bluuebunny/crossref_metadata_2025 huggingface dataset:
Deletion Of XIAP reduces the severity of acute pancreatitis via regulation of cell death and nuclear factor-κB activity
Authors: Liu Yong , Chen Xiao-Dong , Yu Jiang , Chi Jun-Lin , Long Fei-Wu , Yang Hong-Wei , Chen Ke-Ling , Lv Zhao-Ying , Zhou Bin , Peng Zhi-Hai , Sun Xiao-Feng , Li Yuan , Zhou Zong-Guang
Published: March 2017

Severe acute pancreatitis (SAP) still remains a clinical challenge, not only for its high mortality but the uncontrolled inflammatory progression from acute pancreatitis (AP) to SAP. Cell death, including apoptosis and necrosis are critical pathology of AP, since the severity of pancreatitis correlates directly with necrosis and inversely with apoptosis Therefore, regulation of cell death from necrosis to apoptosis may have practicably therapeutic value. X-linked inhibitor of apoptosis protein (XIAP) is the best characterized member of the inhibitor of apoptosis proteins (IAP) family, but its function in AP remains unclear. In the present study, we investigated the potential role of XIAP in regulation of cell death and inflammation during acute pancreatitis. The in vivo pancreatitis model was induced by the administration of cerulein with or without lipopolysaccharide (LPS) or by the administration of l-arginine in wild-type or XIAP-deficient mice, and ex vivo model was induced by the administration of cerulein+LPS in AR42J cell line following XIAP inhibition. The severity of acute pancreatitis was determined by serum amylase activity and histological grading. XIAP deletion on cell apoptosis, necrosis and inflammatory response were examined. Caspases activities, nuclear factor-κB (NF-κB) activation and receptor-interacting protein kinase1 (RIP1) degradation were assessed by western blot. Deletion of XIAP resulted in the reduction of amylase activity, decrease of NF-κB activation and less release of TNF-α and IL-6, together with increased caspases activities and RIP1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. Our results indicate that deletion of XIAP switches cell death away from necrosis to apoptosis and decreases the inflammatory response, effectively attenuating the severity of AP/SAP. The critical role of XIAP in cell death and inflammation suggests that inhibition of XIAP represents a potential therapeutic strategy for the treatment of acute pancreatitis.
NCAPH plays important roles in human colon cancer
Authors: Yin Liang , Jiang Li-Ping , Shen Qiu-Shuo , Xiong Qiu-Xia , Zhuo Xiao , Zhang Long-Long , Yu Hai-Jing , Guo Xiang , Luo Ying , Dong Jian , Kong Qing-Peng , Yang Cui-Ping , Chen Yong-Bin
Published: March 2017

Colon cancer (CC) is one of the major malignancies worldwide, whose pathogenesis is complex and requires the accumulated alteration of multiple genes and signaling pathways. Condensins are multi-protein complexes that play pivotal roles in chromosome assembly and segregation during mitosis, meiosis and even tumorigenesis. Using tissue microarrays by immunohistochemistry and hematoxylin–eosin staining, we found that non-SMC condensin I complex subunit H (NCAPH) in colon cancerous tissues was higher than that in all corresponding adjacent non-cancerous tissues. We then characterized the exact function of the NCAPH in CC. We provided evidences showing that NCAPH is highly expressed in colorectal cancer cell lines comparing with normal human colonic epithelial cells, and identified many NCAPH mutations in CC patients. We found that depletion of NCAPH inhibits CC cell proliferation, migration in vitro and xenograft tumor formation in vivo. Furthermore, NCAPH knockdown promotes cell apoptosis and cell cycle arrest at G2/M phase. Interestingly, the NCAPH high expression in tumor tissues of colon patients had a significantly better prognosis and survival rate than low-expression patients, suggesting that NCAPH high expression promotes colonic cancerous cell proliferation; on the other hand, it may also sensitize these cells responding to chemo- or radio-therapies. Collectively, these findings reveal an important role of NCAPH in CC, indicating that NCAPH could be used as a new therapeutic target in future.
IL-27 triggers IL-10 production in Th17 cells via a c-Maf/RORγt/Blimp-1 signal to promote the progression of endometriosis
Authors: Chang Kai-Kai , Liu Li-Bing , Jin Li-Ping , Zhang Bing , Mei Jie , Li Hui , Wei Chun-Yan , Zhou Wen-Jie , Zhu Xiao-Yong , Shao Jun , Li Da-Jin , Li Ming-Qing
Published: March 2017

Endometriosis is an estrogen-dependent inflammatory disease. The anti-inflammatory cytokine IL-10 is also increased in endometriosis. IL-10 production by Th17 cells is critical for limiting autoimmunity and inflammatory responses. However, the mechanism of inducing IL-10-producing Th17 cells is still largely unknown. The present study investigated the differentiation mechanism and role of IL-10-producing Th17 cells in endometriosis. Here, we report that IL-10+Th17 cells are significantly increased in the peritoneal fluid of women with endometriosis, along with an elevation of IL-27, IL-6 and TGF-β. Compared with peripheral CD4+ T cells, endometrial CD4+ T cells highly expressed IL-27 receptors, especially the ectopic endometrium. Under external (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) and local (estrogen, IL-6 and TGF-β) environmental regulation, IL-27 from macrophages and endometrial stromal cells (ESCs) induces IL-10 production in Th17 cells in vitro and in vivo. This process may be mediated through the interaction between c-musculoaponeurotic fibrosarconna (c-Maf) and retinoic acid-related orphan receptor gamma t (RORγt), and associated with the upregulation of downstream B lymphocyte-induced maturation protein-1 (Blimp-1). IL-10+Th17 cells, in turn, stimulate the proliferation and implantation of ectopic lesions and accelerate the progression of endometriosis. These results suggest that IL-27 is a pivotal regulator in endometriotic immune tolerance by triggering Th17 cells to produce IL-10 and promoting the rapid growth and implantation of ectopic lesions. This finding provides a scientific basis for potential therapeutic strategies aimed at preventing the development of endometriosis, especially for patients with high levels of IL-10+Th17 cells.
Membrane association and release of wild-type and pathological tau from organotypic brain slice cultures
Authors: Croft Cara L , Wade Matthew A , Kurbatskaya Ksenia , Mastrandreas Pavlina , Hughes Martina M , Phillips Emma C , Pooler Amy M , Perkinton Michael S , Hanger Diane P , Noble Wendy
Published: March 2017

