: Emotional communication in music depends on multiple attributes including psychoacoustic features and tonal system information, the latter of which is unique to music. The present study investigated whether congenital amusia, a lifelong disorder of musical processing, impacts sensitivity to musical emotion elicited by timbre and tonal system information. Twenty-six amusics and 26 matched controls made tension judgments on Western (familiar) and Indian (unfamiliar) melodies played on piano and sitar. Like controls, amusics used timbre cues to judge musical tension in Western and Indian melodies. While controls assigned significantly lower tension ratings to Western melodies compared to Indian melodies, thus showing a tonal familiarity effect on tension ratings, amusics provided comparable tension ratings for Western and Indian melodies on both timbres. Furthermore, amusics rated Western melodies as more tense compared to controls, as they relied less on tonality cues than controls in rating tension for Western melodies. The implications of these findings in terms of emotional responses to music are discussed.

Riparian plant litter quality increases with latitude

Abstract: Plant litter represents a major basal resource in streams, where its decomposition is partly regulated by litter traits. Litter-trait variation may determine the latitudinal gradient in decomposition in streams, which is mainly microbial in the tropics and detritivore-mediated at high latitudes. However, this hypothesis remains untested, as we lack information on large-scale trait variation for riparian litter. Variation cannot easily be inferred from existing leaf-trait databases, since nutrient resorption can cause traits of litter and green leaves to diverge. Here we present the first global-scale assessment of riparian litter quality by determining latitudinal variation (spanning 107°) in litter traits (nutrient concentrations; physical and chemical defences) of 151 species from 24 regions and their relationships with environmental factors and phylogeny. We hypothesized that litter quality would increase with latitude (despite variation within regions) and traits would be correlated to produce ‘syndromes’ resulting from phylogeny and environmental variation. We found lower litter quality and higher nitrogen:phosphorus ratios in the tropics. Traits were linked but showed no phylogenetic signal, suggesting that syndromes were environmentally determined. Poorer litter quality and greater phosphorus limitation towards the equator may restrict detritivore-mediated decomposition, contributing to the predominance of microbial decomposers in tropical streams.

Detailed Vascular Anatomy of the Human Retina by Projection-Resolved Optical Coherence Tomography Angiography

Abstract: Optical coherence tomography angiography (OCTA) is a noninvasive method of 3D imaging of the retinal and choroidal circulations. However, vascular depth discrimination is limited by superficial vessels projecting flow signal artifact onto deeper layers. The projection-resolved (PR) OCTA algorithm improves depth resolution by removing projection artifact while retaining in-situ flow signal from real blood vessels in deeper layers. This novel technology allowed us to study the normal retinal vasculature in vivo with better depth resolution than previously possible. Our investigation in normal human volunteers revealed the presence of 2 to 4 distinct vascular plexuses in the retina, depending on location relative to the optic disc and fovea. The vascular pattern in these retinal plexuses and interconnecting layers are consistent with previous histologic studies. Based on these data, we propose an improved system of nomenclature and segmentation boundaries for detailed 3-dimensional retinal vascular anatomy by OCTA. This could serve as a basis for future investigation of both normal retinal anatomy, as well as vascular malformations, nonperfusion, and neovascularization.

Modeling protein quaternary structure of homo- and hetero-oligomers beyond binary interactions by homology

Abstract: Cellular processes often depend on interactions between proteins and the formation of macromolecular complexes. The impairment of such interactions can lead to deregulation of pathways resulting in disease states, and it is hence crucial to gain insights into the nature of macromolecular assemblies. Detailed structural knowledge about complexes and protein-protein interactions is growing, but experimentally determined three-dimensional multimeric assemblies are outnumbered by complexes supported by non-structural experimental evidence. Here, we aim to fill this gap by modeling multimeric structures by homology, only using amino acid sequences to infer the stoichiometry and the overall structure of the assembly. We ask which properties of proteins within a family can assist in the prediction of correct quaternary structure. Specifically, we introduce a description of protein-protein interface conservation as a function of evolutionary distance to reduce the noise in deep multiple sequence alignments. We also define a distance measure to structurally compare homologous multimeric protein complexes. This allows us to hierarchically cluster protein structures and quantify the diversity of alternative biological assemblies known today. We find that a combination of conservation scores, structural clustering, and classical interface descriptors, can improve the selection of homologous protein templates leading to reliable models of protein complexes.

Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota.

Abstract: Alzheimer's disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer's disease is not known. To this end we sequenced bacterial 16S rRNA from fecal samples of Aβ precursor protein (APP) transgenic mouse model and found a remarkable shift in the gut microbiota as compared to non-transgenic wild-type mice. Subsequently we generated germ-free APP transgenic mice and found a drastic reduction of cerebral Aβ amyloid pathology when compared to control mice with intestinal microbiota. Importantly, colonization of germ-free APP transgenic mice with microbiota from conventionally-raised APP transgenic mice increased cerebral Aβ pathology, while colonization with microbiota from wild-type mice was less effective in increasing cerebral Aβ levels. Our results indicate a microbial involvement in the development of Abeta amyloid pathology, and suggest that microbiota may contribute to the development of neurodegenerative diseases.

Variability in sea ice cover and climate elicit sex specific responses in an Antarctic predator

Abstract: Contrasting regional changes in Southern Ocean sea ice have occurred over the last 30 years with distinct regional effects on ecosystem structure and function. Quantifying how Antarctic predators respond to such changes provides the context for predicting how climate variability/change will affect these assemblages into the future. Over an 11-year time-series, we examine how inter-annual variability in sea ice concentration and advance affect the foraging behaviour of a top Antarctic predator, the southern elephant seal. Females foraged longer in pack ice in years with greatest sea ice concentration and earliest sea ice advance, while males foraged longer in polynyas in years of lowest sea ice concentration. There was a positive relationship between near-surface meridional wind anomalies and female foraging effort, but not for males. This study reveals the complexities of foraging responses to climate forcing by a poleward migratory predator through varying sea ice property and dynamic anomalies.

Correction: Corrigendum: Risk Model for Colorectal Cancer in Spanish Population Using Environmental and Genetic Factors: Results from the MCC-Spain study

Abstract: Scientific Reports 7: Article number: 43263; published online: 24 February 2017; updated: 17 May 2017 The original version of this Article contained a typographical error in the spelling of the author Pablo Fernandez-Navarro, which was incorrectly given as Pablo Fernandez Navarro. This has now been corrected in both the PDF and HTML versions of the Article.

Neuromorphic photonic networks using silicon photonic weight banks.

Abstract: Photonic systems for high-performance information processing have attracted renewed interest. Neuromorphic silicon photonics has the potential to integrate processing functions that vastly exceed the capabilities of electronics. We report first observations of a recurrent silicon photonic neural network, in which connections are configured by microring weight banks. A mathematical isomorphism between the silicon photonic circuit and a continuous neural network model is demonstrated through dynamical bifurcation analysis. Exploiting this isomorphism, a simulated 24-node silicon photonic neural network is programmed using “neural compiler” to solve a differential system emulation task. A 294-fold acceleration against a conventional benchmark is predicted. We also propose and derive power consumption analysis for modulator-class neurons that, as opposed to laser-class neurons, are compatible with silicon photonic platforms. At increased scale, Neuromorphic silicon photonics could access new regimes of ultrafast information processing for radio, control, and scientific computing.

Field evidence for transfer of plastic debris along a terrestrial food chain

Abstract: Although plastic pollution happens globally, the micro- (<5 mm) and macroplastic (5–150 mm) transfer of plastic to terrestrial species relevant to human consumption has not been examined. We provide first-time evidence for micro- and macroplastic transfer from soil to chickens in traditional Mayan home gardens in Southeast Mexico where waste mismanagement is common. We assessed micro- and macroplastic in soil, earthworm casts, chicken feces, crops and gizzards (used for human consumption). Microplastic concentrations increased from soil (0.87 ± 1.9 particles g−1), to earthworm casts (14.8 ± 28.8 particles g−1), to chicken feces (129.8 ± 82.3 particles g−1). Chicken gizzards contained 10.2 ± 13.8 microplastic particles, while no microplastic was found in crops. An average of 45.82 ± 42.6 macroplastic particles were found per gizzard and 11 ± 15.3 macroplastic particles per crop, with 1–10 mm particles being significantly more abundant per gizzard (31.8 ± 27.27 particles) compared to the crop (1 ± 2.2 particles). The data show that micro- and macroplastic are capable of entering terrestrial food webs.

