2015 Volume 26 Issue 4

Editorial
Zhan Chen , Brian P. Coppola , Carol A. Fierke
2015, 26(4): 393-394  doi: 10.1016/j.cclet.2015.04.004
[Abstract](466) [FullText HTML] [PDF 285KB](0)
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Listen to the chemical and histological information in biological tissue
Jie Yin , Fei Zhao , Chao Tao , Xue-Ding Wang , Xiao-Jun Liu
2015, 26(4): 395-400  doi: 10.1016/j.cclet.2015.01.030
[Abstract](492) [FullText HTML] [PDF 6047KB](0)
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Photoacoustic imaging (PAI), as an emerging biomedicine diagnostic technique that has been developed quickly in the past decade, inherits the high spatial resolution of ultrasonography in imaging deep tissue and the high sensitivity of optical imaging in evaluating tissue chemical and physiological information. In this paper, after introducing the basic principles of PAI including both photoacoustic tomography and photoacoustic microscopy, we will review some recent progress of PAI in biomedicine and demonstrate the capability of PAI in detecting the chemical compositions and in evaluating the histological microstructures in biological tissue.
Raman spectroscopy monitors adverse bone sequelae of cancer radiotherapy
Bo Gong , Michael D. Morris
2015, 26(4): 401-406  doi: 10.1016/j.cclet.2014.11.034
[Abstract](494) [FullText HTML] [PDF 3292KB](0)
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Raman spectroscopy provides information on bone chemical composition and structure via widely used metrics including mineral to matrix ratio, mineral crystallinity and carbonate content, collagen crosslinking ratio and depolarization ratios. These metrics are correlated with bone material properties, such as hardness, plasticity and Young's modulus. We review application of Raman spectroscopy to two important irradiated animalmodels: the mouse tibia, amodel for damage to cortical bone sites including the rib (breast cancer) and to healthy tissue adjacent to extremity sarcomas, and the rat mandible, a model for radiation damage in head and neck cancer radiotherapy. Longitudinal studies of irradiated mouse tibia demonstrate that radiation-induced matrix abnormalities can persist even 26 weeks postradiation. Polarized Raman spectroscopy shows formation of more ordered orientation of both mineral and collagen. At 8 weeks post-radiation, irradiated rat hemimandible exhibits transient hypermineralization, increased collagen cross-linking and decreased depolarization ratios of mineral and collagen. A standard radioprotectant, amifostine, mitigates rat mandible radiation damage, with none remaining detectable 18 weeks post-radiation. Already a powerful tool to monitor radiation damage, Raman spectroscopy may be important in development of new radiotherapy protocols and radioprotective agents. Further in vivo studies of radiation effects on the rodent models are underway, as are development of methodologies for eventual use in human subjects.
Bioanalytical methods for metabolomic profiling: Detection of head and neck cancer, including oral cancer
Nirbhay S. Jain , Ulrich H. N. Dürr , Ayyalusamy Ramamoorthy
2015, 26(4): 407-415  doi: 10.1016/j.cclet.2015.03.001
[Abstract](645) [FullText HTML] [PDF 464KB](0)
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Metabolomics is an emerging field dealing with the measurement and interpretation of small molecular byproducts of biochemical processes, or metabolites, which can be used to generate profiles from biological samples. Promising for use in pathophysiology, metabolomic profiles give the immediate biological state of a sample. These profiles are altered in diseases and are detectable in biological samples, such as tissue, blood, urine, saliva, and others. Most remarkably, metabolic profiles usually are altered before symptoms appear in a patient. For this reason, metabolomics has potential as a reliable method for an early diagnosis of diseases through disease biomarker identification. This application is most prevalent in cancer, such as head and neck cancer (HNC). Metabolomic studies offer avenues to improve on current medical techniques through the application of mass spectrometry (MS), nuclear magnetic resonance spectroscopy (NMR), and statistical analysis to determine better biomarkers than those currently known. In this review, we discuss the use of MS and NMR tools for detecting biomarkers in tissue and fluid samples, and the appropriateness of metabolomics in analyzing cancer. Advantages, disadvantages, and recent studies on metabolomic profiling techniques in HNC analysis are also discussed herein.