The spatiotemporal transmission of pathological tau in the brain is characteristic of Alzheimer’s disease. Release of both soluble and abnormal tau species from healthy neurons is increased upon stimulation of neuronal activity. It is not yet understood whether the mechanisms controlling soluble tau release from healthy neurons is the same as those involved in the spread of pathological tau species. To begin to understand these events, we have studied tau distribution and release using organotypic brain slice cultures. The slices were cultured from postnatal wild-type and 3xTg-AD mice for up to 1 month. Tau distribution in subcellular compartments was examined by western blotting, and tau release into culture medium was determined using a sensitive sandwich ELISA. We show here that 3xTg-AD cultures have an accelerated development of pathological tau abnormalities including the redistribution of tau to synaptic and membrane compartments. The 3xTg-AD slice cultures show elevated basal tau release relative to total tau when compared with wild-type cultures. However, tau release from 3xTg-AD slices cannot be further stimulated when neuronal activity is increased with potassium chloride. Moreover, we report that there is an increased pool of dephosphorylated membrane-associated tau in conditions where tau release is increased. These data suggest that there may be differential patterns of tau release when using integrated slice culture models of wild-type and transgenic mouse brain, although it will be important to determine the effect of tau overexpression for these findings. These results further increase our knowledge of the molecular mechanisms underlying tau release and propagation in neurodegenerative tauopathies.
Unravelling the hidden link of lithium halides and application in the synthesis of organocuprates
Authors: Yi Hong , Yang Dali , Xin Jie , Qi Xiaotian , Lan Yu , Deng Yi , Pao Chih-Wen , Lee Jyh-Fu , Lei Aiwen
Published: March 2017

As a versatile metal, copper has demonstrated a wide application in acting as both organometallic reagent and catalyst. Organocuprates are among the most used organometallic reagents in the formation of new carbon–carbon bonds in organic synthesis. Therefore, revealing the real structures of organocuprates in solution is crucial to provide insights into the reactivity of organocuprates. Here we provide several important insights into organocuprate chemistry. The main finding contains the following aspects. The Cu(0) particles were detected via the reduction of CuX by nBuLi or PhLi. The Cu(II) precursors CuX2 (X=Cl, Br) could be used for the preparation of Gilman reagents. In addition, we provide direct evidence for the role and effect of LiX in organocuprate synthesis. Moreover, the EXAFS spectrum provides direct evidence for the exact structure of Li+ CuX2− ate complex in solution. This work not only sheds important light on the role of LiX in the formation of organocuprates but also reports two new routes for organocuprate synthesis.
H3 ubiquitination by NEDD4 regulates H3 acetylation and tumorigenesis
Authors: Zhang Xian , Li Binkui , Rezaeian Abdol Hossein , Xu Xiaohong , Chou Ping-Chieh , Jin Guoxiang , Han Fei , Pan Bo-Syong , Wang Chi-Yun , Long Jie , Zhang Anmei , Huang Chih-Yang , Tsai Fuu-Jen , Tsai Chang-Hai , Logothetis Christopher , Lin Hui-Kuan
Published: March 2017

Dynamic changes in histone modifications under various physiological cues play important roles in gene transcription and cancer. Identification of new histone marks critical for cancer development is of particular importance. Here we show that, in a glucose-dependent manner, E3 ubiquitin ligase NEDD4 ubiquitinates histone H3 on lysine 23/36/37 residues, which specifically recruits histone acetyltransferase GCN5 for subsequent H3 acetylation. Genome-wide analysis of chromatin immunoprecipitation followed by sequencing reveals that NEDD4 regulates glucose-induced H3 K9 acetylation at transcription starting site and enhancer regions. Integrative analysis of ChIP-seq and microarray data sets also reveals a consistent role of NEDD4 in transcription activation and H3 K9 acetylation in response to glucose. Functionally, we show that NEDD4-mediated H3 ubiquitination, by transcriptionally activating IL1α, IL1β and GCLM, is important for tumour sphere formation. Together, our study reveals the mechanism for glucose-induced transcriptome reprograming and epigenetic regulation in cancer by inducing NEDD4-dependent H3 ubiquitination.
Mycophagous rove beetles highlight diverse mushrooms in the Cretaceous
Authors: Cai Chenyang , Leschen Richard A. B. , Hibbett David S , Xia Fangyuan , Huang Diying
Published: March 2017

