ALBERT

Description: The inherent attenuation of a homogeneous viscous medium limits radiation propagation, thereby restricting the use of many high-frequency acoustic devices to only short-range applications. Here, we design and experimentally demonstrate an acoustic metamaterial localization cavity which is used for sound pressure level (SPL) gain using double coiled up space like structures thereby increasing the range of detection. This unique behavior occurs within a subwavelength cavity that is 1/10th of the wavelength of the incident acoustic wave, which provides up to a 13 dB SPL gain. We show that the amplification results from the Fabry-Perot resonance of the cavity, which has a simultaneously high effective refractive index and effective impedance. We also experimentally verify the SPL amplification in an underwater environment at higher frequencies using a sample with an identical unit cell size. The versatile scalability of the design shows promising applications in many areas, especially in acoustic imaging and underwater communication. Scientific Reports 4 doi: 10.1038/srep07421

Description: Advanced macrolides, such as azithromycin (AZM) or clarithromycin (CLM), are antibiotics with immunomodulatory properties. Here we have sought to evaluate their in vitro influence on the activation of CD4+ T-cells. Isolated CD4+ T-cells were stimulated with agonistic anti-CD3/anti-CD28 monoclonal antibodies in the presence of 0.6 mg/L, 2.5 mg/L, 10 mg/L or 40 mg/L AZM or CLM. Cell proliferation, cytokine level in supernatants and cell viability was assessed. Intracellular signaling pathways were evaluated using reporter cell lines, FACS analysis, immunoblotting and in vitro kinase assays. AZM inhibited cell proliferation rate and cytokine secretion of CD4+ T-cells in a dose-dependent manner. Similarly, high concentrations of CLM (40 mg/L) also suppressed these T-cell functions. Analysis of molecular signaling pathways revealed that exposure to AZM reduced the phosphorylation of the S6 ribosomal protein, a downstream target of mTOR. This effect was also observed at 40 mg/L CLM. In vitro kinase studies using recombinant mTOR showed that AZM inhibited mTOR activity. In contrast to rapamycin, this inhibition was independent of FKBP12. We show for the first time that AZM and to a lesser extent CLM act as immunosuppressive agents on CD4+ T-cells by inhibiting mTOR activity. Our results might have implications for the clinical use of macrolides. Scientific Reports 4 doi: 10.1038/srep07438

Description: A solid-state nanopore platform with a low noise level and sufficient sensitivity to discriminate single-strand DNA (ssDNA) homopolymers of poly-A40 and poly-T40 using ionic current blockade sensing is proposed and demonstrated. The key features of this platform are (a) highly insulating dielectric substrates that are used to mitigate the effect of parasitic capacitance elements, which decrease the ionic current RMS noise level to sub-10 pA and (b) ultra-thin silicon nitride membranes with a physical thickness of 5 nm (an effective thickness of 2.4 nm estimated from the ionic current) are used to maximize the signal-to-noise ratio and the spatial depth resolution. The utilization of an ultra-thin membrane and a nanopore diameter as small as 1.5 nm allow the successful discrimination of 40 nucleotide ssDNA poly-A40 and poly-T40. Overall, we demonstrate that this platform overcomes several critical limitations of solid-state nanopores and opens the door to a wide range of applications in single-molecule-based detection and analysis. Scientific Reports 4 doi: 10.1038/srep07448

Description: Actions such as sharing food and cooperating to reach a common goal have played a fundamental role in the evolution of human societies. Despite the importance of such good actions, little is known about if and how they can spread from person to person to person. For instance, does being recipient of an altruistic act increase your probability of being cooperative with a third party? We have conducted an experiment on Amazon Mechanical Turk to test this mechanism using economic games. We have measured willingness to be cooperative through a standard Prisoner's dilemma and willingness to act altruistically using a binary Dictator game. In the baseline treatments, the endowments needed to play were given by the experimenters, as usual; in the control treatments, they came from a good action made by someone else. Across four different comparisons and a total of 572 subjects, we have never found a significant increase of cooperation or altruism when the endowment came from a good action. We conclude that good actions do not necessarily inspire good actions in others. While this is consistent with the theoretical prediction, it challenges the majority of other experimental studies. Scientific Reports 4 doi: 10.1038/srep07470

Description: EPAS1 involves in the hypoxic response and is suggested to be responsible for the genetic adaptation of high-altitude hypoxia in Tibetans. However, the detailed molecular mechanism remains unknown. In this study, a single nucleotide polymorphism rs56721780:G〉C and an insertion/deletion (indel) polymorphism −742 indel in the promoter region showed divergence between Tibetans and non-Tibetan lowlanders. rs56721780:G〉C regulated the transcription of EPAS1 by IKAROS family zinc finger 1 (IKZF1), which was identified as a new transcriptional repressor for EPAS1 gene. It demonstrated that the C allele of rs56721780:G〉C decreased the binding of IKZF1, leading to the attenuated transcriptional repression of EPAS1 gene. The insertion at −742 indel provided a new binding site for Sp1 and was related to the activation of EPAS1 promoter. Further functional analysis revealed that lysyl oxidase (LOX) gene, which was reported to be responsible for extracellular matrix protein cross-linking of amnion previously, was a direct target of EPAS1. The CC genotype at rs56721780:G〉C and the insertion genotype at −742 indel were found associated with higher EPAS1 and LOX expression levels in amnion, as well as higher birth weight of Tibetan newborns, suggesting that EPAS1 gene might play important roles in the development of amnion, fetus growth and high-altitude adaptation of Tibetans. Scientific Reports 4 doi: 10.1038/srep07465

Description: It has been recently reported that the reciprocity of real-life weighted networks is very pronounced, however its impact on dynamical processes is poorly understood. In this paper, we study random walks in a scale-free directed weighted network with a trap at the central hub node, where the weight of each directed edge is dominated by a parameter controlling the extent of network reciprocity. We derive two expressions for the mean first passage time (MFPT) to the trap, by using two different techniques, the results of which agree well with each other. We also analytically determine all the eigenvalues as well as their multiplicities for the fundamental matrix of the dynamical process, and show that the largest eigenvalue has an identical dominant scaling as that of the MFPT.We find that the weight parameter has a substantial effect on the MFPT, which behaves as a power-law function of the system size with the power exponent dependent on the parameter, signaling the crucial role of reciprocity in random walks occurring in weighted networks. Scientific Reports 4 doi: 10.1038/srep07460

Description: Most influenza pandemics have been caused by H1N1 viruses of purely or partially avian origin. Here, using Cox proportional hazard model, we attempt to identify the genetic variations in the whole genome of wild-type North American avian H1N1 influenza A viruses that are associated with their virulence in mice by residue variations, host origins of virus (Anseriformes-ducks or Charadriiformes-shorebirds), and host-residue interactions. In addition, through structural modeling, we predicted that several polymorphic sites associated with pathogenicity were located in structurally important sites, especially in the polymerase complex and NS genes. Our study introduces a new approach to identify pathogenic variations in wild-type viruses circulating in the natural reservoirs and ultimately to understand their infectious risks to humans as part of risk assessment efforts towards the emergence of future pandemic strains. Scientific Reports 4 doi: 10.1038/srep07455

Description: We propose a method to enhance the fuel cell efficiency with the simultaneous removal of toxic heavy metal ions. Carbon monoxide (CO), an intermediate of methanol oxidation that is primarily responsible for Pt catalyst deactivation, can be used as an in-situ reducing agent for hexavalent chromium (Cr (VI)) with reactivating the CO-poisoned Pt catalyst. Using electro-oxidation measurements, the oxidation of adsorbed CO molecules coupled with the concurrent conversion of Cr (VI) to Cr (III) was confirmed. This concept was also successfully applied to a methanol fuel cell to enhance its performance efficiency and to remove toxic Cr (VI) at the same time. Scientific Reports 4 doi: 10.1038/srep07450

Description: Alzheimer's disease (AD) is a lethal progressive neurological disorder affecting the memory. Recently, US Food and Drug Administration mitigated the standard for drug approval, allowing symptomatic drugs that only improve cognitive deficits to be allowed to accelerate on to clinical trials. Our study focuses on taurine, an endogenous amino acid found in high concentrations in humans. It has demonstrated neuroprotective properties against many forms of dementia. In this study, we assessed cognitively enhancing property of taurine in transgenic mouse model of AD. We orally administered taurine via drinking water to adult APP/PS1 transgenic mouse model for 6 weeks. Taurine treatment rescued cognitive deficits in APP/PS1 mice up to the age-matching wild-type mice in Y-maze and passive avoidance tests without modifying the behaviours of cognitively normal mice. In the cortex of APP/PS1 mice, taurine slightly decreased insoluble fraction of Aβ. While the exact mechanism of taurine in AD has not yet been ascertained, our results suggest that taurine can aid cognitive impairment and may inhibit Aβ-related damages. Scientific Reports 4 doi: 10.1038/srep07467

Description: Archaeal plasma membranes appear to be extremely durable and almost impermeable to water and ions, in contrast to the membranes of Bacteria and Eucaryota. Additionally, they remain liquid within a temperature range of 0–100°C. These are the properties that have most likely determined the evolutionary fate of Archaea, and it may be possible for bionanotechnology to adopt these from nature. In this work, we use molecular dynamics simulations to assess at the atomistic level the structure and dynamics of a series of model archaeal membranes with lipids that have tetraether chemical nature and “branched” hydrophobic tails. We conclude that the branched structure defines dense packing and low water permeability of archaeal-like membranes, while at the same time ensuring a liquid-crystalline state, which is vital for living cells. This makes tetraether lipid systems promising in bionanotechnology and material science, namely for design of new and unique membrane nanosystems. Scientific Reports 4 doi: 10.1038/srep07462

Description: Scientific Reports 4 doi: 10.1038/srep05692

Description: Typhoid fever poses significant burden on healthcare systems in Southeast Asia and other endemic countries. Several epidemiological and genomic studies have attributed pseudogenisation to be the major driving force for the evolution of Salmonella Typhi although its real potential remains elusive. In the present study, we analyzed genomes of S. Typhi from different parts of Southeast Asia and Oceania, comprising of isolates from outbreak, sporadic and carrier cases. The genomes showed high genetic relatedness with limited opportunity for gene acquisition as evident from pan-genome structure. Given that pseudogenisation is an active process in S. Typhi, we further investigated core and pan-genome profiles of functional and pseudogenes separately. We observed a decline in core functional gene content and a significant increase in accessory pseudogene content. Upon functional classification, genes encoding metabolic functions formed a major constituent of pseudogenes as well as core functional gene clusters with SNPs. Further, an in-depth analysis of accessory pseudogene content revealed the existence of heterogeneous complements of functional and pseudogenes among the strains. In addition, these polymorphic genes were also enriched in metabolism related functions. Thus, the study highlights the existence of heterogeneous strains in a population with varying metabolic potential and that S. Typhi possibly resorts to metabolic fine tuning for its adaptation. Scientific Reports 4 doi: 10.1038/srep07457

Description: Ultraviolet photodetectors have been fabricated from ZnO quantum dots/carbon nanodots hybrid films, and the introduction of carbon nanodots improves the performance of the photodetectors greatly. The photodetectors can be used to detect very weak ultraviolet signals (as low as 12 nW/cm2). The detectivity and noise equivalent power of the photodetector can reach 3.1 × 1017 cmHz1/2/W and 7.8 × 10−20 W, respectively, both of which are the best values ever reported for ZnO-based photodetectors. The mechanism for the high sensitivity of the photodetectors has been attributed to the enhanced carrier-separation at the ZnO/C interface. Scientific Reports 4 doi: 10.1038/srep07469

Description: Microglia represent rational but challenging targets for improving white matter integrity because of their dualistic protective and toxic roles. The present study examines the effect of Omega-3 polyunsaturated fatty acids (n-3 PUFAs) on microglial responses to myelin pathology in primary cultures and in the cuprizone mouse model of multiple sclerosis (MS), a devastating demyelination disease. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the two main forms of n-3 PUFAs in the brain, inhibited the release of nitric oxide and tumor necrosis factor-α from primary microglia upon IFN-γ and myelin stimulation. DHA and EPA also enhanced myelin phagocytosis in vitro. Therefore, n-3 PUFAs can inhibit inflammation while at the same time enhancing beneficial immune responses such as microglial phagocytosis. In vivo studies demonstrated that n-3 PUFA supplementation reduced cuprizone-induced demyelination and improved motor and cognitive function. The positive effects of n-3 PUFAs were accompanied by a shift in microglial polarization toward the beneficial M2 phenotype both in vitro and in vivo. These results suggest that n-3 PUFAs may be clinically useful as immunomodulatory agents for demyelinating diseases through a novel mechanism involving microglial phenotype switching. Scientific Reports 4 doi: 10.1038/srep07458

