bluuebunny/crossref_metadata_2025 huggingface dataset:
Clonal dynamics following p53 loss of heterozygosity in Kras-driven cancers
Authors: Muzumdar Mandar Deepak , Dorans Kimberly Judith , Chung Katherine Minjee , Robbins Rebecca , Tammela Tuomas , Gocheva Vasilena , Li Carman Man-Chung , Jacks Tyler
Published: September 2016

Although it has become increasingly clear that cancers display extensive cellular heterogeneity, the spatial growth dynamics of genetically distinct clones within developing solid tumours remain poorly understood. Here we leverage mosaic analysis with double markers (MADM) to trace subclonal populations retaining or lacking p53 within oncogenic Kras-initiated lung and pancreatic tumours. In both models, p53 constrains progression to advanced adenocarcinomas. Comparison of lineage-related p53 knockout and wild-type clones reveals a minor role of p53 in suppressing cell expansion in lung adenomas. In contrast, p53 loss promotes both the initiation and expansion of low-grade pancreatic intraepithelial neoplasia (PanINs), likely through differential expression of the p53 regulator p19ARF. Strikingly, lineage-related cells are often dispersed in lung adenomas and PanINs, contrasting with more contiguous growth of advanced subclones. Together, these results support cancer type-specific suppressive roles of p53 in early tumour progression and offer insights into clonal growth patterns during tumour development.
Chemoselective synthesis and analysis of naturally occurring phosphorylated cysteine peptides
Authors: Bertran-Vicente Jordi , Penkert Martin , Nieto-Garcia Olaia , Jeckelmann Jean-Marc , Schmieder Peter , Krause Eberhard , Hackenberger Christian P. R.
Published: September 2016

In contrast to protein O-phosphorylation, studying the function of the less frequent N- and S-phosphorylation events have lagged behind because they have chemical features that prevent their manipulation through standard synthetic and analytical methods. Here we report on the development of a chemoselective synthetic method to phosphorylate Cys side-chains in unprotected peptides. This approach makes use of a reaction between nucleophilic phosphites and electrophilic disulfides accessible by standard methods. We achieve the stereochemically defined phosphorylation of a Cys residue and verify the modification using electron-transfer higher-energy dissociation (EThcD) mass spectrometry. To demonstrate the use of the approach in resolving biological questions, we identify an endogenous Cys phosphorylation site in IICBGlc, which is known to be involved in the carbohydrate uptake from the bacterial phosphotransferase system (PTS). This new chemical and analytical approach finally allows further investigating the functions and significance of Cys phosphorylation in a wide range of crucial cellular processes.
Spin-wave propagation steered by electric field modulated exchange interaction
Authors: Wang Sheng , Guan Xiawei , Cheng Xiaomin , Lian Chen , Huang Ting , Miao Xiangshui
Published: September 2016

Combined ab initio and micromagnetic simulations are carried out to demonstrate the feasibility on the electrical manipulation of spin-wave propagation in ultrathin Fe films. It is discovered that the exchange interaction can be substantially weakened under the influence of electric field applied perpendicular to the magnetic film surface. Furthermore, we demonstrate that the electric field modified exchange constant could effectively control the propagation of spin waves. To be specific, an external applied electric field of 5 V/nm can effectively weaken exchange interaction by 80% and is sufficient to induce nearly twofold change of the wavenumber. This discovery may open a door to energy-efficient local manipulation of the spin wave propagation utilizing electric fields, which is crucial for both fundamental research and spin wave based logic applications.
Bacterial succession and metabolite changes during flax (Linum usitatissimum L.) retting with Bacillus cereus HDYM-02
Authors: Zhao Dan , Liu Pengfei , Pan Chao , Du Renpeng , Ping Wenxiang , Ge Jingping
Published: September 2016

High-throughput sequencing and GC-MS (gas chromatography-mass spectrometry) were jointly used to reveal the bacterial succession and metabolite changes during flax (Linum usitatissimum L.) retting. The inoculation of Bacillus cereus HDYM-02 decreased bacterial richness and diversity. This inoculum led to the replacement of Enterobacteriaceae by Bacillaceae. The level of aerobic Pseudomonadaceae (mainly Azotobacter) and anaerobic Clostridiaceae_1 gradually increased and decreased, respectively. Following the addition of B. cereus HDYM-02, the dominant groups were all degumming enzyme producers or have been proven to be involved in microbial retting throughout the entire retting period. These results could be verified by the metabolite changes, either degumming enzymes or their catalytic products galacturonic acid and reducing sugars. The GC-MS data showed a clear separation between flax retting with and without B. cereus HDYM-02, particularly within the first 72 h. These findings reveal the important bacterial groups that are involved in fiber retting and will facilitate improvements in the retting process.
Realization of resistive switching and magnetoresistance in ZnO/ZnO-Co composite materials
Authors: Li Xiaoli , Jia Juan , Li Yanchun , Bai Yuhao , Li Jie , Shi Yana , Wang Lanfang , Xu Xiaohong
Published: September 2016

Combining resistive switching and magnetoresistance in a system exhibits great potential for application in multibit nonvolatile data storage. It is in significance and difficulty to seek a material with resistances that can be stably switched at different resistance states modulated by an electrical field and a magnetic field. In this paper, we propose a novel electrode/ZnO/ZnO-Co/electrode device in which the storage layer combines a nanostructured ZnO-Co layer and a ZnO layer. The device exhibits bipolar resistive switching characteristics, which can be explained by the accumulation of oxygen vacancies due to the migration of oxygen ions by external electrical stimuli and the contribution of Co particles in the ZnO-Co layer. Moreover, the magnetoresistance effect at room temperature can be observed in the device at high and low resistance states. Therefore, through electrical and magnetic control, four resistance states are achieved in this system, presenting a new possibility towards enhancing data densities by many folds.
Erratum: Cannabis and tolerance: acute drug impairment as a function of cannabis use history
Authors: Ramaekers J. G. , van Wel J. H. , Spronk D. B. , Toennes S. W. , Kuypers K. P. C. , Theunissen E. L. , Verkes R. J.
Published: September 2016