New developments in Western blot technology
Shi Jin , Robert T. Kennedy
2015, 26(4): 416-418  doi: 10.1016/j.cclet.2015.01.021
[Abstract](491) [FullText HTML] [PDF 323KB](0)
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Western blotting is a highly valued method for protein identification and relative quantitation in complex samples. It combines size-based electrophoretic separation with immunoaffinity to identify specific proteins. This technique remains popular and has become a workhorse in biochemical research and clinical laboratories. Despite its utility and popularity, this method has many limitations including slow analysis, incompatibility with limited sample application, low throughput and low information content. Recently there has been significant success in improving different aspects of Western blotting. In this review, we provide an overview of the developments in the area of improving conventional Western blotting methods with a focus on recent developments in microfluidic Western blotting. We overview different separation platforms, and discuss studies on protein transfer methods as well as protein immobilization methods and chemistries. We also describe integrated miniaturized platforms that can perform rapid separations and immunodetections.
Optical enhancement effects of plasmonic nanostructures on organic photovoltaic cells
Hui Joon Park , L. Jay Guo
2015, 26(4): 419-425  doi: 10.1016/j.cclet.2015.02.001
[Abstract](452) [FullText HTML] [PDF 8530KB](0)
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In this article, the optical enhancement effects of plasmonic nanostructures on OPV cells were reviewed as an effective way to resolve the mismatch problems between the short exciton diffusion length in organic semiconductors (around 10 nm) and the large thickness required to fully absorb sunlight (e.g. hundreds of nanometers). Especially, the performances of OPVs with plasmonic nanoparticles in photoactive and buffer layers and with periodic nanostructures were investigated. Furthermore, nanoimprint lithography-based nanofabrication processes that can easily control the dimension and uniformity of structures for large-area and uniform plasmonic nanostructures were demonstrated.
Folate binding protein-Outlook for drug delivery applications
Rachel L. Merzel , Jun-Jie Chen , E. Neil G. Marsh , Mark M. Banaszak Holl
2015, 26(4): 426-430  doi: 10.1016/j.cclet.2014.12.015
[Abstract](455) [FullText HTML] [PDF 1142KB](0)
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Serum proteins represent an important class of drug and imaging agent delivery vectors. In this minireview, key advantages of using serum proteins are discussed, followed by the particular advantages and challenges associated with employing soluble folate binding protein. In particular, approaches employing drugs that target folate metabolism are reviewed. Additionally, the slow-onset, tightbinding interaction of folate with folate binding protein and the relationship to a natural oligomerization mechanism is discussed. These unique aspects of folate binding protein suggest interesting applications for the protein as a vector for further drug and imaging agent development.
Recent progress in hydrocarbon biofuel synthesis: Pathways and enzymes
Feng-Ming Lin , E. Neil G. Marsh , Xiaoxia Nina Lin
2015, 26(4): 431-434  doi: 10.1016/j.cclet.2015.03.018
[Abstract](484) [FullText HTML] [PDF 499KB](0)
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Biofuels derived from hydrocarbon biosynthetic pathways have attracted increasing attention. Routes to hydrocarbon biofuels are emerging and mainly fall into two categories based on the metabolic pathways utilized: Fatty acid pathway-based alkanes/alkenes and isoprenoid biosynthetic pathway based terpenes. The primary focus of this review is on recent progress in the application of hydrocarbon biosynthetic pathways for hydrocarbon biofuel production, together with studies on enzymes, including efforts to engineering them for improved performance.
Biomolecular hydration dynamics probed with 2D-IR spectroscopy: From dilute solution to a macromolecular crowd
John T. King , Evan J. Arthur , Derek G. Osborne , Charles L. Brooks Ⅲ , Kevin J. Kubarych
2015, 26(4): 435-438  doi: 10.1016/j.cclet.2015.03.005
[Abstract](446) [FullText HTML] [PDF 1737KB](0)
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Although it is well known that water is essential for biological function, it has been a challenge to determine how water behaves near biomacromolecular interfaces, and what role water plays in influencing the dynamics of the biochemical machinery. By adopting a vibrational labeling strategy coupled with ultrafast two-dimensional infrared (2D-IR) spectroscopy, it has recently become possible to study hydration dynamics, site specifically at the surface of proteins and model membranes. We review our recent progress in measuring hydration dynamics in contexts ranging from small-molecule solutes to biomacromolecules in dilute, viscous, and crowded environments.