Description: With Fe2O3 as a proof-of-concept, free-standing nanomembrane structure is demonstrated to be highly advantageous to improve the performance of Li-ion batteries. The Fe2O3 nanomembrane electrodes exhibit ultra-long cycling life at high current rates with satisfactory capacity (808 mAh g−1 after 1000 cycles at 2 C and 530 mAh g−1 after 3000 cycles at 6 C) as well as repeatable high rate capability up to 50 C. The excellent performance benefits particularly from the unique structural advantages of the nanomembranes. The mechanical feature can buffer the strain of lithiation/delithiation to postpone the pulverization. The two-dimensional transport pathways in between the nanomembranes can promote the pseudo-capacitive type storage. The parallel-laid nanomembranes, which are coated by polymeric gel-like film and SEI layer with the electrolyte in between layers, electrochemically behave like numerous “mini-capacitors” to provide the pseudo-capacitance thus maintain the capacity at high rate. Scientific Reports 4 doi: 10.1038/srep07452

Description: Peptide deformylase (PDF) is a prokaryotic enzyme that catalyzes the deformylation of nascent peptides generated during protein synthesis and water molecules play a key role in these hydrolases. Using X-ray absorption near edge spectroscopy (XANES) and ab initio calculations we accurately probe the local atomic environment of the metal ion binding in the active site of PDF at different pH values and with different metal ions. This new approach is an effective way to monitor existing correlations among functions and structural changes. We show for the first time that the enzymatic activity depends on pH values and metal ions via the bond length of the nearest coordinating water (Wat1) to the metal ion. Combining experimental and theoretical data we may claim that PDF exhibits an enhanced enzymatic activity only when the distance of the Wat1 molecule with the metal ion falls in the limited range from 2.15 to 2.55 Å. Scientific Reports 4 doi: 10.1038/srep07453

Description: Recently a new form of ultra-thin flexible waveguide consisting of a conducting comb-like structure with a thickness of the order of 1/600th of the operating wavelength was presented. However, whilst the thickness of the guide was massively sub-wavelength, the remaining dimensions (the height and period of the comb) were much longer. In this paper we propose, and experimentally verify, that a modified guiding geometry consisting of a chain of ultra-thin conducting spirals allows guiding of electromagnetic waves with wavelengths that are many times (40+) longer than any characteristic dimension of the guide, enabling super-sub-wavelength guiding and localisation of electromagnetic energy. Scientific Reports 4 doi: 10.1038/srep07495

Description: L-3, 4-dihydroxyphenylalanine (L-dopa) is the gold standard for symptomatic treatment of Parkinson's disease (PD), but long-term therapy is associated with the emergence of L-dopa-induced dyskinesia (LID). In the present study, L-dopa and benserazide were loaded by poly (lactic-co-glycolic acid) microspheres (LBM), which can release levodopa and benserazide in a sustained manner in order to continuous stimulate dopaminergic receptors. We investigated the role of striatal DR1/PKA/P-tau signal transduction in the molecular event underlying LID in the 6-OHDA-lesioned rat model of PD. We found that animals rendered dyskinetic by L-dopa treatment, administration of LBM prevented the severity of AIM score, as well as improvement in motor function. Moreover, we also showed L-dopa elicits profound alterations in the activity of three LID molecular markers, namely DR1/PKA/P-tau (ser396). These modifications are totally prevented by LBM treatment, a similar way to achieve continuous dopaminergic delivery (CDD). In conclusion, our experiments provided evidence that intermittent administration of L-dopa, but not continuous delivery, and DR1/PKA/p-tau (ser396) activation played a critical role in the molecular and behavioural induction of LID in 6-OHDA-lesioned rats. In addition, LBM treatment prevented the development of LID by inhibiting the expression of DR1/PKA/p-tau, as well as PPEB mRNA in dyskintic rats. Scientific Reports 4 doi: 10.1038/srep07506

Description: Humpback whales (Megaptera novaeangliae), a mysticete with a cosmopolitan distribution, demonstrate marked behavioural plasticity. Recent studies show evidence of social learning in the transmission of specific population level traits ranging from complex singing to stereotyped prey capturing behaviour. Humpback whales have been observed to employ group foraging techniques, however details on how individuals coordinate behaviour in these groups is challenging to obtain. This study investigates the role of a novel broadband patterned pulsed sound produced by humpback whales engaged in bottom-feeding behaviours, referred to here as a ‘paired burst’ sound. Data collected from 56 archival acoustic tag deployments were investigated to determine the functional significance of these signals. Paired burst sound production was associated exclusively with bottom feeding under low-light conditions, predominantly with evidence of associated conspecifics nearby suggesting that the sound likely serves either as a communicative signal to conspecifics, a signal to affect prey behaviour, or possibly both. This study provides additional evidence for individual variation and phenotypic plasticity of foraging behaviours in humpback whales and provides important evidence for the use of acoustic signals among foraging individuals in this species. Scientific Reports 4 doi: 10.1038/srep07508

Description: Two new ternary compounds in the TiO2-TiC system, Ti5C2O6 and Ti3C2O2, are reported for the first time based on ab initio evolutionary algorithm. Ti5C2O6 has a tube-structure in which sp1 hybridized carbon chains run through the lattice along the b-axis; while in the Ti3C2O2 lattice, double TiO6 polyhedral are separated by the non-coplanar sp2 hybridized hexagon graphite layers along the c-axis, forming a sandwich-like structure. At ambient conditions, the two compounds are found to be mechanically and dynamically stable and intrinsic transparent conductors with high hardness (about twice harder than the conventional transparent conducting oxides). These mechanical, electronic, and optical properties make Ti5C2O6 and Ti3C2O2 ternary compounds be promising robust, hard, transparent, and conductive materials. Scientific Reports 4 doi: 10.1038/srep07503

Description: Genetic and transcriptional profiling, as well as surface marker identification of single circulating tumor cells (CTCs) have been demonstrated. However, quantitatively profiling of functional proteins at single CTC resolution has not yet been achieved, owing to the limited purity of the isolated CTC populations and a lack of single-cell proteomic approaches to handle and analyze rare CTCs. Here, we develop an integrated microfluidic system specifically designed for streamlining isolation, purification and single-cell secretomic profiling of CTCs from whole blood. Key to this platform is the use of photocleavable ssDNA-encoded antibody conjugates to enable a highly purified CTC population with 〈75 ‘contaminated’ blood cells. An enhanced poly-L-lysine barcode pattern is created on the single-cell barcode chip for efficient capture rare CTC cells in microchambers for subsequent secreted protein profiling. This system was extensively evaluated and optimized with EpCAM-positive HCT116 cells seeded into whole blood. Patient blood samples were employed to assess the utility of the system for isolation, purification and single-cell secretion profiling of CTCs. The CTCs present in patient blood samples exhibit highly heterogeneous secretion profile of IL-8 and VEGF. The numbers of secreting CTCs are found not in accordance with CTC enumeration based on immunostaining in the parallel experiments. Scientific Reports 4 doi: 10.1038/srep07499

Description: Peptidoglycan (PGN) is ubiquitous in nearly all bacterial species. The PGN sacculus protects the cells against their own internal turgor making PGN one of the most important targets for antibacterial treatment. Within the last sixty years PGN composition has been intensively studied by various methods. The breakthrough was the application of HPLC technology on the analysis of muropeptides. However, preparation of pure PGN relied on a very time consuming method of about one week. We established a purification protocol for both Gram-positive and Gram-negative bacteria which can be completely performed in plastic reaction tubes yielding pure muropeptides within 24 hours. The muropeptides can be analyzed by UPLC-MS, allowing their immediate determination. This new rapid method provides the feasibility to screen PGN composition even in high throughput, making it a highly useful tool for basic research as well as for the pharmaceutical industry. Scientific Reports 4 doi: 10.1038/srep07494

Description: Nanowires play a crucial role in the development of new generation optoelectronic devices ranging from photovoltaics to photodetectors, as these designs capitalize on the low material usage, utilize leaky-mode optical resonances and possess high conversion efficiencies associated with nanowire geometry. However, their current schemes lack sufficient absorption capacity demanded for their practical applicability, and more efficient materials cannot find widespread usage in these designs due to their rarity and cost. Here we suggest a novel and versatile nanoconcentrator scheme utilizing unique optical features of non-resonant Mie (NRM) scattering regime associated with low-index structures. The scattering regime is highly compatible with resonant Mie absorption effect taking place in nanowire absorbers. This technique in its optimized forms can provide up to 1500% total absorption enhancement, 400-fold material save and is suitable for large-area applications with significant area preservation compared to thin-film of same materials. Proposed superenhancer concept with its exceptional features such as broadband absorption enhancement, polarization immunity and material-independent manner paves the way for development of efficient nanowire photosensors or solar thermophotovoltaic devices and presents novel design opportunities for self-powered nanosystems. Scientific Reports 4 doi: 10.1038/srep07505

Description: Hyperforin is a pharmacologically active component of the medicinal plant Hypericum perforatum (St. John's wort), recommended as a treatment for a range of ailments including mild to moderate depression. Part of its action has been attributed to TRPC6 channel activation. We found that hyperforin induces TRPC6-independent H+ currents in HEK-293 cells, cortical microglia, chromaffin cells and lipid bilayers. The latter demonstrates that hyperforin itself acts as a protonophore. The protonophore activity of hyperforin causes cytosolic acidification, which strongly depends on the holding potential, and which fuels the plasma membrane sodium-proton exchanger. Thereby the free intracellular sodium concentration increases and the neurotransmitter uptake by Na+ cotransport is inhibited. Additionally, hyperforin depletes and reduces loading of large dense core vesicles in chromaffin cells, which requires a pH gradient in order to accumulate monoamines. In summary the pharmacological actions of the “herbal Prozac” hyperforin are essentially determined by its protonophore properties shown here. Scientific Reports 4 doi: 10.1038/srep07500

Description: Using first-principles calculations, we predict that the magnetic anisotropy energy of Co-doped TiO2 sensitively depends on carrier accumulation. This magnetoelectric phenomenon provides a potential route to a direct manipulation of the magnetization direction in diluted magnetic semiconductor by external electric-fields. We calculate the band structures and reveal the origin of the carrier-dependent magnetic anisotropy energy in k-space. It is shown that the carrier accumulation shifts the Fermi energy, and consequently, regulates the competing contributions to the magnetic anisotropy energy. The calculations provide an insight to understanding this magnetoelectric phenomenon, and a straightforward way to search prospective materials for electrically controllable spin direction of carriers. Scientific Reports 4 doi: 10.1038/srep07496

Description: Fe3O4 and Fe nanowires are successfully fabricated by electrospinning method and reduction process. Wiry microstructures were achieved with the phase transformation from α-Fe2O3 to Fe3O4 and Fe by partial and full reduction, while still preserving the wire morphology. The diameters of the Fe3O4 and Fe nanowires are approximately 50–60 nm and 30–40 nm, respectively. The investigation of microwave absorption reveals that the Fe3O4 nanowires exhibit excellent microwave absorbing properties. For paraffin-based composite containing 50% weight concentration of Fe3O4 nanowires, the minimum reflection loss reaches −17.2 dB at 6.2 GHz with the matching thickness of 5.5 mm. Furthermore, the calculation shows that the modulus of the ratio between the complex permittivity and permeability |ε/μ| is far away from unity at the minimum reflection loss point, which is quite different from the traditional opinions. Scientific Reports 4 doi: 10.1038/srep07493

