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  • Effects of genetic variants on platelet reactivity and one-year clinical outcomes after percutaneous coronary intervention: A prospective multicentre registry study
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Hyung Joon Joo, Sung Gyun Ahn, Jae Hyoung Park, Ji Young Park, Soon Jun Hong, Seok-Yeon Kim, WoongGil Choi, HyeonCheol Gwon, Young-Hyo Lim, Weon Kim, Woong Chol Kang, Yun-Hyeong Cho, Yong Hoon Kim, JungHan Yoon, WonYong Shin, Myeong-Ki Hong, Scot Garg, Yangsoo Jang, Do-Sun Lim

    Clopidogrel is the mainstay for antiplatelet treatment after percutaneous coronary intervention (PCI). The relationship of platelet reactivity and genetic polymorphism with clinical outcomes with newer-generation drug-eluting stents is unclear. We analysed 4,587 patients for the most powerful single-nucleotide polymorphisms (CYP2C19, CYP2C9, ABCB1, PON1, and P2Y12) related to on-treatment platelet reactivity (OPR). The optimal cut-off value of high OPR for major adverse thrombotic events was 266. CYP2C19 was significantly associated with high OPR and the number of CYP2C19*R (*2 or *3) alleles was proportional to the increased risk of high OPR. Death, myocardial infarction (MI), stroke, stent thrombosis, and bleeding events were assessed during a 1-year follow-up period. Primary endpoints were death and non-fatal MI. The cumulative 1-year incidence of death and stent thrombosis was significantly higher in patients with CYP2C19*2/*2, CYP2C19*2/*3, and CYP2C19*3/*3 (Group 3) than in patients with CYP2C19*1/*1 (Group 1). Multivariate Cox proportional hazard model showed that cardiac death risk was significantly higher in Group 3 than in Group 1 (hazard ratio 2.69, 95% confidence interval 1.154–6.263, p = 0.022). No association was reported between bleeding and OPR. Thus, CYP2C19 may exert a significant impact on the prognosis of PCI patients even in the era of newer-generation drug-eluting stents.

    更新日期:2018-01-19
  • Tracking the Evolution of Transiently Transfected Individual Cells in a Microfluidic Platform
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Micaela Tamara Vitor, Sébastien Sart, Antoine Barizien, Lucimara Gaziola De La Torre, Charles N. Baroud

    Transient gene expression (TGE) technology enables the rapid production of large amount of recombinant proteins, without the need of fastidious screening of the producing cells required for stable transfection (ST). However, several barriers must be overcome before reaching the production yields using ST. For optimizing the production yields from suspended cells using TGE, a better understanding of the transfection conditions at the single cell level are required. In this study, a universal droplet microfluidic platform was used to assess the heterogeneities of CHO-S population transiently transfected with cationic liposomes (CL) (lipoplexes) complexed with GFP-coding plasmid DNA (pDNA). A single cell analysis of GFP production kinetics revealed the presence of a subpopulation producing higher levels of GFP compared with the main population. The size of high producing (HP) cells, their relative abundance, and their specific productivity were dependent on the charge and the pDNA content of the different lipoplexes: HPs showed increased cell size in comparison to the average population, lipoplexes with positive charge produced more HPs, and lipoplexes carrying a larger amount of pDNA yielded a higher specific productivity of HPs. This study demonstrates the potential for time-resolved single-cell measurements to explain population dynamics from a microscopic point of view.

    更新日期:2018-01-19
  • Multi-species coexistence in Lotka-Volterra competitive systems with crowding effects
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Maica Krizna A. Gavina, Takeru Tahara, Kei-ichi Tainaka, Hiromu Ito, Satoru Morita, Genki Ichinose, Takuya Okabe, Tatsuya Togashi, Takashi Nagatani, Jin Yoshimura

    Classical Lotka-Volterra (LV) competition equation has shown that coexistence of competitive species is only possible when intraspecific competition is stronger than interspecific competition, i.e., the species inhibit their own growth more than the growth of the other species. Note that density effect is assumed to be linear in a classical LV equation. In contrast, in wild populations we can observed that mortality rate often increases when population density is very high, known as crowding effects. Under this perspective, the aggregation models of competitive species have been developed, adding the additional reduction in growth rates at high population densities. This study shows that the coexistence of a few species is promoted. However, an unsolved question is the coexistence of many competitive species often observed in natural communities. Here, we build an LV competition equation with a nonlinear crowding effect. Our results show that under a weak crowding effect, stable coexistence of many species becomes plausible, unlike the previous aggregation model. An analysis indicates that increased mortality rate under high density works as elevated intraspecific competition leading to the coexistence. This may be another mechanism for the coexistence of many competitive species leading high species diversity in nature.

    更新日期:2018-01-19
  • Expression and relevance of the G protein-gated K+ channel in the mouse ventricle
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Allison Anderson, Kanchan Kulkarni, Ezequiel Marron Fernandez de Velasco, Nicholas Carlblom, Zhilian Xia, Atsushi Nakano, Kirill A. Martemyanov, Elena G. Tolkacheva, Kevin Wickman

    The atrial G protein-gated inwardly rectifying K+ (GIRK) channel is a critical mediator of parasympathetic influence on cardiac physiology. Here, we probed the details and relevance of the GIRK channel in mouse ventricle. mRNAs for the atrial GIRK channel subunits (GIRK1, GIRK4), M2 muscarinic receptor (M2R), and RGS6, a negative regulator of atrial GIRK-dependent signaling, were detected in mouse ventricle at relatively low levels. The cholinergic agonist carbachol (CCh) activated small GIRK currents in adult wild-type ventricular myocytes that exhibited relatively slow kinetics and low CCh sensitivity; these currents were absent in ventricular myocytes from Girk1−/− or Girk4−/− mice. While loss of GIRK channels attenuated the CCh-induced shortening of action potential duration and suppression of ventricular myocyte excitability, selective ablation of GIRK channels in ventricle had no effect on heart rate, heart rate variability, or electrocardiogram parameters at baseline or after CCh injection. Additionally, loss of ventricular GIRK channels did not impact susceptibility to ventricular arrhythmias. These data suggest that the mouse ventricular GIRK channel is a GIRK1/GIRK4 heteromer, and show that while it contributes to the cholinergic suppression of ventricular myocyte excitability, this influence does not substantially impact cardiac physiology or ventricular arrhythmogenesis in the mouse.

    更新日期:2018-01-19
  • Phylogenetic and Functional Structure of Wintering Waterbird Communities Associated with Ecological Differences
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Xianli Che, Min Zhang, Yanyan Zhao, Qiang Zhang, Qing Quan, Anders Møller, Fasheng Zou

    Ecological differences may be related to community component divisions between Oriental (west) and Sino-Japanese (east) realms, and such differences may result in weak geographical breaks in migratory species that are highly mobile. Here, we conducted comparative phylogenetic and functional structure analyses of wintering waterbird communities in southern China across two realms and subsequently examined possible climate drivers of the observed patterns. An analysis based on such highly migratory species is particularly telling because migration is bound to reduce or completely eliminate any divergence between communities. Phylogenetic and functional structure of eastern communities showed over-dispersion while western communities were clustered. Basal phylogenetic and functional turnover of western communities was significant lower than that of eastern communities. The break between eastern and western communities was masked by these two realms. Geographic patterns were related to mean temperature changes and temperature fluctuations, suggesting that temperature may filter waterbird lineages and traits, thus underlying geographical community divisions. These results suggest phylogenetic and functional divisions in southern China, coinciding with biogeography. This study shows that temperature fluctuations constitute an essential mechanism shaping geographical divisions that have largely gone undetected previously, even under climate change.

    更新日期:2018-01-19
  • Molting site fidelity accounts for colony elimination of the Formosan subterranean termites (Isoptera: Rhinotermitidae) by chitin synthesis inhibitor baits
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    G. Kakkar, W. Osbrink, N.-Y. Su

    Site fidelity by molting termites in Formosan subterranean termite, Coptotermes formosanus Shiraki colonies is a new addition to our understanding of lower termites’ behavior and biology. Our previous studies indicated that workers moved to the central nest to molt in the presence of eggs and reproductives. The current study showed that noviflumuron-affected workers also return to the central nest and died in the vicinity of reproductives and eggs. The aversion to the dead and decaying workers caused reproductives and brood to leave the original central nest site in a colony and refuge at newer sites every few days in response to newly dead workers near them. Because mortality was an event observed only in workers undergoing molting under the effect of noviflumuron- a CSI, the death of molting individuals was observed only around reproductives and brood. This study reveals a previously undiscovered behavior of molting termites and the mechanics behind a successful arsenal; noviflumuron baits used against subterranean termites.

    更新日期:2018-01-19
  • Transcriptome Analysis in Spleen Reveals Differential Regulation of Response to Newcastle Disease Virus in Two Chicken Lines
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Jibin Zhang, Michael G. Kaiser, Melissa S. Deist, Rodrigo A. Gallardo, David A. Bunn, Terra R. Kelly, Jack C. M. Dekkers, Huaijun Zhou, Susan J. Lamont

    Enhancing genetic resistance of chickens to Newcastle Disease Virus (NDV) provides a promising way to improve poultry health, and to alleviate poverty and food insecurity in developing countries. In this study, two inbred chicken lines with different responses to NDV, Fayoumi and Leghorn, were challenged with LaSota NDV strain at 21 days of age. Through transcriptome analysis, gene expression in spleen at 2 and 6 days post-inoculation was compared between NDV-infected and control groups, as well as between chicken lines. At a false discovery rate <0.05, Fayoumi chickens, which are relatively more resistant to NDV, showed fewer differentially expressed genes (DEGs) than Leghorn chickens. Several interferon-stimulated genes were identified as important DEGs regulating immune response to NDV in chicken. Pathways predicted by IPA analysis, such as "EIF-signaling", "actin cytoskeleton organization nitric oxide production" and "coagulation system" may contribute to resistance to NDV in Fayoumi chickens. The identified DEGs and predicted pathways may contribute to differential responses to NDV between the two chicken lines and provide potential targets for breeding chickens that are more resistant to NDV.