Agaricomycetes, or mushrooms, are familiar, conspicuous and morphologically diverse Fungi. Most Agaricomycete fruiting bodies are ephemeral, and their fossil record is limited. Here we report diverse gilled mushrooms (Agaricales) and mycophagous rove beetles (Staphylinidae) from mid-Cretaceous Burmese amber, the latter belonging to Oxyporinae, modern members of which exhibit an obligate association with soft-textured mushrooms. The discovery of four mushroom forms, most with a complete intact cap containing distinct gills and a stalk, suggests evolutionary stasis of body form for ∼99 Myr and highlights the palaeodiversity of Agaricomycetes. The mouthparts of early oxyporines, including enlarged mandibles and greatly enlarged apical labial palpomeres with dense specialized sensory organs, match those of modern taxa and suggest that they had a mushroom feeding biology. Diverse and morphologically specialized oxyporines from the Early Cretaceous suggests the existence of diverse Agaricomycetes and a specialized trophic interaction and ecological community structure by this early date.
Natural killer cell activation contributes to hepatitis B viral control in a mouse model
Authors: Tong Shiwen , Liu Guangze , Li Minghong , Li Xiumei , Liu Qian , Peng Hong , Li Shiying , Ren Hong , Yin Wenwei
Published: March 2017

The roles of CD4 + T cells and CD8 + T cells in hepatitis B virus (HBV) infection have been well documented. However, the role of innate immunity in HBV infection remains obscure. Here we examined the effect of activation of innate immunity by polyinosinic: polycytidylic acid (PolyI:C) on HBV infection. A chronic HBV replication mouse model was established by hydrodynamical injection of pAAV/HBV1.2 plasmid into C57BL/6 mice. We found that HBV did not seem to induce an active NK-cell response in the mouse model. Early PolyI:C treatment markedly decreased serum HBV levels and led to HBV clearance. Following PolyI:C injection, NK cells were activated and accumulated in the liver. Depletion of NK cells markedly attenuated the anti-HBV activity of PolyI:C. Moreover, we found that IFN-γ production from NK cells was essential for the antiviral effect of PolyI:C in the model. Importantly, activation of NK cells by PolyI:C could also lead to HBV suppression in HBV-tolerant mice and HBV-transgenic mice. These results suggest that activated NK cells might suppress HBV and contribute to HBV clearance during natural HBV infection. In addition, therapeutic activation of NK cells may represent a new strategy for the treatment of chronic HBV infection.
Hyperosmolarity impedes the cross-priming competence of dendritic cells in a TRIF-dependent manner
Authors: Popovic Zoran V. , Embgenbroich Maria , Chessa Federica , Nordström Viola , Bonrouhi Mahnaz , Hielscher Thomas , Gretz Norbert , Wang Shijun , Mathow Daniel , Quast Thomas , Schloetel Jan-Gero , Kolanus Waldemar , Burgdorf Sven , Gröne Hermann-Josef
Published: March 2017

Tissue osmolarity varies among different organs and can be considerably increased under pathologic conditions. Hyperosmolarity has been associated with altered stimulatory properties of immune cells, especially macrophages and dendritic cells. We have recently reported that dendritic cells upon exposure to hypertonic stimuli shift their profile towards a macrophage-M2-like phenotype, resulting in attenuated local alloreactivity during acute kidney graft rejection. Here, we examined how hyperosmotic microenvironment affects the cross-priming capacity of dendritic cells. Using ovalbumin as model antigen, we showed that exposure of dendritic cells to hyperosmolarity strongly inhibits activation of antigen-specific T cells despite enhancement of antigen uptake, processing and presentation. We identified TRIF as key mediator of this phenomenon. Moreover, we detected a hyperosmolarity-triggered, TRIF-dependent clustering of MHCI loaded with the ovalbumin-derived epitope, but not of overall MHCI molecules, providing a possible explanation for a reduced T cell activation. Our findings identify dendritic cells as important players in hyperosmolarity-mediated immune imbalance and provide evidence for a novel pathway of inhibition of antigen specific CD8+ T cell response in a hypertonic micromilieu.
Post-treatment with Ma-Huang-Tang ameliorates cold-warm-cycles induced rat lung injury
Authors: Xiao Meng-Meng , Pan Chun-Shui , Liu Yu-Ying , Ma Li-Qian , Yan Li , Fan Jing-Yu , Wang Chuan-She , Huang Rong , Han Jing-Yan
Published: March 2017

Frequent and drastic ambient temperature variation may cause respiratory diseases such as common cold and pneumonia, the mechanism for which is not fully understood, however, due to lack of appropriate animal models. Ma-Huang-Tang (MHT) is widely used in China for treatment of respiratory diseases. The present study aimed to investigate the effect of MHT on temperature alternation induced rat lung injury and explore underlying mechanisms. Male Sprague-Dawley rats were exposed to a cold environment for 1 h and then shifted to a warm environment for 30 min. This cold and warm alteration cycled 4 times. Rats were administrated with MHT (1.87 g/kg) by gavage 6 h after cold-warm-cycles. Cold-warm-cycles induced pulmonary microcirculatory disorders, lung edema and injury, decrease in the expression of tight junction proteins, increase in VE-cadherin activation, increase in the expression and activation of Caveolin-1, Src and NF-κB, and NADPH oxidase subunits p47phox, p40phox and p67phox membrane translocation and inflammatory cytokines production. All alterations were significantly ameliorated by post-treatment with MHT. This study showed that rats subjected to cold-warm-cycles may be used as an animal model to investigate ambient temperature variation-induced lung injury, and suggested MHT as a potential strategy to combat lung injury induced by temperature variation.
Cholesterol attenuates cytoprotective effects of phosphatidylcholine against bile salts
Authors: Ikeda Yoshito , Morita Shin-ya , Terada Tomohiro
Published: March 2017