Description: With diameter close to the wavelength of the guided light and high index contrast between the fiber and the surrounding, an optical micro-fiber shows a variety of interesting waveguiding properties, including widely tailorable optical confinement, strong evanescent fields and waveguide dispersion. Among various micro-fiber applications, optical sensing has been attracting increasing research interest due to its possibilities of realizing miniaturized fiber optic sensors with small footprint, high sensitivity, and low optical power consumption. Typical micro-fiber based sensing structures, including Michelson interferometer, Mach-Zenhder interferometer, Fabry-Perot interferometer, micro-fiber ring resonator, have been proposed. The sensitivity of these structures heavily related to the fraction of evanescent field outside micro-fiber. In this paper, we report the first theoretical and experimental study of a new type of refractometric sensor based on micro-fiber three-beam interferometer. Theoretical and experimental analysis reveals that the sensitivity is not only determined by the fraction of evanescent field outside the micro-fiber but also related to the values of interferometric arms. The sensitivity can be enhanced significantly when the effective lengths of the interferometric arms tends to be equal. We argue that this has great potential for increasing the sensitivity of refractive index detection. Scientific Reports 4 doi: 10.1038/srep07504

Description: We present a technique that uses an externally applied electric field to self-assemble monolayers of mixtures of particles into molecular-like hierarchical arrangements on fluid-liquid interfaces. The arrangements consist of composite particles (analogous to molecules) which are arranged in a pattern. The structure of a composite particle depends on factors such as the relative sizes of the particles and their polarizabilities, and the electric field intensity. If the particles sizes differ by a factor of two or more, the composite particle has a larger particle at its core and several smaller particles form a ring around it. The number of particles in the ring and the spacing between the composite particles depend on their polarizabilities and the electric field intensity. Approximately same sized particles form chains (analogous to polymeric molecules) in which positively and negatively polarized particles alternate. Scientific Reports 4 doi: 10.1038/srep07427

Description: Could nanostructures act as lenses to focus incident light for efficient utilization of photovoltaics? Is it possible, in order to avoid serious recombination loss, to realize periodic nanostructures in solar cells without direct etching in a light absorbing semiconductor? Here we propose and demonstrate a promising architecture to shape nanolenses on a planar semiconductor. Optically transparent and electrically conductive nanolenses simultaneously provide the optical benefit of modulating the incident light and the electrical advantage of supporting carrier transportation. A transparent indium-tin-oxide (ITO) nanolens was designed to focus the incident light-spectrum in focal lengths overlapping to a strong electric field region for high carrier collection efficiency. The ITO nanolens effectively broadens near-zero reflection and provides high tolerance to the incident light angles. We present a record high light-conversion efficiency of 16.0% for a periodic nanostructured Si solar cell. Scientific Reports 4 doi: 10.1038/srep06879

Description: Pigs are ideal organ donors for xenotransplantation and an excellent model for studying human diseases, such as neurodegenerative disease. Transcription activator-like effector nucleases (TALENs) are used widely for gene targeting in various model animals. Here, we developed a strategy using TALENs to target the GGTA1, Parkin and DJ-1 genes in the porcine genome using Large White porcine fibroblast cells without any foreign gene integration. In total, 5% (2/40), 2.5% (2/80), and 22% (11/50) of the obtained colonies of fibroblast cells were mutated for GGTA1, Parkin, and DJ-1, respectively. Among these mutant colonies, over 1/3 were bi-allelic knockouts (KO), and no off-target cleavage was detected. We also successfully used single-strand oligodeoxynucleotides to introduce a short sequence into the DJ-1 locus. Mixed DJ-1 mutant colonies were used as donor cells for somatic cell nuclear transfer (SCNT), and three female piglets were obtained (two were bi-allelically mutated, and one was mono-allelically mutated). Western blot analysis showed that the expression of the DJ-1 protein was disrupted in KO piglets. These results imply that a combination of TALENs technology with SCNT can efficiently generate bi-allelic KO pigs without the integration of exogenous DNA. These DJ-1 KO pigs will provide valuable information for studying Parkinson's disease. Scientific Reports 4 doi: 10.1038/srep06926

Description: Quantum magnetic phase transition in square-octagon lattice was investigated by cellular dynamical mean field theory combining with continuous time quantum Monte Carlo algorithm. Based on the systematic calculation on the density of states, the double occupancy and the Fermi surface evolution of square-octagon lattice, we presented the phase diagrams of this splendid many particle system. The competition between the temperature and the on-site repulsive interaction in the isotropic square-octagon lattice has shown that both antiferromagnetic and paramagnetic order can be found not only in the metal phase, but also in the insulating phase. Antiferromagnetic metal phase disappeared in the phase diagram that consists of the anisotropic parameter λ and the on-site repulsive interaction U while the other phases still can be detected at T = 0.17. The results found in this work may contribute to understand well the properties of some consuming systems that have square-octagon structure, quasi square-octagon structure, such as ZnO. Scientific Reports 4 doi: 10.1038/srep06918

Description: Thermal and electrical control of magnetic anisotropy were investigated in flexible Fe81Ga19 (FeGa)/Polyvinylidene fluoride (PVDF) multiferroic heterostructures. Due to the large anisotropic thermal deformation of PVDF (α1 = −13 × 10−6 K−1 and α2 = −145 × 10−6 K−1), the in-plane uniaxial magnetic anisotropy (UMA) of FeGa can be reoriented 90° by changing the temperature across 295 K where the films are magnetically isotropic. Thus, the magnetization of FeGa can be reversed by the thermal cycling between 280 and 320 K under a constant magnetic field lower than coercivity. Moreover, under the assistance of thermal deformation with slightly heating the samples to the critical temperature, the electric field of ± 267 kV cm−1 can well align the UMA along the two orthogonal directions. The new route of combining thermal and electrical control of magnetic properties realized in PVDF-based flexible multiferroic materials shows good prospects in application of flexible thermal spintronic devices and flexible microwave magnetic materials. Scientific Reports 4 doi: 10.1038/srep06925

Description: Defensins play a key role in the innate immunity of various organisms. Detailed genomic studies of the defensin cluster have only been reported in a limited number of birds. Herein, we present the first characterization of defensins in a Pelecaniformes species, the crested ibis (Nipponia nippon), which is one of the most endangered birds in the world. We constructed bacterial artificial chromosome libraries, including a 4D-PCR library and a reverse-4D library, which provide at least 40 equivalents of this rare bird's genome. A cluster including 14 β-defensin loci within 129 kb was assigned to chromosome 3 by FISH, and one gene duplication of AvBD1 was found. The ibis defensin genes are characterized by multiform gene organization ranging from two to four exons through extensive exon fusion. Splicing signal variations and alternative splice variants were also found. Comparative analysis of four bird species identified one common and multiple species-specific duplications, which might be associated with high GC content. Evolutionary analysis revealed birth-and-death mode and purifying selection for avian defensin evolution, resulting in different defensin gene numbers among bird species and functional conservation within orthologous genes, respectively. Additionally, we propose various directions for further research on genetic conservation in the crested ibis. Scientific Reports 4 doi: 10.1038/srep06923

Description: We investigated 17 polymorphisms in 11 genes (TS, MTHFR, ERCC1, XRCC1, XRCC3, XPD, GSTT1, GSTP1, GSTM1, ABCC1, ABCC2) for their association with the toxicity of fluoropyrimidines and oxaliplatin in colorectal cancer patients enrolled in a prospective randomized trial of adjuvant chemotherapy. The TOSCA Italian adjuvant trial was conducted in high-risk stage II–III colorectal cancer patients treated with 6 or 3 months of either FOLFOX-4 or XELOX adjuvant chemotherapy. In the concomitant ancillary pharmacogenetic study, the primary endpoint was the association of polymorphisms with grade 3–4 CTCAE toxicity events (grade 2–4 for neurotoxicity). In 517 analyzed patients, grade ≥ 3 neutropenia and grade ≥ 2 neurotoxicity events occurred in 150 (29%) and in 132 patients (24.8%), respectively. Diarrhea grade ≥ 3 events occurred in 34 (6.5%) patients. None of the studied polymorphisms showed clinically relevant association with toxicity. Hopefully, genome-wide association studies will identify new and more promising genetic variants to be tested in future studies. Scientific Reports 4 doi: 10.1038/srep06828

Description: Genital malformations occur at a high frequency in humans, affecting ~1:250 live births. The molecular mechanisms of external genital development are beginning to be identified; however, the origin of cells that give rise to external genitalia is unknown. Here we use cell lineage analysis to show that the genital tubercle, the precursor of the penis and clitoris, arises from two populations of progenitor cells that originate at the lateral edges of the embryo, at the level of the posterior hindlimb buds and anterior tail. During body wall closure, the left and right external genital progenitor pools are brought together at the ventral midline, where they form the paired genital swellings that give rise to the genital tubercle. Unexpectedly, the left and right external genital progenitor pools form two lineage-restricted compartments in the phallus. Together with previous lineage studies of limb buds, our results indicate that, at the pelvic level, the early lateral mesoderm is regionalized from medial to lateral into dorsal limb, ventral limb, and external genital progenitor fields. These findings have implications for the evolutionary diversification of external genitalia and for the association between external genital defects and disruption of body wall closure, as seen in the epispadias-extrophy complex. Scientific Reports 4 doi: 10.1038/srep06896

Description: Periodic segregation behaviors in fine mixtures of copper and alumina particles, including both percolation and eruption stages, are experimentally investigated by varying the ambient air pressure and vibrational acceleration. For the cases with moderate air pressure, the heaping profile of the granular bed keeps symmetrical in the whole periodic segregation. The symmetrical shape of the upper surface of the granular bed in the eruption stage, which resembles a miniature volcanic eruption, could be described by the Mogi model that illuminates the genuine volcanic eruption in the geography. When the air pressure increases, an asymmetrical heaping profile is observed in the eruption stage of periodic segregation. With using the image processing technique, we estimate a relative height difference between the copper and the alumina particles as the order parameter to quantitatively characterize the evolution of periodic segregation. Both eruption and percolation time, extracted from the order parameter, are plotted as a function of the vibration strength. Finally, we briefly discuss the air effect on the granular segregation behaviors. Scientific Reports 4 doi: 10.1038/srep06914

Description: Daniell cell (i.e. Zn-Cu battery) is widely used in chemistry curricula to illustrate how batteries work, although it has been supplanted in the late 19th century by more modern battery designs because of Cu2+-crossover-induced self-discharge and un-rechargeable characteristic. Herein, it is re-built by using a ceramic Li-ion exchange film to separate Cu and Zn electrodes for preventing Cu2+-crossover between two electrodes. The re-built Zn-Cu battery can be cycled for 150 times without capacity attenuation and self-discharge, and displays a theoretical energy density of 68.3 Wh kg−1. It is more important that both electrodes of the battery are renewable, reusable, low toxicity and environmentally friendly. Owing to these advantages mentioned above, the re-built Daniell cell can be considered as a promising and green stationary power source for large-scale energy storage. Scientific Reports 4 doi: 10.1038/srep06916

Description: The growth of transportation networks and their increasing interconnections, although positive, has the downside effect of an increasing complexity which make them difficult to use, to assess, and limits their efficiency. On average in the UK, 23% of travel time is lost in connections for trips with more than one mode, and the lack of synchronization decreases very slowly with population size. This lack of synchronization between modes induces differences between the theoretical quickest trip and the ‘time-respecting’ path, which takes into account waiting times at interconnection nodes. We analyse here the statistics of these paths on the multilayer, temporal network of the entire, multimodal british public transportation system. We propose a statistical decomposition – the ‘anatomy’ – of trips in urban areas, in terms of riding, waiting and walking times, and which shows how the temporal structure of trips varies with distance and allows us to compare different cities. Weaknesses in systems can be either insufficient transportation speed or service frequency, but the key parameter controlling their global efficiency is the total number of stop events per hour for all modes. This analysis suggests the need for better optimization strategies, adapted to short, long unimodal or multimodal trips. Scientific Reports 4 doi: 10.1038/srep06911