Excited electronic states and internal conversion in cyanocobalamin
Theodore E. Wiley , Brenden C. Arruda , Nicholas A. Miller , Michael Lenard , Roseanne J. Sension
2015, 26(4): 439-443  doi: 10.1016/j.cclet.2015.03.003
[Abstract](466) [FullText HTML] [PDF 1171KB](0)
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Cyanocobalamin (CNCbl) is a paradigm system for the study of excited electronic states and biological cofactors including the B12 vitamers. The photophysics of CNCbl has been thoroughly investigated using both ultrafast spectroscopy and time dependent density functional theory (TD-DFT). Herewe review the spectroscopic and theoretical investigations of CNCbl with emphasis on the nature of S1, the lowest excited electronic state, and extend the spectroscopic measurements to include the ultraviolet region of the spectrum. Ultrafast transient absorption measurements in the visible αβ band region and in the midinfrared led to assignment of the S1 state to a ligand-to-metal charge transfer (LMCT) with lengthened axial bonds and a ~3 kcal/mol barrier for internal conversion to the ground state. The present measurements encompassing the γ band region of the spectrum provide further support for the assignment of the S1 state. The experiments are in good agreement with the results of TD-DFT calculations which confirm the expected lengthening of the axial bonds in S1 and account for the observed barrier for internal conversion back to the ground state.
Assembly of zinc metallacrowns with an α-amino hydroxamic acid ligand
Joseph Jankolovits , Jeff W. Kampf , Vincent L. Pecoraro
2015, 26(4): 444-448  doi: 10.1016/j.cclet.2015.01.017
[Abstract](473) [FullText HTML] [PDF 1547KB](0)
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In the assembly of metallacrowns for molecular recognition, luminescence, and molecular magnetism applications, substituting the ring ion can have profound effects on the structure, stability, and physical properties of the inorganic macrocycle. The assembly of Zn(Ⅱ) metallacrowns with an α-amino hydroxamic acid ligand (pheHA) was investigated to compare the assembly behavior with the well studied metallacrowns containing Cu(Ⅱ) and Ni(Ⅱ). Electrospray ionization mass spectrometry reveals that the benchmark species Zn5(pheHA)42+ and LnZn5(pheHA)53+ assemble in pyridine, which is consistent with the behavior of Cu(Ⅱ) and Ni(Ⅱ). A LnZn4(pheHA)43+ species is also observed in a 1:1 DMF-pyridine mixture. An unprecedented La(Ⅲ)[16-MCZn(Ⅱ),pheHA,HpheHA-6]5+ complex was crystallographically characterized that possesses unusual C2 symmetry. These results provide insights into the design of functional metallacrowns through ring ion substitution.
Surface plasma treatment effects on the molecular structure at polyimide/air and buried polyimide/epoxy interfaces
John N. Myers , Zhan Chen
2015, 26(4): 449-454  doi: 10.1016/j.cclet.2015.01.016
[Abstract](484) [FullText HTML] [PDF 2153KB](0)
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Polyimides are widely used as chip passivation layers and organic substrates in microelectronic packaging. Plasma treatment has been used to enhance the interfacial properties of polyimides, but its molecularmechanism is not clear. In this research, the effects of polyimide surface plasma treatment on the molecular structures at corresponding polyimide/air and buried polyimide/epoxy interfaces were investigated in situ using sum frequency generation (SFG) vibrational spectroscopy. SFG results show that the polyimide backbone molecular structure was different at polyimide/air and polyimide/epoxy interfaces before and after plasma treatment. The different molecular structures at each interface indicate that structural reordering of the polyimide backbone occurred as a result of plasma treatment and contact with the epoxy adhesive. Furthermore, quantitative orientation analysis indicated that plasma treatment of polyimide surfaces altered the twist angle of the polyimide backbone at corresponding buried polyimide/epoxy interfaces. These SFG results indicate that plasma treatment of polymer surfaces can alter the molecular structure at corresponding polymer/air and buried polymer interfaces.