Scientific Reports 6: Article number: 26843; published online: 26 May 2016; updated: 02 September 2016 This Article contains an error in the Author Contributions statement. “J.G.R. and R.J.V. designed the study and operated as PIs. J.H.v.W., D.B.S., K.P.C.K. and E.L.T. were responsible for study management.
GRAM domain-containing protein 1A (GRAMD1A) promotes the expansion of hepatocellular carcinoma stem cell and hepatocellular carcinoma growth through STAT5
Authors: Fu Binsheng , Meng Wei , Zhao Hui , Zhang Bing , Tang Hui , Zou Ying , Yao Jia , Li Heping , Zhang Tong
Published: September 2016

Hepatocellular carcinoma (HCC) is the leading cause for cancer death worldwide, new prognostic factors and targets are critical for HCC treatment. Here, we found GRAMD1A was upregulated in HCC tissues, patients with high GRAMD1A levels had poor outcome, statistical analyses found GRAMD1A expression was positively correlated with pathologic differentiation and survival or mortality. It was an unfavorable prognostic factor for HCC patients. Functional analyses revealed GRAMD1A contributed to the self-renewal of HCC stem cells, resistance to chemotherapy and tumor growth of HCC determined by hepatosphere formation assay, side population (SP) analysis, TUNEL assay, soft agar growth ability assay and tumor growth model in vivo. Mechanism analyses found signal transducer and activator of transcription 5 (STAT5) was the target of GRAMD1A, GRAMD1A regulated the target genes of STAT5 and the transcriptional activity of STAT5. Inhibition of STAT5 in indicated HCC cells overexpressing GRAMD1A suppressed the effects of GRAMD1A on the self-renewal of HCC stem cell, resistance to chemotherapy and tumor growth, suggesting GRAMD1A promoted the self-renewal of HCC stem cells and the development of HCC by increasing STAT5 level. GRAMD1A might be a useful biomarker and target for HCC.
Correction: Corrigendum: Wharton’s jelly-derived mesenchymal stem cells combined with praziquantel as a potential therapy for Schistosoma mansoni-induced liver fibrosis
Authors: Hammam Olfat A. , Elkhafif Nagwa , Attia Yasmeen M. , Mansour Mohamed T. , Elmazar Mohamed M. , Abdelsalam Rania M. , Kenawy Sanaa A. , El-Khatib Aiman S.
Published: September 2016

Scientific Reports 6: Article number: 21005; published online: 15 February 2016; updated: 02 September 2016 In this Article, Affiliation 4 is incomplete. The correct affiliation is listed below: Department of Virology and Immunology, Cancer Biology Department, National Cancer Institute, Cairo University, Children’s Cancer Hospital Egypt 57357, Cairo 11712, Egypt.
Correction: Corrigendum: Characterization and target genes of nine human PRD-like homeobox domain genes expressed exclusively in early embryos
Authors: Madissoon Elo , Jouhilahti Eeva-Mari , Vesterlund Liselotte , Töhönen Virpi , Krjutškov Kaarel , Petropoulos Sophie , Einarsdottir Elisabet , Linnarsson Sten , Lanner Fredrik , Månsson Robert , Hovatta Outi , Bürglin Thomas R. , Katayama Shintaro , Kere Juha
Published: September 2016

Scientific Reports 6: Article number: 28995; published online: 14 July 2016; updated: 02 September 2016 The original version of this Article contained a typographical error in the spelling of the author Sophie Petropoulos, which was incorrectly given as Sophie Petropoulous. This has now been corrected in the PDF and HTML versions of the Article.
Ordered array of Ag semishells on different diameter monolayer polystyrene colloidal crystals: An ultrasensitive and reproducible SERS substrate
Authors: Yi Zao , Niu Gao , Luo Jiangshan , Kang Xiaoli , Yao Weitang , Zhang Weibin , Yi Yougen , Yi Yong , Ye Xin , Duan Tao , Tang Yongjian
Published: September 2016

Ag semishells (AgSS) ordered arrays for surface-enhanced Raman scattering (SERS) spectroscopy have been prepared by depositing Ag film onto polystyrene colloidal particle (PSCP) monolayer templates array. The diversified activity for SERS activity with the ordered AgSS arrays mainly depends on the PSCP diameter and Ag film thickness. The high SERS sensitivity and reproducibility are proved by the detection of rhodamine 6G (R6G) and 4-aminothiophenol (4-ATP) molecules. The prominent enhancements of SERS are mainly from the “V”-shaped or “U”-shaped nanogaps on AgSS, which are experimentally and theoretically investigated. The higher SERS activity, stability and reproducibility make the ordered AgSS a promising choice for practical SERS low concentration detection applications.
An Integrated Human/Murine Transcriptome and Pathway Approach To Identify Prenatal Treatments For Down Syndrome
Authors: Guedj Faycal , Pennings Jeroen LA , Massingham Lauren J. , Wick Heather C. , Siegel Ashley E. , Tantravahi Umadevi , Bianchi Diana W.
Published: September 2016