Description: Nanodiamond (ND) has emerged as a promising carbon nanomaterial for therapeutic applications. In previous studies, ND has been reported to have outstanding biocompatibility and high uptake rate in various cell types. ND containing nitrogen-vacancy centers exhibit fluorescence property is called fluorescent nanodiamond (FND), and has been applied for bio-labeling agent. However, the influence and application of FND on the nervous system remain elusive. In order to study the compatibility of FND on the nervous system, neurons treated with FNDs in vitro and in vivo were examined. FND did not induce cytotoxicity in primary neurons from either central (CNS) or peripheral nervous system (PNS); neither did intracranial injection of FND affect animal behavior. The neuronal uptake of FNDs was confirmed using flow cytometry and confocal microscopy. However, FND caused a concentration-dependent decrease in neurite length in both CNS and PNS neurons. Time-lapse live cell imaging showed that the reduction of neurite length was due to the spatial hindrance of FND on advancing axonal growth cone. These findings demonstrate that FNDs exhibit low neuronal toxicity but interfere with neuronal morphogenesis, and should be taken into consideration when applications involve actively growing neurites (e.g. nerve regeneration). Scientific Reports 4 doi: 10.1038/srep06919

Description: Citric acid-based polymer/hydroxyapatite composites (CABP-HAs) are a novel class of biomimetic composites that have recently attracted significant attention in tissue engineering. The objective of this study was to compare the efficacy of using two different CABP-HAs, poly (1,8-octanediol citrate)-click-HA (POC-Click-HA) and crosslinked urethane-doped polyester-HA (CUPE-HA) as an alternative to autologous tissue grafts in the repair of skeletal defects. CABP-HA disc-shaped scaffolds (65 wt.-% HA with 70% porosity) were used as bare implants without the addition of growth factors or cells to renovate 4 mm diameter rat calvarial defects (n = 72, n = 18 per group). Defects were either left empty (negative control group), or treated with CUPE-HA scaffolds, POC-Click-HA scaffolds, or autologous bone grafts (AB group). Radiological and histological data showed a significant enhancement of osteogenesis in defects treated with CUPE-HA scaffolds when compared to POC-Click-HA scaffolds. Both, POC-Click-HA and CUPE-HA scaffolds, resulted in enhanced bone mineral density, trabecular thickness, and angiogenesis when compared to the control groups at 1, 3, and 6 months post-trauma. These results show the potential of CABP-HA bare implants as biocompatible, osteogenic, and off-shelf-available options in the repair of orthopedic defects. Scientific Reports 4 doi: 10.1038/srep06912

Description: A large-scale effort was carried out to test the performance of seven types of ionic electroactive polymer (IEAP) actuators in space-hazardous environmental factors in laboratory conditions. The results substantiate that the IEAP materials are tolerant to long-term freezing and vacuum environments as well as ionizing Gamma-, X-ray, and UV radiation at the levels corresponding to low Earth orbit (LEO) conditions. The main aim of this material behaviour investigation is to understand and predict device service time for prolonged exposure to space environment. Scientific Reports 4 doi: 10.1038/srep06913

Description: MoS2 is a layered two-dimensional material with strong spin-orbit coupling and long spin lifetime, which is promising for electronic and spintronic applications. However, because of its large band gap and small electron affinity, a considerable Schottky barrier exists between MoS2 and contact metal, hindering the further study of spin transport and spin injection in MoS2. Although substantial progress has been made in improving device performance, the existence of metal-semiconductor Schottky barrier has not yet been fully understood. Here, we investigate permalloy (Py) contacts to both multilayer and monolayer MoS2. Ohmic contact is developed between multilayer MoS2 and Py electrodes with a negative Schottky barrier, which yields a high field-effect mobility exceeding 55 cm2V−1s−1 at low temperature. Further, by applying back gate voltage and inserting different thickness of Al2O3 layer between the metal and monolayer MoS2, we have achieved a good tunability of the Schottky barrier height (down to zero). These results are important in improving the performance of MoS2 transistor devices; and it may pave the way to realize spin transport and spin injection in MoS2. Scientific Reports 4 doi: 10.1038/srep06928

Description: The size dependence of the quantized energies of elementary excitations is an essential feature of quantum nanostructures, underlying most of their applications in science and technology. Here we report on a fundamental property of impurity states in semiconductor nanocrystals that appears to have been overlooked—the anticrossing of energy levels exhibiting different size dependencies. We show that this property is inherent to the energy spectra of charge carriers whose spatial motion is simultaneously affected by the Coulomb potential of the impurity ion and the confining potential of the nanocrystal. The coupling of impurity states, which leads to the anticrossing, can be induced by interactions with elementary excitations residing inside the nanocrystal or an external electromagnetic field. We formulate physical conditions that allow a straightforward interpretation of level anticrossings in the nanocrystal energy spectrum and an accurate estimation of the states' coupling strength. Scientific Reports 4 doi: 10.1038/srep06917

Description: Animals are known to select mates to maximize the genetic diversity of their offspring in order to achieve immunity against a broader range of pathogens. Although several bird species preferentially mate with partners that are dissimilar at the major histocompatibility complex (MHC), it remains unknown whether they can use olfactory cues to assess MHC similarity with potential partners. Here we combined gas chromatography data with genetic similarity indices based on MHC to test whether similarity in preen secretion chemicals correlated with MHC relatedness in the black-legged kittiwake (Rissa tridactyla), a species that preferentially mates with genetically dissimilar partners. We found that similarity in preen secretion chemicals was positively correlated with MHC relatedness in male-male and male-female dyads. This study provides the first evidence that preen secretion chemicals can encode information on MHC relatedness and suggests that odor-based mechanisms of MHC-related mate choice may occur in birds. Scientific Reports 4 doi: 10.1038/srep06920

Description: We propose a method to control electromagnetic (EM) radiations by holographic metasurfaces, including to producing multi-beam scanning in one dimension (1D) and two dimensions (2D) with the change of frequency. The metasurfaces are composed of subwavelength metallic patches on grounded dielectric substrate. We present a combined theory of holography and leaky wave to realize the multi-beam radiations by exciting the surface interference patterns, which are generated by interference between the excitation source and required radiation waves. As the frequency changes, we show that the main lobes of EM radiation beams could accomplish 1D or 2D scans regularly by using the proposed holographic metasurfaces shaped with different interference patterns. This is the first time to realize 2D scans of antennas by changing the frequency. Full-wave simulations and experimental results validate the proposed theory and confirm the corresponding physical phenomena. Scientific Reports 4 doi: 10.1038/srep06921

Description: A new method of finely temperature-tuning osmotic pressure allows one to identify the cholesteric → line hexatic transition of oriented or unoriented long-fragment DNA bundles in monovalent salt solutions as first order, with a small but finite volume discontinuity. This transition is similar to the osmotic pressure-induced expanded → condensed DNA transition in polyvalent salt solutions at small enough polyvalent salt concentrations. Therefore there exists a continuity of states between the two. This finding, together with the corresponding empirical equation of state, effectively relates the phase diagram of DNA solutions for monovalent salts to that for polyvalent salts and sheds some light on the complicated interactions between DNA molecules at high densities. Scientific Reports 4 doi: 10.1038/srep06877

Description: E-cadherin belongs to the classic cadherin subfamily of calcium-dependent cell adhesion molecules and is crucial for the formation and function of epithelial adherens junctions. In this study, we demonstrate that Vangl2, a vertebrate regulator of planar cell polarity (PCP), controls E-cadherin in epithelial cells. E-cadherin co-immunoprecipitates with Vangl2 from embryonic kidney extracts, and this association is also observed in transfected fibroblasts. Vangl2 enhances the internalization of E-cadherin when overexpressed. Conversely, the quantitative ratio of E-cadherin exposed to the cell surface is increased in cultured renal epithelial cells derived from Vangl2Lpt/+ mutant mice. Interestingly, Vangl2 is also internalized through protein traffic involving Rab5- and Dynamin-dependent endocytosis. Taken together with recent reports regarding the transport of Frizzled3, MMP14 and nephrin, these results suggest that one of the molecular functions of Vangl2 is to enhance the internalization of specific plasma membrane proteins with broad selectivity. This function may be involved in the control of intercellular PCP signalling or in the PCP-related rearrangement of cell adhesions. Scientific Reports 4 doi: 10.1038/srep06940

Description: Autosomal dominant optic atrophy (ADOA) is the most frequent form of hereditary optic neuropathy and occurs due to the degeneration of the retinal ganglion cells. To identify the genetic defect in a family with putative ADOA, we performed capture next generation sequencing (CNGS) to screen known retinal disease genes. However, six exons failed to be sequenced by CNGS in optic atrophy 1 gene (OPA1). Sequencing of those exons identified a 4 bp deletion mutation (c.2983-1_2985del) in OPA1. Furthermore, we sequenced the transcripts of OPA1 from the patient skin fibroblasts and found there is six-nucleotide deletion (c.2984-c.2989, AGAAAG). Quantitative-PCR and Western blotting showed that OPA1 mRNA and its protein expression have no obvious difference between patient skin fibroblast and control. The analysis of protein structure by molecular modeling suggests that the mutation may change the structure of OPA1 by formation of an alpha helix protruding into an existing pocket. Taken together, we identified an OPA1 mutation in a family with ADOA by filling the missing CNGS data. We also showed that this mutation affects the structural intactness of OPA1. It provides molecular insights for clinical genetic diagnosis and treatment of optic atrophy. Scientific Reports 4 doi: 10.1038/srep06936

Description: Ebola virus (EBOV) causes severe viral hemorrhagic fever in humans and non-human primates, with a case fatality rate of up to 88% in human outbreaks. Over the past 3 years, monoclonal antibody (mAb) cocktails have demonstrated high efficacy as treatments against EBOV infection. One such cocktail is ZMAb, which consists of three mouse antibodies, 1H3, 2G4, and 4G7. Here, we present the epitope binding properties of mAbs 1H3, 2G4, and 4G7. We showed that these antibodies have different variable region sequences, suggesting that the individual mAbs are not clonally related. All three antibodies were found to neutralize EBOV variant Mayinga. Additionally, 2G4 and 4G7 were shown to cross-inhibit each other in vitro and select for an escape mutation at the same position on the EBOV glycoprotein (GP), at amino acid 508. 1H3 selects an escape mutant at amino acid 273 on EBOV GP. Surface plasmon resonance studies showed that all three antibodies have dissociation constants on the order of 10−7. In combination with previous studies evaluating the binding sites of other protective antibodies, our results suggest that antibodies targeting the GP1-GP2 interface and the glycan cap are often selected as efficacious antibodies for post-exposure interventions against EBOV. Scientific Reports 4 doi: 10.1038/srep06881

Description: The neurotoxin β-N-methylamino-L-alanine (BMAA) produced naturally by cyanobacteria, diatoms and dinoflagellates can be transferred and accumulated up the food chain, and may be a risk factor for neurodegenerative diseases. This study provides the first systematic screening of BMAA exposure of a large population through the consumption of seafood sold in metropolitan markets. BMAA was distinguished from known isomers by liquid chromatography tandem mass spectrometry after acidic hydrolysis and derivatization. Using deuterium-labeled internal standard, BMAA was quantified as 0.01–0.90 μg/g wet weight of tissues in blue mussel, oyster, shrimp, plaice, char and herring, but was undetectable (〈0.01 μg/g) in other samples (salmon, cod, perch and crayfish). Provided that the content of BMAA detected is relevant for intake calculations, the data presented may be used for a first estimation of BMAA exposure through seafood from Swedish markets, and to refine the design of future toxicological experiments and assessments. Scientific Reports 4 doi: 10.1038/srep06931

Description: Endoplasmic reticulum (ER) stress and inappropriate adaptation through the unfolded protein response (UPR) are predominant features of pathological processes. However, little is known about the link between ER stress and endovascular injury. We investigated the involvement of ER stress in neointima hyperplasia after vascular injury. The femoral arteries of 7-8-week-old male mice were subjected to wire-induced vascular injury. After 4 weeks, immunohistological analysis showed that ER stress markers were upregulated in the hyperplastic neointima. Neointima formation was increased by 54.8% in X-box binding protein-1 (XBP1) heterozygous mice, a model of compromised UPR. Knockdown of Xbp1 in human coronary artery smooth muscle cells (CASMC) in vitro promoted cell proliferation and migration. Furthermore, treatment with ER stress reducers, 4-phenylbutyrate (4-PBA) and tauroursodeoxycholic acid (TUDCA), decreased the intima-to-media ratio after wire injury by 50.0% and 72.8%, respectively. Chronic stimulation of CASMC with PDGF-BB activated the UPR, and treatment with 4-PBA and TUDCA significantly suppressed the PDGF-BB-induced ER stress markers in CASMC and the proliferation and migration of CASMC. In conclusion, increased ER stress contributes to neointima formation after vascular injury, while UPR signaling downstream of XBP1 plays a suppressive role. Suppression of ER stress would be a novel strategy against post-angioplasty vascular restenosis. Scientific Reports 4 doi: 10.1038/srep06943

