bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enantioselective Hydrolysis of Amino Acid Esters Promoted by Bis(β-cyclodextrin) Copper Complexes
Authors: Xue Shan-Shan , Zhao Meng , Ke Zhuo-Feng , Cheng Bei-Chen , Su Hua , Cao Qian , Cao Zhen-Kun , Wang Jun , Ji Liang-Nian , Mao Zong-Wan 
Published: February 2016

AbstractIt is challenging to create artificial catalysts that approach enzymes with regard to catalytic efficiency and selectivity. The enantioselective catalysis ranks the privileged characteristic of enzymatic transformations. Here, we report two pyridine-linked bis(β-cyclodextrin) (bisCD) copper(II) complexes that enantioselectively hydrolyse chiral esters. Hydrolytic kinetic resolution of three pairs of amino acid ester enantiomers (S1–S3) at neutral pH indicated that the “back-to-back” bisCD complex CuL1 favoured higher catalytic efficiency and more pronounced enantioselectivity than the “face-to-face” complex CuL2. The best enantioselectivity was observed for N-Boc-phenylalanine 4-nitrophenyl ester (S2) enantiomers promoted by CuL1, which exhibited an enantiomer selectivity of 15.7. We observed preferential hydrolysis of L-S2 by CuL1, even in racemic S2, through chiral high-performance liquid chromatography (HPLC). We demonstrated that the enantioselective hydrolysis was related to the cooperative roles of the intramolecular flanking chiral CD cavities with the coordinated copper ion, according to the results of electrospray ionization mass spectrometry (ESI-MS), inhibition experiments, rotating-frame nuclear Overhauser effect spectroscopy (ROESY), and theoretical calculations. Although the catalytic parameters lag behind the level of enzymatic transformation, this study confirms the cooperative effect of the first and second coordination spheres of artificial catalysts in enantioselectivity and provides hints that may guide future explorations of enzyme mimics.
An Integrative Pharmacogenomic Approach Identifies Two-drug Combination Therapies for Personalized Cancer Medicine
Authors: Liu Yin , Fei Teng , Zheng Xiaoqi , Brown Myles , Zhang Peng , Liu X. Shirley , Wang Haiyun 
Published: February 2016

AbstractAn individual tumor harbors multiple molecular alterations that promote cell proliferation and prevent apoptosis and differentiation. Drugs that target specific molecular alterations have been introduced into personalized cancer medicine, but their effects can be modulated by the activities of other genes or molecules. Previous studies aiming to identify multiple molecular alterations for combination therapies are limited by available data. Given the recent large scale of available pharmacogenomic data, it is possible to systematically identify multiple biomarkers that contribute jointly to drug sensitivity and to identify combination therapies for personalized cancer medicine. In this study, we used pharmacogenomic profiling data provided from two independent cohorts in a systematic in silico investigation of perturbed genes cooperatively associated with drug sensitivity. Our study predicted many pairs of molecular biomarkers that may benefit from the use of combination therapies. One of our predicted biomarker pairs, a mutation in the BRAF gene and upregulated expression of the PIM1 gene, was experimentally validated to benefit from a therapy combining BRAF inhibitor and PIM1 inhibitor in lung cancer. This study demonstrates how pharmacogenomic data can be used to systematically identify potentially cooperative genes and provide novel insights to combination therapies in personalized cancer medicine.
Effects of local structural transformation of lipid-like compounds on delivery of messenger RNA
Authors: Li Bin , Luo Xiao , Deng Binbin , Giancola JoLynn B. , McComb David W. , Schmittgen Thomas D. , Dong Yizhou 
Published: February 2016

AbstractLipid-like nanoparticles (LLNs) have shown great potential for RNA delivery. Lipid-like compounds are key components in LLNs. In this study, we investigated the effects of local structural transformation of lipid-like compounds on delivery of messenger RNA. Our results showed that position change of functional groups on lipid-like compounds can dramatically improve delivery efficiency. We then optimized formulation ratios of TNT-b10 LLNs, a lead material, increasing delivery efficiency over 2-fold. More importantly, pegylated TNT-b10 LLNs is stable for over four weeks and is over 10-fold more efficient than that of its counterpart TNT-a10 LLNs. Additionally, the optimal formulation O-TNT-b10 LLNs is capable of delivering mRNA encoding luciferase in vivo. These results provide useful insights into the design of next generation LLNs for mRNA delivery.
Synergistic Processing of Biphenyl and Benzoate: Carbon Flow Through the Bacterial Community in Polychlorinated-Biphenyl-Contaminated Soil
Authors: Leewis Mary-Cathrine , Uhlik Ondrej , Leigh Mary Beth 
Published: February 2016

