Web Based Learning Support for Experimental Design in Molecular Biology.

ERIC Educational Resources Information Center

Wilmsen, Tinri; Bisseling, Ton; Hartog, Rob

An important learning goal of a molecular biology curriculum is a certain proficiency level in experimental design. Currently students are confronted with experimental approaches in textbooks, in lectures and in the laboratory. However, most students do not reach a satisfactory level of competence in the design of experimental approaches. This…

Web-Based Learning Support for Experimental Design in Molecular Biology: A Top-Down Approach

ERIC Educational Resources Information Center

Aegerter-Wilmsen, Tinri; Hartog, Rob; Bisseling, Ton

2003-01-01

An important learning goal of a molecular biology curriculum is the attainment of a certain competence level in experimental design. Currently, undergraduate students are confronted with experimental approaches in textbooks, lectures and laboratory courses. However, most students do not reach a satisfactory level of competence in the designing of…

Molecular design toward highly efficient photovoltaic polymers based on two-dimensional conjugated benzodithiophene.

PubMed

Ye, Long; Zhang, Shaoqing; Huo, Lijun; Zhang, Maojie; Hou, Jianhui

2014-05-20

As researchers continue to develop new organic materials for solar cells, benzo[1,2-b:4,5-b']dithiophene (BDT)-based polymers have come to the fore. To improve the photovoltaic properties of BDT-based polymers, researchers have developed and applied various strategies leading to the successful molecular design of highly efficient photovoltaic polymers. Novel polymer materials composed of two-dimensional conjugated BDT (2D-conjugated BDT) have boosted the power conversion efficiency of polymer solar cells (PSCs) to levels that exceed 9%. In this Account, we summarize recent progress related to the design and synthesis of 2D-conjugated BDT-based polymers and discuss their applications in highly efficient photovoltaic devices. We introduce the basic considerations for the construction of 2D-conjugated BDT-based polymers and systematic molecular design guidelines. For example, simply modifying an alkoxyl-substituted BDT to form an alkylthienyl-substituted BDT can improve the polymer hole mobilities substantially with little effect on their molecular energy level. Secondly, the addition of a variety of chemical moieties to the polymer can produce a 2D-conjugated BDT unit with more functions. For example, the introduction of a conjugated side chain with electron deficient groups (such as para-alkyl-phenyl, meta-alkoxyl-phenyl, and 2-alkyl-3-fluoro-thienyl) allowed us to modulate the molecular energy levels of 2D-conjugated BDT-based polymers. Through the rational design of BDT analogues such as dithienobenzodithiophene (DTBDT) or the insertion of larger π bridges, we can tune the backbone conformations of these polymers and modulate their photovoltaic properties. We also discuss the influence of 2D-conjugated BDT on polymer morphology and the blends of these polymers with phenyl-C61 (or C71)-butyric acid methyl ester (PCBM). Finally, we summarize the various applications of the 2D-conjugated BDT-based polymers in highly efficient PSC devices. Overall, this Account correlates the molecular structures of the 2D-conjugated BDT-based polymers with their photovoltaic properties. As a result, this Account can guide the molecular design of organic photovoltaic materials and the development of organic materials for other types of optoelectronic devices.

Sodium pump molecular activity and membrane lipid composition in two disparate ectotherms, and comparison with endotherms.

PubMed

Turner, Nigel; Hulbert, A J; Else, Paul L

2005-02-01

Previous research has shown that the lower sodium pump molecular activity observed in tissues of ectotherms compared to endotherms, is largely related to the lower levels of polyunsaturates and higher levels of monounsaturates found in the cell membranes of ectotherms. Marine-based ectotherms, however, have very polyunsaturated membranes, and in the current study, we measured molecular activity and membrane lipid composition in tissues of two disparate ectothermic species, the octopus (Octopus vulgaris) and the bearded dragon lizard (Pogona vitticeps), to determine whether the high level of membrane polyunsaturation generally observed in marine-based ectotherms is associated with an increased sodium pump molecular activity relative to other ectotherms. Phospholipids from all tissues of the octopus were highly polyunsaturated and contained high concentrations of the omega-3 polyunsaturate, docosahexaenoic acid (22:6 (n-3)). In contrast, phospholipids from bearded dragon tissues contained higher proportions of monounsaturates and lower proportions of polyunsaturates. Sodium pump molecular activity was only moderately elevated in tissues of the octopus compared to the bearded dragon, despite the much greater level of polyunsaturation in octopus membranes. When the current data were combined with data for the ectothermic cane toad, a significant (P = 0.003) correlation was observed between sodium pump molecular activity and the content of 22:6 (n-3) in the surrounding membrane. These results are discussed in relation to recent work which shows a similar relationship in endotherms.

Fragment-Based Electronic Structure Approach for Computing Nuclear Magnetic Resonance Chemical Shifts in Molecular Crystals.

PubMed

Hartman, Joshua D; Beran, Gregory J O

2014-11-11

First-principles chemical shielding tensor predictions play a critical role in studying molecular crystal structures using nuclear magnetic resonance. Fragment-based electronic structure methods have dramatically improved the ability to model molecular crystal structures and energetics using high-level electronic structure methods. Here, a many-body expansion fragment approach is applied to the calculation of chemical shielding tensors in molecular crystals. First, the impact of truncating the many-body expansion at different orders and the role of electrostatic embedding are examined on a series of molecular clusters extracted from molecular crystals. Second, the ability of these techniques to assign three polymorphic forms of the drug sulfanilamide to the corresponding experimental (13)C spectra is assessed. This challenging example requires discriminating among spectra whose (13)C chemical shifts differ by only a few parts per million (ppm) across the different polymorphs. Fragment-based PBE0/6-311+G(2d,p) level chemical shielding predictions correctly assign these three polymorphs and reproduce the sulfanilamide experimental (13)C chemical shifts with 1 ppm accuracy. The results demonstrate that fragment approaches are competitive with the widely used gauge-invariant projector augmented wave (GIPAW) periodic density functional theory calculations.

A grass molecular identification system for forensic botany: a critical evaluation of the strengths and limitations.

PubMed

Ward, Jodie; Gilmore, Simon R; Robertson, James; Peakall, Rod

2009-11-01

Plant material is frequently encountered in criminal investigations but often overlooked as potential evidence. We designed a DNA-based molecular identification system for 100 Australian grasses that consisted of a series of polymerase chain reaction assays that enabled the progressive identification of grasses to different taxonomic levels. The identification system was based on DNA sequence variation at four chloroplast and two mitochondrial loci. Seventeen informative indels and 68 single-nucleotide polymorphisms were utilized as molecular markers for subfamily to species-level identification. To identify an unknown sample to subfamily level required a minimum of four markers or nine markers for species identification. The accuracy of the system was confirmed by blind tests. We have demonstrated "proof of concept" of a molecular identification system for trace botanical samples. Our evaluation suggests that the adoption of a system that combines this approach with DNA sequencing could assist the morphological identification of grasses found as forensic evidence.

Molecular epidemiology of Plum pox virus in Japan.

PubMed

Maejima, Kensaku; Himeno, Misako; Komatsu, Ken; Takinami, Yusuke; Hashimoto, Masayoshi; Takahashi, Shuichiro; Yamaji, Yasuyuki; Oshima, Kenro; Namba, Shigetou

2011-05-01

For a molecular epidemiological study based on complete genome sequences, 37 Plum pox virus (PPV) isolates were collected from the Kanto region in Japan. Pair-wise analyses revealed that all 37 Japanese isolates belong to the PPV-D strain, with low genetic diversity (less than 0.8%). In phylogenetic analysis of the PPV-D strain based on complete nucleotide sequences, the relationships of the PPV-D strain were reconstructed with high resolution: at the global level, the American, Canadian, and Japanese isolates formed their own distinct monophyletic clusters, suggesting that the routes of viral entry into these countries were independent; at the local level, the actual transmission histories of PPV were precisely reconstructed with high bootstrap support. This is the first description of the molecular epidemiology of PPV based on complete genome sequences.

Molecular-Level Computational Investigation of Mechanical Transverse Behavior of p-Phenylene Terephthalamide (PPTA) Fibers

DTIC Science & Technology

2013-01-01

fabricated today are based on polymer matrix composites containing Kevlarw KM2 reinforcements , the present work will deal with generic PPTA fibers . In...Multi-length scale enriched continuum-level material model for Kevlarw- fiber reinforced polymer-matrix composites”, Journal of Materials...mechanical transverse behavior of p-phenylene terephthalamide (PPTA) fibers Purpose – A series of all-atom molecular-level computational analyses is

Molecular toxicity of nanomaterials.

PubMed

Chang, Xue-Ling; Yang, Sheng-Tao; Xing, Gengmei

2014-10-01

With the rapid developments in the fields of nanoscience and nanotechnlogy, more and more nanomaterials and their based consumer products have been used into our daily life. The safety concerns of nanomaterials have been well recognized by the scientific community and the public. Molecular mechanism of interactions between nanomaterials and biosystems is the most essential topic and final core of the biosafety. In the last two decades, nanotoxicology developed very fast and toxicity phenomena of nanomaterials have been reported. To achieve better understanding and detoxication of nanomaterials, thorough studies of nanotoxicity at molecular level are important. The interactions between nanomaterials and biomolecules have been widely investigated as the first step toward the molecular nanotoxicology. The consequences of such interactions have been discussed in the literature. Besides this, the chemical mechanism of nanotoxicology is gaining more attention, which would lead to a better design of nontoxic nanomaterials. In this review, we focus on the molecular nanotoxicology and explore the toxicity of nanomaterials at molecular level. The molecular level studies of nanotoxicology are summarized and the published nanotoxicological data are revisited.

High-resolution monitoring of marine protists based on an observation strategy integrating automated on-board filtration and molecular analyses

NASA Astrophysics Data System (ADS)

Metfies, Katja; Schroeder, Friedhelm; Hessel, Johanna; Wollschläger, Jochen; Micheller, Sebastian; Wolf, Christian; Kilias, Estelle; Sprong, Pim; Neuhaus, Stefan; Frickenhaus, Stephan; Petersen, Wilhelm

2016-11-01

Information on recent biomass distribution and biogeography of photosynthetic marine protists with adequate temporal and spatial resolution is urgently needed to better understand the consequences of environmental change for marine ecosystems. Here we introduce and review a molecular-based observation strategy for high-resolution assessment of these protists in space and time. It is the result of extensive technology developments, adaptations and evaluations which are documented in a number of different publications, and the results of the recently completed field testing which are introduced in this paper. The observation strategy is organized at four different levels. At level 1, samples are collected at high spatiotemporal resolution using the remotely controlled automated filtration system AUTOFIM. Resulting samples can either be preserved for later laboratory analyses, or directly subjected to molecular surveillance of key species aboard the ship via an automated biosensor system or quantitative polymerase chain reaction (level 2). Preserved samples are analyzed at the next observational levels in the laboratory (levels 3 and 4). At level 3 this involves molecular fingerprinting methods for a quick and reliable overview of differences in protist community composition. Finally, selected samples can be used to generate a detailed analysis of taxonomic protist composition via the latest next generation sequencing technology (NGS) at level 4. An overall integrated dataset of the results based on the different analyses provides comprehensive information on the diversity and biogeography of protists, including all related size classes. At the same time the cost of the observation is optimized with respect to analysis effort and time.

Fibrin-based biomaterials: Modulation of macroscopic properties through rational design at the molecular level

PubMed Central

Brown, Ashley C.; Barker, Thomas H.

2013-01-01

Fibrinogen is one of the primary components of the coagulation cascade and rapidly forms an insoluble matrix following tissue injury. In addition to its important role in hemostasis, fibrin acts as a scaffold for tissue repair and provides important cues for directing cell phenotype following injury. Because of these properties and the ease of polymerization of the material, fibrin has been widely utilized as a biomaterial for over a century. Modifying the macroscopic properties of fibrin, such as elasticity and porosity, has been somewhat elusive until recently, yet with a molecular-level rational design approach can now be somewhat easily modified through alterations of molecular interactions key to the protein’s polymerization process. This review outlines the biochemistry of fibrin and discusses methods for modification of molecular interactions and their application to fibrin based biomaterials. PMID:24056097

Effects of aging on serum levels of lipid molecular species as determined by lipidomics analysis in Japanese men and women.

PubMed

Kawanishi, Noriaki; Kato, Yuki; Yokozeki, Kyosuke; Sawada, Shuji; Sakurai, Ryota; Fujiwara, Yoshinori; Shinkai, Shoji; Goda, Nobuhito; Suzuki, Katsuhiko

2018-06-06

Aging is known to be associated with increased risk of lipid disorders related to the development of type 2 diabetes. Recent evidence revealed that change of lipid molecule species in blood is associated with the risk of type 2 diabetes. However, changes in lipid molecular species induced by aging are still unknown. We assessed the effects of age on the serum levels of lipid molecular species as determined by lipidomics analysis. Serum samples were collected from ten elderly men (71.7 ± 0.5 years old) and women (70.2 ± 1.0 years old), ten young men (23.9 ± 0.4 years old), and women (23.9 ± 0.7 years old). Serum levels of lipid molecular species were determined by liquid chromatography mass spectrometry-based lipidomics analysis. Our mass spectrometry analysis revealed increases in the levels of multiple triacylglycerol molecular species in the serum of elderly men and women. Moreover, serum levels of total ester-linked phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were increased by aging. In contrast, serum levels of specific ether-linked PC and PE molecular species were lower in elderly individuals than in young individuals. Our finding indicates that specific lipid molecular species, such as ether- and ester- linked phospholipids, may be selectively altered by aging.

Phenotypic screening for developmental neurotoxicity ...

EPA Pesticide Factsheets

There are large numbers of environmental chemicals with little or no available information on their toxicity, including developmental neurotoxicity. Because of the resource-intensive nature of traditional animal tests, high-throughput (HTP) methods that can rapidly evaluate chemicals for the potential to affect the developing brain are being explored. Typically, HTP screening uses biochemical and molecular assays to detect the interaction of a chemical with a known target or molecular initiating event (e.g., the mechanism of action). For developmental neurotoxicity, however, the mechanism(s) is often unknown. Thus, we have developed assays for detecting chemical effects on the key events of neurodevelopment at the cellular level (e.g., proliferation, differentiation, neurite growth, synaptogenesis, network formation). Cell-based assays provide a test system at a level of biological complexity that encompasses many potential neurotoxic mechanisms. For example, phenotypic assessment of neurite outgrowth at the cellular level can detect chemicals that target kinases, ion channels, or esterases at the molecular level. The results from cell-based assays can be placed in a conceptual framework using an Adverse Outcome Pathway (AOP) which links molecular, cellular, and organ level effects with apical measures of developmental neurotoxicity. Testing a wide range of concentrations allows for the distinction between selective effects on neurodevelopmental and non-specific

Ab initio molecular simulations on specific interactions between amyloid beta and monosaccharides

NASA Astrophysics Data System (ADS)

Nomura, Kazuya; Okamoto, Akisumi; Yano, Atsushi; Higai, Shin'ichi; Kondo, Takashi; Kamba, Seiji; Kurita, Noriyuki

2012-09-01

Aggregation of amyloid β (Aβ) peptides, which is a key pathogenetic event in Alzheimer's disease, can be caused by cell-surface saccharides. We here investigated stable structures of the solvated complexes of Aβ with some types of monosaccharides using molecular simulations based on protein-ligand docking and classical molecular mechanics methods. Moreover, the specific interactions between Aβ and the monosaccharides were elucidated at an electronic level by ab initio fragment molecular orbital calculations. Based on the results, we proposed which type of monosaccharide prefers to have large binding affinity to Aβ and inhibit the Aβ aggregation.

Modern Spectroscopy

ERIC Educational Resources Information Center

Barrow, Gordon M.

1970-01-01

Presents the basic ideas of modern spectroscopy. Both the angular momenta and wave-nature approaches to the determination of energy level patterns for atomic and molecular systems are discussed. The interpretation of spectra, based on atomic and molecular models, is considered. (LC)

Relative complexation energies for Li(+) ion in solution: molecular level solvation versus polarizable continuum model study.

PubMed

Eilmes, Andrzej; Kubisiak, Piotr

2010-01-21

Relative complexation energies for the lithium cation in acetonitrile and diethyl ether have been studied. Quantum-chemical calculations explicitly describing the solvation of Li(+) have been performed based on structures obtained from molecular dynamics simulations. The effect of an increasing number of solvent molecules beyond the first solvation shell has been found to consist in reduction of the differences in complexation energies for different coordination numbers. Explicit-solvation data have served as a benchmark to the results of polarizable continuum model (PCM) calculations. It has been demonstrated that the PCM approach can yield relative complexation energies comparable to the predictions based on molecular-level solvation, but at significantly lower computational cost. The best agreement between the explicit-solvation and the PCM results has been obtained when the van der Waals surface was adopted to build the molecular cavity.

Electron Transport through Porphyrin Molecular Junctions

NASA Astrophysics Data System (ADS)

Zhou, Qi

The goal of this work is to study the properties that would affect the electron transport through a porphyrin molecular junction. This work contributes to the field of electron transport in molecular junctions in the following 3 aspects. First of all, by carrying out experiments comparing the conductance of the iron (III) porphyrin (protected) and the free base porphyrin (protected), it is confirmed that the molecular energy level broadening and shifting occurs for porphyrin molecules when coupled with the metal electrodes, and this level broadening and shifting plays an important role in the electron transport through molecular junctions. Secondly, by carrying out an in-situ deprotection of the acetyl-protected free base porphyrin molecules, it is found out that the presence of acetyl groups reduces the conductance. Thirdly, by incorporating the Matrix-assisted laser desorption/ionization (MALDI) spectrum and the in-situ deprotection prior to formation of molecular junctions, it allows a more precise understanding of the molecules involved in the formation of molecular junctions, and therefore allows an accurate analysis of the conductance histogram. The molecules are prepared by self-assembly and the junctions are formed using a Scanning Tunneling Microscopy (STM) molecular break junction technique. The porphyrin molecules are characterized by MALDI in solution before self-assembly to a gold/mica substrate. The self-assembled monolayers (SAMs) of porphyrins on gold are characterized by Ultraviolet-visible (UV-Vis) reflection spectroscopy to confirm that the molecules are attached to the substrate. The SAMs are then characterized by Angle-Resolved X-ray photoelectron spectroscopy (ARXPS) to determine the thickness and the average molecular orientation of the molecular layer. The electron transport is measured by conductance-displacement (G-S) experiments under a given bias (-0.4V). The conductance value of a single molecule is identified by a statistical analysis over a large set of measurements. In this thesis, I focus on two factors that would affect the electron transport through the porphyrin molecules, namely, the metal ion center, and the deprotection of the end groups. The effect of metal ion center is studied by comparing the conductance of an iron (III) porphyrin (protected) to that of a free base porphyrin (protected). The in-situ deprotection of the molecules before forming the junctions is completed to study the effect of the molecular-electrode interaction. The first factor studied, that is, the metal ion center in the porphyrin molecule, show that the conductance for iron (III) porphyrin (protected) is 3.74 x10-5 G0, and the conductance for the free base porphyrin (protected) is 4.73x10-5 G0 , where G0 = e2 / pih = (25.8kO)-1 is the quantized unit of electrical conductance. Through our collaborative efforts, first principles calculations carried out by our collaborators for the molecular levels of an isolated molecule (without electrodes) show that the energy levels of an iron (III) porphyrin molecule are slightly shifted compared to that of the free base porphyrin. For the free base porphyrin, the highest occupied molecular orbital (HOMO) level (-4.952 eV) lies between the chemical potentials of the substrate (-4.7 eV) and the STM tip (-5.1 eV). This level serves as a channel for electron transport. For the iron (III) porphyrin, the HOMO is at -5.306 eV, which is not in between the chemical potentials of the substrate. Therefore, a significantly smaller conductance is expected for the iron (III) porphyrin compared to the conductance of a free base porphyrin, because of the lack of the electron transport channel. However, the conductance measured from G-S experiments is comparable, i.e. 3.74 x10-5 G0 for iron (III) porphyrin and 4.73x10-5 G0 for free base porphyrin. This suggests that the molecular energy level broadening and shifting occurs for porphyrin molecules when coupled with the metal electrodes, and this level broadening and shifting may significantly affect the electron transport through molecular junctions. The second factor studied, that is, the deprotection of the porphyrin end groups (acetylthio, -SCOCH3), was completed in-situ for the free base porphyrin through the reaction of the acetylthio with sulfuric acid at 35° Celsius for 3 hours. MALDI spectroscopy confirms that two additional deprotected porphyrin species are formed by deprotection, with protonated (MH+) molecular masses of 721 and 679, corresponding to a partially deprotected porphyrin (i.e. only one of the two end groups deprotected), and a fully deprotected porphyrin molecule. Along with the un-reacted acetyl protected porphyrin, a total of 3 porphyrin species are in the solution. This solution is used for self-assembly on a gold/mica surface. The thickness of the in-situ deprotected SAM is determined to be ˜1.7 nm, confirming a relatively upright molecular orientation (54.0°-63.5° between the substrate surface and the molecule), compared to a thickness of ˜1.5 nm for the protected SAM that has a more flat-lying molecular orientation (˜45.6° between the substrate surface and the molecule). From G-S measurements on SAMs prepared by in-situ deprotection, junctions with lower conductance steps at mid 10-5 G0 and junctions with higher conductance steps around 10-4 G 0 are observed. Supported by computational modeling from our collaborating research group, we associate the lower conductance steps to junctions based on the protected form of thiols at the tip-molecule interface, and the higher conductance steps to the deprotected form of the thiol contacts. We suggest that the reduced conductance in the protected porphyrin originates from the presence of the acetyl end groups (-COCH3), rather than from the elongation of the sulfur-gold (S-Au) bonds at the tip-molecule interface. By studying these two factors, I expect this work to provide insights into electron transport through molecules or metal-molecule-metal junctions, and in applications related to integrating molecules as functional units in electronic devices. Future work related to this thesis may include the molecular conductance based on reduction-oxidation (redox) properties of iron ligated porphyrins for the application of molecular switches and molecular memory elements.

A molecular shift register based on electron transfer

NASA Technical Reports Server (NTRS)

Hopfield, J. J.; Onuchic, Josenelson; Beratan, David N.

1988-01-01

An electronic shift-register memory at the molecular level is described. The memory elements are based on a chain of electron-transfer molecules and the information is shifted by photoinduced electron-transfer reactions. This device integrates designed electronic molecules onto a very large scale integrated (silicon microelectronic) substrate, providing an example of a 'molecular electronic device' that could actually be made. The design requirements for such a device and possible synthetic strategies are discussed. Devices along these lines should have lower energy usage and enhanced storage density.

Light and redox switchable molecular components for molecular electronics.

PubMed

Browne, Wesley R; Feringa, Ben L

2010-01-01

The field of molecular and organic electronics has seen rapid progress in recent years, developing from concept and design to actual demonstration devices in which both single molecules and self-assembled monolayers are employed as light-responsive components. Research in this field has seen numerous unexpected challenges that have slowed progress and the initial promise of complex molecular-based computers has not yet been realised. Primarily this has been due to the realisation at an early stage that molecular-based nano-electronics brings with it the interface between the hard (semiconductor) and soft (molecular) worlds and the challenges which accompany working in such an environment. Issues such as addressability, cross-talk, molecular stability and perturbation of molecular properties (e.g., inhibition of photochemistry) have nevertheless driven development in molecular design and synthesis as well as our ability to interface molecular components with bulk metal contacts to a very high level of sophistication. Numerous groups have played key roles in progressing this field not least teams such as those led by Whitesides, Aviram, Ratner, Stoddart and Heath. In this short review we will however focus on the contributions from our own group and those of our collaborators, in employing diarylethene based molecular components.

Smart Sensing Based on DNA-Metal Interaction Enables a Label-Free and Resettable Security Model of Electrochemical Molecular Keypad Lock.

PubMed

Du, Yan; Han, Xu; Wang, Chenxu; Li, Yunhui; Li, Bingling; Duan, Hongwei

2018-01-26

Recently, molecular keypad locks have received increasing attention. As a new subgroup of smart biosensors, they show great potential for protecting information as a molecular security data processor, rather than merely molecular recognition and quantitation. Herein, label-free electrochemically transduced Ag + and cysteine (Cys) sensors were developed. A molecular keypad lock model with reset function was successfully realized based on the balanced interaction of metal ion with its nucleic acid and chemical ligands. The correct input of "1-2-3" (i.e., "Ag + -Cys-cDNA") is the only password of such molecular keypad lock. Moreover, the resetting process of either correct or wrong input order could be easily made by Cys, buffer, and DI water treatment. Therefore, our system provides an even smarter system of molecular keypad lock, which could inhibit illegal access of unauthorized users, holding great promise in information protection at the molecular level.

Conductance of three-terminal molecular bridge based on tight-binding theory

NASA Astrophysics Data System (ADS)

Wang, Li-Guang; Li, Yong; Yu, Ding-Wen; Katsunori, Tagami; Masaru, Tsukada

2005-05-01

The quantum transmission characteristic of three-benzene ring nano-molecular bridge is investigated theoretically by using Green's function approach based on tight-binding theory with only a π orbital per carbon atom at the site. The transmission probabilities that electrons transport through the molecular bridge from one terminal to the other two terminals are obtained. The electronic current distributions inside the molecular bridge are calculated and shown in graphical analogy by the current density method based on Fisher-Lee formula at the energy points E = ±0.42, ±1.06 and ±1.5, respectively, where the transmission spectra appear peaks. We find that the transmission spectra are related to the incident electronic energy and the molecular levels strongly and the current distributions agree well with Kirchhoff quantum current momentum conservation law.

A logic-based dynamic modeling approach to explicate the evolution of the central dogma of molecular biology.

PubMed

Jafari, Mohieddin; Ansari-Pour, Naser; Azimzadeh, Sadegh; Mirzaie, Mehdi

It is nearly half a century past the age of the introduction of the Central Dogma (CD) of molecular biology. This biological axiom has been developed and currently appears to be all the more complex. In this study, we modified CD by adding further species to the CD information flow and mathematically expressed CD within a dynamic framework by using Boolean network based on its present-day and 1965 editions. We show that the enhancement of the Dogma not only now entails a higher level of complexity, but it also shows a higher level of robustness, thus far more consistent with the nature of biological systems. Using this mathematical modeling approach, we put forward a logic-based expression of our conceptual view of molecular biology. Finally, we show that such biological concepts can be converted into dynamic mathematical models using a logic-based approach and thus may be useful as a framework for improving static conceptual models in biology.

A logic-based dynamic modeling approach to explicate the evolution of the central dogma of molecular biology

PubMed Central

Jafari, Mohieddin; Ansari-Pour, Naser; Azimzadeh, Sadegh; Mirzaie, Mehdi

2017-01-01

It is nearly half a century past the age of the introduction of the Central Dogma (CD) of molecular biology. This biological axiom has been developed and currently appears to be all the more complex. In this study, we modified CD by adding further species to the CD information flow and mathematically expressed CD within a dynamic framework by using Boolean network based on its present-day and 1965 editions. We show that the enhancement of the Dogma not only now entails a higher level of complexity, but it also shows a higher level of robustness, thus far more consistent with the nature of biological systems. Using this mathematical modeling approach, we put forward a logic-based expression of our conceptual view of molecular biology. Finally, we show that such biological concepts can be converted into dynamic mathematical models using a logic-based approach and thus may be useful as a framework for improving static conceptual models in biology. PMID:29267315

NaviCom: a web application to create interactive molecular network portraits using multi-level omics data.

PubMed

Dorel, Mathurin; Viara, Eric; Barillot, Emmanuel; Zinovyev, Andrei; Kuperstein, Inna

2017-01-01

Human diseases such as cancer are routinely characterized by high-throughput molecular technologies, and multi-level omics data are accumulated in public databases at increasing rate. Retrieval and visualization of these data in the context of molecular network maps can provide insights into the pattern of regulation of molecular functions reflected by an omics profile. In order to make this task easy, we developed NaviCom, a Python package and web platform for visualization of multi-level omics data on top of biological network maps. NaviCom is bridging the gap between cBioPortal, the most used resource of large-scale cancer omics data and NaviCell, a data visualization web service that contains several molecular network map collections. NaviCom proposes several standardized modes of data display on top of molecular network maps, allowing addressing specific biological questions. We illustrate how users can easily create interactive network-based cancer molecular portraits via NaviCom web interface using the maps of Atlas of Cancer Signalling Network (ACSN) and other maps. Analysis of these molecular portraits can help in formulating a scientific hypothesis on the molecular mechanisms deregulated in the studied disease. NaviCom is available at https://navicom.curie.fr. © The Author(s) 2017. Published by Oxford University Press.

Electronic transport properties of a quinone-based molecular switch

NASA Astrophysics Data System (ADS)

Zheng, Ya-Peng; Bian, Bao-An; Yuan, Pei-Pei

2016-09-01

In this paper, we carried out first-principles calculations based on density functional theory and non-equilibrium Green's function to investigate the electronic transport properties of a quinone-based molecule sandwiched between two Au electrodes. The molecular switch can be reversibly switched between the reduced hydroquinone (HQ) and oxidized quinone (Q) states via redox reactions. The switching behavior of two forms is analyzed through their I- V curves, transmission spectra and molecular projected self-consistent Hamiltonian at zero bias. Then we discuss the transmission spectra of the HQ and Q forms at different bias, and explain the oscillation of current according to the transmission eigenstates of LUMO energy level for Q form. The results suggest that this kind of a quinone-based molecule is usable as one of the good candidates for redox-controlled molecular switches.

Electronic shift register memory based on molecular electron-transfer reactions

NASA Technical Reports Server (NTRS)

Hopfield, J. J.; Onuchic, Jose Nelson; Beratan, David N.

1989-01-01

The design of a shift register memory at the molecular level is described in detail. The memory elements are based on a chain of electron-transfer molecules incorporated on a very large scale integrated (VLSI) substrate, and the information is shifted by photoinduced electron-transfer reactions. The design requirements for such a system are discussed, and several realistic strategies for synthesizing these systems are presented. The immediate advantage of such a hybrid molecular/VLSI device would arise from the possible information storage density. The prospect of considerable savings of energy per bit processed also exists. This molecular shift register memory element design solves the conceptual problems associated with integrating molecular size components with larger (micron) size features on a chip.

[Pharmacodynamic evaluation and molecular mechanism research of Huanshao capsule on irregular menstruation].

PubMed

Sun, Jian-Hui; Huo, Hai-Ru; Li, Xiao-Qin; Li, Hong-Mei; Qin, De-Huai; Wu, Chun

2018-04-01

Huanshao capsule is widely used in irregular menstruation and has achieved a good effect. Huanshao capsule can promote gonad development in mice, significantly improve the ovarian index in mice, increase estrogen level and reduce FSH level in rats, inhibit the pain response induced by oxytocin and estrogen, inhibit writhing reaction induced by acetic acid pain in mice. Due to the complexity of traditional Chinese medical formula, the pharmacological mechanism of the treatment on the irregular menstruation of the Huanshao capsule is unclear. In this study, the internet-based computation platform (www.tcmip.cn）was used to explore the molecular mechanism of Huanshao capsule on the menstrual. The aim of this study was to find the molecular mechanism of Huanshao capsule in treating menstrual. In the study of the molecular mechanism of Huanshao capsule in the treatment of menstrual by using the internet-based computation platform, Huanshao capsule maybe treat the menstrual by the pathway of endocrine system, GnRH signal transduction pathway, estrogen signal transduction pathway, oxytocin signaling pathway, thyroid hormone signaling pathway, VEGF signaling pathway, FCεRI signaling pathway and purine metabolism and nucleotide metabolism. The early pharmacological study confirmed Huanshao capsule could increase the serum estradiol level and decrease follicle stimulating hormone level and the traditional Chinese medicine pharmacology coincide with the prediction result of internet-based computation platform which roles as the pathway of GnRH signaling pathway and estrogen signal transduction pathway. Other pathway needs further experimental verification. Copyright© by the Chinese Pharmaceutical Association.

Molecular-Level Simulations of Shock Generation and Propagation in Soda-Lime Glass

DTIC Science & Technology

2012-08-01

Molecular-Level Simulations of Shock Generation and Propagation in Soda-Lime Glass M. Grujicic, W.C. Bell, B. Pandurangan, B.A. Cheeseman, C ...transparent structures with thickness approaching several inches; (b) relatively low material and manufacturing costs; and ( c ) compositional modifications... c ) models based on explicit crack representation (Ref 15, 16). Since a M. Grujicic, W.C. Bell, and B. Pandurangan, Department of Mec- hanical

Molecular-level characterization of the structure and the surface chemistry of periodic mesoporous organosilicates using DNP-surface enhanced NMR spectroscopy.

PubMed

Grüning, Wolfram R; Rossini, Aaron J; Zagdoun, Alexandre; Gajan, David; Lesage, Anne; Emsley, Lyndon; Copéret, Christophe

2013-08-28

We present the molecular level characterization of a phenylpyridine-based periodic mesoporous organosilicate and its post-functionalized organometallic derivatives through the fast acquisition of high quality natural isotopic abundance 1D (13)C, (15)N, and (29)Si and 2D (1)H-(13)C and (1)H-(29)Si solid-state NMR spectra enhanced with dynamic nuclear polarization.

Transport Phenomena of Water in Molecular Fluidic Channels

PubMed Central

Vo, Truong Quoc; Kim, BoHung

2016-01-01

In molecular-level fluidic transport, where the discrete characteristics of a molecular system are not negligible (in contrast to a continuum description), the response of the molecular water system might still be similar to the continuum description if the time and ensemble averages satisfy the ergodic hypothesis and the scale of the average is enough to recover the classical thermodynamic properties. However, even in such cases, the continuum description breaks down on the material interfaces. In short, molecular-level liquid flows exhibit substantially different physics from classical fluid transport theories because of (i) the interface/surface force field, (ii) thermal/velocity slip, (iii) the discreteness of fluid molecules at the interface and (iv) local viscosity. Therefore, in this study, we present the result of our investigations using molecular dynamics (MD) simulations with continuum-based energy equations and check the validity and limitations of the continuum hypothesis. Our study shows that when the continuum description is subjected to the proper treatment of the interface effects via modified boundary conditions, the so-called continuum-based modified-analytical solutions, they can adequately predict nanoscale fluid transport phenomena. The findings in this work have broad effects in overcoming current limitations in modeling/predicting the fluid behaviors of molecular fluidic devices. PMID:27650138

Nanomicrointerface to read molecular potentials into current-voltage based electronics.

PubMed

Rangel, Norma L; Seminario, Jorge M

2008-03-21

Molecular potentials are unreadable and unaddressable by any present technology. It is known that the proper assembly of molecules can implement an entire numerical processing system based on digital or even analogical computation. In turn, the outputs of this molecular processing unit need to be amplified in order to be useful. We have developed a nanomicrointerface to read information encoded in molecular level potentials and to amplify this signal to microelectronic levels. The amplification is performed by making the output molecular potential slightly twist the torsional angle between two rings of a pyridazine, 3,6-bis(phenylethynyl) (aza-OPE) molecule, requiring only fractions of kcal/mol energies. In addition, even if the signal from the molecular potentials is not enough to turn the ring or even if the angles are the same for different combinations of outputs, still the current output yields results that resemble the device as a field effect transistor, providing the possibility to reduce channel lengths to the range of just 1 or 2 nm. The slight change in the torsional angle yields readable changes in the current through the aza-OPE biased by an external applied voltage. Using ab initio methods, we computationally demonstrate the amplification of molecular potential signals into currents that can be read by standard circuits.

An easy and effective method to modulate molecular energy level of the polymer based on benzodithiophene for the application in polymer solar cells.

PubMed

Zhang, Maojie; Guo, Xia; Ma, Wei; Zhang, Shaoqing; Huo, Lijun; Ade, Harald; Hou, Jianhui

2014-04-02

Attaching meta-alkoxy-phenyl groups as conjugated side chains is an easy and effective way to modulate the molecular energy level of D-A polymer for photovoltaic application, and the polymer solar cells based on the polymer consisting meta-alkoxy-phenyl groups as conjugated side chain, PBT-OP, shows an enhanced open circuit voltage and thus higher efficiency of 7.50%, under the illumination of AM 1.5G, 100 mW/cm(2) . © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Antimicrobial Use and Resistance in Swine Waste Treatment Systems▿

PubMed Central

Jindal, Archana; Kocherginskaya, Svetlana; Mehboob, Asma; Robert, Matthew; Mackie, Roderick I.; Raskin, Lutgarde; Zilles, Julie L.

2006-01-01

Chlortetracycline and the macrolide tylosin were identified as commonly used antimicrobials for growth promotion and prophylaxis in swine production. Resistance to these antimicrobials was measured throughout the waste treatment processes at five swine farms by culture-based and molecular methods. Conventional farm samples had the highest levels of resistance with both culture-based and molecular methods and had similar levels of resistance despite differences in antimicrobial usage. The levels of resistance in organic farm samples, where no antimicrobials were used, were very low by a culture-based method targeting fecal streptococci. However, when the same samples were analyzed with a molecular method detecting methylation of a specific nucleotide in the 23S rRNA that results in resistance to macrolides, lincosamides, and streptogramin B (MLSB), an unexpectedly high level of resistant rRNA (approximately 50%) was observed, suggesting that the fecal streptococci were not an appropriate target group to evaluate resistance in the overall microbial community and that background levels of MLSB resistance may be substantial. All of the feed samples tested, including those from the organic farm, contained tetracycline resistance genes. Generally, the same tetracycline resistance genes and frequency of detection were found in the manure and lagoon samples for each commercial farm. The levels of tetracycline and MLSB resistance remained high throughout the waste treatment systems, suggesting that the potential impact of land application of treated wastes and waste treatment by-products on environmental levels of resistance should be investigated further. PMID:17041160

Assessing Date Palm Genetic Diversity Using Different Molecular Markers.

PubMed

Atia, Mohamed A M; Sakr, Mahmoud M; Adawy, Sami S

2017-01-01

Molecular marker technologies which rely on DNA analysis provide powerful tools to assess biodiversity at different levels, i.e., among and within species. A range of different molecular marker techniques have been developed and extensively applied for detecting variability in date palm at the DNA level. Recently, the employment of gene-targeting molecular marker approaches to study biodiversity and genetic variations in many plant species has increased the attention of researchers interested in date palm to carry out phylogenetic studies using these novel marker systems. Molecular markers are good indicators of genetic distances among accessions, because DNA-based markers are neutral in the face of selection. Here we describe the employment of multidisciplinary molecular marker approaches: amplified fragment length polymorphism (AFLP), start codon targeted (SCoT) polymorphism, conserved DNA-derived polymorphism (CDDP), intron-targeted amplified polymorphism (ITAP), simple sequence repeats (SSR), and random amplified polymorphic DNA (RAPD) to assess genetic diversity in date palm.

Applications of molecular markers in the discrimination of Panax species and Korean ginseng cultivars (Panax ginseng).

PubMed

Jo, Ick Hyun; Kim, Young Chang; Kim, Dong Hwi; Kim, Kee Hong; Hyun, Tae Kyung; Ryu, Hojin; Bang, Kyong Hwan

2017-10-01

The development of molecular markers is one of the most useful methods for molecular breeding and marker-based molecular associated selections. Even though there is less information on the reference genome, molecular markers are indispensable tools for determination of genetic variation and identification of species with high levels of accuracy and reproducibility. The demand for molecular approaches for marker-based breeding and genetic discriminations in Panax species has greatly increased in recent times and has been successfully applied for various purposes. However, owing to the existence of diverse molecular techniques and differences in their principles and applications, there should be careful consideration while selecting appropriate marker types. In this review, we outline the recent status of different molecular marker applications in ginseng research and industrial fields. In addition, we discuss the basic principles, requirements, and advantages and disadvantages of the most widely used molecular markers, including restriction fragment length polymorphism, random amplified polymorphic DNA, sequence tag sites, simple sequence repeats, and single nucleotide polymorphisms.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sahu, Nityananda; Gadre, Shridhar R., E-mail: gadre@iitk.ac.in

The present work reports the calculation of vibrational infrared (IR) and Raman spectra of large molecular systems employing molecular tailoring approach (MTA). Further, it extends the grafting procedure for the accurate evaluation of IR and Raman spectra of large molecular systems, employing a new methodology termed as Fragments-in-Fragments (FIF), within MTA. Unlike the previous MTA-based studies, the accurate estimation of the requisite molecular properties is achieved without performing any full calculations (FC). The basic idea of the grafting procedure is implemented by invoking the nearly basis-set-independent nature of the MTA-based error vis-à-vis the respective FCs. FIF has been tested outmore » for the estimation of the above molecular properties for three isomers, viz., β-strand, 3{sub 10}- and α-helix of acetyl(alanine){sub n}NH{sub 2} (n = 10, 15) polypeptides, three conformers of doubly protonated gramicidin S decapeptide and trpzip2 protein (PDB id: 1LE1), respectively, employing BP86/TZVP, M06/6-311G**, and M05-2X/6-31G** levels of theory. For most of the cases, a maximum difference of 3 cm{sup −1} is achieved between the grafted-MTA frequencies and the corresponding FC values. Further, a comparison of the BP86/TZVP level IR and Raman spectra of α-helical (alanine){sub 20} and its N-deuterated derivative shows an excellent agreement with the existing experimental spectra. In view of the requirement of only MTA-based calculations and the ability of FIF to work at any level of theory, the current methodology provides a cost-effective solution for obtaining accurate spectra of large molecular systems.« less

Teaching the process of molecular phylogeny and systematics: a multi-part inquiry-based exercise.

PubMed

Lents, Nathan H; Cifuentes, Oscar E; Carpi, Anthony

2010-01-01

Three approaches to molecular phylogenetics are demonstrated to biology students as they explore molecular data from Homo sapiens and four related primates. By analyzing DNA sequences, protein sequences, and chromosomal maps, students are repeatedly challenged to develop hypotheses regarding the ancestry of the five species. Although these exercises were designed to supplement and enhance classroom instruction on phylogeny, cladistics, and systematics in the context of a postsecondary majors-level introductory biology course, the activities themselves require very little prior student exposure to these topics. Thus, they are well suited for students in a wide range of educational levels, including a biology class at the secondary level. In implementing this exercise, we have observed measurable gains, both in student comprehension of molecular phylogeny and in their acceptance of modern evolutionary theory. By engaging students in modern phylogenetic activities, these students better understood how biologists are currently using molecular data to develop a more complete picture of the shared ancestry of all living things.

Evaluation of Contamination Inspection and Analysis Methods through Modeling System Performance

NASA Technical Reports Server (NTRS)

Seasly, Elaine; Dever, Jason; Stuban, Steven M. F.

2016-01-01

Contamination is usually identified as a risk on the risk register for sensitive space systems hardware. Despite detailed, time-consuming, and costly contamination control efforts during assembly, integration, and test of space systems, contaminants are still found during visual inspections of hardware. Improved methods are needed to gather information during systems integration to catch potential contamination issues earlier and manage contamination risks better. This research explores evaluation of contamination inspection and analysis methods to determine optical system sensitivity to minimum detectable molecular contamination levels based on IEST-STD-CC1246E non-volatile residue (NVR) cleanliness levels. Potential future degradation of the system is modeled given chosen modules representative of optical elements in an optical system, minimum detectable molecular contamination levels for a chosen inspection and analysis method, and determining the effect of contamination on the system. By modeling system performance based on when molecular contamination is detected during systems integration and at what cleanliness level, the decision maker can perform trades amongst different inspection and analysis methods and determine if a planned method is adequate to meet system requirements and manage contamination risk.

Stable Molecular Diodes Based on π-π Interactions of the Molecular Frontier Orbitals with Graphene Electrodes.

PubMed

Song, Peng; Guerin, Sarah; Tan, Sherman Jun Rong; Annadata, Harshini Venkata; Yu, Xiaojiang; Scully, Micheál; Han, Ying Mei; Roemer, Max; Loh, Kian Ping; Thompson, Damien; Nijhuis, Christian A

2018-03-01

In molecular electronics, it is important to control the strength of the molecule-electrode interaction to balance the trade-off between electronic coupling strength and broadening of the molecular frontier orbitals: too strong coupling results in severe broadening of the molecular orbitals while the molecular orbitals cannot follow the changes in the Fermi levels under applied bias when the coupling is too weak. Here, a platform based on graphene bottom electrodes to which molecules can bind via π-π interactions is reported. These interactions are strong enough to induce electronic function (rectification) while minimizing broadening of the molecular frontier orbitals. Molecular tunnel junctions are fabricated based on self-assembled monolayers (SAMs) of Fc(CH 2 ) 11 X (Fc = ferrocenyl, X = NH 2 , Br, or H) on graphene bottom electrodes contacted to eutectic alloy of gallium and indium top electrodes. The Fc units interact more strongly with graphene than the X units resulting in SAMs with the Fc at the bottom of the SAM. The molecular diodes perform well with rectification ratios of 30-40, and they are stable against bias stressing under ambient conditions. Thus, tunnel junctions based on graphene with π-π molecule-electrode coupling are promising platforms to fabricate stable and well-performing molecular diodes. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Using graph-based assessments within socratic tutorials to reveal and refine students' analytical thinking about molecular networks.

PubMed

Trujillo, Caleb; Cooper, Melanie M; Klymkowsky, Michael W

2012-01-01

Biological systems, from the molecular to the ecological, involve dynamic interaction networks. To examine student thinking about networks we used graphical responses, since they are easier to evaluate for implied, but unarticulated assumptions. Senior college level molecular biology students were presented with simple molecular level scenarios; surprisingly, most students failed to articulate the basic assumptions needed to generate reasonable graphical representations; their graphs often contradicted their explicit assumptions. We then developed a tiered Socratic tutorial based on leading questions designed to provoke metacognitive reflection. The activity is characterized by leading questions (prompts) designed to provoke meta-cognitive reflection. When applied in a group or individual setting, there was clear improvement in targeted areas. Our results highlight the promise of using graphical responses and Socratic prompts in a tutorial context as both a formative assessment for students and an informative feedback system for instructors, in part because graphical responses are relatively easy to evaluate for implied, but unarticulated assumptions. Copyright © 2011 Wiley Periodicals, Inc.

Prevalence of molecular markers of anti-malarial drug resistance in Plasmodium vivax and Plasmodium falciparum in two districts of Nepal

PubMed Central

2011-01-01

Background Sulphadoxine-pyrimethamine (SP) and chloroquine (CQ) have been used in treatment of falciparum and vivax malaria in Nepal. Recently, resistance to both drugs have necessitated a change towards artemisinin combination therapy (ACT) against Plasmodium falciparum in highly endemic areas. However, SP is still used against P. falciparum infections in low endemic areas while CQ is used in suspected cases in areas with lack of diagnostic facilities. This study examines the prevalence of molecular markers of CQ and SP resistance in P. falciparum and Plasmodium vivax to determine if high levels of in vivo resistance are reflected at molecular level as well. Methods Finger prick blood samples (n = 189) were collected from malaria positive patients from two high endemic districts and analysed for single nucleotide polymorphisms (SNPs) in the resistance related genes of P. falciparum and P. vivax for CQ (Pfcrt, Pfmdr1, Pvmdr1) and SP (Pfdhfr, Pfdhps, Pvdhfr), using various PCR-based methods. Results and discussion Positive P. vivax and P. falciparum infections were identified by PCR in 92 and 41 samples respectively. However, some of these were negative in subsequent PCRs. Based on a few P. falciparum samples, the molecular level of CQ resistance in P. falciparum was high since nearly all parasites had the Pfcrt mutant haplotypes CVIET (55%) or SVMNT (42%), though frequency of the Pfmdr1 wild type haplotype was relatively low (35%). Molecular level of SP resistance in P. falciparum was found to be high. The most prevalent Pfdhfr haplotype was double mutant CNRNI (91%), while frequency of Pfdhps double mutant SGEAA and AGEAA were 38% and 33% respectively. Combined, the frequency of quadruple mutations (CNRNI-SGEAA/AGEAA) was 63%. Based on P. vivax samples, low CQ and SP resistance were most likely due to low prevalence of Pvmdr1 Y976F mutation (5%) and absence of triple/quadruple mutations in Pvdhfr. Conclusions Based on the limited number of samples, prevalence of CQ and SP resistance at molecular levels in the population in the study area were determined as high in P. falciparum and low in P. vivax. Therefore, CQ could still be used in the treatment of P. vivax infections, but this remains to be tested in vivo while the change to ACT for P. falciparum seems justified. PMID:21457533

Molecular Pathways: Extracting Medical Knowledge from High Throughput Genomic Data

PubMed Central

Goldstein, Theodore; Paull, Evan O.; Ellis, Matthew J.; Stuart, Joshua M.

2013-01-01

High-throughput genomic data that measures RNA expression, DNA copy number, mutation status and protein levels provide us with insights into the molecular pathway structure of cancer. Genomic lesions (amplifications, deletions, mutations) and epigenetic modifications disrupt biochemical cellular pathways. While the number of possible lesions is vast, different genomic alterations may result in concordant expression and pathway activities, producing common tumor subtypes that share similar phenotypic outcomes. How can these data be translated into medical knowledge that provides prognostic and predictive information? First generation mRNA expression signatures such as Genomic Health's Oncotype DX already provide prognostic information, but do not provide therapeutic guidance beyond the current standard of care – which is often inadequate in high-risk patients. Rather than building molecular signatures based on gene expression levels, evidence is growing that signatures based on higher-level quantities such as from genetic pathways may provide important prognostic and diagnostic cues. We provide examples of how activities for molecular entities can be predicted from pathway analysis and how the composite of all such activities, referred to here as the “activitome,” help connect genomic events to clinical factors in order to predict the drivers of poor outcome. PMID:23430023

A Cobalt Supramolecular Triple-Stranded Helicate-based Discrete Molecular Cage

PubMed Central

Mai, Hien Duy; Kang, Philjae; Kim, Jin Kyung; Yoo, Hyojong

2017-01-01

We report a strategy to achieve a discrete cage molecule featuring a high level of structural hierarchy through a multiple-assembly process. A cobalt (Co) supramolecular triple-stranded helicate (Co-TSH)-based discrete molecular cage (1) is successfully synthesized and fully characterized. The solid-state structure of 1 shows that it is composed of six triple-stranded helicates interconnected by four linking cobalt species. This is an unusual example of a highly symmetric cage architecture resulting from the coordination-driven assembly of metallosupramolecular modules. The molecular cage 1 shows much higher CO2 uptake properties and selectivity compared with the separate supramolecular modules (Co-TSH, complex 2) and other molecular platforms. PMID:28262690

Recent research in flaxseed (oil seed) on molecular structure and metabolic characteristics of protein, heat processing-induced effect and nutrition with advanced synchrotron-based molecular techniques.

PubMed

Doiron, Kevin J; Yu, Peiqiang

2017-01-02

Advanced synchrotron radiation-based infrared microspectroscopy is able to reveal feed and food structure feature at cellular and molecular levels and simultaneously provides composition, structure, environment, and chemistry within intact tissue. However, to date, this advanced synchrotron-based technique is still seldom known to food and feed scientists. This article aims to provide detailed background for flaxseed (oil seed) protein research and then review recent progress and development in flaxseed research in ruminant nutrition in the areas of (1) dietary inclusion of flaxseed in rations; (2) heat processing effect; (3) assessing dietary protein; (4) synchrotron-based Fourier transform infrared microspectroscopy as a tool of nutritive evaluation within cellular and subcellular dimensions; (5) recent synchrotron applications in flaxseed research on a molecular basis. The information described in this paper gives better insight in flaxseed research progress and update.

Stimulus-responsive light-harvesting complexes based on the pillararene-induced co-assembly of β-carotene and chlorophyll

NASA Astrophysics Data System (ADS)

Sun, Yan; Guo, Fang; Zuo, Tongfei; Hua, Jingjing; Diao, Guowang

2016-06-01

The locations and arrangements of carotenoids at the subcellular level are responsible for their designated functions, which reinforces the necessity of developing methods for constructing carotenoid-based suprastructures beyond the molecular level. Because carotenoids lack the binding sites necessary for controlled interactions, functional structures based on carotenoids are not easily obtained. Here, we show that carotene-based suprastructures were formed via the induction of pillararene through a phase-transfer-mediated host-guest interaction. More importantly, similar to the main component in natural photosynthesis, complexes could be synthesized after chlorophyll was introduced into the carotene-based suprastructure assembly process. Remarkably, compared with molecular carotene or chlorophyll, this synthesized suprastructure exhibits some photocatalytic activity when exposed to light, which can be exploited for photocatalytic reaction studies of energy capture and solar conversion in living organisms.

Plant-based Food and Feed Protein Structure Changes Induced by Gene-transformation heating and bio-ethanol processing: A Synchrotron-based Molecular Structure and Nutrition Research Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

P Yu

Unlike traditional 'wet' analytical methods which during processing for analysis often result in destruction or alteration of the intrinsic protein structures, advanced synchrotron radiation-based Fourier transform infrared microspectroscopy has been developed as a rapid and nondestructive and bioanalytical technique. This cutting-edge synchrotron-based bioanalytical technology, taking advantages of synchrotron light brightness (million times brighter than sun), is capable of exploring the molecular chemistry or structure of a biological tissue without destruction inherent structures at ultra-spatial resolutions. In this article, a novel approach is introduced to show the potential of the advanced synchrotron-based analytical technology, which can be used to study plant-basedmore » food or feed protein molecular structure in relation to nutrient utilization and availability. Recent progress was reported on using synchrotron-based bioanalytical technique synchrotron radiation-based Fourier transform infrared microspectroscopy and diffused reflectance infrared Fourier transform spectroscopy to detect the effects of gene-transformation (Application 1), autoclaving (Application 2), and bio-ethanol processing (Application 3) on plant-based food and feed protein structure changes on a molecular basis. The synchrotron-based technology provides a new approach for plant-based protein structure research at ultra-spatial resolutions at cellular and molecular levels.« less

Sombrero-shaped plasmonic nanoparticles with molecular-level sensitivity and multifunctionality.

PubMed

Wi, Jung-Sub; Barnard, Edward S; Wilson, Robert J; Zhang, Mingliang; Tang, Mary; Brongersma, Mark L; Wang, Shan X

2011-08-23

We demonstrate top-down synthesis of monodisperse plasmonic nanoparticles designed to contain internal Raman hot spots. Our Raman-active nanoparticles are fabricated using nanoimprint lithography and thin-film deposition and are composed of novel internal structures with sublithographic dimensions: a disk-shaped Ag core, a Petri-dish-shaped SiO(2) base whose inner surface is coated with Ag film, and a sub-10 nm scale circular gap between the core and the base. Confocal Raman measurements and electromagnetic simulations show that Raman hot spots appear at the inside perimeter of individual nanoparticles and serve as the source of a 1000-fold improvement of minimum molecular detection level that enables detection of signals from a few molecules near hot spots. A multimodality version of these nanoparticles, which includes the functionality offered by magnetic multilayers, is also demonstrated. These results illustrate the potential of direct fabrication for creating exotic monodisperse nanoparticles, which combine engineered internal nanostructures and multilayer composite materials, for use in nanoparticle-based molecular imaging and detection. © 2011 American Chemical Society

[Morphofunctional and molecular bases of pineal gland aging].

PubMed

Khavinson, V Kh; Lin'kova, N S

2012-01-01

The review analyzed morphology, molecular and functional aspects of pineal gland aging and methods of it correction. The pineal gland is central organ, which regulates activity of neuroimmunoendocrine, antioxidant and other organisms systems. Functional activity of pineal gland is discreased at aging, which is the reason of melatonin level changing. The molecular and morphology research demonstrated, that pineal gland hadn't strongly pronounced atrophy at aging. Long-term experience showed, that peptides extract of pineal gland epithalamin and synthetic tetrapeptide on it base epithalon restored melatonin secretion in pineal gland and had strong regulatory activity at neuroimmunoendocrine and antioxidant organism systems.

Direct Detection Doppler Lidar for Spaceborne Wind Measurement

NASA Technical Reports Server (NTRS)

Korb, C. Laurence; Flesia, Cristina

1999-01-01

The theory of double edge lidar techniques for measuring the atmospheric wind using aerosol and molecular backscatter is described. Two high spectral resolution filters with opposite slopes are located about the laser frequency for the aerosol based measurement or in the wings of the Rayleigh - Brillouin profile for the molecular measurement. This doubles the signal change per unit Doppler shift and improves the measurement accuracy by nearly a factor of 2 relative to the single edge technique. For the aerosol based measurement, the use of two high resolution edge filters reduces the effects of background, Rayleigh scattering, by as much as an order of magnitude and substantially improves the measurement accuracy. Also, we describe a method that allows the Rayleigh and aerosol components of the signal to be independently determined. A measurement accuracy of 1.2 m/s can be obtained for a signal level of 1000 detected photons which corresponds to signal levels in the boundary layer. For the molecular based measurement, we describe the use of a crossover region where the sensitivity of a molecular and aerosol-based measurement are equal. This desensitizes the molecular measurement to the effects of aerosol scattering and greatly simplifies the measurement. Simulations using a conical scanning spaceborne lidar at 355 nm give an accuracy of 2-3 m/s for altitudes of 2-15 km for a 1 km vertical resolution, a satellite altitude of 400 km, and a 200 km x 200 km spatial.

Impaired Associative Taste Learning and Abnormal Brain Activation in Kinase-Defective eEF2K Mice

ERIC Educational Resources Information Center

Gildish, Iness; Manor, David; David, Orit; Sharma, Vijendra; Williams, David; Agarwala, Usha; Wang, Xuemin; Kenney, Justin W.; Proud, Chris G.; Rosenblum, Kobi

2012-01-01

Memory consolidation is defined temporally based on pharmacological interventions such as inhibitors of mRNA translation (molecular consolidation) or post-acquisition deactivation of specific brain regions (systems level consolidation). However, the relationship between molecular and systems consolidation are poorly understood. Molecular…

Use of 16S rRNA gene for identification of a broad range of clinically relevant bacterial pathogens

DOE PAGES

Srinivasan, Ramya; Karaoz, Ulas; Volegova, Marina; ...

2015-02-06

According to World Health Organization statistics of 2011, infectious diseases remain in the top five causes of mortality worldwide. However, despite sophisticated research tools for microbial detection, rapid and accurate molecular diagnostics for identification of infection in humans have not been extensively adopted. Time-consuming culture-based methods remain to the forefront of clinical microbial detection. The 16S rRNA gene, a molecular marker for identification of bacterial species, is ubiquitous to members of this domain and, thanks to ever-expanding databases of sequence information, a useful tool for bacterial identification. In this study, we assembled an extensive repository of clinical isolates (n =more » 617), representing 30 medically important pathogenic species and originally identified using traditional culture-based or non-16S molecular methods. This strain repository was used to systematically evaluate the ability of 16S rRNA for species level identification. To enable the most accurate species level classification based on the paucity of sequence data accumulated in public databases, we built a Naïve Bayes classifier representing a diverse set of high-quality sequences from medically important bacterial organisms. We show that for species identification, a model-based approach is superior to an alignment based method. Overall, between 16S gene based and clinical identities, our study shows a genus-level concordance rate of 96% and a species-level concordance rate of 87.5%. We point to multiple cases of probable clinical misidentification with traditional culture based identification across a wide range of gram-negative rods and gram-positive cocci as well as common gram-negative cocci.« less

Use of 16S rRNA Gene for Identification of a Broad Range of Clinically Relevant Bacterial Pathogens

PubMed Central

Srinivasan, Ramya; Karaoz, Ulas; Volegova, Marina; MacKichan, Joanna; Kato-Maeda, Midori; Miller, Steve; Nadarajan, Rohan; Brodie, Eoin L.; Lynch, Susan V.

2015-01-01

According to World Health Organization statistics of 2011, infectious diseases remain in the top five causes of mortality worldwide. However, despite sophisticated research tools for microbial detection, rapid and accurate molecular diagnostics for identification of infection in humans have not been extensively adopted. Time-consuming culture-based methods remain to the forefront of clinical microbial detection. The 16S rRNA gene, a molecular marker for identification of bacterial species, is ubiquitous to members of this domain and, thanks to ever-expanding databases of sequence information, a useful tool for bacterial identification. In this study, we assembled an extensive repository of clinical isolates (n = 617), representing 30 medically important pathogenic species and originally identified using traditional culture-based or non-16S molecular methods. This strain repository was used to systematically evaluate the ability of 16S rRNA for species level identification. To enable the most accurate species level classification based on the paucity of sequence data accumulated in public databases, we built a Naïve Bayes classifier representing a diverse set of high-quality sequences from medically important bacterial organisms. We show that for species identification, a model-based approach is superior to an alignment based method. Overall, between 16S gene based and clinical identities, our study shows a genus-level concordance rate of 96% and a species-level concordance rate of 87.5%. We point to multiple cases of probable clinical misidentification with traditional culture based identification across a wide range of gram-negative rods and gram-positive cocci as well as common gram-negative cocci. PMID:25658760

Molecular imaging with bioconjugates in mouse models of cancer.

PubMed

Mather, Stephen

2009-04-01

The definition of molecular imaging provided by the Society of Nuclear Medicine is "the visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems". This review gives an overview of the technologies available for and the potential benefits from molecular imaging at the preclinical stage. It focuses on the use of imaging probes based on bioconjugates and for reasons of brevity confines itself to discussion of applications in the field of oncology, although molecular imaging can be equally useful in many fields including cardiovascular medicine, neurosciences, infection, and others.

Molecular Biodynamers: Dynamic Covalent Analogues of Biopolymers

PubMed Central

2017-01-01

Conspectus Constitutional dynamic chemistry (CDC) features the use of reversible linkages at both molecular and supramolecular levels, including reversible covalent bonds (dynamic covalent chemistry, DCC) and noncovalent interactions (dynamic noncovalent chemistry, DNCC). Due to its inherent reversibility and stimuli-responsiveness, CDC has been widely utilized as a powerful tool for the screening of bioactive compounds, the exploitation of receptors or substrates driven by molecular recognition, and the fabrication of constitutionally dynamic materials. Implementation of CDC in biopolymer science leads to the generation of constitutionally dynamic analogues of biopolymers, biodynamers, at the molecular level (molecular biodynamers) through DCC or at the supramolecular level (supramolecular biodynamers) via DNCC. Therefore, biodynamers are prepared by reversible covalent polymerization or noncovalent polyassociation of biorelevant monomers. In particular, molecular biodynamers, biodynamers of the covalent type whose monomeric units are connected by reversible covalent bonds, are generated by reversible polymerization of bio-based monomers and can be seen as a combination of biopolymers with DCC. Owing to the reversible covalent bonds used in DCC, molecular biodynamers can undergo continuous and spontaneous constitutional modifications via incorporation/decorporation and exchange of biorelevant monomers in response to internal or external stimuli. As a result, they behave as adaptive materials with novel properties, such as self-healing, stimuli-responsiveness, and tunable mechanical and optical character. More specifically, molecular biodynamers combine the biorelevant characters (e.g., biocompatibility, biodegradability, biofunctionality) of bioactive monomers with the dynamic features of reversible covalent bonds (e.g., changeable, tunable, controllable, self-healing, and stimuli-responsive capacities), to realize synergistic properties in one system. In addition, molecular biodynamers are commonly produced in aqueous media under mild or even physiological conditions to suit their biorelated applications. In contrast to static biopolymers emphasizing structural stability and unity by using irreversible covalent bonds, molecular biodynamers are seeking relative structural adaptability and diversity through the formation of reversible covalent bonds. Based on these considerations, molecular biodynamers are capable of reorganizing their monomers, generating, identifying, and amplifying the fittest structures in response to environmental factors. Hence, molecular biodynamers have received considerable research attention over the past decades. Accordingly, the construction of molecular biodynamers through equilibrium polymerization of nucleobase-, carbohydrate- or amino-acid-based monomers can lead to the fabrication of dynamic analogues of nucleic acids (DyNAs), polysaccharides (glycodynamers), or proteins (dynamic proteoids), respectively. In this Account, we summarize recent advances in developing different types of molecular biodynamers as structural or functional biomimetics of biopolymers, including DyNAs, glycodynamers, and dynamic proteoids. We introduce how chemists utilize various reversible reactions to generate molecular biodynamers with specific sequences and well-ordered structures in aqueous medium. We also discuss and list their potential applications in various research fields, such as drug delivery, drug discovery, gene sensing, cancer diagnosis, and treatment. PMID:28169527

Specific interactions between DNA and regulatory protein controlled by ligand-binding: Ab initio molecular simulation

NASA Astrophysics Data System (ADS)

Matsushita, Y.; Murakawa, T.; Shimamura, K.; Oishi, M.; Ohyama, T.; Kurita, N.

2015-02-01

The catabolite activator protein (CAP) is one of the regulatory proteins controlling the transcription mechanism of gene. Biochemical experiments elucidated that the complex of CAP with cyclic AMP (cAMP) is indispensable for controlling the mechanism, while previous molecular simulations for the monomer of CAP+cAMP complex revealed the specific interactions between CAP and cAMP. However, the effect of cAMP-binding to CAP on the specific interactions between CAP and DNA is not elucidated at atomic and electronic levels. We here considered the ternary complex of CAP, cAMP and DNA in solvating water molecules and investigated the specific interactions between them at atomic and electronic levels using ab initio molecular simulations based on classical molecular dynamics and ab initio fragment molecular orbital methods. The results highlight the important amino acid residues of CAP for the interactions between CAP and cAMP and between CAP and DNA.

Robustness of equations that define molecular subtypes of glioblastoma tumors based on five transcripts measured by RT-PCR.

PubMed

Castells, Xavier; Acebes, Juan José; Majós, Carles; Boluda, Susana; Julià-Sapé, Margarida; Candiota, Ana Paula; Ariño, Joaquín; Barceló, Anna; Arús, Carles

2015-01-01

Glioblastoma (Gb) is one of the most deadly tumors. Its molecular subtypes are yet to be fully characterized while the attendant efforts for personalized medicine need to be intensified in relation to glioblastoma diagnosis, treatment, and prognosis. Several molecular signatures based on gene expression microarrays were reported, but the use of microarrays for routine clinical practice is challenged by attendant economic costs. Several authors have proposed discriminant equations based on RT-PCR. Still, the discriminant threshold is often incompletely described, which makes proper validation difficult. In a previous work, we have reported two Gb subtypes based on the expression levels of four genes: CHI3L1, LDHA, LGALS1, and IGFBP3. One Gb subtype presented with low expression of the four genes mentioned, and of MGMT in a large portion of the patients (with anticipated high methylation of its promoter), and mutated IDH1. Here, we evaluate the robustness of the equations fitted with these genes using RT-PCR values in a set of 64 cases and importantly, define an unequivocal discriminant threshold with a view to prognostic implications. We developed two approaches to generate the discriminant equations: 1) using the expression level of the four genes mentioned above, and 2) using those genes displaying the highest correlation with survival among the aforementioned four ones, plus MGMT, as an attempt to further reduce the number of genes. The ease of equations' applicability, reduction in cost for raw data, and robustness in terms of resampling-based classification accuracy warrant further evaluation of these equations to discern Gb tumor biopsy heterogeneity at molecular level, diagnose potential malignancy, and prognosis of individual patients with glioblastomas.

Thermoelectricity in fullerene-metal heterojunctions.

PubMed

Yee, Shannon K; Malen, Jonathan A; Majumdar, Arun; Segalman, Rachel A

2011-10-12

Thermoelectricty in heterojunctions, where a single-molecule is trapped between metal electrodes, has been used to understand transport properties at organic-inorganic interfaces. (1) The transport in these systems is highly dependent on the energy level alignment between the molecular orbitals and the Fermi level (or work function) of the metal contacts. To date, the majority of single-molecule measurements have focused on simple small molecules where transport is dominated through the highest occupied molecular orbital. (2, 3) In these systems, energy level alignment is limited by the absence of electrode materials with low Fermi levels (i.e., large work functions). Alternatively, more controllable alignment between molecular orbitals and the Fermi level can be achieved with molecules whose transport is dominated by the lowest unoccupied molecular orbital (LUMO) because of readily available metals with lower work functions. Herein, we report molecular junction thermoelectric measurements of fullerene molecules (i.e., C(60), PCBM, and C(70)) trapped between metallic electrodes (i.e., Pt, Au, Ag). Fullerene junctions demonstrate the first strongly n-type molecular thermopower corresponding to transport through the LUMO, and the highest measured magnitude of molecular thermopower to date. While the electronic conductance of fullerenes is highly variable, due to fullerene's variable bonding geometries with the electrodes, the thermopower shows predictable trends based on the alignment of the LUMO with the work function of the electrodes. Both the magnitude and trend of the thermopower suggest that heterostructuring organic and inorganic materials at the nanoscale can further enhance thermoelectric performance, therein providing a new pathway for designing thermoelectric materials.

Selective solid-phase extraction using a molecularly imprinted polymer for the analysis of patulin in apple-based foods.

PubMed

Lucci, Paolo; Moret, Sabrina; Bettin, Sara; Conte, Lanfranco

2017-01-01

The aim of this work was to evaluate the use of a molecularly imprinted polymer as a selective solid-phase extraction sorbent for the clean-up and pre-concentration of patulin from apple-based food products. Ultra high pressure liquid chromatography coupled to ultraviolet absorbance detection was used for the analysis of patulin. The molecularly imprinted polymer was applied, for the first time, to the determination of patulin in apple juice, puree and jam samples spiked within the maximum levels specified by the European Commission No. 1881/2006. High recoveries (>77%) were obtained. The method was validated and found to be linear in the range 2-100 μg/kg with correlation coefficients greater than 0.965 and repeatability relative standard deviation below 11% in all cases. Compared with dispersive solid-phase extraction (QuEChERS method) and octadecyl sorbent, the molecularly imprinted polymer showed higher recoveries and selectivity for patulin. The application of Affinisep molecularly imprinted polymer as a selective sorbent material for detection of patulin fulfilled the method performance criteria required by the Commission Regulation No. 401/2006, demonstrating the suitability of the technique for the control of patulin at low ppb levels in different apple-based foods such as juice, puree and jam samples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Genetic and molecular bases of yield-associated traits: a translational biology approach between rice and wheat.

PubMed

Valluru, Ravi; Reynolds, Matthew P; Salse, Jerome

2014-07-01

Transferring the knowledge bases between related species may assist in enlarging the yield potential of crop plants. Being cereals, rice and wheat share a high level of gene conservation; however, they differ at metabolic levels as a part of the environmental adaptation resulting in different yield capacities. This review focuses on the current understanding of genetic and molecular regulation of yield-associated traits in both crop species, highlights the similarities and differences and presents the putative knowledge gaps. We focus on the traits associated with phenology, photosynthesis, and assimilate partitioning and lodging resistance; the most important drivers of yield potential. Currently, there are large knowledge gaps in the genetic and molecular control of such major biological processes that can be filled in a translational biology approach in transferring genomics and genetics informations between rice and wheat.

Chemically directing d-block heterometallics to nanocrystal surfaces as molecular beacons of surface structure

DOE PAGES

Rosen, Evelyn L.; Gilmore, Keith; Sawvel, April M.; ...

2015-07-28

Our understanding of structure and bonding in nanoscale materials is incomplete without knowledge of their surface structure. Needed are better surveying capabilities responsive not only to different atoms at the surface, but also their respective coordination environments. We report here that d-block organometallics, when placed at nanocrystal surfaces through heterometallic bonds, serve as molecular beacons broadcasting local surface structure in atomic detail. This unique ability stems from their elemental specificity and the sensitivity of their d-orbital level alignment to local coordination environment, which can be assessed spectroscopically. Re-surfacing cadmium and lead chalcogenide nanocrystals with iron- or ruthenium-based molecular beacons ismore » readily accomplished with trimethylsilylated cyclopentadienyl metal carbonyls. For PbSe nanocrystals with iron-based beacons, we show how core-level X-ray spectroscopies and DFT calculations enrich our understanding of both charge and atomic reorganization at the surface when beacons are bound.« less

Molecular classification based on apomorphic amino acids (Arthropoda, Hexapoda): Integrative taxonomy in the era of phylogenomics.

PubMed

Wu, Hao-Yang; Wang, Yan-Hui; Xie, Qiang; Ke, Yun-Ling; Bu, Wen-Jun

2016-06-17

With the great development of sequencing technologies and systematic methods, our understanding of evolutionary relationships at deeper levels within the tree of life has greatly improved over the last decade. However, the current taxonomic methodology is insufficient to describe the growing levels of diversity in both a standardised and general way due to the limitations of using only morphological traits to describe clades. Herein, we propose the idea of a molecular classification based on hierarchical and discrete amino acid characters. Clades are classified based on the results of phylogenetic analyses and described using amino acids with group specificity in phylograms. Practices based on the recently published phylogenomic datasets of insects together with 15 de novo sequenced transcriptomes in this study demonstrate that such a methodology can accommodate various higher ranks of taxonomy. Such an approach has the advantage of describing organisms in a standard and discrete way within a phylogenetic framework, thereby facilitating the recognition of clades from the view of the whole lineage, as indicated by PhyloCode. By combining identification keys and phylogenies, the molecular classification based on hierarchical and discrete characters may greatly boost the progress of integrative taxonomy.