Description: Plants form symbiotic associations with endophytic bacteria within tissues of leaves, stems, and roots. It is unclear whether or how plants obtain nitrogen from these endophytic bacteria. Here we present evidence showing nitrogen flow from endophytic bacteria to plants in a process that appears to involve oxidative degradation of bacteria. In our experiments we employed Agave tequilana and its seed-transmitted endophyte Bacillus tequilensis to elucidate organic nitrogen transfer from 15N-labeled bacteria to plants. Bacillus tequilensis cells grown in a minimal medium with 15NH4Cl as the nitrogen source were watered onto plants growing in sand. We traced incorporation of 15N into tryptophan, deoxynucleosides and pheophytin derived from chlorophyll a. Probes for hydrogen peroxide show its presence during degradation of bacteria in plant tissues, supporting involvement of reactive oxygen in the degradation process. In another experiment to assess nitrogen absorbed as a result of endophytic colonization of plants we demonstrated that endophytic bacteria potentially transfer more nitrogen to plants and stimulate greater biomass in plants than heat-killed bacteria that do not colonize plants but instead degrade in the soil. Findings presented here support the hypothesis that some plants under nutrient limitation may degrade and obtain nitrogen from endophytic microbes. Scientific Reports 4 doi: 10.1038/srep06938

Description: We study localized photonic excitations in a quasi-two-dimensional non-ideal binary microcavity lattice with use of the virtual crystal approximation. The effect of point defects (vacancies) on the excitation spectrum is investigated by numerical modelling. We obtain the dispersion and the energy gap of the electromagnetic excitations which may be considered as Frenkel exciton-like quasiparticles and analyze the dependence of their density of states on the defect concentrations in a microcavity supercrystal. Scientific Reports 4 doi: 10.1038/srep06945

Description: As an important method for building blocks synthesis, whole cell biocatalysis is hindered by some shortcomings such as unpredictability of reactions, utilization of opportunistic pathogen, and side reactions. Due to its biological and extensively studied genetic background, Pseudomonas putida KT2440 is viewed as a promising host for construction of efficient biocatalysts. After analysis and reconstruction of the lactate utilization system in the P. putida strain, a novel biocatalyst that only exhibited NAD-independent d-lactate dehydrogenase activity was prepared and used in l-2-hydroxy-carboxylates production. Since the side reaction catalyzed by the NAD-independent l-lactate dehydrogenase was eliminated in whole cells of recombinant P. putida KT2440, two important l-2-hydroxy-carboxylates (l-lactate and l-2-hydroxybutyrate) were produced in high yield and high optical purity by kinetic resolution of racemic 2-hydroxy carboxylic acids. The results highlight the promise in biocatalysis by the biotechnologically important organism P. putida KT2440 through genomic analysis and recombination. Scientific Reports 4 doi: 10.1038/srep06939

Description: Although it is recognized that the abnormal accumulation of amino acid is a cause of the symptoms in metabolic disease such as phenylketonuria (PKU), the relationship between disease severity and serum amino acid levels is not well understood due to the lack of experimental model. Here, we present a novel in vitro cellular model using K562-D cells that proliferate slowly in the presence of excessive amount of phenylalanine within the clinically observed range, but not phenylpyruvate. The increased expression of the L-type amino acid transporter (LAT2) and its adapter protein 4F2 heavy chain appeared to be responsible for the higher sensitivity to phenylalanine in K562-D cells. Supplementation with valine over phenylalanine effectively restored cell proliferation, although other amino acids did not improve K562-D cell proliferation over phenylalanine. Biochemical analysis revealed mammalian target of rapamycin complex (mTORC) as a terminal target of phenylalanine in K562-D cell proliferation, and supplementation of valine restored mTORC1 activity. Our results show that K562-D cell can be a potent tool for the investigation of PKU at the molecular level and to explore new therapeutic approaches to the disease. Scientific Reports 4 doi: 10.1038/srep06941

Description: In the present work electrically conductive, flexible, lightweight carbon sponge materials derived from open-pore structure melamine foams are studied and explored. Hydrophobic and hydrophilic surface properties - depending on the chosen treatment conditions - allow the separation and storage of liquid chemical compounds. Activation of the carbonaceous structures substantially increases the specific surface area from ~4 m2g−1 to ~345 m2g−1, while retaining the original three-dimensional, open-pore structure suitable for hosting, for example, Ni catalyst nanoparticles. In turn the structure is rendered suitable for hydrogenating acetone to 2-propanol and methyl isobutyl ketone as well for growing hierarchical carbon nanotube structures used as electric double-layer capacitor electrodes with specific capacitance of ~40 F/g. Mechanical stress-strain analysis indicates the materials are super-compressible (〉70% volume reduction) and viscoelastic with excellent damping behavior (loss of 0.69 ± 0.07), while piezoresistive measurements show very high gauge factors (from ~20 to 50) over a large range of deformations. The cost-effective, robust and scalable synthesis - in conjunction with their fascinating multifunctional utility - makes the demonstrated carbon foams remarkable competitors with other three-dimensional carbon materials typically based on pyrolyzed biopolymers or on covalently bonded graphene and carbon nanotube frameworks. Scientific Reports 4 doi: 10.1038/srep06933

Description: Cytotoxic T lymphocyte-associated antigen 4 immunoglobulin fusion protein (CTLA4Ig, abatacept) is a B7/CD28 costimulation inhibitor that can ward off the immune response by preventing the activation of naïve T cells. This therapeutic agent is administered to patients with autoimmune diseases such as rheumatoid arthritis. Its antiarthritic efficacy is satisfactory, but the limitations are the necessity for frequent injection and high cost. Minicircles can robustly express the target molecule and excrete it outside the cell as an indirect method to produce the protein of interest in vivo. We inserted the sequence of abatacept into the minicircle vector, and by successful in vivo injection the host was able to produce the synthetic protein drug. Intravenous infusion of the minicircle induced spontaneous production of CTLA4Ig in mice with collagen-induced arthritis. Self-produced CTLA4Ig significantly decreased the symptoms of arthritis. Injection of minicircle CTLA4Ig regulated Foxp3+ T cells and Th17 cells. Parental and mock vectors did not ameliorate arthritis or modify the T cell population. We have developed a new concept of spontaneous protein drug delivery using a minicircle vector. Self in vivo production of a synthetic protein drug may be useful when biological drugs cannot be injected because of manufacturing or practical problems. Scientific Reports 4 doi: 10.1038/srep06935

Description: Conventional myeloablative conditioning (MAC) regimens often cause severe regimen-related toxicity (RRT). Furthermore, many patients suffer from poor quality of life in accordance with the increase in long-term survivors. We therefore devised a reduced-toxicity myeloablative conditioning (RTMAC) regimen consisting of 8-Gy total body irradiation (TBI), fludarabine (FLU) and cyclophosphamide (CY) for pediatric hematological malignancies. A retrospective single-center analysis was performed on patients with leukemia or myelodysplastic syndrome (MDS), aged ≤20 years, who had received an 8-Gy TBI/FLU/CY RTMAC regimen followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Thirty-one patients underwent first allo-HSCT after an RTMAC regimen. The diagnoses were acute lymphoblastic leukemia (n = 11), acute myeloid leukemia (n = 13), MDS (n = 4), juvenile myelomonocytic leukemia (n = 1) and acute leukemias of ambiguous lineage (n = 2). While 3 patients showed early hematological relapse, the remaining 28 patients achieved engraftments. None of the patients developed grade 4 or 5 toxicities during the study period. The 5-year overall survival and relapse-free survival were 80% [95% confidence interval: CI, 61–91%] and 71% [95% CI, 52–84%], respectively. Our RTMAC regimen would be less toxic and offers a high probability of survival for children with hematological malignancies. Scientific Reports 4 doi: 10.1038/srep06942

Description: A previous study documented a glycine to glutamic acid mutation (G4946E) in ryanodine receptor (RyR) was highly correlated to diamide insecticide resistance in field populations of Plutella xylostella (Lepidoptera: Plutellidae). In this study, a field population collected in Yunnan province, China, exhibited a 2128-fold resistance to chlorantraniliprole. Sequence comparison between resistant and susceptible P. xylostella revealed three novel mutations including a glutamic acid to valine substitution (E1338D), a glutamine to leucine substitution (Q4594L) and an isoleucine to methionine substitution (I4790M) in highly conserved regions of RyR. Frequency analysis of all four mutations in this field population showed that the three new mutations showed a high frequency of 100%, while the G4946E had a frequency of 20%. Furthermore, the florescent ligand binding assay revealed that the RyR containing multiple mutations displayed a significantly lower affinity to the chlorantraniliprole. The combined results suggested that the co-existence of different combinations of the four mutations was involved in the chlorantraniliprole resistance. An allele-specific PCR based method was developed for the diagnosis of the four mutations in the field populations of P. xylostella. Scientific Reports 4 doi: 10.1038/srep06924

Description: The accuracy of axonal pathfinding and the formation of functional neural circuitry are crucial for an organism to process, store, and retrieve information from internal networks as well as from the environment. Aberrations in axonal migration is believed to lead to loop formation and self-fasciculation, which can lead to highly dysfunctional neural circuitry and therefore self-avoidance of axons is proposed to be the regulatory mechanism for control of synaptogenesis. Here, we report the application of a newly developed non-contact optical method using a weakly-focused, near infrared laser beam for highly efficient axonal guidance, and demonstrate the formation of axonal loops in cortical neurons, which demonstrate that cortical neurons can self-fasciculate in contrast to self-avoidance. The ability of light for axonal nano-loop formation opens up new avenues for the construction of complex neural circuitry, and non-invasive guidance of neurons at long working distances for restoration of impaired neural connections and functions. Scientific Reports 4 doi: 10.1038/srep06902

Description: Cells sense and interpret mechanical cues, including cell-cell and cell-substrate interactions, in the microenvironment to collectively regulate various physiological functions. Understanding the influences of these mechanical factors on cell behavior is critical for fundamental cell biology and for the development of novel strategies in regenerative medicine. Here, we demonstrate plasma lithography patterning on elastomeric substrates for elucidating the influences of mechanical cues on neuronal differentiation and neuritogenesis. The neuroblastoma cells form neuronal spheres on plasma-treated regions, which geometrically confine the cells over two weeks. The elastic modulus of the elastomer is controlled simultaneously by the crosslinker concentration. The cell-substrate mechanical interactions are also investigated by controlling the size of neuronal spheres with different cell seeding densities. These physical cues are shown to modulate with the formation of focal adhesions, neurite outgrowth, and the morphology of neuroblastoma. By systematic adjustment of these cues, along with computational biomechanical analysis, we demonstrate the interrelated mechanoregulatory effects of substrate elasticity and cell size. Taken together, our results reveal that the neuronal differentiation and neuritogenesis of neuroblastoma cells are collectively regulated via the cell-substrate mechanical interactions. Scientific Reports 4 doi: 10.1038/srep06965

Description: Perovskite solar cells (PeSCs) have been considered one of the competitive next generation power sources. To date, light-to-electric conversion efficiencies have rapidly increased to over 10%, and further improvements are expected. However, the poor device reproducibility of PeSCs ascribed to their inhomogeneously covered film morphology has hindered their practical application. Here, we demonstrate high-performance PeSCs with superior reproducibility by introducing small amounts of N-cyclohexyl-2-pyrrolidone (CHP) as a morphology controller into N,N-dimethylformamide (DMF). As a result, highly homogeneous film morphology, similar to that achieved by vacuum-deposition methods, as well as a high PCE of 10% and an extremely small performance deviation within 0.14% were achieved. This study represents a method for realizing efficient and reproducible planar heterojunction (PHJ) PeSCs through morphology control, taking a major step forward in the low-cost and rapid production of PeSCs by solving one of the biggest problems of PHJ perovskite photovoltaic technology through a facile method. Scientific Reports 4 doi: 10.1038/srep06953