    更新日期:2018-01-19
  • Resting state brain networks in the prairie vole
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Juan J. Ortiz, Wendy Portillo, Raul G. Paredes, Larry J. Young, Sarael Alcauter

    Resting state functional magnetic resonance imaging (rsfMRI) has shown the hierarchical organization of the human brain into large-scale complex networks, referred as resting state networks. This technique has turned into a promising translational research tool after the finding of similar resting state networks in non-human primates, rodents and other animal models of great value for neuroscience. Here, we demonstrate and characterize the presence of resting states networks in Microtus ochrogaster, the prairie vole, an extraordinary animal model to study complex human-like social behavior, with potential implications for the research of normal social development, addiction and neuropsychiatric disorders. Independent component analysis of rsfMRI data from isoflurane-anestethized prairie voles resulted in cortical and subcortical networks, including primary motor and sensory networks, but also included putative salience and default mode networks. We further discuss how future research could help to close the gap between the properties of the large scale functional organization and the underlying neurobiology of several aspects of social cognition. These results contribute to the evidence of preserved resting state brain networks across species and provide the foundations to explore the use of rsfMRI in the prairie vole for basic and translational research.

    更新日期:2018-01-19
  • Comprehensive reduction of amino acid set in a protein suggests the importance of prebiotic amino acids for stable proteins
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Rei Shibue, Takahiro Sasamoto, Masami Shimada, Bowen Zhang, Akihiko Yamagishi, Satoshi Akanuma

    Modern organisms commonly use the same set of 20 genetically coded amino acids for protein synthesis with very few exceptions. However, earlier protein synthesis was plausibly much simpler than modern one and utilized only a limited set of amino acids. Nevertheless, few experimental tests of this issue with arbitrarily chosen amino acid sets had been reported prior to this report. Herein we comprehensively and systematically reduced the size of the amino acid set constituting an ancestral nucleoside kinase that was reconstructed in our previous study. We eventually found that two convergent sequences, each comprised of a 13-amino acid alphabet, folded into soluble, stable and catalytically active structures, even though their stabilities and activities were not as high as those of the parent protein. Notably, many but not all of the reduced-set amino acids coincide with those plausibly abundant in primitive Earth. The inconsistent amino acids appeared to be important for catalytic activity but not for stability. Therefore, our findings suggest that the prebiotically abundant amino acids were used for creating stable protein structures and other amino acids with functional side chains were recruited to achieve efficient catalysis.

    更新日期:2018-01-19
  • Compliance-Free, Digital SET and Analog RESET Synaptic Characteristics of Sub-Tantalum Oxide Based Neuromorphic Device
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Yawar Abbas, Yu-Rim Jeon, Andrey Sergeevich Sokolov, Sohyeon Kim, Boncheol Ku, Changhwan Choi

    A two terminal semiconducting device like a memristor is indispensable to emulate the function of synapse in the working memory. The analog switching characteristics of memristor play a vital role in the emulation of biological synapses. The application of consecutive voltage sweeps or pulses (action potentials) changes the conductivity of the memristor which is considered as the fundamental cause of the synaptic plasticity. In this study, a neuromorphic device using an in-situ growth of sub-tantalum oxide switching layer is fabricated, which exhibits the digital SET and analog RESET switching with an electroforming process without any compliance current (compliance free). The process of electroforming and SET is observed at the positive sweeps of +2.4 V and +0.86 V, respectively, while multilevel RESET is observed with the consecutive negative sweeps in the range of 0 V to −1.2 V. The movement of oxygen vacancies and gradual change in the anatomy of the filament is attributed to digital SET and analog RESET switching characteristics. For the Ti/Ta2O3−x/Pt neuromorphic device, the Ti top and Pt bottom electrodes are considered as counterparts of the pre-synaptic input terminal and a post-synaptic output terminal, respectively.

    更新日期:2018-01-19
  • Meta-analysis of soil mercury accumulation by vegetables
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Haixin Yu, Jing Li, Yaning Luan

    Mercury pollution in soil poses serious risks to human health through consumption of contaminated vegetables. We used a meta-analysis to examine the mercury enrichment ability of different vegetables and the main factors affecting mercury uptake. We drew the following conclusions. (1) Plants with a lower bioconcentration factor (BCF) include cowpea, long bean, and radish, whereas plants with a higher BCF include green pepper, spinach, cabbage, and Chinese cabbage. (2) Leaf and cucurbit have the highest and lowest capacity, respectively, for mercury enrichment. (3) When soil pH is <6.5, mercury level uptake by the plant increases, whereas it decreases when the pH is >7.5, meaning that increased soil pH reduces mercury uptake in soil. (4) When soil organic matter (SOM) is lower than 20 g/kg, tuber plants have the highest and eggplant has the lowest mercury adsorption capacity, respectively. When SOM is 20–30 g/kg, cucurbit has the lowest and leaf the highest adsorption capacity, respectively. When SOM is higher than 30 g/kg, however, eggplant has the highest mercury adsorption capacity, but there were no significant differences among the five types of vegetables. We argue that this meta-analysis aids in selecting vegetables suitable for absorption of heavy metals from polluted soil.

    更新日期:2018-01-19
  • Oral administration of Proteus mirabilis damages dopaminergic neurons and motor functions in mice
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Jin Gyu Choi, Namkwon Kim, In Gyoung Ju, Hyeyoon Eo, Su-Min Lim, Se-Eun Jang, Dong-Hyun Kim, Myung Sook Oh

    Recently, studies on the relationship between gut dysbiosis and Parkinson’s disease (PD) have increased, but whether a specific gut bacterium may cause PD remains unexplored. Here, we report, for the first time, that a specific gut bacterium directly induces PD symptoms and dopaminergic neuronal damage in the mouse brain. We found that the number of Enterobacteriaceae, particularly Proteus mirabilis, markedly and commonly increased in PD mouse models. Administration of P. mirabilis isolated from PD mice significantly induced motor deficits, selectively caused dopaminergic neuronal damage and inflammation in substantia nigra and striatum, and stimulated α-synuclein aggregation in the brain as well as in the colon. We found that lipopolysaccharides, a virulence factor of P. mirabilis, may be associated in these pathological changes via gut leakage and inflammatory actions. Our results suggest a role of P. mirabilis on PD pathogenesis in the brain.

    更新日期:2018-01-19
  • Compositional Bias in Naïve and Chemically-modified Phage-Displayed Libraries uncovered by Paired-end Deep Sequencing
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Bifang He, Katrina F. Tjhung, Nicholas J. Bennett, Ying Chou, Andrea Rau, Jian Huang, Ratmir Derda

    Understanding the composition of a genetically-encoded (GE) library is instrumental to the success of ligand discovery. In this manuscript, we investigate the bias in GE-libraries of linear, macrocyclic and chemically post-translationally modified (cPTM) tetrapeptides displayed on the M13KE platform, which are produced via trinucleotide cassette synthesis (19 codons) and NNK-randomized codon. Differential enrichment of synthetic DNA {S}, ligated vector {L} (extension and ligation of synthetic DNA into the vector), naïve libraries {N} (transformation of the ligated vector into the bacteria followed by expression of the library for 4.5 hours to yield a “naïve” library), and libraries chemically modified by aldehyde ligation and cysteine macrocyclization {M} characterized by paired-end deep sequencing, detected a significant drop in diversity in {L} → {N}, but only a minor compositional difference in {S} → {L} and {N} → {M}. Libraries expressed at the N-terminus of phage protein pIII censored positively charged amino acids Arg and Lys; libraries expressed between pIII domains N1 and N2 overcame Arg/Lys-censorship but introduced new bias towards Gly and Ser. Interrogation of biases arising from cPTM by aldehyde ligation and cysteine macrocyclization unveiled censorship of sequences with Ser/Phe. Analogous analysis can be used to explore library diversity in new display platforms and optimize cPTM of these libraries.

    更新日期:2018-01-19
  • Towards an experimental classification system for membrane active peptides
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    G. D. Brand, M. H. S. Ramada, T. C. Genaro-Mattos, C. Bloch

    Mature proteins can act as potential sources of encrypted bioactive peptides that, once released from their parent proteins, might interact with diverse biomolecular targets. In recent work we introduced a systematic methodology to uncover encrypted intragenic antimicrobial peptides (IAPs) within large protein sequence libraries. Given that such peptides may interact with membranes in different ways, resulting in distinct observable outcomes, it is desirable to develop a predictive methodology to categorize membrane active peptides and establish a link to their physicochemical properties. Building upon previous work, we explored the interaction of a range of IAPs with model membranes probed by differential scanning calorimetry (DSC) and circular dichroism (CD) techniques. The biophysical data were submitted to multivariate statistical methods and resulting peptide clusters were correlated to peptide structure and to their antimicrobial activity. A re-evaluation of the physicochemical properties of the peptides was conducted based on peptide cluster memberships. Our data indicate that membranolytic peptides produce characteristic thermal transition (DSC) profiles in model vesicles and that this can be used to categorize novel molecules with unknown biological activity. Incremental expansion of the model presented here might result in a unified experimental framework for the prediction of novel classes of membrane active peptides.

    更新日期:2018-01-19
  • Fabrication of multiple nanopores in a SiNx membrane via controlled breakdown
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Yunlong Wang, Cuifeng Ying, Wenyuan Zhou, Lennart de Vreede, Zhibo Liu, Jianguo Tian

    This paper reports a controlled breakdown (CBD) method to fabricate multiple nanopores in a silicon nitride (SiNx) membrane with control over both nanopore count and nanopore diameter. Despite the stochastic process of the breakdown, we found that the nanopores created via CBD, tend to be of the same diameter. We propose a membrane resistance model to explain and control the multiple nanopores forming in the membrane. We prove that the membrane resistance can reflect the number of nanopores in the membrane and that the diameter of the nanopores is controlled by the exposure time and strength of the electric field. This controllable multiple nanopore formation via CBD avoids the utilization of complicated instruments and time-intensive manufacturing. We anticipate CBD has the potential to become a nanopore fabrication technique which, integrated into an optical setup, could be used as a high-throughput and multichannel characterization technique.