AbstractAerobic mineralization of PCBs, which are toxic and persistent organic pollutants, involves the upper (biphenyl, BP) and lower (benzoate, BZ) degradation pathways. The activity of different members of the soil microbial community in performing one or both pathways and their synergistic interactions during PCB biodegradation, are not well understood. This study investigates BP and BZ biodegradation and subsequent carbon flow through the microbial community in PCB-contaminated soil. DNA stable isotope probing (SIP) was used to identify the bacterial guilds involved in utilizing 13C-biphenyl (unchlorinated analogue of PCBs) and/or 13C-benzoate (product/intermediate of BP degradation and analogue of chlorobenzoates). By performing SIP with two substrates in parallel, we reveal microbes performing the upper (BP) and/or lower (BZ) degradation pathways and heterotrophic bacteria involved indirectly in processing carbon derived from these substrates (i.e. through crossfeeding). Substrate mineralization rates and shifts in relative abundance of labeled taxa suggest that BP and BZ biotransformations were performed by microorganisms with different growth strategies: BZ-associated bacteria were fast growing, potentially copiotrophic organisms, while microbes that transform BP were oligotrophic, slower growing, organisms. Our findings provide novel insight into the functional interactions of soil bacteria active in processing biphenyl and related aromatic compounds in soil, revealing how carbon flows through a bacterial community.
In situ Proteomic Profiling of Curcumin Targets in HCT116 Colon Cancer Cell Line
Authors: Wang Jigang , Zhang Jianbin , Zhang Chong-Jing , Wong Yin Kwan , Lim Teck Kwang , Hua Zi-Chun , Liu Bin , Tannenbaum Steven R. , Shen Han-Ming , Lin Qingsong 
Published: February 2016

AbstractTo date, the exact targets and mechanism of action of curcumin, a natural product with anti-inflammatory and anti-cancer properties, remain elusive. Here we synthesized a cell permeable curcumin probe (Cur-P) with an alkyne moiety, which can be tagged with biotin for affinity enrichment, or with a fluorescent dye for visualization of the direct-binding protein targets of curcumin in situ. iTRAQTM quantitative proteomics approach was applied to distinguish the specific binding targets from the non-specific ones. In total, 197 proteins were confidently identified as curcumin binding targets from HCT116 colon cancer cell line. Gene Ontology analysis showed that the targets are broadly distributed and enriched in the nucleus, mitochondria and plasma membrane, and they are involved in various biological functions including metabolic process, regulation, response to stimulus and cellular process. Ingenuity Pathway AnalysisTM (IPA) suggested that curcumin may exert its anticancer effects over multiple critical biological pathways including the EIF2, eIF4/p70S6K, mTOR signaling and mitochondrial dysfunction pathways. Functional validations confirmed that curcumin downregulates cellular protein synthesis, and induces autophagy, lysosomal activation and increased ROS production, thus leading to cell death.
Membrane type 1-matrix metalloproteinase induces epithelial-to-mesenchymal transition in esophageal squamous cell carcinoma: Observations from clinical and in vitro analyses
Authors: Pang Lijuan , Li Qiuxiang , Li Shugang , He Jianwei , Cao Weiwei , Lan Jiaojiao , Sun Bin , Zou Hong , Wang Chengyan , Liu Ruixue , Wei Cuilei , Wei Yutao , Qi Yan , Hu Jianming , Liang Weihua , Zhang Wen Jie , Wan Mei , Li Feng 
Published: February 2016

AbstractMembrane type 1-matrix metalloproteinase (MT1-MMP) is associated with enhanced tumorigenicity in many cancers. A recent study has revealed that MT1-MMP induces epithelial-to-mesenchymal transition (EMT) in prostate and breast cancer cells. However, its role in esophageal squamous cell carcinoma (ESCC) has not been studied. Here, we investigated the role of MT1-MMP in the dissemination of ESCC. Expression of MT1-MMP was detected by immunohistochemistry and tissue microarray in 88 Kazakh ESCC patients. Western blotting was performed to detect endogenous and overexpressed exogenous MT1-MMP in the Eca109 and Eca9706 cell lines, respectively. Transwell assay was used to estimate MT1-MMP-induced invasion and metastasis. EMT-associated proteins were detected by immunohistochemistry and western blotting. The associations between the expression of MT1-MMP and EMT-associated proteins with clinicopathologic parameters were analyzed. Overexpression of MT1-MMP was confirmed in Kazakh ESCC patients. MT1-MMP levels were found to be correlated with the depth of tumor infiltration. MT1-MMP induced EMT in ESCC both in vivo and in vitro, N-cadherin and Vimentin expression was upregulated upon MT1-MMP transfection into cells. However, E-cadherin was found to be downregulated. MT1-MMP-induced EMT led to increase migration and invasion in ESCC cell lines. In conclusion, our results suggest that MT1-MMP promotes ESCC invasion and metastasis.
Dedicated Industrial Oilseed Crops as Metabolic Engineering Platforms for Sustainable Industrial Feedstock Production
Authors: Zhu Li-Hua , Krens Frans , Smith Mark A. , Li Xueyuan , Qi Weicong , van Loo Eibertus N. , Iven Tim , Feussner Ivo , Nazarenus Tara J. , Huai Dongxin , Taylor David C. , Zhou Xue-Rong , Green Allan G. , Shockey Jay , Klasson K. Thomas , Mullen Robert T. , Huang Bangquan , Dyer John M. , Cahoon Edgar B. 
Published: February 2016