Molecular classification based on apomorphic amino acids (Arthropoda, Hexapoda): Integrative taxonomy in the era of phylogenomics

PubMed Central

Wu, Hao-Yang; Wang, Yan-Hui; Xie, Qiang; Ke, Yun-Ling; Bu, Wen-Jun

2016-01-01

With the great development of sequencing technologies and systematic methods, our understanding of evolutionary relationships at deeper levels within the tree of life has greatly improved over the last decade. However, the current taxonomic methodology is insufficient to describe the growing levels of diversity in both a standardised and general way due to the limitations of using only morphological traits to describe clades. Herein, we propose the idea of a molecular classification based on hierarchical and discrete amino acid characters. Clades are classified based on the results of phylogenetic analyses and described using amino acids with group specificity in phylograms. Practices based on the recently published phylogenomic datasets of insects together with 15 de novo sequenced transcriptomes in this study demonstrate that such a methodology can accommodate various higher ranks of taxonomy. Such an approach has the advantage of describing organisms in a standard and discrete way within a phylogenetic framework, thereby facilitating the recognition of clades from the view of the whole lineage, as indicated by PhyloCode. By combining identification keys and phylogenies, the molecular classification based on hierarchical and discrete characters may greatly boost the progress of integrative taxonomy. PMID:27312960

Computational design of intrinsic molecular rectifiers based on asymmetric functionalization of N-phenylbenzamide

DOE PAGES

Ding, Wendu; Koepf, Matthieu; Koenigsmann, Christopher; ...

2015-11-03

Here, we report a systematic computational search of molecular frameworks for intrinsic rectification of electron transport. The screening of molecular rectifiers includes 52 molecules and conformers spanning over 9 series of structural motifs. N-Phenylbenzamide is found to be a promising framework with both suitable conductance and rectification properties. A targeted screening performed on 30 additional derivatives and conformers of N-phenylbenzamide yielded enhanced rectification based on asymmetric functionalization. We demonstrate that electron-donating substituent groups that maintain an asymmetric distribution of charge in the dominant transport channel (e.g., HOMO) enhance rectification by raising the channel closer to the Fermi level. These findingsmore » are particularly valuable for the design of molecular assemblies that could ensure directionality of electron transport in a wide range of applications, from molecular electronics to catalytic reactions.« less

Tagging and purifying proteins to teach molecular biology and advanced biochemistry.

PubMed

Roecklein-Canfield, Jennifer A; Lopilato, Jane

2004-11-01

Two distinct courses, "Molecular Biology" taught by the Biology Department and "Advanced Biochemistry" taught by the Chemistry Department, complement each other and, when taught in a coordinated and integrated way, can enhance student learning and understanding of complex material. "Molecular Biology" is a comprehensive lecture-based course with a 3-h laboratory once a week, while "Advanced Biochemistry" is a completely laboratory-based course with lecture fully integrated around independent student projects. Both courses emphasize and utilize cutting-edge technology. Teaching across departmental boundaries allows students access to faculty expertise and techniques rarely used at the undergraduate level, namely the tagging of proteins and their use in protein purification. Copyright © 2004 International Union of Biochemistry and Molecular Biology, Inc.

Stimulus-responsive light-harvesting complexes based on the pillararene-induced co-assembly of β-carotene and chlorophyll

PubMed Central

Sun, Yan; Guo, Fang; Zuo, Tongfei; Hua, Jingjing; Diao, Guowang

2016-01-01

The locations and arrangements of carotenoids at the subcellular level are responsible for their designated functions, which reinforces the necessity of developing methods for constructing carotenoid-based suprastructures beyond the molecular level. Because carotenoids lack the binding sites necessary for controlled interactions, functional structures based on carotenoids are not easily obtained. Here, we show that carotene-based suprastructures were formed via the induction of pillararene through a phase-transfer-mediated host–guest interaction. More importantly, similar to the main component in natural photosynthesis, complexes could be synthesized after chlorophyll was introduced into the carotene-based suprastructure assembly process. Remarkably, compared with molecular carotene or chlorophyll, this synthesized suprastructure exhibits some photocatalytic activity when exposed to light, which can be exploited for photocatalytic reaction studies of energy capture and solar conversion in living organisms. PMID:27345928

Gas solubility in dilute solutions: A novel molecular thermodynamic perspective

NASA Astrophysics Data System (ADS)

Chialvo, Ariel A.

2018-05-01

We present an explicit molecular-based interpretation of the thermodynamic phase equilibrium underlying gas solubility in liquids, through rigorous links between the microstructure of the dilute systems and the relevant macroscopic quantities that characterize their solution thermodynamics. We apply the formal analysis to unravel and highlight the molecular-level nature of the approximations behind the widely used Krichevsky-Kasarnovsky [J. Am. Chem. Soc. 57, 2168 (1935)] and Krichevsky-Ilinskaya [Acta Physicochim. 20, 327 (1945)] equations for the modeling of gas solubility. Then, we implement a general molecular-based approach to gas solubility and illustrate it by studying Lennard-Jones binary systems whose microstructure and thermodynamic properties were consistently generated via integral equation calculations. Furthermore, guided by the molecular-based analysis, we propose a novel macroscopic modeling approach to gas solubility, emphasize some usually overlook modeling subtleties, and identify novel interdependences among relevant solubility quantities that can be used as either handy modeling constraints or tools for consistency tests.

Gas solubility in dilute solutions: A novel molecular thermodynamic perspective.

PubMed

Chialvo, Ariel A

2018-05-07

We present an explicit molecular-based interpretation of the thermodynamic phase equilibrium underlying gas solubility in liquids, through rigorous links between the microstructure of the dilute systems and the relevant macroscopic quantities that characterize their solution thermodynamics. We apply the formal analysis to unravel and highlight the molecular-level nature of the approximations behind the widely used Krichevsky-Kasarnovsky [J. Am. Chem. Soc. 57, 2168 (1935)] and Krichevsky-Ilinskaya [Acta Physicochim. 20, 327 (1945)] equations for the modeling of gas solubility. Then, we implement a general molecular-based approach to gas solubility and illustrate it by studying Lennard-Jones binary systems whose microstructure and thermodynamic properties were consistently generated via integral equation calculations. Furthermore, guided by the molecular-based analysis, we propose a novel macroscopic modeling approach to gas solubility, emphasize some usually overlook modeling subtleties, and identify novel interdependences among relevant solubility quantities that can be used as either handy modeling constraints or tools for consistency tests.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nishimura, Takahiro, E-mail: t-nishimura@ist.osaka-u.ac.jp; Fujii, Ryo; Ogura, Yusuke

Molecular logic circuits represent a promising technology for observation and manipulation of biological systems at the molecular level. However, the implementation of molecular logic circuits for temporal and programmable operation remains challenging. In this paper, we demonstrate an optically controllable logic circuit that uses fluorescence resonance energy transfer (FRET) for signaling. The FRET-based signaling process is modulated by both molecular and optical inputs. Based on the distance dependence of FRET, the FRET pathways required to execute molecular logic operations are formed on a DNA nanostructure as a circuit based on its molecular inputs. In addition, the FRET pathways on themore » DNA nanostructure are controlled optically, using photoswitching fluorescent molecules to instruct the execution of the desired operation and the related timings. The behavior of the circuit can thus be controlled using external optical signals. As an example, a molecular logic circuit capable of executing two different logic operations was studied. The circuit contains functional DNAs and a DNA scaffold to construct two FRET routes for executing Input 1 AND Input 2 and Input 1 AND NOT Input 3 operations on molecular inputs. The circuit produced the correct outputs with all possible combinations of the inputs by following the light signals. Moreover, the operation execution timings were controlled based on light irradiation and the circuit responded to time-dependent inputs. The experimental results demonstrate that the circuit changes the output for the required operations following the input of temporal light signals.« less

Dialkylthio Substitution: An Effective Method to Modulate the Molecular Energy Levels of 2D-BDT Photovoltaic Polymers.

PubMed

Yao, Huifeng; Zhang, Hao; Ye, Long; Zhao, Wenchao; Zhang, Shaoqing; Hou, Jianhui

2016-02-17

Dialkylthio-substituted thienyl-benzodithiophene (BDT-DST) was designed and synthesized as a building block to modulate the molecular levels of the conjugated polymers, and three copolymers named PDST-BDD, PDST-TT and PDST-DPP were prepared and applied in polymer solar cells (PSCs). Theoretical calculations and electrochemical cyclic voltammetry (CV) measurement suggested that the dialkylthio group could decrease the molecular energy levels of the resulting polymers distinctly. The open-circuit voltage (VOC) of PSC devices based on PDST-BDD, PDST-TT, and PDST-DPP are as high as 1.0, 0.98, and 0.88 V, respectively, which are ∼0.15 V higher than those of the corresponding alky-substituted analogues. Moreover, the influence of the dialkylthio group on the absorption spectra, crystalline properties, hole mobilities, and blend morphologies of the polymers was also investigated. The results indicate that the dialkythio substitution is an effective method to modulate the molecular energy levels and that the BDT-DST unit has potential for constructing high-efficiency photovoltaic polymers.

Molecular-level Analysis of Shock-wave Physics and Derivation of the Hugoniot Relations for Soda-lime Glass

DTIC Science & Technology

2011-06-17

based glasses like fused silica and soda - lime glass , the polyhedral central cation is silicon. In this case, each silicon is surrounded by four oxygen...to two network forming cations) oxygen atoms per network polyhedron. The equilibrium values for this parameter in fused silica and soda - lime glass ...Molecular-level analysis of shock-wave physics and derivation of the Hugoniot relations for soda - lime glass M. Grujicic • B. Pandurangan • W. C. Bell

Synergistic effect of fluorination on molecular energy level modulation in highly efficient photovoltaic polymers.

PubMed

Zhang, Maojie; Guo, Xia; Zhang, Shaoqing; Hou, Jianhui

2014-02-01

The synergistic effect of fluorination on molecular energy level modulation is realized by introducing fluorine atoms onto both the donor and the acceptor moieties in a D-A polymer, and as a result, the polymer solar cell device based on the trifluorinated polymer, PBT-3F, shows a high efficiency of 8.6%, under illumination of AM 1.5G, 100 mW cm(-) (2) . © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development of a Semester-Long, Inquiry-Based Laboratory Course in Upper-Level Biochemistry and Molecular Biology

ERIC Educational Resources Information Center

Murthy, Pushpalatha P. N.; Thompson, Martin; Hungwe, Kedmon

2014-01-01

A semester-long laboratory course was designed and implemented to familiarize students with modern biochemistry and molecular biology techniques. The designed format involved active student participation, evaluation of data, and critical thinking, and guided students to become independent researchers. The first part of the course focused on…

Impact of Fluorine Atoms on Perylene Diimide Derivative for Fullerene-Free Organic Photovoltaics.

PubMed

Zhao, Liang; Sun, Hua; Liu, Xiaoyuan; Liu, Changmei; Shan, Haiquan; Xia, Jiuxu; Xu, Zongxiang; Chen, Fei; Chen, Zhi-Kuan; Huang, Wei

2017-08-17

The incorporation of fluorine atoms in organic semiconducting materials has attracted much attention recently due to its unique function to manipulate the molecular packing, film morphology and molecular energy levels. In this work, two perylenediimide (PDI) derivatives FPDI-CDTph and FPDI-CDTph2F were designed and synthesized to investigate the impact of fluorination on non-fullerene acceptors. Both FPDI-CDTph and FPDI-CDTph2F exhibited strong and broad absorption profiles, suitable lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) energy levels, and good electron transport ability. Compared with FPDI-CDTph, the fluorinated acceptor (FPDI-CDTph2F) afforded an optimal bulk heterojunction morphology with an interconnected and nanoscale phase separated structure that allowed more efficient exciton dissociation and balanced charge transport. Consequently, organic solar cells based on FPDI-CDTph2F showed a much higher power conversion efficiency (PCE) of 6.03 % than that of FPDI-CDTph based devices (4.10 %) without any post-fabrication treatment. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Thermally modulated nano-trampoline material as smart skin for gas molecular mass detection

NASA Astrophysics Data System (ADS)

Xia, Hua

2012-06-01

Conventional multi-component gas analysis is based either on laser spectroscopy, laser and photoacoustic absorption at specific wavelengths, or on gas chromatography by separating the components of a gas mixture primarily due to boiling point (or vapor pressure) differences. This paper will present a new gas molecular mass detection method based on thermally modulated nano-trampoline material as smart skin for gas molecular mass detection by fiber Bragg grating-based gas sensors. Such a nanomaterial and fiber Bragg grating integrated sensing device has been designed to be operated either at high-energy level (highly thermal strained status) or at low-energy level (low thermal strained status). Thermal energy absorption of gas molecular trigs the sensing device transition from high-thermal-energy status to low-thermal- energy status. Experiment has shown that thermal energy variation due to gas molecular thermal energy absorption is dependent upon the gas molecular mass, and can be detected by fiber Bragg resonant wavelength shift with a linear function from 17 kg/kmol to 32 kg/kmol and a sensitivity of 0.025 kg/kmol for a 5 micron-thick nano-trampoline structure and fiber Bragg grating integrated gas sensing device. The laboratory and field validation data have further demonstrated its fast response characteristics and reliability to be online gas analysis instrument for measuring effective gas molecular mass from single-component gas, binary-component gas mixture, and multi-gas mixture. The potential industrial applications include fouling and surge control for gas charge centrifugal compressor ethylene production, gas purity for hydrogen-cooled generator, gasification for syngas production, gasoline/diesel and natural gas fuel quality monitoring for consumer market.

Design of Energetic Ionic Liquids (Preprint)

DTIC Science & Technology

2008-05-07

mesoscale-level simulations of bulk ionic liquids based upon multiscale coarse graining techniques. 15. SUBJECT TERMS 16. SECURITY...simulations utilizing polarizable force fields, and mesoscale-level simulations of bulk ionic liquids based upon multiscale coarse graining...Simulations of the Energetic Ionic Liquid 1-hydroxyethyl-4-amino-1, 2, 4- triazolium Nitrate (HEATN): Molecular dynamics (MD) simulations have been

A new instrument of VUV laser desorption/ionization mass spectrometry imaging with micrometer spatial resolution and low level of molecular fragmentation.

PubMed

Wang, Jia; Liu, Feng; Mo, Yuxiang; Wang, Zhaoying; Zhang, Sichun; Zhang, Xinrong

2017-11-01

Mass spectrometry imaging (MSI) has important applications in material research, biology, and medicine. The MSI method based on UV laser desorption/ionization (UVLDI) can obtain images of intact samples, but has a high level of molecular fragmentation. In this work, we report a new MSI instrument that uses a VUV laser (125.3 nm) as a desorption/ionization source to exploit its advantages of high single photon energy and small focus size. The new instrument was tested by the mass spectra of Nile red and FGB (Fibrinogen beta chain) samples and mass spectrometric images of a fly brain section. For the tested samples, the VUVDI method offers lower levels of molecular fragmentations and higher sensitivities than those of the UVLDI method and second ion mass spectrometry imaging method using a Bi 3 + beam. The ablation crater produced by the focused VUV laser on a quartz plate has an area of 10 μm 2 . The VUV laser is prepared based on the four-wave mixing method using three collimated laser beams and a heated Hg cell.

A new instrument of VUV laser desorption/ionization mass spectrometry imaging with micrometer spatial resolution and low level of molecular fragmentation

NASA Astrophysics Data System (ADS)

Wang, Jia; Liu, Feng; Mo, Yuxiang; Wang, Zhaoying; Zhang, Sichun; Zhang, Xinrong

2017-11-01

Mass spectrometry imaging (MSI) has important applications in material research, biology, and medicine. The MSI method based on UV laser desorption/ionization (UVLDI) can obtain images of intact samples, but has a high level of molecular fragmentation. In this work, we report a new MSI instrument that uses a VUV laser (125.3 nm) as a desorption/ionization source to exploit its advantages of high single photon energy and small focus size. The new instrument was tested by the mass spectra of Nile red and FGB (Fibrinogen beta chain) samples and mass spectrometric images of a fly brain section. For the tested samples, the VUVDI method offers lower levels of molecular fragmentations and higher sensitivities than those of the UVLDI method and second ion mass spectrometry imaging method using a Bi3+ beam. The ablation crater produced by the focused VUV laser on a quartz plate has an area of 10 μm2. The VUV laser is prepared based on the four-wave mixing method using three collimated laser beams and a heated Hg cell.

[Future perspectives for diagnostic imaging in urology: from anatomic and functional to molecular imaging].

PubMed

Macis, Giuseppe; Di Giovanni, Silvia; Di Franco, Davide; Bonomo, Lorenzo

2013-01-01

The future approach of diagnostic imaging in urology follows the technological progress, which made the visualization of in vivo molecular processes possible. From anatomo-morphological diagnostic imaging and through functional imaging molecular radiology is reached. Based on molecular probes, imaging is aimed at assessing the in vivo molecular processes, their physiology and function at cellular level. The future imaging will investigate the complex tumor functioning as metabolism, aerobic glycolysis in particular, angiogenesis, cell proliferation, metastatic potential, hypoxia, apoptosis and receptors expressed by neoplastic cells. Methods for performing molecular radiology are CT, MRI, PET-CT, PET-MRI, SPECT and optical imaging. Molecular ultrasound combines technological advancement with targeted contrast media based on microbubbles, this allowing the selective registration of microbubble signal while that of stationary tissues is suppressed. An experimental study was carried out where the ultrasound molecular probe BR55 strictly bound to prostate tumor results in strong enhancement in the early phase after contrast, this contrast being maintained in the late phase. This late enhancement is markedly significant for the detection of prostatic cancer foci and to guide the biopsy sampling. The 124I-cG250 molecular antibody which is strictly linked to cellular carbonic anhydrase IX of clear cell renal carcinoma, allows the acquisition of diagnostic PET images of clear cell renal carcinoma without biopsy. This WG-250 (RENCAREX) antibody was used as a therapy in metastatic clear cell renal carcinoma. Future advancements and applications will result in early cancer diagnosis, personalized therapy that will be specific according to the molecular features of cancer and leading to the development of catheter-based multichannel molecular imaging devices for cystoscopy-based molecular imaging diagnosis and intervention.

FlyBase: genes and gene models

PubMed Central

Drysdale, Rachel A.; Crosby, Madeline A.

2005-01-01

FlyBase (http://flybase.org) is the primary repository of genetic and molecular data of the insect family Drosophilidae. For the most extensively studied species, Drosophila melanogaster, a wide range of data are presented in integrated formats. Data types include mutant phenotypes, molecular characterization of mutant alleles and aberrations, cytological maps, wild-type expression patterns, anatomical images, transgenic constructs and insertions, sequence-level gene models and molecular classification of gene product functions. There is a growing body of data for other Drosophila species; this is expected to increase dramatically over the next year, with the completion of draft-quality genomic sequences of an additional 11 Drosphila species. PMID:15608223

Tailor-made Molecular Cobalt Catalyst System for the Selective Transformation of Carbon Dioxide to Dialkoxymethane Ethers.

PubMed

Schieweck, Benjamin G; Klankermayer, Jürgen

2017-08-28

Herein a non-precious transition-metal catalyst system for the selective synthesis of dialkoxymethane ethers from carbon dioxide and molecular hydrogen is presented. The development of a tailored catalyst system based on cobalt salts in combination with selected Triphos ligands and acidic co-catalysts enabled a synthetic pathway, avoiding the oxidation of methanol to attain the formaldehyde level of the central CH 2 unit. This unprecedented productivity based on the molecular cobalt catalyst is the first example of a non-precious transition-metal system for this transformation utilizing renewable carbon dioxide sources. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Accelerated sampling by infinite swapping of path integral molecular dynamics with surface hopping

NASA Astrophysics Data System (ADS)

Lu, Jianfeng; Zhou, Zhennan

2018-02-01

To accelerate the thermal equilibrium sampling of multi-level quantum systems, the infinite swapping limit of a recently proposed multi-level ring polymer representation is investigated. In the infinite swapping limit, the ring polymer evolves according to an averaged Hamiltonian with respect to all possible surface index configurations of the ring polymer and thus connects the surface hopping approach to the mean-field path-integral molecular dynamics. A multiscale integrator for the infinite swapping limit is also proposed to enable efficient sampling based on the limiting dynamics. Numerical results demonstrate the huge improvement of sampling efficiency of the infinite swapping compared with the direct simulation of path-integral molecular dynamics with surface hopping.

Molecular recognition of microbial lipid-based antigens by T cells.

PubMed

Gras, Stephanie; Van Rhijn, Ildiko; Shahine, Adam; Le Nours, Jérôme

2018-05-01

The immune system has evolved to protect hosts from pathogens. T cells represent a critical component of the immune system by their engagement in host defence mechanisms against microbial infections. Our knowledge of the molecular recognition by T cells of pathogen-derived peptidic antigens that are presented by the major histocompatibility complex glycoproteins is now well established. However, lipids represent an additional, distinct chemical class of molecules that when presented by the family of CD1 antigen-presenting molecules can serve as antigens, and be recognized by specialized subsets of T cells leading to antigen-specific activation. Over the past decades, numerous CD1-presented self- and bacterial lipid-based antigens have been isolated and characterized. However, our understanding at the molecular level of T cell immunity to CD1 molecules presenting microbial lipid-based antigens is still largely unexplored. Here, we review the insights and the molecular basis underpinning the recognition of microbial lipid-based antigens by T cells.

SOMO–HOMO Level Inversion in Biologically Important Radicals

PubMed Central

2017-01-01

Conventionally, the singly occupied molecular orbital (SOMO) of a radical species is considered to be the highest occupied molecular orbital (HOMO), but this is not the case always. In this study, we considered a number of radicals from smallest diatomic anion radicals such as superoxide anion radical to one-electron oxidized DNA related base radicals that show the SOMO is energetically lower than one or more doubly occupied molecular orbitals (MOs) (SOMO–HOMO level inversion). The electronic configurations are calculated employing the B3LYP/6-31++G** method, with the inclusion of aqueous phase via the integral equation formalism of the polarized continuum model solvation model. From the extensive study of the electronic configurations of radicals produced by one-electron oxidation or reduction of natural-DNA bases, bromine-, sulfur-, selenium-, and aza-substituted DNA bases, as well as 20 diatomic molecules, we highlight the following important findings: (i) SOMO–HOMO level inversion is a common phenomenon in radical species. (ii) The more localized spin density in σ-orbital on a single atom (carbon, nitrogen, oxygen, sulfur, or selenium), the greater the gap between HOMO and SOMO. (iii) In species with SOMO–HOMO level inversion, one-electron oxidation takes place from HOMO not from the SOMO, which produces a molecule in its triplet ground state. Oxidation of aqueous superoxide anion producing triplet molecular oxygen is one example of many. (iv) These results are for conventional radicals and in contrast with those reported for distonic radical anions in which SOMO–HOMO gaps are smaller for more localized radicals and the orbital inversions vanish in water. Our findings yield new insights into the properties of free radical systems. PMID:29240424

Fine-Tuning of Molecular Packing and Energy Level through Methyl Substitution Enabling Excellent Small Molecule Acceptors for Nonfullerene Polymer Solar Cells with Efficiency up to 12.54.

PubMed

Luo, Zhenghui; Bin, Haijun; Liu, Tao; Zhang, Zhi-Guo; Yang, Yankang; Zhong, Cheng; Qiu, Beibei; Li, Guanghao; Gao, Wei; Xie, Dongjun; Wu, Kailong; Sun, Yanming; Liu, Feng; Li, Yongfang; Yang, Chuluo

2018-03-01

A novel small molecule acceptor MeIC with a methylated end-capping group is developed. Compared to unmethylated counterparts (ITCPTC), MeIC exhibits a higher lowest unoccupied molecular orbital (LUMO) level value, tighter molecular packing, better crystallites quality, and stronger absorption in the range of 520-740 nm. The MeIC-based polymer solar cells (PSCs) with J71 as donor, achieve high power conversion efficiency (PCE), up to 12.54% with a short-circuit current (J SC ) of 18.41 mA cm -2 , significantly higher than that of the device based on J71:ITCPTC (11.63% with a J SC of 17.52 mA cm -2 ). The higher J SC of the PSC based on J71:MeIC can be attributed to more balanced μ h /μ e , higher charge dissociation and charge collection efficiency, better molecular packing, and more proper phase separation features as indicated by grazing incident X-ray diffraction and resonant soft X-ray scattering results. It is worth mentioning that the as-cast PSCs based on MeIC also yield a high PCE of 11.26%, which is among the highest value for the as-cast nonfullerene PSCs so far. Such a small modification that leads to so significant an improvement of the photovoltaic performance is a quite exciting finding, shining a light on the molecular design of the nonfullerene acceptors. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mixed QM/MM molecular electrostatic potentials.

PubMed

Hernández, B; Luque, F J; Orozco, M

2000-05-01

A new method is presented for the calculation of the Molecular Electrostatic Potential (MEP) in large systems. Based on the mixed Quantum Mechanics/Molecular Mechanics (QM/MM) approach, the method assumes both a quantum and classical description for the molecule, and the calculation of the MEP in the space surrounding the molecule is made using this dual treatment. The MEP at points close to the molecule is computed using a full QM formalism, while a pure classical evaluation of the MEP is used for points located at large distances from the molecule. The algorithm allows the user to select the desired level of accuracy in the MEP, so that the definition of the regions where the MEP is computed at the classical or QM levels is adjusted automatically. The potential use of this QM/MM MEP in molecular modeling studies is discussed.

.Network analytics for adverse outcome pathways

EPA Science Inventory

Adverse Outcome Pathways (AOPs) organize toxicological knowledge from the molecular level up to the population level, providing evidence-based causal linkages at each step. The AOPWiki serves as a repository of AOPs. With the international adoption of the AOP framework, the AOPw...

Molecular Species Delimitation and Morphology of Aquatic and Sub-Aquatic Bugs (Heteroptera) in Cameroon

PubMed Central

Le Gall, Philippe; Chen, Ping-Ping; Nieser, Nico; Guilbert, Eric; Njiokou, Flobert; Marsollier, Laurent; Guégan, Jean-François; Pluot-Sigwalt, Dominique; Eyangoh, Sara; Harry, Myriam

2016-01-01

Aquatic and semi-aquatic bugs (Heteroptera) represent a remarkable diversity and a resurging interest has been given to documenting at the species level these insects inhabiting Cameroon in Central Africa due to their potential implication in the transmission of the bacterium Mycobacterium ulcerans, the causal agent of Buruli ulcer, an emerging human disease. A survey was carried out over two years in Cameroon. Morphological analyses were done in two steps. A first step consisted in separating the specimens based on broadly shared characters into morphotypes. The specimens were then separated into two independent batches containing each the same representation of each morphotype. One batch (309 specimens) was used by taxonomy experts on aquatic bugs for species level identification and/or to reconcile nymph with their corresponding adult species. The second batch (188 specimens) was used to define species based on the COI DNA sequences (standard sequence used for “DNA barcoding”) and using the Automatic Barcode Gap Discovery (ABGD) method. The first morphological analysis step separated the specimens into 63 different morphotypes (49 adults and 14 nymphs), which were then found to belong to 54 morphological species in the infra-orders Gerromorpha and Nepomorpha based on the species-level morphological identification, and 41–45 putative molecular species according to the gap value retained in the ABGD. Integrating morphology and “DNA barcoding” reconciled all the specimens into 62 aquatic bug species in Cameroon. Generally, we obtained a good congruence between species a priori identified based on morphology from adult morphotypes and molecular putative species. Moreover, molecular identification has allowed the association of 86% of nymphs with adults. This work illustrates the importance of integrative taxonomy. PMID:27149077

Using Molecular Visualization to Explore Protein Structure and Function and Enhance Student Facility with Computational Tools

ERIC Educational Resources Information Center

Terrell, Cassidy R.; Listenberger, Laura L.

2017-01-01

Recognizing that undergraduate students can benefit from analysis of 3D protein structure and function, we have developed a multiweek, inquiry-based molecular visualization project for Biochemistry I students. This project uses a virtual model of cyclooxygenase-1 (COX-1) to guide students through multiple levels of protein structure analysis. The…

Understanding FRET as a Research Tool for Cellular Studies

PubMed Central

Shrestha, Dilip; Jenei, Attila; Nagy, Péter; Vereb, György; Szöllősi, János

2015-01-01

Communication of molecular species through dynamic association and/or dissociation at various cellular sites governs biological functions. Understanding these physiological processes require delineation of molecular events occurring at the level of individual complexes in a living cell. Among the few non-invasive approaches with nanometer resolution are methods based on Förster Resonance Energy Transfer (FRET). FRET is effective at a distance of 1–10 nm which is equivalent to the size of macromolecules, thus providing an unprecedented level of detail on molecular interactions. The emergence of fluorescent proteins and SNAP- and CLIP- tag proteins provided FRET with the capability to monitor changes in a molecular complex in real-time making it possible to establish the functional significance of the studied molecules in a native environment. Now, FRET is widely used in biological sciences, including the field of proteomics, signal transduction, diagnostics and drug development to address questions almost unimaginable with biochemical methods and conventional microscopies. However, the underlying physics of FRET often scares biologists. Therefore, in this review, our goal is to introduce FRET to non-physicists in a lucid manner. We will also discuss our contributions to various FRET methodologies based on microscopy and flow cytometry, while describing its application for determining the molecular heterogeneity of the plasma membrane in various cell types. PMID:25815593

Molecular analysis of single oocyst of Eimeria by whole genome amplification (WGA) based nested PCR.

PubMed

Wang, Yunzhou; Tao, Geru; Cui, Yujuan; Lv, Qiyao; Xie, Li; Li, Yuan; Suo, Xun; Qin, Yinghe; Xiao, Lihua; Liu, Xianyong

2014-09-01

PCR-based molecular tools are widely used for the identification and characterization of protozoa. Here we report the molecular analysis of Eimeria species using combined methods of whole genome amplification (WGA) and nested PCR. Single oocyst of Eimeria stiedai or Eimeriamedia was directly used for random amplification of the genomic DNA with either primer extension preamplification (PEP) or multiple displacement amplification (MDA), and then the WGA product was used as template in nested PCR with species-specific primers for ITS-1, 18S rDNA and 23S rDNA of E. stiedai and E. media. WGA-based PCR was successful for the amplification of these genes from single oocyst. For the species identification of single oocyst isolated from mixed E. stiedai or E. media, the results from WGA-based PCR were exactly in accordance with those from morphological identification, suggesting the availability of this method in molecular analysis of eimerian parasites at the single oocyst level. WGA-based PCR method can also be applied for the identification and genetic characterization of other protists. Copyright © 2014 Elsevier Inc. All rights reserved.

Playing Tic-Tac-Toe with a Sugar-Based Molecular Computer.

PubMed

Elstner, M; Schiller, A

2015-08-24

Today, molecules can perform Boolean operations and circuits at a level of higher complexity. However, concatenation of logic gates and inhomogeneous inputs and outputs are still challenging tasks. Novel approaches for logic gate integration are possible when chemical programming and software programming are combined. Here it is shown that a molecular finite automaton based on the concatenated implication function (IMP) of a fluorescent two-component sugar probe via a wiring algorithm is able to play tic-tac-toe.

Integrating multiple molecular sources into a clinical risk prediction signature by extracting complementary information.

PubMed

Hieke, Stefanie; Benner, Axel; Schlenl, Richard F; Schumacher, Martin; Bullinger, Lars; Binder, Harald

2016-08-30

High-throughput technology allows for genome-wide measurements at different molecular levels for the same patient, e.g. single nucleotide polymorphisms (SNPs) and gene expression. Correspondingly, it might be beneficial to also integrate complementary information from different molecular levels when building multivariable risk prediction models for a clinical endpoint, such as treatment response or survival. Unfortunately, such a high-dimensional modeling task will often be complicated by a limited overlap of molecular measurements at different levels between patients, i.e. measurements from all molecular levels are available only for a smaller proportion of patients. We propose a sequential strategy for building clinical risk prediction models that integrate genome-wide measurements from two molecular levels in a complementary way. To deal with partial overlap, we develop an imputation approach that allows us to use all available data. This approach is investigated in two acute myeloid leukemia applications combining gene expression with either SNP or DNA methylation data. After obtaining a sparse risk prediction signature e.g. from SNP data, an automatically selected set of prognostic SNPs, by componentwise likelihood-based boosting, imputation is performed for the corresponding linear predictor by a linking model that incorporates e.g. gene expression measurements. The imputed linear predictor is then used for adjustment when building a prognostic signature from the gene expression data. For evaluation, we consider stability, as quantified by inclusion frequencies across resampling data sets. Despite an extremely small overlap in the application example with gene expression and SNPs, several genes are seen to be more stably identified when taking the (imputed) linear predictor from the SNP data into account. In the application with gene expression and DNA methylation, prediction performance with respect to survival also indicates that the proposed approach might work well. We consider imputation of linear predictor values to be a feasible and sensible approach for dealing with partial overlap in complementary integrative analysis of molecular measurements at different levels. More generally, these results indicate that a complementary strategy for integrating different molecular levels can result in more stable risk prediction signatures, potentially providing a more reliable insight into the underlying biology.

Multi-level molecular modelling for plasma medicine

NASA Astrophysics Data System (ADS)

Bogaerts, Annemie; Khosravian, Narjes; Van der Paal, Jonas; Verlackt, Christof C. W.; Yusupov, Maksudbek; Kamaraj, Balu; Neyts, Erik C.

2016-02-01

Modelling at the molecular or atomic scale can be very useful for obtaining a better insight in plasma medicine. This paper gives an overview of different atomic/molecular scale modelling approaches that can be used to study the direct interaction of plasma species with biomolecules or the consequences of these interactions for the biomolecules on a somewhat longer time-scale. These approaches include density functional theory (DFT), density functional based tight binding (DFTB), classical reactive and non-reactive molecular dynamics (MD) and united-atom or coarse-grained MD, as well as hybrid quantum mechanics/molecular mechanics (QM/MM) methods. Specific examples will be given for three important types of biomolecules, present in human cells, i.e. proteins, DNA and phospholipids found in the cell membrane. The results show that each of these modelling approaches has its specific strengths and limitations, and is particularly useful for certain applications. A multi-level approach is therefore most suitable for obtaining a global picture of the plasma-biomolecule interactions.

A molecular dynamics study of polymer/graphene interfacial systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rissanou, Anastassia N.; Harmandaris, Vagelis

2014-05-15

Graphene based polymer nanocomposites are hybrid materials with a very broad range of technological applications. In this work, we study three hybrid polymer/graphene interfacial systems (polystyrene/graphene, poly(methyl methacrylate)/graphene and polyethylene/graphene) through detailed atomistic molecular dynamics (MD) simulations. Density profiles, structural characteristics and mobility aspects are being examined at the molecular level for all model systems. In addition, we compare the properties of the hybrid systems to the properties of the corresponding bulk ones, as well as to theoretical predictions.

Molecular pathology curriculum for medical laboratory scientists: A report of the association for molecular pathology training and education committee.

PubMed

Taylor, Sara; Bennett, Katie M; Deignan, Joshua L; Hendrix, Ericka C; Orton, Susan M; Verma, Shalini; Schutzbank, Ted E

2014-05-01

Molecular diagnostics is a rapidly growing specialty in the clinical laboratory assessment of pathology. Educational programs in medical laboratory science and specialized programs in molecular diagnostics must address the training of clinical scientists in molecular diagnostics, but the educational curriculum for this field is not well defined. Moreover, our understanding of underlying genetic contributions to specific diseases and the technologies used in molecular diagnostics laboratories change rapidly, challenging providers of training programs in molecular diagnostics to keep their curriculum current and relevant. In this article, we provide curriculum recommendations to molecular diagnostics training providers at both the baccalaureate and master's level of education. We base our recommendations on several factors. First, we considered National Accrediting Agency for Clinical Laboratory Sciences guidelines for accreditation of molecular diagnostics programs, because educational programs in clinical laboratory science should obtain its accreditation. Second, the guidelines of several of the best known certifying agencies for clinical laboratory scientists were incorporated into our recommendations. Finally, we relied on feedback from current employers of molecular diagnostics scientists, regarding the skills and knowledge that they believe are essential for clinical scientists who will be performing molecular testing in their laboratories. We have compiled these data into recommendations for a molecular diagnostics curriculum at both the baccalaureate and master's level of education. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

In vitro quantification of specific microRNA using molecular beacons

PubMed Central

Baker, Meredith B.; Bao, Gang; Searles, Charles D.

2012-01-01

MicroRNAs (miRNAs), a class of non-coding RNAs, have become a major focus of molecular biology research because of their diverse genomic origin and ability to regulate an array of cellular processes. Although the biological functions of miRNA are yet to be fully understood, tissue levels of specific miRNAs have been shown to correlate with pathological development of disease. Here, we demonstrate that molecular beacons can readily distinguish mature- and pre-miRNAs, and reliably quantify miRNA expression. We found that molecular beacons with DNA, RNA and combined locked nucleic acid (LNA)–DNA backbones can all detect miRNAs of low (<1 nM) concentrations in vitro, with RNA beacons having the highest detection sensitivity. Furthermore, we found that molecular beacons have the potential to distinguish miRNAs that have slight variations in their nucleotide sequence. These results suggest that the molecular beacon-based approach to assess miRNA expression and distinguish mature and precursor miRNA species is quite robust, and has the promise for assessing miRNA levels in biological samples. PMID:22110035

A phylum-level phylogenetic classification of zygomycete fungi based on genome-scale data

USDA-ARS?s Scientific Manuscript database

Zygomycete fungi were classified as a single phylum, Zygomycota, based on sexual reproduction by zygospores, frequent asexual reproduction by sporangia, absence of multicellular sporocarps, and production of coenocytic hyphae, all with some exceptions. Molecular phylogenies based on one or a few gen...

Therapeutic Approaches for Shankopathies

PubMed Central

Wang, Xiaoming; Bey, Alexandra; Chang, Leeyup; Krystal, Andrew D.; Jiang, Yong-hui

2013-01-01

Despite recent advances in understanding the molecular mechanisms of autism spectrum disorders (ASD), the current treatments for these disorders are mostly focused on behavioral and educational approaches. The considerable clinical and molecular heterogeneity of ASD present a significant challenge to the development of an effective treatment targeting underlying molecular defects. Deficiency of SHANK family genes causing ASD represent an exciting opportunity for developing molecular therapies because of strong genetic evidence for SHANKs as causative genes in ASD and the availability of a panel of Shank mutant mouse models. In this article we review the literature suggesting the potential for developing therapies based on molecular characteristics and discuss several exciting themes that are emerging from studying Shank mutant mice at the molecular level and in terms of synaptic function. PMID:23536326

Integrating Genomics Into Clinical Pediatric Oncology Using the Molecular Tumor Board at the Memorial Sloan Kettering Cancer Center.

PubMed

Ortiz, Michael V; Kobos, Rachel; Walsh, Michael; Slotkin, Emily K; Roberts, Stephen; Berger, Michael F; Hameed, Meera; Solit, David; Ladanyi, Marc; Shukla, Neerav; Kentsis, Alex

2016-08-01

Pediatric oncologists have begun to leverage tumor genetic profiling to match patients with targeted therapies. At the Memorial Sloan Kettering Cancer Center (MSKCC), we developed the Pediatric Molecular Tumor Board (PMTB) to track, integrate, and interpret clinical genomic profiling and potential targeted therapeutic recommendations. This retrospective case series includes all patients reviewed by the MSKCC PMTB from July 2014 to June 2015. Cases were submitted by treating oncologists and potential treatment recommendations were based upon the modified guidelines of the Oxford Centre for Evidence-Based Medicine. There were 41 presentations of 39 individual patients during the study period. Gliomas, acute myeloid leukemia, and neuroblastoma were the most commonly reviewed cases. Thirty nine (87%) of the 45 molecular sequencing profiles utilized hybrid-capture targeted genome sequencing. In 30 (73%) of the 41 presentations, the PMTB provided therapeutic recommendations, of which 19 (46%) were implemented. Twenty-one (70%) of the recommendations involved targeted therapies. Three (14%) targeted therapy recommendations had published evidence to support the proposed recommendations (evidence levels 1-2), eight (36%) recommendations had preclinical evidence (level 3), and 11 (50%) recommendations were based upon hypothetical biological rationales (level 4). The MSKCC PMTB enabled a clinically relevant interpretation of genomic profiling. Effective use of clinical genomics is anticipated to require new and improved tools to ascribe pathogenic significance and therapeutic actionability. The development of specific rule-driven clinical protocols will be needed for the incorporation and evaluation of genomic and molecular profiling in interventional prospective clinical trials. © 2016 Wiley Periodicals, Inc.

Unraveling systematic inventory of Echinops (Asteraceae) with special reference to nrDNA ITS sequence-based molecular typing of Echinops abuzinadianus.

PubMed

Ali, M A; Al-Hemaid, F M; Lee, J; Hatamleh, A A; Gyulai, G; Rahman, M O

2015-10-02

The present study explored the systematic inventory of Echinops L. (Asteraceae) of Saudi Arabia, with special reference to the molecular typing of Echinops abuzinadianus Chaudhary, an endemic species to Saudi Arabia, based on the internal transcribed spacer (ITS) sequences (ITS1-5.8S-ITS2) of nuclear ribosomal DNA. A sequence similarity search using BLAST and a phylogenetic analysis of the ITS sequence of E. abuzinadianus revealed a high level of sequence similarity with E. glaberrimus DC. (section Ritropsis). The novel primary sequence and the secondary structure of ITS2 of E. abuzinadianus could potentially be used for molecular genotyping.

Metabolic Phenotyping Reveals a Lipid Mediator Response to Ionizing Radiation

PubMed Central

2015-01-01

Exposure to ionizing radiation has dramatically increased in modern society, raising serious health concerns. The molecular response to ionizing radiation, however, is still not completely understood. Here, we screened mouse serum for metabolic alterations following an acute exposure to γ radiation using a multiplatform mass-spectrometry-based strategy. A global, molecular profiling revealed that mouse serum undergoes a series of significant molecular alterations following radiation exposure. We identified and quantified bioactive metabolites belonging to key biochemical pathways and low-abundance, oxygenated, polyunsaturated fatty acids (PUFAs) in the two groups of animals. Exposure to γ radiation induced a significant increase in the serum levels of ether phosphatidylcholines (PCs) while decreasing the levels of diacyl PCs carrying PUFAs. In exposed mice, levels of pro-inflammatory, oxygenated metabolites of arachidonic acid increased, whereas levels of anti-inflammatory metabolites of omega-3 PUFAs decreased. Our results indicate a specific serum lipidomic biosignature that could be utilized as an indicator of radiation exposure and as novel target for therapeutic intervention. Monitoring such a molecular response to radiation exposure might have implications not only for radiation pathology but also for countermeasures and personalized medicine. PMID:25126707

A Field-Based Cleaning Protocol for Sampling Devices Used in Life-Detection Studies

NASA Astrophysics Data System (ADS)

Eigenbrode, Jennifer; Benning, Liane G.; Maule, Jake; Wainwright, Norm; Steele, Andrew; Amundsen, Hans E. F.

2009-06-01

Analytical approaches to extant and extinct life detection involve molecular detection often at trace levels. Thus, removal of biological materials and other organic molecules from the surfaces of devices used for sampling is essential for ascertaining meaningful results. Organic decontamination to levels consistent with null values on life-detection instruments is particularly challenging at remote field locations where Mars analog field investigations are carried out. Here, we present a seven-step, multi-reagent decontamination method that can be applied to sampling devices while in the field. In situ lipopolysaccharide detection via low-level endotoxin assays and molecular detection via gas chromatography-mass spectrometry were used to test the effectiveness of the decontamination protocol for sampling of glacial ice with a coring device and for sampling of sediments with a rover scoop during deployment at Arctic Mars-analog sites in Svalbard, Norway. Our results indicate that the protocols and detection technique sufficiently remove and detect low levels of molecular constituents necessary for life-detection tests.

A field-based cleaning protocol for sampling devices used in life-detection studies.

PubMed

Eigenbrode, Jennifer; Benning, Liane G; Maule, Jake; Wainwright, Norm; Steele, Andrew; Amundsen, Hans E F

2009-06-01

Analytical approaches to extant and extinct life detection involve molecular detection often at trace levels. Thus, removal of biological materials and other organic molecules from the surfaces of devices used for sampling is essential for ascertaining meaningful results. Organic decontamination to levels consistent with null values on life-detection instruments is particularly challenging at remote field locations where Mars analog field investigations are carried out. Here, we present a seven-step, multi-reagent decontamination method that can be applied to sampling devices while in the field. In situ lipopolysaccharide detection via low-level endotoxin assays and molecular detection via gas chromatography-mass spectrometry were used to test the effectiveness of the decontamination protocol for sampling of glacial ice with a coring device and for sampling of sediments with a rover scoop during deployment at Arctic Mars-analog sites in Svalbard, Norway. Our results indicate that the protocols and detection technique sufficiently remove and detect low levels of molecular constituents necessary for life-detection tests.

Turning randomness into meaning at the molecular level using Muller's morphs.

PubMed

Henson, Kathleen; Cooper, Melanie M; Klymkowsky, Michael W

2012-04-15

While evolutionary theory follows from observable facts and logical inferences (Mayr, 1985), historically, the origin of novel inheritable variations was a major obstacle to acceptance of natural selection (Bowler, 1992; Bowler, 2005). While molecular mechanisms address this issue (Jablonka and Lamb, 2005), analysis of responses to the Biological Concept Inventory (BCI) (Klymkowsky et al., 2010), revealed that molecular biology majors rarely use molecular level ideas in their discourse, implying that they do not have an accessible framework within which to place evolutionary variation. We developed a "Socratic tutorial" focused on Muller's categorization of mutations' phenotypic effects (Muller, 1932). Using a novel vector-based method to analyzed students' essay responses, we found that a single interaction with this tutorial led to significant changes in thinking toward a clearer articulation of the effects of mutational change. We suggest that Muller's morphs provides an effective framework for facilitating student learning about mutational effects and evolutionary mechanisms.

Impact of surface chemistry

PubMed Central

Somorjai, Gabor A.; Li, Yimin

2011-01-01

The applications of molecular surface chemistry in heterogeneous catalyst technology, semiconductor-based technology, medical technology, anticorrosion and lubricant technology, and nanotechnology are highlighted in this perspective. The evolution of surface chemistry at the molecular level is reviewed, and the key roles of surface instrumentation developments for in situ studies of the gas–solid, liquid–solid, and solid–solid interfaces under reaction conditions are emphasized. PMID:20880833

Molecular Thermometry

PubMed Central

McCabe, Kevin M.; Hernandez, Mark

2010-01-01

Conventional temperature measurements rely on material responses to heat, which can be detected visually. When Galileo developed an air expansion based device to detect temperature changes, Santorio, a contemporary physician, added a scale to create the first thermometer. With this instrument, patients’ temperatures could be measured, recorded and related to changing health conditions. Today, advances in materials science and bioengineering provide new ways to report temperature at the molecular level in real time. In this review the scientific foundations and history of thermometry underpin a discussion of the discoveries emerging from the field of molecular thermometry. Intracellular nanogels and heat sensing biomolecules have been shown to accurately report temperature changes at the nano-scale. Various systems will soon provide the ability to accurately measure temperature changes at the tissue, cellular, and even sub-cellular level, allowing for detection and monitoring of very small changes in local temperature. In the clinic this will lead to enhanced detection of tumors and localized infection, and accurate and precise monitoring of hyperthermia based therapies. Some nanomaterial systems have even demonstrated a theranostic capacity for heat-sensitive, local delivery of chemotherapeutics. Just as early thermometry moved into the clinic, so too will these molecular thermometers. PMID:20139796

Application of single-cell sequencing in human cancer.

PubMed

Rantalainen, Mattias

2017-11-02

Precision medicine is emerging as a cornerstone of future cancer care with the objective of providing targeted therapies based on the molecular phenotype of each individual patient. Traditional bulk-level molecular phenotyping of tumours leads to significant information loss, as the molecular profile represents an average phenotype over large numbers of cells, while cancer is a disease with inherent intra-tumour heterogeneity at the cellular level caused by several factors, including clonal evolution, tissue hierarchies, rare cells and dynamic cell states. Single-cell sequencing provides means to characterize heterogeneity in a large population of cells and opens up opportunity to determine key molecular properties that influence clinical outcomes, including prognosis and probability of treatment response. Single-cell sequencing methods are now reliable enough to be used in many research laboratories, and we are starting to see applications of these technologies for characterization of human primary cancer cells. In this review, we provide an overview of studies that have applied single-cell sequencing to characterize human cancers at the single-cell level, and we discuss some of the current challenges in the field. © The Author 2017. Published by Oxford University Press.

Tungsten nanoparticles influence on radiation protection properties of polymers

NASA Astrophysics Data System (ADS)

Gavrish, V. M.; Baranov, G. A.; Chayka, T. V.; Derbasova, N. M.; Lvov, A. V.; Matsuk, Y. M.

2016-02-01

In the presented article the results of the study of metal-polymer composites based on the ultra-high molecular weight polyethylene GUR 4122 with the addition of superdispersed tungsten nanopowders with 5, 10, 20, 40, and 50 mass percent content levels are given, their thermophysical, radiation-shielding, and mechanical properties are shown, and the influence of content levels of tungsten superdispersed nanopowders on these properties is analyzed. The conducted studies have shown the increase in the listed properties depending on the content level of tungsten superdispersed and nanopowders in the ultra-high molecular weight polyethylene GUR 4122. Owing to their properties, the obtained materials may be used in various fields, such as aviation, space technologies, mechanical engineering, etc.

Integrated Genomic and Network-Based Analyses of Complex Diseases and Human Disease Network.

PubMed

Al-Harazi, Olfat; Al Insaif, Sadiq; Al-Ajlan, Monirah A; Kaya, Namik; Dzimiri, Nduna; Colak, Dilek

2016-06-20

A disease phenotype generally reflects various pathobiological processes that interact in a complex network. The highly interconnected nature of the human protein interaction network (interactome) indicates that, at the molecular level, it is difficult to consider diseases as being independent of one another. Recently, genome-wide molecular measurements, data mining and bioinformatics approaches have provided the means to explore human diseases from a molecular basis. The exploration of diseases and a system of disease relationships based on the integration of genome-wide molecular data with the human interactome could offer a powerful perspective for understanding the molecular architecture of diseases. Recently, subnetwork markers have proven to be more robust and reliable than individual biomarker genes selected based on gene expression profiles alone, and achieve higher accuracy in disease classification. We have applied one of these methodologies to idiopathic dilated cardiomyopathy (IDCM) data that we have generated using a microarray and identified significant subnetworks associated with the disease. In this paper, we review the recent endeavours in this direction, and summarize the existing methodologies and computational tools for network-based analysis of complex diseases and molecular relationships among apparently different disorders and human disease network. We also discuss the future research trends and topics of this promising field. Copyright © 2015 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

A Single-Level Tunnel Model to Account for Electrical Transport through Single Molecule- and Self-Assembled Monolayer-based Junctions

PubMed Central

Garrigues, Alvar R.; Yuan, Li; Wang, Lejia; Mucciolo, Eduardo R.; Thompon, Damien; del Barco, Enrique; Nijhuis, Christian A.

2016-01-01

We present a theoretical analysis aimed at understanding electrical conduction in molecular tunnel junctions. We focus on discussing the validity of coherent versus incoherent theoretical formulations for single-level tunneling to explain experimental results obtained under a wide range of experimental conditions, including measurements in individual molecules connecting the leads of electromigrated single-electron transistors and junctions of self-assembled monolayers (SAM) of molecules sandwiched between two macroscopic contacts. We show that the restriction of transport through a single level in solid state junctions (no solvent) makes coherent and incoherent tunneling formalisms indistinguishable when only one level participates in transport. Similar to Marcus relaxation processes in wet electrochemistry, the thermal broadening of the Fermi distribution describing the electronic occupation energies in the electrodes accounts for the exponential dependence of the tunneling current on temperature. We demonstrate that a single-level tunnel model satisfactorily explains experimental results obtained in three different molecular junctions (both single-molecule and SAM-based) formed by ferrocene-based molecules. Among other things, we use the model to map the electrostatic potential profile in EGaIn-based SAM junctions in which the ferrocene unit is placed at different positions within the molecule, and we find that electrical screening gives rise to a strongly non-linear profile across the junction. PMID:27216489

Biological intuition in alignment-free methods: response to Posada.

PubMed

Ragan, Mark A; Chan, Cheong Xin

2013-08-01

A recent editorial in Journal of Molecular Evolution highlights opportunities and challenges facing molecular evolution in the era of next-generation sequencing. Abundant sequence data should allow more-complex models to be fit at higher confidence, making phylogenetic inference more reliable and improving our understanding of evolution at the molecular level. However, concern that approaches based on multiple sequence alignment may be computationally infeasible for large datasets is driving the development of so-called alignment-free methods for sequence comparison and phylogenetic inference. The recent editorial characterized these approaches as model-free, not based on the concept of homology, and lacking in biological intuition. We argue here that alignment-free methods have not abandoned models or homology, and can be biologically intuitive.

DNA-based species level detection of Glomeromycota: one PCR primer set for all arbuscular mycorrhizal fungi.

PubMed

Krüger, Manuela; Stockinger, Herbert; Krüger, Claudia; Schüssler, Arthur

2009-01-01

* At present, molecular ecological studies of arbuscular mycorrhizal fungi (AMF) are only possible above species level when targeting entire communities. To improve molecular species characterization and to allow species level community analyses in the field, a set of newly designed AMF specific PCR primers was successfully tested. * Nuclear rDNA fragments from diverse phylogenetic AMF lineages were sequenced and analysed to design four primer mixtures, each targeting one binding site in the small subunit (SSU) or large subunit (LSU) rDNA. To allow species resolution, they span a fragment covering the partial SSU, whole internal transcribed spacer (ITS) rDNA region and partial LSU. * The new primers are suitable for specifically amplifying AMF rDNA from material that may be contaminated by other organisms (e.g., samples from pot cultures or the field), characterizing the diversity of AMF species from field samples, and amplifying a SSU-ITS-LSU fragment that allows phylogenetic analyses with species level resolution. * The PCR primers can be used to monitor entire AMF field communities, based on a single rDNA marker region. Their application will improve the base for deep sequencing approaches; moreover, they can be efficiently used as DNA barcoding primers.

Structural and electronic properties of carbon nanotube-reinforced epoxy resins.

PubMed

Suggs, Kelvin; Wang, Xiao-Qian

2010-03-01

Nanocomposites of cured epoxy resin reinforced by single-walled carbon nanotubes exhibit a plethora of interesting behaviors at the molecular level. We have employed a combination of force-field-based molecular mechanics and first-principles calculations to study the corresponding binding and charge-transfer behavior. The simulation study of various nanotube species and curing agent configurations provides insight into the optimal structures in lieu of interfacial stability. An analysis of charge distributions of the epoxy functionalized semiconducting and metallic tubes reveals distinct level hybridizations. The implications of these results for understanding dispersion mechanism and future nano reinforced composite developments are discussed.

Structure of Low-Lying Excited States of Guanine in DNA and Solution: Combined Molecular Mechanics and High-Level Coupled Cluster Studies

DOE PAGES

Kowalski, Karol; Valiev, Marat

2007-01-01

High-level ab-initio equation-of-motion coupled-cluster methods with singles, doubles, and noniterative triples are used, in conjunction with the combined quantum mechanical molecular mechanics approach, to investigate the structure of low-lying excited states of the guanine base in DNA and solvated environments. Our results indicate that while the excitation energy of the first excited state is barely changed compared to its gas-phase counterpart, the excitation energy of the second excited state is blue-shifted by 0.24 eV.

Function-Based Algorithms for Biological Sequences

ERIC Educational Resources Information Center

Mohanty, Pragyan Sheela P.

2015-01-01

Two problems at two different abstraction levels of computational biology are studied. At the molecular level, efficient pattern matching algorithms in DNA sequences are presented. For gene order data, an efficient data structure is presented capable of storing all gene re-orderings in a systematic manner. A common characteristic of presented…

Illustrating the Molecular Origin of Mechanical Stress in Ductile Deformation of Polymer Glasses.

PubMed

Li, Xiaoxiao; Liu, Jianning; Liu, Zhuonan; Tsige, Mesfin; Wang, Shi-Qing

2018-02-16

New experiments show that tensile stress vanishes shortly after preyield deformation of polymer glasses while tensile stress after postyield deformation stays high and relaxes on much longer time scales, thus hinting at a specific molecular origin of stress in ductile cold drawing: chain tension rather than intersegmental interactions. Molecular dynamics simulation based on a coarse-grained model for polystyrene confirms the conclusion that the chain network plays an essential role, causing the glassy state to yield and to respond with a high level of intrachain retractive stress. This identification sheds light on the future development regarding an improved theoretical account for molecular mechanics of polymer glasses and the molecular design of stronger polymeric materials to enhance their mechanical performance.

Illustrating the Molecular Origin of Mechanical Stress in Ductile Deformation of Polymer Glasses

NASA Astrophysics Data System (ADS)

Li, Xiaoxiao; Liu, Jianning; Liu, Zhuonan; Tsige, Mesfin; Wang, Shi-Qing

2018-02-01

New experiments show that tensile stress vanishes shortly after preyield deformation of polymer glasses while tensile stress after postyield deformation stays high and relaxes on much longer time scales, thus hinting at a specific molecular origin of stress in ductile cold drawing: chain tension rather than intersegmental interactions. Molecular dynamics simulation based on a coarse-grained model for polystyrene confirms the conclusion that the chain network plays an essential role, causing the glassy state to yield and to respond with a high level of intrachain retractive stress. This identification sheds light on the future development regarding an improved theoretical account for molecular mechanics of polymer glasses and the molecular design of stronger polymeric materials to enhance their mechanical performance.

Severe childhood asthma and allergy to furry animals: refined assessment using molecular-based allergy diagnostics.

PubMed

Konradsen, Jon R; Nordlund, Björn; Onell, Annica; Borres, Magnus P; Grönlund, Hans; Hedlin, Gunilla

2014-03-01

Allergy to cats and dogs and polysensitization towards these animals are associated with severe childhood asthma. Molecular-based allergy diagnostics offers new opportunities for improved characterization and has been suggested to be particularly useful in patients with polysensitization and/or severe asthma. The aim was to use extract- and molecular-based allergy diagnostics to compare patterns of IgE sensitization towards aeroallergens in children with problematic severe and controlled asthma. Children with a positive ImmunoCAP towards any furry animal (cat, dog or horse) were recruited from a Nationwide Swedish study on severe childhood asthma. Severe (n = 37, age 13 years) and controlled (n = 28, age 14 years) asthmatics underwent assessment of allergic sensitization by ImmunoCap (kUA /l) and immunosolid-phase allergen chip (ISAC). In addition, Asthma Control Test, spirometry and a methacholine challenge were performed. Children with severe asthma had lower asthma control (p < 0.001) and FEV1 (p = 0.001) and more bronchial hyper-responsiveness (p = 0.008) in spite of high doses of inhaled steroids (≥800 μg budesonide). Children with severe asthma displayed higher levels of IgE antibodies towards cat (17 vs. 3.9, p = 0.027), dog (3.8 vs. 1.2, p = 0.012) and horse (7.4 vs. 0.7, p = 0.014). Sensitization towards Can f 2 (22% vs. 0%, p = 0.009) and Equ c 1 (51% vs. 25%, p = 0.03) was more common in severe asthma. IgE levels towards Equ c 1 correlated with asthma control (r = -0.41, p = 0.04). Children with severe allergic asthma had higher sIgE levels to cat, dog and horse. Molecular-based allergy diagnostics revealed a more complex molecular spreading of allergen components in children with the most severe disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Implications of recent research on microstructure modifications, through heat-related processing and trait alteration to bio-functions, molecular thermal stability and mobility, metabolic characteristics and nutrition in cool-climate cereal grains and other types of seeds with advanced molecular techniques.

PubMed

Ying, Yuguang; Zhang, Huihua; Yu, Peiqiang

2018-02-16

The cutting-edge synchrotron radiation based and globar-sourced vibrational infrared microspectroscopy have recently been developed. These novel techniques are able to reveal structure features at cellular and molecular levels with the tested tissues being intact. However, to date, the advanced techniques are unfamiliar or unknown to food and feed scientists and have not been used to study the molecular structure changes in cool-climate cereal grain seeds and other types of bio-oil and bioenergy seeds. This article aims to provide some recent research in cool-climate cereal grains and other types of seeds on molecular structures and metabolic characteristics of carbohydrate and protein, and implication of microstructure modification through heat-related processing and trait alteration to bio-functions, molecular thermal stability and mobility, and nutrition with advanced molecular techniques- synchrotron radiation based and globar-sourced vibrational infrared microspectroscopy in the areas of (1) Inherent microstructure of cereal grain seeds; (2) The nutritional values of cereal grains; (3) Impact and modification of heat-related processing to cereal grain; (4) Conventional nutrition evaluation methodology; (5) Synchrotron radiation-based and globar-sourced vibrational (micro)-spectroscopy for molecular structure study and molecular thermal stability and mobility, and (6) Recent molecular spectroscopic technique applications in research on raw, traits altered and processed cool-climate cereal grains and other types of seeds. The information described in this article gives better insights of research progress and update in cool-climate cereal grains and other seeds with advanced molecular techniques.

Introducing a new methodology for the calculation of local philicity and multiphilic descriptor: an alternative to the finite difference approximation

NASA Astrophysics Data System (ADS)

Sánchez-Márquez, Jesús; Zorrilla, David; García, Víctor; Fernández, Manuel

2018-07-01

This work presents a new development based on the condensation scheme proposed by Chamorro and Pérez, in which new terms to correct the frozen molecular orbital approximation have been introduced (improved frontier molecular orbital approximation). The changes performed on the original development allow taking into account the orbital relaxation effects, providing equivalent results to those achieved by the finite difference approximation and leading also to a methodology with great advantages. Local reactivity indices based on this new development have been obtained for a sample set of molecules and they have been compared with those indices based on the frontier molecular orbital and finite difference approximations. A new definition based on the improved frontier molecular orbital methodology for the dual descriptor index is also shown. In addition, taking advantage of the characteristics of the definitions obtained with the new condensation scheme, the descriptor local philicity is analysed by separating the components corresponding to the frontier molecular orbital approximation and orbital relaxation effects, analysing also the local parameter multiphilic descriptor in the same way. Finally, the effect of using the basis set is studied and calculations using DFT, CI and Möller-Plesset methodologies are performed to analyse the consequence of different electronic-correlation levels.

Anti-inflammatory drugs and prediction of new structures by comparative analysis.

PubMed

Bartzatt, Ronald

2012-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of agents important for their analgesic, anti-inflammatory, and antipyretic properties. This study presents several approaches to predict and elucidate new molecular structures of NSAIDs based on 36 known and proven anti-inflammatory compounds. Based on 36 known NSAIDs the mean value of Log P is found to be 3.338 (standard deviation= 1.237), mean value of polar surface area is 63.176 Angstroms2 (standard deviation = 20.951 A2), and the mean value of molecular weight is 292.665 (standard deviation = 55.627). Nine molecular properties are determined for these 36 NSAID agents, including Log P, number of -OH and -NHn, violations of Rule of 5, number of rotatable bonds, and number of oxygens and nitrogens. Statistical analysis of these nine molecular properties provides numerical parameters to conform to in the design of novel NSAID drug candidates. Multiple regression analysis is accomplished using these properties of 36 agents followed with examples of predicted molecular weight based on minimum and maximum property values. Hierarchical cluster analysis indicated that licofelone, tolfenamic acid, meclofenamic acid, droxicam, and aspirin are substantially distinct from all remaining NSAIDs. Analysis of similarity (ANOSIM) produced R = 0.4947, which indicates low to moderate level of dissimilarity between these 36 NSAIDs. Non-hierarchical K-means cluster analysis separated the 36 NSAIDs into four groups having members of greatest similarity. Likewise, discriminant analysis divided the 36 agents into two groups indicating the greatest level of distinction (discrimination) based on nine properties. These two multivariate methods together provide investigators a means to compare and elucidate novel drug designs to 36 proven compounds and ascertain to which of those are most analogous in pharmacodynamics. In addition, artificial neural network modeling is demonstrated as an approach to predict numerous molecular properties of new drug designs that is based on neural training from 36 proven NSAIDs. Comprehensive and effective approaches are presented in this study for the design of new NSAID type agents which are so very important for inhibition of COX-2 and COX-1 isoenzymes.

Systems Biology Methods for Alzheimer's Disease Research Toward Molecular Signatures, Subtypes, and Stages and Precision Medicine: Application in Cohort Studies and Trials.

PubMed

Castrillo, Juan I; Lista, Simone; Hampel, Harald; Ritchie, Craig W

2018-01-01

Alzheimer's disease (AD) is a complex multifactorial disease, involving a combination of genomic, interactome, and environmental factors, with essential participation of (a) intrinsic genomic susceptibility and (b) a constant dynamic interplay between impaired pathways and central homeostatic networks of nerve cells. The proper investigation of the complexity of AD requires new holistic systems-level approaches, at both the experimental and computational level. Systems biology methods offer the potential to unveil new fundamental insights, basic mechanisms, and networks and their interplay. These may lead to the characterization of mechanism-based molecular signatures, and AD hallmarks at the earliest molecular and cellular levels (and beyond), for characterization of AD subtypes and stages, toward targeted interventions according to the evolving precision medicine paradigm. In this work, an update on advanced systems biology methods and strategies for holistic studies of multifactorial diseases-particularly AD-is presented. This includes next-generation genomics, neuroimaging and multi-omics methods, experimental and computational approaches, relevant disease models, and latest genome editing and single-cell technologies. Their progressive incorporation into basic research, cohort studies, and trials is beginning to provide novel insights into AD essential mechanisms, molecular signatures, and markers toward mechanism-based classification and staging, and tailored interventions. Selected methods which can be applied in cohort studies and trials, with the European Prevention of Alzheimer's Dementia (EPAD) project as a reference example, are presented and discussed.

The emerging genomics and systems biology research lead to systems genomics studies.

PubMed

Yang, Mary Qu; Yoshigoe, Kenji; Yang, William; Tong, Weida; Qin, Xiang; Dunker, A; Chen, Zhongxue; Arbania, Hamid R; Liu, Jun S; Niemierko, Andrzej; Yang, Jack Y

2014-01-01

Synergistically integrating multi-layer genomic data at systems level not only can lead to deeper insights into the molecular mechanisms related to disease initiation and progression, but also can guide pathway-based biomarker and drug target identification. With the advent of high-throughput next-generation sequencing technologies, sequencing both DNA and RNA has generated multi-layer genomic data that can provide DNA polymorphism, non-coding RNA, messenger RNA, gene expression, isoform and alternative splicing information. Systems biology on the other hand studies complex biological systems, particularly systematic study of complex molecular interactions within specific cells or organisms. Genomics and molecular systems biology can be merged into the study of genomic profiles and implicated biological functions at cellular or organism level. The prospectively emerging field can be referred to as systems genomics or genomic systems biology. The Mid-South Bioinformatics Centre (MBC) and Joint Bioinformatics Ph.D. Program of University of Arkansas at Little Rock and University of Arkansas for Medical Sciences are particularly interested in promoting education and research advancement in this prospectively emerging field. Based on past investigations and research outcomes, MBC is further utilizing differential gene and isoform/exon expression from RNA-seq and co-regulation from the ChiP-seq specific for different phenotypes in combination with protein-protein interactions, and protein-DNA interactions to construct high-level gene networks for an integrative genome-phoneme investigation at systems biology level.

Stressing Escherichia coli to educate students about research: A CURE to investigate multiple levels of gene regulation.

PubMed

McDonough, Janet; Goudsouzian, Lara K; Papaj, Agllai; Maceli, Ashley R; Klepac-Ceraj, Vanja; Peterson, Celeste N

2017-09-01

Course-based undergraduate research experiences (CUREs) have been shown to increase student retention and learning in the biological sciences. Most CURES cover only one aspect of gene regulation, such as transcriptional control. Here we present a new inquiry-based lab that engages understanding of gene expression from multiple perspectives. Students carry out a forward genetic screen to identify regulators of the stationary phase master regulator RpoS in the model organism Escherichia coli and then use a series of reporter fusions to determine if the regulation is at the level of transcription or the post-transcription level. This easy-to-implement course has been run both as a 9-week long project and a condensed 5-6 week version in three different schools and types of courses. A majority of the genes found in the screen are novel, thus giving students the opportunity to contribute to original findings to the field. Assessments of this CURE show student gains in learning in many knowledge areas. In addition, attitudinal surveys suggest the students are enthusiastic about the screen and their learning about gene regulation. In summary, this lab would be an appropriate addition to an intermediate or advanced level Molecular Biology, Genetics, or Microbiology curriculum. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(5):449-458, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

Size-dependent single electron transfer and semi-metal-to-insulator transitions in molecular metal oxide electronics

NASA Astrophysics Data System (ADS)

Balliou, Angelika; Bouroushian, Mirtat; Douvas, Antonios M.; Skoulatakis, George; Kennou, Stella; Glezos, Nikos

2018-07-01

All-inorganic self-arranged molecular transition metal oxide hyperstructures based on polyoxometalate molecules (POMs) are fabricated and tested as electronically tunable components in emerging electronic devices. POM hyperstructures reveal great potential as charging nodes of tunable charging level for molecular memories and as enhancers of interfacial electron/hole injection for photovoltaic stacks. STM, UPS, UV–vis spectroscopy and AFM measurements show that this functionality stems from the films’ ability to structurally tune their HOMO–LUMO levels and electron localization length at room temperature. By adapting POM nanocluster size in solution, self-doping and current modulation of four orders of magnitude is monitored on a single nanocluster on SiO2 at voltages as low as 3 Volt. Structurally driven insulator-to-semi-metal transitions and size-dependent current regulation through single electron tunneling are demonstrated and examined with respect to the stereochemical and electronic structure of the molecular entities. This extends the value of self-assembly as a tool for correlation length and electronic properties tuning and demonstrate POM hyperstructures’ plausibility for on-chip molecular electronics operative at room temperature.

Size-dependent single electron transfer and semi-metal-to-insulator transitions in molecular metal oxide electronics.

PubMed

Balliou, Angelika; Bouroushian, Mirtat; Douvas, Antonios M; Skoulatakis, George; Kennou, Stella; Glezos, Nikos

2018-07-06

All-inorganic self-arranged molecular transition metal oxide hyperstructures based on polyoxometalate molecules (POMs) are fabricated and tested as electronically tunable components in emerging electronic devices. POM hyperstructures reveal great potential as charging nodes of tunable charging level for molecular memories and as enhancers of interfacial electron/hole injection for photovoltaic stacks. STM, UPS, UV-vis spectroscopy and AFM measurements show that this functionality stems from the films' ability to structurally tune their HOMO-LUMO levels and electron localization length at room temperature. By adapting POM nanocluster size in solution, self-doping and current modulation of four orders of magnitude is monitored on a single nanocluster on SiO 2 at voltages as low as 3 Volt. Structurally driven insulator-to-semi-metal transitions and size-dependent current regulation through single electron tunneling are demonstrated and examined with respect to the stereochemical and electronic structure of the molecular entities. This extends the value of self-assembly as a tool for correlation length and electronic properties tuning and demonstrate POM hyperstructures' plausibility for on-chip molecular electronics operative at room temperature.

Finding a Potential Dipeptidyl Peptidase-4 (DPP-4) Inhibitor for Type-2 Diabetes Treatment Based on Molecular Docking, Pharmacophore Generation, and Molecular Dynamics Simulation

PubMed Central

Meduru, Harika; Wang, Yeng-Tseng; Tsai, Jeffrey J. P.; Chen, Yu-Ching

2016-01-01

Dipeptidyl peptidase-4 (DPP-4) is the vital enzyme that is responsible for inactivating intestinal peptides glucagon like peptide-1 (GLP-1) and Gastric inhibitory polypeptide (GIP), which stimulates a decline in blood glucose levels. The aim of this study was to explore the inhibition activity of small molecule inhibitors to DPP-4 following a computational strategy based on docking studies and molecular dynamics simulations. The thorough docking protocol we applied allowed us to derive good correlation parameters between the predicted binding affinities (pKi) of the DPP-4 inhibitors and the experimental activity values (pIC50). Based on molecular docking receptor-ligand interactions, pharmacophore generation was carried out in order to identify the binding modes of structurally diverse compounds in the receptor active site. Consideration of the permanence and flexibility of DPP-4 inhibitor complexes by means of molecular dynamics (MD) simulation specified that the inhibitors maintained the binding mode observed in the docking study. The present study helps generate new information for further structural optimization and can influence the development of new DPP-4 inhibitors discoveries in the treatment of type-2 diabetes. PMID:27304951

Finding a Potential Dipeptidyl Peptidase-4 (DPP-4) Inhibitor for Type-2 Diabetes Treatment Based on Molecular Docking, Pharmacophore Generation, and Molecular Dynamics Simulation.