Anatomical and functional brain abnormalities begin during fetal life in Down syndrome (DS). We hypothesize that novel prenatal treatments can be identified by targeting signaling pathways that are consistently perturbed in cell types/tissues obtained from human fetuses with DS and mouse embryos. We analyzed transcriptome data from fetuses with trisomy 21, age and sex-matched euploid controls and embryonic day 15.5 forebrains from Ts1Cje, Ts65Dn and Dp16 mice. The new datasets were compared to other publicly available datasets from humans with DS. We used the human Connectivity Map (CMap) database and created a murine adaptation to identify FDA-approved drugs that can rescue affected pathways.USP16andTTC3were dysregulated in all affected human cells and two mouse models. DS-associated pathway abnormalities were either the result of gene dosage specific effects or the consequence of a global cell stress response with activation of compensatory mechanisms. CMap analyses identified 56 molecules with high predictive scores to rescue abnormal gene expression in both species. Our novel integrated human/murine systems biology approach identified commonly dysregulated genes and pathways. This can help to prioritize therapeutic molecules on which to further test safety and efficacy. Additional studies in human cells are ongoing prior to pre-clinical prenatal treatment in mice.
Support vector regression-guided unravelling: antioxidant capacity and quantitative structure-activity relationship predict reduction and promotion effects of flavonoids on acrylamide formation
Authors: Huang Mengmeng , Wei Yan , Wang Jun , Zhang Yu
Published: September 2016

We used the support vector regression (SVR) approach to predict and unravel reduction/promotion effect of characteristic flavonoids on the acrylamide formation under a low-moisture Maillard reaction system. Results demonstrated the reduction/promotion effects by flavonoids at addition levels of 1–10000 μmol/L. The maximal inhibition rates (51.7%, 68.8% and 26.1%) and promote rates (57.7%, 178.8% and 27.5%) caused by flavones, flavonols and isoflavones were observed at addition levels of 100 μmol/L and 10000 μmol/L, respectively. The reduction/promotion effects were closely related to the change of trolox equivalent antioxidant capacity (ΔTEAC) and well predicted by triple ΔTEAC measurements via SVR models (R: 0.633–0.900). Flavonols exhibit stronger effects on the acrylamide formation than flavones and isoflavones as well as their O-glycosides derivatives, which may be attributed to the number and position of phenolic and 3-enolic hydroxyls. The reduction/promotion effects were well predicted by using optimized quantitative structure-activity relationship (QSAR) descriptors and SVR models (R: 0.926–0.994). Compared to artificial neural network and multi-linear regression models, SVR models exhibited better fitting performance for both TEAC-dependent and QSAR descriptor-dependent predicting work. These observations demonstrated that the SVR models are competent for predicting our understanding on the future use of natural antioxidants for decreasing the acrylamide formation.
Fundamental aspects of electric double layer force-distance measurements at liquid-solid interfaces using atomic force microscopy
Authors: Black Jennifer M. , Zhu Mengyang , Zhang Pengfei , Unocic Raymond R. , Guo Daqiang , Okatan M. Baris , Dai Sheng , Cummings Peter T. , Kalinin Sergei V. , Feng Guang , Balke Nina
Published: September 2016

Atomic force microscopy (AFM) force-distance measurements are used to investigate the layered ion structure of Ionic Liquids (ILs) at the mica surface. The effects of various tip properties on the measured force profiles are examined and reveal that the measured ion position is independent of tip properties, while the tip radius affects the forces required to break through the ion layers as well as the adhesion force. Force data is collected for different ILs and directly compared with interfacial ion density profiles predicted by molecular dynamics. Through this comparison it is concluded that AFM force measurements are sensitive to the position of the ion with the larger volume and mass, suggesting that ion selectivity in force-distance measurements are related to excluded volume effects and not to electrostatic or chemical interactions between ions and AFM tip. The comparison also revealed that at distances greater than 1 nm the system maintains overall electroneutrality between the AFM tip and sample, while at smaller distances other forces (e.g., van der waals interactions) dominate and electroneutrality is no longer maintained.
Curved Beam Computed Tomography based Structural Rigidity Analysis of Bones with Simulated Lytic Defect: A Comparative Study with Finite Element Analysis
Authors: Oftadeh R. , Karimi Z. , Villa-Camacho J. , Tanck E. , Verdonschot N. , Goebel R. , Snyder B. D. , Hashemi H. N. , Vaziri A. , Nazarian A.
Published: September 2016

In this paper, a CT based structural rigidity analysis (CTRA) method that incorporates bone intrinsic local curvature is introduced to assess the compressive failure load of human femur with simulated lytic defects. The proposed CTRA is based on a three dimensional curved beam theory to obtain critical stresses within the human femur model. To test the proposed method, ten human cadaveric femurs with and without simulated defects were mechanically tested under axial compression to failure. Quantitative computed tomography images were acquired from the samples, and CTRA and finite element analysis were performed to obtain the failure load as well as rigidities in both straight and curved cross sections. Experimental results were compared to the results obtained from FEA and CTRA. The failure loads predicated by curved beam CTRA and FEA are in agreement with experimental results. The results also show that the proposed method is an efficient and reliable method to find both the location and magnitude of failure load. Moreover, the results show that the proposed curved CTRA outperforms the regular straight beam CTRA, which ignores the bone intrinsic curvature and can be used as a useful tool in clinical practices.
Serving by local consensus in the public service location game
Authors: Sun Yi-Fan , Zhou Hai-Jun
Published: September 2016

We discuss the issue of distributed and cooperative decision-making in a network game of public service location. Each node of the network can decide to host a certain public service incurring in a construction cost and serving all the neighboring nodes and itself. A pure consumer node has to pay a tax and the collected tax is evenly distributed to all the hosting nodes to remedy their construction costs. If all nodes make individual best-response decisions, the system gets trapped in an inefficient situation of high tax level. Here we introduce a decentralized local-consensus selection mechanism which requires nodes to recommend their neighbors of highest local impact as candidate servers and a node may become a server only if all its non-server neighbors give their assent. We demonstrate that although this mechanism involves only information exchange among neighboring nodes, it leads to socially efficient solutions with tax level approaching the lowest possible value. Our results may help in understanding and improving collective problem-solving in various networked social and robotic systems.
Pseudogap and proximity effect in the Bi2Te3/Fe1+yTe interfacial superconductor
Authors: He M. Q. , Shen J. Y. , Petrović A. P. , He Q. L. , Liu H. C. , Zheng Y. , Wong C. H. , Chen Q. H. , Wang J. N. , Law K. T. , Sou I. K. , Lortz R.
Published: September 2016