Description: Propionic acid (PA) is an important platform chemical in the food, agriculture, and pharmaceutical industries and is mainly biosynthesized by propionibacteria. Acid tolerance in PA-producing strains is crucial. In previous work, we investigated the acid tolerance mechanism of Propionibacterium acidipropionici at microenvironmental levels by analyzing physiological changes in the parental strain and three PA-tolerant mutants obtained by genome shuffling. However, the molecular mechanism of PA tolerance in P. acidipropionici remained unclear. Here, we performed a comparative proteomics study of P. acidipropionici CGMCC 1.2230 and the acid-tolerant mutant P. acidipropionici WSH1105; MALDI-TOF/MS identified 24 proteins that significantly differed between the parental and shuffled strains. The differentially expressed proteins were mainly categorized as key components of crucial biological processes and the acid stress response. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to confirm differential expression of nine key proteins. Overexpression of the secretory protein glyceraldehyde-3-phosphate dehydrogenase and ATP synthase subunit α in Escherichia coli BL21 improved PA and acetic acid tolerance; overexpression of NADH dehydrogenase and methylmalonyl-CoA epimerase improved PA tolerance. These results provide new insights into the acid tolerance of P. acidipropionici and will facilitate the development of PA production through fermentation by propionibacteria. Scientific Reports 4 doi: 10.1038/srep06951

Description: Electronic band structures in semiconductors are uniquely determined by the constituent elements of the lattice. For example, bulk silicon has an indirect bandgap and it prohibits efficient light emission. Here we report the electrical tuning of the direct/indirect band optical transition in an ultrathin silicon-on-insulator (SOI) gated metal-oxide-semiconductor (MOS) light-emitting diode. A special Si/SiO2 interface formed by high-temperature annealing that shows stronger valley coupling enables us to observe phononless direct optical transition. Furthermore, by controlling the gate field, its strength can be electrically tuned to 16 times that of the indirect transition, which is nearly 800 times larger than the weak direct transition in bulk silicon. These results will therefore assist the development of both complementary MOS (CMOS)-compatible silicon photonics and the emerging “valleytronics” based on the control of the valley degree of freedom. Scientific Reports 4 doi: 10.1038/srep06950

Description: To date, numerous analytical methods have been developed to monitor phospholipase A2 (PLA2) activity. However, many of these methods require the use of unnatural PLA2 substrates that may alter enzyme kinetics, and probes that cannot be extended to applications in more complex environments. It would be desirable to develop a versatile assay that monitors PLA2 activity based on interactions with natural phospholipids in complex biological samples. Here, we developed an activatable T1 magnetic resonance (MR) imaging contrast agent to monitor PLA2 activity. Specifically, the clinically approved gadolinium (Gd)-based MR contrast agent, gadoteridol, was encapsulated within nanometer-sized phospholipid liposomes. The encapsulated Gd exhibited a low T1-weighted signal, due to low membrane permeability. However, when the phospholipids within the liposomal membrane were hydrolyzed by PLA2, encapsulated Gd was released into bulk solution, resulting in a measureable change in the T1-relaxation time. These activatable MR contrast agents can potentially be used as nanosensors for monitoring of PLA2 activity in biological samples with minimal sample preparation. Scientific Reports 4 doi: 10.1038/srep06958

Description: Interaction between monomer peptides and seeds is essential for clarifying the fibrillation mechanism of amyloid β (Aβ) peptides. We monitored the deposition reaction of Aβ1–40 peptides on immobilized seeds grown from Aβ1–42, which caused formation of oligomers in the early stage. The deposition reaction and fibrillation procedure were monitored throughout by novel total-internal-reflection-fluorescence microscopy with a quartz-crystal microbalance (TIRFM-QCM) system. This system allows simultaneous evaluation of the amount of deposited peptides on the surface seeds by QCM and fibril nucleation and elongation by TIRFM. Most fibrils reached other nuclei, forming the fibril network across the nucleus hubs in a short time. We found a fibril-elongation rate two-orders-of-magnitude higher in an oligomeric cloud than reported values, indicating ultrafast transition of oligomers into fibrils. Scientific Reports 4 doi: 10.1038/srep06960

Description: Mutations in the mitochondrial Ser/Thr kinase PINK1 cause Parkinson's disease. One of the substrates of PINK1 is the outer mitochondrial membrane protein Miro, which regulates mitochondrial transport. In this study, we uncovered novel physiological functions of PINK1-mediated phosphorylation of Miro, using Drosophila as a model. We replaced endogenous Drosophila Miro (DMiro) with transgenically expressed wildtype, or mutant DMiro predicted to resist PINK1-mediated phosphorylation. We found that the expression of phospho-resistant DMiro in a DMiro null mutant background phenocopied a subset of phenotypes of PINK1 null. Specifically, phospho-resistant DMiro increased mitochondrial movement and synaptic growth at larval neuromuscular junctions, and decreased the number of dopaminergic neurons in adult brains. Therefore, PINK1 may inhibit synaptic growth and protect dopaminergic neurons by phosphorylating DMiro. Furthermore, muscle degeneration, swollen mitochondria and locomotor defects found in PINK1 null flies were not observed in phospho-resistant DMiro flies. Thus, our study established an in vivo platform to define functional consequences of PINK1-mediated phosphorylation of its substrates. Scientific Reports 4 doi: 10.1038/srep06962

Description: Currently there is an explosive increase of the next-generation sequencing (NGS) projects and related datasets, which have to be processed by Quality Control (QC) procedures before they could be utilized for omics analysis. QC procedure usually includes identification and filtration of sequencing artifacts such as low-quality reads and contaminating reads, which would significantly affect and sometimes mislead downstream analysis. Quality control of NGS data for microbial communities is especially challenging. In this work, we have evaluated and compared the performance and effects of various QC pipelines on different types of metagenomic NGS data and from different angles, based on which general principles of using QC pipelines were proposed. Results based on both simulated and real metagenomic datasets have shown that: firstly, QC-Chain is superior in its ability for contamination identification for metagenomic NGS datasets with different complexities with high sensitivity and specificity. Secondly, the high performance computing engine enabled QC-Chain to achieve a significant reduction in processing time compared to other pipelines based on serial computing. Thirdly, QC-Chain could outperform other tools in benefiting downstream metagenomic data analysis. Scientific Reports 4 doi: 10.1038/srep06957

Description: Rab2A, a small GTPase localizing to the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC), regulates COPI-dependent vesicular transport from the ERGIC. Rab2A knockdown inhibited glucose-stimulated insulin secretion and concomitantly enlarged the ERGIC in insulin-secreting cells. Large aggregates of polyubiquitinated proinsulin accumulated in the cytoplasmic vicinity of a unique large spheroidal ERGIC, designated the LUb-ERGIC. Well-known components of ER-associated degradation (ERAD) also accumulated at the LUb-ERGIC, creating a suitable site for ERAD-mediated protein quality control. Moreover, chronically high glucose levels, which induced the enlargement of the LUb-ERGIC and ubiquitinated protein aggregates, impaired Rab2A activity by promoting dissociation from its effector, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in response to poly (ADP-ribosyl)ation of GAPDH. The inactivation of Rab2A relieved glucose-induced ER stress and inhibited ER stress-induced apoptosis. Collectively, these results suggest that Rab2A is a pivotal switch that controls whether insulin should be secreted or degraded at the LUb-ERGIC and Rab2A inactivation ensures alleviation of ER stress and cell survival under chronic glucotoxicity. Scientific Reports 4 doi: 10.1038/srep06952

Description: Nitric oxide (NO) is one of the most important immune molecules in innate immunity of invertebrates, and it can be regulated by norepinephrine in ascidian haemocytes. In the present study, the mutual modulation and underlying mechanism between norepinephrine and NO were explored in haemocytes of the scallop Chlamys farreri. After lipopolysaccharide stimulation, NO production increased to a significant level at 24 h, and norepinephrine concentration rose to remarkable levels at 3 h and 12~48 h. A significant decrease of NO production was observed in the haemocytes concomitantly stimulated with lipopolysaccharide and α-adrenoceptor agonist, while a dramatic increase of NO production was observed in the haemocytes incubated with lipopolysaccharide and β-adrenoceptor agonist. Meanwhile, the concentration of cyclic adenosine monophosphate (cAMP) decreased significantly in the haemocytes treated by lipopolysaccharide and α/β-adrenoceptor agonist, while the content of Ca2+ was elevated in those triggered by lipopolysaccharide and β-adrenoceptor agonist. When the haemocytes was incubated with NO donor, norepinephrine concentration was significantly enhanced during 1~24 h. Collectively, these results suggested that norepinephrine exerted varied effects on NO production at different immune stages via a novel α/β-adrenoceptor-cAMP/Ca2+ regulatory pattern, and NO might have a feedback effect on the synthesis of norepinephrine in the scallop haemocytes. Scientific Reports 4 doi: 10.1038/srep06963

Description: Quantum correlations can be stronger than anything achieved by classical systems, yet they are not reaching the limit imposed by relativity. The principle of information causality offers a possible explanation for why the world is quantum and why there appear to be no even stronger correlations. Generalizing the no-signaling condition it suggests that the amount of accessible information must not be larger than the amount of transmitted information. Here we study this principle experimentally in the classical, quantum and post-quantum regimes. We simulate correlations that are stronger than allowed by quantum mechanics by exploiting the effect of polarization-dependent loss in a photonic Bell-test experiment. Our method also applies to other fundamental principles and our results highlight the special importance of anisotropic regions of the no-signalling polytope in the study of fundamental principles. Scientific Reports 4 doi: 10.1038/srep06955

Description: Wnt/β-catenin signalling regulates numerous developmental and homeostatic processes. Ctnnb1 (also known as β-catenin) is the only protein that transmits signals from various Wnt ligands to downstream genes. In this study, we report that our newly established mouse strain, which harbours a Cys429 to Ser missense mutation in the β-catenin gene, exhibited specific organ defects in contrast to mice with broadly functioning Wnt/β-catenin signalling. Both homozygous mutant males and females produced normal gametes but were infertile because of abnormal seminal vesicle and vaginal morphogenesis. An ins-TOPGAL transgenic reporter spatiotemporally sustained Wnt/β-catenin signalling during the corresponding organogenesis. Therefore, β-cateninC429S should provide new insights into β-catenin as a universal component of Wnt/β-catenin signal transduction. Scientific Reports 4 doi: 10.1038/srep06959

Description: We propose a series of icosahedral matryoshka clusters of A@B12@A20 (A = Sn, Pb; B = Mg, Zn, Cd), which possess large HOMO-LUMO gaps (1.29 to 1.54 eV) and low formation energies (0.06 to 0.21 eV/atom). A global minimum search using a genetic algorithm and density functional theory calculations confirms that such onion-like three-shell structures are the ground states for these A21B12 binary clusters. All of these icosahedral matryoshka clusters, including two previously found ones, i.e., [As@Ni12@As20]3− and [Sn@Cu12@Sn20]12−, follow the 108-electron rule, which originates from the high Ih symmetry and consequently the splitting of superatom orbitals of high angular momentum. More interestingly, two magnetic matryoshka clusters, i.e., Sn@Mn12@Sn20 and Pb@Mn12@Pb20, are designed, which combine a large magnetic moment of 28 µB, a moderate HOMO-LUMO gap, and weak inter-cluster interaction energy, making them ideal building blocks in novel magnetic materials and devices. Scientific Reports 4 doi: 10.1038/srep06915

Description: The innovative design and synthesis of nanofiber based hydro-philic/phobic membranes with a thin hydro-phobic nanofiber layer on the top and a thin hydrophilic nanofiber layer on the bottom of the conventional casted micro-porous layer which opens up a solution for membrane pore wetting and improves the pure water flux in membrane distillation. Scientific Reports 4 doi: 10.1038/srep06949