PubMed

Meduru, Harika; Wang, Yeng-Tseng; Tsai, Jeffrey J P; Chen, Yu-Ching

2016-06-13

Dipeptidyl peptidase-4 (DPP-4) is the vital enzyme that is responsible for inactivating intestinal peptides glucagon like peptide-1 (GLP-1) and Gastric inhibitory polypeptide (GIP), which stimulates a decline in blood glucose levels. The aim of this study was to explore the inhibition activity of small molecule inhibitors to DPP-4 following a computational strategy based on docking studies and molecular dynamics simulations. The thorough docking protocol we applied allowed us to derive good correlation parameters between the predicted binding affinities (pKi) of the DPP-4 inhibitors and the experimental activity values (pIC50). Based on molecular docking receptor-ligand interactions, pharmacophore generation was carried out in order to identify the binding modes of structurally diverse compounds in the receptor active site. Consideration of the permanence and flexibility of DPP-4 inhibitor complexes by means of molecular dynamics (MD) simulation specified that the inhibitors maintained the binding mode observed in the docking study. The present study helps generate new information for further structural optimization and can influence the development of new DPP-4 inhibitors discoveries in the treatment of type-2 diabetes.

Statistical inference on censored data for targeted clinical trials under enrichment design.

PubMed

Chen, Chen-Fang; Lin, Jr-Rung; Liu, Jen-Pei

2013-01-01

For the traditional clinical trials, inclusion and exclusion criteria are usually based on some clinical endpoints; the genetic or genomic variability of the trial participants are not totally utilized in the criteria. After completion of the human genome project, the disease targets at the molecular level can be identified and can be utilized for the treatment of diseases. However, the accuracy of diagnostic devices for identification of such molecular targets is usually not perfect. Some of the patients enrolled in targeted clinical trials with a positive result for the molecular target might not have the specific molecular targets. As a result, the treatment effect may be underestimated in the patient population truly with the molecular target. To resolve this issue, under the exponential distribution, we develop inferential procedures for the treatment effects of the targeted drug based on the censored endpoints in the patients truly with the molecular targets. Under an enrichment design, we propose using the expectation-maximization algorithm in conjunction with the bootstrap technique to incorporate the inaccuracy of the diagnostic device for detection of the molecular targets on the inference of the treatment effects. A simulation study was conducted to empirically investigate the performance of the proposed methods. Simulation results demonstrate that under the exponential distribution, the proposed estimator is nearly unbiased with adequate precision, and the confidence interval can provide adequate coverage probability. In addition, the proposed testing procedure can adequately control the size with sufficient power. On the other hand, when the proportional hazard assumption is violated, additional simulation studies show that the type I error rate is not controlled at the nominal level and is an increasing function of the positive predictive value. A numerical example illustrates the proposed procedures. Copyright © 2013 John Wiley & Sons, Ltd.

Stretch or contraction induced inversion of rectification in diblock molecular junctions

NASA Astrophysics Data System (ADS)

Zhang, Guang-Ping; Hu, Gui-Chao; Song, Yang; Xie, Zhen; Wang, Chuan-Kui

2013-09-01

Based on ab initio theory and nonequilibrium Green's function method, the effect of stretch or contraction on the rectification in diblock co-oligomer molecular diodes is investigated theoretically. Interestingly, an inversion of rectifying direction induced by stretching or contracting the molecular junctions, which is closely related to the number of the pyrimidinyl-phenyl units, is proposed. The analysis of the molecular projected self-consistent Hamiltonian and the evolution of the frontier molecular orbitals as well as transmission coefficients under external biases gives an inside view of the observed results. It reveals that the asymmetric molecular level shift and asymmetric evolution of orbital wave functions under biases are competitive mechanisms for rectification. The stretching or contracting induced inversion of the rectification is due to the conversion of the dominant mechanism. This work suggests a feasible technique to manipulate the rectification performance in molecular diodes by use of the mechanically controllable method.

Cryptosporidium Propidium Monoazide-PCR, a Molecular Biology-Based Technique for Genotyping Viable Cryptosporidium Oocysts

EPA Science Inventory

Cryptosporidium is an important waterborne protozoan parasite that can cause severe diarrhea and death in the immunocompromised. Current methods to monitor for Cryptosporidium oocysts in water are microscopy-based USEPA Methods 1622 and 1623. These methods assess total levels o...

Protein mechanics: from single molecules to functional biomaterials.

PubMed

Li, Hongbin; Cao, Yi

2010-10-19

Elastomeric proteins act as the essential functional units in a wide variety of biomechanical machinery and serve as the basic building blocks for biological materials that exhibit superb mechanical properties. These proteins provide the desired elasticity, mechanical strength, resilience, and toughness within these materials. Understanding the mechanical properties of elastomeric protein-based biomaterials is a multiscale problem spanning from the atomistic/molecular level to the macroscopic level. Uncovering the design principles of individual elastomeric building blocks is critical both for the scientific understanding of multiscale mechanics of biomaterials and for the rational engineering of novel biomaterials with desirable mechanical properties. The development of single-molecule force spectroscopy techniques has provided methods for characterizing mechanical properties of elastomeric proteins one molecule at a time. Single-molecule atomic force microscopy (AFM) is uniquely suited to this purpose. Molecular dynamic simulations, protein engineering techniques, and single-molecule AFM study have collectively revealed tremendous insights into the molecular design of single elastomeric proteins, which can guide the design and engineering of elastomeric proteins with tailored mechanical properties. Researchers are focusing experimental efforts toward engineering artificial elastomeric proteins with mechanical properties that mimic or even surpass those of natural elastomeric proteins. In this Account, we summarize our recent experimental efforts to engineer novel artificial elastomeric proteins and develop general and rational methodologies to tune the nanomechanical properties of elastomeric proteins at the single-molecule level. We focus on general design principles used for enhancing the mechanical stability of proteins. These principles include the development of metal-chelation-based general methodology, strategies to control the unfolding hierarchy of multidomain elastomeric proteins, and the design of novel elastomeric proteins that exhibit stimuli-responsive mechanical properties. Moving forward, we are now exploring the use of these artificial elastomeric proteins as building blocks of protein-based biomaterials. Ultimately, we would like to rationally tailor mechanical properties of elastomeric protein-based materials by programming the molecular sequence, and thus nanomechanical properties, of elastomeric proteins at the single-molecule level. This step would help bridge the gap between single protein mechanics and material biomechanics, revealing how the mechanical properties of individual elastomeric proteins are translated into the properties of macroscopic materials.

Perspective: Reaches of chemical physics in biology.

PubMed

Gruebele, Martin; Thirumalai, D

2013-09-28

Chemical physics as a discipline contributes many experimental tools, algorithms, and fundamental theoretical models that can be applied to biological problems. This is especially true now as the molecular level and the systems level descriptions begin to connect, and multi-scale approaches are being developed to solve cutting edge problems in biology. In some cases, the concepts and tools got their start in non-biological fields, and migrated over, such as the idea of glassy landscapes, fluorescence spectroscopy, or master equation approaches. In other cases, the tools were specifically developed with biological physics applications in mind, such as modeling of single molecule trajectories or super-resolution laser techniques. In this introduction to the special topic section on chemical physics of biological systems, we consider a wide range of contributions, all the way from the molecular level, to molecular assemblies, chemical physics of the cell, and finally systems-level approaches, based on the contributions to this special issue. Chemical physicists can look forward to an exciting future where computational tools, analytical models, and new instrumentation will push the boundaries of biological inquiry.

Perspective: Reaches of chemical physics in biology

PubMed Central

Gruebele, Martin; Thirumalai, D.

2013-01-01

Chemical physics as a discipline contributes many experimental tools, algorithms, and fundamental theoretical models that can be applied to biological problems. This is especially true now as the molecular level and the systems level descriptions begin to connect, and multi-scale approaches are being developed to solve cutting edge problems in biology. In some cases, the concepts and tools got their start in non-biological fields, and migrated over, such as the idea of glassy landscapes, fluorescence spectroscopy, or master equation approaches. In other cases, the tools were specifically developed with biological physics applications in mind, such as modeling of single molecule trajectories or super-resolution laser techniques. In this introduction to the special topic section on chemical physics of biological systems, we consider a wide range of contributions, all the way from the molecular level, to molecular assemblies, chemical physics of the cell, and finally systems-level approaches, based on the contributions to this special issue. Chemical physicists can look forward to an exciting future where computational tools, analytical models, and new instrumentation will push the boundaries of biological inquiry. PMID:24089712

Novel view on the mechanism of water-assisted proton transfer in the DNA bases: bulk water hydration.

PubMed

Furmanchuk, Al'ona; Isayev, Olexandr; Gorb, Leonid; Shishkin, Oleg V; Hovorun, Dmytro M; Leszczynski, Jerzy

2011-03-14

In the present work, the conventional static ab initio picture of a water-assisted mechanism of the tautomerization of Nucleic Acid Bases (NABs) in an aqueous environment is enhanced by the classical and Car-Parrinello molecular dynamics simulations. The inclusion of the dynamical contribution is vital because the formation and longevity of the NAB-water bridge complexes represent decisive factors for further tautomerization. The results of both molecular dynamic techniques indicate that the longest time when such complexes exist is significantly shorter than the time required for proton transfer suggested by the static ab initio level of theory. New rate constants of tautomerization corrected for the dynamic effect of environment are proposed based on the first principles molecular dynamics data. Those values are used for the evaluation of a water-assisted mechanism that is feasible in such biological systems as E. coli cell.

Design of two and three input molecular logic gates using non-Watson-Crick base pairing-based molecular beacons.

PubMed

Lin, Jia-Hui; Tseng, Wei-Lung

2014-03-21

This study presents a single, resettable, and sensitive molecular beacon (MB) used to operate molecular-scale logic gates. The MB consists of a random DNA sequence, a fluorophore at the 5'-end, and a quencher at the 3'-end. The presence of Hg(2+), Ag(+), and coralyne promoted the formation of stable T-Hg(2+)-T, C-Ag(+)-C, and A2-coralyne-A2 coordination in the MB probe, respectively, thereby driving its conformational change. The metal ion or small molecule-mediated coordination of mismatched DNA brought the fluorophore and the quencher into close proximity, resulting in collisional quenching of fluorescence between the two organic dyes. Because thiol can bind Hg(2+) and remove it from the T-Hg(2+)-T-based MB, adding thiol to a solution of the T-Hg(2+)-T-based MB allowed the fluorophore and the quencher to be widely separated. A similar phenomenon was observed when replacing Hg(2+) with Ag(+). Because Ag(+) strongly binds to iodide, cyanide, and cysteine, they were capable of removing Ag(+) from the C-Ag(+)-C-based MB, restoring the fluorescence of the MB. Moreover, the fluorescence of the A2-coralyne-A2-based MB could be switched on by adding polyadenosine. Using these analytes as inputs and the MB as a signal transducer, we successfully developed a series of two-input, three-input, and set-reset logic gates at the molecular level.

Simulational nanoengineering: Molecular dynamics implementation of an atomistic Stirling engine.

PubMed

Rapaport, D C

2009-04-01

A nanoscale-sized Stirling engine with an atomistic working fluid has been modeled using molecular dynamics simulation. The design includes heat exchangers based on thermostats, pistons attached to a flywheel under load, and a regenerator. Key aspects of the behavior, including the time-dependent flows, are described. The model is shown to be capable of stable operation while producing net work at a moderate level of efficiency.

Student Misapplication of a Gas-Like Model to Explain Particle Movement in Heated Solids: Implications for Curriculum and Instruction towards Students' Creation and Revision of Accurate Explanatory Models

ERIC Educational Resources Information Center

Bouwma-Gearhart, Jana; Stewart, James; Brown, Keffrelyn

2009-01-01

Understanding the particulate nature of matter (PNM) is vital for participating in many areas of science. We assessed 11 students' atomic/molecular-level explanations of real-world phenomena after their participation in a modelling-based PNM unit. All 11 students offered a scientifically acceptable model regarding atomic/molecular behaviour in…

[Genetic variation of geographical provenance of Pinus massoniana--review and analysis].

PubMed

Li, D; Peng, S

2000-04-01

Pinus massoniana is a significant tree species constituting the subtropical forests in China. Based on morphological, physio-ecological, chromosome, and molecular levels, the genetic variation of geographical provenance of P. massoniana and its distribution were reviewed, and the methodologies on genetic diversity and the genetic variation patterns of geographical provenance of P. massoniana were synthetically analyzed. The Key problems on molecular ecology of P. massoniana were discussed.

Conceptual Model-Based Systems Biology: Mapping Knowledge and Discovering Gaps in the mRNA Transcription Cycle

PubMed Central

Somekh, Judith; Choder, Mordechai; Dori, Dov

2012-01-01

We propose a Conceptual Model-based Systems Biology framework for qualitative modeling, executing, and eliciting knowledge gaps in molecular biology systems. The framework is an adaptation of Object-Process Methodology (OPM), a graphical and textual executable modeling language. OPM enables concurrent representation of the system's structure—the objects that comprise the system, and behavior—how processes transform objects over time. Applying a top-down approach of recursively zooming into processes, we model a case in point—the mRNA transcription cycle. Starting with this high level cell function, we model increasingly detailed processes along with participating objects. Our modeling approach is capable of modeling molecular processes such as complex formation, localization and trafficking, molecular binding, enzymatic stimulation, and environmental intervention. At the lowest level, similar to the Gene Ontology, all biological processes boil down to three basic molecular functions: catalysis, binding/dissociation, and transporting. During modeling and execution of the mRNA transcription model, we discovered knowledge gaps, which we present and classify into various types. We also show how model execution enhances a coherent model construction. Identification and pinpointing knowledge gaps is an important feature of the framework, as it suggests where research should focus and whether conjectures about uncertain mechanisms fit into the already verified model. PMID:23308089

Supramolecular chemistry: from molecular information towards self-organization and complex matter

NASA Astrophysics Data System (ADS)

Lehn, Jean-Marie

2004-03-01

Molecular chemistry has developed a wide range of very powerful procedures for constructing ever more sophisticated molecules from atoms linked by covalent bonds. Beyond molecular chemistry lies supramolecular chemistry, which aims at developing highly complex chemical systems from components interacting via non-covalent intermolecular forces. By the appropriate manipulation of these interactions, supramolecular chemistry became progressively the chemistry of molecular information, involving the storage of information at the molecular level, in the structural features, and its retrieval, transfer, and processing at the supramolecular level, through molecular recognition processes operating via specific interactional algorithms. This has paved the way towards apprehending chemistry also as an information science. Numerous receptors capable of recognizing, i.e. selectively binding, specific substrates have been developed, based on the molecular information stored in the interacting species. Suitably functionalized receptors may perform supramolecular catalysis and selective transport processes. In combination with polymolecular organization, recognition opens ways towards the design of molecular and supramolecular devices based on functional (photoactive, electroactive, ionoactive, etc) components. A step beyond preorganization consists in the design of systems undergoing self-organization, i.e. systems capable of spontaneously generating well-defined supramolecular architectures by self-assembly from their components. Self-organization processes, directed by the molecular information stored in the components and read out at the supramolecular level through specific interactions, represent the operation of programmed chemical systems. They have been implemented for the generation of a variety of discrete functional architectures of either organic or inorganic nature. Self-organization processes also give access to advanced supramolecular materials, such as supramolecular polymers and liquid crystals, and provide an original approach to nanoscience and nanotechnology. In particular, the spontaneous but controlled generation of well-defined, functional supramolecular architectures of nanometric size through self-organization represents a means of performing programmed engineering and processing of nanomaterials. Supramolecular chemistry is intrinsically a dynamic chemistry, in view of the lability of the interactions connecting the molecular components of a supramolecular entity and the resulting ability of supramolecular species to exchange their constituents. The same holds for molecular chemistry when a molecular entity contains covalent bonds that may form and break reversibly, so as to make possible a continuous change in constitution and structure by reorganization and exchange of building blocks. This behaviour defines a constitutional dynamic chemistry that allows self-organization by selection as well as by design at both the molecular and supramolecular levels. Whereas self-organization by design strives to achieve full control over the output molecular or supramolecular entity by explicit programming, self-organization by selection operates on dynamic constitutional diversity in response to either internal or external factors to achieve adaptation in a Darwinistic fashion. The merging of the features, information and programmability, dynamics and reversibility, constitution and structural diversity, points towards the emergence of adaptative and evolutionary chemistry. Together with the corresponding fields of physics and biology, it constitutes a science of informed matter, of organized, adaptative complex matter. This article was originally published in 2003 by the Israel Academy of Sciences and Humanities in the framework of its Albert Einstein Memorial Lectures series. Reprinted by permission of the Israel Academy of Sciences and Humanities.

Quantitative molecular analysis in mantle cell lymphoma.

PubMed

Brízová, H; Hilská, I; Mrhalová, M; Kodet, R

2011-07-01

A molecular analysis has three major roles in modern oncopathology--as an aid in the differential diagnosis, in molecular monitoring of diseases, and in estimation of the potential prognosis. In this report we review the application of the molecular analysis in a group of patients with mantle cell lymphoma (MCL). We demonstrate that detection of the cyclin D1 mRNA level is a molecular marker in 98% of patients with MCL. Cyclin D1 quantitative monitoring is specific and sensitive for the differential diagnosis and for the molecular monitoring of the disease in the bone marrow. Moreover, the dynamics of cyclin D1 in bone marrow reflects the disease development and it predicts the clinical course. We employed the molecular analysis for a precise quantitative detection of proliferation markers, Ki-67, topoisomerase IIalpha, and TPX2, that are described as effective prognostic factors. Using the molecular approach it is possible to measure the proliferation rate in a reproducible, standard way which is an essential prerequisite for using the proliferation activity as a routine clinical tool. Comparing with immunophenotyping we may conclude that the quantitative PCR-based analysis is a useful, reliable, rapid, reproducible, sensitive and specific method broadening our diagnostic tools in hematopathology. In comparison to interphase FISH in paraffin sections quantitative PCR is less technically demanding and less time-consuming and furthermore it is more sensitive in detecting small changes in the mRNA level. Moreover, quantitative PCR is the only technology which provides precise and reproducible quantitative information about the expression level. Therefore it may be used to demonstrate the decrease or increase of a tumor-specific marker in bone marrow in comparison with a previously aspirated specimen. Thus, it has a powerful potential to monitor the course of the disease in correlation with clinical data.

Si-doping bone composite based on protein template-mediated assembly for enhancing bone regeneration

NASA Astrophysics Data System (ADS)

Yang, Qin; Du, Yingying; Wang, Yifan; Wang, Zhiying; Ma, Jun; Wang, Jianglin; Zhang, Shengmin

2017-06-01

Bio-inspired hybrid materials that contain organic and inorganic networks interpenetration at the molecular level have been a particular focus of interest on designing novel nanoscale composites. Here we firstly synthesized a series of hybrid bone composites, silicon-hydroxyapatites/silk fibroin/collagen, based on a specific molecular assembled strategy. Results of material characterization confirmed that silicate had been successfully doped into nano-hydroxyapatite lattice. In vitro evaluation at the cellular level clearly showed that these Si-doped composites were capable of promoting the adhesion and proliferation of rat mesenchymal stem cells (rMSCs), extremely enhancing osteoblastic differentiation of rMSCs compared with silicon-free composite. More interestingly, we found there was a critical point of silicon content in the composition on regulating multiple cell behaviors. In vivo animal evaluation further demonstrated that Si-doped composites enabled to significantly improve the repair of cranial bone defect. Consequently, our current work not only suggests fabricating a potential bone repair materials by integrating element-doping and molecular assembled strategy in one system, but also paves a new way for constructing multi-functional composite materials in the future.

MIDG-Emerging grid technologies for multi-site preclinical molecular imaging research communities.

PubMed

Lee, Jasper; Documet, Jorge; Liu, Brent; Park, Ryan; Tank, Archana; Huang, H K

2011-03-01

Molecular imaging is the visualization and identification of specific molecules in anatomy for insight into metabolic pathways, tissue consistency, and tracing of solute transport mechanisms. This paper presents the Molecular Imaging Data Grid (MIDG) which utilizes emerging grid technologies in preclinical molecular imaging to facilitate data sharing and discovery between preclinical molecular imaging facilities and their collaborating investigator institutions to expedite translational sciences research. Grid-enabled archiving, management, and distribution of animal-model imaging datasets help preclinical investigators to monitor, access and share their imaging data remotely, and promote preclinical imaging facilities to share published imaging datasets as resources for new investigators. The system architecture of the Molecular Imaging Data Grid is described in a four layer diagram. A data model for preclinical molecular imaging datasets is also presented based on imaging modalities currently used in a molecular imaging center. The MIDG system components and connectivity are presented. And finally, the workflow steps for grid-based archiving, management, and retrieval of preclincial molecular imaging data are described. Initial performance tests of the Molecular Imaging Data Grid system have been conducted at the USC IPILab using dedicated VMware servers. System connectivity, evaluated datasets, and preliminary results are presented. The results show the system's feasibility, limitations, direction of future research. Translational and interdisciplinary research in medicine is increasingly interested in cellular and molecular biology activity at the preclinical levels, utilizing molecular imaging methods on animal models. The task of integrated archiving, management, and distribution of these preclinical molecular imaging datasets at preclinical molecular imaging facilities is challenging due to disparate imaging systems and multiple off-site investigators. A Molecular Imaging Data Grid design, implementation, and initial evaluation is presented to demonstrate the secure and novel data grid solution for sharing preclinical molecular imaging data across the wide-area-network (WAN).

Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer.

PubMed

Hoadley, Katherine A; Yau, Christina; Hinoue, Toshinori; Wolf, Denise M; Lazar, Alexander J; Drill, Esther; Shen, Ronglai; Taylor, Alison M; Cherniack, Andrew D; Thorsson, Vésteinn; Akbani, Rehan; Bowlby, Reanne; Wong, Christopher K; Wiznerowicz, Maciej; Sanchez-Vega, Francisco; Robertson, A Gordon; Schneider, Barbara G; Lawrence, Michael S; Noushmehr, Houtan; Malta, Tathiane M; Stuart, Joshua M; Benz, Christopher C; Laird, Peter W

2018-04-05

We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. We performed molecular clustering using data on chromosome-arm-level aneuploidy, DNA hypermethylation, mRNA, and miRNA expression levels and reverse-phase protein arrays, of which all, except for aneuploidy, revealed clustering primarily organized by histology, tissue type, or anatomic origin. The influence of cell type was evident in DNA-methylation-based clustering, even after excluding sites with known preexisting tissue-type-specific methylation. Integrative clustering further emphasized the dominant role of cell-of-origin patterns. Molecular similarities among histologically or anatomically related cancer types provide a basis for focused pan-cancer analyses, such as pan-gastrointestinal, pan-gynecological, pan-kidney, and pan-squamous cancers, and those related by stemness features, which in turn may inform strategies for future therapeutic development. Copyright © 2018 Elsevier Inc. All rights reserved.

Turning randomness into meaning at the molecular level using Muller's morphs

PubMed Central

Henson, Kathleen; Cooper, Melanie M.; Klymkowsky, Michael W.

2012-01-01

Summary While evolutionary theory follows from observable facts and logical inferences (Mayr, 1985), historically, the origin of novel inheritable variations was a major obstacle to acceptance of natural selection (Bowler, 1992; Bowler, 2005). While molecular mechanisms address this issue (Jablonka and Lamb, 2005), analysis of responses to the Biological Concept Inventory (BCI) (Klymkowsky et al., 2010), revealed that molecular biology majors rarely use molecular level ideas in their discourse, implying that they do not have an accessible framework within which to place evolutionary variation. We developed a “Socratic tutorial” focused on Muller's categorization of mutations' phenotypic effects (Muller, 1932). Using a novel vector-based method to analyzed students' essay responses, we found that a single interaction with this tutorial led to significant changes in thinking toward a clearer articulation of the effects of mutational change. We suggest that Muller's morphs provides an effective framework for facilitating student learning about mutational effects and evolutionary mechanisms. PMID:23213431

Interface electronic structures of reversible double-docking self-assembled monolayers on an Au(111) surface

PubMed Central

Zhang, Tian; Ma, Zhongyun; Wang, Linjun; Xi, Jinyang; Shuai, Zhigang

2014-01-01

Double-docking self-assembled monolayers (DDSAMs), namely self-assembled monolayers (SAMs) formed by molecules possessing two docking groups, provide great flexibility to tune the work function of metal electrodes and the tunnelling barrier between metal electrodes and the SAMs, and thus offer promising applications in both organic and molecular electronics. Based on the dispersion-corrected density functional theory (DFT) in comparison with conventional DFT, we carry out a systematic investigation on the dual configurations of a series of DDSAMs on an Au(111) surface. Through analysing the interface electronic structures, we obtain the relationship between single molecular properties and the SAM-induced work-function modification as well as the level alignment between the metal Fermi level and molecular frontier states. The two possible conformations of one type of DDSAM on a metal surface reveal a strong difference in the work-function modification and the electron/hole tunnelling barriers. Fermi-level pinning is found to be a key factor to understand the interface electronic properties. PMID:24615153

Correlation dynamics and enhanced signals for the identification of serial biomolecules and DNA bases.

PubMed

Ahmed, Towfiq; Haraldsen, Jason T; Rehr, John J; Di Ventra, Massimiliano; Schuller, Ivan; Balatsky, Alexander V

2014-03-28

Nanopore-based sequencing has demonstrated a significant potential for the development of fast, accurate, and cost-efficient fingerprinting techniques for next generation molecular detection and sequencing. We propose a specific multilayered graphene-based nanopore device architecture for the recognition of single biomolecules. Molecular detection and analysis can be accomplished through the detection of transverse currents as the molecule or DNA base translocates through the nanopore. To increase the overall signal-to-noise ratio and the accuracy, we implement a new 'multi-point cross-correlation' technique for identification of DNA bases or other molecules on the single molecular level. We demonstrate that the cross-correlations between each nanopore will greatly enhance the transverse current signal for each molecule. We implement first-principles transport calculations for DNA bases surveyed across a multilayered graphene nanopore system to illustrate the advantages of the proposed geometry. A time-series analysis of the cross-correlation functions illustrates the potential of this method for enhancing the signal-to-noise ratio. This work constitutes a significant step forward in facilitating fingerprinting of single biomolecules using solid state technology.

Network-based integration of systems genetics data reveals pathways associated with lignocellulosic biomass accumulation and processing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mizrachi, Eshchar; Verbeke, Lieven; Christie, Nanette

As a consequence of their remarkable adaptability, fast growth, and superior wood properties, eucalypt tree plantations have emerged as key renewable feedstocks (over 20 million ha globally) for the production of pulp, paper, bioenergy, and other lignocellulosic products. However, most biomass properties such as growth, wood density, and wood chemistry are complex traits that are hard to improve in long-lived perennials. Systems genetics, a process of harnessing multiple levels of component trait information (e.g., transcript, protein, and metabolite variation) in populations that vary in complex traits, has proven effective for dissecting the genetics and biology of such traits. We havemore » applied a network-based data integration (NBDI) method for a systems-level analysis of genes, processes and pathways underlying biomass and bioenergy-related traits using a segregating Eucalyptus hybrid population. We show that the integrative approach can link biologically meaningful sets of genes to complex traits and at the same time reveal the molecular basis of trait variation. Gene sets identified for related woody biomass traits were found to share regulatory loci, cluster in network neighborhoods, and exhibit enrichment for molecular functions such as xylan metabolism and cell wall development. These findings offer a framework for identifying the molecular underpinnings of complex biomass and bioprocessing-related traits. Furthermore, a more thorough understanding of the molecular basis of plant biomass traits should provide additional opportunities for the establishment of a sustainable bio-based economy.« less

Network-based integration of systems genetics data reveals pathways associated with lignocellulosic biomass accumulation and processing

DOE PAGES

Mizrachi, Eshchar; Verbeke, Lieven; Christie, Nanette; ...

2017-01-17

As a consequence of their remarkable adaptability, fast growth, and superior wood properties, eucalypt tree plantations have emerged as key renewable feedstocks (over 20 million ha globally) for the production of pulp, paper, bioenergy, and other lignocellulosic products. However, most biomass properties such as growth, wood density, and wood chemistry are complex traits that are hard to improve in long-lived perennials. Systems genetics, a process of harnessing multiple levels of component trait information (e.g., transcript, protein, and metabolite variation) in populations that vary in complex traits, has proven effective for dissecting the genetics and biology of such traits. We havemore » applied a network-based data integration (NBDI) method for a systems-level analysis of genes, processes and pathways underlying biomass and bioenergy-related traits using a segregating Eucalyptus hybrid population. We show that the integrative approach can link biologically meaningful sets of genes to complex traits and at the same time reveal the molecular basis of trait variation. Gene sets identified for related woody biomass traits were found to share regulatory loci, cluster in network neighborhoods, and exhibit enrichment for molecular functions such as xylan metabolism and cell wall development. These findings offer a framework for identifying the molecular underpinnings of complex biomass and bioprocessing-related traits. Furthermore, a more thorough understanding of the molecular basis of plant biomass traits should provide additional opportunities for the establishment of a sustainable bio-based economy.« less

Network-based integration of systems genetics data reveals pathways associated with lignocellulosic biomass accumulation and processing.

PubMed

Mizrachi, Eshchar; Verbeke, Lieven; Christie, Nanette; Fierro, Ana C; Mansfield, Shawn D; Davis, Mark F; Gjersing, Erica; Tuskan, Gerald A; Van Montagu, Marc; Van de Peer, Yves; Marchal, Kathleen; Myburg, Alexander A

2017-01-31

As a consequence of their remarkable adaptability, fast growth, and superior wood properties, eucalypt tree plantations have emerged as key renewable feedstocks (over 20 million ha globally) for the production of pulp, paper, bioenergy, and other lignocellulosic products. However, most biomass properties such as growth, wood density, and wood chemistry are complex traits that are hard to improve in long-lived perennials. Systems genetics, a process of harnessing multiple levels of component trait information (e.g., transcript, protein, and metabolite variation) in populations that vary in complex traits, has proven effective for dissecting the genetics and biology of such traits. We have applied a network-based data integration (NBDI) method for a systems-level analysis of genes, processes and pathways underlying biomass and bioenergy-related traits using a segregating Eucalyptus hybrid population. We show that the integrative approach can link biologically meaningful sets of genes to complex traits and at the same time reveal the molecular basis of trait variation. Gene sets identified for related woody biomass traits were found to share regulatory loci, cluster in network neighborhoods, and exhibit enrichment for molecular functions such as xylan metabolism and cell wall development. These findings offer a framework for identifying the molecular underpinnings of complex biomass and bioprocessing-related traits. A more thorough understanding of the molecular basis of plant biomass traits should provide additional opportunities for the establishment of a sustainable bio-based economy.

Simulating Energy Relaxation in Pump-Probe Vibrational Spectroscopy of Hydrogen-Bonded Liquids.

PubMed

Dettori, Riccardo; Ceriotti, Michele; Hunger, Johannes; Melis, Claudio; Colombo, Luciano; Donadio, Davide

2017-03-14

We introduce a nonequilibrium molecular dynamics simulation approach, based on the generalized Langevin equation, to study vibrational energy relaxation in pump-probe spectroscopy. A colored noise thermostat is used to selectively excite a set of vibrational modes, leaving the other modes nearly unperturbed, to mimic the effect of a monochromatic laser pump. Energy relaxation is probed by analyzing the evolution of the system after excitation in the microcanonical ensemble, thus providing direct information about the energy redistribution paths at the molecular level and their time scale. The method is applied to hydrogen-bonded molecular liquids, specifically deuterated methanol and water, providing a robust picture of energy relaxation at the molecular scale.

Differentiating high priority pathway-based toxicity from non-specific effects in high throughput toxicity data: A foundation for prioritizing AOP development.

EPA Science Inventory

The ToxCast chemical screening approach enables the rapid assessment of large numbers of chemicals for biological effects, primarily at the molecular level. Adverse outcome pathways (AOPs) offer a means to link biomolecular effects with potential adverse outcomes at the level of...

Understanding Chemical Reaction Kinetics and Equilibrium with Interlocking Building Blocks

ERIC Educational Resources Information Center

Cloonan, Carrie A.; Nichol, Carolyn A.; Hutchinson, John S.

2011-01-01

Chemical reaction kinetics and equilibrium are essential core concepts of chemistry but are challenging topics for many students, both at the high school and undergraduate university level. Visualization at the molecular level is valuable to aid understanding of reaction kinetics and equilibrium. This activity provides a discovery-based method to…

Using yeast to determine the functional consequences of mutations in the human p53 tumor suppressor gene: An introductory course-based undergraduate research experience in molecular and cell biology.

PubMed

Hekmat-Scafe, Daria S; Brownell, Sara E; Seawell, Patricia Chandler; Malladi, Shyamala; Imam, Jamie F Conklin; Singla, Veena; Bradon, Nicole; Cyert, Martha S; Stearns, Tim

2017-03-04

The opportunity to engage in scientific research is an important, but often neglected, component of undergraduate training in biology. We describe the curriculum for an innovative, course-based undergraduate research experience (CURE) appropriate for a large, introductory cell and molecular biology laboratory class that leverages students' high level of interest in cancer. The course is highly collaborative and emphasizes the analysis and interpretation of original scientific data. During the course, students work in teams to characterize a collection of mutations in the human p53 tumor suppressor gene via expression and analysis in yeast. Initially, student pairs use both qualitative and quantitative assays to assess the ability of their p53 mutant to activate expression of reporter genes, and they localize their mutation within the p53 structure. Through facilitated discussion, students suggest possible molecular explanations for the transactivation defects displayed by their p53 mutants and propose experiments to test these hypotheses that they execute during the second part of the course. They use a western blot to determine whether mutant p53 levels are reduced, a DNA-binding assay to test whether recognition of any of three p53 target sequences is compromised, and fluorescence microscopy to assay nuclear localization. Students studying the same p53 mutant periodically convene to discuss and interpret their combined data. The course culminates in a poster session during which students present their findings to peers, instructors, and the greater biosciences community. Based on our experience, we provide recommendations for the development of similar large introductory lab courses. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(2):161-178, 2017. © 2016 The International Union of Biochemistry and Molecular Biology.

Computational Investigation of the pH Dependence of Loop Flexibility and Catalytic Function in Glycoside Hydrolases*

PubMed Central

Bu, Lintao; Crowley, Michael F.; Himmel, Michael E.; Beckham, Gregg T.

2013-01-01

Cellulase enzymes cleave glycosidic bonds in cellulose to produce cellobiose via either retaining or inverting hydrolysis mechanisms, which are significantly pH-dependent. Many fungal cellulases function optimally at pH ∼5, and their activities decrease dramatically at higher or lower pH. To understand the molecular-level implications of pH in cellulase structure, we use a hybrid, solvent-based, constant pH molecular dynamics method combined with pH-based replica exchange to determine the pKa values of titratable residues of a glycoside hydrolase (GH) family 6 cellobiohydrolase (Cel6A) and a GH family 7 cellobiohydrolase (Cel7A) from the fungus Hypocrea jecorina. For both enzymes, we demonstrate that a bound substrate significantly affects the pKa values of the acid residues at the catalytic center. The calculated pKa values of catalytic residues confirm their proposed roles from structural studies and are consistent with the experimentally measured apparent pKa values. Additionally, GHs are known to impart a strained pucker conformation in carbohydrate substrates in active sites for catalysis, and results from free energy calculations combined with constant pH molecular dynamics suggest that the correct ring pucker is stable near the optimal pH for both Cel6A and Cel7A. Much longer molecular dynamics simulations of Cel6A and Cel7A with fixed protonation states based on the calculated pKa values suggest that pH affects the flexibility of tunnel loops, which likely affects processivity and substrate complexation. Taken together, this work demonstrates several molecular-level effects of pH on GH enzymes important for cellulose turnover in the biosphere and relevant to biomass conversion processes. PMID:23504310

Watson-Crick Base Pair Radical Cation as a Model for Oxidative Damage in DNA.

PubMed

Feketeová, Linda; Chan, Bun; Khairallah, George N; Steinmetz, Vincent; Maitre, Philippe; Radom, Leo; O'Hair, Richard A J

2017-07-06

The deleterious cellular effects of ionizing radiation are well-known, but the mechanisms causing DNA damage are poorly understood. The accepted molecular events involve initial oxidation and deprotonation at guanine sites, triggering hydrogen atom abstraction reactions from the sugar moieties, causing DNA strand breaks. Probing the chemistry of the initially formed radical cation has been challenging. Here, we generate, spectroscopically characterize, and examine the reactivity of the Watson-Crick nucleobase pair radical cation in the gas phase. We observe rich chemistry, including proton transfer between the bases and propagation of the radical site in deoxyguanosine from the base to the sugar, thus rupturing the sugar. This first example of a gas-phase model system providing molecular-level details on the chemistry of an ionized DNA base pair paves the way toward a more complete understanding of molecular processes induced by radiation. It also highlights the role of radical propagation in chemistry, biology, and nanotechnology.

Molecular Antimicrobial Resistance Surveillance for Neisseria gonorrhoeae, Northern Territory, Australia.

PubMed

Whiley, David M; Trembizki, Ella; Buckley, Cameron; Freeman, Kevin; Baird, Robert W; Beaman, Miles; Chen, Marcus; Donovan, Basil; Kundu, Ratan L; Fairley, Christopher K; Guy, Rebecca; Hogan, Tiffany; Kaldor, John M; Karimi, Mahdad; Limnios, Athena; Regan, David G; Ryder, Nathan; Su, Jiunn-Yih; Ward, James; Lahra, Monica M

2017-09-01

Neisseria gonorrhoeae antimicrobial resistance (AMR) is a globally recognized health threat; new strategies are needed to enhance AMR surveillance. The Northern Territory of Australia is unique in that 2 different first-line therapies, based primarily on geographic location, are used for gonorrhea treatment. We tested 1,629 N. gonorrhoeae nucleic acid amplification test-positive clinical samples, collected from regions where ceftriaxone plus azithromycin or amoxicillin plus azithromycin are recommended first-line treatments, by using 8 N. gonorrhoeae AMR PCR assays. We compared results with those from routine culture-based surveillance data. PCR data confirmed an absence of ceftriaxone resistance and a low level of azithromycin resistance (0.2%), and that penicillin resistance was <5% in amoxicillin plus azithromycin regions. Rates of ciprofloxacin resistance and penicillinase-producing N. gonorrhoeae were lower when molecular methods were used. Molecular methods to detect N. gonorrhoeae AMR can increase the evidence base for treatment guidelines, particularly in settings where culture-based surveillance is limited.

Contributions to advances in blend pellet products (BPP) research on molecular structure and molecular nutrition interaction by advanced synchrotron and globar molecular (Micro)spectroscopy.

PubMed

Guevara-Oquendo, Víctor H; Zhang, Huihua; Yu, Peiqiang

2018-04-13

To date, advanced synchrotron-based and globar-sourced techniques are almost unknown to food and feed scientists. There has been little application of these advanced techniques to study blend pellet products at a molecular level. This article aims to provide recent research on advanced synchrotron and globar vibrational molecular spectroscopy contributions to advances in blend pellet products research on molecular structure and molecular nutrition interaction. How processing induced molecular structure changes in relation to nutrient availability and utilization of the blend pellet products. The study reviews Utilization of co-product components for blend pellet product in North America; Utilization and benefits of inclusion of pulse screenings; Utilization of additives in blend pellet products; Application of pellet processing in blend pellet products; Conventional evaluation techniques and methods for blend pellet products. The study focus on recent applications of cutting-edge vibrational molecular spectroscopy for molecular structure and molecular structure association with nutrient utilization in blend pellet products. The information described in this article gives better insight on how advanced molecular (micro)spectroscopy contributions to advances in blend pellet products research on molecular structure and molecular nutrition interaction.

Hyperfine excitation of CH in collisions with atomic and molecular hydrogen

NASA Astrophysics Data System (ADS)

Dagdigian, Paul J.

2018-04-01

We investigate here the excitation of methylidene (CH) induced by collisions with atomic and molecular hydrogen (H and H2). The hyperfine-resolved rate coefficients were obtained from close coupling nuclear-spin-free scattering calculations. The calculations are based upon recent, high-accuracy calculations of the CH(X2Π)-H(2S) and CH(X2Π)-H2 potential energy surfaces. Cross-sections and rate coefficients for collisions with atomic H, para-H2, and ortho-H2 were computed for all transitions between the 32 hyperfine levels for CH(X2Π) involving the n ≤ 4 rotational levels for temperatures between 10 and 300 K. These rate coefficients should significantly aid in the interpretation of astronomical observations of CH spectra. As a first application, the excitation of CH is simulated for conditions in typical molecular clouds.

Invasive pulmonary aspergillosis: current diagnostic methodologies and a new molecular approach.

PubMed

Moura, S; Cerqueira, L; Almeida, A

2018-05-13

The fungus Aspergillus fumigatus is the main pathogenic agent responsible for invasive pulmonary aspergillosis. Immunocompromised patients are more likely to develop this pathology due to a decrease in the immune system's defense capacity. Despite of the low occurrence of invasive pulmonary aspergillosis, this pathology presents high rates of mortality, mostly due to late and unspecific diagnosis. Currently, the diagnostic methods used to detect this fungal infection are conventional mycological examination (direct microscopic examination, histological examination, and culture), imaging, non-culture-based tests for the detection of galactomannan, β(1,3)-glucan and an extracellular glycoprotein, and molecular tests based on PCR. However, most of these methods do not detect the species A. fumigatus; they only allow the identification of genus Aspergillus. The development of more specific detection methods is of extreme importance. Fluorescent in situ hybridization-based molecular methods can be a good alternative to achieve this purpose. In this review, it is intended to point out that most of the methods used for the diagnosis of invasive pulmonary aspergillosis do not allow to detect the fungus at the species level and that fluorescence in situ hybridization-based molecular method will be a promising approach in the A. fumigatus detection.

Integrative taxonomy by molecular species delimitation: multi-locus data corroborate a new species of Balkan Drusinae micro-endemics.

PubMed

Vitecek, Simon; Kučinić, Mladen; Previšić, Ana; Živić, Ivana; Stojanović, Katarina; Keresztes, Lujza; Bálint, Miklós; Hoppeler, Felicitas; Waringer, Johann; Graf, Wolfram; Pauls, Steffen U

2017-06-06

Taxonomy offers precise species identification and delimitation and thus provides basic information for biological research, e.g. through assessment of species richness. The importance of molecular taxonomy, i.e., the identification and delimitation of taxa based on molecular markers, has increased in the past decade. Recently developed exploratory tools now allow estimating species-level diversity in multi-locus molecular datasets. Here we use molecular species delimitation tools that either quantify differences in intra- and interspecific variability of loci, or divergence times within and between species, or perform coalescent species tree inference to estimate species-level entities in molecular genetic datasets. We benchmark results from these methods against 14 morphologically readily differentiable species of a well-defined subgroup of the diverse Drusinae subfamily (Trichoptera, Limnephilidae). Using a 3798 bp (6 loci) molecular data set we aim to corroborate a geographically isolated new species by integrating comparative morphological studies and molecular taxonomy. Our results indicate that only multi-locus species delimitation provides taxonomically relevant information. The data further corroborate the new species Drusus zivici sp. nov. We provide differential diagnostic characters and describe the male, female and larva of this new species and discuss diversity patterns of Drusinae in the Balkans. We further discuss potential and significance of molecular species delimitation. Finally we argue that enhancing collaborative integrative taxonomy will accelerate assessment of global diversity and completion of reference libraries for applied fields, e.g., conservation and biomonitoring.

Molecular identification of hard ticks (Ixodes sp.) infesting rodents in Selangor, Malaysia

NASA Astrophysics Data System (ADS)

Ishak, Siti Nabilah; Shiang, Lim Fang; Taib, Farah Shafawati Mohd; Jing, Khoo Jing; Nor, Shukor Md; Yusof, Muhammad Afif; Sah, Shahrul Anuar Mohd; Sitam, Frankie Thomas; Japning, Jeffrine Rovie Ryan

2018-04-01

This study aims to identify hard ticks (Ixodes sp.) infesting rodents in three different sites in Selangor, Malaysia using a molecular approach. A total of 11 individual ticks infesting four different host species (Rattus tiomanicus, Rattus ratus, Maxomys surifer and Sundamys muelleri) were examined based on its morphological features, followed by molecular identification using mitochondrial 16S rDNA gene. Confirmation of the species identity was accomplished by using BLAST program. Clustering analysis based on 16S rDNA sequences was carried out by constructing Neighbour-joining (NJ) and Maximum parsimony (MP) tree using MEGA 7 to clarify the genetic identity of Ixodes sp. Based on morphological features, all individual ticks were only able to be identified up to genus level as most of the samples were fully engorged, damaged and lacked morphological characters. However, molecular analysis of samples revealed 99% similarity with Ixodes granulatus from the GenBank database. Thus, the result of this study showed that all these ticks (Ixodes granulatus) were genetically affiliated to a monophyletic group with highly homogenous sequences.

Metabolism of 4-Aminopiperidine Drugs by Cytochrome P450s: Molecular and Quantum Mechanical Insights into Drug Design

PubMed Central

2011-01-01

4-Aminopiperidines are a variety of therapeutic agents that are extensively metabolized by cytochrome P450s with CYP3A4 as a major isoform catalyzing their N-dealkylation reaction. However, its catalytic mechanism has not been fully elucidated in a molecular interaction level. Here, we applied theoretical approaches including the molecular mechanics-based docking to study the binding patterns and quantum mechanics-based reactivity calculations. They were supported by the experimental human liver microsomal clearance and P450 isoform phenotyping data. Our results herein suggested that the molecular interactions between substrates and CYP3A4 active site residues are essential for the N-dealkylation of 4-aminopiperidines. We also found that the serine 119 residue of CYP3A4 may serve as a key hydrogen-bonding partner to interact with the 4-amino groups of the studied drugs. The reactivity of the side chain α-carbon hydrogens drives the direction of catalysis as well. As a result, structure-based drug design approaches look promising to guide drug discovery programs into the optimized drug metabolism space. PMID:21841964

Electrostatic melting in a single-molecule field-effect transistor with applications in genomic identification

PubMed Central

Vernick, Sefi; Trocchia, Scott M.; Warren, Steven B.; Young, Erik F.; Bouilly, Delphine; Gonzalez, Ruben L.; Nuckolls, Colin; Shepard, Kenneth L.

2017-01-01

The study of biomolecular interactions at the single-molecule level holds great potential for both basic science and biotechnology applications. Single-molecule studies often rely on fluorescence-based reporting, with signal levels limited by photon emission from single optical reporters. The point-functionalized carbon nanotube transistor, known as the single-molecule field-effect transistor, is a bioelectronics alternative based on intrinsic molecular charge that offers significantly higher signal levels for detection. Such devices are effective for characterizing DNA hybridization kinetics and thermodynamics and enabling emerging applications in genomic identification. In this work, we show that hybridization kinetics can be directly controlled by electrostatic bias applied between the device and the surrounding electrolyte. We perform the first single-molecule experiments demonstrating the use of electrostatics to control molecular binding. Using bias as a proxy for temperature, we demonstrate the feasibility of detecting various concentrations of 20-nt target sequences from the Ebolavirus nucleoprotein gene in a constant-temperature environment. PMID:28516911

Atomistic model of the spider silk nanostructure

NASA Astrophysics Data System (ADS)

Keten, Sinan; Buehler, Markus J.

2010-04-01

Spider silk is an ultrastrong and extensible self-assembling biopolymer that outperforms the mechanical characteristics of many synthetic materials including steel. Here we report atomic-level structures that represent aggregates of MaSp1 proteins from the N. Clavipes silk sequence based on a bottom-up computational approach using replica exchange molecular dynamics. We discover that poly-alanine regions predominantly form distinct and orderly beta-sheet crystal domains while disorderly structures are formed by poly-glycine repeats, resembling 31-helices. These could be the molecular source of the large semicrystalline fraction observed in silks, and also form the basis of the so-called "prestretched" molecular configuration. Our structures are validated against experimental data based on dihedral angle pair calculations presented in Ramachandran plots, alpha-carbon atomic distances, as well as secondary structure content.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Antonelli, Perry Edward

A low-level model-to-model interface is presented that will enable independent models to be linked into an integrated system of models. The interface is based on a standard set of functions that contain appropriate export and import schemas that enable models to be linked with no changes to the models themselves. These ideas are presented in the context of a specific multiscale material problem that couples atomistic-based molecular dynamics calculations to continuum calculations of fluid ow. These simulations will be used to examine the influence of interactions of the fluid with an adjacent solid on the fluid ow. The interface willmore » also be examined by adding it to an already existing modeling code, Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) and comparing it with our own molecular dynamics code.« less

The Human Blood Metabolome-Transcriptome Interface

PubMed Central

Schramm, Katharina; Adamski, Jerzy; Gieger, Christian; Herder, Christian; Carstensen, Maren; Peters, Annette; Rathmann, Wolfgang; Roden, Michael; Strauch, Konstantin; Suhre, Karsten; Kastenmüller, Gabi; Prokisch, Holger; Theis, Fabian J.

2015-01-01

Biological systems consist of multiple organizational levels all densely interacting with each other to ensure function and flexibility of the system. Simultaneous analysis of cross-sectional multi-omics data from large population studies is a powerful tool to comprehensively characterize the underlying molecular mechanisms on a physiological scale. In this study, we systematically analyzed the relationship between fasting serum metabolomics and whole blood transcriptomics data from 712 individuals of the German KORA F4 cohort. Correlation-based analysis identified 1,109 significant associations between 522 transcripts and 114 metabolites summarized in an integrated network, the ‘human blood metabolome-transcriptome interface’ (BMTI). Bidirectional causality analysis using Mendelian randomization did not yield any statistically significant causal associations between transcripts and metabolites. A knowledge-based interpretation and integration with a genome-scale human metabolic reconstruction revealed systematic signatures of signaling, transport and metabolic processes, i.e. metabolic reactions mainly belonging to lipid, energy and amino acid metabolism. Moreover, the construction of a network based on functional categories illustrated the cross-talk between the biological layers at a pathway level. Using a transcription factor binding site enrichment analysis, this pathway cross-talk was further confirmed at a regulatory level. Finally, we demonstrated how the constructed networks can be used to gain novel insights into molecular mechanisms associated to intermediate clinical traits. Overall, our results demonstrate the utility of a multi-omics integrative approach to understand the molecular mechanisms underlying both normal physiology and disease. PMID:26086077

Morphometric and molecular characterization of fungus Pestalotiopsis using nuclear ribosomal DNA analysis.

PubMed

Gehlot, Praveen; Singh, S K; Pathak, Rakesh

2012-09-01

Taxonomy of the fungus Pestalotiopsis based on morphological characters has been equivocal. Molecular characterization often Pestalotiopsis species was done based on nuclear ribosomal DNA internal transcribed spacer (ITS) amplifications. Results of the analyses showed that species of genus Pestalotiopsis are monophyletic. We report ITS length variations, single nucleotide polymorphisms (SNPs) and insertions/ deletions (INDELS) among ten species of Pestalotiopsis that did not cause any phylogenetic error at either genus or species designation levels. New gene sequences have been assigned (Gen Accession numbers from HM 190146 to HM 190155) by the National Centre for Biotechnology Information, USA.

A Fluorescence Quenching Assay Based on Molecular Beacon Formation through a Ligase Detection Reaction for Facile and Rapid Detection of Point Mutations.

PubMed

Sawamura, Kensuke; Hashimoto, Masahiko

2017-01-01

A fluorescence quenching assay based on a ligase detection reaction was developed for facile and rapid detection of point mutations present in a mixed population of non-variant DNA. If the test DNA carried a targeted mutation, then the two allele-specific primers were ligated to form a molecular beacon resulting in the expected fluorescence quenching signatures. Using this method, we successfully detected as low as 5% mutant DNA in a mixture of wild-type DNA (t test at 99% confidence level).

Why should biochemistry students be introduced to molecular dynamics simulations--and how can we introduce them?

PubMed

Elmore, Donald E

2016-01-01

Molecular dynamics (MD) simulations play an increasingly important role in many aspects of biochemical research but are often not part of the biochemistry curricula at the undergraduate level. This article discusses the pedagogical value of exposing students to MD simulations and provides information to help instructors consider what software and hardware resources are necessary to successfully introduce these simulations into their courses. In addition, a brief review of the MD-based activities in this issue and other sources are provided. © 2016 The International Union of Biochemistry and Molecular Biology.

Molecular evidence of stereo-specific lactoferrin dimers in solution.

PubMed

Persson, Björn A; Lund, Mikael; Forsman, Jan; Chatterton, Dereck E W; Akesson, Torbjörn

2010-10-01

Gathering experimental evidence suggests that bovine as well as human lactoferrin self-associate in aqueous solution. Still, a molecular level explanation is unavailable. Using force field based molecular modeling of the protein-protein interaction free energy we demonstrate (1) that lactoferrin forms highly stereo-specific dimers at neutral pH and (2) that the self-association is driven by a high charge complementarity across the contact surface of the proteins. Our theoretical predictions of dimer formation are verified by electrophoretic mobility and N-terminal sequence analysis on bovine lactoferrin. 2010 Elsevier B.V. All rights reserved.

Characterization of ovarian clear cell carcinoma using target drug-based molecular biomarkers: implications for personalized cancer therapy.

PubMed

Li, Mengjiao; Li, Haoran; Liu, Fei; Bi, Rui; Tu, Xiaoyu; Chen, Lihua; Ye, Shuang; Cheng, Xi

2017-02-10

It has long been appreciated that different subtypes (serous, clear cell, endometrioid and mucinous) of epithelial ovarian carcinoma (EOC) have distinct pathogenetic pathways. However, clinical management, especially chemotherapeutic regimens, for EOC patients is not subtype specific. Ovarian clear cell carcinoma (CCC) is a rare histological subtype of EOC, which exhibits high rates of recurrence and low chemosensitivity. We assessed potential therapeutic targets for ovarian CCC patients through analyzing the variation of drug-based molecular biomarkers expression between ovarian CCC and high-grade serous carcinoma (HGSC). Seven candidate drug-based molecular biomarkers, human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), phosphatase and tensin homolog deleted on chromosome ten (PTEN), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), breast cancer susceptibility gene 2 (BRCA2) and programmed death-ligand 1 (PD-L1) were measured in 96 ovarian CCC and 113 HGSC by immunohistochemistry in paraffin embedded tissues. The relationship between these biomarkers and clinicopathological factors were explored. The expression level of four of the seven drug-based molecular biomarkers was markedly different between HGSC and CCC. High expression levels of HER2 and PD-L1 were more commonly observed in CCC patients (12.6% vs 2.7%, 21.1% vs 11.6%, P = 0.006, 0.064, respectively), while loss of BRCA1 and BRCA2 expression were more frequently occurred in HGSC patients (72.6% vs 54.3%, 89.4% vs 79.8%, P = 0.007, 0.054, respectively). Survival analysis showed that five of seven biomarkers had prognostic values but varied between subtypes. Furthermore, EGFR expressed frequently in CCC patients with endometriosis than in HGSC patients (44.4% vs 8.3%, P = 0.049). AURKA and PD-L1 correlated with the resistance to platinum-based chemotherapy in CCC patients (P = 0.043, 0.028, respectively) while no similar results were observed in HGSC patients. Ovarian CCC showed a markedly different expression map of drug-based molecular biomarkers from HGSC, which suggested a new personalized target therapy in this rare subtype.

Advances in visual representation of molecular potentials.

PubMed

Du, Qi-Shi; Huang, Ri-Bo; Chou, Kuo-Chen

2010-06-01

The recent advances in visual representations of molecular properties in 3D space are summarized, and their applications in molecular modeling study and rational drug design are introduced. The visual representation methods provide us with detailed insights into protein-ligand interactions, and hence can play a major role in elucidating the structure or reactivity of a biomolecular system. Three newly developed computation and visualization methods for studying the physical and chemical properties of molecules are introduced, including their electrostatic potential, lipophilicity potential and excess chemical potential. The newest application examples of visual representations in structure-based rational drug are presented. The 3D electrostatic potentials, calculated using the empirical method (EM-ESP), in which the classical Coulomb equation and traditional atomic partial changes are discarded, are highly consistent with the results by the higher level quantum chemical method. The 3D lipophilicity potentials, computed by the heuristic molecular lipophilicity potential method based on the principles of quantum mechanics and statistical mechanics, are more accurate and reliable than those by using the traditional empirical methods. The 3D excess chemical potentials, derived by the reference interaction site model-hypernetted chain theory, provide a new tool for computational chemistry and molecular modeling. For structure-based drug design, the visual representations of molecular properties will play a significant role in practical applications. It is anticipated that the new advances in computational chemistry will stimulate the development of molecular modeling methods, further enriching the visual representation techniques for rational drug design, as well as other relevant fields in life science.

Bio-Mimetic Sensors Based on Molecularly Imprinted Membranes

PubMed Central

Algieri, Catia; Drioli, Enrico; Guzzo, Laura; Donato, Laura

2014-01-01

An important challenge for scientific research is the production of artificial systems able to mimic the recognition mechanisms occurring at the molecular level in living systems. A valid contribution in this direction resulted from the development of molecular imprinting. By means of this technology, selective molecular recognition sites are introduced in a polymer, thus conferring it bio-mimetic properties. The potential applications of these systems include affinity separations, medical diagnostics, drug delivery, catalysis, etc. Recently, bio-sensing systems using molecularly imprinted membranes, a special form of imprinted polymers, have received the attention of scientists in various fields. In these systems imprinted membranes are used as bio-mimetic recognition elements which are integrated with a transducer component. The direct and rapid determination of an interaction between the recognition element and the target analyte (template) was an encouraging factor for the development of such systems as alternatives to traditional bio-assay methods. Due to their high stability, sensitivity and specificity, bio-mimetic sensors-based membranes are used for environmental, food, and clinical uses. This review deals with the development of molecularly imprinted polymers and their different preparation methods. Referring to the last decades, the application of these membranes as bio-mimetic sensor devices will be also reported. PMID:25196110

Frontiers of controlling energy levels at interfaces

NASA Astrophysics Data System (ADS)

Koch, Norbert

The alignment of electron energy levels at interfaces between semiconductors, dielectrics, and electrodes determines the function and efficiency of all electronic and optoelectronic devices. Reliable guidelines for predicting the level alignment for a given material combination and methods to adjust the intrinsic energy landscape are needed to enable efficient engineering approaches. These are sufficiently understood for established electronic materials, e.g., Si, but for the increasing number of emerging materials, e.g., organic and 2D semiconductors, perovskites, this is work in progress. The intrinsic level alignment and the underlying mechanisms at interfaces between organic and inorganic semiconductors are discussed first. Next, methods to alter the level alignment are introduced, which all base on proper charge density rearrangement at a heterojunction. As interface modification agents we use molecular electron acceptors and donors, as well as molecular photochromic switches that add a dynamic aspect and allow device multifunctionality. For 2D semiconductors surface transfer doping with molecular acceptors/donors transpires as viable method to locally tune the Fermi-level position in the energy gap. The fundamental electronic properties of a prototypical 1D interface between intrinsic and p-doped 2D semiconductor regions are derived from local (scanning probe) and area-averaged (photoemission) spectroscopy experiments. Future research opportunities for attaining unsurpassed interface control through charge density management are discussed.

Molecular-genetic imaging based on reporter gene expression.

PubMed

Kang, Joo Hyun; Chung, June-Key

2008-06-01

Molecular imaging includes proteomic, metabolic, cellular biologic process, and genetic imaging. In a narrow sense, molecular imaging means genetic imaging and can be called molecular-genetic imaging. Imaging reporter genes play a leading role in molecular-genetic imaging. There are 3 major methods of molecular-genetic imaging, based on optical, MRI, and nuclear medicine modalities. For each of these modalities, various reporter genes and probes have been developed, and these have resulted in successful transitions from bench to bedside applications. Each of these imaging modalities has its unique advantages and disadvantages. Fluorescent and bioluminescent optical imaging modalities are simple, less expensive, more convenient, and more user friendly than other imaging modalities. Another advantage, especially of bioluminescence imaging, is its ability to detect low levels of gene expression. MRI has the advantage of high spatial resolution, whereas nuclear medicine methods are highly sensitive and allow data from small-animal imaging studies to be translated to clinical practice. Moreover, multimodality imaging reporter genes will allow us to choose the imaging technologies that are most appropriate for the biologic problem at hand and facilitate the clinical application of reporter gene technologies. Reporter genes can be used to visualize the levels of expression of particular exogenous and endogenous genes and several intracellular biologic phenomena, including specific signal transduction pathways, nuclear receptor activities, and protein-protein interactions. This technique provides a straightforward means of monitoring tumor mass and can visualize the in vivo distributions of target cells, such as immune cells and stem cells. Molecular imaging has gradually evolved into an important tool for drug discovery and development, and transgenic mice with an imaging reporter gene can be useful during drug and stem cell therapy development. Moreover, instrumentation improvements, the identification of novel targets and genes, and imaging probe developments suggest that molecular-genetic imaging is likely to play an increasingly important role in the diagnosis and therapy of cancer.

Analysis of heparin oligosaccharides by capillary electrophoresis-negative-ion electrospray ionization mass spectrometry.

PubMed

Lin, Lei; Liu, Xinyue; Zhang, Fuming; Chi, Lianli; Amster, I Jonathan; Leach, Franklyn E; Xia, Qiangwei; Linhardt, Robert J

2017-01-01

Most hyphenated analytical approaches that rely on liquid chromatography-MS require relatively long separation times, produce incomplete resolution of oligosaccharide mixtures, use eluents that are incompatible with electrospray ionization, or require oligosaccharide derivatization. Here we demonstrate the analysis of heparin oligosaccharides, including disaccharides, ultralow molecular weight heparin, and a low molecular weight heparin, using a novel electrokinetic pump-based CE-MS coupling eletrospray ion source. Reverse polarity CE separation and negative-mode electrospray ionization were optimized using a volatile methanolic ammonium acetate electrolyte and sheath fluid. The online CE hyphenated negative-ion electrospray ionization MS on an LTQ Orbitrap mass spectrometer was useful in disaccharide compositional analysis and bottom-up and top-down analysis of low molecular weight heparin. The application of this CE-MS method to ultralow molecular heparin suggests that a charge state distribution and the low level of sulfate group loss that is achieved make this method useful for online tandem MS analysis of heparins. Graphical abstract Most hyphenated analytical approaches that rely on liquid chromatography-MS require relatively long separation times, produce incomplete resolution of oligosaccharide mixtures, use eluents that are incompatible with electrospray ionization, or require oligosaccharide derivatization. Here we demonstrate the analysis of heparin oligosaccharides, including disaccharides, ultralow molecular weight heparin, and a low molecular weight heparin, using a novel electrokinetic pump-based CE-MS coupling eletrospray ion source. Reverse polarity CE separation and negative-mode electrospray ionization were optimized using a volatile methanolic ammonium acetate electrolyte and sheath fluid. The online CE hyphenated negative-ion electrospray ionization MS on an LTQ Orbitrap mass spectrometer was useful in disaccharide compositional analysis and bottom-up and top-down analysis of low molecular weight heparin. The application of this CE-MS method to ultralow molecular heparin suggests that a charge state distribution and the low level of sulfate group loss that is achieved make this method useful for online tandem MS analysis of heparins.

Repair Rate of Clustered Abasic DNA Lesions by Human Endonuclease: Molecular Bases of Sequence Specificity.

PubMed

Gattuso, Hugo; Durand, Elodie; Bignon, Emmanuelle; Morell, Christophe; Georgakilas, Alexandros G; Dumont, Elise; Chipot, Christophe; Dehez, François; Monari, Antonio

2016-10-06

In the present contribution, the interaction between damaged DNA and repair enzymes is examined by means of molecular dynamics simulations. More specifically, we consider clustered abasic DNA lesions processed by the primary human apurinic/apyrimidinic (AP) endonuclease, APE1. Our results show that, in stark contrast with the corresponding bacterial endonucleases, human APE1 imposes strong geometrical constraints on the DNA duplex. As a consequence, the level of recognition and, hence, the repair rate is higher. Important features that guide the DNA/protein interactions are the presence of an extended positively charged region and of a molecular tweezers that strongly constrains DNA. Our results are on very good agreement with the experimentally determined repair rate of clustered abasic lesions. The lack of repair for one particular arrangement of the two abasic sites is also explained considering the peculiar destabilizing interaction between the recognition region and the second lesion, resulting in a partial opening of the molecular tweezers and, thus, a less stable complex. This contribution cogently establishes the molecular bases for the recognition and repair of clustered DNA lesions by means of human endonucleases.

Mass spectrometry in life science research.

PubMed

Lehr, Stefan; Markgraf, Daniel

2016-12-01

Investigating complex signatures of biomolecules by mass spectrometry approaches has become indispensable in molecular life science research. Nowadays, various mass spectrometry-based omics technologies are available to monitor qualitative and quantitative changes within hundreds or thousands of biological active components, including proteins/peptides, lipids and metabolites. These comprehensive investigations have the potential to decipher the pathophysiology of disease development at a molecular level and to monitor the individual response of pharmacological treatment or lifestyle intervention.

Recent research on inherent molecular structure, physiochemical properties, and bio-functions of food and feed-type Avena sativa oats and processing-induced changes revealed with molecular microspectroscopic techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prates, Luciana Louzada; Yu, Peiqiang

Avena sativa oat is a cereal widely used as human food and livestock feed. However, the low metabolized energy and the rapid rumen degradations of protein and starch have limited the use of A. sativa oat grains. To overcome this disadvantage, new A. sativa oat varieties have been developed. Additionally, heat-related processing has been performed to decrease the degradation rate and improve the absorption of amino acids in the small intestine. The nutritive value is reflected by both chemical composition and inherent molecular structure conformation. However, the traditional wet chemical analysis is not able to detect the inherent molecular structuresmore » within an intact tissue. The advanced synchrotron-radiation and globar-based molecular microspectroscopy have been developed recently and applied to study internal molecular structures and the processing induced structure changes in A. sativa oats and reveal how molecular structure changes in relation to nutrient availability. This review aimed to obtain the recent information regarding physiochemical properties, molecular structures, metabolic characteristics of protein, and the heat-induced changes in new A. sativa oat varieties. The use of the advanced vibrational molecular spectroscopy was emphasized, synchrotron- and globar-based (micro)spectroscopy, to reveal the inherent structure of A. sativa oats at cellular and molecular levels and to reveal the heat processing effect on the degradation characteristics and the protein molecular structure in A. sativa oats. The relationship between nutrient availability and protein molecular inherent structure was also presented. Information described in this review gives better insight in the physiochemical properties, molecular structure, and the heat-induced changes in A. sativa oat detected with advanced molecular spectroscopic techniques in combinination with conventional nutrition study techniques.« less

Knowledge environments representing molecular entities for the virtual physiological human.

PubMed

Hofmann-Apitius, Martin; Fluck, Juliane; Furlong, Laura; Fornes, Oriol; Kolárik, Corinna; Hanser, Susanne; Boeker, Martin; Schulz, Stefan; Sanz, Ferran; Klinger, Roman; Mevissen, Theo; Gattermayer, Tobias; Oliva, Baldo; Friedrich, Christoph M

2008-09-13

In essence, the virtual physiological human (VPH) is a multiscale representation of human physiology spanning from the molecular level via cellular processes and multicellular organization of tissues to complex organ function. The different scales of the VPH deal with different entities, relationships and processes, and in consequence the models used to describe and simulate biological functions vary significantly. Here, we describe methods and strategies to generate knowledge environments representing molecular entities that can be used for modelling the molecular scale of the VPH. Our strategy to generate knowledge environments representing molecular entities is based on the combination of information extraction from scientific text and the integration of information from biomolecular databases. We introduce @neuLink, a first prototype of an automatically generated, disease-specific knowledge environment combining biomolecular, chemical, genetic and medical information. Finally, we provide a perspective for the future implementation and use of knowledge environments representing molecular entities for the VPH.

Molecular Beacon-Based MicroRNA Imaging During Neurogenesis.

PubMed

Lee, Jonghwan; Kim, Soonhag

2016-01-01

The fluorescence monitoring system for examining endogenous microRNA (miRNA) activity in cellular level provides crucial information on not only understanding a critical role of miRNA involving a variety of biological processes, but also evaluating miRNA expression patterns in a noninvasive manner. In this protocol, we report the details of a new procedure for a molecular beacon-based miRNA monitoring system, which includes the illustration scheme for miRNA detection strategy, exogenous miRNA detection, and measurement of endogenous miRNA expression level during neurogenesis. The fluorescence signal of miR-124a beacon quenched by BHQ2 was gradually recovered as increasing concentration of the miR-124a in tube. The functional work of miR-124a beacon was examined in intracellular environment, allowing for the internalization of the miR-124a beacon by lipofectamine, which resulted in activated fluorescent signals of the miR-124a beacon in the HeLa cells after the addition of synthetic miR-124a. The endogenous miR-124a expression level was detected by miR-124a beacon system during neurogenesis, showing brighter fluorescence intensity in cytoplasmic area of P19 cells after induction of neuronal differentiation by retinoic acid. The molecular beacon based-miRNA detection technique could be applicable to the simultaneous visualization of a variety of miRNA expression patterns using different fluorescence dyes. For the study of examining endogenous miRNA expression level using miRNA-beacon system, if cellular differentiation step is already prepared, transfection step of miR-124a beacon into P19 cells, and acquisition of activated fluorescence signal measured by confocal microscope can be conducted approximately within 6 h.

Molecular diversity and population structure of the forage grass Hemarthria compressa (Poaceae) in south China based on SRAP markers.

PubMed

Huang, L-K; Zhang, X-Q; Xie, W-G; Zhang, J; Cheng, L; Yan, H D

2012-08-16

Hemarthria compressa is one of the most important and widely utilized forage crops in south China, owing to its high forage yield and capability of adaptation to hot and humid conditions. We examined the population structure and genetic variation within and among 12 populations of H. compressa in south China using sequence-related amplified polymorphism (SRAP) markers. High genetic diversity was found in these samples [percentage polymorphic bands (PPB) = 82.21%, Shannon's diversity index (I) = 0.352]. However, there was relatively low level of genetic diversity at the population level (PPB = 29.17%, I = 0.155). A high degree of genetic differentiation among populations was detected based on other measures and molecular markers (Nei's genetic diversity analysis: G(ST) = 54.19%; AMOVA analysis: F(ST) = 53.35%). The SRAP markers were found to be more efficient than ISSR markers for evaluating population diversity. Based on these findings, we propose changes in sampling strategies for appraising and utilizing the genetic resources of this species.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vijayakumar, M.; Nie, Zimin; Walter, Eric D.

Redox flow battery (RFB) is a promising candidate for energy storage component in designing resilient grid scale power supply due to the advantage of the separation of power and energy. However, poorly understood chemical and thermal stability issues of electrolytes currently limit the performance of RFB. Designing of high performance stable electrolytes requires comprehensive knowledge about the molecular level solvation structure and dynamics of their redox active species. The molecular level understanding of detrimental V2O5 precipitation process led to successful designing of mixed acid based electrolytes for vanadium redox flow batteries (VRFB). The higher stability of mixed acid based electrolytesmore » is attributed to the choice of hydrochloric acid as optimal co-solvent, which provides chloride anions for ligand exchange process in vanadium solvation structure. The role of chloride counter anion on solvation structure and dynamics of vanadium species were studied using combined magnetic resonance spectroscopy and DFT based theoretical methods. Finally, the solvation phenomenon of multiple vanadium species and their impact on VRFB electrolyte chemical stability were discussed.« less

Murburn Concept: A Molecular Explanation for Hormetic and Idiosyncratic Dose Responses.

PubMed

Parashar, Abhinav; Gideon, Daniel Andrew; Manoj, Kelath Murali

2018-01-01

Recently, electron transfers and catalyses in a bevy of redox reactions mediated by hemeproteins were explained by murburn concept. The term "murburn" is abstracted from " mur ed burn ing " or " m ild u n r estricted burn ing " and connotes a novel " m olecule- u nbound ion- r adical " interaction paradigm. Quite unlike the genetic regulations and protein-level affinity-based controls that govern order and specificity/selectivity in conventional treatments, murburn concept is based on stochastic/thermodynamic regulatory principles. The novel insight necessitates a "reactivity outside the active-site" perspective, because select redox enzymatic activity is obligatorily mediated via diffusible radical/species. Herein, reactions employing key hemeproteins (as exemplified by CYP2E1) establish direct experimental connection between "additive-influenced redox catalysis" and "unusual dose responses" in reductionist and physiological milieu. Thus, direct and conclusive molecular-level experimental evidence is presented, supporting the mechanistic relevance of murburn concept in "maverick" concentration-based effects brought about by additives. Therefore, murburn concept could potentially explain several physiological hormetic and idiosyncratic dose responses.