Bile salts have potent detergent properties and damaging effects on cell membranes, leading to liver injury. However, the molecular mechanisms for the protection of hepatocytes against bile salts are not fully understood. In this study, we demonstrated that the cytotoxicity of nine human major bile salts to HepG2 cells and primary human hepatocytes was prevented by phosphatidylcholine (PC). In contrast, cholesterol had no direct cytotoxic effects but suppressed the cytoprotective effects of PC. PC reduced the cell-association of bile salt, which was reversed by cholesterol. Light scattering measurements and gel filtration chromatography revealed that cholesterol within bile salt/PC dispersions decreased mixed micelles but increased vesicles, bile salt simple micelles and monomers. These results suggest that cholesterol attenuates the cytoprotective effects of PC against bile salts by facilitating the formation of bile salt simple micelles and monomers. Therefore, biliary PC and cholesterol may play different roles in the pathogenesis of bile salt-induced liver injury.
Imbalance between TNFα and progranulin contributes to memory impairment and anxiety in sleep-deprived mice
Authors: Zhang Kun , Li Yu-jiao , Feng Dan , Zhang Peng , Wang Ya-tao , Li Xiang , Liu Shui-bing , Wu Yu-mei , Zhao Ming-gao
Published: March 2017

Sleep disorder is becoming a widespread problem in current society, and is associated with impaired cognition and emotional disorders. Progranulin (PGRN), also known as granulin epithelin precursor, promotes neurite outgrowth and cell survival, and is encoded by the GRN gene. It is a tumor necrosis factor α receptor (TNFR) ligand which is implicated in many central nervous system diseases. However, the role PGRN in sleep disorder remains unclear. In the present study, we found that sleep deprivation (S-DEP) impaired the memory and produced thigmotaxis/anxiety-like behaviors in mice. S-DEP increased the levels of TNFα but decreased PGRN levels in the hippocampus. The intracerebroventricular (ICV) injection of PGRN or intraperitoneal injection of TNFα synthesis blocker thalidomide (25 mg/kg), prevented the memory impairment and anxiety behaviors induced by S-DEP. PGRN treatment also restored dendritic spine density in the hippocampus CA1 region and neurogenesis in hippocampus dentate gyrus (DG). These results indicate that an imbalance between TNFα and PGRN contributes to memory impairment and thigmotaxis/anxiety caused by sleep deprivation.
Correction: Corrigendum: Investigation into the Advantages of Pure Perovskite Film without PbI2 for High Performance Solar Cell
Authors: Thakur Ujwal , Kwon Uisik , Hasan Md Mehedi , Yin Wenping , Kim Dasom , Ha Na Young , Lee Soonil , Ahn Tae Kyu , Park Hui Joon
Published: March 2017

Scientific Reports 6: Article number: 35994; published online: 27 October 2016; updated: 16 March 2017. Ujwal Thakur was omitted from the author list in the original version of this Article. This has been corrected in the PDF and HTML versions of the Article, as well as the Supplementary Informationfile.
Universality and critical behavior of the dynamical Mott transition in a system with long-range interactions
Authors: Rademaker Louk , Vinokur Valerii M. , Galda Alexey
Published: March 2017

We study numerically the voltage-induced breakdown of a Mott insulating phase in a system of charged classical particles with long-range interactions. At half-filling on a square lattice this system exhibits Mott localization in the form of a checkerboard pattern. We find universal scaling behavior of the current at the dynamic Mott insulator-metal transition and calculate scaling exponents corresponding to the transition. Our results are in agreement, up to a difference in universality class, with recent experimental evidence of a dynamic Mott transition in a system of interacting superconducting vortices.
Extracellular α-synuclein induces sphingosine 1-phosphate receptor subtype 1 uncoupled from inhibitory G-protein leaving β-arrestin signal intact
Authors: Zhang Lifang , Okada Taro , Badawy Shaymaa Mohamed Mohamed , Hirai Chihoko , Kajimoto Taketoshi , Nakamura Shun-ichi
Published: March 2017

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. The presence of α-synuclein (α-Syn)-positive intracytoplasmic inclusions, known as Lewy bodies, is the cytopathological hallmark of PD. Increasing bodies of evidence suggest that cell-to-cell transmission of α-Syn plays a role in the progression of PD. Although extracellular α-Syn is known to cause abnormal cell motility, the precise mechanism remains elusive. Here we show that impairment of platelet-derived growth factor-induced cell motility caused by extracellular α-Syn is mainly attributed to selective inhibition of sphingosine 1-phosphate (S1P) signalling. Treatment of human neuroblastoma cells with recombinant α-Syn caused S1P type 1 (S1P1) receptor-selective uncoupling from inhibitory G-protein (Gi) as determined by both functional and fluorescence resonance energy transfer (FRET)-based structural analyses. By contrast, α-Syn caused little or no effect on S1P2receptor-mediated signalling. Both wild-type and α-Syn(A53T), a mutant found in familiar PD, caused uncoupling of S1P1receptor, although α-Syn(A53T) showed stronger potency in uncoupling. Moreover, S1P1receptor-mediated β-arrestin signal was unaltered by α-Syn(A53T). These results suggest that exogenous α-Syn modulates S1P1receptor-mediated signalling from both Gi and β-arrestin signals into β-arrestin-biased signal. These findings uncovered a novel function of exogenous α-Syn in the cells.
Correction: Corrigendum: PARP inhibitor increases chemosensitivity by upregulating miR-664b-5p in BRCA1-mutated triple-negative breast cancer
Authors: Song Wei , Tang Lin , Xu Yumei , Xu Jing , Zhang Wenwen , Xie Hui , Wang Shui , Guan Xiaoxiang
Published: March 2017