    更新日期:2018-01-19
  • Mechanical behavior of a soft hydrogel reinforced with three-dimensional printed microfibre scaffolds
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Miguel Castilho, Gernot Hochleitner, Wouter Wilson, Bert Rietbergen, Paul D. Dalton, Jürgen Groll, Jos Malda, Keita Ito

    Reinforcing hydrogels with micro-fibre scaffolds obtained by a Melt-Electrospinning Writing (MEW) process has demonstrated great promise for developing tissue engineered (TE) constructs with mechanical properties compatible to native tissues. However, the mechanical performance and reinforcement mechanism of the micro-fibre reinforced hydrogels is not yet fully understood. In this study, FE models, implementing material properties measured experimentally, were used to explore the reinforcement mechanism of fibre-hydrogel composites. First, a continuum FE model based on idealized scaffold geometry was used to capture reinforcement effects related to the suppression of lateral gel expansion by the scaffold, while a second micro-FE model based on micro-CT images of the real construct geometry during compaction captured the effects of load transfer through the scaffold interconnections. Results demonstrate that the reinforcement mechanism at higher scaffold volume fractions was dominated by the load carrying-ability of the fibre scaffold interconnections, which was much higher than expected based on testing scaffolds alone because the hydrogel provides resistance against buckling of the scaffold. We propose that the theoretical understanding presented in this work will assist the design of more effective composite constructs with potential applications in a wide range of TE conditions.

    更新日期:2018-01-19
  • Offline stimulation of human parietal cortex differently affects resting EEG microstates
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Pierpaolo Croce, Filippo Zappasodi, Paolo Capotosto

    The interference effects of transcranial magnetic stimulation (TMS) on several electroencephalographic (EEG) measures in both temporal and frequency domains have been reported. We tested the hypothesis whether the offline external inhibitory interference, although focal, could result in a global reorganization of the functional brain state, as assessed by EEG microstates. In 16 healthy subjects, we inhibited five parietal areas and used a pseudo stimulation (Sham) at rest. The EEG microstates were extracted before and after each stimulation. The canonical A, B, C and D templates were found before and after all stimulation conditions. The Sham, as well as the stimulation of a ventral site did not modify any resting EEG microstates’ topography. On the contrary, interfering with parietal key-nodes of both dorsal attention (DAN) and default mode networks (DMN), we observed that the microstate C clearly changes, whereas the other three topographies are not affected. These results provide the first causal evidence of a microstates modification following magnetic interference. Since the microstate C has been associated to the activity in regions belonging to the cingulo-opercular network (CON), the regional specificity of such inhibition seems to support the theory of a link between CON and both DAN and DMN at rest.

    更新日期:2018-01-19
  • Dual Band Metamaterial Antenna For LTE/Bluetooth/WiMAX System
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Md. Mehedi Hasan, Mohammad Rashed Iqbal Faruque, Mohammad Tariqul Islam

    A compact metamaterial inspired antenna operate at LTE, Bluetooth and WiMAX frequency band is introduced in this paper. For the lower band, the design utilizes an outer square metallic strip forcing the patch to radiate as an equivalent magnetic-current loop. For the upper band, another magnetic current loop is created by adding metamaterial structure near the feed line on the patch. The metamaterial inspired antenna dimension of 42 × 32 mm2 compatible to wireless devices. Finite integration technique based CST Microwave Studio simulator has been used to design and numerical investigation as well as lumped circuit model of the metamaterial antenna is explained with proper mathematical derivation. The achieved measured dual band operation of the conventional antenna are sequentially, 0.561~0.578 GHz, 2.346~2.906 GHz, and 2.91~3.49 GHz, whereas the metamaterial inspired antenna shows dual-band operation from 0.60~0.64 GHz, 2.67~3.40 GHz and 3.61~3.67 GHz, respectively. Therefore, the metamaterial antenna is applicable for LTE and WiMAX applications. Besides, the measured metamaterial antenna gains of 0.15~3.81 dBi and 3.47~3.75 dBi, respectively for the frequency band of 2.67~3.40 GHz and 3.61~3.67 GHz.

    更新日期:2018-01-19
  • Epigenetic control of influenza virus: role of H3K79 methylation in interferon-induced antiviral response
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Laura Marcos-Villar, Juan Díaz-Colunga, Juan Sandoval, Noelia Zamarreño, Sara Landeras-Bueno, Manel Esteller, Ana Falcón, Amelia Nieto

    Influenza virus stablishes a network of virus-host functional interactions, which depends on chromatin dynamic and therefore on epigenetic modifications. Using an unbiased search, we analyzed the epigenetic changes at DNA methylation and post-translational histone modification levels induced by the infection. DNA methylation was unaltered, while we found a general decrease on histone acetylation, which correlates with transcriptional inactivation and may cooperate with the impairment of cellular transcription that causes influenza virus infection. A particular increase in H3K79 methylation was observed and the use of an inhibitor of the specific H3K79 methylase, Dot1L enzyme, or its silencing, increased influenza virus replication. The antiviral response was reduced in conditions of Dot1L downregulation, since decreased nuclear translocation of NF-kB complex, and IFN-β, Mx1 and ISG56 expression was detected. The data suggested a control of antiviral signaling by methylation of H3K79 and consequently, influenza virus replication was unaffected in IFN pathway-compromised, Dot1L-inhibited cells. H3K79 methylation also controlled replication of another potent interferon-inducing virus such as vesicular stomatitis virus, but did not modify amplification of respiratory syncytial virus that poorly induces interferon signaling. Epigenetic methylation of H3K79 might have an important role in controlling interferon-induced signaling against viral pathogens.

    更新日期:2018-01-19
  • Spin Hall-induced auto-oscillations in ultrathin YIG grown on Pt
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    M. Evelt, C. Safranski, Mohammed Aldosary, V. E. Demidov, I. Barsukov, A. P. Nosov, A. B. Rinkevich, K. Sobotkiewich, Xiaoqin Li, Jing Shi, I. N. Krivorotov, S. O. Demokritov

    We experimentally study nanowire-shaped spin-Hall nano-oscillators based on nanometer-thick epitaxial films of Yttrium Iron Garnet grown on top of a layer of Pt. We show that, although these films are characterized by significantly larger magnetic damping in comparison with the films grown directly on Gadolinium Gallium Garnet, they allow one to achieve spin current-driven auto-oscillations at comparable current densities, which can be an indication of the better transparency of the interface to the spin current. These observations suggest a route for improvement of the flexibility of insulator-based spintronic devices and their compatibility with semiconductor technology.

    更新日期:2018-01-19
  • Plasma proteomic study of acute mountain sickness susceptible and resistant individuals
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Hui Lu, Rong Wang, Wenbin Li, Hua Xie, Chang Wang, Ying Hao, Yuhuan Sun, Zhengping Jia

    Although extensive studies have focused on the development of acute mountain sickness (AMS), the exact mechanisms of AMS are still obscure. In this study, we used isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis to identify novel AMS−associated biomarkers in human plasma. After 9 hours of hypobaric hypoxia the abundance of proteins related to tricarboxylic acid (TCA) cycle, glycolysis, ribosome, and proteasome were significantly reduced in AMS resistant (AMS−) group, but not in AMS susceptible (AMS+) group. This suggested that AMS− individuals could reduce oxygen consumption via repressing TCA cycle and glycolysis, and reduce energy consumption through decreasing protein degradation and synthesis compared to AMS+ individuals after acute hypoxic exposure. The inflammatory response might be decreased resulting from the repressed TCA cycle. We propose that the ability for oxygen consumption reduction may play an important role in the development of AMS. Our present plasma proteomic study in plateau of the Han Chinese volunteers gives new data to address the development of AMS and potential AMS correlative biomarkers.

    更新日期:2018-01-19
  • Genetic fingerprinting of salmon louse (Lepeophtheirus salmonis) populations in the North-East Atlantic using a random forest classification approach
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    A. Jacobs, M. Noia, K. Praebel, Ø. Kanstad-Hanssen, M. Paterno, D. Jackson, P. McGinnity, A. Sturm, K. R. Elmer, M. S. Llewellyn

    Caligid sea lice represent a significant threat to salmonid aquaculture worldwide. Population genetic analyses have consistently shown minimal population genetic structure in North Atlantic Lepeophtheirus salmonis, frustrating efforts to track louse populations and improve targeted control measures. The aim of this study was to test the power of reduced representation library sequencing (IIb-RAD sequencing) coupled with random forest machine learning algorithms to define markers for fine-scale discrimination of louse populations. We identified 1286 robustly supported SNPs among four L. salmonis populations from Ireland, Scotland and Northern Norway. Only weak global structure was observed based on the full SNP dataset. The application of a random forest machine-learning algorithm identified 98 discriminatory SNPs that dramatically improved population assignment, increased global genetic structure and resulted in significant genetic population differentiation. A large proportion of SNPs found to be under directional selection were also identified to be highly discriminatory. Our data suggest that it is possible to discriminate between nearby L. salmonis populations given suitable marker selection approaches, and that such differences might have an adaptive basis. We discuss these data in light of sea lice adaption to anthropogenic and environmental pressures as well as novel approaches to track and predict sea louse dispersal.

    更新日期:2018-01-19
  • Structural Covariance of Gray Matter Volume in HIV Vertically Infected Adolescents
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Jielan Li, Lei Gao, Zhi Wen, Jing Zhang, Panying Wang, Ning Tu, Hao Lei, Fuchun Lin, Xi’en Gui, Guangyao Wu

    Human immunodeficiency virus (HIV) infection significantly affect neurodevelopmental and behavioral outcomes. We investigated whether alterations of gray matter organization and structural covariance networks with vertical HIV infection adolescents exist, by using the GAT toolbox. MRI data were analysed from 25 HIV vertically infected adolescents and 33 HIV-exposed-uninfected control participants. The gray matter volume (GMV) was calculated, and structural brain networks were reconstructed from gray matter co-variance. Gray matter losses were pronounced in anterior cingulate cortex (ACC), right pallidum, right occipital lobe, inferior parietal lobe, and bilateral cerebellum crus. The global brain network measures were not significantly different between the groups; however, the nodal alterations were most pronounced in frontal, temporal, basal ganglia, cerebellum, and temporal lobes. Brain hubs in the HIV-infected subjects increased in number and tended to shift to sensorimotor and temporal areas. In the HIV-infected subjects, decreased GMVs in ACC and bilateral cerebellum were related to lower Mini-Mental State Examination scores; the CD4 counts were positively related to the GMVs in ACC and sensorimotor areas. These findings suggest that focally reduced gray matter, disrupted nodal profiles of structural wirings, and a shift in hub distribution may represent neuroanatomical biomarkers of HIV infection on the developing brain.