Molecular classification of gastric cancer.

PubMed

Chia, N-Y; Tan, P

2016-05-01

Gastric cancer (GC), a heterogeneous disease characterized by epidemiologic and histopathologic differences across countries, is a leading cause of cancer-related death. Treatment of GC patients is currently suboptimal due to patients being commonly treated in a uniform fashion irrespective of disease subtype. With the advent of next-generation sequencing and other genomic technologies, GCs are now being investigated in great detail at the molecular level. High-throughput technologies now allow a comprehensive study of genomic and epigenomic alterations associated with GC. Gene mutations, chromosomal aberrations, differential gene expression and epigenetic alterations are some of the genetic/epigenetic influences on GC pathogenesis. In addition, integrative analyses of molecular profiling data have led to the identification of key dysregulated pathways and importantly, the establishment of GC molecular classifiers. Recently, The Cancer Genome Atlas (TCGA) network proposed a four subtype classification scheme for GC based on the underlying tumor molecular biology of each subtype. This landmark study, together with other studies, has expanded our understanding on the characteristics of GC at the molecular level. Such knowledge may improve the medical management of GC in the future. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Site-Directed Mutagenesis Study of an Antibiotic-Sensing Noncoding RNA Integrated into a One-Semester Project-Based Biochemistry Lab Course

ERIC Educational Resources Information Center

Gerczei, Timea

2017-01-01

A laboratory sequence is described that is suitable for upper-level biochemistry or molecular biology laboratories that combines project-based and traditional laboratory experiments. In the project-based sequence, the individual laboratory experiments are thematically linked and aim to show how a bacterial antibiotic sensing noncoding RNA (the…

Physiological and molecular characterization of drought responses and identification of candidate tolerance genes in cassava

PubMed Central

Turyagyenda, Laban F.; Kizito, Elizabeth B.; Ferguson, Morag; Baguma, Yona; Agaba, Morris; Harvey, Jagger J. W.; Osiru, David S. O.

2013-01-01

Cassava is an important root crop to resource-poor farmers in marginal areas, where its production faces drought stress constraints. Given the difficulties associated with cassava breeding, a molecular understanding of drought tolerance in cassava will help in the identification of markers for use in marker-assisted selection and genes for transgenic improvement of drought tolerance. This study was carried out to identify candidate drought-tolerance genes and expression-based markers of drought stress in cassava. One drought-tolerant (improved variety) and one drought-susceptible (farmer-preferred) cassava landrace were grown in the glasshouse under well-watered and water-stressed conditions. Their morphological, physiological and molecular responses to drought were characterized. Morphological and physiological measurements indicate that the tolerance of the improved variety is based on drought avoidance, through reduction of water loss via partial stomatal closure. Ten genes that have previously been biologically validated as conferring or being associated with drought tolerance in other plant species were confirmed as being drought responsive in cassava. Four genes (MeALDH, MeZFP, MeMSD and MeRD28) were identified as candidate cassava drought-tolerance genes, as they were exclusively up-regulated in the drought-tolerant genotype to comparable levels known to confer drought tolerance in other species. Based on these genes, we hypothesize that the basis of the tolerance at the cellular level is probably through mitigation of the oxidative burst and osmotic adjustment. This study provides an initial characterization of the molecular response of cassava to drought stress resembling field conditions. The drought-responsive genes can now be used as expression-based markers of drought stress tolerance in cassava, and the candidate tolerance genes tested in the context of breeding (as possible quantitative trait loci) and engineering drought tolerance in transgenics. PMID:23519782

Coarse-Grained Models Reveal Functional Dynamics – II. Molecular Dynamics Simulation at the Coarse-Grained Level – Theories and Biological Applications

PubMed Central

Chng, Choon-Peng; Yang, Lee-Wei

2008-01-01

Molecular dynamics (MD) simulation has remained the most indispensable tool in studying equilibrium/non-equilibrium conformational dynamics since its advent 30 years ago. With advances in spectroscopy accompanying solved biocomplexes in growing sizes, sampling their dynamics that occur at biologically interesting spatial/temporal scales becomes computationally intractable; this motivated the use of coarse-grained (CG) approaches. CG-MD models are used to study folding and conformational transitions in reduced resolution and can employ enlarged time steps due to the absence of some of the fastest motions in the system. The Boltzmann-Inversion technique, heavily used in parameterizing these models, provides a smoothed-out effective potential on which molecular conformation evolves at a faster pace thus stretching simulations into tens of microseconds. As a result, a complete catalytic cycle of HIV-1 protease or the assembly of lipid-protein mixtures could be investigated by CG-MD to gain biological insights. In this review, we survey the theories developed in recent years, which are categorized into Folding-based and Molecular-Mechanics-based. In addition, physical bases in the selection of CG beads/time-step, the choice of effective potentials, representation of solvent, and restoration of molecular representations back to their atomic details are systematically discussed. PMID:19812774

Inquiry-Based Experiments for Large-Scale Introduction to PCR and Restriction Enzyme Digests

ERIC Educational Resources Information Center

Johanson, Kelly E.; Watt, Terry J.

2015-01-01

Polymerase chain reaction and restriction endonuclease digest are important techniques that should be included in all Biochemistry and Molecular Biology laboratory curriculums. These techniques are frequently taught at an advanced level, requiring many hours of student and faculty time. Here we present two inquiry-based experiments that are…

Application of supervised and unsupervised tools to direct effects-based monitoring efforts in the Great Lakes areas of concern: Maumee River, Ohio

EPA Science Inventory

Effects-based approaches that employ molecular and tissue level tools to detect and characterize biological responses to contaminants can be a useful complement to chemical monitoring approaches. When the source/type of contamination is known, a predetermined, or supervised, set...

Human Prostate Cancer Hallmarks Map

PubMed Central

Datta, Dipamoy; Aftabuddin, Md.; Gupta, Dinesh Kumar; Raha, Sanghamitra; Sen, Prosenjit

2016-01-01

Human prostate cancer is a complex heterogeneous disease that mainly affects elder male population of the western world with a high rate of mortality. Acquisitions of diverse sets of hallmark capabilities along with an aberrant functioning of androgen receptor signaling are the central driving forces behind prostatic tumorigenesis and its transition into metastatic castration resistant disease. These hallmark capabilities arise due to an intense orchestration of several crucial factors, including deregulation of vital cell physiological processes, inactivation of tumor suppressive activity and disruption of prostate gland specific cellular homeostasis. The molecular complexity and redundancy of oncoproteins signaling in prostate cancer demands for concurrent inhibition of multiple hallmark associated pathways. By an extensive manual curation of the published biomedical literature, we have developed Human Prostate Cancer Hallmarks Map (HPCHM), an onco-functional atlas of human prostate cancer associated signaling and events. It explores molecular architecture of prostate cancer signaling at various levels, namely key protein components, molecular connectivity map, oncogenic signaling pathway map, pathway based functional connectivity map etc. Here, we briefly represent the systems level understanding of the molecular mechanisms associated with prostate tumorigenesis by considering each and individual molecular and cell biological events of this disease process. PMID:27476486

Giant rectification in graphene nanoflake molecular devices with asymmetric graphene nanoribbon electrodes

NASA Astrophysics Data System (ADS)

Ji, Xiao-Li; Xie, Zhen; Zuo, Xi; Zhang, Guang-Ping; Li, Zong-Liang; Wang, Chuan-Kui

2016-09-01

By applying density functional theory based nonequilibrium Green's function method, we theoretically investigate the electron transport properties of a zigzag-edged trigonal graphene nanoflake (ZTGNF) sandwiched between two asymmetric zigzag graphene nanoribbon (zGNR) and armchair graphene nanoribbon (aGNR) electrodes with carbon atomic chains (CACs) as the anchoring groups. Significant rectifying effects have been observed for these molecular devices in low bias voltage regions. Interestingly, the rectifying performance of molecular devices can be optimized by changing the width of the aGNR electrode and the number of anchoring CACs. Especially, the molecular device displays giant rectification ratios up to the order of 104 when two CACs are used as the anchoring group between the ZTGNF and the right aGNR electrode. Further analysis indicates that the asymmetric shift of the perturbed molecular energy levels and the spatial parity of the electron wavefunctions in the electrodes around the Fermi level play key roles in determining the rectification performance. And the spatial distributions of tunneling electron wavefunctions under negative bias voltages can be modified to be very localized by changing the number of anchoring CACs, which is found to be the origin of the giant rectification ratios.

Molecular trophic markers in marine food webs and their potential use for coral ecology.

PubMed

Leal, Miguel Costa; Ferrier-Pagès, Christine

2016-10-01

Notable advances in ecological genomics have been driven by high-throughput sequencing technology and taxonomically broad sequence repositories that allow us to accurately assess species interactions with great taxonomic resolution. The use of DNA as a marker for ingested food is particularly relevant to address predator-prey interactions and disentangle complex marine food webs. DNA-based methods benefit from reductionist molecular approaches to address ecosystem scale processes, such as community structure and energy flow across trophic levels, among others. Here we review how molecular trophic markers have been used to better understand trophic interactions in the marine environment and their advantages and limitations. We focus on animal groups where research has been focused, such as marine mammals, seabirds, fishes, pelagic invertebrates and benthic invertebrates, and use case studies to illustrate how DNA-based methods unraveled food-web interactions. The potential of molecular trophic markers for disentangling the complex trophic ecology of corals is also discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Complex basis functions for molecular resonances: Methodology and applications

NASA Astrophysics Data System (ADS)

White, Alec; McCurdy, C. William; Head-Gordon, Martin

The computation of positions and widths of metastable electronic states is a challenge for molecular electronic structure theory because, in addition to the difficulty of the many-body problem, such states obey scattering boundary conditions. These resonances cannot be addressed with naïve application of traditional bound state electronic structure theory. Non-Hermitian electronic structure methods employing complex basis functions is one way that we may rigorously treat resonances within the framework of traditional electronic structure theory. In this talk, I will discuss our recent work in this area including the methodological extension from single determinant SCF-based approaches to highly correlated levels of wavefunction-based theory such as equation of motion coupled cluster and many-body perturbation theory. These approaches provide a hierarchy of theoretical methods for the computation of positions and widths of molecular resonances. Within this framework, we may also examine properties of resonances including the dependence of these parameters on molecular geometry. Some applications of these methods to temporary anions and dianions will also be discussed.

Intra and Interspecific Variations of Gene Expression Levels in Yeast Are Largely Neutral: (Nei Lecture, SMBE 2016, Gold Coast).

PubMed

Yang, Jian-Rong; Maclean, Calum J; Park, Chungoo; Zhao, Huabin; Zhang, Jianzhi

2017-09-01

It is commonly, although not universally, accepted that most intra and interspecific genome sequence variations are more or less neutral, whereas a large fraction of organism-level phenotypic variations are adaptive. Gene expression levels are molecular phenotypes that bridge the gap between genotypes and corresponding organism-level phenotypes. Yet, it is unknown whether natural variations in gene expression levels are mostly neutral or adaptive. Here we address this fundamental question by genome-wide profiling and comparison of gene expression levels in nine yeast strains belonging to three closely related Saccharomyces species and originating from five different ecological environments. We find that the transcriptome-based clustering of the nine strains approximates the genome sequence-based phylogeny irrespective of their ecological environments. Remarkably, only ∼0.5% of genes exhibit similar expression levels among strains from a common ecological environment, no greater than that among strains with comparable phylogenetic relationships but different environments. These and other observations strongly suggest that most intra and interspecific variations in yeast gene expression levels result from the accumulation of random mutations rather than environmental adaptations. This finding has profound implications for understanding the driving force of gene expression evolution, genetic basis of phenotypic adaptation, and general role of stochasticity in evolution. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Endometriosis: translation of molecular insights to management.

PubMed

Langan, K L; Farrell, M E; Keyser, E A; Salyer, B A; Burney, R O

2014-09-01

Endometriosis is a debilitating gynecologic disorder causing pelvic pain and infertility and characterized by the implantation of endometrial tissue to extrauterine locations. Though aspects of the condition remain enigmatic, the molecular pathophysiology of endometriosis appears to be clarifying. Estrogen dependence of the disease is a sentinel endocrine feature and reduction of estrogen bioavailability is the therapeutic principle upon which traditional treatment and prevention approaches have been based. Endometriosis is a chronic inflammatory condition associated with lesional neoangiogenesis and attenuated progesterone action at the level of the endometrium. The elucidation of the molecular pathways mediating these observations has revealed new targets for directed medical and surgical treatment. This paper will review current approaches to the management of endometriosis in the context of the molecular pathophysiology.

Manipulation of individual hyperfine states in cold trapped molecular ions and application to HD+ frequency metrology.

PubMed

Bressel, U; Borodin, A; Shen, J; Hansen, M; Ernsting, I; Schiller, S

2012-05-04

Advanced techniques for manipulation of internal states, standard in atomic physics, are demonstrated for a charged molecular species for the first time. We address individual hyperfine states of rovibrational levels of a diatomic ion by optical excitation of individual hyperfine transitions, and achieve controlled transfer of population into a selected hyperfine state. We use molecular hydrogen ions (HD+) as a model system and employ a novel frequency-comb-based, continuous-wave 5  μm laser spectrometer. The achieved spectral resolution is the highest obtained so far in the optical domain on a molecular ion species. As a consequence, we are also able to perform the most precise test yet of the ab initio theory of a molecule.

Sketching the Invisible to Predict the Visible: From Drawing to Modeling in Chemistry.

PubMed

Cooper, Melanie M; Stieff, Mike; DeSutter, Dane

2017-10-01

Sketching as a scientific practice goes beyond the simple act of inscribing diagrams onto paper. Scientists produce a wide range of representations through sketching, as it is tightly coupled to model-based reasoning. Chemists in particular make extensive use of sketches to reason about chemical phenomena and to communicate their ideas. However, the chemical sciences have a unique problem in that chemists deal with the unseen world of the atomic-molecular level. Using sketches, chemists strive to develop causal mechanisms that emerge from the structure and behavior of molecular-level entities, to explain observations of the macroscopic visible world. Interpreting these representations and constructing sketches of molecular-level processes is a crucial component of student learning in the modern chemistry classroom. Sketches also serve as an important component of assessment in the chemistry classroom as student sketches give insight into developing mental models, which allows instructors to observe how students are thinking about a process. In this paper we discuss how sketching can be used to promote such model-based reasoning in chemistry and discuss two case studies of curricular projects, CLUE and The Connected Chemistry Curriculum, that have demonstrated a benefit of this approach. We show how sketching activities can be centrally integrated into classroom norms to promote model-based reasoning both with and without component visualizations. Importantly, each of these projects deploys sketching in support of other types of inquiry activities, such as making predictions or depicting models to support a claim; sketching is not an isolated activity but is used as a tool to support model-based reasoning in the discipline. Copyright © 2017 Cognitive Science Society, Inc.

SERS- and Electrochemically Active 3D Plasmonic Liquid Marbles for Molecular-Level Spectroelectrochemical Investigation of Microliter Reactions.

PubMed

Koh, Charlynn Sher Lin; Lee, Hiang Kwee; Phan-Quang, Gia Chuong; Han, Xuemei; Lee, Mian Rong; Yang, Zhe; Ling, Xing Yi

2017-07-17

Liquid marbles are emergent microreactors owing to their isolated environment and the flexibility of materials used. Plasmonic liquid marbles (PLMs) are demonstrated as the smallest spectroelectrochemical microliter-scale reactor for concurrent spectro- and electrochemical analyses. The three-dimensional Ag shell of PLMs are exploited as a bifunctional surface-enhanced Raman scattering (SERS) platform and working electrode for redox process modulation. The combination of SERS and electrochemistry (EC) capabilities enables in situ molecular read-out of transient electrochemical species, and elucidate the potential-dependent and multi-step reaction dynamics. The 3D configuration of our PLM-based EC-SERS system exhibits 2-fold and 10-fold superior electrochemical and SERS performance than conventional 2D platforms. The rich molecular-level electrochemical insights and excellent EC-SERS capabilities offered by our 3D spectroelectrochemical system are pertinent in charge transfer processes. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ultracold molecule assembly with photonic crystals

NASA Astrophysics Data System (ADS)

Pérez-Ríos, Jesús; Kim, May E.; Hung, Chen-Lung

2017-12-01

Photoassociation (PA) is a powerful technique to synthesize molecules directly and continuously from cold and ultracold atoms into deeply bound molecular states. In freespace, however, PA efficiency is constrained by the number of spontaneous decay channels linking the initial excited molecular state to a sea of final (meta)stable rovibronic levels. Here, we propose a novel scheme based on molecules strongly coupled to a guided photonic mode in a photonic crystal waveguide that turns PA into a powerful tool for near deterministic formation of ultracold molecules in their ground rovibrational level. Our example shows a potential ground state molecule production efficiency > 90 % , and a saturation rate > {10}6 molecules per second. By combining state-of-the-art cold atomic and molecular physics with nanophotonic engineering, our scheme presents a novel experimental package for trapping, cooling, and optically manipulating ultracold molecules, thus opening up new possibilities in the direction of ultracold chemistry and quantum information.

Quantum chemical characterization of N-(2-hydroxybenzylidene)acetohydrazide (HBAH): a detailed vibrational and NLO analysis.

PubMed

Tamer, Ömer; Avcı, Davut; Atalay, Yusuf

2014-01-03

The molecular modeling of N-(2-hydroxybenzylidene)acetohydrazide (HBAH) was carried out using B3LYP, CAMB3LYP and PBE1PBE levels of density functional theory (DFT). The molecular structure of HBAH was solved by means of IR, NMR and UV-vis spectroscopies. In order to find the stable conformers, conformational analysis was performed based on B3LYP level. A detailed vibrational analysis was made on the basis of potential energy distribution (PED). HOMO and LUMO energies were calculated, and the obtained energies displayed that charge transfer occurs in HBAH. NLO analysis indicated that HBAH can be used as an effective NLO material. NBO analysis also proved that charge transfer, conjugative interactions and intramolecular hydrogen bonding interactions occur through HBAH. Additionally, major contributions from molecular orbitals to the electronic transitions were investigated theoretically. Copyright © 2013 Elsevier B.V. All rights reserved.

Potential toxicity of graphene to cell functions via disrupting protein-protein interactions.

PubMed

Luan, Binquan; Huynh, Tien; Zhao, Lin; Zhou, Ruhong

2015-01-27

While carbon-based nanomaterials such as graphene and carbon nanotubes (CNTs) have become popular in state-of-the-art nanotechnology, their biological safety and underlying molecular mechanism is still largely unknown. Experimental studies have been focused at the cellular level and revealed good correlations between cell's death and the application of CNTs or graphene. Using large-scale all-atom molecular dynamics simulations, we theoretically investigate the potential toxicity of graphene to a biological cell at molecular level. Simulation results show that the hydrophobic protein-protein interaction (or recognition) that is essential to biological functions can be interrupted by a graphene nanosheet. Due to the hydrophobic nature of graphene, it is energetically favorable for a graphene nanosheet to enter the hydrophobic interface of two contacting proteins, such as a dimer. The forced separation of two functional proteins can disrupt the cell's metabolism and even lead to the cell's mortality.

Melt-growth dynamics in CdTe crystals

DOE PAGES

Zhou, X. W.; Ward, D. K.; Wong, B. M.; ...

2012-06-01

We use a new, quantum-mechanics-based bond-order potential (BOP) to reveal melt growth dynamics and fine scale defect formation mechanisms in CdTe crystals. Previous molecular dynamics simulations of semiconductors have shown qualitatively incorrect behavior due to the lack of an interatomic potential capable of predicting both crystalline growth and property trends of many transitional structures encountered during the melt → crystal transformation. Here, we demonstrate successful molecular dynamics simulations of melt growth in CdTe using a BOP that significantly improves over other potentials on property trends of different phases. Our simulations result in a detailed understanding of defect formation during themore » melt growth process. Equally important, we show that the new BOP enables defect formation mechanisms to be studied at a scale level comparable to empirical molecular dynamics simulation methods with a fidelity level approaching quantum-mechanical methods.« less

Self-doped molecular composite battery electrolytes

DOEpatents

Harrup, Mason K.; Wertsching, Alan K.; Stewart, Frederick F.

2003-04-08

This invention is in solid polymer-based electrolytes for battery applications. It uses molecular composite technology, coupled with unique preparation techniques to render a self-doped, stabilized electrolyte material suitable for inclusion in both primary and secondary batteries. In particular, a salt is incorporated in a nano-composite material formed by the in situ catalyzed condensation of a ceramic precursor in the presence of a solvated polymer material, utilizing a condensation agent comprised of at least one cation amenable to SPE applications. As such, the counterion in the condensation agent used in the formation of the molecular composite is already present as the electrolyte matrix develops. This procedure effectively decouples the cation loading levels required for maximum ionic conductivity from electrolyte physical properties associated with condensation agent loading levels by utilizing the inverse relationship discovered between condensation agent loading and the time domain of the aging step.

Sympathetic Cooling of Molecular Ions in Selected Rotational and Vibrational States Produced by Threshold Photoionization

NASA Astrophysics Data System (ADS)

Tong, Xin; Winney, Alexander H.; Willitsch, Stefan

2010-10-01

We present a new method for the generation of rotationally and vibrationally state-selected, translationally cold molecular ions in ion traps. Our technique is based on the state-selective threshold photoionization of neutral molecules followed by sympathetic cooling of the resulting ions with laser-cooled calcium ions. Using N2+ ions as a test system, we achieve >90% selectivity in the preparation of the ground rovibrational level and state lifetimes on the order of 15 minutes limited by collisions with background-gas molecules. The technique can be employed to produce a wide range of apolar and polar molecular ions in the ground and excited rovibrational states. Our approach opens up new perspectives for cold quantum-controlled ion-molecule-collision studies, frequency-metrology experiments with state-selected molecular ions and molecular-ion qubits.

Molecular nano-arches on silicon

NASA Astrophysics Data System (ADS)

Dobrin, S.

2007-08-01

The formation of molecular nano-arches on the Si(1 1 1)-7 × 7 surface was modeled using density functional theory (DFT). It has been suggested, based on the calculations, that the arches are formed by molecular dimers of chlorobenzene at near-monolayer coverages. Molecules of the dimer are covalently bound to two silicon adatoms and to each other thereby forming a molecular arch on the surface. The structure of the molecular dimer was calculated at the B3LYP/6-31G(d) level of theory. The dimers were found to be stable at room temperature, and to form a near-monolayer coverage, which has been observed in the experiment [X.H. Chen, Q. Kong, J.C. Polanyi, D. Rogers, S. So, Surf. Sci. 340 (1995) 224; Y. Cao, J.F. Deng, G.Q. Xu, J. Chem. Phys. 112 (2000) 4759].

Radiomics biomarkers for accurate tumor progression prediction of oropharyngeal cancer

NASA Astrophysics Data System (ADS)

Hadjiiski, Lubomir; Chan, Heang-Ping; Cha, Kenny H.; Srinivasan, Ashok; Wei, Jun; Zhou, Chuan; Prince, Mark; Papagerakis, Silvana

2017-03-01

Accurate tumor progression prediction for oropharyngeal cancers is crucial for identifying patients who would best be treated with optimized treatment and therefore minimize the risk of under- or over-treatment. An objective decision support system that can merge the available radiomics, histopathologic and molecular biomarkers in a predictive model based on statistical outcomes of previous cases and machine learning may assist clinicians in making more accurate assessment of oropharyngeal tumor progression. In this study, we evaluated the feasibility of developing individual and combined predictive models based on quantitative image analysis from radiomics, histopathology and molecular biomarkers for oropharyngeal tumor progression prediction. With IRB approval, 31, 84, and 127 patients with head and neck CT (CT-HN), tumor tissue microarrays (TMAs) and molecular biomarker expressions, respectively, were collected. For 8 of the patients all 3 types of biomarkers were available and they were sequestered in a test set. The CT-HN lesions were automatically segmented using our level sets based method. Morphological, texture and molecular based features were extracted from CT-HN and TMA images, and selected features were merged by a neural network. The classification accuracy was quantified using the area under the ROC curve (AUC). Test AUCs of 0.87, 0.74, and 0.71 were obtained with the individual predictive models based on radiomics, histopathologic, and molecular features, respectively. Combining the radiomics and molecular models increased the test AUC to 0.90. Combining all 3 models increased the test AUC further to 0.94. This preliminary study demonstrates that the individual domains of biomarkers are useful and the integrated multi-domain approach is most promising for tumor progression prediction.

Spin-dependent Otto quantum heat engine based on a molecular substance

NASA Astrophysics Data System (ADS)

Hübner, W.; Lefkidis, G.; Dong, C. D.; Chaudhuri, D.; Chotorlishvili, L.; Berakdar, J.

2014-07-01

We explore the potential of single molecules for thermodynamic cycles. To this end we propose two molecular heat engines based on the Ni2 dimer in the presence of a static magnetic field: (a) a quantum Otto engine and (b) a modified quantum Otto engine for which optical excitations induced by a laser pulse substitute for one of the heat-exchange points. For reliable predictions and to inspect the role of spin and electronic correlations we perform fully correlated ab initio calculations of the molecular electronic structure including spin-orbital effects. We analyze the efficiency of the engines in dependence of the electronic level scheme and the entanglement and find a significant possible enhancement connected to the quantum nature and the heat capacity of the dimer, as well as to the zero-field triplet states splitting.

Ultra-spatial synchrotron radiation for imaging molecular chemical structure: Applications in plant and animal studies

DOE PAGES

Yu, Peiqiang

2007-01-01

Synchrotron-based Fourier transform infrared microspectroscopy (S-FTIR) has been developed as a rapid, direct, non-destructive, bioanalytical technique. This technique takes advantage of synchrotron light brightness and small effective source size and is capable of exploring the molecular chemical features and make-up within microstructures of a biological tissue without destruction of inherent structures at ultra-spatial resolutions within cellular dimension. To date there has been very little application of this advanced synchrotron technique to the study of plant and animal tissues' inherent structure at a cellular or subcellular level. In this article, a novel approach was introduced to show the potential of themore » newly developed, advanced synchrotron-based analytical technology, which can be used to reveal molecular structural-chemical features of various plant and animal tissues.« less

Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap.

PubMed

Gandal, Michael J; Haney, Jillian R; Parikshak, Neelroop N; Leppa, Virpi; Ramaswami, Gokul; Hartl, Chris; Schork, Andrew J; Appadurai, Vivek; Buil, Alfonso; Werge, Thomas M; Liu, Chunyu; White, Kevin P; Horvath, Steve; Geschwind, Daniel H

2018-02-09

The predisposition to neuropsychiatric disease involves a complex, polygenic, and pleiotropic genetic architecture. However, little is known about how genetic variants impart brain dysfunction or pathology. We used transcriptomic profiling as a quantitative readout of molecular brain-based phenotypes across five major psychiatric disorders-autism, schizophrenia, bipolar disorder, depression, and alcoholism-compared with matched controls. We identified patterns of shared and distinct gene-expression perturbations across these conditions. The degree of sharing of transcriptional dysregulation is related to polygenic (single-nucleotide polymorphism-based) overlap across disorders, suggesting a substantial causal genetic component. This comprehensive systems-level view of the neurobiological architecture of major neuropsychiatric illness demonstrates pathways of molecular convergence and specificity. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Potential for protein surface shape analysis using spherical harmonics and 3D Zernike descriptors.

PubMed

Venkatraman, Vishwesh; Sael, Lee; Kihara, Daisuke

2009-01-01

With structure databases expanding at a rapid rate, the task at hand is to provide reliable clues to their molecular function and to be able to do so on a large scale. This, however, requires suitable encodings of the molecular structure which are amenable to fast screening. To this end, moment-based representations provide a compact and nonredundant description of molecular shape and other associated properties. In this article, we present an overview of some commonly used representations with specific focus on two schemes namely spherical harmonics and their extension, the 3D Zernike descriptors. Key features and differences of the two are reviewed and selected applications are highlighted. We further discuss recent advances covering aspects of shape and property-based comparison at both global and local levels and demonstrate their applicability through some of our studies.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Qin; Zhao, Lichen; Wu, Jiang

Hybrid lead halide perovskites have emerged as high-performance photovoltaic materials with their extraordinary optoelectronic properties. In particular, the remarkable device efficiency is strongly influenced by the perovskite crystallinity and the film morphology. Here, we investigate the perovskites crystallisation kinetics and growth mechanism in real time from liquid precursor continually to the final uniform film. We utilize some advanced in situ characterisation techniques including synchrotron-based grazing incident X-ray diffraction to observe crystal structure and chemical transition of perovskites. The nano-assemble model from perovskite intermediated [PbI 6] 4– cage nanoparticles to bulk polycrystals is proposed to understand perovskites formation at a molecular-more » or nano-level. A crystallisation-depletion mechanism is developed to elucidate the periodic crystallisation and the kinetically trapped morphology at a mesoscopic level. Based on these in situ dynamics studies, the whole process of the perovskites formation and transformation from the molecular to the microstructure over relevant temperature and time scales is successfully demonstrated.« less

Can we trust intraoperative culture results in nonunions?

PubMed

Palmer, Michael P; Altman, Daniel T; Altman, Gregory T; Sewecke, Jeffrey J; Ehrlich, Garth D; Hu, Fen Z; Nistico, Laura; Melton-Kreft, Rachel; Gause, Trent M; Costerton, John W

2014-07-01

To identify the presence of bacterial biofilms in nonunions comparing molecular techniques (multiplex polymerase chain reaction and mass spectrometry, fluorescent in situ hybridization) with routine intraoperative cultures. Thirty-four patients with nonunions were scheduled for surgery and enrolled in this ongoing prospective study. Intraoperative specimens were collected from removed implants, surrounding tissue membrane, and local soft tissue followed by standard culture analysis, Ibis's second generation molecular diagnostics (Ibis Biosystems), and bacterial 16S rRNA-based fluorescence in situ hybridization (FISH). Confocal microscopy was used to visualize the tissue specimens reacted with the FISH probes, which were chosen based on the Ibis analysis. Thirty-four patient encounters were analyzed. Eight were diagnosed as infected nonunions by positive intraoperative culture results. Ibis confirmed the presence of bacteria in all 8 samples. Ibis identified bacteria in a total of 30 of 34 encounters, and these data were confirmed by FISH. Twenty-two of 30 Ibis-positive samples were culture-negative. Four samples were negative by all methods of analysis. No samples were positive by culture, but negative by molecular techniques. Our preliminary data indicate that molecular diagnostics are more sensitive for identifying bacteria than cultures in cases of bony nonunion. This is likely because of the inability of cultures to detect biofilms and bacteria previously exposed to antibiotic therapy. Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.

An Imide-Based Pentacyclic Building Block for n-Type Organic Semiconductors

DOE PAGES

Wu, Fu-Peng; Un, Hio-Ieng; Li, Yongxi; ...

2017-10-09

For this study a new electron-deficient unit with fused 5-heterocyclic ring was developed by replacing a cyclopenta-1,3-diene from electron-rich donor indacenodithiophene (IDT) with cyclohepta-4,6-diene-1,3-diimde unit. The imide bridging endows BBI with fixed planar configuration and both low the highest occupied molecular orbital (HOMO) (-6.24 eV) and the lowest unoccupied molecular orbit (LUMO) (-2.57 eV) energy levels. Organic field-effect transistors (OFETs) based on BBI polymers exhibit electron mobility up to 0.34 cm 2 V -1 s -1, which indicates that the BBI is a promising n-type building block for optoelectronics.

An Imide-Based Pentacyclic Building Block for n-Type Organic Semiconductors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Fu-Peng; Un, Hio-Ieng; Li, Yongxi

For this study a new electron-deficient unit with fused 5-heterocyclic ring was developed by replacing a cyclopenta-1,3-diene from electron-rich donor indacenodithiophene (IDT) with cyclohepta-4,6-diene-1,3-diimde unit. The imide bridging endows BBI with fixed planar configuration and both low the highest occupied molecular orbital (HOMO) (-6.24 eV) and the lowest unoccupied molecular orbit (LUMO) (-2.57 eV) energy levels. Organic field-effect transistors (OFETs) based on BBI polymers exhibit electron mobility up to 0.34 cm 2 V -1 s -1, which indicates that the BBI is a promising n-type building block for optoelectronics.

Molecular-level architectural design using benzothiadiazole-based polymers for photovoltaic applications

PubMed Central

Viswanathan, Vinila N; Rao, Arun D; Pandey, Upendra K; Kesavan, Arul Varman

2017-01-01

A series of low band gap, planar conjugated polymers, P1 (PFDTBT), P2 (PFDTDFBT) and P3 (PFDTTBT), based on fluorene and benzothiadiazole, was synthesized. The effect of fluorine substitution and fused aromatic spacers on the optoelectronic and photovoltaic performance was studied. The polymer, derived from dithienylated benzothiodiazole and fluorene, P1, exhibited a highest occupied molecular orbital (HOMO) energy level at −5.48 eV. Density functional theory (DFT) studies as well as experimental measurements suggested that upon substitution of the acceptor with fluorine, both the HOMO and lowest unoccupied molecular orbital (LUMO) energy levels of the resulting polymer, P2, were lowered, leading to a higher open circuit voltage and short circuit current with an overall improvement of more than 110% for the photovoltaic devices. Moreover, a decrease in the torsion angle between the units was also observed for the fluorinated polymer P2 due to the enhanced electrostatic interaction between the fluorine substituents and sulfur atoms, leading to a high hole mobility. The use of a fused π-bridge in polymer P3 for the enhancement of the planarity as compared to the P1 backbone was also studied. This enhanced planarity led to the highest observed mobility among the reported three polymers as well as to an improvement in the device efficiency by more than 40% for P3. PMID:28546844

An artificial muscle model unit based on inorganic nanosheet sliding by photochemical reaction.

PubMed

Nabetani, Yu; Takamura, Hazuki; Hayasaka, Yuika; Sasamoto, Shin; Tanamura, Yoshihiko; Shimada, Tetsuya; Masui, Dai; Takagi, Shinsuke; Tachibana, Hiroshi; Tong, Zhiwei; Inoue, Haruo

2013-04-21

From the viewpoint of developing photoresponsive supramolecular systems in microenvironments to exhibit more sophisticated photo-functions even at the macroscopic level, inorganic/organic hybrid compounds based on clay or niobate nanosheets as the microenvironments were prepared, characterized, and examined for their photoreactions. We show here a novel type of artificial muscle model unit having much similarity with that in natural muscle fibrils. Upon photoirradiation, the organic/inorganic hybrid nanosheets reversibly slide horizontally on a giant scale, and the interlayer spaces in the layered hybrid structure shrink and expand vertically. In particular, our layered hybrid molecular system exhibits a macroscopic morphological change on a giant scale (~1500 nm) compared with the molecular size of ~1 nm, based on a reversible sliding mechanism.

A low Earth orbit molecular beam space simulation facility

NASA Technical Reports Server (NTRS)

Cross, J. B.

1984-01-01

A brief synopsis of the low Earth orbit (LEO) satellite environment is presented including neutral and ionic species. Two ground based atomic and molecular beam instruments are described which are capable of simulating the interaction of spacecraft surfaces with the LEO environment and detecting the results of these interactions. The first detects mass spectrometrically low level fluxes of reactively and nonreactively surface scattered species as a function of scattering angle and velocity while the second ultrahigh velocity (UHV) molecular beam, laser induced fluorescence apparatus is capable of measuring chemiluminescence produced by either gas phase or gas-surface interactions. A number of proposed experiments are described.

Molecular-level chemistry of model single-crystal oxide surfaces with model halogenated compounds

NASA Astrophysics Data System (ADS)

Adib, Kaveh

Synchrotron-based X-ray photoelectron spectroscopy (XPS), temperature-programmed desorption (TPD) and low energy electron diffraction (LEED) have been used to investigate, at a molecular level, the chemistry of different terminations of single crystal iron-oxide surfaces with probe molecules (CCl4 and D2O). Comparisons of the reactivity of these surfaces towards CCl4, indicate that the presence of an uncapped surface Fe cation (strong Lewis acid site) and an adjacent oxygen site capped by that cation can effect the C-Cl bond cleavage in CCl4, resulting in dissociatively adsorbed Cl-adatoms and carbon-containing fragments. If in addition to these sites, an uncapped surface oxygen (Lewis base) site is also available, the carbon-containing moiety can then move that site, coordinate itself with that uncapped oxygen, and stabilize itself. At a later step, the carbon-containing fragment may form a strong covalent bond with the uncapped oxygen and may even abstract that surface oxygen. On the other hand, if an uncapped oxygen is not available to stabilize the carbon-containing fragment, the surface coordination will not occur and upon the subsequent thermal annealing of the surface the Cl-adatoms and the carbon-containing fragments will recombine and desorb as CCl4. Finally, the presence of surface deuteroxyls blocking the strong Lewis acid and base sites of the reactive surface, passivates this surface. Such a deuteroxylated surface will be unreactive towards CCl 4. Such a molecular level understanding of the surface chemistry of metal-oxides will have applications in the areas of selective catalysis, including environmental catalysis, and chemical sensor technology.

Analog synthetic biology.

PubMed

Sarpeshkar, R

2014-03-28

We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog-digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA-protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations.

Analog synthetic biology

PubMed Central

Sarpeshkar, R.

2014-01-01

We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog–digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA–protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations. PMID:24567476

The molecular, electronic structures and vibrational spectra of metal-free, N,N'-dideuterio and magnesium tetra-2,3-pyridino-porphyrazines: Density functional calculations.

PubMed

Liu, Zhongqiang; Zhang, Xianxi; Zhang, Yuexing; Li, Renjie; Jiang, Jianzhuang

2006-10-01

A theoretical investigation of the fully optimized geometries and electronic structures of the metal-free (TPdPzH(2)), N,N'-dideuterio (TPdPzD(2)), and magnesium (TPdPzMg) tetra-2,3-pyridino-porphyrazine has been conducted based on density functional theory. The optimized geometries at density functional theory level for these compounds are reported here for the first time. A comparison between the different molecules for the geometry, molecular orbital, and atomic charge is made. The substituent effect of the N atoms on the molecular structures of these compounds is discussed. The IR and Raman spectra for these three compounds have also been calculated at density functional B3LYP level using the 6-31G(d) basis set. Detailed assignments of the NH, NM, and pyridine ring vibrational bands in the IR and Raman spectra have been made based on assistance of animated pictures. The simulated IR spectra of TPdPzH(2) are compared with the experimental absorption spectra, and very good consistency has been found. The isotope effect on the IR and Raman spectra is also discussed.

Observing interactions between DNA bases using ion dip spectroscopy.

NASA Astrophysics Data System (ADS)

Vries Mattanjah, De

2002-03-01

We investigate biomolecular building blocks and their clusters with each other and with water on a single molecular level. The motivation is the need to distinguish between intrinsic molecular properties and those that result from the biological environment. This is achieved by a combination of laser desorption and jet cooling, applied to aromatic amino acids, small peptides containing those, purine bases and nucleosides. This approach is coupled with a number of gas phase laser spectroscopic techniques. We will present results for DNA bases guanine, adenine, cytosine, and their derivatives, for which we obtained tautomer selected vibronic spectra. Capitalizing on these results we use these bases as chromophores to study interactions in single base pairs, obtained by formation of clusters of laser desorbed bases in a supersonic beam. For analysis we employ both UV/UV and IR/UV ion-dip spectroscopy, the results of which we compare with ab initio calculations.

A Comparison of Molecular Vibrational Theory to Huckel Molecular Orbital Theory.

ERIC Educational Resources Information Center

Keeports, David

1986-01-01

Compares the similar mathematical problems of molecular vibrational calculations (at any intermediate level of sophistication) and molecular orbital calculations (at the Huckel level). Discusses how the generalizations of Huckel treatment of molecular orbitals apply to vibrational theory. (TW)

Network-Based Integration of Disparate Omic Data To Identify "Silent Players" in Cancer

PubMed Central

Ruffalo, Matthew

2015-01-01

Development of high-throughput monitoring technologies enables interrogation of cancer samples at various levels of cellular activity. Capitalizing on these developments, various public efforts such as The Cancer Genome Atlas (TCGA) generate disparate omic data for large patient cohorts. As demonstrated by recent studies, these heterogeneous data sources provide the opportunity to gain insights into the molecular changes that drive cancer pathogenesis and progression. However, these insights are limited by the vast search space and as a result low statistical power to make new discoveries. In this paper, we propose methods for integrating disparate omic data using molecular interaction networks, with a view to gaining mechanistic insights into the relationship between molecular changes at different levels of cellular activity. Namely, we hypothesize that genes that play a role in cancer development and progression may be implicated by neither frequent mutation nor differential expression, and that network-based integration of mutation and differential expression data can reveal these “silent players”. For this purpose, we utilize network-propagation algorithms to simulate the information flow in the cell at a sample-specific resolution. We then use the propagated mutation and expression signals to identify genes that are not necessarily mutated or differentially expressed genes, but have an essential role in tumor development and patient outcome. We test the proposed method on breast cancer and glioblastoma multiforme data obtained from TCGA. Our results show that the proposed method can identify important proteins that are not readily revealed by molecular data, providing insights beyond what can be gleaned by analyzing different types of molecular data in isolation. PMID:26683094

Systematic, spatial imaging of large multimolecular assemblies and the emerging principles of supramolecular order in biological systems

PubMed Central

Schubert, Walter

2013-01-01

Understanding biological systems at the level of their relational (emergent) molecular properties in functional protein networks relies on imaging methods, able to spatially resolve a tissue or a cell as a giant, non-random, topologically defined collection of interacting supermolecules executing myriads of subcellular mechanisms. Here, the development and findings of parameter-unlimited functional super-resolution microscopy are described—a technology based on the fluorescence imaging cycler (IC) principle capable of co-mapping thousands of distinct biomolecular assemblies at high spatial resolution and differentiation (<40 nm distances). It is shown that the subcellular and transcellular features of such supermolecules can be described at the compositional and constitutional levels; that the spatial connection, relational stoichiometry, and topology of supermolecules generate hitherto unrecognized functional self-segmentation of biological tissues; that hierarchical features, common to thousands of simultaneously imaged supermolecules, can be identified; and how the resulting supramolecular order relates to spatial coding of cellular functionalities in biological systems. A large body of observations with IC molecular systems microscopy collected over 20 years have disclosed principles governed by a law of supramolecular segregation of cellular functionalities. This pervades phenomena, such as exceptional orderliness, functional selectivity, combinatorial and spatial periodicity, and hierarchical organization of large molecular systems, across all species investigated so far. This insight is based on the high degree of specificity, selectivity, and sensitivity of molecular recognition processes for fluorescence imaging beyond the spectral resolution limit, using probe libraries controlled by ICs. © 2013 The Authors. Journal of Molecular Recognition published by John Wiley & Sons, Ltd. PMID:24375580

Molecular identification of organic compounds in atmospheric complex mixtures and relationship to atmospheric chemistry and sources.

PubMed

Mazurek, Monica A

2002-12-01

This article describes a chemical characterization approach for complex organic compound mixtures associated with fine atmospheric particles of diameters less than 2.5 m (PM2.5). It relates molecular- and bulk-level chemical characteristics of the complex mixture to atmospheric chemistry and to emission sources. Overall, the analytical approach describes the organic complex mixtures in terms of a chemical mass balance (CMB). Here, the complex mixture is related to a bulk elemental measurement (total carbon) and is broken down systematically into functional groups and molecular compositions. The CMB and molecular-level information can be used to understand the sources of the atmospheric fine particles through conversion of chromatographic data and by incorporation into receptor-based CMB models. Once described and quantified within a mass balance framework, the chemical profiles for aerosol organic matter can be applied to existing air quality issues. Examples include understanding health effects of PM2.5 and defining and controlling key sources of anthropogenic fine particles. Overall, the organic aerosol compositional data provide chemical information needed for effective PM2.5 management.

Live Cell Imaging of Viscosity in 3D Tumour Cell Models.

PubMed

Shirmanova, Marina V; Shimolina, Lubov' E; Lukina, Maria M; Zagaynova, Elena V; Kuimova, Marina K

2017-01-01

Abnormal levels of viscosity in tissues and cells are known to be associated with disease and malfunction. While methods to measure bulk macroscopic viscosity of bio-tissues are well developed, imaging viscosity at the microscopic scale remains a challenge, especially in vivo. Molecular rotors are small synthetic viscosity-sensitive fluorophores in which fluorescence parameters are strongly correlated to the microviscosity of their immediate environment. Hence, molecular rotors represent a promising instrument for mapping of viscosity in living cells and tissues at the microscopic level. Quantitative measurements of viscosity can be achieved by recording time-resolved fluorescence decays of molecular rotor using fluorescence lifetime imaging microscopy (FLIM), which is also suitable for dynamic viscosity mapping, both in cellulo and in vivo. Among tools of experimental oncology, 3D tumour cultures, or spheroids, are considered a more adequate in vitro model compared to a cellular monolayer, and represent a less labour-intensive and more unified approach compared to animal tumour models. This chapter describes a methodology for microviscosity imaging in tumour spheroids using BODIPY-based molecular rotors and two photon-excited FLIM.

Multigene Molecular Phylogeny and Biogeographic Diversification of the Earth Tongue Fungi in the Genera Cudonia and Spathularia (Rhytismatales, Ascomycota)

PubMed Central

Ge, Zai-Wei; Yang, Zhu L.; Pfister, Donald H.; Carbone, Matteo; Bau, Tolgor; Smith, Matthew E.

2014-01-01

The family Cudoniaceae (Rhytismatales, Ascomycota) was erected to accommodate the “earth tongue fungi” in the genera Cudonia and Spathularia. There have been no recent taxonomic studies of these genera, and the evolutionary relationships within and among these fungi are largely unknown. Here we explore the molecular phylogenetic relationships within Cudonia and Spathularia using maximum likelihood and Bayesian inference analyses based on 111 collections from across the Northern Hemisphere. Phylogenies based on the combined data from ITS, nrLSU, rpb2 and tef-1α sequences support the monophyly of three main clades, the /flavida, /velutipes, and /cudonia clades. The genus Cudonia and the family Cudoniaceae are supported as monophyletic groups, while the genus Spathularia is not monophyletic. Although Cudoniaceae is monophyletic, our analyses agree with previous studies that this family is nested within the Rhytismataceae. Our phylogenetic analyses circumscribes 32 species-level clades, including the putative recognition of 23 undescribed phylogenetic species. Our molecular phylogeny also revealed an unexpectedly high species diversity of Cudonia and Spathularia in eastern Asia, with 16 (out of 21) species-level clades of Cudonia and 8 (out of 11) species-level clades of Spathularia. We estimate that the divergence time of the Cudoniaceae was in the Paleogene approximately 28 Million years ago (Mya) and that the ancestral area for this group of fungi was in Eastern Asia based on the current data. We hypothesize that the large-scale geological and climatic events in Oligocene (e.g. the global cooling and the uplift of the Tibetan plateau) may have triggered evolutionary radiations in this group of fungi in East Asia. This work provides a foundation for future studies on the phylogeny, diversity, and evolution of Cudonia and Spathularia and highlights the need for more molecular studies on collections from Europe and North America. PMID:25084276

Superluminescence from an optically pumped molecular tunneling junction by injection of plasmon induced hot electrons

PubMed Central

Braun, Kai; Wang, Xiao; Kern, Andreas M; Adler, Hilmar; Peisert, Heiko; Chassé, Thomas; Zhang, Dai

2015-01-01

Summary Here, we demonstrate a bias-driven superluminescent point light-source based on an optically pumped molecular junction (gold substrate/self-assembled molecular monolayer/gold tip) of a scanning tunneling microscope, operating at ambient conditions and providing almost three orders of magnitude higher electron-to-photon conversion efficiency than electroluminescence induced by inelastic tunneling without optical pumping. A positive, steadily increasing bias voltage induces a step-like rise of the Stokes shifted optical signal emitted from the junction. This emission is strongly attenuated by reversing the applied bias voltage. At high bias voltage, the emission intensity depends non-linearly on the optical pump power. The enhanced emission can be modelled by rate equations taking into account hole injection from the tip (anode) into the highest occupied orbital of the closest substrate-bound molecule (lower level) and radiative recombination with an electron from above the Fermi level (upper level), hence feeding photons back by stimulated emission resonant with the gap mode. The system reflects many essential features of a superluminescent light emitting diode. PMID:26171286

iTRAQ-Based Quantitative Proteomic Analysis of the Antimicrobial Mechanism of Peptide F1 against Escherichia coli.

PubMed

Miao, Jianyin; Chen, Feilong; Duan, Shan; Gao, Xiangyang; Liu, Guo; Chen, Yunjiao; Dixon, William; Xiao, Hang; Cao, Yong

2015-08-19

Antimicrobial peptides have received increasing attention in the agricultural and food industries due to their potential to control pathogens. However, to facilitate the development of novel peptide-based antimicrobial agents, details regarding the molecular mechanisms of these peptides need to be elucidated. The aim of this study was to investigate the antimicrobial mechanism of peptide F1, a bacteriocin found in Tibetan kefir, against Escherichia coli at protein levels using iTRAQ-based quantitative proteomic analysis. In response to treatment with peptide F1, 31 of the 280 identified proteins in E. coli showed alterations in their expression, including 10 down-regulated proteins and 21 up-regulated proteins. These 31 proteins all possess different molecular functions and are involved in different molecular pathways, as is evident in referencing the Kyoto Encyclopedia of Genes and Genomes pathways. Specifically, pathways that were significantly altered in E. coli in response to peptide F1 treatment include the tricarboxylic acid cycle, oxidative phosphorylation, glycerophospholipid metabolism, and the cell cycle-caulobacter pathways, which was also associated with inhibition of the cell growth, induction of morphological changes, and cell death. The results provide novel insights into the molecular mechanisms of antimicrobial peptides.

Molecular interactions in high conductive gel electrolytes based on low molecular weight gelator.

PubMed

Bielejewski, Michał; Łapiński, Andrzej; Demchuk, Oleg

2017-03-15

Organic ionic gel (OIG) electrolytes, also known as gel electrolytes or ionogels are one example of modern functional materials with the potential to use in wide range of electrochemical applications. The functionality of OIGs arises from the thermally reversible solidification of electrolytes or ionic liquids and their superior ionic conductivity. To understand and to predict the properties of these systems it is important to get the knowledge about the interactions on molecular level between the solid gelator matrix and the electrolyte solution. This paper reports the spectroscopic studies (FT-IR, UV-Vis and Raman) of the gel electrolyte based on low molecular weight gelator methyl-4,6-O-(p-nitrobenzylidene)-α-d-glucopyranoside and solution of quaternary ammonium salt, tetramethylammonium bromide. The solidification process was based on sol-gel technique. Below characteristic temperature, defined as gel to sol phase transition temperature, T gs , the samples were solid-like and showed high conductivity values of the same order as observed for pure liquid electrolytes. The investigations were performed for a OIGs in a wide range of molar concentrations of the electrolyte solution. Copyright © 2016 Elsevier Inc. All rights reserved.

Fragmented Knowledge and Missing Connections between Knowledge from Different Hierarchical Organisational Levels of Reproduction among Adolescents and Young Adults

ERIC Educational Resources Information Center

Šorgo, Andrej; Šiling, Rebeka

2017-01-01

Based on the responses of our sample (N = 310) of adolescents and young adults from Slovenia (students of secondary and tertiary schools, university students) to a number of tasks covering reproduction, from the molecular to organismal levels, it can be concluded that their knowledge is seriously flawed. Correlations of knowledge between…

Problems of low-parameter equations of state

NASA Astrophysics Data System (ADS)

Petrik, G. G.

2017-11-01

The paper focuses on the system approach to problems of low-parametric equations of state (EOS). It is a continuation of the investigations in the field of substantiated prognosis of properties on two levels, molecular and thermodynamic. Two sets of low-parameter EOS have been considered based on two very simple molecular-level models. The first one consists of EOS of van der Waals type (a modification of van der Waals EOS proposed for spheres). The main problem of these EOS is a weak connection with the micro-level, which raise many uncertainties. The second group of EOS has been derived by the author independently of the ideas of van der Waals based on the model of interacting point centers (IPC). All the parameters of the EOS have a meaning and are associated with the manifestation of attractive and repulsive forces. The relationship between them is found to be the control parameter of the thermodynamic level. In this case, EOS IPC passes into a one-parameter family. It is shown that many EOS of vdW-type can be included in the framework of the PC model. Simultaneously, all their parameters acquire a physical meaning.

Single walled boron nitride nanotube-based biosensor: an atomistic finite element modelling approach.

PubMed

Panchal, Mitesh B; Upadhyay, Sanjay H

2014-09-01

The unprecedented dynamic characteristics of nanoelectromechanical systems make them suitable for nanoscale mass sensing applications. Owing to superior biocompatibility, boron nitride nanotubes (BNNTs) are being increasingly used for such applications. In this study, the feasibility of single walled BNNT (SWBNNT)-based bio-sensor has been explored. Molecular structural mechanics-based finite element (FE) modelling approach has been used to analyse the dynamic behaviour of SWBNNT-based biosensors. The application of an SWBNNT-based mass sensing for zeptogram level of mass has been reported. Also, the effect of size of the nanotube in terms of length as well as different chiral atomic structures of SWBNNT has been analysed for their sensitivity analysis. The vibrational behaviour of SWBNNT has been analysed for higher-order modes of vibrations to identify the intermediate landing position of biological object of zeptogram scale. The present molecular structural mechanics-based FE modelling approach is found to be very effectual to incorporate different chiralities of the atomic structures. Also, different boundary conditions can be effectively simulated using the present approach to analyse the dynamic behaviour of the SWBNNT-based mass sensor. The presented study has explored the potential of SWBNNT, as a nanobiosensor having the capability of zeptogram level mass sensing.

Reconstruction of fluorescence molecular tomography with a cosinoidal level set method.

PubMed

Zhang, Xuanxuan; Cao, Xu; Zhu, Shouping

2017-06-27

Implicit shape-based reconstruction method in fluorescence molecular tomography (FMT) is capable of achieving higher image clarity than image-based reconstruction method. However, the implicit shape method suffers from a low convergence speed and performs unstably due to the utilization of gradient-based optimization methods. Moreover, the implicit shape method requires priori information about the number of targets. A shape-based reconstruction scheme of FMT with a cosinoidal level set method is proposed in this paper. The Heaviside function in the classical implicit shape method is replaced with a cosine function, and then the reconstruction can be accomplished with the Levenberg-Marquardt method rather than gradient-based methods. As a result, the priori information about the number of targets is not required anymore and the choice of step length is avoided. Numerical simulations and phantom experiments were carried out to validate the proposed method. Results of the proposed method show higher contrast to noise ratios and Pearson correlations than the implicit shape method and image-based reconstruction method. Moreover, the number of iterations required in the proposed method is much less than the implicit shape method. The proposed method performs more stably, provides a faster convergence speed than the implicit shape method, and achieves higher image clarity than the image-based reconstruction method.

Molecular-Scale Electronics: From Concept to Function.

PubMed

Xiang, Dong; Wang, Xiaolong; Jia, Chuancheng; Lee, Takhee; Guo, Xuefeng

2016-04-13

Creating functional electrical circuits using individual or ensemble molecules, often termed as "molecular-scale electronics", not only meets the increasing technical demands of the miniaturization of traditional Si-based electronic devices, but also provides an ideal window of exploring the intrinsic properties of materials at the molecular level. This Review covers the major advances with the most general applicability and emphasizes new insights into the development of efficient platform methodologies for building reliable molecular electronic devices with desired functionalities through the combination of programmed bottom-up self-assembly and sophisticated top-down device fabrication. First, we summarize a number of different approaches of forming molecular-scale junctions and discuss various experimental techniques for examining these nanoscale circuits in details. We then give a full introduction of characterization techniques and theoretical simulations for molecular electronics. Third, we highlight the major contributions and new concepts of integrating molecular functionalities into electrical circuits. Finally, we provide a critical discussion of limitations and main challenges that still exist for the development of molecular electronics. These analyses should be valuable for deeply understanding charge transport through molecular junctions, the device fabrication process, and the roadmap for future practical molecular electronics.

The impact of computer science in molecular medicine: enabling high-throughput research.

PubMed

de la Iglesia, Diana; García-Remesal, Miguel; de la Calle, Guillermo; Kulikowski, Casimir; Sanz, Ferran; Maojo, Víctor

2013-01-01

The Human Genome Project and the explosion of high-throughput data have transformed the areas of molecular and personalized medicine, which are producing a wide range of studies and experimental results and providing new insights for developing medical applications. Research in many interdisciplinary fields is resulting in data repositories and computational tools that support a wide diversity of tasks: genome sequencing, genome-wide association studies, analysis of genotype-phenotype interactions, drug toxicity and side effects assessment, prediction of protein interactions and diseases, development of computational models, biomarker discovery, and many others. The authors of the present paper have developed several inventories covering tools, initiatives and studies in different computational fields related to molecular medicine: medical informatics, bioinformatics, clinical informatics and nanoinformatics. With these inventories, created by mining the scientific literature, we have carried out several reviews of these fields, providing researchers with a useful framework to locate, discover, search and integrate resources. In this paper we present an analysis of the state-of-the-art as it relates to computational resources for molecular medicine, based on results compiled in our inventories, as well as results extracted from a systematic review of the literature and other scientific media. The present review is based on the impact of their related publications and the available data and software resources for molecular medicine. It aims to provide information that can be useful to support ongoing research and work to improve diagnostics and therapeutics based on molecular-level insights.

Integrative analysis of genes and miRNA alterations in human embryonic stem cells-derived neural cells after exposure to silver nanoparticles.

PubMed

Oh, Jung-Hwa; Son, Mi-Young; Choi, Mi-Sun; Kim, Soojin; Choi, A-Young; Lee, Hyang-Ae; Kim, Ki-Suk; Kim, Janghwan; Song, Chang Woo; Yoon, Seokjoo

2016-05-15

Given the rapid growth of engineered and customer products made of silver nanoparticles (Ag NPs), understanding their biological and toxicological effects on humans is critically important. The molecular developmental neurotoxic effects associated with exposure to Ag NPs were analyzed at the physiological and molecular levels, using an alternative cell model: human embryonic stem cell (hESC)-derived neural stem/progenitor cells (NPCs). In this study, the cytotoxic effects of Ag NPs (10-200μg/ml) were examined in these hESC-derived NPCs, which have a capacity for neurogenesis in vitro, at 6 and 24h. The results showed that Ag NPs evoked significant toxicity in hESC-derived NPCs at 24h in a dose-dependent manner. In addition, Ag NPs induced cell cycle arrest and apoptosis following a significant increase in oxidative stress in these cells. To further clarify the molecular mechanisms of the toxicological effects of Ag NPs at the transcriptional and post-transcriptional levels, the global expression profiles of genes and miRNAs were analyzed in hESC-derived NPCs after Ag NP exposure. The results showed that Ag NPs induced oxidative stress and dysfunctional neurogenesis at the molecular level in hESC-derived NPCs. Based on this hESC-derived neural cell model, these findings have increased our understanding of the molecular events underlying developmental neurotoxicity induced by Ag NPs in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

Molecular structure, mechanical behavior and failure mechanism of the C-terminal cross-link domain in type I collagen.

PubMed

Uzel, Sebastien G M; Buehler, Markus J

2011-02-01

Collagen is a key constituent in structural materials found in biology, including bone, tendon, skin and blood vessels. Here we report a first molecular level model of an entire overlap region of a C-terminal cross-linked type I collagen assembly and carry out a nanomechanical characterization based on large-scale molecular dynamics simulation in explicit water solvent. Our results show that the deformation mechanism and strength of the structure are greatly affected by the presence of the cross-link, and by the specific loading condition of how the stretching is applied. We find that the presence of a cross-link results in greater strength during deformation as complete intermolecular slip is prevented, and thereby particularly affects larger deformation levels. Conversely, the lack of a cross-link results in the onset of intermolecular sliding during deformation and as a result an overall weaker structure is obtained. Through a detailed analysis of the distribution of deformation by calculating the molecular strain we show that the location of largest strains does not occur around the covalent bonding region, but is found in regions further away from this location. The insight developed from understanding collagenous materials from a fundamental molecular level upwards could play a role in advancing our understanding of physiological and disease states of connective tissues, and also enable the development of new scaffolding material for applications in regenerative medicine and biologically inspired materials. Copyright © 2011. Elsevier Ltd. All rights reserved.

Ab initio molecular simulations with numeric atom-centered orbitals

NASA Astrophysics Data System (ADS)

Blum, Volker; Gehrke, Ralf; Hanke, Felix; Havu, Paula; Havu, Ville; Ren, Xinguo; Reuter, Karsten; Scheffler, Matthias

2009-11-01

We describe a complete set of algorithms for ab initio molecular simulations based on numerically tabulated atom-centered orbitals (NAOs) to capture a wide range of molecular and materials properties from quantum-mechanical first principles. The full algorithmic framework described here is embodied in the Fritz Haber Institute "ab initio molecular simulations" (FHI-aims) computer program package. Its comprehensive description should be relevant to any other first-principles implementation based on NAOs. The focus here is on density-functional theory (DFT) in the local and semilocal (generalized gradient) approximations, but an extension to hybrid functionals, Hartree-Fock theory, and MP2/GW electron self-energies for total energies and excited states is possible within the same underlying algorithms. An all-electron/full-potential treatment that is both computationally efficient and accurate is achieved for periodic and cluster geometries on equal footing, including relaxation and ab initio molecular dynamics. We demonstrate the construction of transferable, hierarchical basis sets, allowing the calculation to range from qualitative tight-binding like accuracy to meV-level total energy convergence with the basis set. Since all basis functions are strictly localized, the otherwise computationally dominant grid-based operations scale as O(N) with system size N. Together with a scalar-relativistic treatment, the basis sets provide access to all elements from light to heavy. Both low-communication parallelization of all real-space grid based algorithms and a ScaLapack-based, customized handling of the linear algebra for all matrix operations are possible, guaranteeing efficient scaling (CPU time and memory) up to massively parallel computer systems with thousands of CPUs.

Molecular Physiology of Root System Architecture in Model Grasses

NASA Astrophysics Data System (ADS)

Hixson, K.; Ahkami, A. H.; Anderton, C.; Veličković, D.; Myers, G. L.; Chrisler, W.; Lindenmaier, R.; Fang, Y.; Yabusaki, S.; Rosnow, J. J.; Farris, Y.; Khan, N. E.; Bernstein, H. C.; Jansson, C.

2017-12-01

Unraveling the molecular and physiological mechanisms involved in responses of Root System Architecture (RSA) to abiotic stresses and shifts in microbiome structure is critical to understand and engineer plant-microbe-soil interactions in the rhizosphere. In this study, accessions of Brachypodium distachyon Bd21 (C3 model grass) and Setaria viridis A10.1 (C4 model grass) were grown in phytotron chambers under current and elevated CO2 levels. Detailed growth stage-based phenotypic analysis revealed different above- and below-ground morphological and physiological responses in C3 and C4 grasses to enhanced CO2 levels. Based on our preliminary results and by screening values of total biomass, water use efficiency, root to shoot ratio, RSA parameters and net assimilation rates, we postulated a three-phase physiological mechanism, i.e. RootPlus, BiomassPlus and YieldPlus phases, for grass growth under elevated CO2 conditions. Moreover, this comprehensive set of morphological and process-based observations are currently in use to develop, test, and calibrate biophysical whole-plant models and in particular to simulate leaf-level photosynthesis at various developmental stages of C3 and C4 using the model BioCro. To further link the observed phenotypic traits at the organismal level to tissue and molecular levels, and to spatially resolve the origin and fate of key metabolites involved in primary carbohydrate metabolism in different root sections, we complement root phenotypic observations with spatial metabolomics data using mass spectrometry imaging (MSI) methods. Focusing on plant-microbe interactions in the rhizosphere, six bacterial strains with plant growth promoting features are currently in use in both gel-based and soil systems to screen root growth and development in Brachypodium. Using confocal microscopy, GFP-tagged bacterial systems are utilized to study the initiation of different root types of RSA, including primary root (PR), coleoptile node axile root (CNR) and leaf node axile root (LNR) during developmental stages of root formation. The root exudates also will be quantified and preliminary data will be used to engineer our microbial consortium to improve plant growth.

Comparison between Proteome and Transcriptome Response in Potato (Solanum tuberosum L.) Leaves Following Potato Virus Y (PVY) Infection.

PubMed

Stare, Tjaša; Stare, Katja; Weckwerth, Wolfram; Wienkoop, Stefanie; Gruden, Kristina

2017-07-06

Plant diseases caused by viral infection are affecting all major crops. Being an obligate intracellular organisms, chemical control of these pathogens is so far not applied in the field except to control the insect vectors of the viruses. Understanding of molecular responses of plant immunity is therefore economically important, guiding the enforcement of crop resistance. To disentangle complex regulatory mechanisms of the plant immune responses, understanding system as a whole is a must. However, integrating data from different molecular analysis (transcriptomics, proteomics, metabolomics, smallRNA regulation etc.) is not straightforward. We evaluated the response of potato ( Solanum tuberosum L.) following the infection with potato virus Y (PVY). The response has been analyzed on two molecular levels, with microarray transcriptome analysis and mass spectroscopy-based proteomics. Within this report, we performed detailed analysis of the results on both levels and compared two different approaches for analysis of proteomic data (spectral count versus MaxQuant). To link the data on different molecular levels, each protein was mapped to the corresponding potato transcript according to StNIB paralogue grouping. Only 33% of the proteins mapped to microarray probes in a one-to-one relation and additionally many showed discordance in detected levels of proteins with corresponding transcripts. We discussed functional importance of true biological differences between both levels and showed that the reason for the discordance between transcript and protein abundance lies partly in complexity and structure of biological regulation of proteome and transcriptome and partly in technical issues contributing to it.

Comparison between Proteome and Transcriptome Response in Potato (Solanum tuberosum L.) Leaves Following Potato Virus Y (PVY) Infection

PubMed Central

Stare, Tjaša; Stare, Katja; Weckwerth, Wolfram; Wienkoop, Stefanie

2017-01-01

Plant diseases caused by viral infection are affecting all major crops. Being an obligate intracellular organisms, chemical control of these pathogens is so far not applied in the field except to control the insect vectors of the viruses. Understanding of molecular responses of plant immunity is therefore economically important, guiding the enforcement of crop resistance. To disentangle complex regulatory mechanisms of the plant immune responses, understanding system as a whole is a must. However, integrating data from different molecular analysis (transcriptomics, proteomics, metabolomics, smallRNA regulation etc.) is not straightforward. We evaluated the response of potato (Solanum tuberosum L.) following the infection with potato virus Y (PVY). The response has been analyzed on two molecular levels, with microarray transcriptome analysis and mass spectroscopy-based proteomics. Within this report, we performed detailed analysis of the results on both levels and compared two different approaches for analysis of proteomic data (spectral count versus MaxQuant). To link the data on different molecular levels, each protein was mapped to the corresponding potato transcript according to StNIB paralogue grouping. Only 33% of the proteins mapped to microarray probes in a one-to-one relation and additionally many showed discordance in detected levels of proteins with corresponding transcripts. We discussed functional importance of true biological differences between both levels and showed that the reason for the discordance between transcript and protein abundance lies partly in complexity and structure of biological regulation of proteome and transcriptome and partly in technical issues contributing to it. PMID:28684682

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Fu-Peng; Un, Hio-Ieng; Li, Yongxi

A new electron-deficient unit with fused 5-heterocyclic ring was developed by replacing a cyclopenta-1,3-diene from electron-rich donor indacenodithiophene (IDT) with cyclohepta- 4,6-diene-1,3-diimde unit. The imide bridging endows BBI with fixed planar configuration and both low the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbit (LUMO) energy levels. Organic field-effect transistors (OFETs) based on BBI polymers exhibit electron mobility up to 0.34 cm2 V-1 s-1, which indicates that the BBI is a promising ntype semiconductor for optoelectronics.

Next Generation LOCAD-PTS Cartridge Development

NASA Technical Reports Server (NTRS)

Morris, H.; Nutter, D.; Weite, E.; Wells, M.; Maule, J.; Damon, M.; Monaco, L.; Steele, A.; Wainwright, N.

2008-01-01

Future astrobiology exploration missions will require rapid, point-of-use techniques for surface science experiments and contamination monitoring. The Lab-On-a-Chip Application Development (LOCAD) team is developing operational instruments that advance spaceflight technologies to molecular-based methods. Currently, LOCAD-Portable Test System (PTS) is quantifying levels of the bacterial molecule endotoxin onboard the Internatioal Space Station. Future research and development will focus on more sensitive molecular techniques that expand the number of compounds detected to include beta-glucan from fungal cell walls.

An all-electric single-molecule motor.

PubMed

Seldenthuis, Johannes S; Prins, Ferry; Thijssen, Joseph M; van der Zant, Herre S J

2010-11-23

Many types of molecular motors have been proposed and synthesized in recent years, displaying different kinds of motion, and fueled by different driving forces such as light, heat, or chemical reactions. We propose a new type of molecular motor based on electric field actuation and electric current detection of the rotational motion of a molecular dipole embedded in a three-terminal single-molecule device. The key aspect of this all-electronic design is the conjugated backbone of the molecule, which simultaneously provides the potential landscape of the rotor orientation and a real-time measure of that orientation through the modulation of the conductivity. Using quantum chemistry calculations, we show that this approach provides full control over the speed and continuity of motion, thereby combining electrical and mechanical control at the molecular level over a wide range of temperatures. Moreover, chemistry can be used to change all key parameters of the device, enabling a variety of new experiments on molecular motors.

Metal-organic frameworks with dynamic interlocked components

NASA Astrophysics Data System (ADS)

Vukotic, V. Nicholas; Harris, Kristopher J.; Zhu, Kelong; Schurko, Robert W.; Loeb, Stephen J.

2012-06-01

The dynamics of mechanically interlocked molecules such as rotaxanes and catenanes have been studied in solution as examples of rudimentary molecular switches and machines, but in this medium, the molecules are randomly dispersed and their motion incoherent. As a strategy for achieving a higher level of molecular organization, we have constructed a metal-organic framework material using a [2]rotaxane as the organic linker and binuclear Cu(II) units as the nodes. Activation of the as-synthesized material creates a void space inside the rigid framework that allows the soft macrocyclic ring of the [2]rotaxane to rotate rapidly, unimpeded by neighbouring molecular components. Variable-temperature 13C and 2H solid-state NMR experiments are used to characterize the nature and rate of the dynamic processes occurring inside this unique material. These results provide a blueprint for the future creation of solid-state molecular switches and molecular machines based on mechanically interlocked molecules.

Impaired associative taste learning and abnormal brain activation in kinase-defective eEF2K mice.

PubMed

Gildish, Iness; Manor, David; David, Orit; Sharma, Vijendra; Williams, David; Agarwala, Usha; Wang, Xuemin; Kenney, Justin W; Proud, Chris G; Rosenblum, Kobi

2012-02-24

Memory consolidation is defined temporally based on pharmacological interventions such as inhibitors of mRNA translation (molecular consolidation) or post-acquisition deactivation of specific brain regions (systems level consolidation). However, the relationship between molecular and systems consolidation are poorly understood. Molecular consolidation mechanisms involved in translation initiation and elongation have previously been studied in the cortex using taste-learning paradigms. For example, the levels of phosphorylation of eukaryotic elongation factor 2 (eEF2) were found to be correlated with taste learning in the gustatory cortex (GC), minutes following learning. In order to isolate the role of the eEF2 phosphorylation state at Thr-56 in both molecular and system consolidation, we analyzed cortical-dependent taste learning in eEF2K (the only known kinase for eEF2) ki mice, which exhibit reduced levels of eEF2 phosphorylation but normal levels of eEF2 and eEF2K. These mice exhibit clear attenuation of cortical-dependent associative, but not of incidental, taste learning. In order to gain a better understanding of the underlying mechanisms, we compared brain activity as measured by MEMRI (manganese-enhanced magnetic resonance imaging) between eEF2K ki mice and WT mice during conditioned taste aversion (CTA) learning and observed clear differences between the two but saw no differences under basal conditions. Our results demonstrate that adequate levels of phosphorylation of eEF2 are essential for cortical-dependent associative learning and suggest that malfunction of memory processing at the systems level underlies this associative memory impairment. © 2012 Cold Spring Harbor Laboratory Press

Quantitative in vivo cell-surface receptor imaging in oncology: kinetic modeling & paired-agent principles from nuclear medicine and optical imaging

PubMed Central

Tichauer, Kenneth M.; Wang, Yu; Pogue, Brian W.; Liu, Jonathan T. C.