In the interfacial superconductor Bi2Te3/Fe1+yTe, two dimensional superconductivity occurs in direct vicinity to the surface state of a topological insulator. If this state were to become involved in superconductivity, under certain conditions a topological superconducting state could be formed, which is of high interest due to the possibility of creating Majorana fermionic states. We report directional point-contact spectroscopy data on the novel Bi2Te3/Fe1+yTe interfacial superconductor for a Bi2Te3 thickness of 9 quintuple layers, bonded by van der Waals epitaxy to a Fe1+yTe film at an atomically sharp interface. Our data show highly unconventional superconductivity, which appears as complex as in the cuprate high temperature superconductors. A very large superconducting twin-gap structure is replaced by a pseudogap above ~12 K which persists up to 40 K. While the larger gap shows unconventional order parameter symmetry and is attributed to a thin FeTe layer in proximity to the interface, the smaller gap is associated with superconductivity induced via the proximity effect in the topological insulator Bi2Te3.
Efficient Production of Gene-Modified Mice using Staphylococcus aureus Cas9
Authors: Zhang Xiya , Liang Puping , Ding Chenhui , Zhang Zhen , Zhou Jianwen , Xie Xiaowei , Huang Rui , Sun Ying , Sun Hongwei , Zhang Jinran , Xu Yanwen , Songyang Zhou , Huang Junjiu
Published: September 2016

The CRISPR/Cas system is an efficient genome-editing tool to modify genes in mouse zygotes. However, only the Streptococcus pyogenes Cas9 (SpCas9) has been systematically tested for generating gene-modified mice. The protospacer adjacent motif (PAM, 5′-NGG-3′) recognized by SpCas9 limits the number of potential target sites for this system. Staphylococcus aureus Cas9 (SaCas9), with its smaller size and unique PAM (5′-NNGRRT-3′) preferences, presents an alternative for genome editing in zygotes. Here, we showed that SaCas9 could efficiently and specifically edit the X-linked gene Slx2 and the autosomal gene Zp1 in mouse zygotes. SaCas9-mediated disruption of the tyrosinase (Tyr) gene led to C57BL/6J mice with mosaic coat color. Furthermore, multiplex targeting proved efficient multiple genes disruption when we co-injected gRNAs targeting Slx2, Zp1, and Tyr together with SaCas9 mRNA. We were also able to insert a Flag tag at the C-terminus of histone H1c, when a Flag-encoding single-stranded DNA oligo was co-introduced into mouse zygotes with SaCas9 mRNA and the gRNA. These results indicate that SaCas9 can specifically cleave the target gene locus, leading to successful gene knock-out and precise knock-in in mouse zygotes, and highlight the potential of using SaCas9 for genome editing in preimplantation embryos and producing gene-modified animal models.
Inverse design of an ultra-compact broadband optical diode based on asymmetric spatial mode conversion
Authors: Callewaert Francois , Butun Serkan , Li Zhongyang , Aydin Koray
Published: September 2016

The objective-first inverse-design algorithm is used to design an ultra-compact optical diode. Based on silicon and air only, this optical diode relies on asymmetric spatial mode conversion between the left and right ports. The first even mode incident from the left port is transmitted to the right port after being converted into an odd mode. On the other hand, same mode incident from the right port is reflected back by the optical diode dielectric structure. The convergence and performance of the algorithm are studied, along with a transform method that converts continuous permittivity medium into a binary material design. The optimal device is studied with full-wave electromagnetic simulations to compare its behavior under right and left incidences, in 2D and 3D settings as well. A parametric study is designed to understand the impact of the design space size and initial conditions on the optimized devices performance. A broadband optical diode behavior is observed after optimization, with a large rejection ratio between the two transmission directions. This illustrates the potential of the objective-first inverse-design method to design ultra-compact broadband photonic devices.
Suppression of fat deposition in broiler chickens by (-)-hydroxycitric acid supplementation: A proteomics perspective
Authors: Peng Mengling , Han Jing , Li Longlong , Ma Haitian
Published: September 2016

(-)-Hydroxycitric acid (HCA) suppresses fatty acid synthesis in animals, but its biochemical mechanism in poultry is unclear. This study identified the key proteins associated with fat metabolism and elucidated the biochemical mechanism of (-)-HCA in broiler chickens. Four groups (n = 30 each) received a diet supplemented with 0, 1000, 2000 or 3000 mg/kg (-)-HCA for 4 weeks. Of the differentially expressed liver proteins, 40 and 26 were identified in the mitochondrial and cytoplasm respectively. Pyruvate dehydrogenase E1 components (PDHA1 and PDHB), dihydrolipoyl dehydrogenase (DLD), aconitase (ACO2), a-ketoglutarate dehydrogenase complex (DLST), enoyl-CoA hydratase (ECHS1) and phosphoglycerate kinase (PGK) were upregulated, while NADP-dependent malic enzyme (ME1) was downregulated. Biological network analysis showed that the identified proteins were involved in glycometabolism and lipid metabolism, whereas PDHA1, PDHB, ECHS1, and ME1 were identified in the canonical pathway by Ingenuity Pathway Analysis. The data indicated that (-)-HCA inhibited fatty acid synthesis by reducing the acetyl-CoA supply, via promotion of the tricarboxylic acid cycle (upregulation of PDHA1, PDHB, ACO2, and DLST expression) and inhibition of ME1 expression. Moreover, (-)-HCA promoted fatty acid beta-oxidation by upregulating ECHS1 expression. These results reflect a biochemically relevant mechanism of fat reduction by (-)-HCA in broiler chickens.
Integration of transcriptomic and genomic data suggests candidate mechanisms for APOE4-mediated pathogenic action in Alzheimer’s disease
Authors: Caberlotto Laura , Marchetti Luca , Lauria Mario , Scotti Marco , Parolo Silvia
Published: September 2016