    更新日期:2018-01-19
  • Blocking Zika virus vertical transmission
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Pinar Mesci, Angela Macia, Spencer M. Moore, Sergey A. Shiryaev, Antonella Pinto, Chun-Teng Huang, Leon Tejwani, Isabella R. Fernandes, Nicole A. Suarez, Matthew J. Kolar, Sandro Montefusco, Scott C. Rosenberg, Roberto H. Herai, Fernanda R. Cugola, Fabiele B. Russo, Nicholas Sheets, Alan Saghatelian, Sujan Shresta, Jeremiah D. Momper, Jair L. Siqueira-Neto, Kevin D. Corbett, Patricia C. B. Beltrão-Braga, Alexey V. Terskikh, Alysson R. Muotri

    The outbreak of the Zika virus (ZIKV) has been associated with increased incidence of congenital malformations. Although recent efforts have focused on vaccine development, treatments for infected individuals are needed urgently. Sofosbuvir (SOF), an FDA-approved nucleotide analog inhibitor of the Hepatitis C (HCV) RNA-dependent RNA polymerase (RdRp) was recently shown to be protective against ZIKV both in vitro and in vivo. Here, we show that SOF protected human neural progenitor cells (NPC) and 3D neurospheres from ZIKV infection-mediated cell death and importantly restored the antiviral immune response in NPCs. In vivo, SOF treatment post-infection (p.i.) decreased viral burden in an immunodeficient mouse model. Finally, we show for the first time that acute SOF treatment of pregnant dams p.i. was well-tolerated and prevented vertical transmission of the virus to the fetus. Taken together, our data confirmed SOF-mediated sparing of human neural cell types from ZIKV-mediated cell death in vitro and reduced viral burden in vivo in animal models of chronic infection and vertical transmission, strengthening the growing body of evidence for SOF anti-ZIKV activity.

    更新日期:2018-01-19
  • Association between modified CHA2DS2-VASc Score with Ankle-Brachial index < 0.9
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Po-Chao Hsu, Wen-Hsien Lee, Hsiang-Chun Lee, Wei-Chung Tsai, Chun-Yuan Chu, Ying-Chih Chen, Chee-Siong Lee, Tsung-Hsien Lin, Wen-Chol Voon, Sheng-Hsiung Sheu, Ho-Ming Su

    The ankle-brachial index (ABI) is a reliable diagnostic examination for peripheral arterial occlusive disease (PAOD). We previously reported CHADS2 score was significantly correlated with PAOD. However, the association between CHA2DS2-VASc score and ABI < 0.9 is not evaluated in the literature. The aim of the present study was to investigate whether CHA2DS2-VASc score has a strong association with PAOD. We enrolled 1482 patients in this study. PAOD was defined as ABI < 0.9 in either leg. Vascular disease in CHA2DS2-VASc score was modified as vascular disease except PAOD. Of the 1482 subjects, the prevalence of ABI < 0.9 was 5.6%. Multivariate analysis showed that the increased age, decreased estimated glomerular filtration rate and increased modified CHA2DS2-VASc score (OR, 1.764; p < 0.001) were independent associated with ABI < 0.9. In addition, the percentage of ABI < 0.9 in patients with modified CHA2DS2-VASc score of 0, 1, and <2 were 0%, 0.9%, and 0.7%, respectively (All < 1%). Our study demonstrated modified CHA2DS2-VASc score was significantly associated with ABI < 0.9. Calculation of modified CHA2DS2-VASc score might be useful in identifying patients with PAOD and in stratifying the risk of PAOD in non-AF patients.

    更新日期:2018-01-19
  • Reduction in hepatic secondary bile acids caused by short-term antibiotic-induced dysbiosis decreases mouse serum glucose and triglyceride levels
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Takuya Kuno, Mio Hirayama-Kurogi, Shingo Ito, Sumio Ohtsuki

    Antibiotic-caused changes in intestinal flora (dysbiosis) can have various effects on the host. Secondary bile acids produced by intestinal bacteria are ligands for specific nuclear receptors, which regulate glucose, lipid, and drug metabolism in the liver. The present study aimed to clarify the effect of changes in secondary bile acids caused by antibiotic-induced dysbiosis on the host physiology, especially glucose, lipid, and drug metabolism. After oral administration of non-absorbable antibiotics for 5 days, decreased amounts of secondary bile acid-producing bacteria in faeces and a reduction in secondary bile acid [lithocholic acid (LCA) and deoxycholic acid (DCA)] levels in the liver were observed. Serum glucose and triglyceride levels were also decreased, and these decreases were reversed by LCA and DCA supplementation. Quantitative proteomics demonstrated that the expression levels of proteins involved in glycogen metabolism, cholesterol, bile acid biosynthesis, and drug metabolism (Cyp2b10, Cyp3a25, and Cyp51a1) were altered in the liver in dysbiosis, and these changes were reversed by LCA and DCA supplementation. These results suggested that secondary bile acid-producing bacteria contribute to the homeostasis of glucose and triglyceride levels and drug metabolism in the host, and have potential as therapeutic targets for treating metabolic disease.

    更新日期:2018-01-19
  • Conflict-sensitive neurons gate interocular suppression in human visual cortex
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Sucharit Katyal, Mark Vergeer, Sheng He, Bin He, Stephen A. Engel

    Neural suppression plays an important role in cortical function, including sensory, memory, and motor systems. It remains, however, relatively poorly understood. A paradigmatic case arises when conflicting images are presented to the two eyes. These images can compete for awareness, and one is usually strongly suppressed. The mechanisms that resolve such interocular conflict remain unclear. Suppression could arise solely from “winner-take-all” competition between neurons responsive to each eye. Alternatively, suppression could also depend upon neurons detecting interocular conflict. Here, we provide physiological evidence in human visual cortex for the latter: suppression depends upon conflict-sensitive neurons. We recorded steady-state visual evoked potentials (SSVEP), and used the logic of selective adaptation. The amplitude of SSVEP responses at intermodulation frequencies strengthened as interocular conflict in the stimulus increased, suggesting the presence of neurons responsive to conflict. Critically, adaptation to conflict both reduced this SSVEP effect, and increased the amount of conflict needed to produce perceptual suppression. The simplest account of these results is that interocular-conflict-sensitive neurons exist in human cortex: adaptation likely reduced the responsiveness of these neurons which in turn raised the amount of conflict required to produce perceptual suppression. Similar mechanisms may be used to resolve other varieties of perceptual conflict.

    更新日期:2018-01-19
  • Identification and quantification of plasma calciprotein particles with distinct physical properties in patients with chronic kidney disease
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Yutaka Miura, Yoshitaka Iwazu, Kazuhiro Shiizaki, Tetsu Akimoto, Kazuhiko Kotani, Masahiko Kurabayashi, Hiroshi Kurosu, Makoto Kuro-o

    Calciprotein particles (CPP) are solid-phase calcium-phosphate bound to serum protein fetuin-A and dispersed as colloids in the blood. Recent clinical studies indicated that serum CPP levels were increased with decline of renal function and associated with inflammation and vascular calcification. However, CPP assays used in these studies measured only a part of CPP over a certain particle size and density. Here we show that such CPP are mostly artifacts generated during processing of serum samples in vitro. The native CPP in fresh plasma are smaller in size and lower in density than those artifactual CPP, composed of fetuin-A carrying amorphous and/or crystalline calcium-phosphate, and increased primarily with serum phosphate levels. We have identified several physicochemical factors that promote aggregation/dissolution of CPP and transition of the calcium-phosphate from the amorphous phase to the crystalline phase in vitro, including addition of anti-coagulants, composition of buffer for sample dilution, the number of freeze-thaw cycles, the speed for sample freezing, and how many hours the samples were left at what temperature. Therefore, it is of critical importance to standardize these factors during sample preparation in clinical studies on CPP and to investigate the biological activity of the native CPP.

    更新日期:2018-01-19
  • Pre-conception maternal erythrocyte saturated to unsaturated fatty acid ratio predicts pregnancy after natural cycle frozen embryo transfer
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Christopher C. Onyiaodike, Heather M. Murray, Ruiqi Zhang, Barbara J. Meyer, Fiona Jordan, E. Ann Brown, Robert J. B. Nibbs, Helen Lyall, Naveed Sattar, Scott M. Nelson, Dilys J. Freeman

    The environment for embryo implantation and fetal growth and development is affected by maternal nutritional, metabolic and health status. The aim of this prospective, cohort study was to test whether plasma metabolic and inflammatory biomarkers can predict pregnancy resulting from in vitro fertilisation (IVF). Women with a natural menstrual cycle undergoing frozen embryo transfer (FET) were recruited and fasting baseline blood samples were collected a mean of 3.4 days prior to the luteinising hormone (LH) surge and a non-fasting blood sample was taken on the day of FET. Ongoing pregnancy was defined by positive fetal heartbeat on ultrasound scan at day 45 post LH surge. Thirty-six pregnancies resulted from FET in 143 women. In an overall stepwise multivariable analysis, erythrocyte saturated to unsaturated fatty acid ratio was positively associated with ongoing pregnancy. A similar model incorporating day of FET covariates found that erythrocyte saturated to unsaturated fatty acid ratio, erythrocyte fatty acid average chain length and plasma log-triglycerides predicted ongoing pregnancy. In conclusion, a higher peri-conceptional saturated to unsaturated fatty acid ratio predicted ongoing pregnancy after natural cycle frozen embryo transfer and may reflect a maternal nutritional status that facilitates pregnancy success in this assisted conception scenario.

    更新日期:2018-01-19
  • Elucidating the mechanism of the considerable mechanical stiffening of DNA induced by the couple Zn2+/Calix[4]arene-1,3-O-diphosphorous acid
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Yannick Tauran, Mehmet C. Tarhan, Laurent Mollet, Jean Baptiste Gerves, Momoko Kumemura, Laurent Jalabert, Nicolas Lafitte, Ikjoo Byun, Beomjoon Kim, Hiroyuki Fujita, Dominique Collard, Florent Perret, Mickael Desbrosses, Didier Leonard, Christelle Goutaudier, Anthony W. Coleman

    The couple Calix[4]arene-1,3-O-diphosphorous acid (C4diP) and zinc ions (Zn2+) acts as a synergistic DNA binder. Silicon NanoTweezer (SNT) measurements show an increase in the mechanical stiffness of DNA bundles by a factor of >150, at Zn2+ to C4diP ratios above 8, as compared to Zinc alone whereas C4diP alone decreases the stiffness of DNA. Electroanalytical measurements using 3D printed devices demonstrate a progression of events in the assembly of C4diP on DNA promoted by zinc ions. A mechanism at the molecular level can be deduced in which C4diP initially coordinates to DNA by phosphate-phosphate hydrogen bonds or in the presence of Zn2+ by Zn2+ bridging coordination of the phosphate groups. Then, at high ratios of Zn2+ to C4diP, interdigitated dimerization of C4diP is followed by cross coordination of DNA strands through Zn2+/C4diP inter-strand interaction. The sum of these interactions leads to strong stiffening of the DNA bundles and increased inter-strand binding.