2015-01-01

The development of methods to accurately quantify cell-surface receptors in living tissues would have a seminal impact in oncology. For example, accurate measures of receptor density in vivo could enhance early detection or surgical resection of tumors via protein-based contrast, allowing removal of cancer with high phenotype specificity. Alternatively, accurate receptor expression estimation could be used as a biomarker to guide patient-specific clinical oncology targeting of the same molecular pathway. Unfortunately, conventional molecular contrast-based imaging approaches are not well adapted to accurately estimating the nanomolar-level cell-surface receptor concentrations in tumors, as most images are dominated by nonspecific sources of contrast such as high vascular permeability and lymphatic inhibition. This article reviews approaches for overcoming these limitations based upon tracer kinetic modeling and the use of emerging protocols to estimate binding potential and the related receptor concentration. Methods such as using single time point imaging or a reference-tissue approach tend to have low accuracy in tumors, whereas paired-agent methods or advanced kinetic analyses are more promising to eliminate the dominance of interstitial space in the signals. Nuclear medicine and optical molecular imaging are the primary modalities used, as they have the nanomolar level sensitivity needed to quantify cell-surface receptor concentrations present in tissue, although each likely has a different clinical niche. PMID:26134619

Accuracy of Protein Embedding Potentials: An Analysis in Terms of Electrostatic Potentials.

PubMed

Olsen, Jógvan Magnus Haugaard; List, Nanna Holmgaard; Kristensen, Kasper; Kongsted, Jacob

2015-04-14

Quantum-mechanical embedding methods have in recent years gained significant interest and may now be applied to predict a wide range of molecular properties calculated at different levels of theory. To reach a high level of accuracy in embedding methods, both the electronic structure model of the active region and the embedding potential need to be of sufficiently high quality. In fact, failures in quantum mechanics/molecular mechanics (QM/MM)-based embedding methods have often been associated with the QM/MM methodology itself; however, in many cases the reason for such failures is due to the use of an inaccurate embedding potential. In this paper, we investigate in detail the quality of the electronic component of embedding potentials designed for calculations on protein biostructures. We show that very accurate explicitly polarizable embedding potentials may be efficiently designed using fragmentation strategies combined with single-fragment ab initio calculations. In fact, due to the self-interaction error in Kohn-Sham density functional theory (KS-DFT), use of large full-structure quantum-mechanical calculations based on conventional (hybrid) functionals leads to less accurate embedding potentials than fragment-based approaches. We also find that standard protein force fields yield poor embedding potentials, and it is therefore not advisable to use such force fields in general QM/MM-type calculations of molecular properties other than energies and structures.

Molecular stratification and precision medicine in systemic sclerosis from genomic and proteomic data.

PubMed

Martyanov, Viktor; Whitfield, Michael L

2016-01-01

The goal of this review is to summarize recent advances into the pathogenesis and treatment of systemic sclerosis (SSc) from genomic and proteomic studies. Intrinsic gene expression-driven molecular subtypes of SSc are reproducible across three independent datasets. These subsets are a consistent feature of SSc and are found in multiple end-target tissues, such as skin and esophagus. Intrinsic subsets as well as baseline levels of molecular target pathways are potentially predictive of clinical response to specific therapeutics, based on three recent clinical trials. A gene expression-based biomarker of modified Rodnan skin score, a measure of SSc skin severity, can be used as a surrogate outcome metric and has been validated in a recent trial. Proteome analyses have identified novel biomarkers of SSc that correlate with SSc clinical phenotypes. Integrating intrinsic gene expression subset data, baseline molecular pathway information, and serum biomarkers along with surrogate measures of modified Rodnan skin score provides molecular context in SSc clinical trials. With validation, these approaches could be used to match patients with the therapies from which they are most likely to benefit and thus increase the likelihood of clinical improvement.

The evolution of respiratory O2/NO reductases: an out-of-the-phylogenetic-box perspective

PubMed Central

Ducluzeau, Anne-Lise; Schoepp-Cothenet, Barbara; van Lis, Robert; Baymann, Frauke; Russell, Michael J.; Nitschke, Wolfgang

2014-01-01

Complex life on our planet crucially depends on strong redox disequilibria afforded by the almost ubiquitous presence of highly oxidizing molecular oxygen. However, the history of O2-levels in the atmosphere is complex and prior to the Great Oxidation Event some 2.3 billion years ago, the amount of O2 in the biosphere is considered to have been extremely low as compared with present-day values. Therefore the evolutionary histories of life and of O2-levels are likely intricately intertwined. The obvious biological proxy for inferring the impact of changing O2-levels on life is the evolutionary history of the enzyme allowing organisms to tap into the redox power of molecular oxygen, i.e. the bioenergetic O2 reductases, alias the cytochrome and quinol oxidases. Consequently, molecular phylogenies reconstructed for this enzyme superfamily have been exploited over the last two decades in attempts to elucidate the interlocking between O2 levels in the environment and the evolution of respiratory bioenergetic processes. Although based on strictly identical datasets, these phylogenetic approaches have led to diametrically opposite scenarios with respect to the history of both the enzyme superfamily and molecular oxygen on the Earth. In an effort to overcome the deadlock of molecular phylogeny, we here review presently available structural, functional, palaeogeochemical and thermodynamic information pertinent to the evolution of the superfamily (which notably also encompasses the subfamily of nitric oxide reductases). The scenario which, in our eyes, most closely fits the ensemble of these non-phylogenetic data, sees the low O2-affinity SoxM- (or A-) type enzymes as the most recent evolutionary innovation and the high-affinity O2 reductases (SoxB or B and cbb3 or C) as arising independently from NO-reducing precursor enzymes. PMID:24968694

Molecular and ionic diffusion in aqueous - deep eutectic solvent mixtures: probing inter-molecular interactions using PFG NMR.

PubMed

D'Agostino, Carmine; Gladden, Lynn F; Mantle, Mick D; Abbott, Andrew P; Ahmed, Essa I; Al-Murshedi, Azhar Y M; Harris, Robert C

2015-06-21

Pulsed field gradient (PFG) NMR has been used to probe self-diffusion of molecular and ionic species in aqueous mixtures of choline chloride (ChCl) based deep eutectic solvents (DESs), in order to elucidate the effect of water on motion and inter-molecular interactions between the different species in the mixtures, namely the Ch(+) cation and hydrogen bond donor (HBD). The results reveal an interesting and complex behaviour of such mixtures at a molecular level. In general, it is observed that the hydroxyl protons ((1)H) of Ch(+) and the hydrogen bond donor have diffusion coefficients significantly different from those measured for their parent molecules when water is added. This indicates a clear and significant change in inter-molecular interactions. In aqueous Ethaline, the hydroxyl species of Ch(+) and HBD show a stronger interaction with water as water is added to the system. In the case of Glyceline, water has little effect on both hydroxyl proton diffusion of Ch(+) and HBD. In Reline, it is likely that water allows the formation of small amounts of ammonium hydroxide. The most surprising observation is from the self-diffusion of water, which is considerably higher that expected from a homogeneous liquid. This leads to the conclusion that Reline and Glyceline form mixtures that are inhomogeneous at a microscopic level despite the hydrophilicity of the salt and HBD. This work shows that PFG NMR is a powerful tool to elucidate both molecular dynamics and inter-molecular interactions in complex liquid mixtures, such as the aqueous DES mixtures.

Molecular phylogeny of Banjo catfishes (Ostaryophisi: Siluriformes: Aspredinidae): A continental radiation in South American freshwaters.

PubMed

Carvalho, Tiago P; Arce H, Mariangeles; Reis, Roberto E; Sabaj, Mark H

2018-04-30

The family Aspredinidae is a moderately diverse and broadly distributed group of freshwater fishes endemic to South America. Commonly known as Banjo Catfishes, Aspredinidae currently includes 44 valid species divided among 13 genera. The first species-comprehensive hypothesis on phylogenetic relationships among aspredinids is presented. The phylogeny is based on DNA sequence data for five gene fragments (mitochondrial 16S and COI; nuclear RAG1, MYH6 and SH3PX3) from 114 individuals representing 31 species in 12 aspredinid genera. Analyses of molecular data support the monophyly of most genera (Bunocephalus excepted) and several higher-level relationships previously proposed by morphological studies. Based on the molecular phylogeny, a new suprageneric classification for Aspredinidae is proposed with the new monotypic subfamily Pseudobunocephalinae as the sister taxon to all other aspredinids. Copyright © 2018 Elsevier Inc. All rights reserved.

Surveillance at the molecular level: Developing an integrated network for detecting variation in avian influenza viruses in Indonesia.

PubMed

Hartaningsih, Nining; Wibawa, Hendra; Pudjiatmoko; Rasa, Fadjar Sumping Tjatur; Irianingsih, Sri Handayani; Dharmawan, Rama; Azhar, Muhammad; Siregar, Elly Sawitri; McGrane, James; Wong, Frank; Selleck, Paul; Allen, John; Broz, Ivano; Torchetti, Mia Kim; Dauphin, Gwenaelle; Claes, Filip; Sastraningrat, Wiryadi; Durr, Peter A

2015-06-01

Since 2006, Indonesia has used vaccination as the principal means of control of H5N1-HPAI. During this time, the virus has undergone gradual antigenic drift, which has necessitated changes in seed strains for vaccine production and associated modifications to diagnostic antigens. In order to improve the system of monitoring such viral evolution, the Government of Indonesia, with the assistance of FAO/OFFLU, has developed an innovative network whereby H5N1 isolates are antigenically and genetically characterised. This molecular surveillance network ("Influenza Virus Monitoring" or "IVM") is based on the regional network of veterinary diagnostic laboratories, and is supported by a web-based data management system ("IVM Online"). The example of the Indonesian IVM network has relevance for other countries seeking to establish laboratory networks for the molecular surveillance of avian influenza and other pathogens. Copyright © 2015 Elsevier B.V. All rights reserved.

A room-temperature non-volatile CNT-based molecular memory cell

NASA Astrophysics Data System (ADS)

Ye, Senbin; Jing, Qingshen; Han, Ray P. S.

2013-04-01

Recent experiments with a carbon nanotube (CNT) system confirmed that the innertube can oscillate back-and-forth even under a room-temperature excitation. This demonstration of relative motion suggests that it is now feasible to build a CNT-based molecular memory cell (MC), and the key to bring the concept to reality is the precision control of the moving tube for sustained and reliable read/write (RW) operations. Here, we show that by using a 2-section outertube design, we are able to suitably recalibrate the system energetics and obtain the designed performance characteristics of a MC. Further, the resulting energy modification enables the MC to operate as a non-volatile memory element at room temperatures. Our paper explores a fundamental understanding of a MC and its response at the molecular level to roadmap a novel approach in memory technologies that can be harnessed to overcome the miniaturization limit and memory volatility in memory technologies.

Theranostic Profiling for Actionable Aberrations in Advanced High Risk Osteosarcoma with Aggressive Biology Reveals High Molecular Diversity: The Human Fingerprint Hypothesis.

PubMed

Egas-Bejar, Daniela; Anderson, Pete M; Agarwal, Rishi; Corrales-Medina, Fernando; Devarajan, Eswaran; Huh, Winston W; Brown, Robert E; Subbiah, Vivek

2014-03-12

The survival of patients with advanced osteosarcoma is poor with limited therapeutic options. There is an urgent need for new targeted therapies based on biomarkers. Recently, theranostic molecular profiling services for cancer patients by CLIA-certified commercial companies as well as in-house profiling in academic medical centers have expanded exponentially. We evaluated molecular profiles of patients with advanced osteosarcoma whose tumor tissue had been analyzed by one of the following methods: 1. 182-gene next-generation exome sequencing (Foundation Medicine, Boston, MA), 2. Immunohistochemistry (IHC)/PCR-based panel (CARIS Target Now, Irving, Tx), 3.Comparative genome hybridization (Oncopath, San Antonio, TX). 4. Single-gene PCR assays, PTEN IHC (MDACC CLIA), 5. UT Houston morphoproteomics (Houston, TX). The most common actionable aberrations occur in the PI3K/PTEN/mTOR pathway. No patterns in genomic alterations beyond the above are readily identifiable, and suggest both high molecular diversity in osteosarcoma and the need for more analyses to define distinct subgroups of osteosarcoma defined by genomic alterations. Based on our preliminary observations we hypothesize that the biology of aggressive and the metastatic phenotype osteosarcoma at the molecular level is similar to human fingerprints, in that no two tumors are identical. Further large scale analyses of osteosarcoma samples are warranted to test this hypothesis.

Polymeric molecular sieve membranes via in situ cross-linking of non-porous polymer membrane templates.

PubMed

Qiao, Zhen-An; Chai, Song-Hai; Nelson, Kimberly; Bi, Zhonghe; Chen, Jihua; Mahurin, Shannon M; Zhu, Xiang; Dai, Sheng

2014-04-16

High-performance polymeric membranes for gas separation are attractive for molecular-level separations in industrial-scale chemical, energy and environmental processes. Molecular sieving materials are widely regarded as the next-generation membranes to simultaneously achieve high permeability and selectivity. However, most polymeric molecular sieve membranes are based on a few solution-processable polymers such as polymers of intrinsic microporosity. Here we report an in situ cross-linking strategy for the preparation of polymeric molecular sieve membranes with hierarchical and tailorable porosity. These membranes demonstrate exceptional performance as molecular sieves with high gas permeabilities and selectivities for smaller gas molecules, such as carbon dioxide and oxygen, over larger molecules such as nitrogen. Hence, these membranes have potential for large-scale gas separations of commercial and environmental relevance. Moreover, this strategy could provide a possible alternative to 'classical' methods for the preparation of porous membranes and, in some cases, the only viable synthetic route towards certain membranes.

Molecular analysis of Aspergillus section Flavi isolated from Brazil nuts.

PubMed

Gonçalves, Juliana Soares; Ferracin, Lara Munique; Carneiro Vieira, Maria Lucia; Iamanaka, Beatriz Thie; Taniwaki, Marta Hiromi; Pelegrinelli Fungaro, Maria Helena

2012-04-01

Brazil nuts are an important export market in its main producing countries, including Brazil, Bolivia, and Peru. Approximately 30,000 tons of Brazil nuts are harvested each year. However, substantial nut contamination by Aspergillus section Flavi occurs with subsequent production of aflatoxins. In our study, Aspergillus section Flavi were isolated from Brazil nuts (Bertholletia excelsa), and identified by morphological and molecular means. We obtained 241 isolates from nut samples, 41% positive for aflatoxin production. Eighty-one isolates were selected for molecular investigation. Pairwise genetic distances among isolates and phylogenetic relationships were assessed. The following Aspergillus species were identified: A. flavus, A. caelatus, A. nomius, A. tamarii, A. bombycis, and A. arachidicola. Additionally, molecular profiles indicated a high level of nucleotide variation within β-tubulin and calmodulin gene sequences associated with high genetic divergence from RAPD data. Among the 81 isolates analyzed by molecular means, three of them were phylogenetically distinct from all other isolates representing the six species of section Flavi. A putative novel species was identified based on molecular profiles.

Educational Gaps in Molecular Diagnostics, Genomics, and Personalized Medicine in Dermatopathology Training: A Survey of U.S. Dermatopathology Fellowship Program Directors.

PubMed

Torre, Kristin; Russomanno, Kristen; Ferringer, Tammie; Elston, Dirk; Murphy, Michael J

2018-01-01

Molecular technologies offer clinicians the tools to provide high-quality, cost-effective patient care. We evaluated education focused on molecular diagnostics, genomics, and personalized medicine in dermatopathology fellowship training. A 20-question online survey was emailed to all (n = 53) Accreditation Council for Graduate Medical Education (ACGME)-accredited dermatopathology training programs in the United States. Thirty-one of 53 program directors responded (response rate = 58%). Molecular training is undertaken in 74% of responding dermatopathology fellowships, with levels of instruction varying among dermatology-based and pathology-based programs. Education differed for dermatology- and pathology-trained fellows in approximately one-fifth (19%) of programs. Almost half (48%) of responding program directors believe that fellows are not currently receiving adequate molecular education, although the majority (97%) expect to incorporate additional instruction in the next 2-5 years. Factors influencing the incorporation of relevant education include perceived clinical utility and Accreditation Council for Graduate Medical Education/residency review committee (RRC) requirements. Potential benefits of molecular education include increased medical knowledge, improved patient care, and promotion of effective communication with other healthcare professionals. More than two-thirds (68%) of responding program directors believe that instruction in molecular technologies should be required in dermatopathology fellowship training. Although all responding dermatopathology fellowship program directors agreed that molecular education is important, only a little over half of survey participants believe that their fellows receive adequate instruction. This represents an important educational gap. Discussion among those who oversee fellow education is necessary to best integrate and evaluate teaching of molecular dermatopathology.

The family structure of the Mucorales: a synoptic revision based on comprehensive multigene-genealogies.

PubMed

Hoffmann, K; Pawłowska, J; Walther, G; Wrzosek, M; de Hoog, G S; Benny, G L; Kirk, P M; Voigt, K

2013-06-01

The Mucorales (Mucoromycotina) are one of the most ancient groups of fungi comprising ubiquitous, mostly saprotrophic organisms. The first comprehensive molecular studies 11 yr ago revealed the traditional classification scheme, mainly based on morphology, as highly artificial. Since then only single clades have been investigated in detail but a robust classification of the higher levels based on DNA data has not been published yet. Therefore we provide a classification based on a phylogenetic analysis of four molecular markers including the large and the small subunit of the ribosomal DNA, the partial actin gene and the partial gene for the translation elongation factor 1-alpha. The dataset comprises 201 isolates in 103 species and represents about one half of the currently accepted species in this order. Previous family concepts are reviewed and the family structure inferred from the multilocus phylogeny is introduced and discussed. Main differences between the current classification and preceding concepts affects the existing families Lichtheimiaceae and Cunninghamellaceae, as well as the genera Backusella and Lentamyces which recently obtained the status of families along with the Rhizopodaceae comprising Rhizopus, Sporodiniella and Syzygites. Compensatory base change analyses in the Lichtheimiaceae confirmed the lower level classification of Lichtheimia and Rhizomucor while genera such as Circinella or Syncephalastrum completely lacked compensatory base changes.

Taxane-mediated radiosensitization derives from chromosomal missegregation on tripolar mitotic spindles orchestrated by AURKA and TPX2.

PubMed

Orth, M; Unger, K; Schoetz, U; Belka, C; Lauber, K

2018-01-04

Taxane-based radiochemotherapy is a central treatment option for various cancer entities in locally advanced stages. The therapeutic synergism of this combined modality approach due to taxane-mediated radiosensitization of cancer cells is well-known. However, the underlying molecular mechanisms remain largely elusive, and mechanism-derived predictive markers of taxane-based radiochemotherapy are currently not available. Here, we show that clinically relevant doses of Paclitaxel, the prototype taxane, stimulate a tripolar mode of mitosis leading to chromosomal missegregation and aneuploidization rather than interfering with cell cycle progression. This distinct mitotic phenotype was interlinked with Paclitaxel-mediated radiosensitization via overexpression of mitotic Aurora kinase A (AURKA) and its cofactor TPX2 whose knockdown rescued the bipolar mode of cell division and largely attenuated the radiosensitizing effects of Paclitaxel. In the cancer genome atlas (TCGA) lung adenocarcinoma cohort, high expression levels of AURKA and TPX2 were associated with specifically improved overall survival upon taxane-based radiochemotherapy, but not in case of non-taxane-based radiochemotherapy, chemo- or radiotherapy only. Thus, our data provide insights into Paclitaxel-mediated radiosensitization on a mechanistic and molecular level and identify AURKA and TPX2 as the first potential mechanism-based, predictive markers of taxane-based radiochemotherapy.

Can we better predict the biologic behavior of incidental IPMN? A comprehensive analysis of molecular diagnostics and biomarkers in intraductal papillary mucinous neoplasms of the pancreas.

PubMed

Tulla, Kiara A; Maker, Ajay V

2018-03-01

Predicting the biologic behavior of intraductal papillary mucinous neoplasm (IPMN) remains challenging. Current guidelines utilize patient symptoms and imaging characteristics to determine appropriate surgical candidates. However, the majority of resected cysts remain low-risk lesions, many of which may be feasible to have under surveillance. We herein characterize the most promising and up-to-date molecular diagnostics in order to identify optimal components of a molecular signature to distinguish levels of IPMN dysplasia. A comprehensive systematic review of pertinent literature, including our own experience, was conducted based on the PRISMA guidelines. Molecular diagnostics in IPMN patient tissue, duodenal secretions, cyst fluid, saliva, and serum were evaluated and organized into the following categories: oncogenes, tumor suppressor genes, glycoproteins, markers of the immune response, proteomics, DNA/RNA mutations, and next-generation sequencing/microRNA. Specific targets in each of these categories, and in aggregate, were identified by their ability to both characterize a cyst as an IPMN and determine the level of cyst dysplasia. Combining molecular signatures with clinical and imaging features in this era of next-generation sequencing and advanced computational analysis will enable enhanced sensitivity and specificity of current models to predict the biologic behavior of IPMN.

Integrative analysis of genes and miRNA alterations in human embryonic stem cells-derived neural cells after exposure to silver nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oh, Jung-Hwa; Department of human and environmental toxicology, University of Science & Technology, Daejeon 34113; Son, Mi-Young

Given the rapid growth of engineered and customer products made of silver nanoparticles (Ag NPs), understanding their biological and toxicological effects on humans is critically important. The molecular developmental neurotoxic effects associated with exposure to Ag NPs were analyzed at the physiological and molecular levels, using an alternative cell model: human embryonic stem cell (hESC)-derived neural stem/progenitor cells (NPCs). In this study, the cytotoxic effects of Ag NPs (10–200 μg/ml) were examined in these hESC-derived NPCs, which have a capacity for neurogenesis in vitro, at 6 and 24 h. The results showed that Ag NPs evoked significant toxicity in hESC-derivedmore » NPCs at 24 h in a dose-dependent manner. In addition, Ag NPs induced cell cycle arrest and apoptosis following a significant increase in oxidative stress in these cells. To further clarify the molecular mechanisms of the toxicological effects of Ag NPs at the transcriptional and post-transcriptional levels, the global expression profiles of genes and miRNAs were analyzed in hESC-derived NPCs after Ag NP exposure. The results showed that Ag NPs induced oxidative stress and dysfunctional neurogenesis at the molecular level in hESC-derived NPCs. Based on this hESC-derived neural cell model, these findings have increased our understanding of the molecular events underlying developmental neurotoxicity induced by Ag NPs in humans. - Highlights: • This system served as a suitable model for developmental neurotoxicity testing. • Ag NPs induce the apoptosis in human neural cells by ROS generation. • Genes for development of neurons were dysregulated in response to Ag NPs. • Molecular events during early developmental neurotoxicity were proposed.« less

A meta-GGA level screened range-separated hybrid functional by employing short range Hartree-Fock with a long range semilocal functional.

PubMed

Jana, Subrata; Samal, Prasanjit

2018-03-28

The range-separated hybrid density functionals are very successful in describing a wide range of molecular and solid-state properties accurately. In principle, such functionals are designed from spherically averaged or system averaged as well as reverse engineered exchange holes. In the present attempt, the screened range-separated hybrid functional scheme has been applied to the meta-GGA rung by using the density matrix expansion based semilocal exchange hole (or functional). The hybrid functional proposed here utilizes the spherically averaged density matrix expansion based exchange hole in the range separation scheme. For slowly varying density correction the range separation scheme is employed only through the local density approximation based exchange hole coupled with the corresponding fourth order gradient approximate Tao-Mo enhancement factor. The comprehensive testing and performance of the newly constructed functional indicates its applicability in describing several molecular properties. The most appealing feature of this present screened hybrid functional is that it will be practically very useful in describing solid-state properties at the meta-GGA level.

Modelling Molecular Mechanisms: A Framework of Scientific Reasoning to Construct Molecular-Level Explanations for Cellular Behaviour

ERIC Educational Resources Information Center

van Mil, Marc H. W.; Boerwinkel, Dirk Jan; Waarlo, Arend Jan

2013-01-01

Although molecular-level details are part of the upper-secondary biology curriculum in most countries, many studies report that students fail to connect molecular knowledge to phenomena at the level of cells, organs and organisms. Recent studies suggest that students lack a framework to reason about complex systems to make this connection. In this…

Using yeast to determine the functional consequences of mutations in the human p53 tumor suppressor gene: An introductory course‐based undergraduate research experience in molecular and cell biology

PubMed Central

Brownell, Sara E.; Seawell, Patricia Chandler; Malladi, Shyamala; Imam, Jamie F. Conklin; Singla, Veena; Bradon, Nicole; Cyert, Martha S.; Stearns, Tim

2016-01-01

Abstract The opportunity to engage in scientific research is an important, but often neglected, component of undergraduate training in biology. We describe the curriculum for an innovative, course‐based undergraduate research experience (CURE) appropriate for a large, introductory cell and molecular biology laboratory class that leverages students′ high level of interest in cancer. The course is highly collaborative and emphasizes the analysis and interpretation of original scientific data. During the course, students work in teams to characterize a collection of mutations in the human p53 tumor suppressor gene via expression and analysis in yeast. Initially, student pairs use both qualitative and quantitative assays to assess the ability of their p53 mutant to activate expression of reporter genes, and they localize their mutation within the p53 structure. Through facilitated discussion, students suggest possible molecular explanations for the transactivation defects displayed by their p53 mutants and propose experiments to test these hypotheses that they execute during the second part of the course. They use a western blot to determine whether mutant p53 levels are reduced, a DNA‐binding assay to test whether recognition of any of three p53 target sequences is compromised, and fluorescence microscopy to assay nuclear localization. Students studying the same p53 mutant periodically convene to discuss and interpret their combined data. The course culminates in a poster session during which students present their findings to peers, instructors, and the greater biosciences community. Based on our experience, we provide recommendations for the development of similar large introductory lab courses. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(2):161–178, 2017. PMID:27873457

Chirped Laser Dispersion Spectroscopy for Remote Open-Path Trace-Gas Sensing

PubMed Central

Nikodem, Michal; Wysocki, Gerard

2012-01-01

In this paper we present a prototype instrument for remote open-path detection of nitrous oxide. The sensor is based on a 4.53 μm quantum cascade laser and uses the chirped laser dispersion spectroscopy (CLaDS) technique for molecular concentration measurements. To the best of our knowledge this is the first demonstration of open-path laser-based trace-gas detection using a molecular dispersion measurement. The prototype sensor achieves a detection limit down to the single-ppbv level and exhibits excellent stability and robustness. The instrument characterization, field deployment performance, and the advantages of applying dispersion sensing to sensitive trace-gas detection in a remote open-path configuration are presented. PMID:23443389

Chirped laser dispersion spectroscopy for remote open-path trace-gas sensing.

PubMed

Nikodem, Michal; Wysocki, Gerard

2012-11-28

In this paper we present a prototype instrument for remote open-path detection of nitrous oxide. The sensor is based on a 4.53 μm quantum cascade laser and uses the chirped laser dispersion spectroscopy (CLaDS) technique for molecular concentration measurements. To the best of our knowledge this is the first demonstration of open-path laser-based trace-gas detection using a molecular dispersion measurement. The prototype sensor achieves a detection limit down to the single-ppbv level and exhibits excellent stability and robustness. The instrument characterization, field deployment performance, and the advantages of applying dispersion sensing to sensitive trace-gas detection in a remote open-path configuration are presented.

Intra-tumor heterogeneity in breast cancer has limited impact on transcriptomic-based molecular profiling.

PubMed

Karthik, Govindasamy-Muralidharan; Rantalainen, Mattias; Stålhammar, Gustav; Lövrot, John; Ullah, Ikram; Alkodsi, Amjad; Ma, Ran; Wedlund, Lena; Lindberg, Johan; Frisell, Jan; Bergh, Jonas; Hartman, Johan

2017-11-29

Transcriptomic profiling of breast tumors provides opportunity for subtyping and molecular-based patient stratification. In diagnostic applications the specimen profiled should be representative of the expression profile of the whole tumor and ideally capture properties of the most aggressive part of the tumor. However, breast cancers commonly exhibit intra-tumor heterogeneity at molecular, genomic and in phenotypic level, which can arise during tumor evolution. Currently it is not established to what extent a random sampling approach may influence molecular breast cancer diagnostics. In this study we applied RNA-sequencing to quantify gene expression in 43 pieces (2-5 pieces per tumor) from 12 breast tumors (Cohort 1). We determined molecular subtype and transcriptomic grade for all tumor pieces and analysed to what extent pieces originating from the same tumors are concordant or discordant with each other. Additionally, we validated our finding in an independent cohort consisting of 19 pieces (2-6 pieces per tumor) from 6 breast tumors (Cohort 2) profiled using microarray technique. Exome sequencing was also performed on this cohort, to investigate the extent of intra-tumor genomic heterogeneity versus the intra-tumor molecular subtype classifications. Molecular subtyping was consistent in 11 out of 12 tumors and transcriptomic grade assignments were consistent in 11 out of 12 tumors as well. Molecular subtype predictions revealed consistent subtypes in four out of six patients in this cohort 2. Interestingly, we observed extensive intra-tumor genomic heterogeneity in these tumor pieces but not in their molecular subtype classifications. Our results suggest that macroscopic intra-tumoral transcriptomic heterogeneity is limited and unlikely to have an impact on molecular diagnostics for most patients.

MaMiCo: Software design for parallel molecular-continuum flow simulations

NASA Astrophysics Data System (ADS)

Neumann, Philipp; Flohr, Hanno; Arora, Rahul; Jarmatz, Piet; Tchipev, Nikola; Bungartz, Hans-Joachim

2016-03-01

The macro-micro-coupling tool (MaMiCo) was developed to ease the development of and modularize molecular-continuum simulations, retaining sequential and parallel performance. We demonstrate the functionality and performance of MaMiCo by coupling the spatially adaptive Lattice Boltzmann framework waLBerla with four molecular dynamics (MD) codes: the light-weight Lennard-Jones-based implementation SimpleMD, the node-level optimized software ls1 mardyn, and the community codes ESPResSo and LAMMPS. We detail interface implementations to connect each solver with MaMiCo. The coupling for each waLBerla-MD setup is validated in three-dimensional channel flow simulations which are solved by means of a state-based coupling method. We provide sequential and strong scaling measurements for the four molecular-continuum simulations. The overhead of MaMiCo is found to come at 10%-20% of the total (MD) runtime. The measurements further show that scalability of the hybrid simulations is reached on up to 500 Intel SandyBridge, and more than 1000 AMD Bulldozer compute cores.

Bis(PheOH) maleic acid amide-fumaric acid amide photoizomerization induces microsphere-to-gel fiber morphological transition: the photoinduced gelation system.

PubMed

Frkanec, Leo; Jokić, Milan; Makarević, Janja; Wolsperger, Kristina; Zinić, Mladen

2002-08-21

The photoinduced gelation system based on 1 (non-gelling) to 2 (gelling) molecular photoisomerization in water results by microspheres (1) to gel fibers (2) transformation at the supramolecular level.

Molecular diagnosis and precision medicine in allergy management.

PubMed

Riccio, Anna Maria; De Ferrari, Laura; Chiappori, Alessandra; Ledda, Sabina; Passalacqua, Giovanni; Melioli, Giovanni; Canonica, Giorgio Walter

2016-11-01

Precision medicine (PM) can be defined as a structural model aimed at customizing healthcare, with medical decisions/products tailored on an individual patient at a highly detailed level. In this sense, allergy diagnostics based on molecular allergen components allows to accurately define the patient's IgE repertoire. The availability of highly specialized singleplexed and multiplexed platforms support allergists with an advanced diagnostic armamentarium. The therapeutic intervention, driven by the standard diagnostic approach, but further supported by these innovative tools may result, for instance, in a more appropriate prescription of allergen immunotherapy (AIT). Also, the phenotyping of patients, which may have relevant effects on the treatment strategy, could be take advantage by the molecular allergy diagnosis.

Differences in the molecular biology of adenocarcinoma of the esophagus, gastric cardia, and upper gastric third.

PubMed

Lehmann, Kuno; Schneider, Paul M

2010-01-01

Adenocarcinoma of the distal esophagus, gastric cardia, and upper gastric third are grouped in type I-III by the Siewert classification. This classification is based on the endoscopic localisation of the tumor center, and is the most important diagnostic tool to group these tumors. On a molecular level, there is currently no marker that would allow to differentiate the three different types. Furthermore, the Siewert classification was not uniformly used in the recent literature, making interpretation and generalization of these results difficult. However, several potential targets have been identified that may help to separate these tumors by molecular markers, and are summarized in this chapter.

Lotus Dust Mitigation Coating and Molecular Adsorber Coating

NASA Technical Reports Server (NTRS)

O'Connor, Kenneth M.; Abraham, Nithin S.

2015-01-01

NASA Goddard Space Flight Center has developed two unique coating formulations that will keep surfaces clean and sanitary and contain contaminants.The Lotus Dust Mitigation Coating, modeled after the self-cleaning, water-repellant lotus leaf, disallows buildup of dust, dirt, water, and more on surfaces. This coating, has been successfully tested on painted, aluminum, glass, silica, and some composite surfaces, could aid in keeping medical assets clean.The Molecular Adsorber Coating is a zeolite-based, sprayable molecular adsorber coating, designed to prevent outgassing in materials in vacuums. The coating works well to adsorb volatiles and contaminates in manufacturing and processing, such as in pharmaceutical production. The addition of a biocide would also aid in controlling bacteria levels.

A molecular spin-photovoltaic device.

PubMed

Sun, Xiangnan; Vélez, Saül; Atxabal, Ainhoa; Bedoya-Pinto, Amilcar; Parui, Subir; Zhu, Xiangwei; Llopis, Roger; Casanova, Fèlix; Hueso, Luis E

2017-08-18

We fabricated a C 60 fullerene-based molecular spin-photovoltaic device that integrates a photovoltaic response with the spin transport across the molecular layer. The photovoltaic response can be modified under the application of a small magnetic field, with a magnetophotovoltage of up to 5% at room temperature. Device functionalities include a magnetic current inverter and the presence of diverging magnetocurrent at certain illumination levels that could be useful for sensing. Completely spin-polarized currents can be created by balancing the external partially spin-polarized injection with the photogenerated carriers. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Concomitant prediction of function and fold at the domain level with GO-based profiles.

PubMed

Lopez, Daniel; Pazos, Florencio

2013-01-01

Predicting the function of newly sequenced proteins is crucial due to the pace at which these raw sequences are being obtained. Almost all resources for predicting protein function assign functional terms to whole chains, and do not distinguish which particular domain is responsible for the allocated function. This is not a limitation of the methodologies themselves but it is due to the fact that in the databases of functional annotations these methods use for transferring functional terms to new proteins, these annotations are done on a whole-chain basis. Nevertheless, domains are the basic evolutionary and often functional units of proteins. In many cases, the domains of a protein chain have distinct molecular functions, independent from each other. For that reason resources with functional annotations at the domain level, as well as methodologies for predicting function for individual domains adapted to these resources are required.We present a methodology for predicting the molecular function of individual domains, based on a previously developed database of functional annotations at the domain level. The approach, which we show outperforms a standard method based on sequence searches in assigning function, concomitantly predicts the structural fold of the domains and can give hints on the functionally important residues associated to the predicted function.

An Efficient Method to Evaluate Intermolecular Interaction Energies in Large Systems Using Overlapping Multicenter ONIOM and the Fragment Molecular Orbital Method

PubMed Central

Asada, Naoya; Fedorov, Dmitri G.; Kitaura, Kazuo; Nakanishi, Isao; Merz, Kenneth M.

2012-01-01

We propose an approach based on the overlapping multicenter ONIOM to evaluate intermolecular interaction energies in large systems and demonstrate its accuracy on several representative systems in the complete basis set limit at the MP2 and CCSD(T) level of theory. In the application to the intermolecular interaction energy between insulin dimer and 4′-hydroxyacetanilide at the MP2/CBS level, we use the fragment molecular orbital method for the calculation of the entire complex assigned to the lowest layer in three-layer ONIOM. The developed method is shown to be efficient and accurate in the evaluation of the protein-ligand interaction energies. PMID:23050059

Advanced solvent based methods for molecular characterization of soil organic matter by high-resolution mass spectrometry.

PubMed

Tfaily, Malak M; Chu, Rosalie K; Tolić, Nikola; Roscioli, Kristyn M; Anderton, Christopher R; Paša-Tolić, Ljiljana; Robinson, Errol W; Hess, Nancy J

2015-01-01

Soil organic matter (SOM), a complex, heterogeneous mixture of above and belowground plant litter and animal and microbial residues at various degrees of decomposition, is a key reservoir for carbon (C) and nutrient biogeochemical cycling in soil based ecosystems. A limited understanding of the molecular composition of SOM limits the ability to routinely decipher chemical processes within soil and accurately predict how terrestrial carbon fluxes will respond to changing climatic conditions and land use. To elucidate the molecular-level structure of SOM, we selectively extracted a broad range of intact SOM compounds by a combination of different organic solvents from soils with a wide range of C content. Our use of electrospray ionization (ESI) coupled with Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) and a suite of solvents with varying polarity significantly expands the inventory of the types of organic molecules present in soils. Specifically, we found that hexane is selective for lipid-like compounds with very low O/C ratios (<0.1); water (H2O) was selective for carbohydrates with high O/C ratios; acetonitrile (ACN) preferentially extracts lignin, condensed structures, and tannin polyphenolic compounds with O/C > 0.5; methanol (MeOH) has higher selectivity toward compounds characterized with low O/C < 0.5; and hexane, MeOH, ACN, and H2O solvents increase the number and types of organic molecules extracted from soil for a broader range of chemically diverse soil types. Our study of SOM molecules by ESI FTICR MS revealed new insight into the molecular-level complexity of organics contained in soils. We present the first comparative study of the molecular composition of SOM from different ecosystems using ultra high-resolution mass spectrometry.

Molecular Imaging: Current Status and Emerging Strategies

PubMed Central

Pysz, Marybeth A.; Gambhir, Sanjiv S.; Willmann, Jürgen K.

2011-01-01

In vivo molecular imaging has a great potential to impact medicine by detecting diseases in early stages (screening), identifying extent of disease, selecting disease- and patient-specific therapeutic treatment (personalized medicine), applying a directed or targeted therapy, and measuring molecular-specific effects of treatment. Current clinical molecular imaging approaches primarily use PET- or SPECT-based techniques. In ongoing preclinical research novel molecular targets of different diseases are identified and, sophisticated and multifunctional contrast agents for imaging these molecular targets are developed along with new technologies and instrumentation for multimodality molecular imaging. Contrast-enhanced molecular ultrasound with molecularly-targeted contrast microbubbles is explored as a clinically translatable molecular imaging strategy for screening, diagnosing, and monitoring diseases at the molecular level. Optical imaging with fluorescent molecular probes and ultrasound imaging with molecularly-targeted microbubbles are attractive strategies since they provide real-time imaging, are relatively inexpensive, produce images with high spatial resolution, and do not involve exposure to ionizing irradiation. Raman spectroscopy/microscopy has emerged as a molecular optical imaging strategy for ultrasensitive detection of multiple biomolecules/biochemicals with both in vivo and ex vivo versatility. Photoacoustic imaging is a hybrid of optical and ultrasound modalities involving optically-excitable molecularly-targeted contrast agents and quantitative detection of resulting oscillatory contrast agent movement with ultrasound. Current preclinical findings and advances in instrumentation such as endoscopes and microcatheters suggest that these molecular imaging modalities have numerous clinical applications and will be translated into clinical use in the near future. PMID:20541650

Anti-inflammatory effects and the molecular pattern of the therapeutic effects of dietary seeds of Adenanthera Pavonina in albino rats

NASA Astrophysics Data System (ADS)

Afolabi, Israel Sunmola; Olawole, Tolulope Dorcas; Adams, Khadijat Abiola; Shopeju, Omolola Ashiedu; Ezeaku, Mmaegbunem Chidera

2018-04-01

Adenanthera pavonina is a woody specie of Leguminosae-Mimosiodaea that is widely present across the globe. Little attention has been given to the dietary importance of the seeds, which have been linked with the traditional management of inflammatory conditions and several other diseases. This study determines the anti-inflammatory potential and the molecular effects of consuming the seeds compared to the commonly eaten Vigna uniguiculata (cowpea). The control, group administered with 10 g (AP-10), 20 g (AP-20) and 30 g (AP-30) of A. pavonina based diets; and those previously induced with inflammation administered with 20 kg of V. uniguiculata (BK/BM), normal saline (K-Sal), 20 g A. pavonina based diet (K-AP) and indomethacin (K-Ind) were examined for cyclooxygenase (COX-2), tumor necrosis factor (TNF-α), soluble intracellular adhesion molecule (sICAM) levels in the serum and the effect of diets on the integrity of DNA using RAPD PCR analysis for monitoring their anti-inflammatory activity and the molecular effects. AP-30 based diets significantly reduced (P<0.05) serum sICAM-1 levels compared to that of cowpea. A. pavonina and V. uniguiculata diets exhibited similar ability to significantly reduced (P<0.05) the serum sICAM level of the inflammation induced rats compared with the K-Sal group. Both diet from A. pavonina and V. unguiculata significantly increases (P<0.05) COX-2 activity and the restoration of TNF-α activity. A. pavonina can act as a preventive food for inflammation and other diseases without damaging the DNA integrity in the kidney, liver and the heart.

Scanning tunneling microscopy, orbital-mediated tunneling spectroscopy, and ultraviolet photoelectron spectroscopy of metal(II) tetraphenylporphyrins deposited from vapor.

PubMed

Scudiero, L; Barlow, D E; Mazur, U; Hipps, K W

2001-05-02

Thin films of vapor-deposited Ni(II) and Co(II) complexes of tetraphenylporphyrin (NiTPP and CoTPP) were studied supported on gold and embedded in Al-Al(2)O(3)-MTPP-Pb tunnel diodes, where M = Ni or Co. Thin films deposited onto polycrystalline gold were analyzed by ultraviolet photoelectron spectroscopy (UPS) using He I radiation. Scanning tunneling microscopy (STM) and orbital-mediated tunneling spectroscopy (STM-OMTS) were performed on submonolayer films of CoTPP and NiTPP supported on Au(111). Inelastic electron tunneling spectroscopy (IETS) and OMTS were measured in conventional tunnel diode structures. The highest occupied pi molecular orbital of the porphyrin ring was seen in both STM-OMTS and UPS at about 6.4 eV below the vacuum level. The lowest unoccupied pi molecular orbital of the porphyrin ring was observed by STM-OMTS and by IETS-OMTS to be located near 3.4 eV below the vacuum level. The OMTS spectra of CoTPP had a band near 5.2 eV (below the vacuum level) that was attributed to transient oxidation of the central Co(II) ion. That is, it is due to electron OMT via the half-filled d(z)(2) orbital present in Co(II) of CoTPP. The NiTPP OMTS spectra show no such band, consistent with the known difficulty of oxidation of the Ni(II) ion. The STM-based OMTS allowed these two porphyrin complexes to be easily distinguished. The present work is the first report of the observation of STM-OMTS, tunnel junction OMTS, and UPS of the same compounds. Scanning tunneling microscope-based orbital-mediated tunneling provides more information than UPS or tunnel junction-based OMTS and does so with molecular-scale resolution.

Treatment-Induced Viral Cure of Hepatitis C Virus-Infected Patients Involves a Dynamic Interplay among three Important Molecular Players in Lipid Homeostasis: Circulating microRNA (miR)-24, miR-223, and Proprotein Convertase Subtilisin/Kexin Type 9.

PubMed

Hyrina, Anastasia; Olmstead, Andrea D; Steven, Paul; Krajden, Mel; Tam, Edward; Jean, François

2017-09-01

In patients with chronic hepatitis C virus (HCV) infection, viral hijacking of the host-cell biosynthetic pathways is associated with altered lipid metabolism, which contributes to disease progression and may influence antiviral response. We investigated the molecular interplay among four key regulators of lipid homeostasis [microRNA (miR)-122, miR-24, miR-223, and proprotein convertase subtilisin/kexin type 9 (PCSK9)] in HCV-infected patients (n=72) who achieved a treatment-based viral cure after interferon-based therapy with first-generation direct-acting antivirals. Real-time PCR was used to quantify microRNA plasma levels, and ELISA assays were used to determine plasma concentrations of PCSK9. We report that levels of miR-24 and miR-223 significantly increased in patients achieving sustained virologic response (SVR), whereas the levels of miR-122, a liver-specific cofactor for HCV infection, decreased in these patients. PCSK9 concentrations were significantly increased in SVRs, suggesting that PCSK9 may help impede viral infection. The modulatory effect of PCSK9 on HCV infection was also demonstrated in the context of HCV-infected Huh-7.5.1 cells employing recombinant human PCSK9 mutants. Together, these results provide insights into a novel coordinated interplay among three important molecular players in lipid homeostasis - circulating miR-24, miR-223 and PCSK9 - whose regulation is affected by HCV infection and treatment-based viral cure. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

iTRAQ-Based Quantitative Proteomic Analysis of the Initiation of Head Regeneration in Planarians.

PubMed

Geng, Xiaofang; Wang, Gaiping; Qin, Yanli; Zang, Xiayan; Li, Pengfei; Geng, Zhi; Xue, Deming; Dong, Zimei; Ma, Kexue; Chen, Guangwen; Xu, Cunshuan

2015-01-01

The planarian Dugesia japonica has amazing ability to regenerate a head from the anterior ends of the amputated stump with maintenance of the original anterior-posterior polarity. Although planarians present an attractive system for molecular investigation of regeneration and research has focused on clarifying the molecular mechanism of regeneration initiation in planarians at transcriptional level, but the initiation mechanism of planarian head regeneration (PHR) remains unclear at the protein level. Here, a global analysis of proteome dynamics during the early stage of PHR was performed using isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics strategy, and our data are available via ProteomeXchange with identifier PXD002100. The results showed that 162 proteins were differentially expressed at 2 h and 6 h following amputation. Furthermore, the analysis of expression patterns and functional enrichment of the differentially expressed proteins showed that proteins involved in muscle contraction, oxidation reduction and protein synthesis were up-regulated in the initiation of PHR. Moreover, ingenuity pathway analysis showed that predominant signaling pathways such as ILK, calcium, EIF2 and mTOR signaling which were associated with cell migration, cell proliferation and protein synthesis were likely to be involved in the initiation of PHR. The results for the first time demonstrated that muscle contraction and ILK signaling might played important roles in the initiation of PHR at the global protein level. The findings of this research provide a molecular basis for further unraveling the mechanism of head regeneration initiation in planarians.

Correlating Single Crystal Structure, Nanomechanical, and Bulk Compaction Behavior of Febuxostat Polymorphs.

PubMed

Yadav, Jayprakash A; Khomane, Kailas S; Modi, Sameer R; Ugale, Bharat; Yadav, Ram Naresh; Nagaraja, C M; Kumar, Navin; Bansal, Arvind K

2017-03-06

Febuxostat exhibits unprecedented solid forms with a total of 40 polymorphs and pseudopolymorphs reported. Polymorphs differ in molecular arrangement and conformation, intermolecular interactions, and various physicochemical properties, including mechanical properties. Febuxostat Form Q (FXT Q) and Form H1 (FXT H1) were investigated for crystal structure, nanomechanical parameters, and bulk deformation behavior. FXT Q showed greater compressibility, densification, and plastic deformation as compared to FXT H1 at a given compaction pressure. Lower mechanical hardness of FXT Q (0.214 GPa) as compared to FXT H1 (0.310 GPa) was found to be consistent with greater compressibility and lower mean yield pressure (38 MPa) of FXT Q. Superior compaction behavior of FXT Q was attributed to the presence of active slip systems in crystals which offered greater plastic deformation. By virtue of greater compressibility and densification, FXT Q showed higher tabletability over FXT H1. Significant correlation was found with anticipation that the preferred orientation of molecular planes into a crystal lattice translated nanomechanical parameters to a bulk compaction process. Moreover, prediction of compactibility of materials based on true density or molecular packing should be carefully evaluated, as slip-planes may cause deviation in the structure-property relationship. This study supported how molecular level crystal structure confers a bridge between particle level nanomechanical parameters and bulk level deformation behavior.

Novel serine-based gemini surfactants as chemical permeation enhancers of local anesthetics: A comprehensive study on structure-activity relationships, molecular dynamics and dermal delivery.

PubMed

Teixeira, Raquel S; Cova, Tânia F G G; Silva, Sérgio M C; Oliveira, Rita; do Vale, M Luísa C; Marques, Eduardo F; Pais, Alberto A C C; Veiga, Francisco J B

2015-06-01

This work aims at studying the efficacy of a series of novel biocompatible, serine-based surfactants as chemical permeation enhancers for two different local anesthetics, tetracaine and ropivacaine, combining an experimental and computational approach. The surfactants consist of gemini molecules structurally related, but with variations in headgroup charge (nonionic vs. cationic) and in the hydrocarbon chain lengths (main and spacer chains). In vitro permeation and molecular dynamics studies combined with cytotoxicity profiles were performed to investigate the permeation of both drugs, probe skin integrity, and rationalize the interactions at molecular level. Results show that these enhancers do not have significant deleterious effects on the skin structure and do not cause relevant changes on cell viability. Permeation across the skin is clearly improved using some of the selected serine-based gemini surfactants, namely the cationic ones with long alkyl chains and shorter spacer. This is noteworthy in the case of ropivacaine hydrochloride, which is not easily administered through the stratum corneum. Molecular dynamics results provide a mechanistic view of the surfactant action on lipid membranes that essentially corroborate the experimental observations. Overall, this study suggests the viability of these serine-based surfactants as suitable and promising delivery agents in pharmaceutical formulations. Copyright © 2015. Published by Elsevier B.V.

KEGG Bioinformatics Resource for Plant Genomics and Metabolomics.

PubMed

Kanehisa, Minoru

2016-01-01

In the era of high-throughput biology it is necessary to develop not only elaborate computational methods but also well-curated databases that can be used as reference for data interpretation. KEGG ( http://www.kegg.jp/ ) is such a reference knowledge base with two specific aims. One is to compile knowledge on high-level functions of the cell and the organism in terms of the molecular interaction and reaction networks, which is implemented in KEGG pathway maps, BRITE functional hierarchies, and KEGG modules. The other is to expand knowledge on genes and proteins involved in the molecular networks from experimentally observed organisms to other organisms using the concept of orthologs, which is implemented in the KEGG Orthology (KO) system. Thus, KEGG is a generic resource applicable to all organisms and enables interpretation of high-level functions from genomic and molecular data. Here we first present a brief overview of the entire KEGG resource, and then give an introduction of how to use KEGG in plant genomics and metabolomics research.

Uncovering the structure-function relationship in spider silk

NASA Astrophysics Data System (ADS)

Yarger, Jeffery L.; Cherry, Brian R.; van der Vaart, Arjan

2018-03-01

All spiders produce protein-based biopolymer fibres that we call silk. The most studied of these silks is spider dragline silk, which is very tough and relatively abundant compared with other types of spider silks. Considerable research has been devoted to understanding the relationship between the molecular structure and mechanical properties of spider dragline silks. In this Review, we overview experimental and computational studies that have provided a wealth of detail at the molecular level on the highly conserved repetitive core and terminal regions of spider dragline silk. We also discuss the role of the nanocrystalline β-sheets and amorphous regions in determining the properties of spider silk fibres, endowing them with strength and elasticity. Additionally, we outline imaging techniques and modelling studies that elucidate the importance of the hierarchical structure of silk fibres at the molecular level. These insights into structure-function relationships can guide the reverse engineering of spider silk to enable the production of superior synthetic fibres.

Processing of oil palm empty fruit bunch as filler material of polymer recycles

NASA Astrophysics Data System (ADS)

Saepulloh, D. R.; Nikmatin, S.; Hardhienata, H.

2017-05-01

Oil palm empty fruit bunches (OPEFB) is waste from crude palm oil (CPO) processing plants. This research aims to process OPEFB to be a reinforcement polymer recycle with the mechanical milling method and identify each establishment molecular with the orbital hybridization theory. OPEFB fibers were synthesized using a mechanical milling until the size shortfiber and microfiber. Then do the biocomposite granular synthesis with single screw extruder. TAPPI chemical test shows levels of α-cellulose fibers amounted 41.68%. Based on density, the most optimum composition contained in the filler amounted 15% with the size is the microfiber. The test results of morphology with SEM showed deployment of filler OPEFB fiber is fairly equitable distributed. Regarding the molecular interaction between matrix with OPEFB fiber, described by the theory of orbital hybridization. But the explanation establishment of the bond for more complex molecules likes this from the side of the molecular orbital theory is necessary complete information of the hybrid levels.

GATE: software for the analysis and visualization of high-dimensional time series expression data.

PubMed

MacArthur, Ben D; Lachmann, Alexander; Lemischka, Ihor R; Ma'ayan, Avi

2010-01-01

We present Grid Analysis of Time series Expression (GATE), an integrated computational software platform for the analysis and visualization of high-dimensional biomolecular time series. GATE uses a correlation-based clustering algorithm to arrange molecular time series on a two-dimensional hexagonal array and dynamically colors individual hexagons according to the expression level of the molecular component to which they are assigned, to create animated movies of systems-level molecular regulatory dynamics. In order to infer potential regulatory control mechanisms from patterns of correlation, GATE also allows interactive interroga-tion of movies against a wide variety of prior knowledge datasets. GATE movies can be paused and are interactive, allowing users to reconstruct networks and perform functional enrichment analyses. Movies created with GATE can be saved in Flash format and can be inserted directly into PDF manuscript files as interactive figures. GATE is available for download and is free for academic use from http://amp.pharm.mssm.edu/maayan-lab/gate.htm

Gliomatosis cerebri: Prognosis based on current molecular markers.

PubMed

Maharaj, Monish M; Phan, Kevin; Xu, Joshua; Fairhall, Jacob; Reddy, Rajesh; Rao, Prashanth J V

2017-09-01

This study aims to review the literature and identify key molecular markers affecting the prognosis of Gliomatosis cerebri (2) to evaluate the level of evidence and identify outstanding markers requiring further study. A literature search was conducted across 5 major databases using the key terms: "Molecular markers" AND "Gliomatosis cerebri" OR "diffuse astrocytoma." Critical appraisal and data presentation was performed inline with the PRISMA guidelines. Following search strategy implementation, 11 studies were included in the final review process. Our data demonstrates significant prognostic value associated with IDH1 132H mutation and variable evidence surrounding the role of INA expression, MGMT promoter methylation and other factors. However, there are significant limitations in the level of evidence obtained. As the genetic basis for the pathogenesis of Gliomatosis cerebri continues to widen, there is little data on markers aside from IDH1 mutation available. IDH1 132H mutation has been demonstrated to have significant effect on survival, particularly in patients with Gliomatosis cerebri type 2. Copyright © 2017 Elsevier Ltd. All rights reserved.

Computational Modeling of Airway and Pulmonary Vascular Structure and Function: Development of a “Lung Physiome”

PubMed Central

Tawhai, M. H.; Clark, A. R.; Donovan, G. M.; Burrowes, K. S.

2011-01-01

Computational models of lung structure and function necessarily span multiple spatial and temporal scales, i.e., dynamic molecular interactions give rise to whole organ function, and the link between these scales cannot be fully understood if only molecular or organ-level function is considered. Here, we review progress in constructing multiscale finite element models of lung structure and function that are aimed at providing a computational framework for bridging the spatial scales from molecular to whole organ. These include structural models of the intact lung, embedded models of the pulmonary airways that couple to model lung tissue, and models of the pulmonary vasculature that account for distinct structural differences at the extra- and intra-acinar levels. Biophysically based functional models for tissue deformation, pulmonary blood flow, and airway bronchoconstriction are also described. The development of these advanced multiscale models has led to a better understanding of complex physiological mechanisms that govern regional lung perfusion and emergent heterogeneity during bronchoconstriction. PMID:22011236

Exploring parameter space effects on structure-property relationships of surfactants at liquid-liquid interfaces.

PubMed

Emborsky, Christopher P; Cox, Kenneth R; Chapman, Walter G

2011-08-28

The ubiquitous use of surfactants in commercial and industrial applications has led to many experimental, theoretical, and simulation based studies. These efforts seek to provide a molecular level understanding of the effects on structuring behavior and the corresponding impacts on observable properties (e.g., interfacial tension). With such physical detail, targeted system design can be improved over typical techniques of observational trends and phenomenological correlations by taking advantage of predictive system response. This research provides a systematic study of part of the broad parameter space effects on equilibrium microstructure and interfacial properties of amphiphiles at a liquid-liquid interface using the interfacial statistical associating fluid theory density functional theory as a molecular model for the system from the bulk to the interface. Insights into the molecular level physics and thermodynamics governing the system behavior are discussed as they relate to both predictions qualitatively consistent with experimental observations and extensions beyond currently available studies. © 2011 American Institute of Physics

Toward Molecular Level of the “Salmonella-Victim” Ecology, Genetics, and Evolution

PubMed Central

Rumyantsev, S.N.

2004-01-01

Bacteria of the Salmonella genus are polypathogenic agents that can affect both men and animals, causing devastating and fatal illness. Despite considerable immunological, epidemiological, and genetic efforts, and increased understanding of how the Salmonella infection develops, many key questions concerning Salmonella infection remain unanswered. Salmonella can be carried as harmless commensals in some sectors of the population. In some individuals, however, the same microbes cause illness while others display immunity to primary Salmonella infection. Nothing is known about the molecular base of the Salmonella pathogenicity. Even the ability of Salmonella to destroy the victims cells has been the subject of century-long discussions. In this article, some key findings concerning ecology, molecular ecology, and cell level of the Salmonella infection genetics are summarized and interpreted from the viewpoint of evolutionary theory with certitude that this approach can help to decipher the undiscovered secrets of Salmonella infections epidemiology and pathogenesis, as well as the clinical course and severity, and to select ways for fighting against Salmonella. PMID:15105959

Assessment of molecular contamination in mask pod

NASA Astrophysics Data System (ADS)

Foray, Jean Marie; Dejaune, Patrice; Sergent, Pierre; Gough, Stuart; Cheung, D.; Davenet, Magali; Favre, Arnaud; Rude, C.; Trautmann, T.; Tissier, Michel; Fontaine, H.; Veillerot, M.; Avary, K.; Hollein, I.; Lerit, R.

2008-04-01

Context/ study Motivation: Contamination and especially Airbone Molecular Contamination (AMC) is a critical issue for mask material flow with a severe and fairly unpredictable risk of induced contamination and damages especially for 193 nm lithography. It is therefore essential to measure, to understand and then try to reduce AMC in mask environment. Mask material flow was studied in a global approach by a pool of European partners, especially within the frame of European MEDEA+ project, so called "MUSCLE". This paper deals with results and assessment of mask pod environment in term of molecular contamination in a first step, then in a second step preliminary studies to reduce mask pod influence and contamination due to material out gassing. Approach and techniques: A specific assessment of environmental / molecular contamination along the supply chain was performed by all partners. After previous work presented at EMLC 07, further studies were performed on real time contamination measurement pod at different sites locations (including Mask manufacturing site, blank manufacturing sites, IC fab). Studies were linked to the main critical issues: cleaning, storage, handling, materials and processes. Contamination measurement campaigns were carried out along the mask supply chain using specific Adixen analyzer in order to monitor in real time organic contaminants (ppb level) in mask pods. Key results would be presented: VOC, AMC and humidity level on different kinds of mask carriers, impact of basic cleaning on pod outgassing measurement (VOC, NH3), and process influence on pod contamination... In a second step, preliminary specific pod conditioning studies for better pod environment were performed based on Adixen vacuum process. Process influence had been experimentally measured in term of molecular outgassing from mask pods. Different AMC experimental characterization methods had been carried out leading to results on a wide range of organic and inorganic contaminants: by inline techniques based on Adixen humidity, also VOC and organic sensors, together by off-line techniques already used in the extensive previous mask pods benchmark (TD-GCMS & Ionic Chromatography). Humidity and VOC levels from mask carriers had shown significant reduction after Adixen pod conditioning process. Focus had been made on optimized vacuum step (for AMC) after particles carrier cleaning cycle. Based upon these key results new procedures, as well as guidelines for mask carrier cleaning optimization are proposed to improve pod contamination control. Summary results/next steps: This paper reports molecular contamination measurement campaigns performed by a pool of European partners along the mask supply chain. It allows us to investigate, identify and quantify critical molecular contamination in mask pod, as well as VOC and humidity, issues depending on locations, uses, and carrier's type. Preliminary studies highlight initial process solutions for pods conditioning that are being used for short term industrialization and further industrialized.

The Influence of Fluorination on Nano-Scale Phase Separation and Photovoltaic Performance of Small Molecular/PC71BM Blends

PubMed Central

Lu, Zhen; Liu, Wen; Li, Jingjing; Fang, Tao; Li, Wanning; Zhang, Jicheng; Feng, Feng; Li, Wenhua

2016-01-01

To investigate the fluorination influence on the photovoltaic performance of small molecular based organic solar cells (OSCs), six small molecules based on 2,1,3-benzothiadiazole (BT), and diketopyrrolopyrrole (DPP) as core and fluorinated phenyl (DFP) and triphenyl amine (TPA) as different terminal units (DFP-BT-DFP, DFP-BT-TPA, TPA-BT-TPA, DFP-DPP-DFP, DFP-DPP-TPA, and TPA-DPP-TPA) were synthesized. With one or two fluorinated phenyl as the end group(s), HOMO level of BT and DPP based small molecular donors were gradually decreased, inducing high open circuit voltage for fluorinated phenyl based OSCs. DFP-BT-TPA and DFP-DPP-TPA based blend films both displayed stronger nano-scale aggregation in comparison to TPA-BT-TPA and TPA-DPP-TPA, respectively, which would also lead to higher hole motilities in devices. Ultimately, improved power conversion efficiency (PCE) of 2.17% and 1.22% was acquired for DFP-BT-TPA and DFP-DPP-TPA based devices, respectively. These results demonstrated that the nano-scale aggregation size of small molecules in photovoltaic devices could be significantly enhanced by introducing a fluorine atom at the donor unit of small molecules, which will provide understanding about the relationship of chemical structure and nano-scale phase separation in OSCs. PMID:28335208

Optimized unconventional superconductivity in a molecular Jahn-Teller metal

PubMed Central

Zadik, Ruth H.; Takabayashi, Yasuhiro; Klupp, Gyöngyi; Colman, Ross H.; Ganin, Alexey Y.; Potočnik, Anton; Jeglič, Peter; Arčon, Denis; Matus, Péter; Kamarás, Katalin; Kasahara, Yuichi; Iwasa, Yoshihiro; Fitch, Andrew N.; Ohishi, Yasuo; Garbarino, Gaston; Kato, Kenichi; Rosseinsky, Matthew J.; Prassides, Kosmas

2015-01-01

Understanding the relationship between the superconducting, the neighboring insulating, and the normal metallic state above Tc is a major challenge for all unconventional superconductors. The molecular A3C60 fulleride superconductors have a parent antiferromagnetic insulator in common with the atom-based cuprates, but here, the C603– electronic structure controls the geometry and spin state of the structural building unit via the on-molecule Jahn-Teller effect. We identify the Jahn-Teller metal as a fluctuating microscopically heterogeneous coexistence of both localized Jahn-Teller–active and itinerant electrons that connects the insulating and superconducting states of fullerides. The balance between these molecular and extended lattice features of the electrons at the Fermi level gives a dome-shaped variation of Tc with interfulleride separation, demonstrating molecular electronic structure control of superconductivity. PMID:26601168

May Diet and Dietary Supplements Improve the Wellness of Multiple Sclerosis Patients? A Molecular Approach

PubMed Central

Riccio, Paolo; Rossano, Rocco; Liuzzi, Grazia Maria

2010-01-01

Multiple sclerosis is a complex and multifactorial neurological disease, and nutrition is one of the environmental factors possibly involved in its pathogenesis. At present, the role of nutrition is unclear, and MS therapy is not associated to a particular diet. MS clinical trials based on specific diets or dietary supplements are very few and in some cases controversial. To understand how diet can influence the course of MS and improve the wellness of MS patients, it is necessary to identify the dietary molecules, their targets and the molecular mechanisms involved in the control of the disease. The aim of this paper is to provide a molecular basis for the nutritional intervention in MS by evaluating at molecular level the effect of dietary molecules on the inflammatory and autoimmune processes involved in the disease. PMID:21461338

Carbon Nanotube Biosensors for Space Molecule Detection and Clinical Molecular Diagnostics

NASA Technical Reports Server (NTRS)

Han, Jie

2001-01-01

Both space molecule detection and clinical molecule diagnostics need to develop ultra sensitive biosensors for detection of less than attomole molecules such as amino acids for DNA. However all the electrode sensor systems including those fabricated from the existing carbon nanotubes, have a background level of nA (nanoAmp). This has limited DNA or other molecule detection to nA level or molecules whose concentration is, much higher than attomole level. A program has been created by NASA and NCI (National Cancer Institute) to exploit the possibility of carbon nanotube based biosensors to solve this problem for both's interest. In this talk, I will present our effort on the evaluation and novel design of carbon nanotubes as electrode biosensors with strategies to minimize background currents while maximizing signal intensity.The fabrication of nanotube electrode arrays, immobilization of molecular probes on nanotube electrodes and in vitro biosensor testing will also be discussed.

Level crossings and zero-field splitting in the {Cr8}-cubane spin cluster studied using inelastic neutron scattering and magnetization

NASA Astrophysics Data System (ADS)

Vaknin, D.; Garlea, V. O.; Demmel, F.; Mamontov, E.; Nojiri, H.; Martin, C.; Chiorescu, I.; Qiu, Y.; Kögerler, P.; Fielden, J.; Engelhardt, L.; Rainey, C.; Luban, M.

2010-11-01

Inelastic neutron scattering (INS) in variable magnetic field and high-field magnetization measurements in the millikelvin temperature range were performed to gain insight into the low-energy magnetic excitation spectrum and the field-induced level crossings in the molecular spin cluster {Cr8}-cubane. These complementary techniques provide consistent estimates of the lowest level-crossing field. The overall features of the experimental data are explained using an isotropic Heisenberg model, based on three distinct exchange interactions linking the eight CrIII paramagnetic centers (spins s = 3/2), that is supplemented with a relatively large molecular magnetic anisotropy term for the lowest S = 1 multiplet. It is noted that the existence of the anisotropy is clearly evident from the magnetic field dependence of the excitations in the INS measurements, while the magnetization measurements are not sensitive to its effects.

Level crossings and zero-field splitting in the {Cr8}-cubane spin-cluster studied using inelastic neutron scattering and magnetization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vaknin, D.; Garlea, Vasile O; Demmel, F.

Inelastic neutron scattering (INS) in variable magnetic field and high-field magnetization measurements in the millikelvin temperature range were performed to gain insight into the low-energy magnetic excitation spectrum and the field-induced level crossings in the molecular spin cluster {Cr8}-cubane. These complementary techniques provide consistent estimates of the lowest level-crossing field. The overall features of the experimental data are explained using an isotropic Heisenberg model, based on three distinct exchange interactions linking the eight CrIII paramagnetic centers (spins s = 3/2), that is supplemented with a relatively large molecular magnetic anisotropy term for the lowest S = 1 multiplet. It ismore » noted that the existence of the anisotropy is clearly evident from the magnetic field dependence of the excitations in the INS measurements, while the magnetization measurements are not sensitive to its effects.« less

Elucidation of molecular kinetic schemes from macroscopic traces using system identification

PubMed Central

González-Maeso, Javier; Sealfon, Stuart C.; Galocha-Iragüen, Belén; Brezina, Vladimir

2017-01-01

Overall cellular responses to biologically-relevant stimuli are mediated by networks of simpler lower-level processes. Although information about some of these processes can now be obtained by visualizing and recording events at the molecular level, this is still possible only in especially favorable cases. Therefore the development of methods to extract the dynamics and relationships between the different lower-level (microscopic) processes from the overall (macroscopic) response remains a crucial challenge in the understanding of many aspects of physiology. Here we have devised a hybrid computational-analytical method to accomplish this task, the SYStems-based MOLecular kinetic scheme Extractor (SYSMOLE). SYSMOLE utilizes system-identification input-output analysis to obtain a transfer function between the stimulus and the overall cellular response in the Laplace-transformed domain. It then derives a Markov-chain state molecular kinetic scheme uniquely associated with the transfer function by means of a classification procedure and an analytical step that imposes general biological constraints. We first tested SYSMOLE with synthetic data and evaluated its performance in terms of its rate of convergence to the correct molecular kinetic scheme and its robustness to noise. We then examined its performance on real experimental traces by analyzing macroscopic calcium-current traces elicited by membrane depolarization. SYSMOLE derived the correct, previously known molecular kinetic scheme describing the activation and inactivation of the underlying calcium channels and correctly identified the accepted mechanism of action of nifedipine, a calcium-channel blocker clinically used in patients with cardiovascular disease. Finally, we applied SYSMOLE to study the pharmacology of a new class of glutamate antipsychotic drugs and their crosstalk mechanism through a heteromeric complex of G protein-coupled receptors. Our results indicate that our methodology can be successfully applied to accurately derive molecular kinetic schemes from experimental macroscopic traces, and we anticipate that it may be useful in the study of a wide variety of biological systems. PMID:28192423

Hybrid Materials Based on Magnetic Layered Double Hydroxides: A Molecular Perspective.

PubMed

Abellán, Gonzalo; Martí-Gastaldo, Carlos; Ribera, Antonio; Coronado, Eugenio

2015-06-16

Design of functional hybrids lies at the very core of synthetic chemistry as it has enabled the development of an unlimited number of solids displaying unprecedented or even improved properties built upon the association at the molecular level of quite disparate components by chemical design. Multifunctional hybrids are a particularly appealing case among hybrid organic/inorganic materials. Here, chemical knowledge is used to deploy molecular components bearing different functionalities within a single solid so that these properties can coexist or event interact leading to unprecedented phenomena. From a molecular perspective, this can be done either by controlled assembly of organic/inorganic molecular tectons into an extended architecture of hybrid nature or by intercalation of organic moieties within the empty channels or interlamellar space offered by inorganic solids with three-dimensional (MOFs, zeolites, and mesoporous hosts) or layered structures (phosphates, silicates, metal dichalcogenides, or anionic clays). This Account specifically illustrates the use of layered double hydroxides (LDHs) in the preparation of magnetic hybrids, in line with the development of soft inorganic chemistry processes (also called "Chimie Douce"), which has significantly contributed to boost the preparation hybrid materials based on solid-state hosts and subsequent development of applications. Several features sustain the importance of LDHs in this context. Their magnetism can be manipulated at a molecular level by adequate choice of constituting metals and interlayer separation for tuning the nature and extent of magnetic interactions across and between planes. They display unparalleled versatility in accommodating a broad range of anionic species in their interlamellar space that encompasses not only simple anions but chemical systems of increasing dimensionality and functionalities. Their swelling characteristics allow for their exfoliation in organic solvents with high dielectric strength, to produce two-dimensional nanosheets with atomic thickness that can be used as macromolecular building blocks in the assembly of nanocomposites. We describe how these advantageous properties turn LDHs into excellent vehicles for the preparation of multifunctional materials with increasing levels of complexity. For clarity, the reader will first find a succinct description of the most relevant aspects controlling the magnetism of LDHs followed by their use in the preparation of magnetic hybrids from a molecular perspective. This includes the intercalation anionic species of increasing nuclearity like paramagnetic mononuclear complexes, stimulus-responsive molecular guests, one- and two-dimensional coordination polymers, or even preassembled 2D networks. This approach allows us to evolve from "dual-function" materials with coexistence, for example, of magnetism and superconductivity, to smart materials in which the magnetic or structural properties of the LDH layers can be tuned by applying an external stimulus like light or temperature. We will conclude with a brief look into the promising features offered by magnetic nanocomposites based on LDHs and our views on the most promising directions to be pursued in this context.

Isoflavone-free soy protein diet inhibits LPS-induced inflammatory responses

USDA-ARS?s Scientific Manuscript database

Recently, we showed reduced atherosclerotic lesions in a hyperlipidemic mouse model fed isoflavone-free soy protein diet (SPI–) compared to casein (CAS)-fed mice, despite unchanged serum lipid levels. However, the molecular mechanisms contributing to the atheroprotective effect of soy-based diets is...