Among the genetic factors known to increase the risk of late onset Alzheimer’s diseases (AD), the presence of the apolipoproteine e4 (APOE4) allele has been recognized as the one with the strongest effect. However, despite decades of research, the pathogenic role of APOE4 in Alzheimer’s disease has not been clearly elucidated yet. In order to investigate the pathogenic action of APOE4, we applied a systems biology approach to the analysis of transcriptomic and genomic data of APOE44 vs. APOE33 allele carriers affected by Alzheimer’s disease. Network analysis combined with a novel technique for biomarker computation allowed the identification of an alteration in aging-associated processes such as inflammation, oxidative stress and metabolic pathways, indicating that APOE4 possibly accelerates pathological processes physiologically induced by aging. Subsequent integration with genomic data indicates that the Notch pathway could be the nodal molecular mechanism altered in APOE44 allele carriers with Alzheimer’s disease. Interestingly, PSEN1 and APP, genes whose mutation are known to be linked to early onset Alzheimer’s disease, are closely linked to this pathway. In conclusion, APOE4 role on inflammation and oxidation through the Notch signaling pathway could be crucial in elucidating the risk factors of Alzheimer’s disease.
Colchicine prevents NSAID-induced small intestinal injury by inhibiting activation of the NLRP3 inflammasome
Authors: Otani Koji , Watanabe Toshio , Shimada Sunao , Takeda Shogo , Itani Shigehiro , Higashimori Akira , Nadatani Yuji , Nagami Yasuaki , Tanaka Fumio , Kamata Noriko , Yamagami Hirokazu , Tanigawa Tetsuya , Shiba Masatsugu , Tominaga Kazunari , Fujiwara Yasuhiro , Arakawa Tetsuo
Published: September 2016

The inflammasome is a large, multiprotein complex that consists of a nucleotide-binding oligomerization domain-like receptor (NLR), an apoptosis-associated speck-like protein containing a caspase recruitment domain, and pro-caspase-1. Activation of the inflammasome results in cleavage of pro-caspase-1 into cleaved caspase-1, which promotes the processing of pro-interleukin (IL)-1β into mature IL-1β. We investigated the effects of colchicine on non-steroidal anti-inflammatory drug (NSAID)-induced small intestinal injury and activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome. Colchicine treatment inhibited indomethacin-induced small intestinal injury by 86% (1 mg/kg) and 94% (3 mg/kg) as indicated by the lesion index 24 h after indomethacin administration. Colchicine inhibited the protein expression of cleaved caspase-1 and mature IL-1β, without affecting the mRNA expression of NLRP3 and IL-1β. Although treatment with recombinant IL-1β (0.1 μg/kg) did not change the severity of small intestinal damage, the preventive effects of colchicine were abolished by supplementation with the same dose of recombinant IL-1β. Indomethacin-induced small intestinal damage was reduced by 77%, as determined by the lesion index in NLRP3−/− mice, and colchicine treatment failed to inhibit small intestinal damage in NLRP3−/− mice. These results demonstrate that colchicine prevents NSAID-induced small intestinal injury by inhibiting activation of the NLRP3 inflammasome.
Arterial stiffness & Sri Lankan chronic kidney disease of unknown origin
Authors: Gifford Fiona , Kimmitt Robert , Herath Chula , Webb David J , Melville Vanessa , Siribaddana Sisira , Eddleston Michael , Dhaun Neeraj
Published: September 2016

Chronic kidney disease (CKD) is common and independently associated with cardiovascular disease (CVD). Arterial stiffness contributes to CVD risk in CKD. In many developing countries a considerable proportion of CKD remains unexplained, termed CKDu. We assessed arterial stiffness in subjects with Sri Lankan CKDu, in matched controls without CKD and in those with defined CKD. Aortic blood pressure (BP), pulse wave velocity (PWV) and augmentation index (AIx) were assessed in 130 subjects (50 with CKDu, 45 with CKD and 35 without CKD) using the validated TensioMed™ Arteriograph monitor. Brachial and aortic BP was lower in controls than in CKDu and CKD subjects but no different between CKDu and CKD. Controls had a lower PWV compared to subjects with CKDu and CKD. Despite equivalent BP and renal dysfunction, CKDu subjects had a lower PWV than those with CKD (8.7 ± 1.5 vs. 9.9 ± 2.2 m/s, p < 0.01). Excluding diabetes accentuated the differences in PWV seen between groups (controls vs. CKDu vs. CKD: 6.7 ± 0.9 vs. 8.7 ± 1.5 vs. 10.4 ± 1.5 m/s, p < 0.001 for all). Sri Lankan CKDu is associated with less arterial stiffening than defined causes of CKD. Whether this translates to lower cardiovascular morbidity and mortality long term is unclear and should be the focus of future studies.
Activation of P2X7 and P2Y11 purinergic receptors inhibits migration and normalizes tumor-derived endothelial cells via cAMP signaling
Authors: Avanzato D. , Genova T. , Fiorio Pla A. , Bernardini M. , Bianco S. , Bussolati B. , Mancardi D. , Giraudo E. , Maione F. , Cassoni P. , Castellano I. , Munaron L.
Published: September 2016