Structure-based design of conformationally constrained cyclic peptidomimetics to target the MLL1-WDR5 protein-protein interaction as inhibitors of the MLL1 methyltransferase activity
Hacer Karatas , Shirley Y. Lee , Elizabeth C. Townsend , Fang Cao , Jing Xu , Denzil Bernard , Liu Liu , Yali Dou , Shaomeng Wang
2015, 26(4): 455-458  doi: 10.1016/j.cclet.2015.03.030
[Abstract](438) [FullText HTML] [PDF 1179KB](0)
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We described herein structure-based design, synthesis and evaluation of conformationally constrained, cyclic peptidomimetics to block the MLL1-WDR5 protein-protein interaction as inhibitors of the MLL1 histone methyltransferase activity. Our study has yielded cyclic peptidomimetics with very high binding affinities to WDR5 (Ki values <1 nmol/L) and function as antagonists of the MLL1 histone methyltransferase activity.
Thermal and environmental stability of poly(4-ethynyl-p-xylylene-co-p-xylylene) thin films
Yu Liang , Xiaopei Deng , Jay J. Senkevich , Hao Ding , Joerg Lahann
2015, 26(4): 459-463  doi: 10.1016/j.cclet.2015.01.018
[Abstract](437) [FullText HTML] [PDF 936KB](0)
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The aim of this paper was to test the thermal and environmental stability of poly(4-ethynyl-p-xylyleneco- p-xylylene) thin films prepared by chemical vapor deposition (CVD) and to optimize the reaction conditions of the polymer. Fourier transformed infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and fluorescence microscopy were employed to investigate the stability of the reactive polymer coatings in various environmental conditions. Chemical reactivity of the thin films were then tested by Huisgen 1,3-dipolar cycloaddition reaction ("click" reaction). The alkyne functional groups on poly(4- ethynyl-p-xylylene-co-p-xylylene) thin films were found to be stable under ambient storage conditions and thermally stable up to 100℃ when annealed at 0.08 Torr in argon. We also optimized the click reaction conditions of azide-functionalized molecules with poly(4-ethynyl-p-xylylene-co-p-xylylene). The best reaction result was achieved, when copper concentration was 0.5 mmol/L, sodium ascorbate concentration to copper concentration was 5:1. In contrast, the azide concentration and temperature had no obvious effect on the surface reaction.
Improved thromboresistance and analytical performance of intravascular amperometric glucose sensors using optimized nitric oxide release coatings
Alexander K. Wolf , Yu Qin , Terry C. Major , Mark E. Meyerhoff
2015, 26(4): 464-468  doi: 10.1016/j.cclet.2015.03.002
[Abstract](454) [FullText HTML] [PDF 2565KB](0)
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In this work, nitric oxide (NO) release coatings designed for intravenous amperometric glucose sensors are optimized through the use of a polylactic acid (PLA) layer doped with a lipophilic diazeniumdiolated species that releases NO through a proton-driven mechanism. An Elast-Eon E2As polyurethane coating is used to both moderate NO release from the sensor surface and increase the sensor's linear detection range toward glucose. These sensors were evaluated for thromboresistance and in vivo glucose performance through implantation in rabbit veins. By maintaining NO flux on a similar scale to endogenous endothelial cells, implanted glucose sensors exhibited reduced surface clot formation which enables more accurate quantitative glucose measurements continuously. An in vivo time trace of implanted venous sensors demonstrated glucose values that correlated well with the discrete measurements of blood samples on a benchtop point-of-care sensor-based instrument. The raw measured currents from the implanted glucose sensors over 7 h time periods were converted to glucose concentration through use of both a one-point in vivo calibration and a calibration curve obtained in vitro within a bovine serum solution. Control sensors, assembled without NO release functionality, exhibit distinctive surface clotting over the 7 h in vivo implantation period.
Hybrid solar cells constructed of macroporous n-type GaP coated with PEDOT:PSS
Zhijie Wang , Elizabeth S. Brown , Stephen Maldonado
2015, 26(4): 469-473  doi: 10.1016/j.cclet.2015.03.009
[Abstract](449) [FullText HTML] [PDF 965KB](0)
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Hybrid organic-inorganic solar cell devices were fabricated utilizing macroporous n-type GaP and poly(3,4-ethylenedioxythiophene):poly(4-styrene sulfonate) (PEDOT:PSS). The high-aspect ratio structures of the macroporous GaP resulted in higher photocurrent and external quantum yield as a function of wavelength. Photocurrent-voltage measurements as a function of light intensity revealed information on the dependence of short-circuit current (Jsc) and open-circuit voltage (Voc) on light intensity. Under 1.0 Sun illumination, hybrid macroporous GaP/PEDOT:PSS devices showed Jsc of 2.34 mA cm-2, Voc of 0.95 V, fill factor of 0.54, and overall efficiency of 1.21%. The extent of the influence of dopant density of GaP on hybrid device performance was probed with current density-voltage measurements. The addition of a gold nanoparticle coating on macroporous GaP prior to PEDOT:PSS coating showed increased device performance, with overall efficiency of 1.81%. Gold-modified planar GaP/PEDOT:PSS showed decreased Jsc and Voc values and lower external quantum yield over all wavelengths.