    更新日期:2018-01-19
  • Comparative transcriptomic and proteomic analysis of Arthrobacter sp. CGMCC 3584 responding to dissolved oxygen for cAMP production
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Huanqing Niu, Junzhi Wang, Wei Zhuang, Dong Liu, Yong Chen, Chenjie Zhu, Hanjie Ying

    Arthrobacter sp. CGMCC 3584 is able to produce high yields of extracellular cyclic adenosine monophosphate (cAMP), which plays a vital role in the field of treatment of disease and animal food, during aerobic fermentation. However, the molecular basis of cAMP production in Arthrobacter species is rarely explored. Here, for the first time, we report the comparative transcriptomic and proteomic study of Arthrobacter cells to elucidate the higher productivity of cAMP under high oxygen supply. We finally obtained 14.1% and 19.3% of the Arthrobacter genome genes which were up-regulated and down-regulated notably, respectively, with high oxygen supply, and identified 54 differently expressed proteins. Our results revealed that high oxygen supply had two major effects on metabolism: inhibition of glycolysis, pyruvate metabolism, nitrogen metabolism, and amino acid metabolism (histidine, branched-chain amino acids and glutamate metabolism); enhancement of the tricarboxylic acid cycle and purine metabolism. We also found that regulation of adenylate cyclase and phosphodiesterase was not significant under high oxygen supply, suggesting efficient cAMP export might be important in cAMP production. These findings may contribute to further understanding of capacities of Arthrobacter species and would be highly useful in genetic regulation for desirable production.

    更新日期:2018-01-19
  • Stochastic optimization of broadband reflecting photonic structures
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    D. Estrada-Wiese, E. A. del Río-Chanona, J. A. del Río

    Photonic crystals (PCs) are built to control the propagation of light within their structure. These can be used for an assortment of applications where custom designed devices are of interest. Among them, one-dimensional PCs can be produced to achieve the reflection of specific and broad wavelength ranges. However, their design and fabrication are challenging due to the diversity of periodic arrangement and layer configuration that each different PC needs. In this study, we present a framework to design high reflecting PCs for any desired wavelength range. Our method combines three stochastic optimization algorithms (Random Search, Particle Swarm Optimization and Simulated Annealing) along with a reduced space-search methodology to obtain a custom and optimized PC configuration. The optimization procedure is evaluated through theoretical reflectance spectra calculated by using the Equispaced Thickness Method, which improves the simulations due to the consideration of incoherent light transmission. We prove the viability of our procedure by fabricating different reflecting PCs made of porous silicon and obtain good agreement between experiment and theory using a merit function. With this methodology, diverse reflecting PCs can be designed for any applications and fabricated with different materials.

    更新日期:2018-01-19
  • Advanced Modified Polyacrylonitrile Membrane with Enhanced Adsorption Property for Heavy Metal Ions
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Xinfeng Zhang, Shujing Yang, Bing Yu, Qinglong Tan, Xiaoyan Zhang, Hailin Cong

    Advanced modified polyacrylonitrile (PAN) membrane with high adsorption property for heavy metal ions was designed and fabricated for the first time. The introduced diazoresin-ethylenediaminetetraacetic acid (DR-EDTA) layer could effectively absorb the metal ion, such as Cu2+, Pb2+, Hg2+ in the waste water. The effects of layers, metal ion concentration, pH, temperature and cycle time were investigated. The results showed that the adsorption isotherms for Cu2+ were well fitted by Langmuir model. The maximum adsorption capacity of the modified membrane for Cu2+ was approximately 47.6 mg/g. In addition, the prepared PAN-(DR-EDTA)3 membrane could be regenerated more than 720 h based on their adsorption/desorption cycles. The results demonstrated that the modified PAN membrane could be used as effective adsorbents for heavy metal removal from waste water.

    更新日期:2018-01-19
  • Artificial chameleon skin that controls spectral radiation: Development of Chameleon Cool Coating (C3)
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Hiroki Gonome, Masashi Nakamura, Junnosuke Okajima, Shigenao Maruyama

    Chameleons have a diagnostic thermal protection that enables them to live under various conditions. Our developed special radiative control therefore is inspired by the chameleon thermal protection ability by imitating its two superposed layers as two pigment particles in one coating layer. One particle imitates a chameleon superficial surface for color control (visible light), and another particle imitates a deep surface to reflect solar irradiation, especially in the near-infrared region. Optical modeling allows us to optimally design the particle size and volume fraction. Experimental evaluation shows that the desired spectral reflectance, i.e., low in the VIS region and high in NIR region, can be achieved. Comparison between the measured and calculated reflectances shows that control of the particle size and dispersion/aggregation of particle cloud is important in improving the thermal-protection performance of the coating. Using our developed coating, the interior temperature decreases and the cooling load is reduced while keeping the dark tone of the object.

    更新日期:2018-01-19
  • 3,3′-Diaminobenzidine staining interferes with PCR-based DNA analysis
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Christian Dölle, Laurence A. Bindoff, Charalampos Tzoulis

    3,3′-Diaminobenzidine (DAB) is a widely used chromogen in histological staining methods and stained tissue is often used in downstream molecular analyses such as quantitative PCR (qPCR). Using microdissected muscle fibers from sequential muscle sections stained by DAB-dependent and -independent methods, we show that DAB exerts a strong inhibitory effect on qPCR-based mitochondrial DNA quantification. This effect introduces a significant bias in the estimation of mitochondrial DNA copy number and deletion levels between DAB-positive and -negative fibers. We reproduce our findings in microdissected neurons from human brain tissue, suggesting a general effect of DAB staining on PCR analyses independent of the underlying tissue or cell type. Using an exogenous DNA template added to tissue samples we provide evidence that DAB-staining predominantly interferes with the tissue-derived DNA template rather than inhibiting DNA polymerase activity. Our results suggest that DAB-based staining is incompatible with PCR-based quantification methods and some of the previously reported results employing this approach should be reconsidered.

    更新日期:2018-01-19
  • Local structure, nucleation sites and crystallization behavior and their effects on magnetic properties of Fe81Si x B10P8−xCu1 (x = 0~8)
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    C. C. Cao, Y. G. Wang, L. Zhu, Y. Meng, X. B. Zhai, Y. D. Dai, J. K. Chen, F. M. Pan

    In this work, an attempt has been made to reveal critical factors dominating the crystallization and soft magnetic properties of Fe81Si x B10P8−xCu1 (x = 0, 2, 4, 6 and 8) alloys. Both melt spun and annealed alloys are characterized by differential scanning calorimetry, X-ray diffractometry, Mössbauer spectroscopy, transmission electron microscopy, positron annihilation lifetime spectroscopy and magnetometry. The changes in magnetic interaction between Fe atoms and chemical homogeneity can well explain the variation of magnetic properties of Fe81Si x B10P8−xCu1 amorphous alloys. The density of nucleation sites in the amorphous precursors decreases in the substitution of P by Si. Meanwhile, the precipitated nanograins gradually coarsen, but the inhibiting effect of P on grain growth diminishes causing the increase of the crystallinity. Moreover, various site occupancies of Si are observed in the nanocrystallites and the Si occupancy in bcc Fe decreases the average magnetic moment of nanograins. Without sacrificing amorphous forming ability, we can obtain FeSiBPCu nanocrystalline alloy with excellent soft magnetic properties by optimizing the content of Si and P in the amorphous precursors.

    更新日期:2018-01-19
  • GPhenoVision: A Ground Mobile System with Multi-modal Imaging for Field-Based High Throughput Phenotyping of Cotton
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Yu Jiang, Changying Li, Jon S. Robertson, Shangpeng Sun, Rui Xu, Andrew H. Paterson

    Imaging sensors can extend phenotyping capability, but they require a system to handle high-volume data. The overall goal of this study was to develop and evaluate a field-based high throughput phenotyping system accommodating high-resolution imagers. The system consisted of a high-clearance tractor and sensing and electrical systems. The sensing system was based on a distributed structure, integrating environmental sensors, real-time kinematic GPS, and multiple imaging sensors including RGB-D, thermal, and hyperspectral cameras. Custom software was developed with a multilayered architecture for system control and data collection. The system was evaluated by scanning a cotton field with 23 genotypes for quantification of canopy growth and development. A data processing pipeline was developed to extract phenotypes at the canopy level, including height, width, projected leaf area, and volume from RGB-D data and temperature from thermal images. Growth rates of morphological traits were accordingly calculated. The traits had strong correlations (r = 0.54–0.74) with fiber yield and good broad sense heritability (H2 = 0.27–0.72), suggesting the potential for conducting quantitative genetic analysis and contributing to yield prediction models. The developed system is a useful tool for a wide range of breeding/genetic, agronomic/physiological, and economic studies.

    更新日期:2018-01-19
  • Iron Biogeochemistry in the High Latitude North Atlantic Ocean
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Eric P. Achterberg, Sebastian Steigenberger, Chris M. Marsay, Frédéric A. C. LeMoigne, Stuart C. Painter, Alex R. Baker, Douglas P. Connelly, C. Mark Moore, Alessandro Tagliabue, Toste Tanhua

    Iron (Fe) is an essential micronutrient for marine microbial organisms, and low supply controls productivity in large parts of the world’s ocean. The high latitude North Atlantic is seasonally Fe limited, but Fe distributions and source strengths are poorly constrained. Surface ocean dissolved Fe (DFe) concentrations were low in the study region (<0.1 nM) in summer 2010, with significant perturbations during spring 2010 in the Iceland Basin as a result of an eruption of the Eyjafjallajökull volcano (up to 2.5 nM DFe near Iceland) with biogeochemical consequences. Deep water concentrations in the vicinity of the Reykjanes Ridge system were influenced by pronounced sediment resuspension, with indications for additional inputs by hydrothermal vents, with subsequent lateral transport of Fe and manganese plumes of up to 250–300 km. Particulate Fe formed the dominant pool, as evidenced by 4–17 fold higher total dissolvable Fe compared with DFe concentrations, and a dynamic exchange between the fractions appeared to buffer deep water DFe. Here we show that Fe supply associated with deep winter mixing (up to 103 nmol m−2 d−1) was at least ca. 4–10 times higher than atmospheric deposition, diffusive fluxes at the base of the summer mixed layer, and horizontal surface ocean fluxes.