Purinergic signaling is involved in inflammation and cancer. Extracellular ATP accumulates in tumor interstitium, reaching hundreds micromolar concentrations, but its functional role on tumor vasculature and endothelium is unknown. Here we show that high ATP doses (>20 μM) strongly inhibit migration of endothelial cells from human breast carcinoma (BTEC), but not of normal human microvascular EC. Lower doses (1–10 μM) result ineffective. The anti-migratory activity is associated with cytoskeleton remodeling and is significantly prevented by hypoxia. Pharmacological and molecular evidences suggest a major role for P2X7R and P2Y11R in ATP-mediated inhibition of TEC migration: selective activation of these purinergic receptors by BzATP mimics the anti-migratory effect of ATP, which is in turn impaired by their pharmacological or molecular silencing. Downstream pathway includes calcium-dependent Adenilyl Cyclase 10 (AC10) recruitment, cAMP release and EPAC-1 activation. Notably, high ATP enhances TEC-mediated attraction of human pericytes, leading to a decrease of endothelial permeability, a hallmark of vessel normalization. Finally, we provide the first evidence of in vivo P2X7R expression in blood vessels of murine and human breast carcinoma. In conclusion, we have identified a purinergic pathway selectively acting as an antiangiogenic and normalizing signal for human tumor-derived vascular endothelium.
Crosswell electromagnetic modeling from impulsive source: Optimization strategy for dispersion suppression in convolutional perfectly matched layer
Authors: Fang Sinan , Pan Heping , Du Ting , Konaté Ahmed Amara , Deng Chengxiang , Qin Zhen , Guo Bo , Peng Ling , Ma Huolin , Li Gang , Zhou Feng
Published: September 2016

This study applied the finite-difference time-domain (FDTD) method to forward modeling of the low-frequency crosswell electromagnetic (EM) method. Specifically, we implemented impulse sources and convolutional perfectly matched layer (CPML). In the process to strengthen CPML, we observed that some dispersion was induced by the real stretch κ, together with an angular variation of the phase velocity of the transverse electric plane wave; the conclusion was that this dispersion was positively related to the real stretch and was little affected by grid interval. To suppress the dispersion in the CPML, we first derived the analytical solution for the radiation field of the magneto-dipole impulse source in the time domain. Then, a numerical simulation of CPML absorption with high-frequency pulses qualitatively amplified the dispersion laws through wave field snapshots. A numerical simulation using low-frequency pulses suggested an optimal parameter strategy for CPML from the established criteria. Based on its physical nature, the CPML method of simply warping space-time was predicted to be a promising approach to achieve ideal absorption, although it was still difficult to entirely remove the dispersion.
The characterization of an intestine-like genomic signature maintained during Barrett’s-associated adenocarcinogenesis reveals an NR5A2-mediated promotion of cancer cell survival
Authors: Duggan Shane P. , Behan Fiona M. , Kirca Murat , Zaheer Abdul , McGarrigle Sarah A. , Reynolds John V. , Vaz Gisela M. F. , Senge Mathias O. , Kelleher Dermot
Published: September 2016

Barrett’s oesophagus (BO), an intestinal-type metaplasia (IM), typically arising in conjunction with gastro-oesophageal reflux disease, is a prominent risk factor for the development of oesophageal adenocarcinoma (OAC). The molecular similarities between IM and normal intestinal tissues are ill-defined. Consequently, the contribution of intestine-enriched factors expressed within BO to oncogenesis is unclear. Herein, using transcriptomics we define the intestine-enriched genes expressed in meta-profiles of BO and OAC. Interestingly, 77% of the genes differentially expressed in a meta-profile of BO were similarly expressed in intestinal tissues. Furthermore, 85% of this intestine-like signature was maintained upon transition to OAC. Gene networking analysis of transcription factors within this signature revealed a network centred upon NR5A2, GATA6 and FOXA2, whose over-expression was determined in a cohort of BO and OAC patients. Simulated acid reflux was observed to induce the expression of both NR5A2 and GATA6. Using siRNA-mediated silencing and an NR5A2 antagonist we demonstrate that NR5A2-mediated cancer cell survival is facilitated through augmentation of GATA6 and anti-apoptotic factor BCL-XL levels. Abrogation of NR5A2-GATA6 expression in conjunction with BCL-XL co-silencing resulted in synergistically increased sensitivity to chemotherapeutics and photo-dynamic therapeutics. These findings characterize the intestine-like signature associated with IM which may have important consequences to adenocarcinogenesis.
Genome-wide analysis of heat shock proteins in C4 model, foxtail millet identifies potential candidates for crop improvement under abiotic stress
Authors: Singh Roshan Kumar , Jaishankar Jananee , Muthamilarasan Mehanathan , Shweta Shweta , Dangi Anand , Prasad Manoj
Published: September 2016

Heat shock proteins (HSPs) perform significant roles in conferring abiotic stress tolerance to crop plants. In view of this, HSPs and their encoding genes were extensively characterized in several plant species; however, understanding their structure, organization, evolution and expression profiling in a naturally stress tolerant crop is necessary to delineate their precise roles in stress-responsive molecular machinery. In this context, the present study has been performed in C4 panicoid model, foxtail millet, which resulted in identification of 20, 9, 27, 20 and 37 genes belonging to SiHSP100, SiHSP90, SiHSP70, SiHSP60 and SisHSP families, respectively. Comprehensive in silico characterization of these genes followed by their expression profiling in response to dehydration, heat, salinity and cold stresses in foxtail millet cultivars contrastingly differing in stress tolerance revealed significant upregulation of several genes in tolerant cultivar. SisHSP-27 showed substantial higher expression in response to heat stress in tolerant cultivar, and its over-expression in yeast system conferred tolerance to several abiotic stresses. Methylation analysis of SiHSP genes suggested that, in susceptible cultivar, higher levels of methylation might be the reason for reduced expression of these genes during stress. Altogether, the study provides novel clues on the role of HSPs in conferring stress tolerance.
Controlled Defects of Fluorine-incorporated ZnO Nanorods for Photovoltaic Enhancement
Authors: Lee Hock Beng , Ginting Riski Titian , Tan Sin Tee , Tan Chun Hui , Alshanableh Abdelelah , Oleiwi Hind Fadhil , Yap Chi Chin , Jumali Mohd Hafizuddin Hj. , Yahaya Muhammad
Published: September 2016