Scientific Reports 7: Article number: 42319; published online: 08 February 2017; updated: 16 March 2017 This Article contains an error in Figure 4A where the graphs were labelled incorrectly. The correct Figure 4A appears below as Figure 1.
Brucella spp. of amphibians comprise genomically diverse motile strains competent for replication in macrophages and survival in mammalian hosts
Authors: Al Dahouk Sascha , Köhler Stephan , Occhialini Alessandra , Jiménez de Bagüés María Pilar , Hammerl Jens Andre , Eisenberg Tobias , Vergnaud Gilles , Cloeckaert Axel , Zygmunt Michel S. , Whatmore Adrian M. , Melzer Falk , Drees Kevin P. , Foster Jeffrey T. , Wattam Alice R. , Scholz Holger C.
Published: March 2017

Twenty-one small Gram-negative motile coccobacilli were isolated from 15 systemically diseased African bullfrogs (Pyxicephalus edulis), and were initially identified as Ochrobactrum anthropi by standard microbiological identification systems. Phylogenetic reconstructions using combined molecular analyses and comparative whole genome analysis of the most diverse of the bullfrog strains verified affiliation with the genus Brucella and placed the isolates in a cluster containing B. inopinata and the other non-classical Brucella species but also revealed significant genetic differences within the group. Four representative but molecularly and phenotypically diverse strains were used for in vitro and in vivo infection experiments. All readily multiplied in macrophage-like murine J774-cells, and their overall intramacrophagic growth rate was comparable to that of B. inopinata BO1 and slightly higher than that of B. microti CCM 4915. In the BALB/c murine model of infection these strains replicated in both spleen and liver, but were less efficient than B. suis 1330. Some strains survived in the mammalian host for up to 12 weeks. The heterogeneity of these novel strains hampers a single species description but their phenotypic and genetic features suggest that they represent an evolutionary link between a soil-associated ancestor and the mammalian host-adapted pathogenic Brucella species.
Biogenic silver nanoparticles based on trichoderma harzianum: synthesis, characterization, toxicity evaluation and biological activity
Authors: Guilger Mariana , Pasquoto-Stigliani Tatiane , Bilesky-Jose Natália , Grillo Renato , Abhilash P. C. , Fraceto Leonardo Fernandes , Lima Renata de
Published: March 2017

White mold is an agricultural disease caused by the fungusSclerotinia sclerotiorum, which affects important crops. There are different ways of controlling this organism, but none provides inhibition of its resistance structures (sclerotia). Nanotechnology offers promising applications in agricultural area. Here, silver nanoparticles were biogenically synthesized using the fungusTrichoderma harzianumand characterized. Cytotoxicity and genotoxicity were evaluated, and the nanoparticles were initially tested against white mold sclerotia. Their effects on soybean were also investigated with no effects observed. The nanoparticles showed potential againstS. sclerotiorum, inhibiting sclerotia germination and mycelial growth. Nanoparticle characterization data indicated spherical morphology, satisfactory polydispersity and size distribution. Cytotoxicity and genotoxicity assays showed that the nanoparticles caused both the effects, although, the most toxic concentrations were above those applied for white mold control. Given the potential of the nanoparticles againstS. sclerotiorum, we conclude that this study presents a first step for a new alternative in white mold control.
ThermoAlign: a genome-aware primer design tool for tiled amplicon resequencing
Authors: Francis Felix , Dumas Michael D. , Wisser Randall J.
Published: March 2017

Isolating and sequencing specific regions in a genome is a cornerstone of molecular biology. This has been facilitated by computationally encoding the thermodynamics of DNA hybridization for automated design of hybridization and priming oligonucleotides. However, the repetitive composition of genomes challenges the identification of target-specific oligonucleotides, which limits genetics and genomics research on many species. Here, a tool called ThermoAlign was developed that ensures the design of target-specific primer pairs for DNA amplification. This is achieved by evaluating the thermodynamics of hybridization for full-length oligonucleotide-template alignments — thermoalignments — across the genome to identify primers predicted to bind specifically to the target site. For amplification-based resequencing of regions that cannot be amplified by a single primer pair, a directed graph analysis method is used to identify minimum amplicon tiling paths. Laboratory validation by standard and long-range polymerase chain reaction and amplicon resequencing with maize, one of the most repetitive genomes sequenced to date (≈85% repeat content), demonstrated the specificity-by-design functionality of ThermoAlign. ThermoAlign is released under an open source license and bundled in a dependency-free container for wide distribution. It is anticipated that this tool will facilitate multiple applications in genetics and genomics and be useful in the workflow of high-throughput targeted resequencing studies.
Reduced DNA methylation and psychopathology following endogenous hypercortisolism – a genome-wide study
Authors: Glad Camilla A. M. , Andersson-Assarsson Johanna C. , Berglund Peter , Bergthorsdottir Ragnhildur , Ragnarsson Oskar , Johannsson Gudmundur
Published: March 2017