AbstractFeedstocks for industrial applications ranging from polymers to lubricants are largely derived from petroleum, a non-renewable resource. Vegetable oils with fatty acid structures and storage forms tailored for specific industrial uses offer renewable and potentially sustainable sources of petrochemical-type functionalities. A wide array of industrial vegetable oils can be generated through biotechnology, but will likely require non-commodity oilseed platforms dedicated to specialty oil production for commercial acceptance. Here we show the feasibility of three Brassicaceae oilseeds crambe, camelina, and carinata, none of which are widely cultivated for food use, as hosts for complex metabolic engineering of wax esters for lubricant applications. Lines producing wax esters >20% of total seed oil were generated for each crop and further improved for high temperature oxidative stability by down-regulation of fatty acid polyunsaturation. Field cultivation of optimized wax ester-producing crambe demonstrated commercial utility of these engineered crops and a path for sustainable production of other industrial oils in dedicated specialty oilseeds.
Singular observation of the polarization-conversion effect for a gammadion-shaped metasurface
Authors: Lin Chu-En , Yen Ta-Jen , Yu Chih-Jen , Hsieh Cheng-Min , Lee Min-Han , Chen Chii-Chang , Chang Cheng-Wei 
Published: February 2016

AbstractIn this article, the polarization-conversion effects of a gammadion-shaped metasurface in transmission and reflection modes are discussed. In our experiment, the polarization-conversion effect of a gammadion-shaped metasurface is investigated because of the contribution of the phase and amplitude anisotropies. According to our experimental and simulated results, the polarization property of the first-order transmitted diffraction is dominated by linear anisotropy and has weak depolarization; the first-order reflected diffraction exhibits both linear and circular anisotropies and has stronger depolarization than the transmission mode. These results are different from previously published research. The Mueller matrix ellipsometer and polar decomposition method will aid in the investigation of the polarization properties of other nanostructures.
Functional modules of sigma factor regulons guarantee adaptability and evolvability
Authors: Binder Sebastian C. , Eckweiler Denitsa , Schulz Sebastian , Bielecka Agata , Nicolai Tanja , Franke Raimo , Häussler Susanne , Meyer-Hermann Michael 
Published: February 2016

AbstractThe focus of modern molecular biology turns from assigning functions to individual genes towards understanding the expression and regulation of complex sets of molecules. Here, we provide evidence that alternative sigma factor regulons in the pathogenPseudomonas aeruginosalargely represent insulated functional modules which provide a critical level of biological organization involved in general adaptation and survival processes. Analysis of the operational state of the sigma factor network revealed that transcription factors functionally couple the sigma factor regulons and significantly modulate the transcription levels in the face of challenging environments. The threshold quality of newly evolved transcription factors was reached faster and more robustly inin silicotesting when the structural organization of sigma factor networks was taken into account. These results indicate that the modular structures of alternative sigma factor regulons provideP. aeruginosawith a robust framework to function adequately in its environment and at the same time facilitate evolutionary change. Our data support the view that widespread modularity guarantees robustness of biological networks and is a key driver of evolvability.
A novel self-enhanced electrochemiluminescence immunosensor based on hollow Ru-SiO2@PEI nanoparticles for NSE analysis
Authors: Zhou Limin , Huang Jianshe , Yu Bin , You Tianyan 
Published: February 2016