Anion passivation effect on metal-oxide nano-architecture offers a highly controllable platform for improving charge selectivity and extraction, with direct relevance to their implementation in hybrid solar cells. In current work, we demonstrated the incorporation of fluorine (F) as an anion dopant to address the defect-rich nature of ZnO nanorods (ZNR) and improve the feasibility of its role as electron acceptor. The detailed morphology evolution and defect engineering on ZNR were studied as a function of F-doping concentration (x). Specifically, the rod-shaped arrays of ZnO were transformed into taper-shaped arrays at high x. A hypsochromic shift was observed in optical energy band gap due to the Burstein-Moss effect. A substantial suppression on intrinsic defects in ZnO lattice directly epitomized the novel role of fluorine as an oxygen defect quencher. The results show that 10-FZNR/P3HT device exhibited two-fold higher power conversion efficiency than the pristine ZNR/P3HT device, primarily due to the reduced Schottky defects and charge transfer barrier. Essentially, the reported findings yielded insights on the functions of fluorine on (i) surface –OH passivation, (ii) oxygen vacancies (Vo) occupation and (iii) lattice oxygen substitution, thereby enhancing the photo-physical processes, carrier mobility and concentration of FZNR based device.
Cytotoxic Meroterpenoids with Rare Skeletons from Psidium guajava Cultivated in Temperate Zone
Authors: Qin Xu-Jie , Yan Huan , Ni Wei , Yu Mu-Yuan , Khan Afsar , Liu Hui , Zhang Hong-Xia , He Li , Hao Xiao-Jiang , Di Ying-Tong , Liu Hai-Yang
Published: September 2016

Three new meroterpenoids, guajavadials A–C (1–3), were isolated from Psidium guajava cultivated in temperate zone. Their structures were established by extensive spectroscopic evidence and electronic circular dichroism (ECD) calculations. Guajavadial A (1) represents a novel skeleton of the 3,5-diformylbenzyl phloroglucinol-coupled monoterpenoid, while guajavadials B (2) and C (3) are new adducts of the 3,5-diformylbenzyl phloroglucinol and a sesquiterpene with different coupling models. The plausible biosynthetic pathways as well as antimicrobial and cytotoxic activities of these meroterpenoids are also discussed. All these isolates exhibited moderate cytotoxicities against five human cancer cell lines, with 3 being most effective with an IC50 value of 3.54 μM toward SMMC-7721 cell lines.
A comparative, retrospective, observational study of the clinical and microbiological profiles of post-penetrating keratoplasty keratitis
Authors: Lin I-Huang , Chang Yi-Sheng , Tseng Sung-Huei , Huang Yi-Hsun
Published: September 2016

Infectious keratitis after penetrating keratoplasty (PK) is a devastating condition that may result in graft failure and poor visual outcome. In this study, we retrospectively reviewed the medical records of patients who underwent PK between 2009 and 2014, and recorded those who developed infectious keratitis. We compared the predisposing factors and organisms isolated to those identified in our previous study, conducted between 1989 and 1994. The incidence of post-PK infectious keratitis decreased from 11.6% (41 out of 354 cases, 1989–1994) to 6.5% (9 out of 138 cases, 2009–2014). Graft epithelial defect and suture-related problems remained the leading two risk factors of infectious keratitis after PK. Gram-positive and Gram-negative bacterial infection decreased from 58.5% and 46.3% to 11.1% and 22.2%, respectively (P = 0.023 and P = 0.271). In contrast, fungus infection increased from 9.8% to 66.7% (P = 0.001); fungi have become the major pathogen for post-PK infectious keratitis. In conclusion, while the incidence of post-PK infectious keratitis has decreased over time, the number and frequency of fungal infections have significantly increased in the recent study period. Clinicians should be aware of the shifting trend in pathogens involved in post-PK infectious keratitis.
The fabrication of a label-free electrochemical immunosensor using an aldehyde-functionalized pyridinium salt for antibody immobilization
Authors: Zhang Chunxiang , Pi Yibing , Shen Youming , Shen Guangyu , Zhang Youyu , Yao Shouzhuo
Published: September 2016

This paper reported a strategy based on the use of an aldehyde-functionalized pyridinium salt for the fabrication of a label-free electrochemical immunosensor.
Brønsted acid catalyzed transoximation reaction: synthesis of aldoximes and ketoximes without use of hydroxylamine salts
Authors: Hyodo Kengo , Togashi Kosuke , Oishi Naoki , Hasegawa Genna , Uchida Kingo
Published: September 2016

Inspired by bio-synthesis, we demonstrate Brønsted acid catalyzed transoximation for the synthesis of oximes without using hydroxylamine salts in water.
Self-curing furan-based elastic thermosets derived from citric acid
Authors: Fan Chuanchuan , Pang Chengcai , Liu Xiaohan , Ma Jianbiao , Gao Hui
Published: September 2016

Self-curing elastic thermosets derived from citric acid were successfully prepared, and potentially useful as one-component coating, elastomers, and adhesives.
Self-immolative versatile fluorogenic probes for screening of hydrolytic enzyme activity
Authors: Żądło-Dobrowolska Anna , Szczygieł Martyna , Koszelewski Dominik , Paprocki Daniel , Ostaszewski Ryszard
Published: September 2016

Self-immolative probes for rapid and sensitive hydrolase detection are reported. This system allows hydrolytic enzyme screening through a cascade reaction triggered by enzymatic cleavage.
Design and characterization of red fluorogenic push–pull chromophores holding great potential for bioimaging and biosensing
Authors: Li Chenge , Plamont Marie-Aude , Aujard Isabelle , Le Saux Thomas , Jullien Ludovic , Gautier Arnaud
Published: September 2016