Constructing Adverse Outcome Pathways: a Demonstration of an Ontology-based Semantics Mapping Approach

EPA Science Inventory

Adverse outcome pathway (AOP) provides a conceptual framework to evaluate and integrate chemical toxicity and its effects across the levels of biological organization. As such, it is essential to develop a resource-efficient and effective approach to extend molecular initiating ...

A coupled two-dimensional main chain torsional potential for protein dynamics: generation and implementation.

PubMed

Li, Yongxiu; Gao, Ya; Zhang, Xuqiang; Wang, Xingyu; Mou, Lirong; Duan, Lili; He, Xiao; Mei, Ye; Zhang, John Z H

2013-09-01

Main chain torsions of alanine dipeptide are parameterized into coupled 2-dimensional Fourier expansions based on quantum mechanical (QM) calculations at M06 2X/aug-cc-pvtz//HF/6-31G** level. Solvation effect is considered by employing polarizable continuum model. Utilization of the M06 2X functional leads to precise potential energy surface that is comparable to or even better than MP2 level, but with much less computational demand. Parameterization of the 2D expansions is against the full main chain torsion space instead of just a few low energy conformations. This procedure is similar to that for the development of AMBER03 force field, except unique weighting factor was assigned to all the grid points. To avoid inconsistency between quantum mechanical calculations and molecular modeling, the model peptide is further optimized at molecular mechanics level with main chain dihedral angles fixed before the calculation of the conformational energy on molecular mechanical level at each grid point, during which generalized Born model is employed. Difference in solvation models at quantum mechanics and molecular mechanics levels makes this parameterization procedure less straightforward. All force field parameters other than main chain torsions are taken from existing AMBER force field. With this new main chain torsion terms, we have studied the main chain dihedral distributions of ALA dipeptide and pentapeptide in aqueous solution. The results demonstrate that 2D main chain torsion is effective in delineating the energy variation associated with rotations along main chain dihedrals. This work is an implication for the necessity of more accurate description of main chain torsions in the future development of ab initio force field and it also raises a challenge to the development of quantum mechanical methods, especially the quantum mechanical solvation models.

In situ dynamic observations of perovskite crystallisation and microstructure evolution intermediated from [PbI6]4- cage nanoparticles

NASA Astrophysics Data System (ADS)

Hu, Qin; Zhao, Lichen; Wu, Jiang; Gao, Ke; Luo, Deying; Jiang, Yufeng; Zhang, Ziyi; Zhu, Chenhui; Schaible, Eric; Hexemer, Alexander; Wang, Cheng; Liu, Yi; Zhang, Wei; Grätzel, Michael; Liu, Feng; Russell, Thomas P.; Zhu, Rui; Gong, Qihuang

2017-06-01

Hybrid lead halide perovskites have emerged as high-performance photovoltaic materials with their extraordinary optoelectronic properties. In particular, the remarkable device efficiency is strongly influenced by the perovskite crystallinity and the film morphology. Here, we investigate the perovskites crystallisation kinetics and growth mechanism in real time from liquid precursor continually to the final uniform film. We utilize some advanced in situ characterisation techniques including synchrotron-based grazing incident X-ray diffraction to observe crystal structure and chemical transition of perovskites. The nano-assemble model from perovskite intermediated [PbI6]4- cage nanoparticles to bulk polycrystals is proposed to understand perovskites formation at a molecular- or nano-level. A crystallisation-depletion mechanism is developed to elucidate the periodic crystallisation and the kinetically trapped morphology at a mesoscopic level. Based on these in situ dynamics studies, the whole process of the perovskites formation and transformation from the molecular to the microstructure over relevant temperature and time scales is successfully demonstrated.

How may targeted proteomics complement genomic data in breast cancer?

PubMed

Guerin, Mathilde; Gonçalves, Anthony; Toiron, Yves; Baudelet, Emilie; Audebert, Stéphane; Boyer, Jean-Baptiste; Borg, Jean-Paul; Camoin, Luc

2017-01-01

Breast cancer (BC) is the most common female cancer in the world and was recently deconstructed in different molecular entities. Although most of the recent assays to characterize tumors at the molecular level are genomic-based, proteins are the actual executors of cellular functions and represent the vast majority of targets for anticancer drugs. Accumulated data has demonstrated an important level of quantitative and qualitative discrepancies between genomic/transcriptomic alterations and their protein counterparts, mostly related to the large number of post-translational modifications. Areas covered: This review will present novel proteomics technologies such as Reverse Phase Protein Array (RPPA) or mass-spectrometry (MS) based approaches that have emerged and that could progressively replace old-fashioned methods (e.g. immunohistochemistry, ELISA, etc.) to validate proteins as diagnostic, prognostic or predictive biomarkers, and eventually monitor them in the routine practice. Expert commentary: These different targeted proteomic approaches, able to complement genomic data in BC and characterize tumors more precisely, will permit to go through a more personalized treatment for each patient and tumor.

In situ dynamic observations of perovskite crystallisation and microstructure evolution intermediated from [PbI6]4− cage nanoparticles

PubMed Central

Hu, Qin; Zhao, Lichen; Wu, Jiang; Gao, Ke; Luo, Deying; Jiang, Yufeng; Zhang, Ziyi; Zhu, Chenhui; Schaible, Eric; Hexemer, Alexander; Wang, Cheng; Liu, Yi; Zhang, Wei; Grätzel, Michael; Liu, Feng; Russell, Thomas P.; Zhu, Rui; Gong, Qihuang

2017-01-01

Hybrid lead halide perovskites have emerged as high-performance photovoltaic materials with their extraordinary optoelectronic properties. In particular, the remarkable device efficiency is strongly influenced by the perovskite crystallinity and the film morphology. Here, we investigate the perovskites crystallisation kinetics and growth mechanism in real time from liquid precursor continually to the final uniform film. We utilize some advanced in situ characterisation techniques including synchrotron-based grazing incident X-ray diffraction to observe crystal structure and chemical transition of perovskites. The nano-assemble model from perovskite intermediated [PbI6]4− cage nanoparticles to bulk polycrystals is proposed to understand perovskites formation at a molecular- or nano-level. A crystallisation-depletion mechanism is developed to elucidate the periodic crystallisation and the kinetically trapped morphology at a mesoscopic level. Based on these in situ dynamics studies, the whole process of the perovskites formation and transformation from the molecular to the microstructure over relevant temperature and time scales is successfully demonstrated. PMID:28635947

In Situ Observations of UV-Induced Restructuring of Self-Assembled Porphyrin Monolayer on Liquid/Au(111) Interface at Molecular Level.

PubMed

Kim, Yongman; Doh, Won Hui; Kim, Jeongjin; Park, Jeong Young

2018-05-29

Porphyrin-derived molecules have received much attention for use in solar energy conversion devices, such as artificial leaves and dye-sensitized solar cells. Because of their technological importance, a molecular-level understanding of the mechanism for supramolecular structure formation in a liquid, as well as their stability under ultraviolet (UV) irradiation, is important. Here, we observed the self-assembled structure of free-base, copper(II), and nickel(II) octaethylporphyrin formed on Au(111) in a dodecane solution using scanning tunneling microscopy (STM). As evident in the STM images, the self-assembled monolayers (SAMs) of these three porphyrins on the Au(111) surface showed hexagonal close-packed structures when in dodecane solution. Under UV irradiation (λ = 365 nm), the porphyrin molecules in the SAM or the dodecane solution move extensively and form new porphyrin clusters on the Au sites that have a high degree of freedom. Consequently, the Au(111) surface was covered with disordered porphyrin clusters. However, we found that the porphyrin molecules decomposed under UV irradiation at 254 nm. Molecular-scale observation of the morphological evolution of the porphyrin SAM under UV irradiation can provide a fundamental understanding of the degradation processes of porphyrin-based energy conversion devices.

Effect of PEO molecular weight on the miscibility and dynamics in epoxy/PEO blends.

PubMed

Lu, Shoudong; Zhang, Rongchun; Wang, Xiaoliang; Sun, Pingchuan; Lv, Weifeng; Liu, Qingjie; Jia, Ninghong

2015-11-01

In this work, the effect of poly(ethylene oxide) (PEO) molecular weight in blends of epoxy (ER) and PEO on the miscibility, inter-chain weak interactions and local dynamics were systematically investigated by multi-frequency temperature modulation DSC and solid-state NMR techniques. We found that the molecular weight (M(w)) of PEO was a crucial factor in controlling the miscibility, chain dynamics and hydrogen bonding interactions between PEO and ER. A critical PEO molecular weight (M(crit)) around 4.5k was found. PEO was well miscible with ER when the molecular weight was below M(crit), where the chain motion of PEO was restricted due to strong inter-chain hydrogen bonding interactions. However, for the blends with high molecular weight PEO (M(w) > M(crit)), the miscibility between PEO and ER was poor, and most of PEO chains were considerably mobile. Finally, polarization inversion spin exchange at magic angle (PISEMA) solid-state NMR experiment further revealed the different mobility of the PEO in ER/PEO blends with different molecular weight of PEO at molecular level. Based on the DSC and NMR results, a tentative model was proposed to illustrate the miscibility in ER/PEO blends.

Molecular design of donor-acceptor dyes for efficient dye-sensitized solar cells I: a DFT study.

PubMed

El-Shishtawy, Reda M; Asiri, Abdullah M; Aziz, Saadullah G; Elroby, Shaaban A K

2014-06-01

Dye-sensitized solar cells (DSSCs) have drawn great attention as low cost and high performance alternatives to conventional photovoltaic devices. The molecular design presented in this work is based on the use of pyran type dyes as donor based on frontier molecular orbitals (FMO) and theoretical UV-visible spectra in combination with squaraine type dyes as an acceptor. Density functional theory has been used to investigate several derivatives of pyran type dyes for a better dye design based on optimization of absorption, regeneration, and recombination processes in gas phase. The frontier molecular orbital (FMO) of the HOMO and LUMO energy levels plays an important role in the efficiency of DSSCs. These energies contribute to the generation of exciton, charge transfer, dissociation and exciton recombination. The computations of the geometries and electronic structures for the predicted dyes were performed using the B3LYP/6-31+G** level of theory. The FMO energies (EHOMO, ELUMO) of the studied dyes are calculated and analyzed in the terms of the UV-visible absorption spectra, which have been examined using time-dependent density functional theory (TD-DFT) techniques. This study examined absorption properties of pyran based on theoretical UV-visible absorption spectra, with comparisons between TD-DFT using B3LYP, PBE, and TPSSH functionals with 6-31+G (d) and 6-311++G** basis sets. The results provide a valuable guide for the design of donor-acceptor (D-A) dyes with high molar absorptivity and current conversion in DSSCs. The theoretical results indicated 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran dye (D2-Me) can be effectively used as a donor dye for DSSCs. This dye has a low energy gap by itself and a high energy gap with squaraine acceptor type dye, the design that reduces the recombination and improves the photocurrent generation in solar cell.

Charge transport with single molecules--an electrochemical approach.

PubMed

Li, Chen; Mishchenko, Artem; Pobelov, Ilya; Wandlowski, Thomas

2010-01-01

After an introduction and brief review of charge transport in nanoscale molecular systems we report on experimental studies in gold / (single) molecule / gold junctions at solid / liquid interfaces employing a scanning tunneling microscopy (STM)-based 'break junction' technique. We demonstrate attempts in developing basic relationships between molecular structure, conductance properties and nanoscale electrochemical concepts based on four case studies from our own work. In experiments with alpha, omega-alkanedithiol and biphenyldithiol molecular junctions we address the role of sulfur-gold couplings and molecular conformation, such as gauche defects in the alkyl chains and the torsion angle between two phenyl rings. Combination with quantum chemistry calculations enabled a detailed molecular-level understanding of the electronic structure and transport characteristics of both systems. Employing the concept of 'electrolyte gating' with redox-active molecules, such as thiol-terminated derivatives of viologens (HS-6V6-SH or (HS-6V6)) we demonstrate the construction of symmetric and asymmetric active molecular junctions with transistor- or diode-like behavior upon polarization in an electrochemical environment. The experimental data could be represented quantitatively by the Kutznetsov/Ulstrup model assuming a two-step electron transfer with partial vibration relaxation. Finally, we show that surface-immobilized gold nanoparticles with a diameter of (2.4 +/- 0.5) nm exhibit features of locally addressable multi-state electronic switching upon electrolyte gating, which appears to be reminiscent of a sequential charging through several 'oxidation/reduction states'.

Redox-Triggered Bonding-Induced Emission of Thiol-Functionalized Gold Nanoclusters for Luminescence Turn-On Detection of Molecular Oxygen.

PubMed

Ao, Hang; Feng, Hui; Zhao, Mengting; Zhao, Meizhi; Chen, Jianrong; Qian, Zhaosheng

2017-11-22

Most optical sensors for molecular oxygen were developed based on the quenching effect of the luminescence of oxygen-sensitive probes; however, the signal turn-off mode of these probes is undesirable to quantify and visualize molecular oxygen. Herein, we report a novel luminescence turn-on detection strategy for molecular oxygen via the specific oxygen-triggered bonding-induced emission of thiol-functionalized gold nanoclusters. Thiol-functionalized gold nanoclusters were prepared by a facile one-step synthesis, and as-prepared gold nanoclusters possess significant aggregation-induced emission (AIE) property. It is the first time to discover the oxygen-triggered bonding-induced emission (BIE) behavior of gold nanoclusters, which results in disulfide-linked covalent bonding assemblies with intensely red luminescence. This specific redox-triggered BIE is capable of quantitatively detecting dissolved oxygen in aqueous solution in a light-up manner, and trace amount of dissolved oxygen at ppb level is achieved based on this detection method. A facile and convenient test strip for oxygen detection was also developed to monitor molecular oxygen in a gas matrix. Covalent bonding-induced emission is proven to be a more efficient way to attain high brightness of AIEgens than a physical aggregation-induced emission process, and provides a more convenient and desirable detection method for molecular oxygen than the previous sensors.

Luminescence studies of HgCdTe- and InAsSb-based quantum-well structures

NASA Astrophysics Data System (ADS)

Izhnin, I. I.; Izhnin, A. I.; Fitsych, O. I.; Voitsekhovskii, A. V.; Gorn, D. I.; Semakova, A. A.; Bazhenov, N. L.; Mynbaev, K. D.; Zegrya, G. G.

2018-04-01

Results of photoluminescence studies of single-quantum-well HgCdTe-based structures and electroluminescence studies of multiple-quantum-well InAsSb-based structures are reported. HgCdTe structures were grown with molecular beam epitaxy on GaAs substrates. InAsSb-based structures were grown with metal-organic chemical vapor deposition on InAs substrates. The common feature of luminescence spectra of all the structures was the presence of peaks with the energy much larger than that of calculated optical transitions between the first quantization levels for electrons and heavy holes. Possibility of observation of optical transitions between the quantization levels of electrons and first and/or second heavy and light hole levels is discussed in the paper in relation to the specifics of the electronic structure of the materials under consideration.

Data driven linear algebraic methods for analysis of molecular pathways: application to disease progression in shock/trauma.

PubMed

McGuire, Mary F; Sriram Iyengar, M; Mercer, David W

2012-04-01

Although trauma is the leading cause of death for those below 45years of age, there is a dearth of information about the temporal behavior of the underlying biological mechanisms in those who survive the initial trauma only to later suffer from syndromes such as multiple organ failure. Levels of serum cytokines potentially affect the clinical outcomes of trauma; understanding how cytokine levels modulate intra-cellular signaling pathways can yield insights into molecular mechanisms of disease progression and help to identify targeted therapies. However, developing such analyses is challenging since it necessitates the integration and interpretation of large amounts of heterogeneous, quantitative and qualitative data. Here we present the Pathway Semantics Algorithm (PSA), an algebraic process of node and edge analyses of evoked biological pathways over time for in silico discovery of biomedical hypotheses, using data from a prospective controlled clinical study of the role of cytokines in multiple organ failure (MOF) at a major US trauma center. A matrix algebra approach was used in both the PSA node and PSA edge analyses with different matrix configurations and computations based on the biomedical questions to be examined. In the edge analysis, a percentage measure of crosstalk called XTALK was also developed to assess cross-pathway interference. In the node/molecular analysis of the first 24h from trauma, PSA uncovered seven molecules evoked computationally that differentiated outcomes of MOF or non-MOF (NMOF), of which three molecules had not been previously associated with any shock/trauma syndrome. In the edge/molecular interaction analysis, PSA examined four categories of functional molecular interaction relationships--activation, expression, inhibition, and transcription--and found that the interaction patterns and crosstalk changed over time and outcome. The PSA edge analysis suggests that a diagnosis, prognosis or therapy based on molecular interaction mechanisms may be most effective within a certain time period and for a specific functional relationship. Copyright © 2011 Elsevier Inc. All rights reserved.

Data driven linear algebraic methods for analysis of molecular pathways: application to disease progression in shock/trauma

PubMed Central

McGuire, Mary F.; Iyengar, M. Sriram; Mercer, David W.

2012-01-01

Motivation Although trauma is the leading cause of death for those below 45 years of age, there is a dearth of information about the temporal behavior of the underlying biological mechanisms in those who survive the initial trauma only to later suffer from syndromes such as multiple organ failure. Levels of serum cytokines potentially affect the clinical outcomes of trauma; understanding how cytokine levels modulate intra-cellular signaling pathways can yield insights into molecular mechanisms of disease progression and help to identify targeted therapies. However, developing such analyses is challenging since it necessitates the integration and interpretation of large amounts of heterogeneous, quantitative and qualitative data. Here we present the Pathway Semantics Algorithm (PSA), an algebraic process of node and edge analyses of evoked biological pathways over time for in silico discovery of biomedical hypotheses, using data from a prospective controlled clinical study of the role of cytokines in multiple organ failure (MOF) at a major US trauma center. A matrix algebra approach was used in both the PSA node and PSA edge analyses with different matrix configurations and computations based on the biomedical questions to be examined. In the edge analysis, a percentage measure of crosstalk called XTALK was also developed to assess cross-pathway interference. Results In the node/molecular analysis of the first 24 hours from trauma, PSA uncovered 7 molecules evoked computationally that differentiated outcomes of MOF or non-MOF (NMOF), of which 3 molecules had not been previously associated with any shock / trauma syndrome. In the edge/molecular interaction analysis, PSA examined four categories of functional molecular interaction relationships – activation, expression, inhibition, and transcription – and found that the interaction patterns and crosstalk changed over time and outcome. The PSA edge analysis suggests that a diagnosis, prognosis or therapy based on molecular interaction mechanisms may be most effective within a certain time period and for a specific functional relationship. PMID:22200681

Wide-field SCUBA-2 observations of NGC 2264: submillimetre clumps and filaments

NASA Astrophysics Data System (ADS)

Buckle, J. V.; Richer, J. S.

2015-10-01

We present wide-field observations of the NGC 2264 molecular cloud in the dust continuum at 850 and 450 μm using SCUBA-2 on the James Clerk Maxwell Telescope. Using 12CO 3 → 2 molecular line data, we determine that emission from CO contaminates the 850 μm emission at levels ˜30 per cent in localized regions associated with high-velocity molecular outflows. Much higher contamination levels of 60 per cent are seen in shocked regions near the massive star S Mon. If not removed, the levels of CO contamination would contribute an extra 13 per cent to the dust mass in NGC 2264. We use the FELLWALKER routine to decompose the dust into clumpy structures, and a Hessian-based routine to decompose the dust into filamentary structures. The filaments can be described as a hub-filament structure, with lower column density filaments radiating from the NGC 2264 C protocluster hub. Above mean filament column densities of 2.4 × 1022 cm-2, star formation proceeds with the formation of two or more protostars. Below these column densities, filaments are starless, or contain only a single protostar.

The pathophysiology of post-stroke aphasia: A network approach.

PubMed

Thiel, Alexander; Zumbansen, Anna

2016-06-13

Post-stroke aphasia syndromes as a clinical entity arise from the disruption of brain networks specialized in language production and comprehension due to permanent focal ischemia. This approach to post-stroke aphasia is based on two pathophysiological concepts: 1) Understanding language processing in terms of distributed networks rather than language centers and 2) understanding the molecular pathophysiology of ischemic brain injury as a dynamic process beyond the direct destruction of network centers and their connections. While considerable progress has been made in the past 10 years to develop such models on a systems as well as a molecular level, the influence of these approaches on understanding and treating clinical aphasia syndromes has been limited. In this article, we review current pathophysiological concepts of ischemic brain injury, their relationship to altered information processing in language networks after ischemic stroke and how these mechanisms may be influenced therapeutically to improve treatment of post-stroke aphasia. Understanding the pathophysiological mechanism of post-stroke aphasia on a neurophysiological systems level as well as on the molecular level becomes more and more important for aphasia treatment, as the field moves from standardized therapies towards more targeted individualized treatment strategies comprising behavioural therapies as well as non-invasive brain stimulation (NIBS).

Using gene transcription to assess ecological and anthropological stressors in brown bears

USGS Publications Warehouse

Bowen, Lizabeth; Miles, A. Keith; Waters, Shannon C.; Gustine, Dave; Joly, Kyle; Hilderbrand, Grant V.

2018-01-01

Increasingly, population- and ecosystem-level health assessments are performed using sophisticated molecular tools. Advances in molecular technology enable the identification of synergistic effects of multiple stressors on the individual physiology of different species. Brown bears (Ursus arctos) are an apex predator; thus, they are ideal candidates for detecting potentially ecosystem-level systemic perturbations using molecular-based tools. We used gene transcription to analyze 130 brown bear samples from three National Parks and Preserves in Alaska. Although the populations we studied are apparently stable in abundance and exist within protected and intact environments, differences in transcript profiles were noted. The most prevalent differences were among locations. The transcript patterns among groups reflect the influence of environmental factors, such as nutritional status, disease, and xenobiotic exposure. However, these profiles also likely represent baselines for each unique environment by which future measures can be made to identify early indication of population-level changes due to, for example, increasing Arctic temperatures. Some of those environmental changes are predicted to be potentially positive for brown bears, but other effects such as the manifestation of disease or indirect effects of oceanic acidification may produce negative impacts.

Molecular recognition of the environment and mechanisms of the origin of species in quantum-like modeling of evolution.

PubMed

Melkikh, Alexey V; Khrennikov, Andrei

2017-11-01

A review of the mechanisms of speciation is performed. The mechanisms of the evolution of species, taking into account the feedback of the state of the environment and mechanisms of the emergence of complexity, are considered. It is shown that these mechanisms, at the molecular level, cannot work steadily in terms of classical mechanics. Quantum mechanisms of changes in the genome, based on the long-range interaction potential between biologically important molecules, are proposed as one of possible explanation. Different variants of interactions of the organism and environment based on molecular recognition and leading to new species origins are considered. Experiments to verify the model are proposed. This bio-physical study is completed by the general operational model of based on quantum information theory. The latter is applied to model of epigenetic evolution. We briefly present the basics of the quantum-like approach to modeling of bio-informational processes. This approach is illustrated by the quantum-like model of epigenetic evolution. Copyright © 2017 Elsevier Ltd. All rights reserved.

The new WHO 2016 classification of brain tumors-what neurosurgeons need to know.

PubMed

Banan, Rouzbeh; Hartmann, Christian

2017-03-01

The understanding of molecular alterations of tumors has severely changed the concept of classification in all fields of pathology. The availability of high-throughput technologies such as next-generation sequencing allows for a much more precise definition of tumor entities. Also in the field of brain tumors a dramatic increase of knowledge has occurred over the last years partially calling into question the purely morphologically based concepts that were used as exclusive defining criteria in the WHO 2007 classification. Review of the WHO 2016 classification of brain tumors as well as a search and review of publications in the literature relevant for brain tumor classification from 2007 up to now. The idea of incorporating the molecular features in classifying tumors of the central nervous system led the authors of the new WHO 2016 classification to encounter inevitable conceptual problems, particularly with respect to linking morphology to molecular alterations. As a solution they introduced the concept of a "layered diagnosis" to the classification of brain tumors that still allows at a lower level a purely morphologically based diagnosis while partially forcing the incorporation of molecular characteristics for an "integrated diagnosis" at the highest diagnostic level. In this context the broad availability of molecular assays was debated. On the one hand molecular antibodies specifically targeting mutated proteins should be available in nearly all neuropathological laboratories. On the other hand, different high-throughput assays are accessible only in few first-world neuropathological institutions. As examples oligodendrogliomas are now primarily defined by molecular characteristics since the required assays are generally established, whereas molecular grouping of ependymomas, found to clearly outperform morphologically based tumor interpretation, was rejected from inclusion in the WHO 2016 classification because the required assays are currently only established in a small number of institutions. In summary, while neuropathologists have now encountered various challenges in the transitional phase from the previous WHO 2007 version to the new WHO 2016 classification of brain tumors, clinical neurooncologists now face many new diagnoses allowing a clearly improved understanding that could offer them more effective therapeutic opportunities in neurooncological treatment. The new WHO 2016 classification presumably presents the highest number of modifications since the initial WHO classification of 1979 and thereby forces all professionals in the field of neurooncology to intensively understand the new concepts. This review article aims to present the basic concepts of the new WHO 2016 brain tumor classification for neurosurgeons with a focus on neurooncology.

Reactive molecular simulation on the calcium silicate hydrates/polyethylene glycol composites

NASA Astrophysics Data System (ADS)

Zhou, Yang; Hou, Dongshuai; Jiang, Jinyang; She, Wei; Yu, Jiao

2017-11-01

Calcium silicate hydrates (C-S-H) may potentially exhibit extraordinary performance when modified by polymers, in which way the properties of cement-based materials can be improved from the genetic level. In this molecular dynamics simulation of the interaction between C-S-H and polyethylene glycol, apart from the H bond network connection in the interface, another chemical adsorption was observed. Calcium of C-S-H broke the Csbnd O bond of PEG and formed a new Casbnd C connection, which created a stronger link between the organic and inorganic phases.

"Washing-out" ionic liquids from polyethylene glycol to form aqueous biphasic systems.

PubMed

Tomé, Luciana I N; Pereira, Jorge F B; Rogers, Robin D; Freire, Mara G; Gomes, José R B; Coutinho, João A P

2014-02-14

The molecular-level mechanisms behind the formation of aqueous biphasic systems (ABS) composed of ionic liquids (ILs) and polymers are hitherto not completely understood. For the first time, it is herein shown that polymer-IL-based ABS are a result of a "washing-out" phenomenon, and not of a salting-out effect of the IL over the polymer as assumed in the past few years. Novel evidence is herein provided by experimental results combined with molecular dynamics (MD) simulations and density functional theory (DFT) calculations.

Nanoscale inhomogeneity and photoacid generation dynamics in extreme ultraviolet resist materials

NASA Astrophysics Data System (ADS)

Wu, Ping-Jui; Wang, Yu-Fu; Chen, Wei-Chi; Wang, Chien-Wei; Cheng, Joy; Chang, Vencent; Chang, Ching-Yu; Lin, John; Cheng, Yuan-Chung

2018-03-01

The development of extreme ultraviolet (EUV) lithography towards the 22 nm node and beyond depends critically on the availability of resist materials that meet stringent control requirements in resolution, line edge roughness, and sensitivity. However, the molecular mechanisms that govern the structure-function relationships in current EUV resist systems are not well understood. In particular, the nanoscale structures of the polymer base and the distributions of photoacid generators (PAGs) should play a critical roles in the performance of a resist system, yet currently available models for photochemical reactions in EUV resist systems are exclusively based on homogeneous bulk models that ignore molecular-level details of solid resist films. In this work, we investigate how microscopic molecular organizations in EUV resist affect photoacid generations in a bottom-up approach that describes structure-dependent electron-transfer dynamics in a solid film model. To this end, molecular dynamics simulations and stimulated annealing are used to obtain structures of a large simulation box containing poly(4-hydroxystyrene) (PHS) base polymers and triphenylsulfonium based PAGs. Our calculations reveal that ion-pair interactions govern the microscopic distributions of the polymer base and PAG molecules, resulting in a highly inhomogeneous system with nonuniform nanoscale chemical domains. Furthermore, the theoretical structures were used in combination of quantum chemical calculations and the Marcus theory to evaluate electron transfer rates between molecular sites, and then kinetic Monte Carlo simulations were carried out to model electron transfer dynamics with molecular structure details taken into consideration. As a result, the portion of thermalized electrons that are absorbed by the PAGs and the nanoscale spatial distribution of generated acids can be estimated. Our data reveal that the nanoscale inhomogeneous distributions of base polymers and PAGs strongly affect the electron transfer and the performance of the resist system. The implications to the performances of EUV resists and key engineering requirements for improved resist systems will also be discussed in this work. Our results shed light on the fundamental structure dependence of photoacid generation and the control of the nanoscale structures as well as base polymer-PAG interactions in EVU resist systems, and we expect these knowledge will be useful for the future development of improved EUV resist systems.

Molecular blood typing augments serologic testing and allows for enhanced matching of red blood cells for transfusion in patients with sickle cell disease.

PubMed

Wilkinson, Katie; Harris, Samantha; Gaur, Prashant; Haile, Askale; Armour, Rosalind; Teramura, Gayle; Delaney, Meghan

2012-02-01

Sickle cell disease (SCD) patients have dissimilar red blood cell (RBC) phenotypes compared to the primarily Caucasian blood donor base due, in part, to underlying complex Rh and silenced Duffy expression. Gene array-based technology offers high-throughput antigen typing of blood donors and can identify patients with altered genotypes. The purpose of the study was to ascertain if RBC components drawn from predominantly Caucasian donors could provide highly antigen-matched products for molecularly typed SCD patients. SCD patients were genotyped by a molecular array (HEA Beadchip, BioArray Solutions). The extended antigen phenotype (C, c, E, e, K, k, Jk(a) , Jk(b) , Fy(a) , Fy(b) , S, s) was used to query the inventory using different matching algorithms; the resulting number of products was recorded. A mean of 96.2 RBC products was available for each patient at basic-level, 34 at mid-level, and 16.3 at high-level stringency. The number of negative antigens correlated negatively with the number of available products. The Duffy silencing mutation in the promoter region (67T>C) (GATA) was found in 96.5% of patients. Allowing Fy(b+) products for patients with GATA increased the number of available products by up to 180%, although it does not ensure prevention of Duffy antibodies in all patients. This feasibility study provides evidence that centers with primarily Caucasian donors may be able to provide highly antigen-matched products. Knowledge of the GATA status expands the inventory of antigen-matched products. Further work is needed to determine the most clinically appropriate match level for SCD patients. © 2012 American Association of Blood Banks.

DSSR-enhanced visualization of nucleic acid structures in Jmol

PubMed Central

Hanson, Robert M.

2017-01-01

Abstract Sophisticated and interactive visualizations are essential for making sense of the intricate 3D structures of macromolecules. For proteins, secondary structural components are routinely featured in molecular graphics visualizations. However, the field of RNA structural bioinformatics is still lagging behind; for example, current molecular graphics tools lack built-in support even for base pairs, double helices, or hairpin loops. DSSR (Dissecting the Spatial Structure of RNA) is an integrated and automated command-line tool for the analysis and annotation of RNA tertiary structures. It calculates a comprehensive and unique set of features for characterizing RNA, as well as DNA structures. Jmol is a widely used, open-source Java viewer for 3D structures, with a powerful scripting language. JSmol, its reincarnation based on native JavaScript, has a predominant position in the post Java-applet era for web-based visualization of molecular structures. The DSSR-Jmol integration presented here makes salient features of DSSR readily accessible, either via the Java-based Jmol application itself, or its HTML5-based equivalent, JSmol. The DSSR web service accepts 3D coordinate files (in mmCIF or PDB format) initiated from a Jmol or JSmol session and returns DSSR-derived structural features in JSON format. This seamless combination of DSSR and Jmol/JSmol brings the molecular graphics of 3D RNA structures to a similar level as that for proteins, and enables a much deeper analysis of structural characteristics. It fills a gap in RNA structural bioinformatics, and is freely accessible (via the Jmol application or the JSmol-based website http://jmol.x3dna.org). PMID:28472503

Reasoning across Ontologically Distinct Levels: Students' Understandings of Molecular Genetics

ERIC Educational Resources Information Center

Duncan, Ravit Golan; Reiser, Brian J.

2007-01-01

In this article we apply a novel analytical framework to explore students' difficulties in understanding molecular genetics--a domain that is particularly challenging to learn. Our analytical framework posits that reasoning in molecular genetics entails mapping across ontologically distinct levels--an information level containing the genetic…

Preparation and characterization of fusion processed solid dispersions containing a viscous thermally labile polymeric carrier.

PubMed

Hughey, Justin R; Keen, Justin M; Miller, Dave A; Brough, Chris; McGinity, James W

2012-11-15

The primary aim of the present study was to investigate the ability of hydroxypropyl and methoxyl substituted cellulose ethers to stabilize supersaturated concentrations of itraconazole (ITZ), a poorly water-soluble weak base, after an acid-to-neutral pH transition. A secondary aim of the study was to evaluate the effect of fusion processes on polymer stability and molecular weight. Polymer screening studies showed that stabilization of ITZ supersaturation was related to the molecular weight of the polymer and levels of hydroxypropyl and methoxyl substitution. METHOCEL E50LV (E50LV), which is characterized as having a high melt viscosity, was selected for solid dispersion formulation studies. Hot-melt extrusion processing of E50LV based compositions resulted in high torque loads, low material throughput and polymer degradation. KinetiSol Dispersing, a novel fusion based processing technique, was evaluated as a method to prepare the solid dispersions with reduced levels of polymer degradation. An experimental design revealed that polymer molecular weight was sensitive to shearing forces and high temperatures. However, optimal processing conditions resulted in significantly reduced E50LV degradation relative to HME processing. The technique was effectively utilized to prepare homogenous solid solutions of E50LV and ITZ, characterized as having a single glass transition temperature over a wide range of drug loadings. All prepared compositions provided for a high degree of ITZ supersaturation stabilization. Copyright © 2012 Elsevier B.V. All rights reserved.

A Therapeutic Connection between Dietary Phytochemicals and ATP Synthase.

PubMed

Ahmad, Zulfiqar; Hassan, Sherif S; Azim, Sofiya

2017-11-20

For centuries, phytochemicals have been used to prevent and cure multiple health ailments. Phytochemicals have been reported to have antioxidant, antidiabetic, antitussive, antiparasitic, anticancer, and antimicrobial properties. Generally, the therapeutic use of phytochemicals is based on tradition or word of mouth with few evidence-based studies. Moreover, molecular level interactions or molecular targets for the majority of phytochemicals are unknown. In recent years, antibiotic resistance by microbes has become a major healthcare concern. As such, the use of phytochemicals with antimicrobial properties has become pertinent. Natural compounds from plants, vegetables, herbs, and spices with strong antimicrobial properties present an excellent opportunity for preventing and combating antibiotic resistant microbial infections. ATP synthase is the fundamental means of cellular energy. Inhibition of ATP synthase may deprive cells of required energy leading to cell death, and a variety of dietary phytochemicals are known to inhibit ATP synthase. Structural modifications of phytochemicals have been shown to increase the inhibitory potency and extent of inhibition. Sitedirected mutagenic analysis has elucidated the binding site(s) for some phytochemicals on ATP synthase. Amino acid variations in and around the phytochemical binding sites can result in selective binding and inhibition of microbial ATP synthase. In this review, the therapeutic connection between dietary phytochemicals and ATP synthase is summarized based on the inhibition of ATP synthase by dietary phytochemicals. Research suggests selective targeting of ATP synthase is a valuable alternative molecular level approach to combat antibiotic resistant microbial infections. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A Therapeutic Connection between Dietary Phytochemicals and ATP Synthase

PubMed Central

Ahmad, Zulfiqar; Hassan, Sherif S.; Azim, Sofiya

2017-01-01

For centuries, phytochemicals have been used to prevent and cure multiple health ailments. Phytochemicals have been reported to have antioxidant, antidiabetic, antitussive, antiparasitic, anticancer, and antimicrobial properties. Generally, the therapeutic use of phy-tochemicals is based on tradition or word of mouth with few evidence-based studies. Moreo-ver, molecular level interactions or molecular targets for the majority of phytochemicals are unknown. In recent years, antibiotic resistance by microbes has become a major healthcare concern. As such, the use of phytochemicals with antimicrobial properties has become perti-nent. Natural compounds from plants, vegetables, herbs, and spices with strong antimicrobial properties present an excellent opportunity for preventing and combating antibiotic resistant microbial infections. ATP synthase is the fundamental means of cellular energy. Inhibition of ATP synthase may deprive cells of required energy leading to cell death, and a variety of die-tary phytochemicals are known to inhibit ATP synthase. Structural modifications of phyto-chemicals have been shown to increase the inhibitory potency and extent of inhibition. Site-directed mutagenic analysis has elucidated the binding site(s) for some phytochemicals on ATP synthase. Amino acid variations in and around the phytochemical binding sites can re-sult in selective binding and inhibition of microbial ATP synthase. In this review, the therapeu-tic connection between dietary phytochemicals and ATP synthase is summarized based on the inhibition of ATP synthase by dietary phytochemicals. Research suggests selective target-ing of ATP synthase is a valuable alternative molecular level approach to combat antibiotic resistant microbial infections. PMID:28831918

The chemistry side of AOP: implications for toxicity ...

EPA Pesticide Factsheets

An adverse outcome pathway (AOP) is a structured representation of the biological events that lead to adverse impacts following a molecular initiating event caused by chemical interaction with a macromolecule. AOPs have been proposed to facilitate toxicity extrapolation across species through understanding of species similarity in the sequence of molecular, cellular, organ and organismal level responses. However, AOPs are non-specific regarding the identity of the chemical initiators, and the range of structures for which an AOP is considered applicable has generally been poorly defined. Applicability domain has been widely understood in the field of QSAR as the response and chemical structure space in which the model makes predictions with a given reliability, and has been traditionally applied to define the similarity of query molecules within the training set. Three dimensional (3D) receptor modeling offers an approach to better define the applicability domain for selected AOPs through determination of the chemical space of the molecular initiating event. Universal 3D-QSAR models were developed for acetylcholinesterase inhibitors and estrogen receptor agonists and antagonists using a combination of fingerprint, molecular docking and structure-based pharmacophore approaches. The models were based on the critical molecular interactions within each receptor ligand binding domain, and included the key amino acid residues responsible for high binding affinity. T

Logic integration of mRNA signals by an RNAi-based molecular computer.

PubMed

Xie, Zhen; Liu, Siyuan John; Bleris, Leonidas; Benenson, Yaakov

2010-05-01

Synthetic in vivo molecular 'computers' could rewire biological processes by establishing programmable, non-native pathways between molecular signals and biological responses. Multiple molecular computer prototypes have been shown to work in simple buffered solutions. Many of those prototypes were made of DNA strands and performed computations using cycles of annealing-digestion or strand displacement. We have previously introduced RNA interference (RNAi)-based computing as a way of implementing complex molecular logic in vivo. Because it also relies on nucleic acids for its operation, RNAi computing could benefit from the tools developed for DNA systems. However, these tools must be harnessed to produce bioactive components and be adapted for harsh operating environments that reflect in vivo conditions. In a step toward this goal, we report the construction and implementation of biosensors that 'transduce' mRNA levels into bioactive, small interfering RNA molecules via RNA strand exchange in a cell-free Drosophila embryo lysate, a step beyond simple buffered environments. We further integrate the sensors with our RNAi 'computational' module to evaluate two-input logic functions on mRNA concentrations. Our results show how RNA strand exchange can expand the utility of RNAi computing and point toward the possibility of using strand exchange in a native biological setting.

Logic integration of mRNA signals by an RNAi-based molecular computer

PubMed Central

Xie, Zhen; Liu, Siyuan John; Bleris, Leonidas; Benenson, Yaakov

2010-01-01

Synthetic in vivo molecular ‘computers’ could rewire biological processes by establishing programmable, non-native pathways between molecular signals and biological responses. Multiple molecular computer prototypes have been shown to work in simple buffered solutions. Many of those prototypes were made of DNA strands and performed computations using cycles of annealing-digestion or strand displacement. We have previously introduced RNA interference (RNAi)-based computing as a way of implementing complex molecular logic in vivo. Because it also relies on nucleic acids for its operation, RNAi computing could benefit from the tools developed for DNA systems. However, these tools must be harnessed to produce bioactive components and be adapted for harsh operating environments that reflect in vivo conditions. In a step toward this goal, we report the construction and implementation of biosensors that ‘transduce’ mRNA levels into bioactive, small interfering RNA molecules via RNA strand exchange in a cell-free Drosophila embryo lysate, a step beyond simple buffered environments. We further integrate the sensors with our RNAi ‘computational’ module to evaluate two-input logic functions on mRNA concentrations. Our results show how RNA strand exchange can expand the utility of RNAi computing and point toward the possibility of using strand exchange in a native biological setting. PMID:20194121

Genetic engineered molecular imaging probes for applications in cell therapy: emphasis on MRI approach

PubMed Central

Cho, In K; Wang, Silun; Mao, Hui; Chan, Anthony WS

2016-01-01

Recent advances in stem cell-based regenerative medicine, cell replacement therapy, and genome editing technologies (i.e. CRISPR-Cas 9) have sparked great interest in in vivo cell monitoring. Molecular imaging promises a unique approach to noninvasively monitor cellular and molecular phenomena, including cell survival, migration, proliferation, and even differentiation at the whole organismal level. Several imaging modalities and strategies have been explored for monitoring cell grafts in vivo. We begin this review with an introduction describing the progress in stem cell technology, with a perspective toward cell replacement therapy. The importance of molecular imaging in reporting and assessing the status of cell grafts and their relation to the local microenvironment is highlighted since the current knowledge gap is one of the major obstacles in clinical translation of stem cell therapy. Based on currently available imaging techniques, we provide a brief discussion on the pros and cons of each imaging modality used for monitoring cell grafts with particular emphasis on magnetic resonance imaging (MRI) and the reporter gene approach. Finally, we conclude with a comprehensive discussion of future directions of applying molecular imaging in regenerative medicine to emphasize further the importance of correlating cell graft conditions and clinical outcomes to advance regenerative medicine. PMID:27766183

NanoString, a novel digital color-coded barcode technology: current and future applications in molecular diagnostics.

PubMed

Tsang, Hin-Fung; Xue, Vivian Weiwen; Koh, Su-Pin; Chiu, Ya-Ming; Ng, Lawrence Po-Wah; Wong, Sze-Chuen Cesar

2017-01-01

Formalin-fixed, paraffin-embedded (FFPE) tissue sample is a gold mine of resources for molecular diagnosis and retrospective clinical studies. Although molecular technologies have expanded the range of mutations identified in FFPE samples, the applications of existing technologies are limited by the low nucleic acids yield and poor extraction quality. As a result, the routine clinical applications of molecular diagnosis using FFPE samples has been associated with many practical challenges. NanoString technologies utilize a novel digital color-coded barcode technology based on direct multiplexed measurement of gene expression and offer high levels of precision and sensitivity. Each color-coded barcode is attached to a single target-specific probe corresponding to a single gene which can be individually counted without amplification. Therefore, NanoString is especially useful for measuring gene expression in degraded clinical specimens. Areas covered: This article describes the applications of NanoString technologies in molecular diagnostics and challenges associated with its applications and the future development. Expert commentary: Although NanoString technology is still in the early stages of clinical use, it is expected that NanoString-based cancer expression panels would play more important roles in the future in classifying cancer patients and in predicting the response to therapy for better personal therapeutic care.

MARVEL analysis of the rotational-vibrational states of the molecular ions H2D+ and D2H+.

PubMed

Furtenbacher, Tibor; Szidarovszky, Tamás; Fábri, Csaba; Császár, Attila G

2013-07-07

Critically evaluated rotational-vibrational line positions and energy levels, with associated critically reviewed labels and uncertainties, are reported for two deuterated isotopologues of the H3(+) molecular ion: H2D(+) and D2H(+). The procedure MARVEL, standing for Measured Active Rotational-Vibrational Energy Levels, is used to determine the validated levels and lines and their self-consistent uncertainties based on the experimentally available information. The spectral ranges covered for the isotopologues H2D(+) and D2H(+) are 5.2-7105.5 and 23.0-6581.1 cm(-1), respectively. The MARVEL energy levels of the ortho and para forms of the ions are checked against ones determined from accurate variational nuclear motion computations employing the best available adiabatic ab initio potential energy surfaces of these isotopologues. The number of critically evaluated, validated and recommended experimental (levels, lines) are (109, 185) and (104, 136) for H2D(+) and D2H(+), respectively. The lists of assigned MARVEL lines and levels and variational levels obtained for H2D(+) and D2H(+) as part of this study are deposited in the ESI to this paper.

Molecular-level Simulations of Shock Generation and Propagation in Polyurea

DTIC Science & Technology

2011-01-26

homepage: www.e lsev ier .com/ locate /msea Molecular-level simulations of shock generation and propagation in polyurea M. Grujicica,∗, B. Pandurangana... Polyurea Shock-wave generation and propagation Molecular-level calculations a b s t r a c t A non-equilibrium molecular dynamics method is employed in order...to study various phenomena accompanying the generation and propagation of shock waves in polyurea (a micro-phase segregated elastomer). Several

Foveated Wide Field-of-View Imaging for Missile Warning/Tracking using Adaptive Optics

DTIC Science & Technology

2007-11-30

their melting temperatures are relatively high because of their long molecular conjugation. To lower the melting points, we have formulated eutectic ...compounds during recrystallization processes. 3. Polar, partially dissociated like organic acids, phenols or bases. Their dissociation level depends on the

Informatics and computational strategies for the study of lipids.

PubMed

Yetukuri, Laxman; Ekroos, Kim; Vidal-Puig, Antonio; Oresic, Matej

2008-02-01

Recent advances in mass spectrometry (MS)-based techniques for lipidomic analysis have empowered us with the tools that afford studies of lipidomes at the systems level. However, these techniques pose a number of challenges for lipidomic raw data processing, lipid informatics, and the interpretation of lipidomic data in the context of lipid function and structure. Integration of lipidomic data with other systemic levels, such as genomic or proteomic, in the context of molecular pathways and biophysical processes provides a basis for the understanding of lipid function at the systems level. The present report, based on the limited literature, is an update on a young but rapidly emerging field of lipid informatics and related pathway reconstruction strategies.

BODIPY-Based Donor-Acceptor Pi-Conjugated Alternating Copolymers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Popere, Bhooshan C.; Della Pelle, Andrea M.; Thayumanavan, S.

2011-06-28

Four novel π-conjugated copolymers incorporating 4,4-difluoro-4-borata-3a-azonia-4a-aza-s-indacene (BODIPY) core as the “donor” and quinoxaline (Qx), 2,1,3-benzothiadiazole (BzT), N,N'-di(2'-ethyl)hexyl-3,4,7,8-naphthalenetetracarboxylic diimide (NDI), and N,N'-di(2'-ethyl)hexyl-3,4,9,10-perylene tetracarboxylic diimide (PDI) as acceptors were designed and synthesized via Sonogashira polymerization. The polymers were characterized by ¹H NMR spectroscopy, gel permeation chromatography (GPC), UV–vis absorption spectroscopy, and cyclic voltammetry. Density functional theory (DFT) calculations were performed on polymer repeat units, and the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energy levels were estimated from the optimized geometry using B3LYP functional and 6-311g(d,p) basis set. Copolymers with Qx and BzT possessed HOMO and LUMOmore » energy levels comparable to those of BODIPY homopolymer, while PDI stabilized both HOMO and LUMO levels. Semiconductor behavior of these polymers was estimated in organic thin-film transistors (OTFT). While the homopolymer, Qx, and BzT-based copolymers showed only p-type semiconductor behavior, copolymers with PDI and NDI showed only n-type behavior.« less

Effect of Material Ion Exchanges on the Mechanical Stiffness Properties and Shear Deformation of Hydrated Cement Material Chemistry Structure C-S-H Jennite -- A Computational Modeling Study

NASA Astrophysics Data System (ADS)

Adebiyi, Babatunde Mattew

Material properties and performance are governed by material molecular chemistry structures and molecular level interactions. Methods to understand relationships between the material properties and performance and their correlation to the molecular level chemistry and morphology, and thus find ways of manipulating and adjusting matters at the atomistic level in order to improve material performance, are required. A computational material modeling methodology is investigated and demonstrated for a key cement hydrated component material chemistry structure of Calcium-Silicate-Hydrate (C-S-H) Jennite in this work. The effect of material ion exchanges on the mechanical stiffness properties and shear deformation behavior of hydrated cement material chemistry structure of Calcium Silicate Hydrate (C-S-H) Jennite was studied. Calcium ions were replaced with Magnesium ions in Jennite structure of the C-S-H gel. Different level of substitution of the ions was used. The traditional Jennite structure was obtained from the American Mineralogist Crystal Structure Database and super cells of the structures were created using a Molecular Dynamics Analyzer and Visualizer Material Studio. Molecular dynamics parameters used in the modeling analysis were determined by carrying out initial dynamic studies. 64 unit cell of C-S-H Jennite was used in material modeling analysis studies based on convergence results obtained from the elastic modulus and total energies. NVT forcite dynamics using COMPASS force field based on 200 ps dynamics time was used to determine mechanical modulus of the traditional C-S-H gel and the Magnesium ion modified structures. NVT Discover dynamics using COMPASS forcefield was used in the material modeling studies to investigate the influence of ionic exchange on the shear deformation of the associated material chemistry structures. A prior established quasi-static deformation method to emulate shear deformation of C-S-H material chemistry structure that is based on a triclinic crystal structure was used, by deforming the triclinic crystal structure at 0.2 degree per time step for 75 steps of deformation. It was observed that there is a decrease in the total energies of the systems as the percentage of magnesium ion increases in the C-S-H Jennite molecular structure systems. Investigation of effect of ion exchange on the elastic modulus shows that the elastic stiffness modulus tends to decrease as the amount of Mg in the systems increases, using either COMPASS or universal force field. On the other hand, shear moduli obtained after deforming the structures computed from the stress-strain curve obtained from material modeling increases as the amount of Mg increases in the system. The present investigations also showed that ultimate shear stress obtained from predicted shear stress---strain also increases with amount of Mg in the chemistry structure. Present study clearly demonstrates that computational material modeling following molecular dynamics analysis methodology is an effective way to predict and understand the effective material chemistry and additive changes on the stiffness and deformation characteristics in cementitious materials, and the results suggest that this method can be extended to other materials.

Breast Cancer Treatment in the Era of Molecular Imaging

PubMed Central

Edelhauser, Gundula; Funovics, Martin

2008-01-01

Summary Molecular imaging employs molecularly targeted probes to visualize and often quantify distinct disease-specific markers and pathways. Modalities like intravital confocal or multiphoton microscopy, near-infrared fluorescence combined with endoscopy, surface reflectance imaging, or fluorescence-mediated tomography, and radionuclide imaging with positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are increasingly used for small animal high-throughput screening, drug development and testing, and monitoring gene therapy experiments. In the clinical treatment of breast cancer, PET and SPECT as well as magnetic resonance-based molecular imaging are already established for the staging of distant disease and intrathoracic nodal status, for patient selection regarding receptor-directed treatments, and to gain early information about treatment efficacy. In the near future, reporter gene imaging during gene therapy and further spatial and qualitative characterization of the disease can become clinically possible with radionuclide and optical methods. Ultimately, it may be expected that every level of breast cancer treatment will be affected by molecular imaging, including screening. PMID:21048912

"Plug and play" logic gates based on fluorescence switching regulated by self-assembly of nucleotide and lanthanide ions.

PubMed

Pu, Fang; Ren, Jinsong; Qu, Xiaogang

2014-06-25

Molecular logic gates in response to chemical, biological, or optical input signals at a molecular level have received much interest over the past decade. Herein, we construct "plug and play" logic systems based on the fluorescence switching of guest molecules confined in coordination polymer nanoparticles generated from nucleotide and lanthanide ions. In the system, the addition of new modules directly enables new logic functions. PASS 0, YES, PASS 1, NOT, IMP, OR, and AND gates are successfully constructed in sequence. Moreover, different logic gates (AND, INH, and IMP) can be constructed using different guest molecules and the same input combinations. The work will be beneficial to the future logic design and expand the applications of coordination polymers.

Epidemiology and Molecular Biology of Head and Neck Cancer.

PubMed

Jou, Adriana; Hess, Jochen

2017-01-01

Head and neck cancer is a common and aggressive malignancy with a high morbidity and mortality profile. Although the large majority of cases resemble head and neck squamous cell carcinoma (HNSCC), the current classification based on anatomic site and tumor stage fails to capture the high level of biologic heterogeneity, and appropriate clinical management remains a major challenge. Hence, a better understanding of the molecular biology of HNSCC is urgently needed to support biomarker development and personalized care for patients. This review focuses on recent findings based on integrative genomics analysis and multi-scale modeling approaches and how they are beginning to provide more sophisticated clues as to the biological and clinical diversity of HNSCC. © 2017 S. Karger GmbH, Freiburg.

CUREs in biochemistry-where we are and where we should go.

PubMed

Bell, Jessica K; Eckdahl, Todd T; Hecht, David A; Killion, Patrick J; Latzer, Joachim; Mans, Tamara L; Provost, Joseph J; Rakus, John F; Siebrasse, Erica A; Ellis Bell, J

2017-01-02

Integration of research experience into classroom is an important and vital experience for all undergraduates. These course-based undergraduate research experiences (CUREs) have grown from independent instructor lead projects to large consortium driven experiences. The impact and importance of CUREs on students at all levels in biochemistry was the focus of a National Science Foundation funded think tank. The state of biochemistry CUREs and suggestions for moving biochemistry forward as well as a practical guide (supplementary material) are reported here. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):7-12, 2017. © 2016 The Authors Biochemistry and Molecular Biology Education published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology.

Molecular phylogenetics of mastodon and Tyrannosaurus rex.

PubMed

Organ, Chris L; Schweitzer, Mary H; Zheng, Wenxia; Freimark, Lisa M; Cantley, Lewis C; Asara, John M

2008-04-25

We report a molecular phylogeny for a nonavian dinosaur, extending our knowledge of trait evolution within nonavian dinosaurs into the macromolecular level of biological organization. Fragments of collagen alpha1(I) and alpha2(I) proteins extracted from fossil bones of Tyrannosaurus rex and Mammut americanum (mastodon) were analyzed with a variety of phylogenetic methods. Despite missing sequence data, the mastodon groups with elephant and the T. rex groups with birds, consistent with predictions based on genetic and morphological data for mastodon and on morphological data for T. rex. Our findings suggest that molecular data from long-extinct organisms may have the potential for resolving relationships at critical areas in the vertebrate evolutionary tree that have, so far, been phylogenetically intractable.

Molecular insights into the novel aspects of diatom biology.

PubMed

Scala, S; Bowler, C

2001-10-01

Diatoms are unicellular photosynthetic eukaryotes that are thought to contribute as much as 25% of global primary productivity. In spite of their ecological importance in the worlds oceans, very little information is available at the molecular level about the novel aspects of their biology. Recent advances, such as the development of gene transfer protocols, are now allowing the genetic dissection of diatom biology. Notable examples are advances in understanding the genetic basis for the silica-based bioinorganic pattern formation of their cell walls and for elucidating key aspects of diatom ecophysiology. The potentiation of current research will allow an evaluation of the use of diatoms to construct submicrometre-scale silicon structures for the nanotechnology industry and will reveal the molecular secrets underlying their ecological success.

Probing Silica-Biomolecule Interactions by Solid-State NMR and Molecular Dynamics Simulations.

PubMed

Brückner, Stephan Ingmar; Donets, Sergii; Dianat, Arezoo; Bobeth, Manfred; Gutiérrez, Rafael; Cuniberti, Gianaurelio; Brunner, Eike

2016-11-08

Understanding the molecular interactions between inorganic phases such as silica and organic material is fundamental for chromatographic applications, for tailoring silica-enzyme interactions, and for elucidating the mechanisms of biomineralization. The formation, structure, and properties of the organic/inorganic interface is crucial in this context. Here, we investigate the interaction of selectively 13 C-labeled choline with 29 Si-labeled monosilicic acid/silica at the molecular level. Silica/choline nanocomposites were analyzed by solid-state NMR spectroscopy in combination with extended molecular dynamics (MD) simulations to understand the silica/organic interface. Cross-polarization magic angle spinning (CP MAS)-based NMR experiments like 1 H- 13 C CP-REDOR (rotational-echo double resonance), 1 H- 13 C HETCOR (heteronuclear correlation), and 1 H- 29 Si- 1 H double CP are employed to determine spatial parameters. The measurement of 29 Si- 13 C internuclear distances for selectively 13 C-labeled choline provides an experimental parameter that allows the direct verification of MD simulations. Atomistic modeling using classical MD methodologies is performed using the INTERFACE force field. The modeling results are in excellent agreement with the experimental data and reveal the relevant molecular conformations as well as the nature and interplay of the interactions between the choline cation and the silica surface. Electrostatic interactions and hydrogen bonding are both important and depend strongly on the hydration level as well as the charge state of the silica surface.

Charge-leveling and proper treatment of long-range electrostatics in all-atom molecular dynamics at constant pH.

PubMed

Wallace, Jason A; Shen, Jana K

2012-11-14

Recent development of constant pH molecular dynamics (CpHMD) methods has offered promise for adding pH-stat in molecular dynamics simulations. However, until now the working pH molecular dynamics (pHMD) implementations are dependent in part or whole on implicit-solvent models. Here we show that proper treatment of long-range electrostatics and maintaining charge neutrality of the system are critical for extending the continuous pHMD framework to the all-atom representation. The former is achieved here by adding forces to titration coordinates due to long-range electrostatics based on the generalized reaction field method, while the latter is made possible by a charge-leveling technique that couples proton titration with simultaneous ionization or neutralization of a co-ion in solution. We test the new method using the pH-replica-exchange CpHMD simulations of a series of aliphatic dicarboxylic acids with varying carbon chain length. The average absolute deviation from the experimental pK(a) values is merely 0.18 units. The results show that accounting for the forces due to extended electrostatics removes the large random noise in propagating titration coordinates, while maintaining charge neutrality of the system improves the accuracy in the calculated electrostatic interaction between ionizable sites. Thus, we believe that the way is paved for realizing pH-controlled all-atom molecular dynamics in the near future.

Charge-leveling and proper treatment of long-range electrostatics in all-atom molecular dynamics at constant pH

PubMed Central

Wallace, Jason A.; Shen, Jana K.

2012-01-01

Recent development of constant pH molecular dynamics (CpHMD) methods has offered promise for adding pH-stat in molecular dynamics simulations. However, until now the working pH molecular dynamics (pHMD) implementations are dependent in part or whole on implicit-solvent models. Here we show that proper treatment of long-range electrostatics and maintaining charge neutrality of the system are critical for extending the continuous pHMD framework to the all-atom representation. The former is achieved here by adding forces to titration coordinates due to long-range electrostatics based on the generalized reaction field method, while the latter is made possible by a charge-leveling technique that couples proton titration with simultaneous ionization or neutralization of a co-ion in solution. We test the new method using the pH-replica-exchange CpHMD simulations of a series of aliphatic dicarboxylic acids with varying carbon chain length. The average absolute deviation from the experimental pKa values is merely 0.18 units. The results show that accounting for the forces due to extended electrostatics removes the large random noise in propagating titration coordinates, while maintaining charge neutrality of the system improves the accuracy in the calculated electrostatic interaction between ionizable sites. Thus, we believe that the way is paved for realizing pH-controlled all-atom molecular dynamics in the near future. PMID:23163362

Molecular Insights into the Potential Toxicological Interaction of 2-Mercaptothiazoline with the Antioxidant Enzyme—Catalase

PubMed Central

Huang, Zhenxing; Huang, Ming; Mi, Chenyu; Wang, Tao; Chen, Dong; Teng, Yue

2016-01-01

2-mercaptothiazoline (2-MT) is widely used in many industrial fields, but its residue is potentially harmful to the environment. In this study, to evaluate the biological toxicity of 2-MT at protein level, the interaction between 2-MT and the pivotal antioxidant enzyme—catalase (CAT) was investigated using multiple spectroscopic techniques and molecular modeling. The results indicated that the CAT fluorescence quenching caused by 2-MT should be dominated by a static quenching mechanism through formation of a 2-MT/CAT complex. Furthermore, the identifications of the binding constant, binding forces, and the number of binding sites demonstrated that 2-MT could spontaneously interact with CAT at one binding site mainly via Van der Waals’ forces and hydrogen bonding. Based on the molecular docking simulation and conformation dynamic characterization, it was found that 2-MT could bind into the junctional region of CAT subdomains and that the binding site was close to enzyme active sites, which induced secondary structural and micro-environmental changes in CAT. The experiments on 2-MT toxicity verified that 2-MT significantly inhibited CAT activity via its molecular interaction, where 2-MT concentration and exposure time both affected the inhibitory action. Therefore, the present investigation provides useful information for understanding the toxicological mechanism of 2-MT at the molecular level. PMID:27537873

Force-field parameters from the SAFT-γ equation of state for use in coarse-grained molecular simulations.

PubMed

Müller, Erich A; Jackson, George

2014-01-01

A description of fluid systems with molecular-based algebraic equations of state (EoSs) and by direct molecular simulation is common practice in chemical engineering and the physical sciences, but the two approaches are rarely closely coupled. The key for an integrated representation is through a well-defined force field and Hamiltonian at the molecular level. In developing coarse-grained intermolecular potential functions for the fluid state, one typically starts with a detailed, bottom-up quantum-mechanical or atomic-level description and then integrates out the unwanted degrees of freedom using a variety of techniques; an iterative heuristic simulation procedure is then used to refine the parameters of the model. By contrast, with a top-down technique, one can use an accurate EoS to link the macroscopic properties of the fluid and the force-field parameters. We discuss the latest developments in a top-down representation of fluids, with a particular focus on a group-contribution formulation of the statistical associating fluid theory (SAFT-γ). The accurate SAFT-γ EoS is used to estimate the parameters of the Mie force field, which can then be used with confidence in direct molecular simulations to obtain thermodynamic, structural, interfacial, and dynamical properties that are otherwise inaccessible from the EoS. This is exemplified for several prototypical fluids and mixtures, including carbon dioxide, hydrocarbons, perfluorohydrocarbons, and aqueous surfactants.

Doping of free-standing zinc-blende GaN layers grown by molecular beam epitaxy

NASA Astrophysics Data System (ADS)

Novikov, S. V.; Powell, R. E. L.; Staddon, C. R.; Kent, A. J.; Foxon, C. T.

2014-10-01

Currently there is high level of interest in developing of vertical device structures based on the group III nitrides. We have studied n- and p-doping of free-standing zinc-blende GaN grown by plasma-assisted molecular beam epitaxy (PA-MBE). Si was used as the n-dopant and Mg as the p-dopant for zinc-blende GaN. Controllable levels of doping with Si and Mg in free-standing zinc-blende GaN have been achieved by PA-MBE. The Si and Mg doping depth uniformity through the zinc-blende GaN layers have been confirmed by secondary ion mass spectrometry (SIMS). Controllable Si and Mg doping makes PA-MBE a promising method for the growth of conducting group III-nitrides bulk crystals.

Challenges in breeding for yield increase for drought.

PubMed

Sinclair, Thomas R

2011-06-01

Crop genetic improvement for environmental stress at the molecular and physiological level is very complex and challenging. Unlike the example of the current major commercial transgenic crops for which biotic stress tolerance is based on chemicals alien to plants, the complex, redundant and homeostatic molecular and physiological systems existing in plants must be altered for drought tolerance improvement. Sophisticated tools must be developed to monitor phenotype expression at the crop level to characterize variation among genotypes across a range of environments. Once stress-tolerant cultivars are developed, regional probability distributions describing yield response across years will be necessary. This information can then aid in identifying environmental conditions for positive and negative responses to genetic modification to guide farmer selection of stress-tolerant cultivars. Copyright © 2011 Elsevier Ltd. All rights reserved.

Exploring the molecular basis of insecticide resistance in the dengue vector Aedes aegypti: a case study in Martinique Island (French West Indies).

PubMed

Marcombe, Sébastien; Poupardin, Rodolphe; Darriet, Frederic; Reynaud, Stéphane; Bonnet, Julien; Strode, Clare; Brengues, Cecile; Yébakima, André; Ranson, Hilary; Corbel, Vincent; David, Jean-Philippe

2009-10-26

The yellow fever mosquito Aedes aegypti is a major vector of dengue and hemorrhagic fevers, causing up to 100 million dengue infections every year. As there is still no medicine and efficient vaccine available, vector control largely based on insecticide treatments remains the only method to reduce dengue virus transmission. Unfortunately, vector control programs are facing operational challenges with mosquitoes becoming resistant to commonly used insecticides. Resistance of Ae. aegypti to chemical insecticides has been reported worldwide and the underlying molecular mechanisms, including the identification of enzymes involved in insecticide detoxification are not completely understood. The present paper investigates the molecular basis of insecticide resistance in a population of Ae. aegypti collected in Martinique (French West Indies). Bioassays with insecticides on adults and larvae revealed high levels of resistance to organophosphate and pyrethroid insecticides. Molecular screening for common insecticide target-site mutations showed a high frequency (71%) of the sodium channel 'knock down resistance' (kdr) mutation. Exposing mosquitoes to detoxification enzymes inhibitors prior to bioassays induced a significant increased susceptibility of mosquitoes to insecticides, revealing the presence of metabolic-based resistance mechanisms. This trend was biochemically confirmed by significant elevated activities of cytochrome P450 monooxygenases, glutathione S-transferases and carboxylesterases at both larval and adult stages. Utilization of the microarray Aedes Detox Chip containing probes for all members of detoxification and other insecticide resistance-related enzymes revealed the significant constitutive over-transcription of multiple detoxification genes at both larval and adult stages. The over-transcription of detoxification genes in the resistant strain was confirmed by using real-time quantitative RT-PCR. These results suggest that the high level of insecticide resistance found in Ae. aegypti mosquitoes from Martinique island is the consequence of both target-site and metabolic based resistance mechanisms. Insecticide resistance levels and associated mechanisms are discussed in relation with the environmental context of Martinique Island. These finding have important implications for dengue vector control in Martinique and emphasizes the need to develop new tools and strategies for maintaining an effective control of Aedes mosquito populations worldwide.

Exploring the molecular basis of insecticide resistance in the dengue vector Aedes aegypti: a case study in Martinique Island (French West Indies)

PubMed Central

Marcombe, Sébastien; Poupardin, Rodolphe; Darriet, Frederic; Reynaud, Stéphane; Bonnet, Julien; Strode, Clare; Brengues, Cecile; Yébakima, André; Ranson, Hilary; Corbel, Vincent; David, Jean-Philippe

2009-01-01

Background The yellow fever mosquito Aedes aegypti is a major vector of dengue and hemorrhagic fevers, causing up to 100 million dengue infections every year. As there is still no medicine and efficient vaccine available, vector control largely based on insecticide treatments remains the only method to reduce dengue virus transmission. Unfortunately, vector control programs are facing operational challenges with mosquitoes becoming resistant to commonly used insecticides. Resistance of Ae. aegypti to chemical insecticides has been reported worldwide and the underlying molecular mechanisms, including the identification of enzymes involved in insecticide detoxification are not completely understood. Results The present paper investigates the molecular basis of insecticide resistance in a population of Ae. aegypti collected in Martinique (French West Indies). Bioassays with insecticides on adults and larvae revealed high levels of resistance to organophosphate and pyrethroid insecticides. Molecular screening for common insecticide target-site mutations showed a high frequency (71%) of the sodium channel 'knock down resistance' (kdr) mutation. Exposing mosquitoes to detoxification enzymes inhibitors prior to bioassays induced a significant increased susceptibility of mosquitoes to insecticides, revealing the presence of metabolic-based resistance mechanisms. This trend was biochemically confirmed by significant elevated activities of cytochrome P450 monooxygenases, glutathione S-transferases and carboxylesterases at both larval and adult stages. Utilization of the microarray Aedes Detox Chip containing probes for all members of detoxification and other insecticide resistance-related enzymes revealed the significant constitutive over-transcription of multiple detoxification genes at both larval and adult stages. The over-transcription of detoxification genes in the resistant strain was confirmed by using real-time quantitative RT-PCR. Conclusion These results suggest that the high level of insecticide resistance found in Ae. aegypti mosquitoes from Martinique island is the consequence of both target-site and metabolic based resistance mechanisms. Insecticide resistance levels and associated mechanisms are discussed in relation with the environmental context of Martinique Island. These finding have important implications for dengue vector control in Martinique and emphasizes the need to develop new tools and strategies for maintaining an effective control of Aedes mosquito populations worldwide. PMID:19857255

Effects of Context on Students' Molecular-Level Ideas

ERIC Educational Resources Information Center

Teichert, Melonie A.; Tien, Lydia T.; Anthony, Seth; Rickey, Dawn

2008-01-01

In the studies reported here, we investigate the effects of context on students' molecular-level ideas regarding aqueous solutions. During one-on-one interviews, 19 general chemistry students recruited from a two-year community college and a research university in the United States were asked to describe their molecular-level ideas about various…

Continuously Adjustable, Molecular-Sieving “Gate” on 5A Zeolite for Distinguishing Small Organic Molecules by Size

PubMed Central

Song, Zhuonan; Huang, Yi; Xu, Weiwei L.; Wang, Lei; Bao, Yu; Li, Shiguang; Yu, Miao

2015-01-01

Zeolites/molecular sieves with uniform, molecular-sized pores are important for many adsorption-based separation processes. Pore size gaps, however, exist in the current zeolite family. This leads to a great challenge of separating molecules with size differences at ~0.01 nm level. Here, we report a novel concept, pore misalignment, to form a continuously adjustable, molecular-sieving “gate” at the 5A zeolite pore entrance without sacrificing the internal capacity. Misalignment of the micropores of the alumina coating with the 5A zeolite pores was related with and facilely adjusted by the coating thickness. For the first time, organic molecules with sub-0.01 nm size differences were effectively distinguished via appropriate misalignment. This novel concept may have great potential to fill the pore size gaps of the zeolite family and realize size-selective adsorption separation. PMID:26358480

Geminiviruses and Plant Hosts: A Closer Examination of the Molecular Arms Race.

PubMed

Ramesh, Shunmugiah V; Sahu, Pranav P; Prasad, Manoj; Praveen, Shelly; Pappu, Hanu R

2017-09-15

Geminiviruses are plant-infecting viruses characterized by a single-stranded DNA (ssDNA) genome. Geminivirus-derived proteins are multifunctional and effective regulators in modulating the host cellular processes resulting in successful infection. Virus-host interactions result in changes in host gene expression patterns, reprogram plant signaling controls, disrupt central cellular metabolic pathways, impair plant's defense system, and effectively evade RNA silencing response leading to host susceptibility. This review summarizes what is known about the cellular processes in the continuing tug of war between geminiviruses and their plant hosts at the molecular level. In addition, implications for engineered resistance to geminivirus infection in the context of a greater understanding of the molecular processes are also discussed. Finally, the prospect of employing geminivirus-based vectors in plant genome engineering and the emergence of powerful genome editing tools to confer geminivirus resistance are highlighted to complete the perspective on geminivirus-plant molecular interactions.

Insight into the Mechanism of Hydrolysis of Meropenem by OXA-23 Serine-β-lactamase Gained by Quantum Mechanics/Molecular Mechanics Calculations.

PubMed

Sgrignani, Jacopo; Grazioso, Giovanni; De Amici, Marco

2016-09-13

The fast and constant development of drug resistant bacteria represents a serious medical emergency. To overcome this problem, the development of drugs with new structures and modes of action is urgently needed. In this work, we investigated, at the atomistic level, the mechanisms of hydrolysis of Meropenem by OXA-23, a class D β-lactamase, combining unbiased classical molecular dynamics and umbrella sampling simulations with classical force field-based and quantum mechanics/molecular mechanics potentials. Our calculations provide a detailed structural and dynamic picture of the molecular steps leading to the formation of the Meropenem-OXA-23 covalent adduct, the subsequent hydrolysis, and the final release of the inactive antibiotic. In this mechanistic framework, the predicted activation energy is in good agreement with experimental kinetic measurements, validating the expected reaction path.

Faunus: An object oriented framework for molecular simulation

PubMed Central

Lund, Mikael; Trulsson, Martin; Persson, Björn

2008-01-01

Background We present a C++ class library for Monte Carlo simulation of molecular systems, including proteins in solution. The design is generic and highly modular, enabling multiple developers to easily implement additional features. The statistical mechanical methods are documented by extensive use of code comments that – subsequently – are collected to automatically build a web-based manual. Results We show how an object oriented design can be used to create an intuitively appealing coding framework for molecular simulation. This is exemplified in a minimalistic C++ program that can calculate protein protonation states. We further discuss performance issues related to high level coding abstraction. Conclusion C++ and the Standard Template Library (STL) provide a high-performance platform for generic molecular modeling. Automatic generation of code documentation from inline comments has proven particularly useful in that no separate manual needs to be maintained. PMID:18241331

Continuously adjustable, molecular-sieving “gate” on 5A zeolite for distinguishing small organic molecules by size

DOE PAGES

Song, Zhuonan; Huang, Yi; Xu, Weiwei L.; ...