    更新日期:2018-01-19
  • Tumor Tissue Detection using Blood-Oxygen-Level-Dependent Functional MRI based on Independent Component Analysis
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Huiyuan Huang, Junfeng Lu, Jinsong Wu, Zhongxiang Ding, Shuda Chen, Lisha Duan, Jianling Cui, Fuyong Chen, Dezhi Kang, Le Qi, Wusi Qiu, Seong-Whan Lee, ShiJun Qiu, Dinggang Shen, Yu-Feng Zang, Han Zhang

    Accurate delineation of gliomas from the surrounding normal brain areas helps maximize tumor resection and improves outcome. Blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) has been routinely adopted for presurgical mapping of the surrounding functional areas. For completely utilizing such imaging data, here we show the feasibility of using presurgical fMRI for tumor delineation. In particular, we introduce a novel method dedicated to tumor detection based on independent component analysis (ICA) of resting-state fMRI (rs-fMRI) with automatic tumor component identification. Multi-center rs-fMRI data of 32 glioma patients from three centers, plus the additional proof-of-concept data of 28 patients from the fourth center with non-brain musculoskeletal tumors, are fed into individual ICA with different total number of components (TNCs). The best-fitted tumor-related components derived from the optimized TNCs setting are automatically determined based on a new template-matching algorithm. The success rates are 100%, 100% and 93.75% for glioma tissue detection for the three centers, respectively, and 85.19% for musculoskeletal tumor detection. We propose that the high success rate could come from the previously overlooked ability of BOLD rs-fMRI in characterizing the abnormal vascularization, vasomotion and perfusion caused by tumors. Our findings suggest an additional usage of the rs-fMRI for comprehensive presurgical assessment.

    更新日期:2018-01-19
  • Hemoglobin catalyzes CoA degradation and thiol addition to flavonoids
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Toshiki Nagakubo, Takuto Kumano, Yoshiteru Hashimoto, Michihiko Kobayashi

    In the presence of CoA, cell-free extracts prepared from porcine liver was found to convert 7,8-dihydroxyflavone (DHF) to a pantetheine conjugate, which was a novel flavonoid. We purified a 7,8-DHF-converting enzyme from the extracts, and identified it as hemoglobin (Hb). The purified Hb showed the following two activities: (i) degradation of CoA into pantetheine through hydrolytic cleavage to yield pantetheine and 3′-phospho-adenosine-5′-diphosphate (ADP) independently of heme, and (ii) addition of a thiol (e.g., pantetheine, glutathione and cysteine) to 7,8-DHF through C-S bond formation. Human Hb also exhibited the above flavonoid-converting activity. In addition, heme-containing enzymes such as peroxidase and catalase added each of pantetheine, glutathione and cysteine to the flavonoid, although no pantetheine conjugates were synthesized when CoA was used as a substrate. These findings indicated that the thiol-conjugating activity is widely observed in heme-containing proteins. On the other hand, only Hb catalyzed the hydrolysis of CoA, followed by the thiol conjugation to synthesize the pantetheine conjugate. To the best of our knowledge, this is the first report showing that Hb has the catalytic ability to convert naturally occurring bioactive compounds, such as dietary flavonoids, to the corresponding conjugates in the presence of thiol donors or CoA.

    更新日期:2018-01-19
  • Black-legged kittiwakes as messengers of Atlantification in the Arctic
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Mikko Vihtakari, Jorg Welcker, Børge Moe, Olivier Chastel, Sabrina Tartu, Haakon Hop, Claus Bech, Sébastien Descamps, Geir Wing Gabrielsen

    Climate warming is rapidly altering marine ecosystems towards a more temperate state on the European side of the Arctic. However, this “Atlantification” has rarely been confirmed, as long-term datasets on Arctic marine organisms are scarce. We present a 19-year time series (1982–2016) of diet samples from black-legged kittiwakes as an indicator of the changes in a high Arctic marine ecosystem (Kongsfjorden, Svalbard). Our results highlight a shift from Arctic prey dominance until 2006 to a more mixed diet with high contribution of Atlantic fishes. Capelin, an Atlantic species, dominated the diet composition in 2007, marking a shift in the food web. The occurrence of polar cod, a key Arctic fish species, positively correlated with sea ice index, whereas Atlantic species demonstrated the opposite correlation indicating that the diet shift was likely connected with recent climate warming. Kittiwakes, which gather available fish and zooplankton near the sea surface to feed their chicks, can act as messengers of ecosystem change. Changes in their diet reveal that the Kongsfjord system has drifted in an Atlantic direction over the last decade.

    更新日期:2018-01-19
  • Word Mode: a crowding-free reading protocol for individuals with macular disease
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Stuart Wallis, Yit Yang, Stephen J. Anderson

    Central retinal loss through macular disease markedly reduces the ability to read largely because identification of a word using peripheral vision is negatively influenced by nearby text, a phenomenon termed visual crowding. Here, we present a novel peripheral reading protocol, termed Word Mode, that eliminates crowding by presenting each word in isolation but in a position that mimics its natural position in the line of text being read, with each new word elicited using a self-paced button press. We used a gaze-contingent paradigm to simulate a central scotoma in four normally-sighted observers, and measured oral reading speed for text positioned 7.5° in the inferior field. Compared with reading whole sentences, our crowding-free protocol increased peripheral reading speeds by up to a factor of seven, resulted in significantly fewer reading errors and fixations per sentence, and reduced both the critical print size and the text size required for spot reading by 0.2–0.3 logMAR. We conclude that the level of reading efficiency afforded by the crowding-free reading protocol Word Mode may return reading as a viable activity to many individuals with macular disease.

    更新日期:2018-01-19
  • Design of non-equiatomic medium-entropy alloys
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Yang Zhou, Dong Zhou, Xi Jin, Lu Zhang, Xingyu Du, Bangsheng Li

    High-entropy alloys have attracted much attention due to their unique microstructures and excellent properties. Since their invention more than ten years ago, research attention has been mainly focused on the study of multicomponent alloys with equiatomic or near-equiatomic compositions. Here we propose a novel design of non-equiatomic medium-entropy alloys that contain one matrix element and several equiatomic alloying elements. To verify the utility of this new design, a series of Co-free Fex(CrNiAl)100−x (at.%, 25 ≤ x ≤ 65) medium-entropy alloys were designed from the much-studied FeNiCrCoAl high-entropy alloy. Detailed characterization reveals that the alloys exhibit novel two-phase microstructures consisting of B2-ordered nanoprecipitates and BCC-disordered matrix. As the alloys deviate far from equiatomic composition, the structure of the nanoprecipitates transfers from a spinodal-like intertwined structure to a nanoparticle dispersed structure. Previous parametric approaches to predict phase formation rules for high-entropy alloys are unable to describe the phase separation behaviors in the studied alloys. Our findings provide a new route to design medium-entropy alloys and also demonstrate a strategy for designing nanostructured alloys from multicomponent alloy systems through simple variations in non-equiatomic compositions.

    更新日期:2018-01-19
  • Role of subcortical structures on cognitive and social function in schizophrenia
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Daisuke Koshiyama, Masaki Fukunaga, Naohiro Okada, Fumio Yamashita, Hidenaga Yamamori, Yuka Yasuda, Michiko Fujimoto, Kazutaka Ohi, Haruo Fujino, Yoshiyuki Watanabe, Kiyoto Kasai, Ryota Hashimoto

    Subcortical regions have a pivotal role in cognitive, affective, and social functions in humans, and the structural and functional abnormalities of the regions have been associated with various psychiatric disorders. Although previous studies focused on the neurocognitive and socio-functional consequences of prefrontal and tempolo-limbic abnormalities in psychiatric disorders, those of subcortical structures remain largely unknown. Recently, MRI volume alterations in subcortical structures in patients with schizophrenia have been replicated in large-scale meta-analytic studies. Here we investigated the relationship between volumes of subcortical structures and neurocognitive and socio-functional indices in a large sample of patients with schizophrenia. First, we replicated the results of meta-analyses: the regional volumes of the bilateral hippocampus, amygdala, thalamus and nucleus accumbens were significantly smaller for patients (N = 163) than for healthy controls (HCs, N = 620). Second, in the patient group, the right nucleus accumbens volume was significantly correlated with the Digit Symbol Coding score, which is known as a distinctively characteristic index of cognitive deficits in schizophrenia. Furthermore, the right thalamic volume was significantly correlated with social function scores. In HCs, no significant correlation was found. The results from this large-scale investigation shed light upon the role of specific subcortical nuclei on cognitive and social functioning in schizophrenia.

    更新日期:2018-01-19
  • LY2087101 and dFBr share transmembrane binding sites in the (α4)3(β2)2 Nicotinic Acetylcholine Receptor
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Farah Deba, Hamed I. Ali, Abisola Tairu, Kara Ramos, Jihad Ali, Ayman K. Hamouda

    Positive allosteric modulators (PAMs) of nicotinic acetylcholine receptors (nAChRs) have potential therapeutic application in neuropathologies associated with decrease in function or loss of nAChRs. In this study, we characterize the pharmacological interactions of the nAChRs PAM, LY2087101, with the α4β2 nAChR using mutational and computational analyses. LY2087101 potentiated ACh-induced currents of low-sensitivity (α4)3(β2)2 and high-sensitivity (α4)2(β2)3 nAChRs with similar potencies albeit to a different maximum potentiation (potentiation I max = ~840 and 450%, respectively). Amino acid substitutions within the α4 subunit transmembrane domain [e.g. α4Leu256 and α4Leu260 within the transmembrane helix 1 (TM1); α4Phe316 within the TM3; and α4Gly613 within TM4] significantly reduced LY2087101 potentiation of (α4)3(β2)2 nAChR. The locations of these amino acid residues and LY2087101 computational docking analyses identify two LY2087101 binding sites: an intrasubunit binding site within the transmembrane helix bundle of α4 subunit at the level of α4Leu260/α4Phe316 and intersubunit binding site at the α4:α4 subunit interface at the level of α4Leu256/α4Ile315 with both sites extending toward the extracellular end of the transmembrane domain. We also show that desformylflustrabromine (dFBr) binds to these two sites identified for LY2087101. These results provide structural information that are pertinent to structure-based design of nAChR allosteric modulators.