Description: Cyclins are essential for cell proliferation, the cell cycle and tumorigenesis in all eukaryotes. UbcH10 regulates the degradation of cyclins in a ubiquitin-dependent manner. Here, we report that UbcH10 is likely involved in tumorigenesis. We found that cancer cells exposed to n-acetyl-leu-leu-norleucinal (ALLN) treatment and UbcH10 depletion exhibit a synergistic therapeutic effect. Abundant expression of UbcH10 drives resistance to ALLN-induced cell death, while cells deficient in UbcH10 were susceptible to ALLN-induced cell death. The depletion of UbcH10 hindered tumorigenesis both in vitro and in vivo, as assessed by colony formation, growth curve, soft agar and xenograft assays. These phenotypes were efficiently rescued through the introduction of recombinant UbcH10. In the UbcH10-deficient cells, alterations in the expression of cyclins led to cell cycle changes and subsequently decreases in tumorigenesis. The tumorigenesis of xenograft tumors from UbcH10-deficient cells treated with ALLN was decreased relative to wild-type cells treated with ALLN in nude mice. On the molecular level, we observed that UbcH10 deficiency enhances the activation of caspase 8 and caspase 3 but not caspase 9 to impair cell viability upon ALLN treatment. Collectively, our results suggest that, as an oncogene, UbcH10 is a potential drug target for the treatment of colorectal cancer. Scientific Reports 4 doi: 10.1038/srep06910

Description: Growth of thin crystals on external substrate surfaces by many different methods is a well-known technique, but its extension to inner, enclosed surfaces of large defects in monocrystalline materials has not yet been reported. The literature on thin film growth and defects in materials can be leveraged to fabricate new structures for a variety of applications. Here we show a physical process of nucleation and evolution of nanocrystalline silver inside voids in monocrystalline silicon. We found that the Ag growth is hetero-epitaxial using a coincident site lattice. Alignment of Ag and Si atomic planes is uniformly observed by high resolution transmission electron microscopy and macroscopically by channeling Rutherford backscattering spectrometry. Scientific Reports 4 doi: 10.1038/srep06744

Description: The BMP ligand Dpp, operates as a long range morphogen to control many important functions during Drosophila development from tissue patterning to growth. The BMP signal is transduced intracellularly via C-terminal phosphorylation of the BMP transcription factor Mad, which forms an activity gradient in developing embryonic tissues. Here we show that Cyclin dependent kinase 8 and Shaggy phosphorylate three Mad linker serines. We demonstrate that linker phosphorylations control the peak intensity and range of the BMP signal across rapidly developing embryonic tissues. Shaggy knockdown broadened the range of the BMP-activity gradient and increased high threshold target gene expression in the early embryo, while expression of a Mad linker mutant in the wing disc resulted in enhanced levels of C-terminally phosphorylated Mad, a 30% increase in wing tissue, and elevated BMP target genes. In conclusion, our results describe how Mad linker phosphorylations work to control the peak intensity and range of the BMP signal in rapidly developing Drosophila tissues. Scientific Reports 4 doi: 10.1038/srep06927

Description: Although microbes directly accepting electrons from a cathode have been applied for CO2 reduction to produce multicarbon-compounds, a high electron demand and low product concentration are critical limitations. Alternatively, the utilization of electrons as a co-reducing power during fermentation has been attempted, but there must be exogenous mediators due to the lack of an electroactive heterotroph. Here, we show that Clostridium pasteurianum DSM 525 simultaneously utilizes both cathode and substrate as electron donors through direct electron transfer. In a cathode compartment poised at +0.045 V vs. SHE, a metabolic shift in C. pasteurianum occurs toward NADH-consuming metabolite production such as butanol from glucose (20% shift in terms of NADH consumption) and 1,3-propandiol from glycerol (21% shift in terms of NADH consumption). Notably, a small amount of electron uptake significantly induces NADH-consuming pathways over the stoichiometric contribution of the electrons as reducing equivalents. Our results demonstrate a previously unknown electroactivity and metabolic shift in the biochemical-producing heterotroph, opening up the possibility of efficient and enhanced production of electron-dense metabolites using electricity. Scientific Reports 4 doi: 10.1038/srep06961

Description: Quantum discord is the minimal bipartite resource which is needed for a secure quantum key distribution, being a cryptographic primitive equivalent to non-orthogonality. Its role becomes crucial in device-dependent quantum cryptography, where the presence of preparation and detection noise (inaccessible to all parties) may be so strong to prevent the distribution and distillation of entanglement. The necessity of entanglement is re-affirmed in the stronger scenario of device-independent quantum cryptography, where all sources of noise are ascribed to the eavesdropper. Scientific Reports 4 doi: 10.1038/srep06956

Description: The evolution of cooperation is a hot and challenging topic in the field of evolutionary game theory. Altruistic behavior, as a particular form of cooperation, has been widely studied by the ultimatum game but not by the dictator game, which provides a more elegant way to identify the altruistic component of behaviors. In this paper, the evolutionary dictator game is applied to model the real motivations of altruism. A degree-based regime is utilized to assess the impact of the assignation of roles on evolutionary outcome in populations of heterogeneous structure with two kinds of strategic updating mechanisms, which are based on Darwin's theory of evolution and punctuated equilibrium, respectively. The results show that the evolutionary outcome is affected by the role assignation and that this impact also depends on the strategic updating mechanisms, the function used to evaluate players' success, and the structure of populations. Scientific Reports 4 doi: 10.1038/srep06937

Description: Germanium-based materials and device architectures have recently appeared as exciting material systems for future low-power nanoscale transistors and photonic devices. Heterogeneous integration of germanium (Ge)-based materials on silicon (Si) using large bandgap buffer architectures could enable the monolithic integration of electronics and photonics. In this paper, we report on the heterogeneous integration of device-quality epitaxial Ge on Si using composite AlAs/GaAs large bandgap buffer, grown by molecular beam epitaxy that is suitable for fabricating low-power fin field-effect transistors required for continuing transistor miniaturization. The superior structural quality of the integrated Ge on Si using AlAs/GaAs was demonstrated using high-resolution x-ray diffraction analysis. High-resolution transmission electron microscopy confirmed relaxed Ge with high crystalline quality and a sharp Ge/AlAs heterointerface. X-ray photoelectron spectroscopy demonstrated a large valence band offset at the Ge/AlAs interface, as compared to Ge/GaAs heterostructure, which is a prerequisite for superior carrier confinement. The temperature-dependent electrical transport properties of the n-type Ge layer demonstrated a Hall mobility of 370 cm2/Vs at 290 K and 457 cm2/Vs at 90 K, which suggests epitaxial Ge grown on Si using an AlAs/GaAs buffer architecture would be a promising candidate for next-generation high-performance and energy-efficient fin field-effect transistor applications. Scientific Reports 4 doi: 10.1038/srep06964

Description: Drug addiction is characterized by compulsive drug-taking behaviors and a high propensity to relapse following drug cessation. Drug craving and seeking can increase during a period of abstinence, but this phenomenon is not observed in drug-induced reinstatement models. To investigate the effect of withdrawal on cocaine relapse, rats were exposed to extended-access cocaine self-administration and subjected to either 1 or 30 d of withdrawal. When tested during 12 h unlimited access to cocaine (binge), the duration of the withdrawal did not influence cocaine intake. However, using a histamine punishment procedure that greatly suppresses drug-taking behavior, we demonstrate that longer periods of abstinence from cocaine induce a greater persistence in responding for drug in the face of negative consequences. Scientific Reports 4 doi: 10.1038/srep06876

Description: High-performance ultra-thin oxide layers are required for various next-generation electronic and optical devices. In particular, ultra-thin resistive switching (RS) oxide layers are expected to become fundamental building blocks of three-dimensional high-density non-volatile memory devices. Until now, special deposition techniques have been introduced for realization of high-quality ultra-thin oxide layers. Here, we report that ultra-thin oxide layers with reliable RS behavior can be self-assembled by field-induced oxygen migration (FIOM) at the interface of an oxide-conductor/oxide-insulator or oxide-conductor/metal. The formation via FIOM of an ultra-thin oxide layer with a thickness of approximately 2–5 nm and 2.5% excess oxygen content is demonstrated using cross-sectional transmission electron microscopy and secondary ion mass spectroscopy depth profile. The observed RS behavior, such as the polarity dependent forming process, can be attributed to the formation of an ultra-thin oxide layer. In general, as oxygen ions are mobile in many oxide-conductors, FIOM can be used for the formation of ultra-thin oxide layers with desired properties at the interfaces or surfaces of oxide-conductors in high-performance oxide-based devices. Scientific Reports 4 doi: 10.1038/srep06871

Description: Quantum dynamics of light waves traveling through a time-varying turbulent plasma is investigated via the SU(1,1) Lie algebraic approach. Plasma oscillations that accompany time-dependence of electromagnetic parameters of the plasma are considered. In particular, we assume that the conductivity of plasma involves a sinusoidally varying term in addition to a constant one. Regarding the time behavior of electromagnetic parameters in media, the light fields are modeled as a modified CK (Caldirola-Kanai) oscillator that is more complex than the standard CK oscillator. Diverse quantum properties of the system are analyzed under the consideration of time-dependent characteristics of electromagnetic parameters. Quantum energy of the light waves is derived and compared with the counterpart classical energy. Gaussian wave packet of the field whose probability density oscillates with time like that of classical states is constructed through a choice of suitable initial condition and its quantum behavior is investigated in detail. Our development presented here provides a useful way for analyzing time behavior of quantized light in complex plasma. Scientific Reports 4 doi: 10.1038/srep06880

Description: Atoh1 is a basic helix-loop-helix transcription factor that controls differentiation of hair cells (HCs) in the inner ear and its enhancer region has been used to create several HC-specific mouse lines. We generated a transgenic tetracycline-inducible mouse line (called Atoh1-rtTA) using the Atoh1 enhancer to drive expression of the reverse tetracycline transactivator (rtTA) protein and human placental alkaline phosphatase. Presence of the transgene was confirmed by alkaline phosphatase staining and rtTA activity was measured using two tetracycline operator (TetO) reporter alleles with doxycycline administered between postnatal days 0–3. This characterization of five founder lines demonstrated that Atoh1-rtTA is expressed in the majority of cochlear and utricular HCs. Although the tetracycline-inducible system is thought to produce transient changes in gene expression, reporter positive HCs were still observed at 6 weeks of age. To confirm that Atoh1-rtTA activity was specific to Atoh1-expressing cells, we also analyzed the cerebellum and found rtTA-driven reporter expression in cerebellar granule neuron precursor cells. The Atoh1-rtTA mouse line provides a powerful tool for the field and can be used in combination with other existing Cre recombinase mouse lines to manipulate expression of multiple genes at different times in the same animal. Scientific Reports 4 doi: 10.1038/srep06885

Description: The intrinsic structural disorder dramatically affects the thermal and electronic transport in semiconductors. Although normally considered an ordered compound, the half-Heusler ZrNiSn displays many transport characteristics of a disordered alloy. Similar to the (Zr,Hf)NiSn based solid solutions, the unsubstituted ZrNiSn compound also exhibits charge transport dominated by alloy scattering, as demonstrated in this work. The unexpected charge transport, even in ZrNiSn which is normally considered fully ordered, can be explained by the Ni partially filling interstitial sites in this half-Heusler system. The influence of the disordering and defects in crystal structure on the electron transport process has also been quantitatively analyzed in ZrNiSn1-xSbx with carrier concentration nH ranging from 5.0×1019 to 2.3×1021 cm−3 by changing Sb dopant content. The optimized carrier concentration nH ≈ 3–4×1020 cm−2 results in ZT ≈ 0.8 at 875K. This work suggests that MNiSn (M = Hf, Zr, Ti) and perhaps most other half-Heusler thermoelectric materials should be considered highly disordered especially when trying to understand the electronic and phonon structure and transport features. Scientific Reports 4 doi: 10.1038/srep06888

Description: Scientific Reports 4 doi: 10.1038/srep06897

Description: Clinical inhibitors Darunavir (DRV) and Amprenavir (APV) are less effective on HIV-2 protease (PR2) than on HIV-1 protease (PR1). To identify molecular basis associated with the lower inhibition, molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations were performed to investigate the effectiveness of the PR1 inhibitors DRV and APV against PR1/PR2. The rank of predicted binding free energies agrees with the experimental determined one. Moreover, our results show that two inhibitors bind less strongly to PR2 than to PR1, again in agreement with the experimental findings. The decrease in binding free energies for PR2 relative to PR1 is found to arise from the reduction of the van der Waals interactions induced by the structural adjustment of the triple mutant V32I, I47V and V82I. This result is further supported by the difference between the van der Waals interactions of inhibitors with each residue in PR2 and in PR1. The results from the principle component analysis suggest that inhibitor binding tends to make the flaps of PR2 close and the one of PR1 open. We expect that this study can theoretically provide significant guidance and dynamics information for the design of potent dual inhibitors targeting PR1/PR2. Scientific Reports 4 doi: 10.1038/srep06872