2015-09-11

Zeolites/molecular sieves with uniform, molecular-sized pores are important for many adsorption-based separation processes. Pore size gaps, however, exist in the current zeolite family. This leads to a great challenge of separating molecules with size differences at ~0.01 nm level. Here, we report a novel concept, pore misalignment, to form a continuously adjustable, molecular-sieving “gate” at the 5A zeolite pore entrance without sacrificing the internal capacity. Misalignment of the micropores of the alumina coating with the 5A zeolite pores was related with and facilely adjusted by the coating thickness. For the first time, organic molecules with sub-0.01 nm size differences weremore » effectively distinguished via appropriate misalignment. Lastly, this novel concept may have great potential to fill the pore size gaps of the zeolite family and realize size-selective adsorption separation.« less

Geminiviruses and Plant Hosts: A Closer Examination of the Molecular Arms Race

PubMed Central

Ramesh, Shunmugiah V.; Sahu, Pranav P.; Prasad, Manoj; Praveen, Shelly; Pappu, Hanu R.

2017-01-01

Geminiviruses are plant-infecting viruses characterized by a single-stranded DNA (ssDNA) genome. Geminivirus-derived proteins are multifunctional and effective regulators in modulating the host cellular processes resulting in successful infection. Virus-host interactions result in changes in host gene expression patterns, reprogram plant signaling controls, disrupt central cellular metabolic pathways, impair plant’s defense system, and effectively evade RNA silencing response leading to host susceptibility. This review summarizes what is known about the cellular processes in the continuing tug of war between geminiviruses and their plant hosts at the molecular level. In addition, implications for engineered resistance to geminivirus infection in the context of a greater understanding of the molecular processes are also discussed. Finally, the prospect of employing geminivirus-based vectors in plant genome engineering and the emergence of powerful genome editing tools to confer geminivirus resistance are highlighted to complete the perspective on geminivirus-plant molecular interactions. PMID:28914771

Proteomic Adaptations to Starvation Prepare Escherichia coli for Disinfection Tolerance

PubMed Central

Du, Zhe; Nandakumar, Renu; Nickerson, Kenneth; Li, Xu

2015-01-01

Despite the low nutrient level and constant presence of secondary disinfectants, bacterial re-growth still occurs in drinking water distribution systems. The molecular mechanisms that starved bacteria use to survive low-level chlorine-based disinfectants are not well understood. The objective of this study is to investigate these molecular mechanisms at the protein level that prepare starved cells for disinfection tolerance. Two commonly used secondary disinfectants chlorine and monochloramine, both at 1 mg/L, were used in this study. The proteomes of normal and starved Escherichia coli (K12 MG1655) cells were studied using quantitative proteomics. Over 60-min disinfection, starved cells showed significantly higher disinfection tolerance than normal cells based on the inactivation curves for both chlorine and monochloramine. Proteomic analyses suggest that starvation may prepare cells for the oxidative stress that chlorine-based disinfection will cause by affecting glutathione metabolism. In addition, proteins involved in stress regulation and stress responses were among the ones up-regulated under both starvation and chlorine/monochloramine disinfection. By comparing the fold changes under different conditions, it is suggested that starvation prepares E. coli for disinfection tolerance by increasing the expression of enzymes that can help cells survive chlorine/monochloramine disinfection. Protein co-expression analyses show that proteins in glycolysis and pentose phosphate pathway that were up-regulated under starvation are also involved in disinfection tolerance. Finally, the production and detoxification of methylglyoxal may be involved in the chlorine-based disinfection and cell defense mechanisms. PMID:25463932

Proteomic adaptations to starvation prepare Escherichia coli for disinfection tolerance.

PubMed

Du, Zhe; Nandakumar, Renu; Nickerson, Kenneth W; Li, Xu

2015-02-01

Despite the low nutrient level and constant presence of secondary disinfectants, bacterial re-growth still occurs in drinking water distribution systems. The molecular mechanisms that starved bacteria use to survive low-level chlorine-based disinfectants are not well understood. The objective of this study is to investigate these molecular mechanisms at the protein level that prepare starved cells for disinfection tolerance. Two commonly used secondary disinfectants chlorine and monochloramine, both at 1 mg/L, were used in this study. The proteomes of normal and starved Escherichia coli (K12 MG1655) cells were studied using quantitative proteomics. Over 60-min disinfection, starved cells showed significantly higher disinfection tolerance than normal cells based on the inactivation curves for both chlorine and monochloramine. Proteomic analyses suggest that starvation may prepare cells for the oxidative stress that chlorine-based disinfection will cause by affecting glutathione metabolism. In addition, proteins involved in stress regulation and stress responses were among the ones up-regulated under both starvation and chlorine/monochloramine disinfection. By comparing the fold changes under different conditions, it is suggested that starvation prepares E. coli for disinfection tolerance by increasing the expression of enzymes that can help cells survive chlorine/monochloramine disinfection. Protein co-expression analyses show that proteins in glycolysis and pentose phosphate pathway that were up-regulated under starvation are also involved in disinfection tolerance. Finally, the production and detoxification of methylglyoxal may be involved in the chlorine-based disinfection and cell defense mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

Programmable chemical controllers made from DNA.

PubMed

Chen, Yuan-Jyue; Dalchau, Neil; Srinivas, Niranjan; Phillips, Andrew; Cardelli, Luca; Soloveichik, David; Seelig, Georg

2013-10-01

Biological organisms use complex molecular networks to navigate their environment and regulate their internal state. The development of synthetic systems with similar capabilities could lead to applications such as smart therapeutics or fabrication methods based on self-organization. To achieve this, molecular control circuits need to be engineered to perform integrated sensing, computation and actuation. Here we report a DNA-based technology for implementing the computational core of such controllers. We use the formalism of chemical reaction networks as a 'programming language' and our DNA architecture can, in principle, implement any behaviour that can be mathematically expressed as such. Unlike logic circuits, our formulation naturally allows complex signal processing of intrinsically analogue biological and chemical inputs. Controller components can be derived from biologically synthesized (plasmid) DNA, which reduces errors associated with chemically synthesized DNA. We implement several building-block reaction types and then combine them into a network that realizes, at the molecular level, an algorithm used in distributed control systems for achieving consensus between multiple agents.

Programmable chemical controllers made from DNA

NASA Astrophysics Data System (ADS)

Chen, Yuan-Jyue; Dalchau, Neil; Srinivas, Niranjan; Phillips, Andrew; Cardelli, Luca; Soloveichik, David; Seelig, Georg

2013-10-01

Biological organisms use complex molecular networks to navigate their environment and regulate their internal state. The development of synthetic systems with similar capabilities could lead to applications such as smart therapeutics or fabrication methods based on self-organization. To achieve this, molecular control circuits need to be engineered to perform integrated sensing, computation and actuation. Here we report a DNA-based technology for implementing the computational core of such controllers. We use the formalism of chemical reaction networks as a 'programming language' and our DNA architecture can, in principle, implement any behaviour that can be mathematically expressed as such. Unlike logic circuits, our formulation naturally allows complex signal processing of intrinsically analogue biological and chemical inputs. Controller components can be derived from biologically synthesized (plasmid) DNA, which reduces errors associated with chemically synthesized DNA. We implement several building-block reaction types and then combine them into a network that realizes, at the molecular level, an algorithm used in distributed control systems for achieving consensus between multiple agents.

BODIPY-Based Fluorescent Probes for Sensing Protein Surface-Hydrophobicity.

PubMed

Dorh, Nethaniah; Zhu, Shilei; Dhungana, Kamal B; Pati, Ranjit; Luo, Fen-Tair; Liu, Haiying; Tiwari, Ashutosh

2015-12-18

Mapping surface hydrophobic interactions in proteins is key to understanding molecular recognition, biological functions, and is central to many protein misfolding diseases. Herein, we report synthesis and application of new BODIPY-based hydrophobic sensors (HPsensors) that are stable and highly fluorescent for pH values ranging from 7.0 to 9.0. Surface hydrophobic measurements of proteins (BSA, apomyoglobin, and myoglobin) by these HPsensors display much stronger signal compared to 8-anilino-1-naphthalene sulfonic acid (ANS), a commonly used hydrophobic probe; HPsensors show a 10- to 60-fold increase in signal strength for the BSA protein with affinity in the nanomolar range. This suggests that these HPsensors can be used as a sensitive indicator of protein surface hydrophobicity. A first principle approach is used to identify the molecular level mechanism for the substantial increase in the fluorescence signal strength. Our results show that conformational change and increased molecular rigidity of the dye due to its hydrophobic interaction with protein lead to fluorescence enhancement.

Fabrication of field-effect transistor utilizing oriented thin film of octahexyl-substituted phthalocyanine and its electrical anisotropy based on columnar structure

NASA Astrophysics Data System (ADS)

Ohmori, Masashi; Nakatani, Mitsuhiro; Kajii, Hirotake; Miyamoto, Ayano; Yoneya, Makoto; Fujii, Akihiko; Ozaki, Masanori

2018-03-01

Field-effect transistors with molecularly oriented thin films of metal-free non-peripherally octahexyl-substituted phthalocyanine (C6PcH2), which characteristically form a columnar structure, have been fabricated, and the electrical anisotropy of C6PcH2 has been investigated. The molecularly oriented thin films of C6PcH2 were prepared by the bar-coating technique, and the uniform orientation in a large area and the surface roughness at a molecular level were observed by polarized spectroscopy and atomic force microscopy, respectively. The field effect mobilities parallel and perpendicular to the column axis of C6PcH2 were estimated to be (1.54 ± 0.24) × 10-2 and (2.10 ± 0.23) × 10-3 cm2 V-1 s-1, respectively. The electrical anisotropy based on the columnar structure has been discussed by taking the simulated results obtained by density functional theory calculation into consideration.

Integrated Solvent Design for CO 2 Capture and Viscosity Tuning

DOE PAGES

Cantu, David C.; Malhotra, Deepika; Koech, Phillip K.; ...

2017-08-18

We present novel design strategies for reduced viscosity single-component, water-lean CO 2 capture organic solvent systems. Through molecular simulation, we identify the main molecular-level descriptor that influences bulk solvent viscosity. Upon loading, a zwitterionic structure forms with a small activation energy of ca 16 kJ/mol and a small stabilization of ca 6 kJ/mol. Viscosity increases exponentially with CO 2 loading due to hydrogen-bonding between neighboring Zwitterions. We find that molecular structures that promote internal hydrogen bonding (within the same molecule) and suppress interactions with neighboring molecules have low viscosities. In addition, tuning the acid/base properties leads to a shift ofmore » the equilibrium toward a non-charged (acid) form that further reduces the viscosity. Here, based on the above structural criteria, a reduced order model is also presented that allows for the quick screening of large compound libraries and down selection of promising candidates for synthesis and testing.« less

System Analysis of LWDH Related Genes Based on Text Mining in Biological Networks

PubMed Central

Miao, Yingbo; Zhang, Liangcai; Wang, Yang; Feng, Rennan; Yang, Lei; Zhang, Shihua; Jiang, Yongshuai; Liu, Guiyou

2014-01-01

Liuwei-dihuang (LWDH) is widely used in traditional Chinese medicine (TCM), but its molecular mechanism about gene interactions is unclear. LWDH genes were extracted from the existing literatures based on text mining technology. To simulate the complex molecular interactions that occur in the whole body, protein-protein interaction networks (PPINs) were constructed and the topological properties of LWDH genes were analyzed. LWDH genes have higher centrality properties and may play important roles in the complex biological network environment. It was also found that the distances within LWDH genes are smaller than expected, which means that the communication of LWDH genes during the biological process is rapid and effectual. At last, a comprehensive network of LWDH genes, including the related drugs and regulatory pathways at both the transcriptional and posttranscriptional levels, was constructed and analyzed. The biological network analysis strategy used in this study may be helpful for the understanding of molecular mechanism of TCM. PMID:25243143

Smart Materials Based on DNA Aptamers: Taking Aptasensing to the Next Level

PubMed Central

Mastronardi, Emily; Foster, Amanda; Zhang, Xueru; DeRosa, Maria C.

2014-01-01

“Smart” materials are an emerging category of multifunctional materials with physical or chemical properties that can be controllably altered in response to an external stimulus. By combining the standard properties of the advanced material with the unique ability to recognize and adapt in response to a change in their environment, these materials are finding applications in areas such as sensing and drug delivery. While the majority of these materials are responsive to physical or chemical changes, a particularly exciting area of research seeks to develop smart materials that are sensitive to specific molecular or biomolecular stimuli. These systems require the integration of a molecular recognition probe specific to the target molecule of interest. The ease of synthesis and labeling, low cost, and stability of DNA aptamers make them uniquely suited to effectively serve as molecular recognition probes in novel smart material systems. This review will highlight current work in the area of aptamer-based smart materials and prospects for their future applications. PMID:24553083

Programmable chemical controllers made from DNA

PubMed Central

Chen, Yuan-Jyue; Dalchau, Neil; Srinivas, Niranjan; Phillips, Andrew; Cardelli, Luca; Soloveichik, David; Seelig, Georg

2014-01-01

Biological organisms use complex molecular networks to navigate their environment and regulate their internal state. The development of synthetic systems with similar capabilities could lead to applications such as smart therapeutics or fabrication methods based on self-organization. To achieve this, molecular control circuits need to be engineered to perform integrated sensing, computation and actuation. Here we report a DNA-based technology for implementing the computational core of such controllers. We use the formalism of chemical reaction networks as a 'programming language', and our DNA architecture can, in principle, implement any behaviour that can be mathematically expressed as such. Unlike logic circuits, our formulation naturally allows complex signal processing of intrinsically analogue biological and chemical inputs. Controller components can be derived from biologically synthesized (plasmid) DNA, which reduces errors associated with chemically synthesized DNA. We implement several building-block reaction types and then combine them into a network that realizes, at the molecular level, an algorithm used in distributed control systems for achieving consensus between multiple agents. PMID:24077029

A metabolomics-based approach identifies changes in the small molecular weight compound composition of the peanut as a result of dry-roasting.

PubMed

Klevorn, Claire M; Dean, Lisa L

2018-02-01

Raw peanuts in the USA are subjected to thermal processing, such as dry-roasting, prior to consumption. A multi-instrument metabolomics-based platform along with targeted analyses was used to determine changes in the low-molecular-weight compound composition of peanuts due to dry-roasting. Runner and virginia-type peanut seeds were characterized using several analytical platforms including (RP)/UPLC-MS/MS (positive and negative ion mode ESI) and HILIC/UPLC-MS/MS with negative ion mode ESI. Of the 383 compounds identified, 16 compounds were unique to the roasted peanuts. Using pathway analysis, compounds associated with arginine and proline metabolism were found to be the most changed. Products of chemical degradation and compounds contained within the vesicular bodies of the peanut increased after roasting. Dry-roasting had a significant impact on the levels and types of low-molecular-weight compounds present. These findings provide useful information about composition changes due to roasting. Published by Elsevier Ltd.

Nanostructure and molecular mechanics of spider dragline silk protein assemblies

PubMed Central

Keten, Sinan; Buehler, Markus J.

2010-01-01

Spider silk is a self-assembling biopolymer that outperforms most known materials in terms of its mechanical performance, despite its underlying weak chemical bonding based on H-bonds. While experimental studies have shown that the molecular structure of silk proteins has a direct influence on the stiffness, toughness and failure strength of silk, no molecular-level analysis of the nanostructure and associated mechanical properties of silk assemblies have been reported. Here, we report atomic-level structures of MaSp1 and MaSp2 proteins from the Nephila clavipes spider dragline silk sequence, obtained using replica exchange molecular dynamics, and subject these structures to mechanical loading for a detailed nanomechanical analysis. The structural analysis reveals that poly-alanine regions in silk predominantly form distinct and orderly beta-sheet crystal domains, while disorderly regions are formed by glycine-rich repeats that consist of 31-helix type structures and beta-turns. Our structural predictions are validated against experimental data based on dihedral angle pair calculations presented in Ramachandran plots, alpha-carbon atomic distances, as well as secondary structure content. Mechanical shearing simulations on selected structures illustrate that the nanoscale behaviour of silk protein assemblies is controlled by the distinctly different secondary structure content and hydrogen bonding in the crystalline and semi-amorphous regions. Both structural and mechanical characterization results show excellent agreement with available experimental evidence. Our findings set the stage for extensive atomistic investigations of silk, which may contribute towards an improved understanding of the source of the strength and toughness of this biological superfibre. PMID:20519206

Nanostructure and molecular mechanics of spider dragline silk protein assemblies.

PubMed

Keten, Sinan; Buehler, Markus J

2010-12-06

Spider silk is a self-assembling biopolymer that outperforms most known materials in terms of its mechanical performance, despite its underlying weak chemical bonding based on H-bonds. While experimental studies have shown that the molecular structure of silk proteins has a direct influence on the stiffness, toughness and failure strength of silk, no molecular-level analysis of the nanostructure and associated mechanical properties of silk assemblies have been reported. Here, we report atomic-level structures of MaSp1 and MaSp2 proteins from the Nephila clavipes spider dragline silk sequence, obtained using replica exchange molecular dynamics, and subject these structures to mechanical loading for a detailed nanomechanical analysis. The structural analysis reveals that poly-alanine regions in silk predominantly form distinct and orderly beta-sheet crystal domains, while disorderly regions are formed by glycine-rich repeats that consist of 3₁-helix type structures and beta-turns. Our structural predictions are validated against experimental data based on dihedral angle pair calculations presented in Ramachandran plots, alpha-carbon atomic distances, as well as secondary structure content. Mechanical shearing simulations on selected structures illustrate that the nanoscale behaviour of silk protein assemblies is controlled by the distinctly different secondary structure content and hydrogen bonding in the crystalline and semi-amorphous regions. Both structural and mechanical characterization results show excellent agreement with available experimental evidence. Our findings set the stage for extensive atomistic investigations of silk, which may contribute towards an improved understanding of the source of the strength and toughness of this biological superfibre.

π-Extended Isoindigo-Based Derivative: A Promising Electron-Deficient Building Block for Polymer Semiconductors.

PubMed

Xu, Long; Zhao, Zhiyuan; Xiao, Mingchao; Yang, Jie; Xiao, Jian; Yi, Zhengran; Wang, Shuai; Liu, Yunqi

2017-11-22

The exploration of novel electron-deficient building blocks is a key task for developing high-performance polymer semiconductors in organic thin-film transistors. In view of the situation of the lack of strong electron-deficient building blocks, we designed two novel π-extended isoindigo-based electron-deficient building blocks, IVI and F 4 IVI. Owing to the strong electron-deficient nature and the extended π-conjugated system of the two acceptor units, their copolymers, PIVI2T and PF 4 IVI2T, containing 2,2'-bithiophene donor units, are endowed with deep-lying highest occupied molecular orbital (HOMO)/lowest unoccupied molecular orbital (LUMO) energy levels and strong intermolecular interactions. In comparison to PIVI2T, the fluorinated PF 4 IVI2T exhibits stronger intra- and intermolecular interactions, lower HOMO/LUMO energy levels up to -5.74/-4.17 eV, and more ordered molecular packing with a smaller π-π stacking distance of up to 3.53 Å, resulting in an excellent ambipolar transporting behavior and a promising application in logic circuits for PF 4 IVI2T in ambient with hole and electron mobilities of up to 1.03 and 1.82 cm 2 V -1 s -1 , respectively. The results reveal that F 4 IVI is a promising and strong electron-deficient building unit to construct high-performance semiconducting polymers, which provides an insight into the structure-property relationships for the exploration and molecular engineering of excellent electron-deficient building blocks in the field of organic electronics.

Advanced solvent based methods for molecular characterization of soil organic matter by high-resolution mass spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tfaily, Malak M.; Chu, Rosalie K.; Tolic, Nikola

2015-05-19

Soil organic matter (SOM) a complex, heterogeneous mixture of above and belowground plant litter and animal and microbial residues at various degrees of decomposition, is a key reservoir for carbon (C) and nutrient biogeochemical cycling in soil based ecosystems. A limited understanding of the molecular composition of SOM limits the ability to routinely decipher chemical processes within soil and predict accurately how terrestrial carbon fluxes will response to changing climatic conditions and land use. To elucidate the molecular-level structure of SOM, we selectively extracted a broad range of intact SOM compounds by a combination of different organic solvents from soilsmore » with a wide range of C content. Our use of Electrospray ionization (ESI) coupled with Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) and a suite of solvents with varying polarity significantly expands the inventory of the types of organic molecules present in soils. Specifically, we found that hexane is selective for lipid-like compounds with very low O:C ratios; water was selective for carbohydrates with high O:C ratios; acetonitrile preferentially extracts lignin, condensed structures, and tannin poly phenolic compounds with O:C > 0.5; methanol has higher selectivity towards compounds characterized with low O:C < 0.5; and hexane, MeOH, ACN and water solvents increase the number and types of organic molecules extracted from soil for a broader range of chemically diverse soil types. Our study of SOM molecules by ESI-FTICR MS revealed new insight into the molecular-level complexity of organics contained in soils.« less

Measurement and control of detailed electronic properties in a single molecule break junction.

PubMed

Wang, Kun; Hamill, Joseph; Zhou, Jianfeng; Guo, Cunlan; Xu, Bingqian

2014-01-01

The lack of detailed experimental controls has been one of the major obstacles hindering progress in molecular electronics. While large fluctuations have been occurring in the experimental data, specific details, related mechanisms, and data analysis techniques are in high demand to promote our physical understanding at the single-molecule level. A series of modulations we recently developed, based on traditional scanning probe microscopy break junctions (SPMBJs), have helped to discover significant properties in detail which are hidden in the contact interfaces of a single-molecule break junction (SMBJ). For example, in the past we have shown that the correlated force and conductance changes under the saw tooth modulation and stretch-hold mode of PZT movement revealed inherent differences in the contact geometries of a molecular junction. In this paper, using a bias-modulated SPMBJ and utilizing emerging data analysis techniques, we report on the measurement of the altered alignment of the HOMO of benzene molecules with changing the anchoring group which coupled the molecule to metal electrodes. Further calculations based on Landauer fitting and transition voltage spectroscopy (TVS) demonstrated the effects of modulated bias on the location of the frontier molecular orbitals. Understanding the alignment of the molecular orbitals with the Fermi level of the electrodes is essential for understanding the behaviour of SMBJs and for the future design of more complex devices. With these modulations and analysis techniques, fruitful information has been found about the nature of the metal-molecule junction, providing us insightful clues towards the next step for in-depth study.

Processing for maximizing the level of crystallinity in linear aromatic polyimides

NASA Technical Reports Server (NTRS)

St.clair, Terry L. (Inventor)

1991-01-01

The process of the present invention includes first treating a polyamide acid (such as LARC-TPI polyamide acid) in an amide-containing solvent (such as N-methyl pyrrolidone) with an aprotic organic base (such as triethylamine), followed by dehydrating with an organic dehydrating agent (such as acetic anhydride). The level of crystallinity in the linear aromatic polyimide so produced is maximized without any degradation in the molecular weight thereof.

Use of Adverse Outcome Pathways for Assessing Effects of the Fungicide Propiconazole on Fish Reproduction

EPA Science Inventory

Adverse outcome pathways (AOP) are used to describe the linkage of biological events from a molecular initiating point, to individual-level-endpoints relevant to risk assessment. This study was done to assess toxicity outcomes for the conazole fungicide propiconazole based on a p...

Molecular Decay of the Tooth Gene Enamelin (ENAM) Mirrors the Loss of Enamel in the Fossil Record of Placental Mammals

PubMed Central

Meredith, Robert W.; Gatesy, John; Murphy, William J.; Ryder, Oliver A.; Springer, Mark S.

2009-01-01

Vestigial structures occur at both the anatomical and molecular levels, but studies documenting the co-occurrence of morphological degeneration in the fossil record and molecular decay in the genome are rare. Here, we use morphology, the fossil record, and phylogenetics to predict the occurrence of “molecular fossils” of the enamelin (ENAM) gene in four different orders of placental mammals (Tubulidentata, Pholidota, Cetacea, Xenarthra) with toothless and/or enamelless taxa. Our results support the “molecular fossil” hypothesis and demonstrate the occurrence of frameshift mutations and/or stop codons in all toothless and enamelless taxa. We then use a novel method based on selection intensity estimates for codons (ω) to calculate the timing of iterated enamel loss in the fossil record of aardvarks and pangolins, and further show that the molecular evolutionary history of ENAM predicts the occurrence of enamel in basal representatives of Xenarthra (sloths, anteaters, armadillos) even though frameshift mutations are ubiquitous in ENAM sequences of living xenarthrans. The molecular decay of ENAM parallels the morphological degeneration of enamel in the fossil record of placental mammals and provides manifest evidence for the predictive power of Darwin's theory. PMID:19730686

Poly(vinyl Chloride) Photostabilization in the Presence of Schiff Bases Containing a Thiadiazole Moiety.

PubMed

Shaalan, Naser; Laftah, Nawres; El-Hiti, Gamal A; Alotaibi, Mohammad Hayal; Muslih, Raad; Ahmed, Dina S; Yousif, Emad

2018-04-15

Five Schiff bases containing a thiadiazole moiety have been used as poly(vinyl chloride) photostabilizers at low concentrations. The efficiency of Schiff bases as photostabilizers was investigated using various techniques, for example, the changes in poly(vinyl chloride) infrared spectra, molecular weight, chain scission quantum yield, and surface morphology were monitored upon irradiation with an ultraviolet light. Evidently, all the additives used inhibited poly(vinyl chloride) photodegradation at a significant level. The most efficient Schiff base exhibited a high level of aromaticity and contained a hydroxyl group. It seems possible that such photostabilization could be due to the direct absorption of ultraviolet radiation by the additives. In addition, Schiff bases could act as radical scavengers and proton transfer facilitators to stabilize the polymeric materials.

Disentangling the multigenic and pleiotropic nature of molecular function

PubMed Central

2015-01-01

Background Biological processes at the molecular level are usually represented by molecular interaction networks. Function is organised and modularity identified based on network topology, however, this approach often fails to account for the dynamic and multifunctional nature of molecular components. For example, a molecule engaging in spatially or temporally independent functions may be inappropriately clustered into a single functional module. To capture biologically meaningful sets of interacting molecules, we use experimentally defined pathways as spatial/temporal units of molecular activity. Results We defined functional profiles of Saccharomyces cerevisiae based on a minimal set of Gene Ontology terms sufficient to represent each pathway's genes. The Gene Ontology terms were used to annotate 271 pathways, accounting for pathway multi-functionality and gene pleiotropy. Pathways were then arranged into a network, linked by shared functionality. Of the genes in our data set, 44% appeared in multiple pathways performing a diverse set of functions. Linking pathways by overlapping functionality revealed a modular network with energy metabolism forming a sparse centre, surrounded by several denser clusters comprised of regulatory and metabolic pathways. Signalling pathways formed a relatively discrete cluster connected to the centre of the network. Genetic interactions were enriched within the clusters of pathways by a factor of 5.5, confirming the organisation of our pathway network is biologically significant. Conclusions Our representation of molecular function according to pathway relationships enables analysis of gene/protein activity in the context of specific functional roles, as an alternative to typical molecule-centric graph-based methods. The pathway network demonstrates the cooperation of multiple pathways to perform biological processes and organises pathways into functionally related clusters with interdependent outcomes. PMID:26678917

Molecular Evolution in Historical Perspective.

PubMed

Suárez-Díaz, Edna

2016-12-01

In the 1960s, advances in protein chemistry and molecular genetics provided new means for the study of biological evolution. Amino acid sequencing, nucleic acid hybridization, zone gel electrophoresis, and immunochemistry were some of the experimental techniques that brought about new perspectives to the study of the patterns and mechanisms of evolution. New concepts, such as the molecular evolutionary clock, and the discovery of unexpected molecular phenomena, like the presence of repetitive sequences in eukaryotic genomes, eventually led to the realization that evolution might occur at a different pace at the organismic and the molecular levels, and according to different mechanisms. These developments sparked important debates between defendants of the molecular and organismic approaches. The most vocal confrontations focused on the relation between primates and humans, and the neutral theory of molecular evolution. By the 1980s and 1990s, the construction of large protein and DNA sequences databases, and the development of computer-based statistical tools, facilitated the coming together of molecular and evolutionary biology. Although in its contemporary form the field of molecular evolution can be traced back to the last five decades, the field has deep roots in twentieth century experimental life sciences. For historians of science, the origins and consolidation of molecular evolution provide a privileged field for the study of scientific debates, the relation between technological advances and scientific knowledge, and the connection between science and broader social concerns.

Synthesis, crystal structures and spectroscopic properties of triazine-based hydrazone derivatives; a comparative experimental-theoretical study.

PubMed

Arshad, Muhammad Nadeem; Bibi, Aisha; Mahmood, Tariq; Asiri, Abdullah M; Ayub, Khurshid

2015-04-03

We report here a comparative theoretical and experimental study of four triazine-based hydrazone derivatives. The hydrazones are synthesized by a three step process from commercially available benzil and thiosemicarbazide. The structures of all compounds were determined by using the UV-Vis., FT-IR, NMR (1H and 13C) spectroscopic techniques and finally confirmed unequivocally by single crystal X-ray diffraction analysis. Experimental geometric parameters and spectroscopic properties of the triazine based hydrazones are compared with those obtained from density functional theory (DFT) studies. The model developed here comprises of geometry optimization at B3LYP/6-31G (d, p) level of DFT. Optimized geometric parameters of all four compounds showed excellent correlations with the results obtained from X-ray diffraction studies. The vibrational spectra show nice correlations with the experimental IR spectra. Moreover, the simulated absorption spectra also agree well with experimental results (within 10-20 nm). The molecular electrostatic potential (MEP) mapped over the entire stabilized geometries of the compounds indicated their chemical reactivates. Furthermore, frontier molecular orbital (electronic properties) and first hyperpolarizability (nonlinear optical response) were also computed at the B3LYP/6-31G (d, p) level of theory.

Foundations of metabolic organization: coherence as a basis of computational properties in metabolic networks.

PubMed

Igamberdiev, A U

1999-04-01

Biological organization is based on the coherent energy transfer allowing for macromolecules to operate with high efficiency and realize computation. Computation is executed with virtually 100% efficiency via the coherent operation of molecular machines in which low-energy recognitions trigger energy-driven non-equilibrium dynamic processes. The recognition process is of quantum mechanical nature being a non-demolition measurement. It underlies the enzymatic conversion of a substrate into the product (an elementary metabolic phenomenon); the switching via separation of the direct and reverse routes in futile cycles provides the generation and complication of metabolic networks (coherence within cycles is maintained by the supramolecular organization of enzymes); the genetic level corresponding to the appearance of digital information is based on reflective arrows (catalysts realize their own self-reproduction) and operation of hypercycles. Every metabolic cycle via reciprocal regulation of both its halves can generate rhythms and spatial structures (resulting from the temporally organized depositions from the cycles). Via coherent events which percolate from the elementary submolecular level to organismic entities, self-assembly based on the molecular complementarity is realized and the dynamic informational field operating within the metabolic network is generated.

FRET sensor-based quantification of intracellular trehalose in mammalian cells.

PubMed

Kikuta, Shingo; Hou, Bi-Huei; Sato, Ryoichi; Frommer, Wolf B; Kikawada, Takahiro

2016-01-01

Trehalose acts as a stress protectant and an autophagy inducer in mammalian cells. The molecular mechanisms of action remain obscure because intracellular trehalose at micromolar level is difficult to quantitate. Here, we show a novel trehalose monitoring technology based on FRET. FLIP-suc90μ∆1Venus sensor expressed in mammalian cells enables to quickly and non-destructively detect an infinitesimal amount of intracellular trehalose.

Discovering transnosological molecular basis of human brain diseases using biclustering analysis of integrated gene expression data.

PubMed

Cha, Kihoon; Hwang, Taeho; Oh, Kimin; Yi, Gwan-Su

2015-01-01

It has been reported that several brain diseases can be treated as transnosological manner implicating possible common molecular basis under those diseases. However, molecular level commonality among those brain diseases has been largely unexplored. Gene expression analyses of human brain have been used to find genes associated with brain diseases but most of those studies were restricted either to an individual disease or to a couple of diseases. In addition, identifying significant genes in such brain diseases mostly failed when it used typical methods depending on differentially expressed genes. In this study, we used a correlation-based biclustering approach to find coexpressed gene sets in five neurodegenerative diseases and three psychiatric disorders. By using biclustering analysis, we could efficiently and fairly identified various gene sets expressed specifically in both single and multiple brain diseases. We could find 4,307 gene sets correlatively expressed in multiple brain diseases and 3,409 gene sets exclusively specified in individual brain diseases. The function enrichment analysis of those gene sets showed many new possible functional bases as well as neurological processes that are common or specific for those eight diseases. This study introduces possible common molecular bases for several brain diseases, which open the opportunity to clarify the transnosological perspective assumed in brain diseases. It also showed the advantages of correlation-based biclustering analysis and accompanying function enrichment analysis for gene expression data in this type of investigation.

Discovering transnosological molecular basis of human brain diseases using biclustering analysis of integrated gene expression data

PubMed Central

2015-01-01

Background It has been reported that several brain diseases can be treated as transnosological manner implicating possible common molecular basis under those diseases. However, molecular level commonality among those brain diseases has been largely unexplored. Gene expression analyses of human brain have been used to find genes associated with brain diseases but most of those studies were restricted either to an individual disease or to a couple of diseases. In addition, identifying significant genes in such brain diseases mostly failed when it used typical methods depending on differentially expressed genes. Results In this study, we used a correlation-based biclustering approach to find coexpressed gene sets in five neurodegenerative diseases and three psychiatric disorders. By using biclustering analysis, we could efficiently and fairly identified various gene sets expressed specifically in both single and multiple brain diseases. We could find 4,307 gene sets correlatively expressed in multiple brain diseases and 3,409 gene sets exclusively specified in individual brain diseases. The function enrichment analysis of those gene sets showed many new possible functional bases as well as neurological processes that are common or specific for those eight diseases. Conclusions This study introduces possible common molecular bases for several brain diseases, which open the opportunity to clarify the transnosological perspective assumed in brain diseases. It also showed the advantages of correlation-based biclustering analysis and accompanying function enrichment analysis for gene expression data in this type of investigation. PMID:26043779

Basis set construction for molecular electronic structure theory: natural orbital and Gauss-Slater basis for smooth pseudopotentials.

PubMed

Petruzielo, F R; Toulouse, Julien; Umrigar, C J

2011-02-14

A simple yet general method for constructing basis sets for molecular electronic structure calculations is presented. These basis sets consist of atomic natural orbitals from a multiconfigurational self-consistent field calculation supplemented with primitive functions, chosen such that the asymptotics are appropriate for the potential of the system. Primitives are optimized for the homonuclear diatomic molecule to produce a balanced basis set. Two general features that facilitate this basis construction are demonstrated. First, weak coupling exists between the optimal exponents of primitives with different angular momenta. Second, the optimal primitive exponents for a chosen system depend weakly on the particular level of theory employed for optimization. The explicit case considered here is a basis set appropriate for the Burkatzki-Filippi-Dolg pseudopotentials. Since these pseudopotentials are finite at nuclei and have a Coulomb tail, the recently proposed Gauss-Slater functions are the appropriate primitives. Double- and triple-zeta bases are developed for elements hydrogen through argon. These new bases offer significant gains over the corresponding Burkatzki-Filippi-Dolg bases at various levels of theory. Using a Gaussian expansion of the basis functions, these bases can be employed in any electronic structure method. Quantum Monte Carlo provides an added benefit: expansions are unnecessary since the integrals are evaluated numerically.

Population structure and genotypic variation of Crataegus pontica inferred by molecular markers.

PubMed

Rahmani, Mohammad-Shafie; Shabanian, Naghi; Khadivi-Khub, Abdollah; Woeste, Keith E; Badakhshan, Hedieh; Alikhani, Leila

2015-11-01

Information about the natural patterns of genetic variability and their evolutionary bases are of fundamental practical importance for sustainable forest management and conservation. In the present study, the genetic diversity of 164 individuals from fourteen natural populations of Crataegus pontica K.Koch was assessed for the first time using three genome-based molecular techniques; inter-retrotransposon amplified polymorphism (IRAP); inter-simple sequence repeats (ISSR) and start codon targeted (SCoT) polymorphism. IRAP, ISSR and SCoT analyses yielded 126, 254 and 199 scorable amplified bands, respectively, of which 90.48, 93.37 and 83.78% were polymorphic. ISSR revealed efficiency over IRAP and SCoT due to high effective multiplex ratio, marker index and resolving power. The dendrograms based on the markers used and combined data divided individuals into three major clusters. The correlation between the coefficient matrices for the IRAP, ISSR and SCoT data was significant. A higher level of genetic variation was observed within populations than among populations based on the markers used. The lower divergence levels depicted among the studied populations could be seen as evidence of gene flow. The promotion of gene exchange will be very beneficial to conserve and utilize the enormous genetic variability. Copyright © 2015 Elsevier B.V. All rights reserved.

Molecular insights into species phylogeny, biogeography, and morphological stasis in the ancient spider genus Hypochilus (Araneae: Hypochilidae).

PubMed

Hedin, M C

2001-02-01

The spider genus Hypochilus is currently restricted to cool, moist microhabitats in three widely separated montane regions of North America, providing an opportunity to study both deep (i.e., continental level) and shallow (within montane region) biogeographic history. Members of the genus also retain many plesiomorphic morphological characteristics, inviting the study of comparative rates of morphological evolution. In this paper, Hypochilus phylogeny and associated evolutionary problems are addressed using both new molecular (28S nDNA and CO1 mtDNA) and previously published (K. M. Catley, 1994, Am. Mus. Nov. 3088, 1-27) morphological data. Although the molecular data provide limited resolution of root placement within Hypochilus, most analyses are at least consistent with morphology-supported montane relationships of (Rockies (California, Appalachian)). The monophyly of Hypochilus species distributed in the California mountains is ambiguous, with several analyses indicating that this fauna may be paraphyletic with respect to a monophyletic Appalachian lineage. The montane regions differ in consistent ways in depths of both mitochondrial and nuclear phylogenetic divergence. Molecular clock analyses, in combination with arthropod-based mtDNA rate calibrations, suggest that the regional faunas are of different ages and that speciation in all faunas likely occurred prior to the Pleistocene. Limited intraspecific sampling reveals extraordinarily high levels of mtDNA cytochrome oxidase sequence divergence. These extreme divergences are most consistent with morphological stasis at the species level, despite preliminary evidence that Hypochilus taxa are characterized by fragmented population structures. Copyright 2001 Academic Press.

A diversity-oriented synthesis strategy enabling the combinatorial-type variation of macrocyclic peptidomimetic scaffolds.

PubMed

Isidro-Llobet, Albert; Hadje Georgiou, Kathy; Galloway, Warren R J D; Giacomini, Elisa; Hansen, Mette R; Méndez-Abt, Gabriela; Tan, Yaw Sing; Carro, Laura; Sore, Hannah F; Spring, David R

2015-04-21

Macrocyclic peptidomimetics are associated with a broad range of biological activities. However, despite such potentially valuable properties, the macrocyclic peptidomimetic structural class is generally considered as being poorly explored within drug discovery. This has been attributed to the lack of general methods for producing collections of macrocyclic peptidomimetics with high levels of structural, and thus shape, diversity. In particular, there is a lack of scaffold diversity in current macrocyclic peptidomimetic libraries; indeed, the efficient construction of diverse molecular scaffolds presents a formidable general challenge to the synthetic chemist. Herein we describe a new, advanced strategy for the diversity-oriented synthesis (DOS) of macrocyclic peptidomimetics that enables the combinatorial variation of molecular scaffolds (core macrocyclic ring architectures). The generality and robustness of this DOS strategy is demonstrated by the step-efficient synthesis of a structurally diverse library of over 200 macrocyclic peptidomimetic compounds, each based around a distinct molecular scaffold and isolated in milligram quantities, from readily available building-blocks. To the best of our knowledge this represents an unprecedented level of scaffold diversity in a synthetically derived library of macrocyclic peptidomimetics. Cheminformatic analysis indicated that the library compounds access regions of chemical space that are distinct from those addressed by top-selling brand-name drugs and macrocyclic natural products, illustrating the value of our DOS approach to sample regions of chemical space underexploited in current drug discovery efforts. An analysis of three-dimensional molecular shapes illustrated that the DOS library has a relatively high level of shape diversity.

Multilevel functional genomics data integration as a tool for understanding physiology: a network biology perspective.

PubMed

Davidsen, Peter K; Turan, Nil; Egginton, Stuart; Falciani, Francesco

2016-02-01

The overall aim of physiological research is to understand how living systems function in an integrative manner. Consequently, the discipline of physiology has since its infancy attempted to link multiple levels of biological organization. Increasingly this has involved mathematical and computational approaches, typically to model a small number of components spanning several levels of biological organization. With the advent of "omics" technologies, which can characterize the molecular state of a cell or tissue (intended as the level of expression and/or activity of its molecular components), the number of molecular components we can quantify has increased exponentially. Paradoxically, the unprecedented amount of experimental data has made it more difficult to derive conceptual models underlying essential mechanisms regulating mammalian physiology. We present an overview of state-of-the-art methods currently used to identifying biological networks underlying genomewide responses. These are based on a data-driven approach that relies on advanced computational methods designed to "learn" biology from observational data. In this review, we illustrate an application of these computational methodologies using a case study integrating an in vivo model representing the transcriptional state of hypoxic skeletal muscle with a clinical study representing muscle wasting in chronic obstructive pulmonary disease patients. The broader application of these approaches to modeling multiple levels of biological data in the context of modern physiology is discussed. Copyright © 2016 the American Physiological Society.

In Vivo Imaging of Immuno-Spin Trapped Radicals With Molecular Magnetic Resonance Imaging in a Diabetic Mouse Model

PubMed Central

Towner, Rheal A.; Smith, Nataliya; Saunders, Debra; Henderson, Michael; Downum, Kristen; Lupu, Florea; Silasi-Mansat, Robert; Ramirez, Dario C.; Gomez-Mejiba, Sandra E.; Bonini, Marcelo G.; Ehrenshaft, Marilyn; Mason, Ronald P.

2012-01-01

Oxidative stress plays a major role in diabetes. In vivo levels of membrane-bound radicals (MBRs) in a streptozotocin-induced diabetic mouse model were uniquely detected by combining molecular magnetic resonance imaging (mMRI) and immunotrapping techniques. An anti-DMPO (5,5-dimethyl-1-pyrroline N-oxide) antibody (Ab) covalently bound to an albumin (BSA)-Gd (gadolinium)-DTPA (diethylene triamine penta acetic acid)-biotin MRI contrast agent (anti-DMPO probe), and mMRI, were used to detect in vivo levels of DMPO-MBR adducts in kidneys, livers, and lungs of diabetic mice, after DMPO administration. Magnetic resonance signal intensities, which increase in the presence of a Gd-based molecular probe, were significantly higher within the livers, kidneys, and lungs of diabetic animals administered the anti-DMPO probe compared with controls. Fluorescence images validated the location of the anti-DMPO probe in excised tissues via conjugation of streptavidin-Cy3, which targeted the probe biotin moiety, and immunohistochemistry was used to validate the presence of DMPO adducts in diabetic mouse livers. This is the first report of noninvasively imaging in vivo levels of MBRs within any disease model. This method can be specifically applied toward diabetes models for in vivo assessment of free radical levels, providing an avenue to more fully understand the role of free radicals in diabetes. PMID:22698922

Addressing Loss of Efficiency Due to Misclassification Error in Enriched Clinical Trials for the Evaluation of Targeted Therapies Based on the Cox Proportional Hazards Model.

PubMed

Tsai, Chen-An; Lee, Kuan-Ting; Liu, Jen-Pei

2016-01-01

A key feature of precision medicine is that it takes individual variability at the genetic or molecular level into account in determining the best treatment for patients diagnosed with diseases detected by recently developed novel biotechnologies. The enrichment design is an efficient design that enrolls only the patients testing positive for specific molecular targets and randomly assigns them for the targeted treatment or the concurrent control. However there is no diagnostic device with perfect accuracy and precision for detecting molecular targets. In particular, the positive predictive value (PPV) can be quite low for rare diseases with low prevalence. Under the enrichment design, some patients testing positive for specific molecular targets may not have the molecular targets. The efficacy of the targeted therapy may be underestimated in the patients that actually do have the molecular targets. To address the loss of efficiency due to misclassification error, we apply the discrete mixture modeling for time-to-event data proposed by Eng and Hanlon [8] to develop an inferential procedure, based on the Cox proportional hazard model, for treatment effects of the targeted treatment effect for the true-positive patients with the molecular targets. Our proposed procedure incorporates both inaccuracy of diagnostic devices and uncertainty of estimated accuracy measures. We employed the expectation-maximization algorithm in conjunction with the bootstrap technique for estimation of the hazard ratio and its estimated variance. We report the results of simulation studies which empirically investigated the performance of the proposed method. Our proposed method is illustrated by a numerical example.

The evolution of respiratory O2/NO reductases: an out-of-the-phylogenetic-box perspective.

PubMed

Ducluzeau, Anne-Lise; Schoepp-Cothenet, Barbara; van Lis, Robert; Baymann, Frauke; Russell, Michael J; Nitschke, Wolfgang

2014-09-06

Complex life on our planet crucially depends on strong redox disequilibria afforded by the almost ubiquitous presence of highly oxidizing molecular oxygen. However, the history of O2-levels in the atmosphere is complex and prior to the Great Oxidation Event some 2.3 billion years ago, the amount of O2 in the biosphere is considered to have been extremely low as compared with present-day values. Therefore the evolutionary histories of life and of O2-levels are likely intricately intertwined. The obvious biological proxy for inferring the impact of changing O2-levels on life is the evolutionary history of the enzyme allowing organisms to tap into the redox power of molecular oxygen, i.e. the bioenergetic O2 reductases, alias the cytochrome and quinol oxidases. Consequently, molecular phylogenies reconstructed for this enzyme superfamily have been exploited over the last two decades in attempts to elucidate the interlocking between O2 levels in the environment and the evolution of respiratory bioenergetic processes. Although based on strictly identical datasets, these phylogenetic approaches have led to diametrically opposite scenarios with respect to the history of both the enzyme superfamily and molecular oxygen on the Earth. In an effort to overcome the deadlock of molecular phylogeny, we here review presently available structural, functional, palaeogeochemical and thermodynamic information pertinent to the evolution of the superfamily (which notably also encompasses the subfamily of nitric oxide reductases). The scenario which, in our eyes, most closely fits the ensemble of these non-phylogenetic data, sees the low O2-affinity SoxM- (or A-) type enzymes as the most recent evolutionary innovation and the high-affinity O2 reductases (SoxB or B and cbb3 or C) as arising independently from NO-reducing precursor enzymes. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Molecular and agro-morphological characterization of ancient wheat landraces of turkey.

PubMed

Gurcan, Kahraman; Demirel, Fatih; Tekin, Mehmet; Demirel, Serap; Akar, Taner

2017-11-14

Turkey is one of the important gene centers for many crop species. In this research, some ancient wheats such as tetraploid and diploid hulled wheats together with hexaploid tir wheats (Triticum aestivum ssp. leucospermum Korn.) landraces mainly adapted to harsh winter conditions of Eastern Anatolian region of Turkey were characterized at agro-morphological and molecular level. Totally 50 hulled wheat population from Kastamonu, Konya and Kayseri provinces and 15 tir wheats from Kars provinces of Turkey were in-situ collected for characterization in 2013. Some quantitative and qualitative traits of each population were determined. Twenty three hulled wheat population collected from Kastamonu province were distinguished into nine emmer and 14 einkorn wheats at morphological level. Additionally, Konya, Kayseri and Kars population were characterized as einkorn, emmer and tir wheat, respectively. Among the evaluated traits, protein ratios of hulled wheats were strikingly higher than registered cultivars. All the populations were also examined by molecular level by using fluorescently labelled 11 polymorphic SSRs primers. The primers exhibited 104 bands, ranging from 6 to 16 with a mean value 9.45 per loci. The clustering analysis separated the germplasm into two clusters which were also divided into two subclusters based on genetic similarity coefficient. Sixty-five population and five checks were analyzed to estimate mean number of alleles (N), expected and observed heterozygoties (He and Ho), polymorphism information content (PIC), Wright fix index (F), genetic deviation from Hardy-Weinberg expectation (Fit-Fis) and genetic variation (Fst) were determined as 9.45, 0.71, 0.07, 0.67, 0.90, 0.39, 0.87 and 0.39, respectively. A clear genetic deviation from Hardy - Weinberg expectation was observed among population in particular. These results showed considerable genetic variation among landraces rather than within population. These molecular information has revealed genetically diverse einkorn, emmer wheat and tir wheat population could be used as parents for further breeding studies in both Turkey and abroad. Furthermore, the molecular analysis has also generally discriminated the germplasm into ploidy level.

DNA Barcodes for Species Identification in the Hyperdiverse Ant Genus Pheidole (Formicidae: Myrmicinae)

PubMed Central

Ng'endo, R.N.; Osiemo, Z.B.; Brandl, R.

2013-01-01

DNA sequencing is increasingly being used to assist in species identification in order to overcome taxonomic impediment. However, few studies attempt to compare the results of these molecular studies with a more traditional species delineation approach based on morphological characters. Mitochondrial DNA Cytochrome oxidase subunit 1 (CO1) gene was sequenced, measuring 636 base pairs, from 47 ants of the genus Pheidole (Formicidae: Myrmicinae) collected in the Brazilian Atlantic Forest to test whether the morphology-based assignment of individuals into species is supported by DNA-based species delimitation. Twenty morphospecies were identified, whereas the barcoding analysis identified 19 Molecular Operational Taxonomic Units (MOTUs). Fifteen out of the 19 DNA-based clusters allocated, using sequence divergence thresholds of 2% and 3%, matched with morphospecies. Both thresholds yielded the same number of MOTUs. Only one MOTU was successfully identified to species level using the CO1 sequences of Pheidole species already in the Genbank. The average pairwise sequence divergence for all 47 sequences was 19%, ranging between 0–25%. In some cases, however, morphology and molecular based methods differed in their assignment of individuals to morphospecies or MOTUs. The occurrence of distinct mitochondrial lineages within morphological species highlights groups for further detailed genetic and morphological studies, and therefore a pluralistic approach using several methods to understand the taxonomy of difficult lineages is advocated. PMID:23902257

Pan-Cancer Molecular Classes Transcending Tumor Lineage Across 32 Cancer Types, Multiple Data Platforms, and over 10,000 Cases.

PubMed

Chen, Fengju; Zhang, Yiqun; Gibbons, Don L; Deneen, Benjamin; Kwiatkowski, David J; Ittmann, Michael; Creighton, Chad J

2018-05-01

Purpose: The Cancer Genome Atlas data resources represent an opportunity to explore commonalities across cancer types involving multiple molecular levels, but tumor lineage and histology can represent a barrier in moving beyond differences related to cancer type. Experimental Design: On the basis of gene expression data, we classified 10,224 cancers, representing 32 major types, into 10 molecular-based "classes." Molecular patterns representing tissue or histologic dominant effects were first removed computationally, with the resulting classes representing emergent themes across tumor lineages. Results: Key differences involving mRNAs, miRNAs, proteins, and DNA methylation underscored the pan-cancer classes. One class expressing neuroendocrine and cancer-testis antigen markers represented ∼4% of cancers surveyed. Basal-like breast cancers segregated into an exclusive class, distinct from all other cancers. Immune checkpoint pathway markers and molecular signatures of immune infiltrates were most strongly manifested within a class representing ∼13% of cancers. Pathway-level differences involving hypoxia, NRF2-ARE, Wnt, and Notch were manifested in two additional classes enriched for mesenchymal markers and miR200 silencing. Conclusions: All pan-cancer molecular classes uncovered here, with the important exception of the basal-like breast cancer class, involve a wide range of cancer types and would facilitate understanding the molecular underpinnings of cancers beyond tissue-oriented domains. Numerous biological processes associated with cancer in the laboratory setting were found here to be coordinately manifested across large subsets of human cancers. The number of cancers manifesting features of neuroendocrine tumors may be much higher than previously thought, which disease is known to occur in many different tissues. Clin Cancer Res; 24(9); 2182-93. ©2018 AACR . ©2018 American Association for Cancer Research.

Investigating molecular changes in organic matter composition in two Holocene lake-sediment records from central Sweden using pyrolysis-GC/MS

NASA Astrophysics Data System (ADS)

Ninnes, Sofia; Tolu, Julie; Meyer-Jacob, Carsten; Mighall, Tim M.; Bindler, Richard

2017-06-01

Organic matter (OM) is a key component of lake sediments, affecting carbon, nutrient, and trace metal cycling at local and global scales. Yet little is known about long-term (millennial) changes in OM composition due to the inherent chemical complexity arising from multiple OM sources and from secondary transformations. In this study we explore how the molecular composition of OM changes throughout the Holocene in two adjacent boreal lakes in central Sweden and compare molecular-level information with conventional OM variables, including total carbon, total nitrogen, C:N ratios, δ13C, and δ15N. To characterize the molecular OM composition, we employed a new method based on pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS), which yields semiquantitative data on >100 organic compounds of different origin and degradation status. We identify large changes in OM composition after deglaciation (circa 8500 ± 500 B.C.), associated with early landscape development, and during the most recent 40-50 years, driven by degradation processes. With molecular-level information we can also distinguish between natural landscape development and human catchment disturbance during the last 1700 years. Our study demonstrates that characterization of the molecular OM composition by the high-throughput Py-GC/MS method is an efficient complement to conventional OM variables for identification and understanding of past OM dynamics in lake-sediment records. Holocene changes observed for pyrolytic compounds and compound classes known for having different reactivity indicate the need for further paleo-reconstruction of the molecular OM composition to better understand both past and future OM dynamics and associated environmental changes.

An Experiment-Oriented Approach to Teaching the Kinetic Molecular Theory.

ERIC Educational Resources Information Center

Wiseman, Frank L., Jr.

1979-01-01

This paper reports an experiment in the teaching of the kinetic molecular theory to nonscience majors by the inquiry method. It allows the student to develop an essentially correct view of gases, liquids, and solids on the atomic or molecular level, and illustrates how one can draw conclusions about the molecular level by simple visual…

Achieving deeper molecular response is associated with a better clinical outcome in chronic myeloid leukemia patients on imatinib front-line therapy

PubMed Central

Etienne, Gabriel; Dulucq, Stéphanie; Nicolini, Franck-Emmanuel; Morisset, Stéphane; Fort, Marie-Pierre; Schmitt, Anna; Etienne, Madeleine; Hayette, Sandrine; Lippert, Eric; Bureau, Caroline; Tigaud, Isabelle; Adiko, Didier; Marit, Gérald; Reiffers, Josy; Mahon, François-Xavier

2014-01-01

Sustained imatinib treatment in chronic myeloid leukemia patients can result in complete molecular response allowing discontinuation without relapse. We set out to evaluate the frequency of complete molecular response in imatinib de novo chronic phase chronic myeloid leukemia patients, to identify base-line and under-treatment predictive factors of complete molecular response in patients achieving complete cytogenetic response, and to assess if complete molecular response is associated with a better outcome. A random selection of patients on front-line imatinib therapy (n=266) were considered for inclusion. Complete molecular response was confirmed and defined as MR 4.5 with undetectable BCR-ABL transcript levels. Median follow up was 4.43 years (range 0.79–10.8 years). Sixty-five patients (24%) achieved complete molecular response within a median time of 32.7 months. Absence of spleen enlargement at diagnosis, achieving complete cytogenetic response before 12 months of therapy, and major molecular response during the year following complete cytogenetic response was predictive of achieving further complete molecular response. Patients who achieved complete molecular response had better event-free and failure-free survivals than those with complete cytogenetic response irrespective of major molecular response status (95.2% vs. 64.7% vs. 27.7%, P=0.00124; 98.4% vs. 82.3% vs. 56%, P=0.0335), respectively. Overall survival was identical in the 3 groups. In addition to complete cytogenetic response and major molecular response, further deeper molecular response is associated with better event-free and failure-free survivals, and complete molecular response confers the best outcome. PMID:24362549

Computing molecular fluctuations in biochemical reaction systems based on a mechanistic, statistical theory of irreversible processes.

PubMed

Kulasiri, Don

2011-01-01

We discuss the quantification of molecular fluctuations in the biochemical reaction systems within the context of intracellular processes associated with gene expression. We take the molecular reactions pertaining to circadian rhythms to develop models of molecular fluctuations in this chapter. There are a significant number of studies on stochastic fluctuations in intracellular genetic regulatory networks based on single cell-level experiments. In order to understand the fluctuations associated with the gene expression in circadian rhythm networks, it is important to model the interactions of transcriptional factors with the E-boxes in the promoter regions of some of the genes. The pertinent aspects of a near-equilibrium theory that would integrate the thermodynamical and particle dynamic characteristics of intracellular molecular fluctuations would be discussed, and the theory is extended by using the theory of stochastic differential equations. We then model the fluctuations associated with the promoter regions using general mathematical settings. We implemented ubiquitous Gillespie's algorithms, which are used to simulate stochasticity in biochemical networks, for each of the motifs. Both the theory and the Gillespie's algorithms gave the same results in terms of the time evolution of means and variances of molecular numbers. As biochemical reactions occur far away from equilibrium-hence the use of the Gillespie algorithm-these results suggest that the near-equilibrium theory should be a good approximation for some of the biochemical reactions. © 2011 Elsevier Inc. All rights reserved.

Molecular biomarkers for chronological age in animal ecology.

PubMed

Jarman, Simon N; Polanowski, Andrea M; Faux, Cassandra E; Robbins, Jooke; De Paoli-Iseppi, Ricardo; Bravington, Mark; Deagle, Bruce E

2015-10-01

The chronological age of an individual animal predicts many of its biological characteristics, and these in turn influence population-level ecological processes. Animal age information can therefore be valuable in ecological research, but many species have no external features that allow age to be reliably determined. Molecular age biomarkers provide a potential solution to this problem. Research in this area of molecular ecology has so far focused on a limited range of age biomarkers. The most commonly tested molecular age biomarker is change in average telomere length, which predicts age well in a small number of species and tissues, but performs poorly in many other situations. Epigenetic regulation of gene expression has recently been shown to cause age-related modifications to DNA and to cause changes in abundance of several RNA types throughout animal lifespans. Age biomarkers based on these epigenetic changes, and other new DNA-based assays, have already been applied to model organisms, humans and a limited number of wild animals. There is clear potential to apply these marker types more widely in ecological studies. For many species, these new approaches will produce age estimates where this was previously impractical. They will also enable age information to be gathered in cross-sectional studies and expand the range of demographic characteristics that can be quantified with molecular methods. We describe the range of molecular age biomarkers that have been investigated to date and suggest approaches for developing the newer marker types as age assays in nonmodel animal species. © 2015 John Wiley & Sons Ltd.

To-date spacecraft applications and demonstration testing results, and future product development for new molecular adsorber technologies

NASA Technical Reports Server (NTRS)

Thomson, Shaun; Hansen, Patricia; Straka, Sharon; Chen, Philip; Triolo, Jack; Bettini, Ron; Carosso, Paolo; Carosso, Nancy

1997-01-01

The use of molecular adsorbers, in order to aid in the reduction of the spacecraft contamination levels, is discussed. Molecular adsorbers are characterized by an extremely large surface area, molecularly-porous substructure, and processing charged sites capable of retaining molecular contaminant species. Molecular adsorbers were applied on two Hubble Space Telescope servicing missions, as well as on the tropical rainfall measuring mission. The use of molecular adsorbers carries the potential for low cost, easy fabrication and integration of reliable means for reducing the contamination level around spacecraft.

Network-based differential gene expression analysis suggests cell cycle related genes regulated by E2F1 underlie the molecular difference between smoker and non-smoker lung adenocarcinoma

PubMed Central

2013-01-01

Background Differential gene expression (DGE) analysis is commonly used to reveal the deregulated molecular mechanisms of complex diseases. However, traditional DGE analysis (e.g., the t test or the rank sum test) tests each gene independently without considering interactions between them. Top-ranked differentially regulated genes prioritized by the analysis may not directly relate to the coherent molecular changes underlying complex diseases. Joint analyses of co-expression and DGE have been applied to reveal the deregulated molecular modules underlying complex diseases. Most of these methods consist of separate steps: first to identify gene-gene relationships under the studied phenotype then to integrate them with gene expression changes for prioritizing signature genes, or vice versa. It is warrant a method that can simultaneously consider gene-gene co-expression strength and corresponding expression level changes so that both types of information can be leveraged optimally. Results In this paper, we develop a gene module based method for differential gene expression analysis, named network-based differential gene expression (nDGE) analysis, a one-step integrative process for prioritizing deregulated genes and grouping them into gene modules. We demonstrate that nDGE outperforms existing methods in prioritizing deregulated genes and discovering deregulated gene modules using simulated data sets. When tested on a series of smoker and non-smoker lung adenocarcinoma data sets, we show that top differentially regulated genes identified by the rank sum test in different sets are not consistent while top ranked genes defined by nDGE in different data sets significantly overlap. nDGE results suggest that a differentially regulated gene module, which is enriched for cell cycle related genes and E2F1 targeted genes, plays a role in the molecular differences between smoker and non-smoker lung adenocarcinoma. Conclusions In this paper, we develop nDGE to prioritize deregulated genes and group them into gene modules by simultaneously considering gene expression level changes and gene-gene co-regulations. When applied to both simulated and empirical data, nDGE outperforms the traditional DGE method. More specifically, when applied to smoker and non-smoker lung cancer sets, nDGE results illustrate the molecular differences between smoker and non-smoker lung cancer. PMID:24341432

Understanding the Differences in Molecular Conformation of Carbohydrate and Protein in Endosperm Tissues of Grains with Different Biodegradation Kinetics Using Advanced Synchrotron Technology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, P.; Block, H; Doiron, K

Conventional 'wet' chemical analyses rely heavily on the use of harsh chemicals and derivatization, thereby altering native seed structures leaving them unable to detect any original inherent structures within an intact tissue sample. A synchrotron is a giant particle accelerator that turns electrons into light (million times brighter than sunlight) which can be used to study the structure of materials at the molecular level. Synchrotron radiation-based Fourier transform IR microspectroscopy (SR-FTIRM) has been developed as a rapid, direct, non-destructive and bioanalytical technique. This technique, taking advantage of the brightness of synchrotron light and a small effective source size, is capablemore » of exploring the molecular chemistry within the microstructures of a biological tissue without the destruction of inherent structures at ultraspatial resolutions within cellular dimensions. This is in contrast to traditional 'wet' chemical methods, which, during processing for analysis, often result in the destruction of the intrinsic structures of feeds. To date there has been very little application of this technique to the study of plant seed tissue in relation to nutrient utilization. The objective of this study was to use novel synchrotron radiation-based technology (SR-FTIRM) to identify the differences in the molecular chemistry and conformation of carbohydrate and protein in various plant seed endosperms within intact tissues at cellular and subcellular level from grains with different biodegradation kinetics. Barley grain (cv. Harrington) with a high rate (31.3%/h) and extent (78%), corn grain (cv. Pioneer) with a low rate (9.6%/h) and extent of (57%), and wheat grain (cv. AC Barrie) with an intermediate rate (23%/h) and extent (72%) of ruminal DM degradation were selected for evaluation. SR-FTIRM evaluations were performed at the National Synchrotron Light Source at the Brookhaven National Laboratory (Brookhaven, NY). These results suggest that SR-FTIRM plus the multivariate analyses can be used to identify spectral features associated with the molecular structure of endosperm from grains with different biodegradation kinetics, especially in relation to protein structure. The Novel synchrotron radiation-based bioanalytical technique provides a new approach for plant seed structural molecular studies at ultraspatial resolution and within intact tissue in relation to nutrient availability.« less

DSSR-enhanced visualization of nucleic acid structures in Jmol.

PubMed

Hanson, Robert M; Lu, Xiang-Jun

2017-07-03

Sophisticated and interactive visualizations are essential for making sense of the intricate 3D structures of macromolecules. For proteins, secondary structural components are routinely featured in molecular graphics visualizations. However, the field of RNA structural bioinformatics is still lagging behind; for example, current molecular graphics tools lack built-in support even for base pairs, double helices, or hairpin loops. DSSR (Dissecting the Spatial Structure of RNA) is an integrated and automated command-line tool for the analysis and annotation of RNA tertiary structures. It calculates a comprehensive and unique set of features for characterizing RNA, as well as DNA structures. Jmol is a widely used, open-source Java viewer for 3D structures, with a powerful scripting language. JSmol, its reincarnation based on native JavaScript, has a predominant position in the post Java-applet era for web-based visualization of molecular structures. The DSSR-Jmol integration presented here makes salient features of DSSR readily accessible, either via the Java-based Jmol application itself, or its HTML5-based equivalent, JSmol. The DSSR web service accepts 3D coordinate files (in mmCIF or PDB format) initiated from a Jmol or JSmol session and returns DSSR-derived structural features in JSON format. This seamless combination of DSSR and Jmol/JSmol brings the molecular graphics of 3D RNA structures to a similar level as that for proteins, and enables a much deeper analysis of structural characteristics. It fills a gap in RNA structural bioinformatics, and is freely accessible (via the Jmol application or the JSmol-based website http://jmol.x3dna.org). © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Empirical evaluation of data normalization methods for molecular classification.

PubMed

Huang, Huei-Chung; Qin, Li-Xuan

2018-01-01

Data artifacts due to variations in experimental handling are ubiquitous in microarray studies, and they can lead to biased and irreproducible findings. A popular approach to correct for such artifacts is through post hoc data adjustment such as data normalization. Statistical methods for data normalization have been developed and evaluated primarily for the discovery of individual molecular biomarkers. Their performance has rarely been studied for the development of multi-marker molecular classifiers-an increasingly important application of microarrays in the era of personalized medicine. In this study, we set out to evaluate the performance of three commonly used methods for data normalization in the context of molecular classification, using extensive simulations based on re-sampling from a unique pair of microRNA microarray datasets for the same set of samples. The data and code for our simulations are freely available as R packages at GitHub. In the presence of confounding handling effects, all three normalization methods tended to improve the accuracy of the classifier when evaluated in an independent test data. The level of improvement and the relative performance among the normalization methods depended on the relative level of molecular signal, the distributional pattern of handling effects (e.g., location shift vs scale change), and the statistical method used for building the classifier. In addition, cross-validation was associated with biased estimation of classification accuracy in the over-optimistic direction for all three normalization methods. Normalization may improve the accuracy of molecular classification for data with confounding handling effects; however, it cannot circumvent the over-optimistic findings associated with cross-validation for assessing classification accuracy.

Simultaneous G-Quadruplex DNA Logic.

PubMed

Bader, Antoine; Cockroft, Scott L

2018-04-03

A fundamental principle of digital computer operation is Boolean logic, where inputs and outputs are described by binary integer voltages. Similarly, inputs and outputs may be processed on the molecular level as exemplified by synthetic circuits that exploit the programmability of DNA base-pairing. Unlike modern computers, which execute large numbers of logic gates in parallel, most implementations of molecular logic have been limited to single computing tasks, or sensing applications. This work reports three G-quadruplex-based logic gates that operate simultaneously in a single reaction vessel. The gates respond to unique Boolean DNA inputs by undergoing topological conversion from duplex to G-quadruplex states that were resolved using a thioflavin T dye and gel electrophoresis. The modular, addressable, and label-free approach could be incorporated into DNA-based sensors, or used for resolving and debugging parallel processes in DNA computing applications. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

p-π Conjugated Polymers Based on Stable Triarylborane with n-Type Behavior in Optoelectronic Devices.

PubMed

Meng, Bin; Ren, Yi; Liu, Jun; Jäkle, Frieder; Wang, Lixiang

2018-02-19

p-π conjugation with embedded heteroatoms offers unique opportunities to tune the electronic structure of conjugated polymers. An approach is presented to form highly electron-deficient p-π conjugated polymers based on triarylboranes, demonstrate their n-type behavior, and explore device applications. By combining alternating [2,4,6-tris(trifluoromethyl)phenyl]di(thien-2-yl)borane (FBDT) and electron-deficient isoindigo (IID)/pyridine-flanked diketopyrrolopyrrole (DPPPy) units, we achieve low-lying lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) energy levels, high electron mobilities, and broad absorptions in the visible region. All-polymer solar cells with these polymers as electron acceptors exhibit encouraging photovoltaic performance with power conversion efficiencies of up to 2.83 %. These results unambiguously prove the n-type behavior and demonstrate the photovoltaic applications of p-π conjugated polymers based on triarylborane. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Innovative molecular-based fluorescent nanoparticles for multicolor single particle tracking in cells

NASA Astrophysics Data System (ADS)

Daniel, Jonathan; Godin, Antoine G.; Palayret, Matthieu; Lounis, Brahim; Cognet, Laurent; Blanchard-Desce, Mireille

2016-03-01

Based on an original molecular-based design, we present bright and photostable fluorescent organic nanoparticles (FONs) showing excellent colloidal stability in various aqueous environments. Complementary near-infrared emitting and green emitting FONs were prepared using a simple, fast and robust protocol. Both types of FONs could be simultaneously imaged at the single-particle level in solution as well as in biological environments using a monochromatic excitation and a dual-color fluorescence microscope. No evidence of acute cytotoxicity was found upon incubation of live cells with mixed solutions of FONs, and both types of nanoparticles were found internalized in the cells where their motion could be simultaneously tracked at video-rate up to minutes. These fluorescent organic nanoparticles open a novel non-toxic alternative to existing nanoparticles for imaging biological structures, compatible with live-cell experiments and specially fitted for multicolor single particle tracking.

Molecular taxonomy, phylogeny and evolution in the family Stichopodidae (Aspidochirotida: Holothuroidea) based on COI and 16S mitochondrial DNA.

PubMed

Byrne, Maria; Rowe, Frank; Uthicke, Sven

2010-09-01

The Stichopodidae comprise a diverse assemblage of holothuroids most of which occur in the Indo-Pacific. Phylogenetic analyses of mitochondrial gene (COI, 16S rRNA) sequence for 111 individuals (7 genera, 17 species) clarified taxonomic uncertainties, species relationships, biogeography and evolution of the family. A monophyly of the genus Stichopus was supported with the exception of Stichopus ellipes. Molecular analyses confirmed genus level taxonomy based on morphology. Most specimens harvested as S. horrens fell in the S. monotuberculatus clade, a morphologically variable assemblage with others from the S. naso clade. Taxonomic clarification of species fished as S. horrens will assist conservation measures. Evolutionary rates based on comparison of sequence from trans-ithmian Isostichopus species estimated that Stichopus and Isostichopus diverged ca. 5.5-10.7Ma (Miocene). More recent splits were estimated to be younger than 1Ma. Copyright 2010 Elsevier Inc. All rights reserved.

Charge Transport Processes in Molecular Junctions

NASA Astrophysics Data System (ADS)

Smith, Christopher Eugene

Molecular electronics (ME) has evolved into a rich area of exploration that combines the fields of chemistry, materials, electronic engineering and computational modeling to explore the physics behind electronic conduction at the molecular level. Through studying charge transport properties of single molecules and nanoscale molecular materials the field has gained the potential to bring about new avenues for the miniaturization of electrical components where quantum phenomena are utilized to achieve solid state molecular device functionality. Molecular junctions are platforms that enable these studies and consist of a single molecule or a small group of molecules directly connected to electrodes. The work presented in this thesis has built upon the current understanding of the mechanisms of charge transport in ordered junctions using self-assembled monolayer (SAM) molecular thin films. Donor and acceptor compounds were synthesized and incorporated into SAMs grown on metal substrates then the transport properties were measured with conducting probe atomic force microscopy (CP-AFM). In addition to experimentally measured current-voltage (I-V) curves, the transport properties were addressed computationally and modeled theoretically. The key objectives of this project were to 1) investigate the impact of molecular structure on hole and electron charge transport, 2) understand the nature of the charge carriers and their structure-transport properties through long (<4 nm) conjugated molecular wires, and 3) quantitatively extract interfacial properties characteristic to macroscopic junctions, such as energy level alignment and molecule-contact electronic coupling from experimental I-V curves. Here, we lay ground work for creating a more complete picture of charge transport in macroscopically ordered molecular junctions of controlled architecture, length and charge carrier. The polaronic nature of hopping transport has been predicted in long, conjugated molecular wires. Using quantum-based calculations, we modeled 'p-type' polaron transport through oligophenylenethiophene (OPTI) wires and assigned transport activation energies to specific modes of nuclear motion. We also show control over 'n-type', LUMO-mediated transport in short ( 2 nm) redox-active perylenediimide (PDI) SAMs bound to contacts through isocyano linkers. By changing the contact work function (φ) and temperature, we were able to verify thermally-assisted LUMO transport. Transition voltage spectroscopy and the single level model was employed to fit the experimental I-V curves and extract the electronic coupling (epsilon) and the EF-LUMO offset (epsilonl). It was found that epsilonl does not change with φ (LUMO pinning), while Gamma changes with both φ and temperature. Further, the PDI SAMs could be reversibly chemically gated to modulate the transport. These results help advance our understanding of transport behavior in semiconducting molecular thin films, and open opportunities to engineer improved electronic functionality into molecular devices.