A rapid-screening approach to detect and quantify microplastics based on fluorescent tagging with Nile Red

Abstract: A new approach is presented for analysis of microplastics in environmental samples, based on selective fluorescent staining using Nile Red (NR), followed by density-based extraction and filtration. The dye adsorbs onto plastic surfaces and renders them fluorescent when irradiated with blue light. Fluorescence emission is detected using simple photography through an orange filter. Image-analysis allows fluorescent particles to be identified and counted. Magnified images can be recorded and tiled to cover the whole filter area, allowing particles down to a few micrometres to be detected. The solvatochromic nature of Nile Red also offers the possibility of plastic categorisation based on surface polarity characteristics of identified particles. This article details the development of this staining method and its initial cross-validation by comparison with infrared (IR) microscopy. Microplastics of different sizes could be detected and counted in marine sediment samples. The fluorescence staining identified the same particles as those found by scanning a filter area with IR-microscopy.

Real-time monitoring of laser powder bed fusion process using high-speed X-ray imaging and diffraction

Abstract: We employ the high-speed synchrotron hard X-ray imaging and diffraction techniques to monitor the laser powder bed fusion (LPBF) process of Ti-6Al-4V in situ and in real time. We demonstrate that many scientifically and technologically significant phenomena in LPBF, including melt pool dynamics, powder ejection, rapid solidification, and phase transformation, can be probed with unprecedented spatial and temporal resolutions. In particular, the keyhole pore formation is experimentally revealed with high spatial and temporal resolutions. The solidification rate is quantitatively measured, and the slowly decrease in solidification rate during the relatively steady state could be a manifestation of the recalescence phenomenon. The high-speed diffraction enables a reasonable estimation of the cooling rate and phase transformation rate, and the diffusionless transformation from β to α ’ phase is evident. The data present here will facilitate the understanding of dynamics and kinetics in metal LPBF process, and the experiment platform established will undoubtedly become a new paradigm for future research and development of metal additive manufacturing.

Doubling of coastal flooding frequency within decades due to sea-level rise

Abstract: Global climate change drives sea-level rise, increasing the frequency of coastal flooding. In most coastal regions, the amount of sea-level rise occurring over years to decades is significantly smaller than normal ocean-level fluctuations caused by tides, waves, and storm surge. However, even gradual sea-level rise can rapidly increase the frequency and severity of coastal flooding. So far, global-scale estimates of increased coastal flooding due to sea-level rise have not considered elevated water levels due to waves, and thus underestimate the potential impact. Here we use extreme value theory to combine sea-level projections with wave, tide, and storm surge models to estimate increases in coastal flooding on a continuous global scale. We find that regions with limited water-level variability, i.e., short-tailed flood-level distributions, located mainly in the Tropics, will experience the largest increases in flooding frequency. The 10 to 20 cm of sea-level rise expected no later than 2050 will more than double the frequency of extreme water-level events in the Tropics, impairing the developing economies of equatorial coastal cities and the habitability of low-lying Pacific island nations.

Generalized Mechanism of Field Emission from Nanostructured Semiconductor Film Cathodes

Abstract: Considering the effect of both the buffer layer and substrate, a series of ultrathin multilayered structure cathodes (UTMC) is constructed to simulate the field emission (FE) process of nanostructured semiconductor film cathodes (NSFCs). We find a generalized FE mechanism of the NSFCs, in which there are three distinct FE modes with the change of the applied field. Our results clearly show significant differences of FE between conventional emitters and nanofilm emitters, which the non-Fowler-Nordheim characteristics and the resonant FE will be inevitable for NSFCs. Moreover, the controllable FE can be realized by fine-tuning the quantum structure of NSFCs. The generalized mechanism of NSFCs presented here may be particularly useful for design high-speed and high-frequency vacuum nano-electronic devices.