Synthesis of α-SnWO4 thin-film electrodes by hydrothermal conversion from crystalline WO3
Kayla J. Pyper , Taylor C. Evans , Bart M. Bartlett
2015, 26(4): 474-478  doi: 10.1016/j.cclet.2015.01.027
[Abstract](477) [FullText HTML] [PDF 3242KB](0)
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Thin film electrodes of the orthorhombic form of tin tungstate (α-SnWO4) were prepared using a hydrothermal method to convert thin films of WO3 in aqueous SnCl2. The pH dependence of the growth mechanism was identified by scanning electron microscopy (SEM) and X-ray diffraction (XRD). The XRD patterns show complete conversion of WO3(s) to SnWO4(s) at pH 1, 4, and 7. SEM images reveal a morphology change from sponge-like platelets to sharp nanowires as the pH increases from 1 to 7. The α-SnWO4 thin films were reddish brown in color, and display an indirect band gap of 1.9 eV by diffuse reflectance UV-vis spectroscopy. α-SnWO4 is therefore solar-responsive, and a chopped light linear sweep voltammogram recorded under 100 mW/cm2 AM1.5 simulated solar illumination in a pH 5 0.1 mol/L KPi buffer show a visible light response for photoelectrochemical water oxidation, producing 32 mA/cm2 at 1.23 V vs. RHE.
Kinetic study of all-or-none hemolysis induced by cationic amphiphilic polymethacrylates with antimicrobial activity
Kazuma Yasuhara , Kenichi Kuroda
2015, 26(4): 479-484  doi: 10.1016/j.cclet.2015.01.029
[Abstract](448) [FullText HTML] [PDF 890KB](0)
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To gain an understanding of the toxicity of antimicrobial polymers to human cells, their hemolytic action was investigated using human red blood cells (RBCs). We examined the hemolysis induced by cationic amphiphilicmethacrylate random copolymers, which have amino ethyl sidechains as cationic units and either butyl or methyl methacrylate as hydrophobic units. The polymer with 30 mol% butyl sidechains (B30) displayed higher hemolytic toxicity than the polymer with 59 mol% methyl sidechains (M59). B30 also induced faster release of hemoglobin from RBCs than M59. A new theoretical model is proposed based on two consecutive steps to form active polymer species on the RBC membranes, which are associated to RBC lysis. This model takes the all-or-none release of hemoglobin by the rupture of RBCs into account, providing new insight into the polymer-induced hemolysis regarding how individual or collective cells respond to the polymers.
Stability and orientation of cecropin P1 on maleimide self-assembled monolayer (SAM) surfaces and suggested functional mutations
Shuai Wei , Charles L. Brooks Ⅲ
2015, 26(4): 485-490  doi: 10.1016/j.cclet.2015.03.020
[Abstract](442) [FullText HTML] [PDF 1062KB](0)
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One of the main challenges of biosensor design is to understand the protein or peptide stability on the chip in high resolution structural detail. Since conventional experimental methods are limited by the resolution for their applications on surface tethered peptides/proteins, a recently developed coarse grained simulation method is employed to explore the peptide/surface interaction in residue-level resolution. This work shows how the coarse grained model successfully describes peptide-surface interactions by evaluating thermal stability of the peptide cecropin P1 in bulk solution and on surfaces by physical adsorption and chemical tethering. The simulation also reproduces observations of peptide orientations on the self-assembled monolayer surface from earlier experimental work. Additionally, using knowledge obtained from the simulations, specific mutations are suggested and the desired structure and pose on the surface is obtained. In summary, this work sheds a light on the reasonable biosensor design that is guided by simulations.
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