Description: Climate change causes species range shifts and potentially alters biological invasions. The invasion of European earthworm species across northern North America has severe impacts on native ecosystems. Given the long and cold winters in that region that to date supposedly have slowed earthworm invasion, future warming is hypothesized to accelerate earthworm invasions into yet non-invaded regions. Alternatively, warming-induced reductions in soil water content (SWC) can also decrease earthworm performance. We tested these hypotheses in a field warming experiment at two sites in Minnesota, USA by sampling earthworms in closed and open canopy in three temperature treatments in 2010 and 2012. Structural equation modeling revealed that detrimental warming effects on earthworm densities and biomass could indeed be partly explained by warming-induced reductions in SWC. The direction of warming effects depended on the current average SWC: warming had neutral to positive effects at high SWC, whereas the opposite was true at low SWC. Our results suggest that warming limits the invasion of earthworms in northern North America by causing less favorable soil abiotic conditions, unless warming is accompanied by increased and temporally even distributions of rainfall sufficient to offset greater water losses from higher evapotranspiration. Scientific Reports 4 doi: 10.1038/srep06890

Description: This study investigated a typical secondary Betula platyphylla forest in the Ziwuling Mountains, Loess Plateau, China. In the sample plot, the DBH (diameter at breast height) class structure of B. platyphylla was bimodal. Individuals with small and large DBH values were abundant. The DBH structures of Quercus wutaishanica and Pinus tabulaeformis were close to that of the logistic model, thus suggesting the increasing population of these species. B. platyphylla and Populus davidiana showed random spatial distributions at almost all scales. However, Q. wutaishanica and P. tabulaeformis were significantly clumped at small scales. B. platyphylla had a negative spatial relation with Q. wutaishanica at small spatial scales. P. tabulaeformis and Q. wutaishanica showed negative spatial correlations at small scales, but they had positive correlations at large scales. These results suggest that P. tabulaeformis and Q. wutaishanica shared habitat preferences at these scales. In the future, the secondary B. platyphylla forest in the Ziwuling Mountains in the Loess Plateau will probably change into a multi-species mixed forest (Quercus–Pinus mixed forest). Assisted restoration strategies must be employed to improve the regeneration dynamics of the forest in the long term. Scientific Reports 4 doi: 10.1038/srep06873

Description: Reproduction is an important life process in insects; however, few studies have attempted to demonstrate the association between reproductive activity and energy metabolism. To address this problem, we focused on the reproductive changes in Bactrocera dorsalis males. We analyzed B. dorsalis male gene expression profiles during mating (DM), 3 h after mating (A3HM) and 12 h after mating (A12HM). Gene annotation and pathway analyses of differentially expressed genes show that galactose metabolism and the starch and sucrose metabolism pathway activities were significantly higher in A12HM group. Moreover, the maltase D gene was the most strongly up-regulated gene. The D-glucose levels were significantly higher in A12HM group. Maltase D expression level was significantly higher in males reared with sucrose. Body weights of the males reared with D-glucose and sucrose were significantly higher than those of the males reared with yeast extract. We observed more mated males from the groups fed sucrose and D-glucose than from those fed yeast extract. The D-glucose levels in individual males were highest at 18:00 h, when flies exhibit the most active mating behavior. This study shows that the maltase D gene and D-glucose are the critical gene and substrate, respectively, in male B. dorsalis mating process. Scientific Reports 4 doi: 10.1038/srep07489

Description: ZnSe nanospirals including structures with polarity continuation and polarity frustration are simultaneously observed at atomic resolution. Through careful analysis of polarity within each dumbbell based on aberration-corrected high-angle annular-dark-field imaging, polarity continuation across parallel polytype interfaces as well as the surrounding Z-shape faulted dipoles is verified. Moreover, polarity frustration across regions with different stacking sequence, which would lead to accumulations of boundary interface charges in the triangular-shaped mixed regions with potential optoelectronic applications, is carefully studied. Scientific Reports 4 doi: 10.1038/srep07447

Description: Despite a wealth of information on sexual reproduction in scleractinian corals, there are regional gaps in reproductive records. In the Gulf of the Oman in the Arabian Sea, reproductive timing was assessed in four common species of broadcast spawning corals using field surveys of gamete maturity and aquarium observations of spawning activity. The appearance of mature gametes within the same month for Acropora downingi, A. hemprichii, Cyphastrea microphthalma and Platygyra daedalea (≥ 75% of colonies, n = 848) indicated a synchronous and multi-specific spawning season. Based on gamete disappearance and direct observations, spawning predominantly occurred during April in 2013 (75–100% of colonies) and May in 2014 (77–94% of colonies). The difference in spawning months between survey years was most likely explained by sea temperature and the timing of lunar cycles during late-stage gametogenesis. These reproductive records are consistent with a latitudinal gradient in peak broadcast spawning activity at reefs in the northwestern Indian Ocean which occurs early in the year at low latitudes (January to March) and progressively later in the year at mid (March to May) and high (June to September) latitudes. Scientific Reports 4 doi: 10.1038/srep07484

Description: SIRT1, a NAD+ dependent class III deacetylase, takes part in many important biological processes. Previous studies show that SIRT1 is overexpressed in some cancers and plays an essential role in tumorigenesis. However, the association between SIRT1 and colorectal cancer (CRC) is still unclear. We found that many CRC specimens had strong SIRT1 expression, which had an obvious correlation with poor prognosis of CRC patients. Meanwhile, SIRT1 expression had a co-localization with CD133, a current universal marker to characterize colorectal cancer stem cells (CSCs). In vitro studies also revealed that SIRT1 was overexpressed in colorectal CSC-like cells. Moreover, SIRT1 deficiency decreased percentage of CD133+ cells, attenuated the abilities of colony and sphere formation, and inhibited tumorigenicity in vivo in CRC cells. Further study demonstrated that the expressions of several stemness-associated genes, including Oct4, Nanog, Cripto, Tert and Lin28, were reduced by SIRT1 knockdown in CRC cells. Taken together, our findings suggest that SIRT1 plays a crucial role in keeping the characteristics of CSCs cells. SIRT1 is a potential independent prognostic factor of CRC patients after tumor resection with curative intent, and will contribute to providing a promising new approach to target at CSCs in CRC treatment. Scientific Reports 4 doi: 10.1038/srep07481

Description: Evolutionary dynamical models for cyclic competitions of three species (e.g., rock, paper, and scissors, or RPS) provide a paradigm, at the microscopic level of individual interactions, to address many issues in coexistence and biodiversity. Real ecosystems often involve competitions among more than three species. By extending the RPS game model to five (rock-paper-scissors-lizard-Spock, or RPSLS) mobile species, we uncover a fundamental type of mesoscopic interactions among subgroups of species. In particular, competitions at the microscopic level lead to the emergence of various local groups in different regions of the space, each involving three species. It is the interactions among the groups that fundamentally determine how many species can coexist. In fact, as the mobility is increased from zero, two transitions can occur: one from a five- to a three-species coexistence state and another from the latter to a uniform, single-species state. We develop a mean-field theory to show that, in order to understand the first transition, group interactions at the mesoscopic scale must be taken into account. Our findings suggest, more broadly, the importance of mesoscopic interactions in coexistence of great many species. Scientific Reports 4 doi: 10.1038/srep07486

Description: Microbial syntrophic metabolism has been well accepted as the heart of how methanogenic and other anaerobic microbial communities function. In this work, we applied a single-cell RT-qPCR approach to reveal gene-expression heterogeneity in a model syntrophic system of Desulfovibrio vulgaris and Methanosarcina barkeri, as compared with the D. vulgaris monoculture. Using the optimized primers and single-cell analytical protocol, we quantitatively determine gene-expression levels of 6 selected target genes in each of the 120 single cells of D. vulgaris isolated from its monoculture and dual-culture with M. barkeri. The results demonstrated very significant cell-to-cell gene-expression heterogeneity for the selected D. vulgaris genes in both the monoculture and the syntrophic dual-culture. Interestingly, no obvious increase in gene-expression heterogeneity for the selected genes was observed for the syntrophic dual-culture when compared with its monoculture, although the community structure and cell-cell interactions have become more complicated in the syntrophic dual-culture. In addition, the single-cell RT-qPCR analysis also provided further evidence that the gene cluster (DVU0148-DVU0150) may be involved syntrophic metabolism between D. vulgaris and M. barkeri. Finally, the study validated that single-cell RT-qPCR analysis could be a valuable tool in deciphering gene functions and metabolism in mixed-cultured microbial communities. Scientific Reports 4 doi: 10.1038/srep07478

Description: We have developed a very sensitive, highly selective, non-destructive technique for screening inhomogeneous materials for the presence of superconductivity. This technique, based on phase sensitive detection of microwave absorption is capable of detecting 10−12 cc of a superconductor embedded in a non-superconducting, non-magnetic matrix. For the first time, we apply this technique to the search for superconductivity in extraterrestrial samples. We tested approximately 65 micrometeorites collected from the water well at the Amundsen-Scott South pole station and compared their spectra with those of eight reference materials. None of these micrometeorites contained superconducting compounds, but we saw the Verwey transition of magnetite in our microwave system. This demonstrates that we are able to detect electro-magnetic phase transitions in extraterrestrial materials at cryogenic temperatures. Scientific Reports 4 doi: 10.1038/srep07333

Description: Spider silk fibers were produced through an alternative processing route that differs widely from natural spinning. The process follows a procedure traditionally used to obtain fibers directly from the glands of silkworms and requires exposure to an acid environment and subsequent stretching. The microstructure and mechanical behavior of the so-called spider silk gut fibers can be tailored to concur with those observed in naturally spun spider silk, except for effects related with the much larger cross-sectional area of the former. In particular spider silk gut has a proper ground state to which the material can revert independently from its previous loading history by supercontraction. A larger cross-sectional area implies that spider silk gut outperforms the natural material in terms of the loads that the fiber can sustain. This property suggests that it could substitute conventional spider silk fibers in some intended uses, such as sutures and scaffolds in tissue engineering. Scientific Reports 4 doi: 10.1038/srep07326

Description: BaMn2Bi2 possesses an iso-structure of iron pnictide superconductors and similar antiferromagnetic (AFM) ground state to that of cuprates, therefore, it receives much more attention on its properties and is expected to be the parent compound of a new family of superconductors. When doped with potassium (K), BaMn2Bi2 undergoes a transition from an AFM insulator to an AFM metal. Consequently, it is of great interest to suppress the AFM order in the K-doped BaMn2Bi2 with the aim of exploring the potential superconductivity. Here, we report that external pressure up to 35.6 GPa cannot suppress the AFM order in the K-doped BaMn2Bi2 to develop superconductivity in the temperature range of 300 K–1.5 K, but induces a tetragonal (T) to an orthorhombic (OR) phase transition at ~20 GPa. Theoretical calculations for the T and OR phases, on basis of our high-pressure XRD data, indicate that the AFM order is robust in the pressurized Ba0.61K0.39Mn2Bi2. Both of our experimental and theoretical results suggest that the robust AFM order essentially prevents the emergence of superconductivity. Scientific Reports 4 doi: 10.1038/srep07342

Description: We describe a novel method (FLICS, FLow Image Correlation Spectroscopy) to extract flow speeds in complex vessel networks from a single raster-scanned optical xy-image, acquired in vivo by confocal or two-photon excitation microscopy. Fluorescent flowing objects produce diagonal lines in the raster-scanned image superimposed to static morphological details. The flow velocity is obtained by computing the Cross Correlation Function (CCF) of the intensity fluctuations detected in pairs of columns of the image. The analytical expression of the CCF has been derived by applying scanning fluorescence correlation concepts to drifting optically resolved objects and the theoretical framework has been validated in systems of increasing complexity. The power of the technique is revealed by its application to the intricate murine hepatic microcirculatory system where blood flow speed has been mapped simultaneously in several capillaries from a single xy-image and followed in time at high spatial and temporal resolution. Scientific Reports 4 doi: 10.1038/srep07341