Patients with Cushing’s Syndrome (CS) in remission were used as a model to test the hypothesis that long-standing excessive cortisol exposure induces changes in DNA methylation that are associated with persisting neuropsychological consequences. Genome-wide DNA methylation was assessed in 48 women with CS in long-term remission (cases) and 16 controls matched for age, gender and education. The Fatigue impact scale and the comprehensive psychopathological rating scale were used to evaluate fatigue, depression and anxiety. Cases had lower average global DNA methylation than controls (81.2% vs 82.7%; p = 0.002). Four hundred and sixty-one differentially methylated regions, containing 3,246 probes mapping to 337 genes were identified. After adjustment for age and smoking, 731 probes in 236 genes were associated with psychopathology (fatigue, depression and/or anxiety). Twenty-four gene ontology terms were associated with psychopathology; terms related to retinoic acid receptor signalling were the most common (adjusted p = 0.0007). One gene in particular, COL11A2, was associated with fatigue following a false discovery rate correction. Our findings indicate that hypomethylation of FKBP5 and retinoic acid receptor related genes serve a potential mechanistic explanation for long-lasting GC-induced psychopathology.
A rapid-screening approach to detect and quantify microplastics based on fluorescent tagging with Nile Red
Authors: Maes Thomas , Jessop Rebecca , Wellner Nikolaus , Haupt Karsten , Mayes Andrew G.
Published: March 2017

A new approach is presented for analysis of microplastics in environmental samples, based on selective fluorescent staining using Nile Red (NR), followed by density-based extraction and filtration. The dye adsorbs onto plastic surfaces and renders them fluorescent when irradiated with blue light. Fluorescence emission is detected using simple photography through an orange filter. Image-analysis allows fluorescent particles to be identified and counted. Magnified images can be recorded and tiled to cover the whole filter area, allowing particles down to a few micrometres to be detected. The solvatochromic nature of Nile Red also offers the possibility of plastic categorisation based on surface polarity characteristics of identified particles. This article details the development of this staining method and its initial cross-validation by comparison with infrared (IR) microscopy. Microplastics of different sizes could be detected and counted in marine sediment samples. The fluorescence staining identified the same particles as those found by scanning a filter area with IR-microscopy.
Correction: Corrigendum: Innate positive chemotaxis to pollen from crops and banker plants in predaceous biological control agents: towards new field lures?
Authors: Li Shu , Tan Xiaoling , Desneux Nicolas , Benelli Giovanni , Zhao Jing , Li Xinhai , Zhang Fan , Gao Xiwu , Wang Su
Published: March 2017

Scientific Reports 5: Article number: 12729; published online: 03 August 2015; updated: 16 March 2017 The Acknowledgements section in this Article is incomplete: “This research is supported by the National Basic Research Program of China (973 Program) (grant 2013CB127605), the Special Fund for Agroscientific Research in the Public Interest (grant nos 201303024 and 201303108), the Beijing NOVA program (No.
Correction: Corrigendum: EColiCore2: a reference network model of the central metabolism of Escherichia coli and relationships to its genome-scale parent model
Authors: Hädicke Oliver , Klamt Steffen
Published: March 2017

Scientific Reports 7: Article number: 39647; published online: 03 January 2017; updated: 16 March 2017 The SBML models provided in the original Supplementary Information files published with this Article contained formatting errors. These errors have been corrected in the Supplementary Information files that now accompany the Article.
Insights into early pig domestication provided by ancient DNA analysis
Authors: Caliebe Amke , Nebel Almut , Makarewicz Cheryl , Krawczak Michael , Krause-Kyora Ben
Published: March 2017

Pigs (Sus scrofa) were first domesticated between 8,500 and 8,000 cal BC in the Near East, from where they were subsequently brought into Europe by agriculturalists. Soon after the arrival of the first domestic pigs in northern Europe (~4500 BC), farmers are thought to have started to incorporate local wild boars into their swine herds. This husbandry strategy ultimately resulted in the domestication of European wild boars. Here, we set out to provide a more precise geographic and temporal framework of the early management of suid populations in northern Europe, drawing upon mitochondrial DNA haplotype data from 116 Neolithic Sus specimens. We developed a quantitative mathematical model tracing the haplotypes of the domestic pigs back to their most likely geographic origin. Our modelling results suggest that, between 5000 and 4000 BC, almost all matrilines in the north originated from domesticated animals from the south of central Europe. In the following period (4000–3000 BC), an estimated 78–100% of domesticates in the north were of northern matrilineal origin, largely from local wild boars. These findings point towards a dramatic change in suid management strategies taking place throughout south-central and northern Europe after 4000 BC.
Structure zone diagram and particle incorporation of nickel brush plated composite coatings
Authors: Isern L. , Impey S. , Almond H. , Clouser S. J. , Endrino J. L.
Published: March 2017

This work studies the deposition of aluminium-incorporated nickel coatings by brush electroplating, focusing on the electroplating setup and processing parameters. The setup was optimised in order to increase the volume of particle incorporation. The optimised design focused on increasing the plating solution flow to avoid sedimentation, and as a result the particle transport experienced a three-fold increase when compared with the traditional setup. The influence of bath load, current density and the brush material used was investigated. Both current density and brush material have a significant impact on the morphology and composition of the coatings. Higher current densities and non-abrasive brushes produce rough, particle-rich samples. Different combinations of these two parameters influence the surface characteristics differently, as illustrated in a Structure Zone Diagram. Finally, surfaces featuring crevices and peaks incorporate between 3.5 and 20 times more particles than smoother coatings. The presence of such features has been quantified using average surface roughness Ra and Abbott-Firestone curves. The combination of optimised setup and rough surface increased the particle content of the composite to 28 at.%.
Statistics of localized phase slips in tunable width planar point contacts
Authors: Baumans Xavier D.A. , Zharinov Vyacheslav S. , Raymenants Eline , Blanco Alvarez Sylvain , Scheerder Jeroen E. , Brisbois Jérémy , Massarotti Davide , Caruso Roberta , Tafuri Francesco , Janssens Ewald , Moshchalkov Victor V. , Van de Vondel Joris , Silhanek Alejandro V.
Published: March 2017