AbstractPoly(ethylenimine) (PEI) and Ru(bpy)32+-doped silica (Ru-SiO2) nanoparticles were simply mixed together to prepare a novel self-enhanced electrochemiluminescence (ECL) composite of Ru-SiO2@PEI. The hollow Ru-SiO2@PEI nanoparticles were used to build an ECL immunosensor for the analysis of neuron specific enolase (NSE). PEI not only assembled on the surface of Ru-SiO2 nanoparticles through the electrostatic interaction to act as co-reactant for Ru(bpy)32+ ECL, but also provided alkaline condition to etch the Ru-SiO2 nanoparticles to form the hollow Ru-SiO2@PEI nanoparticles with porous shell. The unique structure of the Ru-SiO2@PEI nanoparticles loaded both a large amount of Ru(bpy)32+ and its co-reactant PEI at the same time, which shortened the electron-transfer distance, thereby greatly enhanced the luminous efficiency and amplified the ECL signal. The developed immunosensor showed a wide linear range from 1.0 × 10−11 to 1.0 × 10−5 mg mL−1 with a low detection limit of 1.0 × 10−11 mg mL−1 for NSE. When the immunosensor was used for the determination of NSE in clinical human serum, the results were comparable with those obtained by using enzyme-linked immunosorbent assay (ELISA) method. The proposed method provides a promising alternative for NSE analysis in clinical samples.
Mutation analysis of the phospholamban gene in 315 South Africans with dilated, hypertrophic, peripartum and arrhythmogenic right ventricular cardiomyopathies
Authors: Fish Maryam , Shaboodien Gasnat , Kraus Sarah , Sliwa Karen , Seidman Christine E. , Burke Michael A. , Crotti Lia , Schwartz Peter J. , Mayosi Bongani M. 
Published: February 2016

AbstractCardiomyopathy is an important cause of heart failure in Sub-Saharan Africa, accounting for up to 30% of adult heart failure hospitalisations. This high prevalence poses a challenge in societies without access to resources and interventions essential for disease management. Over 80 genes have been implicated as a cause of cardiomyopathy. Mutations in the phospholamban (PLN) gene are associated with dilated cardiomyopathy (DCM) and severe heart failure. In Africa, the prevalence of PLN mutations in cardiomyopathy patients is unknown. Our aim was to screen 315 patients with arrhythmogenic right ventricular cardiomyopathy (n = 111), DCM (n = 95), hypertrophic cardiomyopathy (n = 40) and peripartum cardiomyopathy (n = 69) for disease-causing PLN mutations by high resolution melt analysis and DNA sequencing. We detected the previously reported PLN c.25C > T (p.R9C) mutation in a South African family with severe autosomal dominant DCM. Haplotype analysis revealed that this mutation occurred against a different haplotype background to that of the original North American family and was therefore unlikely to have been inherited from a common ancestor. No other mutations in PLN were detected (mutation prevalence = 0.2%). We conclude that PLN is a rare cause of cardiomyopathy in African patients. The PLN p.R9C mutation is not well-tolerated, emphasising the importance of this gene in cardiac function.
Incorporating TiO2 nanotubes with a peptide of D-amino K122-4 (D) for enhanced mechanical and photocatalytic properties
Authors: Guo L. Q. , Hu Y. W. , Yu B. , Davis E. , Irvin R. , Yan X. G. , Li D. Y. 
Published: February 2016

AbstractTitanium dioxide (TiO2) nanotubes are promising for a wide variety of potential applications in energy, biomedical and environmental sectors. However, their low mechanical strength and wide band gap limit their widespread technological use. This article reports our recent efforts to increase the mechanical strength of TiO2 nanotubes with lowered band gap by immobilizing a peptide of D-amino K122-4 (D) onto the nanotubes. Topographies and chemical compositions of the peptide-coated and uncoated TiO2 nanotubular arrays were characterized by scanning electron microscopy and X-ray photoelectron spectroscopy (XPS). Properties of the peptide-coated and uncoated TiO2 nanotubular arrays, including hardness, elastic modulus, electron work function and photocurrent, were evaluated using micromechanical probe, Kelvin Probe and electrochemical system. Effect of the peptide on surface conductivity was also investigated through current mapping and I–V curve analysis with conductive atomic force microscopy. It is demonstrated that the peptide coating simultaneously enhances the mechanical strength, photocatalytic and electrical properties of TiO2 nanotubes.
Distinct Expression Patterns Of Causative Genes Responsible For Hereditary Progressive Hearing Loss In Non-Human Primate Cochlea
Authors: Hosoya Makoto , Fujioka Masato , Ogawa Kaoru , Okano Hideyuki 
Published: February 2016