Information processing in the CNS: a supramolecular chemistry?

PubMed

Tozzi, Arturo

2015-10-01

How does central nervous system process information? Current theories are based on two tenets: (a) information is transmitted by action potentials, the language by which neurons communicate with each other-and (b) homogeneous neuronal assemblies of cortical circuits operate on these neuronal messages where the operations are characterized by the intrinsic connectivity among neuronal populations. In this view, the size and time course of any spike is stereotypic and the information is restricted to the temporal sequence of the spikes; namely, the "neural code". However, an increasing amount of novel data point towards an alternative hypothesis: (a) the role of neural code in information processing is overemphasized. Instead of simply passing messages, action potentials play a role in dynamic coordination at multiple spatial and temporal scales, establishing network interactions across several levels of a hierarchical modular architecture, modulating and regulating the propagation of neuronal messages. (b) Information is processed at all levels of neuronal infrastructure from macromolecules to population dynamics. For example, intra-neuronal (changes in protein conformation, concentration and synthesis) and extra-neuronal factors (extracellular proteolysis, substrate patterning, myelin plasticity, microbes, metabolic status) can have a profound effect on neuronal computations. This means molecular message passing may have cognitive connotations. This essay introduces the concept of "supramolecular chemistry", involving the storage of information at the molecular level and its retrieval, transfer and processing at the supramolecular level, through transitory non-covalent molecular processes that are self-organized, self-assembled and dynamic. Finally, we note that the cortex comprises extremely heterogeneous cells, with distinct regional variations, macromolecular assembly, receptor repertoire and intrinsic microcircuitry. This suggests that every neuron (or group of neurons) embodies different molecular information that hands an operational effect on neuronal computation.

Evaporation kinetics of Mg2SiO4 crystals and melts from molecular dynamics simulations

NASA Technical Reports Server (NTRS)

Kubicki, J. D.; Stolper, E. M.

1993-01-01

Computer simulations based on the molecular dynamics (MD) technique were used to study the mechanisms and kinetics of free evaporation from crystalline and molten forsterite (i.e., Mg2SiO4) on an atomic level. The interatomic potential employed for these simulations reproduces the energetics of bonding in forsterite and in gas-phase MgO and SiO2 reasonably accurately. Results of the simulation include predicted evaporation rates, diffusion rates, and reaction mechanisms for Mg2SiO4(s or l) yields 2Mg(g) + 20(g) + SiO2(g).

Defect states and their energetic position and distribution in organic molecular semiconductors

NASA Astrophysics Data System (ADS)

Sharma, Akanksha; Yadav, Sarita; Kumar, Pramod; Ray Chaudhuri, Sumita; Ghosh, Subhasis

2013-04-01

Energetic position and distribution of defect states due to structural disorder in pentacene and copper phthalocyanine have been obtained by capacitance based spectroscopic techniques. It has been shown that capacitance-frequency and capacitance-voltage characteristics exhibit Gaussian distribution of traps with an energetic position at around 0.5 eV above the highest occupied molecular orbital level of the pentacene and CuPc. These traps have been created by varying growth conditions and almost identical trap parameters in pentacene and copper phthalocyanine indicate that similar structural disorder is responsible for these traps.

Microfluidic-Based Enrichment and Retrieval of Circulating Tumor Cells for RT-PCR Analysis.

PubMed

Gogoi, Priya; Sepehri, Saedeh; Chow, Will; Handique, Kalyan; Wang, Yixin

2017-01-01

Molecular analysis of circulating tumor cells (CTCs) is hindered by low sensitivity and high level of background leukocytes of currently available CTC enrichment technologies. We have developed a novel device to enrich and retrieve CTCs from blood samples by using a microfluidic chip. The Celsee PREP100 device captures CTCs with high sensitivity and allows the captured CTCs to be retrieved for molecular analysis. It uses the microfluidic chip which has approximately 56,320 capture chambers. Based on differences in cell size and deformability, each chamber ensures that small blood escape while larger CTCs of varying sizes are trapped and isolated in the chambers. In this report, we used the Celsee PREP100 to capture cancer cells spiked into normal donor blood samples. We were able to show that the device can capture as low as 10 cells with high reproducibility. The captured CTCs were retrieved from the microfluidic chip. The cell recovery rate of this back-flow procedure is 100% and the level of remaining background leukocytes is very low (about 300-400 cells). RNA from the retrieved cells are extracted and converted to cDNA, and gene expression analysis of selected cancer markers can be carried out by using RT-PCR assays. The sensitive and easy-to-use Celsee PREP100 system represents a promising technology for capturing and molecular characterization of CTCs.

Discovering the intelligence in molecular biology.

PubMed

Uberbacher, E

1995-12-01

The Third International Conference on Intelligent Systems in Molecular Biology was truly an outstanding event. Computational methods in molecular biology have reached a new level of maturity and utility, resulting in many high-impact applications. The success of this meeting bodes well for the rapid and continuing development of computational methods, intelligent systems and information-based approaches for the biosciences. The basic technology, originally most often applied to 'feasibility' problems, is now dealing effectively with the most difficult real-world problems. Significant progress has been made in understanding protein-structure information, structural classification, and how functional information and the relevant features of active-site geometry can be gleaned from structures by automated computational approaches. The value and limits of homology-based methods, and the ability to classify proteins by structure in the absence of homology, have reached a new level of sophistication. New methods for covariation analysis in the folding of large structures such as RNAs have shown remarkably good results, indicating the long-term potential to understand very complicated molecules and multimolecular complexes using computational means. Novel methods, such as HMMs, context-free grammars and the uses of mutual information theory, have taken center stage as highly valuable tools in our quest to represent and characterize biological information. A focus on creative uses of intelligent systems technologies and the trend toward biological application will undoubtedly continue and grow at the 1996 ISMB meeting in St Louis.

Overview: Nucleation of clathrate hydrates

NASA Astrophysics Data System (ADS)

Warrier, Pramod; Khan, M. Naveed; Srivastava, Vishal; Maupin, C. Mark; Koh, Carolyn A.

2016-12-01

Molecular level knowledge of nucleation and growth of clathrate hydrates is of importance for advancing fundamental understanding on the nature of water and hydrophobic hydrate formers, and their interactions that result in the formation of ice-like solids at temperatures higher than the ice-point. The stochastic nature and the inability to probe the small length and time scales associated with the nucleation process make it very difficult to experimentally determine the molecular level changes that lead to the nucleation event. Conversely, for this reason, there have been increasing efforts to obtain this information using molecular simulations. Accurate knowledge of how and when hydrate structures nucleate will be tremendously beneficial for the development of sustainable hydrate management strategies in oil and gas flowlines, as well as for their application in energy storage and recovery, gas separation, carbon sequestration, seawater desalination, and refrigeration. This article reviews various aspects of hydrate nucleation. First, properties of supercooled water and ice nucleation are reviewed briefly due to their apparent similarity to hydrates. Hydrate nucleation is then reviewed starting from macroscopic observations as obtained from experiments in laboratories and operations in industries, followed by various hydrate nucleation hypotheses and hydrate nucleation driving force calculations based on the classical nucleation theory. Finally, molecular simulations on hydrate nucleation are discussed in detail followed by potential future research directions.

Extraction of information on macromolecular interactions from fluorescence micro-spectroscopy measurements in the presence and absence of FRET.

PubMed

Raicu, Valerică

2018-06-15

Investigations of static or dynamic interactions between proteins or other biological macromolecules in living cells often rely on the use of fluorescent tags with two different colors in conjunction with adequate theoretical descriptions of Förster Resonance Energy Transfer (FRET) and molecular-level micro-spectroscopic technology. One such method based on these general principles is FRET spectrometry, which allows determination of the quaternary structure of biomolecules from cell-level images of the distributions, or spectra of occurrence frequency of FRET efficiencies. Subsequent refinements allowed combining FRET frequency spectra with molecular concentration information, thereby providing the proportion of molecular complexes with various quaternary structures as well as their binding/dissociation energies. In this paper, we build on the mathematical principles underlying FRET spectrometry to propose two new spectrometric methods, which have distinct advantages compared to other methods. One of these methods relies on statistical analysis of color mixing in subpopulations of fluorescently tagged molecules to probe molecular association stoichiometry, while the other exploits the color shift induced by FRET to also derive geometric information in addition to stoichiometry. The appeal of the first method stems from its sheer simplicity, while the strength of the second consists in its ability to provide structural information. Copyright © 2018 Elsevier B.V. All rights reserved.

Extraction of information on macromolecular interactions from fluorescence micro-spectroscopy measurements in the presence and absence of FRET

NASA Astrophysics Data System (ADS)

Raicu, Valerică

2018-06-01

Investigations of static or dynamic interactions between proteins or other biological macromolecules in living cells often rely on the use of fluorescent tags with two different colors in conjunction with adequate theoretical descriptions of Förster Resonance Energy Transfer (FRET) and molecular-level micro-spectroscopic technology. One such method based on these general principles is FRET spectrometry, which allows determination of the quaternary structure of biomolecules from cell-level images of the distributions, or spectra of occurrence frequency of FRET efficiencies. Subsequent refinements allowed combining FRET frequency spectra with molecular concentration information, thereby providing the proportion of molecular complexes with various quaternary structures as well as their binding/dissociation energies. In this paper, we build on the mathematical principles underlying FRET spectrometry to propose two new spectrometric methods, which have distinct advantages compared to other methods. One of these methods relies on statistical analysis of color mixing in subpopulations of fluorescently tagged molecules to probe molecular association stoichiometry, while the other exploits the color shift induced by FRET to also derive geometric information in addition to stoichiometry. The appeal of the first method stems from its sheer simplicity, while the strength of the second consists in its ability to provide structural information.

Overview: Nucleation of clathrate hydrates.

PubMed

Warrier, Pramod; Khan, M Naveed; Srivastava, Vishal; Maupin, C Mark; Koh, Carolyn A

2016-12-07

Molecular level knowledge of nucleation and growth of clathrate hydrates is of importance for advancing fundamental understanding on the nature of water and hydrophobic hydrate formers, and their interactions that result in the formation of ice-like solids at temperatures higher than the ice-point. The stochastic nature and the inability to probe the small length and time scales associated with the nucleation process make it very difficult to experimentally determine the molecular level changes that lead to the nucleation event. Conversely, for this reason, there have been increasing efforts to obtain this information using molecular simulations. Accurate knowledge of how and when hydrate structures nucleate will be tremendously beneficial for the development of sustainable hydrate management strategies in oil and gas flowlines, as well as for their application in energy storage and recovery, gas separation, carbon sequestration, seawater desalination, and refrigeration. This article reviews various aspects of hydrate nucleation. First, properties of supercooled water and ice nucleation are reviewed briefly due to their apparent similarity to hydrates. Hydrate nucleation is then reviewed starting from macroscopic observations as obtained from experiments in laboratories and operations in industries, followed by various hydrate nucleation hypotheses and hydrate nucleation driving force calculations based on the classical nucleation theory. Finally, molecular simulations on hydrate nucleation are discussed in detail followed by potential future research directions.

Regulating Biocompatibility of Carbon Spheres via Defined Nanoscale Chemistry and a Careful Selection of Surface Functionalities

NASA Astrophysics Data System (ADS)

Misra, Santosh K.; Chang, Huei-Huei; Mukherjee, Prabuddha; Tiwari, Saumya; Ohoka, Ayako; Pan, Dipanjan

2015-10-01

A plethora of nanoarchitectures have been evaluated preclincially for applications in early detection and treatment of diseases at molecular and cellular levels resulted in limited success of their clinical translation. It is important to identify the factors that directly or indirectly affect their use in human. We bring a fundamental understanding of how to adjust the biocompatibility of carbon based spherical nanoparticles (CNPs) through defined chemistry and a vigilant choice of surface functionalities. CNPs of various size are designed by tweaking size (2-250 nm), surface chemistries (positive, or negatively charged), molecular chemistries (linear, dendritic, hyperbranched) and the molecular weight of the coating agents (MW 400-20 kDa). A combination of in vitro assays as tools were performed to determine the critical parameters that may trigger toxicity. Results indicated that hydrodynamic sizes are potentially not a risk factor for triggering cellular and systemic toxicity, whereas the presence of a highly positive surface charge and increasing molecular weight enhance the chance of inducing complement activation. Bare and carboxyl-terminated CNPs did present some toxicity at the cellular level which, however, is not comparable to those caused by positively charged CNPs. Similarly, negatively charged CNPs with hydroxyl and carboxylic functionalities did not cause any hemolysis.

Network Based Approach in the Establishment of the Relationship between Type 2 Diabetes Mellitus and Its Complications at the Molecular Level Coupled with Molecular Docking Mechanism

PubMed Central

Rampogu Lemuel, Mary

2016-01-01

Diabetes mellitus (DM) is one of the major metabolic disorders that is currently threatening the world. DM is seen associated with obesity and diabetic retinopathy (DR). In the present paper we tried to evaluate the relationship between the three aliments at the gene level and further performed the molecular docking to identify the common drug for all the three diseases. We have adopted several software programs such as Phenopedia, VennViewer, and CDOCKER to accomplish the objective. Our results revealed six genes that commonly associated and are involved in the signalling pathway. Furthermore, evaluation of common gene association from the selected set of genes projected the presence of SIRT1 in all the three aliments. Therefore, we targeted protein 4KXQ which was produced from the gene SIRT1 and challenged it with eight phytochemicals, adopting the CDOCKER. C1 compound has displayed highest -CDOCKER energy and -CDOCKER interaction energy of 43.6905 and 43.3953, respectively. Therefore, this compound is regarded as the most potential lead molecule. PMID:27699170

Network Based Approach in the Establishment of the Relationship between Type 2 Diabetes Mellitus and Its Complications at the Molecular Level Coupled with Molecular Docking Mechanism.

PubMed

Rampogu, Shailima; Rampogu Lemuel, Mary

2016-01-01

Diabetes mellitus (DM) is one of the major metabolic disorders that is currently threatening the world. DM is seen associated with obesity and diabetic retinopathy (DR). In the present paper we tried to evaluate the relationship between the three aliments at the gene level and further performed the molecular docking to identify the common drug for all the three diseases. We have adopted several software programs such as Phenopedia, VennViewer, and CDOCKER to accomplish the objective. Our results revealed six genes that commonly associated and are involved in the signalling pathway. Furthermore, evaluation of common gene association from the selected set of genes projected the presence of SIRT1 in all the three aliments. Therefore, we targeted protein 4KXQ which was produced from the gene SIRT1 and challenged it with eight phytochemicals, adopting the CDOCKER. C1 compound has displayed highest -CDOCKER energy and -CDOCKER interaction energy of 43.6905 and 43.3953, respectively. Therefore, this compound is regarded as the most potential lead molecule.

Clinical application of a microfluidic chip for immunocapture and quantification of circulating exosomes to assist breast cancer diagnosis and molecular classification.

PubMed

Fang, Shimeng; Tian, Hongzhu; Li, Xiancheng; Jin, Dong; Li, Xiaojie; Kong, Jing; Yang, Chun; Yang, Xuesong; Lu, Yao; Luo, Yong; Lin, Bingcheng; Niu, Weidong; Liu, Tingjiao

2017-01-01

Increasing attention has been attracted by exosomes in blood-based diagnosis because cancer cells release more exosomes in serum than normal cells and these exosomes overexpress a certain number of cancer-related biomarkers. However, capture and biomarker analysis of exosomes for clinical application are technically challenging. In this study, we developed a microfluidic chip for immunocapture and quantification of circulating exosomes from small sample volume and applied this device in clinical study. Circulating EpCAM-positive exosomes were measured in 6 cases breast cancer patients and 3 healthy controls to assist diagnosis. A significant increase in the EpCAM-positive exosome level in these patients was detected, compared to healthy controls. Furthermore, we quantified circulating HER2-positive exosomes in 19 cases of breast cancer patients for molecular classification. We demonstrated that the exosomal HER2 expression levels were almost consistent with that in tumor tissues assessed by immunohistochemical staining. The microfluidic chip might provide a new platform to assist breast cancer diagnosis and molecular classification.

PomBase: The Scientific Resource for Fission Yeast.

PubMed

Lock, Antonia; Rutherford, Kim; Harris, Midori A; Wood, Valerie

2018-01-01

The fission yeast Schizosaccharomyces pombe has become well established as a model species for studying conserved cell-level biological processes, especially the mechanics and regulation of cell division. PomBase integrates the S. pombe genome sequence with traditional genetic, molecular, and cell biological experimental data as well as the growing body of large datasets generated by emerging high-throughput methods. This chapter provides insight into the curation philosophy and data organization at PomBase, and provides a guide to using PomBase for infrequent visitors and anyone considering exploring S. pombe in their research.

Sequence-structure correlations in silk: Poly-Ala repeat of N. clavipes MaSp1 is naturally optimized at a critical length scale.

PubMed

Bratzel, Graham; Buehler, Markus J

2012-03-01

Spider silk is a self-assembling biopolymer that outperforms many known materials in terms of its mechanical performance despite being constructed from simple and inferior building blocks. While experimental studies have shown that the molecular structure of silk has a direct influence on the stiffness, toughness, and failure strength of silk, few molecular-level analyses of the nanostructure of silk assemblies in particular under variations of genetic sequences have been reported. Here we report atomistic-level structures of the MaSp1 protein from the Nephila Clavipes spider dragline silk sequence, obtained using an in silico approach based on replica exchange molecular dynamics (REMD) and explicit water molecular dynamics. We apply this method to study the effects of a systematic variation of the poly-alanine repeat lengths, a parameter controlled by the genetic makeup of silk, on the resulting molecular structure of silk at the nanoscale. Confirming earlier experimental and computational work, a structural analysis reveals that poly-alanine regions in silk predominantly form distinct and orderly β-sheet crystal domains while disorderly regions are formed by glycine-rich repeats that consist of 3(10)-helix type structures and β-turns. Our predictions are directly validated against experimental data based on dihedral angle pair calculations presented in Ramachandran plots combined with an analysis of the secondary structure content. The key result of our study is our finding of a strong dependence of the resulting silk nanostructure depending on the poly-alanine length. We observe that the wildtype poly-alanine repeat length of six residues defines a critical minimum length that consistently results in clearly defined β-sheet nanocrystals. For poly-alanine lengths below six, the β-sheet nanocrystals are not well-defined or not visible at all, while for poly-alanine lengths at and above six, the characteristic nanocomposite structure of silk emerges with no significant improvement of the quality of the β-sheet nanocrystal geometry. We present a simple biophysical model that explains these computational observations based on the mechanistic insight gained from the molecular simulations. Our findings set the stage for understanding how variations in the spidroin sequence can be used to engineer the structure and thereby functional properties of this biological superfiber, and present a design strategy for the genetic optimization of spidroins for enhanced mechanical properties. The approach used here may also find application in the design of other self-assembled molecular structures and fibers and in particular biologically inspired or completely synthetic systems. Copyright © 2011 Elsevier Ltd. All rights reserved.

The merger of electrochemistry and molecular electronics.

PubMed

McCreery, Richard L

2012-02-01

Molecular Electronics has the potential to greatly enhance existing silicon-based microelectronics to realize new functions, higher device density, lower power consumption, and lower cost. Although the investigation of electron transport through single molecules and molecular monolayers in "molecular junctions" is a recent development, many of the relevant concepts and phenomena are derived from electrochemistry, as practiced for the past several decades. The past 10+ years have seen an explosion of research activity directed toward how the structure of molecules affects electron transport in molecular junctions, with the ultimate objective of "rational design" of molecular components with new electronic functions, such as chemical sensing, interactions with light, and low-cost, low-power consumer electronics. In order to achieve these scientifically and commercially important objectives, the factors controlling charge transport in molecules "connected" to conducting contacts must be understood, and methods for massively parallel manufacturing of molecular circuits must be developed. This Personal Account describes the development of reproducible and robust molecular electronic devices, starting with modified electrodes used in electrochemistry and progressing to manufacturable molecular junctions. Although the field faced some early difficulties in reliability and characterization, the pieces are now in place for rapid advances in understanding charge transport at the molecular level. Inherent in the field of Molecular Electronics are many electrochemical concepts, including tunneling, redox exchange, activated electron transfer, and electron coupling between molecules and conducting contacts. Copyright © 2012 The Japan Chemical Journal Forum and Wiley Periodicals, Inc.

Molecular Structure and Sequence in Complex Coacervates

NASA Astrophysics Data System (ADS)

Sing, Charles; Lytle, Tyler; Madinya, Jason; Radhakrishna, Mithun

Oppositely-charged polyelectrolytes in aqueous solution can undergo associative phase separation, in a process known as complex coacervation. This results in a polyelectrolyte-dense phase (coacervate) and polyelectrolyte-dilute phase (supernatant). There remain challenges in understanding this process, despite a long history in polymer physics. We use Monte Carlo simulation to demonstrate that molecular features (charge spacing, size) play a crucial role in governing the equilibrium in coacervates. We show how these molecular features give rise to strong monomer sequence effects, due to a combination of counterion condensation and correlation effects. We distinguish between structural and sequence-based correlations, which can be designed to tune the phase diagram of coacervation. Sequence effects further inform the physical understanding of coacervation, and provide the basis for new coacervation models that take monomer-level features into account.

Conformation-based signal transfer and processing at the single-molecule level

NASA Astrophysics Data System (ADS)

Li, Chao; Wang, Zhongping; Lu, Yan; Liu, Xiaoqing; Wang, Li

2017-11-01

Building electronic components made of individual molecules is a promising strategy for the miniaturization and integration of electronic devices. However, the practical realization of molecular devices and circuits for signal transmission and processing at room temperature has proven challenging. Here, we present room-temperature intermolecular signal transfer and processing using SnCl2Pc molecules on a Cu(100) surface. The in-plane orientations of the molecules are effectively coupled via intermolecular interaction and serve as the information carrier. In the coupled molecular arrays, the signal can be transferred from one molecule to another in the in-plane direction along predesigned routes and processed to realize logical operations. These phenomena enable the use of molecules displaying intrinsic bistable states as complex molecular devices and circuits with novel functions.

Stacking Orientation Mediation of Pentacene and Derivatives for High Open-Circuit Voltage Organic Solar Cells.

PubMed

Chou, Chi-Ta; Lin, Chien-Hung; Tai, Yian; Liu, Chin-Hsin J; Chen, Li-Chyong; Chen, Kuei-Hsien

2012-05-03

In this Letter, we investigated the effect of the molecular stacking orientation on the open circuit voltage (VOC) of pentacene-based organic solar cells. Two functionalized pentacenes, namely, 6,13-diphenyl-pentacene (DP-penta) and 6,13-dibiphenyl-4-yl-pentacene (DB-penta), were utilized. Different molecular stacking orientations of the pentacene derivatives from the pristine pentacene were identified by angle-dependent near-edge X-ray absorption fine structure measurements. It is concluded that pentacene molecules stand up on the substrate surface, while both functionalized pentacenes lie down. A significant increase of the VOC from 0.28 to 0.83 V can be achieved upon the utilization of functionalized pentacene, owing to the modulation of molecular stacking orientation, which induced a vacuum-level shift.

Surface plasmon resonance-based molecular detection of Hb S [beta6(A3)Glu-->Val, GAG-->GTG] at the gene level.

PubMed

Atalay, Erol O; Ustel, Emre; Yildiz, Sanem; Atalay, Ayfer

2006-01-01

The surface plasmon resonance (SPR) approach, being a relatively novel biophysical method, is used to detect many different targets by biomolecular interaction. The SPR system uses optical and evanescent wave phenomenon. This approach does not need any labels, such as enzymes or isotopes, and the monitored interactions are in real time. In DNA-DNA interaction, the SPR approach is Tm-independent. Here we report our preliminary results for the molecular detection of the Hb S (GAG -->GTG) mutation at codon 6 of the human beta-globin gene. Our preliminary results show that the SPR approach could be applied as an inexpensive and fast routine test system for the molecular diagnosis of abnormal hemoglobins (Hbs), especially in premarital screening programs.

A perspective on extracellular vesicles proteomics

NASA Astrophysics Data System (ADS)

Rosa-Fernandes, Livia; Rocha, Victória Bombarda; Carregari, Victor Corasolla; Urbani, Andrea; Palmisano, Giuseppe

2017-11-01

Increasing attention has been given to secreted extracellular vesicles (EVs) in the past decades, especially in the portrayal of their molecular cargo and role as messengers in both homeostasis and pathophysiological conditions. This review presents the state-of-the-art proteomic technologies to identify and quantify EVs proteins along with their PTMs, interacting partners and structural details. The rapid growth of mass spectrometry-based analytical strategies for protein sequencing, PTMs and structural characterization has improved the level of molecular details that can be achieve from limited amount of EVs isolated from different biological sources. Here we will provide a perspective view on the achievements and challenges on EVs proteome characterization using mass spectrometry. A detailed bioinformatics approach will help us to picture the molecular fingerprint of EVs and understand better their pathophysiological function.

Eutectic-based wafer-level-packaging technique for piezoresistive MEMS accelerometers and bond characterization using molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Aono, T.; Kazama, A.; Okada, R.; Iwasaki, T.; Isono, Y.

2018-03-01

We developed a eutectic-based wafer-level-packaging (WLP) technique for piezoresistive micro-electromechanical systems (MEMS) accelerometers on the basis of molecular dynamics analyses and shear tests of WLP accelerometers. The bonding conditions were experimentally and analytically determined to realize a high shear strength without solder material atoms diffusing to adhesion layers. Molecular dynamics (MD) simulations and energy dispersive x-ray (EDX) spectrometry done after the shear tests clarified the eutectic reaction of the solder materials used in this research. Energy relaxation calculations in MD showed that the diffusion of solder material atoms into the adhesive layer was promoted at a higher temperature. Tensile creep MD simulations also suggested that the local potential energy in a solder material model determined the fracture points of the model. These numerical results were supported by the shear tests and EDX analyses for WLP accelerometers. Consequently, a bonding load of 9.8 kN and temperature of 300 °C were found to be rational conditions because the shear strength was sufficient to endure the polishing process after the WLP process and there was little diffusion of solder material atoms to the adhesion layer. Also, eutectic-bonding-based WLP was effective for controlling the attenuation of the accelerometers by determining the thickness of electroplated solder materials that played the role of a cavity between the accelerometers and lids. If the gap distance between the two was less than 6.2 µm, the signal gains for x- and z-axis acceleration were less than 20 dB even at the resonance frequency due to air-damping.

Thermal stability of the complex formed between carotenoids from sea buckthorn (Hippophae rhamnoides L.) and bovine β-lactoglobulin

NASA Astrophysics Data System (ADS)

Aprodu, Iuliana; Ursache, Florentina-Mihaela; Turturică, Mihaela; Râpeanu, Gabriela; Stănciuc, Nicoleta

2017-02-01

Sea buckthorn has gained importance as a versatile nutraceutical, due to its high nutritive value in terms of carotenoids content. β-Lactoglobulin (β-LG) is a natural carrier for various bioactive compounds. In this study, the effect of thermal treatment in the temperature range of 25 to 100 °C for 15 min on the complex formed by β-LG and carotenoids from sea buckthorn was reported, based on fluorescence spectroscopy, molecular docking and molecular dynamics simulation results. Also, the berries extracts were analyzed for their carotenoids content. The chromatographic profile of the sea buckthorn extracts revealed the presence of zeaxanthin and β-carotene, as major compounds. The Stern-Volmer constants and binding parameters between β-LG and β-carotene were estimated based on quenching experiments. When thermally treating the β-LG-carotenoids mixtures, an increase in intrinsic and extrinsic fluorescence intensity up to 90 °C was observed, together with blue-shifts in maximum emission in the lower temperature range and red-shifts at higher temperature. Based on fluorescence spectroscopy results, the unfolding of the protein molecules at high temperature was suggested. Detailed information obtained at atomic level revealed that events taking place in the complex heated at high temperature caused important changes in the β-carotene binding site, therefore leading to a more thermodynamically stable assembly. This study can be used to understand the changes occurring at molecular level that could help food operators to design new ingredients and functional foods, and to optimize the processing methods in order to obtain healthier food products.

Nanotechnology: Fundamental Principles and Applications

NASA Astrophysics Data System (ADS)

Ranjit, Koodali T.; Klabunde, Kenneth J.

Nanotechnology research is based primarily on molecular manufacturing. Although several definitions have been widely used in the past to describe the field of nanotechnology, it is worthwhile to point out that the National Nanotechnology Initiative (NNI), a federal research and development scheme approved by the congress in 2001 defines nanotechnology only if the following three aspects are involved: (1) research and technology development at the atomic, molecular, or macromolecular levels, in the length scale of approximately 1-100 nanometer range, (2) creating and using structures, devices, and systems that have novel properties and functions because of their small and/or intermediate size, and (3) ability to control or manipulate on the atomic scale. Nanotechnology in essence is the technology based on the manipulation of individual atoms and molecules to build complex structures that have atomic specifications.

Treatment Algorithms Based on Tumor Molecular Profiling: The Essence of Precision Medicine Trials.

PubMed

Le Tourneau, Christophe; Kamal, Maud; Tsimberidou, Apostolia-Maria; Bedard, Philippe; Pierron, Gaëlle; Callens, Céline; Rouleau, Etienne; Vincent-Salomon, Anne; Servant, Nicolas; Alt, Marie; Rouzier, Roman; Paoletti, Xavier; Delattre, Olivier; Bièche, Ivan

2016-04-01

With the advent of high-throughput molecular technologies, several precision medicine (PM) studies are currently ongoing that include molecular screening programs and PM clinical trials. Molecular profiling programs establish the molecular profile of patients' tumors with the aim to guide therapy based on identified molecular alterations. The aim of prospective PM clinical trials is to assess the clinical utility of tumor molecular profiling and to determine whether treatment selection based on molecular alterations produces superior outcomes compared with unselected treatment. These trials use treatment algorithms to assign patients to specific targeted therapies based on tumor molecular alterations. These algorithms should be governed by fixed rules to ensure standardization and reproducibility. Here, we summarize key molecular, biological, and technical criteria that, in our view, should be addressed when establishing treatment algorithms based on tumor molecular profiling for PM trials. © The Author 2015. Published by Oxford University Press.

Structural and vibrational studies on 1-(5-methyl-[1,3,4] thiadiazol-2-yl)-pyrolidin-2-ol

NASA Astrophysics Data System (ADS)

Ramesh Babu, N.; Saleem, H.; Subashchandrabose, S.; Padusha, M. Syed Ali; Bharanidharan, S.

2016-01-01

FT-Raman and FT-IR spectra were recorded for1-(5-methyl-[1,3,4]thiadiazol-2-yl)-pyrolidin-2-ol (MTPN) sample in solid state. The equilibrium geometries, harmonic vibrational frequencies, IR and the Raman scattering intensities were computed using DFT/6-311++G (d,p) level. Results obtained at this level of theory were used for a detailed interpretation of the IR and Raman spectra, based on the TED of the normal modes. Molecular parameters such as bond lengths, bond angles and dihedral angles were calculated. The intra-molecular charge transfer was calculated by means of NBO. Hyperconjugative interaction energy was more during the π-π∗ transition. Energy gap of the molecule has been found using HOMO and LUMO calculation, hence the less band gap, which seems to be more stable.

Molecularly imprinted polymer-based solid phase clean-up for analysis of ochratoxin A in beer, red wine, and grape juice.

PubMed

Cao, Jiliang; Kong, Weijun; Zhou, Shujun; Yin, Lihui; Wan, Li; Yang, Meihua

2013-04-01

A simple, reliable, and low-cost method based on molecularly imprinted polymer as a selective sorbent of SPE was proposed for the determination of ochratoxin A (OTA) in beer, red wine, and grape juice by HPLC coupled with fluorescence detection (HPLC-FLD). Samples were diluted with water and cleaned up with an AFFINIMIP® SPE OTA column. After washing and eluting, the analyte was analyzed by HPLC-FLD. Under the optimized conditions, LOD and LOQ for OTA were 0.025 and 0.08 ng/mL, respectively. The recoveries of OTA from beer, red wine, and grape spiked at 0.1, 2, and 5 ng/mL ranged from 91.6 to 101.7%. Furthermore, after a simple regenerated procedure, the molecularly imprinted polymer based SPE column could be reused at least 14 times to achieve more than 80% recoveries of OTA in real samples. The developed method was applied to the detection of 30 beer, red wine, and grape juice samples and only four samples were contaminated by OTA with levels below the legal limits. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preparation of molecular imprinted microspheres based on inorganic-organic co-functional monomer for miniaturized solid-phase extraction of fluoroquinolones in milk.

PubMed

Wang, Hui; Wang, Ruiling; Han, Yehong

2014-02-15

An inorganic-organic co-functional monomer, methacrylic acid-vinyltriethoxysilan (MAA-VTES) was designed for the synthesis of molecularly imprinted microspheres (MIMs). By virtue of the aqueous suspension polymerization and dummy template (pazufloxacin), the obtained MAA-VTES based MIMs exhibited good recognition and selectivity to fluoroquinolones (FQs), and were successfully applied as selective sorbents of a miniaturized home-made solid phase extraction device for the determination of ofloxacin (OFL), lomefloxacin (LOM) and ciprofloxacin (CIP) in milk samples. Under the optimum conditions of the miniaturized molecularly imprinted solid phase extraction (mini-MISPE) coupled with liquid chromatography-ultraviolet detector (LC-UV), good linearities were obtained for three FQs in a range of 0.2-20.0μgmL(-1) and the average recoveries at three spiked levels were ranged from 87.2% to 106.1% with the relative standard deviation (RSD) less than 5.4%. The presented co-functional monomer based mini-MISPE-LC-UV protocol introduced the rigidity and flexibility of inorganic silicon materials, exhibited excellent extraction performance towards targets, and could be potentially applied to the determination of FQs in milk samples. Copyright © 2013 Elsevier B.V. All rights reserved.

Accurate description of charged excitations in molecular solids from embedded many-body perturbation theory

NASA Astrophysics Data System (ADS)

Li, Jing; D'Avino, Gabriele; Duchemin, Ivan; Beljonne, David; Blase, Xavier

2018-01-01

We present a novel hybrid quantum/classical approach to the calculation of charged excitations in molecular solids based on the many-body Green's function G W formalism. Molecules described at the G W level are embedded into the crystalline environment modeled with an accurate classical polarizable scheme. This allows the calculation of electron addition and removal energies in the bulk and at crystal surfaces where charged excitations are probed in photoelectron experiments. By considering the paradigmatic case of pentacene and perfluoropentacene crystals, we discuss the different contributions from intermolecular interactions to electronic energy levels, distinguishing between polarization, which is accounted for combining quantum and classical polarizabilities, and crystal field effects, that can impact energy levels by up to ±0.6 eV. After introducing band dispersion, we achieve quantitative agreement (within 0.2 eV) on the ionization potential and electron affinity measured at pentacene and perfluoropentacene crystal surfaces characterized by standing molecules.

Length dependence of electron transport through molecular wires--a first principles perspective.

PubMed

Khoo, Khoong Hong; Chen, Yifeng; Li, Suchun; Quek, Su Ying

2015-01-07

One-dimensional wires constitute a fundamental building block in nanoscale electronics. However, truly one-dimensional metallic wires do not exist due to Peierls distortion. Molecular wires come close to being stable one-dimensional wires, but are typically semiconductors, with charge transport occurring via tunneling or thermally-activated hopping. In this review, we discuss electron transport through molecular wires, from a theoretical, quantum mechanical perspective based on first principles. We focus specifically on the off-resonant tunneling regime, applicable to shorter molecular wires (<∼4-5 nm) where quantum mechanics dictates electron transport. Here, conductance decays exponentially with the wire length, with an exponential decay constant, beta, that is independent of temperature. Different levels of first principles theory are discussed, starting with the computational workhorse - density functional theory (DFT), and moving on to many-electron GW methods as well as GW-inspired DFT + Sigma calculations. These different levels of theory are applied in two major computational frameworks - complex band structure (CBS) calculations to estimate the tunneling decay constant, beta, and Landauer-Buttiker transport calculations that consider explicitly the effects of contact geometry, and compute the transmission spectra directly. In general, for the same level of theory, the Landauer-Buttiker calculations give more quantitative values of beta than the CBS calculations. However, the CBS calculations have a long history and are particularly useful for quick estimates of beta. Comparing different levels of theory, it is clear that GW and DFT + Sigma calculations give significantly improved agreement with experiment compared to DFT, especially for the conductance values. Quantitative agreement can also be obtained for the Seebeck coefficient - another independent probe of electron transport. This excellent agreement provides confirmative evidence of off-resonant tunneling in the systems under investigation. Calculations show that the tunneling decay constant beta is a robust quantity that does not depend on details of the contact geometry, provided that the same contact geometry is used for all molecular lengths considered. However, because conductance is sensitive to contact geometry, values of beta obtained by considering conductance values where the contact geometry is changing with the molecular junction length can be quite different. Experimentally measured values of beta in general compare well with beta obtained using DFT + Sigma and GW transport calculations, while discrepancies can be attributed to changes in the experimental contact geometries with molecular length. This review also summarizes experimental and theoretical efforts towards finding perfect molecular wires with high conductance and small beta values.

Synergistic effects of chlorination and a fully two-dimensional side-chain design on molecular energy level modulation toward non-fullerene photovoltaics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chao, Pengjie; Wang, Huan; Mo, Daize

By taking the advantage of chlorination and fully conjugated side chains,2D-PBTClshows a PCE of up to 8.81% in non-fullerene solar cells, which corresponds to an approximately 28% improvement compared to that ofPTB7-Th-based devices.

Synergistic effects of chlorination and a fully two-dimensional side-chain design on molecular energy level modulation toward non-fullerene photovoltaics

DOE PAGES

Chao, Pengjie; Wang, Huan; Mo, Daize; ...

2017-12-18

By taking the advantage of chlorination and fully conjugated side chains,2D-PBTClshows a PCE of up to 8.81% in non-fullerene solar cells, which corresponds to an approximately 28% improvement compared to that ofPTB7-Th-based devices.

A Simple Refraction Experiment for Probing Diffusion in Ternary Mixtures

ERIC Educational Resources Information Center

Coutinho, Cecil A.; Mankidy, Bijith D.; Gupta, Vinay K.

2010-01-01

Diffusion is a fundamental phenomenon that is vital in many chemical processes such as mass transport in living cells, corrosion, and separations. We describe a simple undergraduate-level experiment based on Weiner's Method to probe diffusion in a ternary aqueous mixture of small molecular-weight molecules. As an illustration, the experiment…

Unit: Energy for Life, Inspection Pack, National Trial Print.

ERIC Educational Resources Information Center

Australian Science Education Project, Toorak, Victoria.

This unit, providing information about human nutrition and energy use, has been prepared for students whose level of thinking is transitional between concrete and formal stages. The unit is based upon an analogy between combustion and respiration and upon the molecular structure of food components. The core portion of the unit presents activities…

Structure and dynamics of human vimentin intermediate filament dimer and tetramer in explicit and implicit solvent models.

PubMed

Qin, Zhao; Buehler, Markus J

2011-01-01

Intermediate filaments, in addition to microtubules and microfilaments, are one of the three major components of the cytoskeleton in eukaryotic cells, and play an important role in mechanotransduction as well as in providing mechanical stability to cells at large stretch. The molecular structures, mechanical and dynamical properties of the intermediate filament basic building blocks, the dimer and the tetramer, however, have remained elusive due to persistent experimental challenges owing to the large size and fibrillar geometry of this protein. We have recently reported an atomistic-level model of the human vimentin dimer and tetramer, obtained through a bottom-up approach based on structural optimization via molecular simulation based on an implicit solvent model (Qin et al. in PLoS ONE 2009 4(10):e7294, 9). Here we present extensive simulations and structural analyses of the model based on ultra large-scale atomistic-level simulations in an explicit solvent model, with system sizes exceeding 500,000 atoms and simulations carried out at 20 ns time-scales. We report a detailed comparison of the structural and dynamical behavior of this large biomolecular model with implicit and explicit solvent models. Our simulations confirm the stability of the molecular model and provide insight into the dynamical properties of the dimer and tetramer. Specifically, our simulations reveal a heterogeneous distribution of the bending stiffness along the molecular axis with the formation of rather soft and highly flexible hinge-like regions defined by non-alpha-helical linker domains. We report a comparison of Ramachandran maps and the solvent accessible surface area between implicit and explicit solvent models, and compute the persistence length of the dimer and tetramer structure of vimentin intermediate filaments for various subdomains of the protein. Our simulations provide detailed insight into the dynamical properties of the vimentin dimer and tetramer intermediate filament building blocks, which may guide the development of novel coarse-grained models of intermediate filaments, and could also help in understanding assembly mechanisms.

Characterization of micro-flocs of NOM coagulated by PACl, alum and polysilicate-iron in terms of molecular weight and floc size.

PubMed

Fusheng, Li; Akira, Yuasa; Yuka, Ando

2008-01-01

Micro-flocs of NOM coagulated by polyaluminium chloride (PACl), alum and polysilicate-iron (PSI) were characterized by flocs size, HPSEC-based molecular weight and the captured content of coagulants-based aluminium and iron. Changes in floc composition with respect to the mass ratios of captured NOM to Al and Fe were examined. Lowering water pH to optimum levels was found to be capable of removing small NOM constituents that are generally difficult to be precipitated at neutral pH levels. For PACl and PSI, the distribution of micro flocs (0.1-5.0 microm) reached steady stage after rapid mixing for 30 seconds, with NOM being found existent within the non-coagulated fraction (d<0.1 microm) and the coagulated fraction with floc sizes above 5.0 microm (d >5.0 microm). For alum, however, the existence of NOM inside intermediate floc fractions of d = 0.1-1.0 microm, 1.0-3.0microm and 3.0-5.0 microm was confirmed.

Comparative molecular field analysis of artemisinin derivatives: Ab initio versus semiempirical optimized structures

NASA Astrophysics Data System (ADS)

Tonmunphean, Somsak; Kokpol, Sirirat; Parasuk, Vudhichai; Wolschann, Peter; Winger, Rudolf H.; Liedl, Klaus R.; Rode, Bernd M.

1998-07-01

Based on the belief that structural optimization methods, producing structures more closely to the experimental ones, should give better, i.e. more relevant, steric fields and hence more predictive CoMFA models, comparative molecular field analyses of artemisinin derivatives were performed based on semiempirical AM1 and HF/3-21G optimized geometries. Using these optimized geometries, the CoMFA results derived from the HF/3-21G method are found to be usually but not drastically better than those from AM1. Additional calculations were performed to investigate the electrostatic field difference using the Gasteiger and Marsili charges, the electrostatic potential fit charges at the AM1 level, and the natural population analysis charges at the HF/3-21G level of theory. For the HF/3-21G optimized structures no difference in predictability was observed, whereas for AM1 optimized structures such differences were found. Interestingly, if ionic compounds are omitted, differences between the various HF/3-21G optimized structure models using these electrostatic fields were found.

Radiative Heat Transfer and Turbulence-Radiation Interactions in a Heavy-Duty Diesel Engine

NASA Astrophysics Data System (ADS)

Paul, C.; Sircar, A.; Ferreyro, S.; Imren, A.; Haworth, D. C.; Roy, S.; Ge, W.; Modest, M. F.

2016-11-01

Radiation in piston engines has received relatively little attention to date. Recently, it is being revisited in light of current trends towards higher operating pressures and higher levels of exhaust-gas recirculation, both of which enhance molecular gas radiation. Advanced high-efficiency engines also are expected to function closer to the limits of stable operation, where even small perturbations to the energy balance can have a large influence on system behavior. Here several different spectral radiation property models and radiative transfer equation (RTE) solvers have been implemented in an OpenFOAM-based engine CFD code, and simulations have been performed for a heavy-duty diesel engine. Differences in computed temperature fields, NO and soot levels, and wall heat transfer rates are shown for different combinations of spectral models and RTE solvers. The relative importance of molecular gas radiation versus soot radiation is examined. And the influence of turbulence-radiation interactions is determined by comparing results obtained using local mean values of composition and temperature to compute radiative emission and absorption with those obtained using a particle-based transported probability density function method. DOE, NSF.

Radiative Heat Transfer modelling in a Heavy-Duty Diesel Engine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paul, Chandan; Sircar, Arpan; Ferreyro-Fernandez, Sebastian

Detailed radiation modelling in piston engines has received relatively little attention to date. Recently, it is being revisited in light of current trends towards higher operating pressures and higher levels of exhaust-gas recirculation, both of which enhance molecular gas radiation. Advanced high-efficiency engines also are expected to function closer to the limits of stable operation, where even small perturbations to the energy balance can have a large influence on system behavior. Here several different spectral radiation property models and radiative transfer equation (RTE) solvers have been implemented in an OpenFOAM-based engine CFD code, and simulations have been performed for amore » heavy-duty diesel engine. Differences in computed temperature fields, NO and soot levels, and wall heat transfer rates are shown for different combinations of spectral models and RTE solvers. The relative importance of molecular gas radiation versus soot radiation is examined. And the influence of turbulence-radiation interactions is determined by comparing results obtained using local mean values of composition and temperature to compute radiative emission and absorption with those obtained using a particle-based transported probability density function method.« less

In situ dynamic observations of perovskite crystallisation and microstructure evolution intermediated from [PbI 6] 4– cage nanoparticles

DOE PAGES

Hu, Qin; Zhao, Lichen; Wu, Jiang; ...

2017-06-21

Hybrid lead halide perovskites have emerged as high-performance photovoltaic materials with their extraordinary optoelectronic properties. In particular, the remarkable device efficiency is strongly influenced by the perovskite crystallinity and the film morphology. Here, we investigate the perovskites crystallisation kinetics and growth mechanism in real time from liquid precursor continually to the final uniform film. We utilize some advanced in situ characterisation techniques including synchrotron-based grazing incident X-ray diffraction to observe crystal structure and chemical transition of perovskites. The nano-assemble model from perovskite intermediated [PbI 6] 4– cage nanoparticles to bulk polycrystals is proposed to understand perovskites formation at a molecular-more » or nano-level. A crystallisation-depletion mechanism is developed to elucidate the periodic crystallisation and the kinetically trapped morphology at a mesoscopic level. Based on these in situ dynamics studies, the whole process of the perovskites formation and transformation from the molecular to the microstructure over relevant temperature and time scales is successfully demonstrated.« less

Efficient Ultraviolet Light Detector Based on a Crystalline Viologen-Based Metal-Organic Framework with Rapid Visible Color Change under Irradiation.

PubMed

Hu, Shuzhi; Zhang, Jie; Chen, Shuhuang; Dai, Jingcao; Fu, Zhiyong

2017-11-22

A convenient colorimetric molecular system constructed by the zinc viologen-carboxylate framework is developed for naked eye detection of instantaneous UV exposure levels. Only narrow-band absorption in UV regions and a unique interpenetrated structure of its colorless crystal enable the system to give a fast response toward UV irradiance with intensity as low as 0.001 mw/cm 2 .

Molecular Environmental Science: An Assessment of Research Accomplishments, Available Synchrotron Radiation Facilities, and Needs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, G

2004-02-05

Synchrotron-based techniques are fundamental to research in ''Molecular Environmental Science'' (MES), an emerging field that involves molecular-level studies of chemical and biological processes affecting the speciation, properties, and behavior of contaminants, pollutants, and nutrients in the ecosphere. These techniques enable the study of aqueous solute complexes, poorly crystalline materials, solid-liquid interfaces, mineral-aqueous solution interactions, microbial biofilm-heavy metal interactions, heavy metal-plant interactions, complex material microstructures, and nanomaterials, all of which are important components or processes in the environment. Basic understanding of environmental materials and processes at the molecular scale is essential for risk assessment and management, and reduction of environmental pollutantsmore » at field, landscape, and global scales. One of the main purposes of this report is to illustrate the role of synchrotron radiation (SR)-based studies in environmental science and related fields and their impact on environmental problems of importance to society. A major driving force for MES research is the need to characterize, treat, and/or dispose of vast quantities of contaminated materials, including groundwater, sediments, and soils, and to process wastes, at an estimated cost exceeding 150 billion dollars through 2070. A major component of this problem derives from high-level nuclear waste. Other significant components come from mining and industrial wastes, atmospheric pollutants derived from fossil fuel consumption, agricultural pesticides and fertilizers, and the pollution problems associated with animal waste run-off, all of which have major impacts on human health and welfare. Addressing these problems requires the development of new characterization and processing technologies--efforts that require information on the chemical speciation of heavy metals, radionuclides, and xenobiotic organic compounds and their reactions with environmental materials. To achieve this goal, both fundamental and targeted studies of complex environmental systems at a molecular level are needed, and examples of both types of studies are presented herein. These examples illustrate the fact that MES SR studies have led to a revolution in our understanding of the fundamental physical and chemical aspects of natural systems. The MES SR user community has continued to experience strong growth at U.S. SR laboratories, with MES researchers comprising up to 15% of the total user base. Further growth and development of the MES community is being hindered by insufficient resources, including support personnel, materials preparation facilities, and available beam time at U.S. SR laboratories. ''EnviroSync'' recommends the following actions, in cooperation with U.S. SR laboratory directors, to meet the MES community's needs.« less

Rapid screening of phytoremediation effluents by off-line tetramethylammonium hydroxide assisted thermochemolysis.

PubMed

Poerschmann, Juergen; Schultze-Nobre, Luciana

2015-06-15

Tetramethylammonium hydroxide-assisted thermochemolysis performed in an off-line mode proved a useful tool in determining organic compounds in the effluent from laboratory-scale phytoremediation systems. Studies were performed with artificial wastewaters contaminated with xylenols and densely rooted Juncus effuses plants. Analytes in these molecular-level based studies included xylenol substrates, an array of stable intermediates such as low molecular weight carboxylic acids and oxidative coupling products (tetramethyl biphenyldiols, tetramethyl diphenylether monools), diagnostic fatty acid biomarkers, as well as lignin-, carbohydrate-, and protein-based phenols and carboxylic acids. Lignin-based breakdown products belonged to p-hydroxyphenyl- and guaiacyl-units, with lower abundance of syringyl units and the dominance of acids over phenols. Monomeric lignin-, protein- and carbohydrate-based breakdown products could not be detected in the non-treated lyophilized effluent. The formation of diketopiperazines pointed to soluble peptides and proteins. The procedure described herein can easily be applied in every modern laboratory to characterize underlying processes in phytoremediation. Copyright © 2015 Elsevier B.V. All rights reserved.

Inquiry-based experiments for large-scale introduction to PCR and restriction enzyme digests.

PubMed

Johanson, Kelly E; Watt, Terry J

2015-01-01

Polymerase chain reaction and restriction endonuclease digest are important techniques that should be included in all Biochemistry and Molecular Biology laboratory curriculums. These techniques are frequently taught at an advanced level, requiring many hours of student and faculty time. Here we present two inquiry-based experiments that are designed for introductory laboratory courses and combine both techniques. In both approaches, students must determine the identity of an unknown DNA sequence, either a gene sequence or a primer sequence, based on a combination of PCR product size and restriction digest pattern. The experimental design is flexible, and can be adapted based on available instructor preparation time and resources, and both approaches can accommodate large numbers of students. We implemented these experiments in our courses with a combined total of 584 students and have an 85% success rate. Overall, students demonstrated an increase in their understanding of the experimental topics, ability to interpret the resulting data, and proficiency in general laboratory skills. © 2015 The International Union of Biochemistry and Molecular Biology.

A Strategic Design of an Opto-Chemical Security Device with Resettable and Reconfigurable Password Based Upon Dual Channel Two-in-One Chemosensor Molecule.

PubMed

Majumdar, Tapas; Haldar, Basudeb; Mallick, Arabinda

2017-02-20

A simple strategy is proposed to design and develop an intelligent device based on dual channel ion responsive spectral properties of a commercially available molecule, harmine (HM). The system can process different sets of opto-chemical inputs generating different patterns as fluorescence outputs at specific wavelengths which can provide an additional level of protection exploiting both password and pattern recognitions. The proposed system could have the potential to come up with highly secured combinatorial locks at the molecular level that could pose valuable real time and on-site applications for user authentication.

A Strategic Design of an Opto-Chemical Security Device with Resettable and Reconfigurable Password Based Upon Dual Channel Two-in-One Chemosensor Molecule

NASA Astrophysics Data System (ADS)

Majumdar, Tapas; Haldar, Basudeb; Mallick, Arabinda

2017-02-01

A simple strategy is proposed to design and develop an intelligent device based on dual channel ion responsive spectral properties of a commercially available molecule, harmine (HM). The system can process different sets of opto-chemical inputs generating different patterns as fluorescence outputs at specific wavelengths which can provide an additional level of protection exploiting both password and pattern recognitions. The proposed system could have the potential to come up with highly secured combinatorial locks at the molecular level that could pose valuable real time and on-site applications for user authentication.

Biological Networks for Cancer Candidate Biomarkers Discovery

PubMed Central

Yan, Wenying; Xue, Wenjin; Chen, Jiajia; Hu, Guang

2016-01-01

Due to its extraordinary heterogeneity and complexity, cancer is often proposed as a model case of a systems biology disease or network disease. There is a critical need of effective biomarkers for cancer diagnosis and/or outcome prediction from system level analyses. Methods based on integrating omics data into networks have the potential to revolutionize the identification of cancer biomarkers. Deciphering the biological networks underlying cancer is undoubtedly important for understanding the molecular mechanisms of the disease and identifying effective biomarkers. In this review, the networks constructed for cancer biomarker discovery based on different omics level data are described and illustrated from recent advances in the field. PMID:27625573

Bioenergy Research | Bioenergy | NREL

Science.gov Websites

range of research from exploring biomass at the molecular level through biorefinery process optimization Bioenergetics We work at the molecular and cellular level to understand and optimize microbial production of biofuels and bioproducts. fanciful illustration of fuel nozzle with molecular structures drawn in

'Ogura'-based 'CMS' lines with different nuclear backgrounds of cabbage revealed substantial diversity at morphological and molecular levels.

PubMed

Parkash, Chander; Kumar, Sandeep; Singh, Rajender; Kumar, Ajay; Kumar, Satish; Dey, Shyam Sundar; Bhatia, Reeta; Kumar, Raj

2018-01-01

A comprehensive study on characterization and genetic diversity analysis was carried out in 16 'Ogura'-based 'CMS' lines of cabbage using 14 agro-morphological traits and 29 SSR markers. Agro-morphological characterization depicted considerable variations for different horticultural traits studied. The genotype, ZHA-2, performed better for most of the economically important quantitative traits. Further, gross head weight (0.76), head length (0.60) and head width (0.83) revealed significant positive correlation with net head weight. Dendrogram based on 10 quantitative traits exhibited considerable diversity among different CMS lines and principle component analysis (PCA) indicated that net and gross head weight, and head length and width are the main components of divergence between 16 CMS lines of cabbage. In molecular study, a total of 58 alleles were amplified by 29 SSR primers, averaging to 2.0 alleles in each locus. High mean values of Shannon's Information index (0.62), expected (0.45) and observed (0.32) heterozygosity and polymorphic information content (0.35) depicted substantial polymorphism. Dendrogram based on Jaccard's similarity coefficient constructed two major groups and eight sub-groups, which revealed substantial diversity among different CMS lines. In overall, based on agro-morphological and molecular studies genotype RRMA, ZHA-2 and RCA were found most divergent. Hence, they have immense potential in future breeding programs for the high-yielding hybrid development in cabbage.

In vivo interstitial glucose characterization and monitoring in the skin by ATR-FTIR spectroscopy

NASA Astrophysics Data System (ADS)

Skrebova Eikje, Natalja

2011-03-01

Successful development of real-time non-invasive glucose monitoring would represent a major advancement not only in the treatment and management of patients with diabetes mellitus and carbohydrate metabolism disorders, but also for understanding in those biochemical, metabolic and (patho-)physiological processes of glucose at the molecular level in vivo. Here, ATR-FTIR spectroscopy technique has been challenged not only for in vivo measurement of interstitial glucose levels, but also for their non-invasive molecular qualitative and quantitative comparative characterization in the skin tissue. The results, based on calculated mean values of determined 5 glucose-specific peaks in the glucose-related 1000-1160 cm-1 region, showed intra- and inter-subject differences in interstitial glucose activity levels with their changes at different times and doses of OGTT, while raising questions about the relationships between interstitial and blood glucose levels. In conclusion, the introduction of ATR-FTIR spectroscopy technique has opened up an access to the interstitial fluid space in the skin tissue for interstitial glucose characterization and monitoring in vivo. Though interstitial versus blood glucose monitoring has different characteristics, it can be argued that accurate and precise measurements of interstitial glucose levels may be more important clinically.

Evaluation of the molecular level visualisation approach for teaching and learning chemistry in Thailand

NASA Astrophysics Data System (ADS)

Phenglengdi, Butsari

This research evaluates the use of a molecular level visualisation approach in Thai secondary schools. The goal is to obtain insights about the usefulness of this approach, and to examine possible improvements in how the approach might be applied in the future. The methodology used for this research used both qualitative and quantitative approaches. Data were collected in the form of pre- and post-intervention multiple choice questions, open-ended-questions, drawing exercises, one-to-one interviews and video recordings of class activity. The research was conducted in two phases, involving a total of 261 students from the 11th Grade in Thailand. The use of VisChem animations in three studies was evaluated in Phase I. Study 1 was a pilot study exploring the benefits of incorporating VisChem animations to portray the molecular level. Study 2 compared test results between students exposed to these animations of molecular level events, and those not. Finally, in Study 3, test results were gathered from different types of schools (a rural school, a city school, and a university school). The results showed that students (and teachers) had misconceptions at the molecular level, and VisChem animations could help students understand chemistry concepts at the molecular level across all three types of schools. While the animation treatment group had a better score on the topic of states of water, the non-animation treatment group had a better score on the topic of dissolving sodium chloride in water than the animation group. The molecular level visualisation approach as a learning design was evaluated in Phase II. This approach involved a combination of VisChem animations, pictures, and diagrams together with the seven-step VisChem learning design. The study involved three classes of students, each with a different treatment, described as Class A - Traditional approach; Class B - VisChem animations with traditional approach; and Class C - Molecular level visualisation approach. Pre-test and post-test scores were compared across the three classes. The results from the multiple choice and calculation tests showed that the Class C - molecular level visualisation approach group demonstrated a deeper understanding of chemistry concepts than students in Classes A and B. However, the results showed that all the students were unable to perform satisfactorily on the calculation tests because the students had insufficient prior knowledge about stoichiometry to connect with the new knowledge. In the drawing tests the students exposed to the molecular level visualisation approach had a better mental model than the other classes, albeit with some remaining misconceptions. The findings highlight the intersecting nature of the teacher, student, and modelling in chemistry teaching. Use of a multi-step molecular level visualisation approach that encourages observation, reflection of prior understanding, and multiple opportunities at viewing (and using various visualisation elements), are key elements leading to a deeper understanding of chemistry. Presentation of the multi-step molecular level visualisation approach must be coupled with careful consideration of student prior knowledge, and with adequate guidance from a teacher who understands the topics at a deep level.

Coestimation of recombination, substitution and molecular adaptation rates by approximate Bayesian computation.

PubMed

Lopes, J S; Arenas, M; Posada, D; Beaumont, M A

2014-03-01

The estimation of parameters in molecular evolution may be biased when some processes are not considered. For example, the estimation of selection at the molecular level using codon-substitution models can have an upward bias when recombination is ignored. Here we address the joint estimation of recombination, molecular adaptation and substitution rates from coding sequences using approximate Bayesian computation (ABC). We describe the implementation of a regression-based strategy for choosing subsets of summary statistics for coding data, and show that this approach can accurately infer recombination allowing for intracodon recombination breakpoints, molecular adaptation and codon substitution rates. We demonstrate that our ABC approach can outperform other analytical methods under a variety of evolutionary scenarios. We also show that although the choice of the codon-substitution model is important, our inferences are robust to a moderate degree of model misspecification. In addition, we demonstrate that our approach can accurately choose the evolutionary model that best fits the data, providing an alternative for when the use of full-likelihood methods is impracticable. Finally, we applied our ABC method to co-estimate recombination, substitution and molecular adaptation rates from 24 published human immunodeficiency virus 1 coding data sets.

Humidity-controlled rectification switching in ruthenium-complex molecular junctions

NASA Astrophysics Data System (ADS)

Atesci, Huseyin; Kaliginedi, Veerabhadrarao; Celis Gil, Jose A.; Ozawa, Hiroaki; Thijssen, Joseph M.; Broekmann, Peter; Haga, Masa-aki; van der Molen, Sense Jan

2018-02-01

Although molecular rectifiers were proposed over four decades ago1,2, until recently reported rectification ratios (RR) were rather moderate2-11 (RR 101). This ceiling was convincingly broken using a eutectic GaIn top contact12 to probe molecular monolayers of coupled ferrocene groups (RR 105), as well as using scanning tunnelling microscopy-break junctions13-16 and mechanically controlled break junctions17 to probe single molecules (RR 102-103). Here, we demonstrate a device based on a molecular monolayer in which the RR can be switched by more than three orders of magnitude (between RR 100 and RR ≥ 103) in response to humidity. As the relative humidity is toggled between 5% and 60%, the current-voltage (I-V) characteristics of a monolayer of di-nuclear Ru-complex molecules reversibly change from symmetric to strongly asymmetric (diode-like). Key to this behaviour is the presence of two localized molecular orbitals in series, which are nearly degenerate in dry circumstances but become misaligned under high humidity conditions, due to the displacement of counter ions (PF6-). This asymmetric gating of the two relevant localized molecular orbital levels results in humidity-controlled diode-like behaviour.

Multiplex bioimaging of piRNA molecular pathway-regulated theragnostic effects in a single breast cancer cell using a piRNA molecular beacon.

PubMed

Lee, Youn Jung; Moon, Sung Ung; Park, Min Geun; Jung, Woon Yong; Park, Yong Keun; Song, Sung Kyu; Ryu, Je Gyu; Lee, Yong Seung; Heo, Hye Jung; Gu, Ha Na; Cho, Su Jeong; Ali, Bahy A; Al-Khedhairy, Abdulaziz A; Lee, Ilkyun; Kim, Soonhag

2016-09-01

Recently, PIWI-interacting small non-coding RNAs (piRNAs) have emerged as novel cancer biomarkers candidate because of their high expression level in various cancer types and role in the control of tumor suppressor genes. In this study, a novel breast cancer theragnostics probe based on a single system targeting the piRNA-36026 (piR-36026) molecular pathway was developed using a piR-36026 molecular beacon (MB). The piR-36026 MB successfully visualized endogenous piR-36026 biogenesis, which is highly expressed in MCF7 cells (a human breast cancer cell line), and simultaneously inhibited piR-36026-mediated cancer progression in vitro and in vivo. We discovered two tumor suppressor proteins, SERPINA1 and LRAT, that were directly regulated as endogenous piR-36026 target genes in MCF7 cells. Furthermore, multiplex bioimaging of a single MCF7 cell following treatment with piR-36026 MB clearly visualized the direct molecular interaction of piRNA-36026 with SERPINA1 or LRAT and subsequent molecular therapeutic responses including caspase-3 and PI in the nucleus. Copyright © 2016 Elsevier Ltd. All rights reserved.

Spectroscopic analysis and molecular docking of imidazole derivatives and investigation of its reactive properties by DFT and molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Thomas, Renjith; Hossain, Mossaraf; Mary, Y. Sheena; Resmi, K. S.; Armaković, Stevan; Armaković, Sanja J.; Nanda, Ashis Kumar; Ranjan, Vivek Kumar; Vijayakumar, G.; Van Alsenoy, C.

2018-04-01

Solvent-free synthesis pathway for obtaining two imidazole derivatives (2-chloro-1-(4-methoxyphenyl)-4,5-dimethyl-1H-imidazole (CLMPDI) and 1-(4-bromophenyl)-2-chloro-4,5-dimethyl-1H-imidazole (BPCLDI) has been reported in this work, followed by detailed experimental and computational spectroscopic characterization and reactivity study. Spectroscopic methods encompassed IR, FT-Raman and NMR techniques, with the mutual comparison of experimentally and computationally obtained results at DFT/B3LYP level of theory. Reactivity study based on DFT calculations encompassed molecular orbitals analysis, followed by calculations of molecular electrostatic potential (MEP) and average local ionization energy (ALIE) values, Fukui functions and bond dissociation energies (BDE). Additionally, the stability of title molecules in water has been investigated via molecular dynamics (MD) simulations, while interactivity with aspulvinonedimethylallyl transferase protein has been evaluated by molecular docking procedure. CLMPDI compound showed antimicrobial activity against all four bacterial strain in both gram positive and gram negative bacteria while, BPCLDI showed only in gram positive bacteria, Staphylococcus Aureus (MTCC1144). The first order hyperpolarizability of CLMPDI and BPCLDI are 20.15 and 6.10 times that of the standard NLO material urea.

Two-dimensional ice mapping of molecular cores

NASA Astrophysics Data System (ADS)

Noble, J. A.; Fraser, H. J.; Pontoppidan, K. M.; Craigon, A. M.

2017-06-01

We present maps of the column densities of H2O, CO2 and CO ices towards the molecular cores B 35A, DC 274.2-00.4, BHR 59 and DC 300.7-01.0. These ice maps, probing spatial distances in molecular cores as low as 2200 au, challenge the traditional hypothesis that the denser the region observed, the more ice is present, providing evidence that the relationships between solid molecular species are more varied than the generic picture we often adopt to model gas-grain chemical processes and explain feedback between solid phase processes and gas phase abundances. We present the first combined solid-gas maps of a single molecular species, based upon observations of both CO ice and gas phase C18O towards B 35A, a star-forming dense core in Orion. We conclude that molecular species in the solid phase are powerful tracers of 'small-scale' chemical diversity, prior to the onset of star formation. With a component analysis approach, we can probe the solid phase chemistry of a region at a level of detail greater than that provided by statistical analyses or generic conclusions drawn from single pointing line-of-sight observations alone.

Optimized molecular design of ADAPT-based HER2-imaging probes labelled with 111In and 68Ga.

PubMed

Lindbo, Sarah; Garousi, Javad; Mitran, Bogdan; Vorobyeva, Anzhelika; Oroujeni, Maryam; Orlova, Anna; Hober, Sophia; Tolmachev, Vladimir

2018-06-04

Radionuclide molecular imaging is a promising tool for visualization of cancer associated molecular abnormalities in vivo and stratification of patients for specific therapies. ADAPT is a new type of small engineered proteins based on the scaffold of an albumin binding domain of protein G. ADAPTs have been utilized to select and develop high affinity binders to different proteinaceous targets. ADAPT6 binds to human epidermal growth factor 2 (HER2) with low nanomolar affinity and can be used for its in vivo visualization. Molecular design of 111 In-labeled anti-HER2 ADAPT has been optimized in several earlier studies. In this study, we made a direct comparison of two of the most promising variants, having either a DEAVDANS or a (HE) 3 DANS sequence at the N-terminus, conjugated with a maleimido derivative of DOTA to a GSSC amino acids sequence at the C-terminus. The variants (designated DOTA-C 59 - DEAVDANS-ADAPT6-GSSC and DOTA-C 61 -(HE) 3 DANS-ADAPT6-GSSC) were stably labeled with 111 In for SPECT and 68 Ga for PET. Biodistribution of labeled ADAPT variants was evaluated in nude mice bearing human tumor xenografts with different levels of HER2 expression. Both variants enabled clear discrimination between tumors with high and low levels of HER2 expression. 111 In-labeled ADAPT6 derivatives provided higher tumor-to-organ ratios compared to 68 Ga-labeled counterparts. The best performing variant was DOTA-C 61 -(HE) 3 DANS-ADAPT6-GSSC, providing tumor-to-blood ratios of 208±36 and 109±17 at 3 h for 111 In and 68 Ga labels, respectively.

Stochastic thermodynamics, fluctuation theorems and molecular machines.

PubMed

Seifert, Udo

2012-12-01

Stochastic thermodynamics as reviewed here systematically provides a framework for extending the notions of classical thermodynamics such as work, heat and entropy production to the level of individual trajectories of well-defined non-equilibrium ensembles. It applies whenever a non-equilibrium process is still coupled to one (or several) heat bath(s) of constant temperature. Paradigmatic systems are single colloidal particles in time-dependent laser traps, polymers in external flow, enzymes and molecular motors in single molecule assays, small biochemical networks and thermoelectric devices involving single electron transport. For such systems, a first-law like energy balance can be identified along fluctuating trajectories. For a basic Markovian dynamics implemented either on the continuum level with Langevin equations or on a discrete set of states as a master equation, thermodynamic consistency imposes a local-detailed balance constraint on noise and rates, respectively. Various integral and detailed fluctuation theorems, which are derived here in a unifying approach from one master theorem, constrain the probability distributions for work, heat and entropy production depending on the nature of the system and the choice of non-equilibrium conditions. For non-equilibrium steady states, particularly strong results hold like a generalized fluctuation-dissipation theorem involving entropy production. Ramifications and applications of these concepts include optimal driving between specified states in finite time, the role of measurement-based feedback processes and the relation between dissipation and irreversibility. Efficiency and, in particular, efficiency at maximum power can be discussed systematically beyond the linear response regime for two classes of molecular machines, isothermal ones such as molecular motors, and heat engines such as thermoelectric devices, using a common framework based on a cycle decomposition of entropy production.

The promise of molecular epidemiology in defining the association between radiation and cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neta, R.

2000-07-01

Molecular epidemiology involves the inclusion in epidemiologic studies of biologic measurements made at a genetic and molecular level and aims to improve the current knowledge of disease etiology and risk. One of the goals of molecular epidemiology studies of cancer is to determine the role of environmental and genetic factors in initiation and progression of malignancies and to use this knowledge to develop preventive strategies. This approach promises extraordinary opportunities for revolutionizing the practice of medicine and reducing risk. However, this will be accompanied by the need to address and resolve many challenges, such as ensuring the appropriate interpretation ofmore » molecular testing and resolving associated ethical, legal, and social issues. Traditional epidemiologic approaches determined that exposure to ionizing radiation poses significantly increased risk of leukemia and several other types of cancer. Such studies provided the basis for setting exposure standards to protect the public and the workforce from potentially adverse effects of ionizing radiation. These standards were set by using modeling approaches to extrapolate from the biological effects observed in high-dose radiation studies to predicted, but mostly immeasurable, effects at low radiation doses. It is anticipated that the addition of the molecular parameters to the population-based studies will help identify the genes and pathways characteristic of cancers due to radiation exposure of individuals, as well as identify susceptible or resistant subpopulations. In turn, the information about the molecular mechanisms should aid to improve risk assessment. While studies on radiogenic concerns are currently limited to only a few candidate genes, the exponential growth of scientific knowledge and technology promises expansion of knowledge about identity of participating genes and pathways in the future. This article is meant to provide an introductory overview of recent advances in understanding of carcinogenesis at the molecular level, with an emphasis of the aspects that may be of use in establishing the association between radiation and cancer.« less

Autonomous model protocell division driven by molecular replication.

PubMed

Taylor, J W; Eghtesadi, S A; Points, L J; Liu, T; Cronin, L

2017-08-10

The coupling of compartmentalisation with molecular replication is thought to be crucial for the emergence of the first evolvable chemical systems. Minimal artificial replicators have been designed based on molecular recognition, inspired by the template copying of DNA, but none yet have been coupled to compartmentalisation. Here, we present an oil-in-water droplet system comprising an amphiphilic imine dissolved in chloroform that catalyses its own formation by bringing together a hydrophilic and a hydrophobic precursor, which leads to repeated droplet division. We demonstrate that the presence of the amphiphilic replicator, by lowering the interfacial tension between droplets of the reaction mixture and the aqueous phase, causes them to divide. Periodic sampling by a droplet-robot demonstrates that the extent of fission is increased as the reaction progresses, producing more compartments with increased self-replication. This bridges a divide, showing how replication at the molecular level can be used to drive macroscale droplet fission.Coupling compartmentalisation and molecular replication is essential for the development of evolving chemical systems. Here the authors show an oil-in-water droplet containing a self-replicating amphiphilic imine that can undergo repeated droplet division.