    更新日期:2018-01-19
  • Relationship between serum cortisol level and degree of false lumen thrombosis in patients with uncomplicated type B aortic dissection
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Yani Wu, Yudong Sun, Xiaolong Wei, Lei Zhang, Tonglei Han, Zhiqing Zhao, Jian Zhou, Zaiping Jing

    Partial thrombosis of the false lumen in uncomplicated type B aortic dissection (uTBAD) is associated with an increased late mortality risk. Whether the serum cortisol level can affect false lumen thrombosis in patients with uTBAD has not been well characterized. This study was performed on 87 patients with uTBAD. A curve-fitting method was used to analyze the relationship between serum cortisol and partial thrombosis of false lumen. Univariate and multivariate logistic regression analyses were used to identify false lumen partial thrombosis–associated serum cortisol. Curve-fitting’s result revealed a characteristic U shape, and 14.0 µg/dL was considered as the cutoff point for serum cortisol. The results of univariate and multivariate logistic regression analyses suggested that when trisecting the serum cortisol level into three parts, the low and high levels of serum cortisol could significantly affect the occurrence of false lumen partial thrombosis compared with the middle level. The odds ratio value of the low and high levels of serum cortisol was 6.12 and 4.65, respectively, in the univariate analysis, and 24.32 and 3.93, respectively, in the multivariate analysis. Low or high levels of serum cortisol might influence the natural result of uTBAD through affecting the false lumen thrombosis.

    更新日期:2018-01-19
  • Prevention of Retinal Degeneration in a Rat Model of Smith-Lemli-Opitz Syndrome
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Steven J. Fliesler, Neal S. Peachey, Josi Herron, Kelly M. Hines, Nadav I. Weinstock, Sriganesh Ramachandra Rao, Libin Xu

    Smith-Lemli-Opitz Syndrome (SLOS) is a recessive human disease caused by defective cholesterol (CHOL) synthesis at the level of DHCR7 (7-dehydrocholesterol reductase), which normally catalyzes the conversion of 7-dehydrocholesterol (7DHC) to CHOL. Formation and abnormal accumulation of 7DHC and 7DHC-derived oxysterols occur in SLOS patients and in rats treated with the DHCR7 inhibitor AY9944. The rat SLOS model exhibits progressive and irreversible retinal dysfunction and degeneration, which is only partially ameliorated by dietary CHOL supplementation. We hypothesized that 7DHC-derived oxysterols are causally involved in this retinal degeneration, and that blocking or reducing their formation should minimize the phenotype. Here, using the SLOS rat model, we demonstrate that combined dietary supplementation with CHOL plus antioxidants (vitamins E and C, plus sodium selenite) provides better outcomes than dietary CHOL supplementation alone with regard to preservation of retinal structure and function and lowering 7DHC-derived oxysterol formation. These proof-of-principle findings provide a translational, pre-clinical framework for designing clinical trials using CHOL-antioxidant combination therapy as an improved therapeutic intervention over the current standard of care for the treatment of SLOS.

    更新日期:2018-01-19
  • Robust phenotype prediction from gene expression data using differential shrinkage of co-regulated genes
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Kourosh Zarringhalam, David Degras, Christoph Brockel, Daniel Ziemek

    Discovery of robust diagnostic or prognostic biomarkers is a key to optimizing therapeutic benefit for select patient cohorts - an idea commonly referred to as precision medicine. Most discovery studies to derive such markers from high-dimensional transcriptomics datasets are weakly powered with sample sizes in the tens of patients. Therefore, highly regularized statistical approaches are essential to making generalizable predictions. At the same time, prior knowledge-driven approaches have been successfully applied to the manual interpretation of high-dimensional transcriptomics datasets. In this work, we assess the impact of combining two orthogonal approaches for the discovery of biomarker signatures, namely (1) well-known lasso-based regression approaches and its more recent derivative, the group lasso, and (2) the discovery of significant upstream regulators in literature-derived biological networks. Our method integrates both approaches in a weighted group-lasso model and differentially weights gene sets based on inferred active regulatory mechanism. Using nested cross-validation as well as independent clinical datasets, we demonstrate that our approach leads to increased accuracy and generalizable results. We implement our approach in a computationally efficient, user-friendly R package called creNET. The package can be downloaded at https://github.com/kouroshz/creNethttps://github.com/kouroshz/creNet and is accompanied by a parsed version of the STRING DB data base.

    更新日期:2018-01-19
  • Pseudoalteromonas haloplanktis TAC125 produces 4-hydroxybenzoic acid that induces pyroptosis in human A459 lung adenocarcinoma cells
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Filomena Sannino, Clementina Sansone, Christian Galasso, Sara Kildgaard, Pietro Tedesco, Renato Fani, Gennaro Marino, Donatella Pascale, Adrianna Ianora, Ermenegilda Parrilli, Thomas Ostenfeld Larsen, Giovanna Romano, Maria Luisa Tutino

    In order to exploit the rich reservoir of marine cold-adapted bacteria as a source of bioactive metabolites, ethyl acetate crude extracts of thirteen polar marine bacteria were tested for their antiproliferative activity on A549 lung epithelial cancer cells. The crude extract from Pseudoalteromonas haloplanktis TAC125 was the most active in inhibiting cell proliferation. Extensive bioassay-guided purification and mass spectrometric characterization allowed the identification of 4-hydroxybenzoic acid (4-HBA) as the molecule responsible for this bioactivity. We further demonstrate that 4-HBA inhibits A549 cancer cell proliferation with an IC50 value ≤ 1 μg ml−1, and that the effect is specific, since the other two HBA isomers (i.e. 2-HBA and 3-HBA) were unable to inhibit cell proliferation. The effect of 4-HBA is also selective since treatment of normal lung epithelial cells (WI-38) with 4-HBA did not affect cell viability. Finally, we show that 4-HBA is able to activate, at the gene and protein levels, a specific cell death signaling pathway named pyroptosis. Accordingly, the treatment of A549 cells with 4-HBA induces the transcription of (amongst others) caspase-1, IL1β, and IL18 encoding genes. Studies needed for the elucidation of mode of action of 4-HBA will be instrumental in depicting novel details of pyroptosis.

    更新日期:2018-01-19
  • Determinants of breast size in Asian women
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Li Yan Lim, Peh Joo Ho, Jenny Liu, Wen Yee Chay, Min-Han Tan, Mikael Hartman, Jingmei Li

    Breast size as a risk factor of breast cancer has been studied extensively with inconclusive results. Here we examined the associations between breast size and breast cancer risk factors in 24,353 Asian women aged 50 to 64 years old enrolled in a nationwide mammography screening project conducted between October 1994 and February 1997. Information on demographic and reproductive factors was obtained via a questionnaire. Breast size was ascertained as bust line measured at study recruitment and total breast area measured from a mammogram. The average bust line and total breast area was 91.2 cm and 102.3 cm2, respectively. The two breast measurements were moderately correlated (Spearman correlation coefficient = 0.65). Age, BMI, marital and working status were independently associated with bust line and total breast area. In the multivariable analyses, the most pronounced effects were observed for BMI (24.2 cm difference in bust line and 39.4 cm2 in breast area comparing women with BMI ≥30 kg/m2 to BMI <20 kg/m2). Ethnicity was a positive predictor for total breast area, but not bust line.

    更新日期:2018-01-19
  • Spatio-temporal characteristics of urban air pollutions and their causal relationships: Evidence from Beijing and its neighboring cities
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Lei Jiang, Ling Bai

    China has been suffering from serious air pollution for years in response to the rapid industrialization and urbanization. Notably Beijing is one of the most polluted capitals in the world. Hence, the focus of the study area is on Beijing. In the first stage, we analyze spatial and temporal characteristics of air pollution of the 6 cities while in the second stage the Granger causality test is applied to investigate whether air pollution of a city is affected by its neighbors, and vice versa. The findings are the following. Overall, AQI values are high in winter and early spring while low in summer and autumn. Among the 6 cities, Baoding is the major contributor to air pollution in this entire area. Besides, Granger causality test results show that there is a unidirectional relationship running from Baoding to Beijing and a bidirectional relationship between Beijing and Tianjin. In other words, apart from local air pollutants, for example, exhaust gas, air quality of Beijing is affected by air pollution of Tianjin, and vice versa. However, regarding the relationship between Beijing and Baoding, air quality of Beijing is just affected by air pollution of Baoding, since Baoding is much polluted than Beijing.

    更新日期:2018-01-19
  • Biomolecular regulation, composition and nanoarchitecture of bone mineral
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Atharva A. Poundarik, Adele Boskey, Caren Gundberg, Deepak Vashishth

    Tough natural nanocomposites like bone, nacre and sea sponges contain within their hierarchy, a mineral (phosphate, silicate or carbonate) phase that interacts with an organic phase. In bone, the role of mineral ultrastructure (organization, morphology, composition) is crucial to the mechanical and biological properties of the tissue. Better understanding of mineral interaction with the organic matrix, in particular non-collagenous proteins, osteocalcin (OC) and osteopontin (OPN), can lead to better design of biomimetic materials. Using small angle x-ray scattering (SAXS) and wavelength dispersive spectroscopy (WDS) on single (OC−/− and OPN−/−) and double (OC-OPN−/−;−/−) genetic knockout mice bones, we demonstrate that both osteocalcin and osteopontin have specific roles in the biomolecular regulation of mineral in bone and together they are major determinants of the quality of bone mineral. Specifically, for the first time, we show that proteins osteocalcin and osteopontin regulate bone mineral crystal size and organization in a codependent manner, while they independently determine crystal shape. We found that OC is more dominant in the regulation of the physical properties of bone mineral, while OPN is more dominant in the regulation of the mineral composition.

    更新日期:2018-01-19
  • Wearable Sweat Rate Sensors for Human Thermal Comfort Monitoring
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Jai Kyoung Sim, Sunghyun Yoon, Young-Ho Cho

    We propose watch-type sweat rate sensors capable of automatic natural ventilation by integrating miniaturized thermo-pneumatic actuators, and experimentally verify their performances and applicability. Previous sensors using natural ventilation require manual ventilation process or high-power bulky thermo-pneumatic actuators to lift sweat rate detection chambers above skin for continuous measurement. The proposed watch-type sweat rate sensors reduce operation power by minimizing expansion fluid volume to 0.4 ml through heat circuit modeling. The proposed sensors reduce operation power to 12.8% and weight to 47.6% compared to previous portable sensors, operating for 4 hours at 6 V batteries. Human experiment for thermal comfort monitoring is performed by using the proposed sensors having sensitivity of 0.039 (pF/s)/(g/m2h) and linearity of 97.9% in human sweat rate range. Average sweat rate difference for each thermal status measured in three subjects shows (32.06 ± 27.19) g/m2h in thermal statuses including ‘comfortable’, ‘slightly warm’, ‘warm’, and ‘hot’. The proposed sensors thereby can discriminate and compare four stages of thermal status. Sweat rate measurement error of the proposed sensors is less than 10% under air velocity of 1.5 m/s corresponding to human walking speed. The proposed sensors are applicable for wearable and portable use, having potentials for daily thermal comfort monitoring applications.