This paper presents novel red fluorogenic push–pull chromophores, holding great potential for the development of fluorogen-based reporters and intracellular markers.
Facile synthesis of multiarmed and multicomponent star polymers by a new iterative methodology using (formyl-protected 1,3-dioxolane)-end-functionalized polymer anions
Authors: Goseki Raita , Ito Shotaro , Akemine Emi , Hirao Akira
Published: September 2016

In this manuscript, we have developed a new and efficient iterative methodology using formyl-protected 1,3-dioxolane-end-functionalized polymer anions for the facile synthesis of multiarmed and multicomponent miktoarm star polymers.
Structure determination of modulated structures by powder X-ray diffraction and electron diffraction
Authors: Zhou Zhengyang , Palatinus Lukáš , Sun Junliang
Published: September 2016

The combination of PXRD and ED is applied to determine modulated structures which resist solution by more conventional methods.
A new polymorphic form and polymorphic transformation of loratadine
Authors: Chang Ruimiao , Fu Qiang , Yu Pei , Wang Lu , Li Yong , Du Wei , Chang Chun , Zeng Aiguo
Published: September 2016

In this work, a new form of loratadine (Form B) was prepared from a 20% methanol and 80% water mixture and characterized by polarizing microscopy, scanning electron microscopy, powder X-ray diffraction and differential scanning calorimetry.
Dihydropyridine-based fluorescence probe for nitric oxide
Authors: Ma Su-Fang , Wang Qiu-Hua , Liu Fu-Tao , Wang Hui-Li , Fang De-Cai , Gong Bing , He Lan , Lu Zhong-Lin
Published: September 2016

A fluorescence probe for detecting nitric oxide based on dihydropyridine showed high selectivity and sensitivity as well as cell imaging ability.
Biosynthesis, characterization and potentiality of lipopeptides produced by Bacillus flexus S1 without inductive carbon sources
Authors: Wan Chunli , Chen Si , Wen Lei , Liu Xiang , Lee Duu-Jong , Yang Xue
Published: September 2016

This study newly isolated a bacterial stain ofBacillus flexusS1 which had abilities of synthesizing lipopeptides without any inductive operations, and thus it could effectively save operational procedures or cost.
Excited-state proton transfer in 4-2′-hydroxyphneylpyridine: full-dimensional surface-hopping dynamics simulations
Authors: Guo Wei-Wei , Liu Xiang-Yang , Chen Wen-Kai , Cui Ganglong
Published: September 2016

We have employed combined electronic structure calculations and “on-the-fly” fewest switches surface-hopping dynamics simulations to study the S1 excited-state intramolecular proton transfer (ESIPT) and decay dynamics of 4-(2′-hydroxyphenyl)pyridine.
Synthesis of amphiphilic semigrafted pseudo-Pluronics for self-assemblies carrying indomethacin
Authors: Maksym P. , Neugebauer D.
Published: September 2016

Influence of PEG length and OPG grafting density on self-assembly, particle size, drug loading content and release rate has been verified.
Synthesis of unsaturated secondary amines by direct reductive amination of aliphatic aldehydes with nitroarenes over Au/Al2O3catalyst in continuous flow mode
Authors: Nuzhdin A. L. , Artiukha E. A. , Bukhtiyarova G. A. , Zaytsev S. Yu , Plyusnin P. E. , Shubin Yu V. , Bukhtiyarov V. I.
Published: September 2016

Unsaturated secondary amines were successfully synthesized by reductive amination of aldehydes with nitroarenes over Au/Al2O3catalyst in a flow reactor.
Weaving colloidal webs around droplets: spontaneous assembly of extended colloidal networks encasing microfluidic droplet ensembles
Authors: Zheng Lu , Ho Leon Yoon , Khan Saif A.
Published: September 2016

We demonstrate transient, self-assembling solid networks that ‘cocoon’ emulsion droplets on-demand, and allow new possibilities in microfluidic droplet-based materials science.
Relating side chain organization of PNIPAm with its conformation in aqueous methanol
Authors: Mukherji Debashish , Wagner Manfred , Watson Mark D. , Winzen Svenja , de Oliveira Tiago E. , Marques Carlos M. , Kremer Kurt
Published: September 2016

Combination of nuclear magnetic resonance, dynamic light scattering, and μs long all-atom simulations of 2 million particles reveal that the PNIPAm collapse in aqueous methanol mixtures is driven by enthalpy and the reopening at higher mole fractions of methanol is entropy driven.
Harmonic multiplication based on Ge–Sb–Te resistive‐switching devices
Authors: Kanehira T. , Imanishi Y. , Hayashi H. , Nakaoka T.
Published: September 2016

Harmonic resistive multipliers that exploit the unique current–voltage (I–V) characteristics of Ag/Ge–(Sb)–Te/Pt resistive‐switching devices are demonstrated. For a Ge17Sb29Te54‐based device, an antisymmetric non‐linear I–V curve with a hump‐like structure at ±0.4 V is obtained, whereas for a Ge51Te49‐based device, an asymmetric non‐linear I–V curve with SET switching at +0.4 V and RESET switching at –0.1 V is observed. The Ge17Sb29Te54‐based device performs third harmonic multiplication for a 160 MHz input at 0 dBm, and sixth harmonic multiplication at 5 dBm under unbiased conditions without any matching circuit. For the latter device, biasing at a voltage of ±0.4 V leads to fifth harmonic multiplication, which is absent for a 0 dBm input under unbiased conditions. No harmonic multiplication is observed for an unbiased Ge51Te49‐based device due to its high resistance, but biasing at the switching voltage of 0.4 V leads to fourth harmonic multiplication for a 0 dBm input. The unique non‐linear characteristics of these devices suggest their potential for radio frequency applications.