The main dissipation mechanism in superconducting nanowires arises from phase slips. Thus far, most of the studies focus on long nanowires where coexisting events appear randomly along the nanowire. In the present work we investigate highly confined phase slips at the contact point of two superconducting leads. Profiting from the high current crowding at this spot, we are able to shrinkin-situthe nanoconstriction. This procedure allows us to investigate, in the very same sample, thermally activated phase slips and the probability density function of the switching currentIswneeded to trigger an avalanche of events. Furthermore, for an applied current larger thanIsw, we unveil the existence of two distinct thermal regimes. One corresponding to efficient heat removal where the constriction and bath temperatures remain close to each other, and another one in which the constriction temperature can be substantially larger than the bath temperature leading to the formation of a hot spot. Considering that the switching current distribution depends on the exact thermal properties of the sample, the identification of different thermal regimes is of utmost importance for properly interpreting the dissipation mechanisms in narrow point contacts.
Ticks elicit variable fibrinogenolytic activities upon feeding on hosts with different immune backgrounds
Authors: Vora Ashish , Taank Vikas , Dutta Sucharita M. , Anderson John F. , Fish Durland , Sonenshine Daniel E. , Catravas John D. , Sultana Hameeda , Neelakanta Girish
Published: March 2017

Ticks secrete several anti-hemostatic factors in their saliva to suppress the host innate and acquired immune defenses against infestations. Using Ixodes scapularis ticks and age-matched mice purchased from two independent commercial vendors with two different immune backgrounds as a model, we show that ticks fed on immunodeficient animals demonstrate decreased fibrinogenolytic activity in comparison to ticks fed on immunocompetent animals. Reduced levels of D-dimer (fibrin degradation product) were evident in ticks fed on immunodeficient animals in comparison to ticks fed on immunocompetent animals. Increased engorgement weights were noted for ticks fed on immunodeficient animals in comparison to ticks fed on immunocompetent animals. Furthermore, the LC-MS/MS and quantitative real-time-PCR analysis followed by inhibitor and antibody-blocking assays revealed that the arthropod HSP70-like molecule contributes to differential fibrinogenolysis during tick feeding. Collectively, these results not only indicate that ticks elicit variable fibrinogenolysis upon feeding on hosts with different immune backgrounds but also provide insights for the novel role of arthropod HSP70-like molecule in fibrinogenolysis during blood feeding.
LOCALIZER: subcellular localization prediction of both plant and effector proteins in the plant cell
Authors: Sperschneider Jana , Catanzariti Ann-Maree , DeBoer Kathleen , Petre Benjamin , Gardiner Donald M. , Singh Karam B. , Dodds Peter N. , Taylor Jennifer M.
Published: March 2017

Pathogens secrete effector proteins and many operate inside plant cells to enable infection. Some effectors have been found to enter subcellular compartments by mimicking host targeting sequences. Although many computational methods exist to predict plant protein subcellular localization, they perform poorly for effectors. We introduce LOCALIZER for predicting plant and effector protein localization to chloroplasts, mitochondria, and nuclei. LOCALIZER shows greater prediction accuracy for chloroplast and mitochondrial targeting compared to other methods for 652 plant proteins. For 107 eukaryotic effectors, LOCALIZER outperforms other methods and predicts a previously unrecognized chloroplast transit peptide for the ToxA effector, which we show translocates into tobacco chloroplasts. Secretome-wide predictions and confocal microscopy reveal that rust fungi might have evolved multiple effectors that target chloroplasts or nuclei. LOCALIZER is the first method for predicting effector localisation in plants and is a valuable tool for prioritizing effector candidates for functional investigations. LOCALIZER is available at http://localizer.csiro.au/.
Platform for combined analysis of functional and biomolecular phenotypes of the same cell
Authors: Kelbauskas L. , Ashili S. , Zeng J. , Rezaie A. , Lee K. , Derkach D. , Ueberroth B. , Gao W. , Paulson T. , Wang H. , Tian Y. , Smith D. , Reid B. , Meldrum Deirdre R.
Published: March 2017

Functional and molecular cell-to-cell variability is pivotal at the cellular, tissue and whole-organism levels. Yet, the ultimate goal of directly correlating the function of the individual cell with its biomolecular profile remains elusive. We present a platform for integrated analysis of functional and transcriptional phenotypes in the same single cells. We investigated changes in the cellular respiration and gene expression diversity resulting from adaptation to repeated episodes of acute hypoxia in a premalignant progression model. We find differential, progression stage-specific alterations in phenotypic heterogeneity and identify cells with aberrant phenotypes. To our knowledge, this study is the first demonstration of an integrated approach to elucidate how heterogeneity at the transcriptional level manifests in the physiologic profile of individual cells in the context of disease progression.
Quantum mechanical calculation of nanomaterial-ligand interaction energies by molecular fractionation with conjugated caps method
Authors: Zhang Dawei
Published: March 2017