Microplastic transport in soil by earthworms

Abstract: Despite great general benefits derived from plastic use, accumulation of plastic material in ecosystems, and especially microplastic, is becoming an increasing environmental concern. Microplastic has been extensively studied in aquatic environments, with very few studies focusing on soils. We here tested the idea that microplastic particles (polyethylene beads) could be transported from the soil surface down the soil profile via earthworms. We used Lumbricus terrestris L., an anecic earthworm species, in a factorial greenhouse experiment with four different microplastic sizes. Presence of earthworms greatly increased the presence of microplastic particles at depth (we examined 3 soil layers, each 3.5 cm deep), with smaller PE microbeads having been transported downward to a greater extent. Our study clearly shows that earthworms can be significant transport agents of microplastics in soils, incorporating this material into soil, likely via casts, burrows (affecting soil hydraulics), egestion and adherence to the earthworm exterior. This movement has potential consequences for exposure of other soil biota to microplastics, for the residence times of microplastic at greater depth, and for the possible eventual arrival of microplastics in the groundwater.

CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells.

Abstract: Immunotherapies with chimeric antigen receptor (CAR) T cells and checkpoint inhibitors (including antibodies that antagonize programmed cell death protein 1 [PD-1]) have both opened new avenues for cancer treatment, but the clinical potential of combined disruption of inhibitory checkpoints and CAR T cell therapy remains incompletely explored. Here we show that programmed death ligand 1 (PD-L1) expression on tumor cells can render human CAR T cells (anti-CD19 4-1BBζ) hypo-functional, resulting in impaired tumor clearance in a sub-cutaneous xenograft model. To overcome this suppressed anti-tumor response, we developed a protocol for combined Cas9 ribonucleoprotein (Cas9 RNP)-mediated gene editing and lentiviral transduction to generate PD-1 deficient anti-CD19 CAR T cells. Pdcd1 (PD-1) disruption augmented CAR T cell mediated killing of tumor cells in vitro and enhanced clearance of PD-L1+ tumor xenografts in vivo. This study demonstrates improved therapeutic efficacy of Cas9-edited CAR T cells and highlights the potential of precision genome engineering to enhance next-generation cell therapies.

Correction: Corrigendum: Endocytic recycling protein EHD1 regulates primary cilia morphogenesis and SHH signaling during neural tube development

Abstract: Scientific Reports 6: Article number: 20727; published online: 17 February 2016; updated: 23 March 2017 A reader alerted us of a potential error in Figure 12B and its accompanying Supplementary Figure 13B, since the indicated bands for GST fusion proteins did not correspond to the distinct expected sizes.

Correction: Corrigendum: Full Valley and Spin Polarizations in Strained Graphene with Rashba Spin Orbit Coupling and Magnetic Barrier

Abstract: Scientific Reports 6: Article number: 21590; published online: 22 February 2016; updated: 23 January 2017 This Article contains errors in Reference 15 which was incorrectly given as: Song, Y., Zhai, F. & Guo, Y. Strain-tunable spin transport in ferromagnetic graphene junctions. Appl. Phys. Lett.103, 183111 (2013).

Rapid generation of a transgene-free powdery mildew resistant tomato by genome deletion

Abstract: Genome editing has emerged as a technology with a potential to revolutionize plant breeding. In this study, we report on generating, in less than ten months, Tomelo, a non-transgenic tomato variety resistant to the powdery mildew fungal pathogen using the CRISPR/Cas9 technology. We used whole-genome sequencing to show that Tomelo does not carry any foreign DNA sequences but only carries a deletion that is indistinguishable from naturally occurring mutations. We also present evidence for CRISPR/Cas9 being a highly precise tool, as we did not detect off-target mutations in Tomelo. Using our pipeline, mutations can be readily introduced into elite or locally adapted tomato varieties in less than a year with relatively minimal effort and investment.