AbstractHearing impairment is the most frequent sensory deficit in humans. Deafness genes, which harbor pathogenic mutations that have been identified in families with hereditary hearing loss, are commonly expressed in the auditory end organ or the cochlea and may contribute to normal hearing function, yet some of the mouse models carrying these mutations fail to recapitulate the hearing loss phenotype. In this study, we find that distinct expression patterns of those deafness genes in the cochlea of a non-human primate, the common marmoset (Callithrix jacchus). We examined 20 genes whose expression in the cochlea has already been reported. The deafness genes GJB3, CRYM, GRHL2, DFNA5 and ATP6B1 were expressed in marmoset cochleae in patterns different from those in mouse cochleae. Of note, all those genes are causative for progressive hearing loss in humans, but not in mice. The other tested genes, including the deafness gene COCH, in which mutation recapitulates deafness in mice, were expressed in a similar manner in both species. The result suggests that the discrepancy in the expression between rodents and primates may account for the phenotypic difference. This limitation of the rodent models can be bypassed by using non-human primate models such as the marmoset.
Culture-independent method for identification of microbial enzyme-encoding genes by activity-based single-cell sequencing using a water-in-oil microdroplet platform
Authors: Nakamura Kazuki , Iizuka Ryo , Nishi Shinro , Yoshida Takao , Hatada Yuji , Takaki Yoshihiro , Iguchi Ayaka , Yoon Dong Hyun , Sekiguchi Tetsushi , Shoji Shuichi , Funatsu Takashi 
Published: February 2016

AbstractEnvironmental microbes are a great source of industrially valuable enzymes with potent and unique catalytic activities. Unfortunately, the majority of microbes remain unculturable and thus are not accessible by culture-based methods. Recently, culture-independent metagenomic approaches have been successfully applied, opening access to untapped genetic resources. Here we present a methodological approach for the identification of genes that encode metabolically active enzymes in environmental microbes in a culture-independent manner. Our method is based on activity-based single-cell sequencing, which focuses on microbial cells showing specific enzymatic activities. First, at the single-cell level, environmental microbes were encapsulated in water-in-oil microdroplets with a fluorogenic substrate for the target enzyme to screen for microdroplets that contain microbially active cells. Second, the microbial cells were recovered and subjected to whole genome amplification. Finally, the amplified genomes were sequenced to identify the genes encoding target enzymes. Employing this method, we successfully identified 14 novel β-glucosidase genes from uncultured bacterial cells in marine samples. Our method contributes to the screening and identification of genes encoding industrially valuable enzymes.
Absence of cytotoxicity towards microglia of iron oxide (α-Fe2O3) nanorhombohedra
Authors: Lewis Crystal S. , Torres Luisa , Miyauchi Jeremy T. , Rastegar Cyrus , Patete Jonathan M. , Smith Jacqueline M. , Wong Stanislaus S. , Tsirka Stella E. 
Published: February 2016

AbstractUnderstanding the nature of interactions between nanomaterials, such as commercially ubiquitous hematite (α-Fe2O3) nanorhombohedra (N-Rhomb) and biological systems is of critical importance for gaining insight into the practical applicability of nanomaterials. Microglia represent the first line of defense in the central nervous system (CNS) during severe injury or disease such as Parkinson's and Alzheimer's disease as illustrative examples. Hence, to analyze the potential cytotoxic effect of N-Rhomb exposure in the presence of microglia, we have synthesized Rhodamine B (RhB)-labeled α-Fe2O3 N-Rhomb, with lengths of 47 ± 10 nm and widths of 35 ± 8 nm. Internalization of RhB-labeled α-Fe2O3 N-Rhomb by microglia in the mouse brain was observed, and a dose-dependent increase in the cellular iron content as probed by cellular fluorescence was detected in cultured microglia after nanoparticle exposure. The cells maintained clear functional viability, exhibiting little to no cytotoxic effects after 24 and 48 hours at acceptable, physiological concentrations. Importantly, the nanoparticle exposure did not induce microglial cells to produce either tumor necrosis factor alpha (TNFα) or interleukin 1-beta (IL1β), two pro-inflammatory cytokines, nor did exposure stimulate the production of nitrites and reactive oxygen species (ROS), which are common indicators for the onset of inflammation. Finally, we propose that under the conditions of our experiments, i.e. in the presence of RhB labeled-α-Fe2O3 N-Rhomb maintaining concentrations of up to 100 μg mL−1 after 48 hours of incubation, the in vitro and in vivo internalization of RhB-labeled α-Fe2O3 N-Rhomb are likely to be clathrin-dependent, which represents a conventional mechanistic uptake route for most cells. Given the crucial role that microglia play in many neurological disorders, understanding the potential cytotoxic effects of these nanostructures is of fundamental importance if they are to be used in a therapeutic setting.