    更新日期:2018-01-19
  • Bedside assessment of regional cerebral perfusion using near-infrared spectroscopy and indocyanine green in patients with atherosclerotic occlusive disease
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Hiroshi Saito, Tatsuya Ishikawa, Jun Tanabe, Shinya Kobayashi, Junta Moroi

    This pilot study aimed to investigate the utility of near-infrared spectroscopy/indocyanine green (NIRS/ICG) for examining patients with occlusive cerebrovascular disease. Twenty-nine patients with chronic-stage atherosclerotic occlusive cerebrovascular disease were included. The patients were monitored using NIRS at the bedside. Using ICG time-intensity curves, the affected-to-unaffected side ratios were calculated for several parameters, including the maximum ICG concentration (ΔICGmax), time to peak (TTP), rise time (RT), and blood flow index (BFI = ΔICGmax/RT), and were compared to the affected-to-unaffected side ratios of the regional cerebral blood flow (rCBF) and regional oxygen extraction fraction (rOEF) obtained using positron emission tomography with 15O-labeled gas. The BFI ratio showed the best correlation with the rCBF ratio among these parameters (r = 0.618; P = 0.0004), and the RT ratio showed the best correlation with the rOEF ratio (r = 0.593; P = 0.0007). The patients were further divided into reduced rCBF or elevated rOEF groups, and the analysis revealed significant related differences. The present results advance the measurement of ICG kinetics using NIRS as a useful tool for the detection of severely impaired perfusion with reduced rCBF or elevated rOEF. This method may be applicable as a monitoring tool for patients with acute ischemic stroke.

    更新日期:2018-01-19
  • Effect of in vitro storage duration on measured mechanical properties of brain tissue
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Wei Zhang, Li-fu Liu, Yue-jiao Xiong, Yi-fan Liu, Sheng-bo Yu, Cheng-wei Wu, Weihong Guo

    Accurate characterization of the mechanical properties of brain tissue is essential for understanding the mechanisms of traumatic brain injuries and developing protective gears or facilities. However, how storage conditions might affect the mechanical properties of brain tissue remains unclear. The objective of this study is to investigate the effect of in vitro storage duration on the mechanical performance of brain tissue since measurements are usually carried out in vitro. Differential Scanning Calorimetry (DSC) measurements and uniaxial compression mechanical experiments are carried out. The results indicate that, for brain tissue stored at 1 °C without any liquid medium, the bio-molecular interactions and the mechanical strength of both white and grey matter deteriorate with prolonged storage duration. Transmission Electron Microscopy (TEM) results reveal the degeneration of myelin sheaths and the vacuolization of cristae with prolonged storage duration, suggesting that the in vitro storage duration should be carefully controlled. The findings from this study might facilitate the development of guidelines and standards for the in vitro storage of brain tissue.

    更新日期:2018-01-19
  • The Direction of Tumour Growth in Glioblastoma Patients
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Morteza Esmaeili, Anne Line Stensjøen, Erik Magnus Berntsen, Ole Solheim, Ingerid Reinertsen

    Generating MR-derived growth pattern models for glioblastoma multiforme (GBM) has been an attractive approach in neuro-oncology, suggesting a distinct pattern of lesion spread with a tendency in growing along the white matter (WM) fibre direction for the invasive component. However, the direction of growth is not much studied in vivo. In this study, we sought to study the dominant directions of tumour expansion/shrinkage pre-treatment. We examined fifty-six GBMs at two time-points: at radiological diagnosis and as part of the pre-operative planning, both with contrast-enhanced T1-weighted MRIs. The tumour volumes were semi-automatically segmented. A non-linear registration resulting in a deformation field characterizing the changes between the two time points was used together with the segmented tumours to determine the dominant directions of tumour change. To compute the degree of alignment between tumour growth vectors and WM fibres, an angle map was calculated. Our results demonstrate that tumours tend to grow predominantly along the WM, as evidenced by the dominant vector population with the maximum alignments. Our findings represent a step forward in investigating the hypothesis that tumour cells tend to migrate preferentially along the WM.

    更新日期:2018-01-19
  • Degree of severity of molar incisor hypomineralization and its relation to dental caries
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    A. Negre-Barber, J. M. Montiel-Company, M. Catalá-Pizarro, J. M. Almerich-Silla

    Molar incisor hypomineralization is a developmental defect of dental enamel associated with rapid caries progression. In order to discover whether molar incisor hypomineralization predisposes to dental caries, a cross-sectional cohort study was conducted in a sample of 414 children aged between eight and nine years. It was found that 24.2% of the children presented molar incisor hypomineralization. Of these, 72% had a mild form and 28% a severe form. Caries prevalence was greater among the children with severe form (60.7%) than in those with mild form (43.1%) or no molar incisor hypomineralization (45.5%). The caries indices were higher in out molar incisor hypomineralization (1.18) or with mild form (1.08). The tooth-surface caries ratio was significantly higher in surfaces with severe hypomineralization than in those with no hypomineralization or mild hypomineralization. A linear regression model showed that cariogenic food intake and the presence of severe molar incisor hypomineralization were significantly associated with DMFS. Consequently, an association was found to exist between dental caries and the presence of surfaces affected by severe molar incisor hypomineralization, which should be considered a risk factor within the multifactorial etiology of caries.

    更新日期:2018-01-19
  • Renal scattered tubular-like cells confer protective effects in the stenotic murine kidney mediated by release of extracellular vesicles
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Xiangyu Zou, Soon Hyo Kwon, Kai Jiang, Christopher M. Ferguson, Amrutesh S. Puranik, Xiangyang Zhu, Lilach O. Lerman

    To test the hypothesis that intrinsic renal scattered tubular cells (STC-like cells) contribute to repairing injured tubular epithelial cells (TEC) by releasing extracellular vesicle (EV). EV released from primary cultured pig STC-like cells were confirmed by electron microscopy. Antimycin-A (AMA)-induced injured proximal TEC (PK1 cells) were co-cultured with STC-like cells, STC-like cells-derived EV, or EV-free conditioned-medium for 3 days. Cellular injury, oxidative stress and mitochondrial function were assessed. Transfer of mitochondria from STC-like cells to TEC was assessed using Mito-trackers, and their viability by mitochondrial membrane potential assays. STC-like cells-derived EV were intra-arterially injected into mice 2 weeks after induction of unilateral renal artery stenosis. Two weeks later, renal hemodynamics were studied using magnetic-resonance-imaging, and renal fibrosis assessed ex-vivo. Cultured STC-like cells released EV that were uptaken by TEC. A protective effect conferred by STC-like cells in AMA-induced TEC injury was partly mimicked by their EV. Furthermore, STC-like cells-EV carried and transferred mitochondrial material to injured TEC, which partly restored mitochondrial function. In vivo, STC-like cells-derived EV engrafted in the stenotic kidney, and improved its perfusion and oxygenation. STC-like cells-EV exert protective effects on injured tubular cells in vitro and in vivo, partly by transferring STC-like cells mitochondria, which remain at least partly functional in recipient TEC.

    更新日期:2018-01-19
  • Distribution and the origin of invasive apple snails, Pomacea canaliculata and P. maculata (Gastropoda: Ampullariidae) in China
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Qian-Qian Yang, Su-Wen Liu, Chao He, Xiao-Ping Yu

    Species of Pomacea, commonly known as apple snails, are native to South America, and have become widely distributed agricultural and environmental pests in southern China since their introduction in the 1980s. However, only since 2010 have researchers recognized that at least two species, P. canaliculata and P. maculata, are present in China. Although impacts of apple snails have been extensively documented, confusion still persists regarding current distributions and origin of the species in China. To resolve this confusion, we used phylogenetic and phylogeographic methods to analyze 1464 mitochondrial COI sequences, including 349 new sequences from samples collected in southern China and 1115 publicly available sequences from snails collected in the native and introduced ranges. Pomacea canaliculata was found at all sampled localities, while P. maculata was found at only five sampled localities in the Sichuan basin and Zhejiang province. Our data indicate that Chinese populations of P. canaliculata share an Argentinian origin, consistent with multiple introductions of this species elsewhere in Asia. In addition, just a single lineage of P. maculata is established in China, which shares with populations in Brazil.

    更新日期:2018-01-19
  • Microbial regulation of the L cell transcriptome
    Sci. Rep. (IF 4.259) Pub Date : 2018-01-19
    Tulika Arora, Rozita Akrami, Ramona Pais, Linda Bergqvist, Bengt R. Johansson, Thue W. Schwartz, Frank Reimann, Fiona M. Gribble, Fredrik Bäckhed

    L cells are an important class of enteroendocrine cells secreting hormones such as glucagon like peptide-1 and peptide YY that have several metabolic and physiological effects. The gut is home to trillions of bacteria affecting host physiology, but there has been limited understanding about how the microbiota affects gene expression in L cells. Thus, we rederived the reporter mouse strain, GLU-Venus expressing yellow fluorescent protein under the control of the proglucagon gene, as germ-free (GF). Lpos cells from ileum and colon of GF and conventionally raised (CONV-R) GLU-Venus mice were isolated and subjected to transcriptomic profiling. We observed that the microbiota exerted major effects on ileal L cells. Gene Ontology enrichment analysis revealed that microbiota suppressed biological processes related to vesicle localization and synaptic vesicle cycling in Lpos cells from ileum. This finding was corroborated by electron microscopy of Lpos cells showing reduced numbers of vesicles as well as by demonstrating decreased intracellular GLP-1 content in primary cultures from ileum of CONV-R compared with GF GLU-Venus mice. By analysing Lpos cells following colonization of GF mice we observed that the greatest transcriptional regulation was evident within 1 day of colonization. Thus, the microbiota has a rapid and pronounced effect on the L cell transcriptome, predominantly in the ileum.

    更新日期:2018-01-19
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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