Molecular fractionation with conjugate caps (MFCC) method is introduced for the efficient estimation of quantum mechanical (QM) interaction energies between nanomaterial (carbon nanotube, fullerene, and graphene surface) and ligand (charged and neutral). In the calculations, nanomaterials are partitioned into small fragments and conjugated caps that are properly capped, and the interaction energies can be obtained through the summation of QM calculations of the fragments from which the contribution of the conjugated caps is removed. All the calculations were performed by density functional theory (DFT) and dispersion contributions for the attractive interactions were investigated by dispersion corrected DFT method. The predicted interaction energies by MFCC at each computational level are found to give excellent agreement with full system (FS) calculations with the mean energy deviation just a fractional kcal/mol. The accurate determination of nanomaterial-ligand interaction energies by MFCC suggests that it is an effective method for performing QM calculations on nanomaterial-ligand systems.
Quantum-dot-based suspension microarray for multiplex detection of lung cancer markers: preclinical validation and comparison with the Luminex xMAP® system
Authors: Bilan Regina , Ametzazurra Amagoia , Brazhnik Kristina , Escorza Sergio , Fernández David , Uríbarri María , Nabiev Igor , Sukhanova Alyona
Published: March 2017

A novel suspension multiplex immunoassay for the simultaneous specific detection of lung cancer markers in bronchoalveolar lavage fluid (BALF) clinical samples based on fluorescent microspheres having different size and spectrally encoded with quantum dots (QDEM) was developed. The designed suspension immunoassay was validated for the quantitative detection of three lung cancer markers in BALF samples from 42 lung cancer patients and 10 control subjects. Tumor markers were detected through simultaneous formation of specific immune complexes consisting of a capture molecule, the target antigen, and biotinylated recognition molecule on the surface of the different QDEM in a mixture. The immune complexes were visualized by fluorescently labeled streptavidin and simultaneously analyzed using a flow cytometer. Preclinical validation of the immunoassay was performed and results were compared with those obtained using an alternative 3-plex immunoassay based on Luminex xMAP® technology, developed on classical organic fluorophores. The comparison showed that the QDEM and xMAP® assays yielded almost identical results, with clear discrimination between control and clinical samples. Thus, developed QDEM technology can become a good alternative to xMAP® assays permitting analysis of multiple protein biomarkers using conventional flow cytometers.
Single-Crystalline Gold Nanowires Synthesized from Light-Driven Oriented Attachment and Plasmon-Mediated Self-Assembly of Gold Nanorods or Nanoparticles
Authors: Yu Shang-Yang , Gunawan Hariyanto , Tsai Shiao-Wen , Chen Yun-Ju , Yen Tzu-Chen , Liaw Jiunn-Woei
Published: March 2017

Through the light-driven geometrically oriented attachment (OA) and self-assembly of Au nanorods (NRs) or nanoparticles (NPs), single-crystalline Au nanowires (NWs) were synthesized by the irradiation of a linearly-polarized (LP) laser. The process was conducted in a droplet of Au colloid on a glass irradiated by LP near-infrared (e.g. 1064 nm and 785 nm) laser beam of low power at room temperature and atmospheric pressure, without any additive. The FE-SEM images show that the cross sections of NWs are various: tetragonal, pentagonal or hexagonal. The EDS spectrum verifies the composition is Au, and the pattern of X-ray diffraction identifies the crystallinity of NWs with the facets of {111}, {200}, {220} and {311}. We proposed a hypothesis for the mechanism that the primary building units are aligned and coalesced by the plasmon-mediated optical torque and force to form the secondary building units. Subsequently, the secondary building units undergo the next self-assembly, and so forth the tertiary ones. The LP light guides the translational and rotational motions of these building units to perform geometrically OA in the side-by-side, end-to-end and T-shaped manners. Consequently, micron-sized ordered mesocrystals are produced. Additionally, the concomitant plasmonic heating causes the annealing for recrystallizing the mesocrystals in water.
Enhanced thermal conductivity of form-stable phase change composite with single-walled carbon nanotubes for thermal energy storage
Authors: Qian Tingting , Li Jinhong , Feng Wuwei , Nian Hong’en
Published: March 2017

A striking contrast in the thermal conductivities of polyethylene glycol (PEG)/diatomite form-stable phase change composite (fs-PCC) with single-walled carbon nanotubes (SWCNs) as nano-additive has been reported in our present study. Compared to the pure PEG, the thermal conductivity of the prepared fs-PCC has increased from 0.24 W/mK to 0.87 W/Mk with a small SWCNs loading of 2 wt%. SWCNs are decorated on the inner surface of diatomite pores whilst retaining its porous structure. Compared to PEG/diatomite fs-PCC, the melting and solidification time of the PEG/diatomite/SWCNs fs-PCC are respectively decreased by 54.7% and 51.1%, and its thermal conductivity is 2.8 times higher. The composite can contain PEG as high as 60 wt% and maintain its original shape perfectly without any PEG leakage after subjected to 200 melt-freeze cycles. DSC results indicates that the melting point of the PEG/diatomite/SWCNs fs-PCC shifts to a lower temperature while the solidification point shifts to a higher temperature due to the presence of SWCNs. Importantly, the use of SWCNs is found to have clear beneficial effects for enhancing the thermal conductivity and thermal storage/release rates, without affecting thermal properties, chemical compatibility and thermal stability. The prepared PEG/diatomite/SWCNs fs-PCC exhibits excellent chemical and thermal durability and has potential application in solar thermal energy storage and solar heating.